Neurology Flashcards
dura mater (inc 4 septal folds, which 3 CN innervates dura)
dura mater is outermost meningeal layer made of dense CT, cranial dura mater divided into outer endosteal layer which is continuous with pericranium through sutures and foramina and an inner meningeal layer, which are united apart form where they separate to form venous sinuses, and only one layer surrounds spinal cord; meningeal layer reflects to form 4 septa/dural folds, 2 main are falx cerebri (attaches to crista galli ant, midline internal surface of skull, upper surface of tentorium cerebelli post where straight sinus formed, also contains sup/inf sag sinuses) separating cerebral hemispheres and tentorium cerebelli (attaches to inner surface of occipital/petrous temporal bones, contains transverse/sup pet sinuses) separating cerebellum from two post parts of cerebral hemispheres; also falx cerebelli lies between cerebellar hemispheres and small horizontal shelf, diaphragma sellae, covers pituitary fossa in the sella turcica; CNV innervates the dura (mostly) also cervical nerves, CNIX/X for post cranial fossa`
pia and arachnoid mater
pia is highly vascular, delicate layer which closely covers brain/spinal cord and arachnoid is thin non-vascular layer between pia and dura; cranial pia is thinner than that of spinal cord and is only loosely attached to brain, spinal cord has ventral median fissure into which pia follows, just like it invests the grooves and sulci of the brain; cranial arachnoid is thicker than spinal and connected to cranial pia by fibrous strands which cross the subarachnoid space, it does not line grooves/sulci and so these areas are filled with CSF in brain/spinal cord; large CSF accumulations are found where cranial arachnoid bridges large grooves in brain surface called subarachnoid cisterns
meningeal spaces
spinal epidural space lies between dura mater and periosteum and contains LCT, lymphatics and venous plexuses, whereas cranial epidural/extradural space is potential space between endosteal layer and skull only realised pathologically; subdural space is potential space between dura/arachnoid; subarachnoid space contains CSF which extends in adults to termination of lumbar cistern at S2
dural venous sinuses
lined by vascular endothelium with no valves or muscular tissue, forming complex network of venous channels draining blood from brain and cranium; sup sagittal sinus begins at crista galli and runs in sup margin of falx cerebri forming a median groove in cranial vault and usually draining into right transverse sinus, with inf sagittal sinus running in posteroinferior border of falx cerebri, joining great cerebral/right/left basal veins to form the straight sinus which runs in junction of falx cerebri and tentorium cerebelli to continue as left transverse sinus; transverse sinus runs in lateral margin of tentorum cerebelli, receiving sup petrosal sinus and continuing on as sigmoid sinus which is S-shaped sinus that deeply grooves petrous temporal bone, curving forward onto occipital bone and curving forward to join inferior petrosal sinus and form IJV, with mastoid air cells next to it; sup petrosal runs in margin of tentorum cerebelli where it attaches to petrous temporal bone and thus connects cavernous sinus with transverse; inf petrosal lies in groove between occipital bone and petrous temporal bone, connecting/draining cavernous sinus to IJV; cavernous sinus lies either side of body of sphenoid with delicate interlacing strands of CT creating cavern-like meshwork in one blood filled space, it receives sup/inf opthalmic veins, thus forming extra-to-intracranial venous connections via the facial vein and pterygoid plexus: ICA runs through sinus with CN VI, and CNs III, IV, Va, Vb lie in its lateral wall; sphenoparietal sinus drains into cavernous and is under small wing of sphenoid
vertebral artery (branches, basilar, then what)
travels up neck to enter cranial cavity through foramen magnum, giving small post meningeal branch, ant/post spinal arteries, branches to medulla and post inf cerebellar artery; merge on ventral surface of brainstem to basilar, gives branches to brainstem, ant inf/sup cerebellar arteries and then anteriorly dividing into post cerebral arteries to supply occipital lobes
internal carotid artery
enters carotid foramen at base of skull, making right angled turn to pass anteromedially towards apex of petrous temporal bone, emerging sup to cartilage filling foramen lacerum; makes another right angled turn to cavernous sinus and runs ant within it, grooving body of sphenoid then turning upwards to pierce dural roof of cavernous sinus to give off opthalmic artery; within subarachnoid space turns back towards optic chiasma and on reaching lateral edge of post clinoid process it turns sup towards brain, giving ant/mid cerebral arteries; abducent nerve passes lateral to it in cavernous sinus
circle of willis (inc subclavian steal syndrome)
anastomotic connection between ICA and vertebral arteries at base of brain in region of optic chiasma/pituitary stalk with ant comm a’s between ant cerebral and post cerebral to corresponding ICA by post comm a; blood from vessels on one side of body can reach other side, or blood from vertebral can reach ICA distribution when necessary; no veins run along intracranial part of either artery sets, veins from brain follow independent courses to dural venous sinuses; highly variable with cadaveric study showing classic structure seen in 34.5% of people; in subclavian steal syndrome, prox stenosis of subclavian gives retrograde flow down ipsilateral vertebral artery giving similar symptoms to vertebrobasilar insufficiency inc syncope
cavernous sinus - 5 contents, what is above it, what is posterior to it, what fistula gives (5 sx, 3 causes [one of similar thing]), 3 sx of cavernous sinus syndrome (and 4 causes), route from face to meninges, 3x sx of venous sinus thrombosis generally
oculomotor and abducent next to artery; trochlear nerve; Vb travels through lower part of sinus, exits via foramen rotundum then gives off branches for IOF; optic chiasm above and outside sinus; trigeminal ganglion posterior to sinus, and 2 branches go through it but Vc goes inferiorly from ganglion through foramen ovale
carotid sinus fistula gives humming sound in skull due to high blood pressure, progressive visual loss, pulsatile proptosis (bulging of eye) due to dilatation of veins, pain, redness in eye, linked to hypertension and may be due to trauma or spontaneous; see something similar to sphenoid wing dysplasia in NF
lesions of sinus may affect nerves causing cavernous sinus syndrome: ophthalmoplegia from compressing CNIII/IV/VI, Va/Vb sensory loss, horner’s syndrome though difficult to see as CNIII palsy gives complete ptosis
pituitary adenoma expands in direction of least resistance, compressing cavernous sinus to cause CSS CSS also from other tumours, ICA aneurysm, CS thrombosis
external face injury: facial vein to sup ophthalmic to cavernous sinus thence to meninges
venous sinus thrombosis usually gives headache which may be only symptom, may also give symptoms of stroke (not isolated to one side all the time) and 40% get seizures, usually unilateral
bloodflow to brain (amount, icp link, 2 main pairs, course of each)
high level of activity requiring 200-800ml per min or around 15-20% CO; tightly regulated as too much causes intra-cranial pressure to rise (should be 5-15mmHg) and too low in ischaemia ledas to hypoxia and loss of function; anterior pair is internal carotid arteries, posterior pair is vertebral arteries, and both pairs undergo tortuous loops before entering cranial cavity which may serve to reduce pulse pressure to provide steadier pressure head for cerebral flow
ICA bifurcate into anterior cerebral arteries which run between the hemispheres and curve over the corpus callosum to supply much of the frontal lobes and medial aspect of parietal lobes, and middle cerebral arteries run in fissure between temporal lobes and frontal/parietal to supply lateral aspects of all lobes and deep structures: basal ganglia and tracts connecting cerebral cortex to rest of brain
enter skull through foramen magnum and merge into basilar artery which runs on ventral surface of brainstem; give rise to branches supplying the brainstem including posterior/anterior inferior cerebellar arteries, which have variable origins but strokes here are often very serious; basilar terminates as two pairs arteries: superior cerebellar are smaller and supply most of the cerebellum, and posterior cerebral are larger and supply most of the occipital and parts of the temporal lobes, as well as midbrain and diencephalon (inc thalamus); circle of willis formed by large communicating branches from ACA and smaller (sometimes absent) branches from MCA and PCA, though described as an anastomosis it is non-functional in the adult, blood supply essentially being end-arterial in the brain
blood brain barrier (what it is/why it exists, 3 ways to cross and what are excluded, barrier for CSF vs ECF, what areas lack BBB, what happens in inflam, glut1 role, tight junctions made of what 4 things)
potent regulatory system as neurons so sensitive to changes in external environment; cap endothelium non-fenestrated with tight junctions so all substances must pass through the cells, processes of astrocytes also cover the surface of the cells, cap basement membrane and pericytes (latter possibly involved in TJ formation and angiogenesis)
large molecules, cells, bacteria are excluded; some small hydrophillic molecules (O2/CO2) diffuse freely across; ions cross by pumps, channels and exchangers; glucose and aa cross by facilitated or carrier mediated transport; circulating pathogens and large toxin molecules thus do not enter the brain and [aa] (plus other molecules) tightly regulated, aa esp important as some used as NTs eg glycine and glutamate; no viruses either; ependymal cells are barrier for CSF and cap endothelium for ECF; circumventricular structures (eg laminar terminalis) plus post pituitary lack BBB
BBB partly breaks down in areas of inflam during bacterial meningitis in part due to eg MMPs, TNFs collecting (makes antibiotics more effective); mutations in glut1 affect glucose transport, less glucose in CSF, babies appear normal at birth but develop seizures and retardation
TJs made of claudins (bind claudins on adjacent cells to form TJ attachment), occludins (assemble with claudins into polymer intramembranous strands and one/both proteins deregulated in tumors with leaky BBB), junction adhesion molecules and cytoplasmic accessory proteins; neuron astrocyte signalling may play role in controlling BBB permeability
bloodflow and brain regions
ICA supply parts of forebrain, vertebral arteries supply the brainstem, cerebellum and some ventral/posterior parts of the forebrain with most vessels running in the subarachnoid space; ICA enters skull through carotid canal, makes an S shape in the cavernous sinus called the carotid siphon and penetrates the dura then bifurcates into: ACA supplies frontal lobes and passes into longitudinal fissure to run above corpus callosum and supply medial aspects of occipital/parietal lobes, including medial aspects of somatosensory and motor cortical areas which correspond to the lower limbs; MCA is largest cerebral artery and passes into lateral and inferior parts of hemispheres through the lateral sulcus, suppling the somatosensory and motor cortical regions corresponding to the face/upper limbs, the basal ganglia and the cerebral white matter
one or both vertebral arteries can be found on ventral medulla, frequently unequal in size and converge at midline pons to form basilar artery which grooves the ventral surface of the pons; they give AICA/PICA which supply brainstem and with superior cerebellar arteries supply the cerebellum; basilar terminates by bifurcating into posterior cerebral arteries which supply medial occpital lobes, notably visual cortex, and parts of temporal lobe; ACA unite via anterior communicating artery, and posterior communicating arteries from ICA or MCA pass back to anastomose with PCA on either side, forming the circle of Willis around the optic chiasm and stalk of pituitary, to provide potential anastomotic channels (learn to sketch regional blood supply for cerebral arteries)
cerebral venous drainage (sup vs deep veins)
blood from the cerebral vascular system drains into the venous sinuses: superficial veins into sup/inf sagittal sinuses, deep veins into great cerebral vein and then straight or transverse sinuses; sinuses converge and drain into IJV, draining CSF and venous blood; sinuses lie between folds of dura
brainstem strokes (when to suspect, localising based on 3 criteria (inc 4Ms and 4Ss), 4 egs)
suspect when crosses signs (ie face signs on one side and body signs on a different side)
localise: side (face signs tend to be ipsi and body signs tend to be contra), level (CN 3/4 in midbrain, 5-8 in pons, 9-12 in medulla), and lat vs medial (medial structures inc motor pathway, medial leminiscus, medial longitudinal fasciculus, motor component of some cranial nerves; lateral includes spinocerebellar pathway, spinothalamic tract, sympathetic pathway (hypothalamospinal tract), and sensation from face
medial medullary syndrome: ipsilateral tongue weakness, contralateral weakness or hemiparesis and contralat loss of proprioception, vibration, and touch sensation; generally ant spinal artery
lateral medullary syndrome: loss of pain and temperature sensation (ipsilateral in face and contralat in body), ipsilateral horners syndrome, ipsilateral ataxia and nystagmus (fall to side of lesion, , and dysarthria/dysphagia
medial midbrain: contralateral weakness, ipsilateral CNIII/IV palsy
locked in syndrome: stroke in basilar artery is one cause, due to damage to corticospinal tract and cranial nerve motor nuclei (sometimes higher nuclei ie ocular may be spared)
MCA stroke 6 sequelae inc diff inattention from HH; ACA 5 sequelae, PCA 2 sequelae; vertibrobasilar 6 sequelae; carotid art 3 sequelae; 2 causes and dist of lobar bleed, 3 causes and dist of deep bleed; 7 mx of intracereb bleed (4 surg crit)
MCA – Aphasia, Visual Field Defects, Hemipareisis/hemiplegia,hemisensory loss,
inattention (neglect - usually damage to right parietal area; difference from homonymous hemianop is in latter they know they can’t see
so move their head to look at the missing side, in neglect its like the missing side doesnt exist, pt may not be aware at all), apraxia
2. ACA – Personality changes, confusion, weakness more distally (legs), hemiplegia,
incontinence
3. PCA – Cortical blindness, dyslexia
4. Vertibro basilar artery – Diplopia, dysarthria, ataxia, poor motor coordination,
vertigo, nausea/vomiting
5. Carotid artery – Altered level of consciousness, weakness and numbness
intraceb bleed: lobar (amyloid angio, hypertens, parietal/occipital lobes) and deep (hypertense, drugs (anticoags), AVM in kids, putamen,
midbrain, pons, cerebellum); Reverse Anticoagulation
2. Control BP – 140 /90
3. Head up tilt 30degree
4. N Saline
5. ICU or HASU Bed
6. desmopressin can be given (1 dose avoid if heart failure) to reverse antiplatelets by triggering vWF and factor VIII release
surgical if: Cerebellar bleed > 3 cm
2. Brain stem bleed
3. Intraventricullar extension – hydrocephalus
4. Supratentorial - 30 ml, <1 cm from surface 3
MCA anatomy - where each bifurcation occurs, at which level is dense vessel sign usually seen
The largest terminal branch of the internal carotid artery, the MCA divides into four main surgical segments, denominated M1 to M4. M1 originates at the terminal bifurcation of the internal carotid artery and terminates at main bifurcation. M2 runs posterosuperiorly in insular cleft and becomes M3 when it turns back to run laterally to the external surface of the sylvian fissure where it becomes M4 and these branches run over the cortex. Most commonly there are 2 M2, one running sup and one inf, but some pts have 3 branches or many small ones. M3 may also split into 2 or 3.
dense vessel sign is seen mainly in M2 strokes and is specific but not sensitive; it appears within 90 mins
stroke management principles (3 things; 4 parameters of cerebral haemodynamics inc MTT equation; level of these parameters in infarcation vs penumbra, how infarct spreads; 2 ix needed; long term mx for large art athero, cardioemb, small vessel; where is brocas? wernickes? what area causes prosopagnosia?
a)Identify Salvageable Brain
b)Reperfusion if possible
c) Stroke Unit for Rehab
Parameters of cerebral hemodynamics:
1. Cerebral Blood Flow (CBF): Represents instantaneous capillary flow in tissue.
2. Cerebral Blood Volume (CBV): Describes the blood volume of the cerebral capillaries and venules per cerebral tissue volume.
3. Mean Transit Time (MTT): Measures the length of time a certain volume of blood spends in the cerebral capillary circulation.
4. Time To Peak (TTP): A parameter inversely related to CBF in which reduction of blood flow results in an increase in the time
needed for the contrast to reach its peak in the perfused volume of brain tissue.
MTT = CBV/CBF
Infarction core – Dead Brain
* CBF and CBV are both low due to failure of the autoregulation and the end result is DEAD tissue.
* MTT will be variable depending on how low CBV and CBF go below the critical level.
Penumbra – Salvageable Brain
* Low CBF: secondary to compromised main branch blood supply.
* Normal CBV or High: secondary to collateral blood flow from neighboring territories and active autoregulation that causes
vasodilatation. This maintains the O2 delivery in the range that keeps the cells viable, but not sufficient for normal
function.
* High MTT: secondary to the slow collateral flow; maximize O2 unloading to the cells.
* Viable dysfunctional neuronal tissue
First few hours of vascular insult there is only a penumbral pattern (low CBF and high CBV)
* Because - maximally functioning autoregulation mechanism and collateral circulation.
* This is viable tissue at risk that could be saved – Penumbra
* Later autoregulation mechanism starts to fail and the infarction core spreads,
* Finally the entire penumbra (low CBF region) becomes the Core infarct
CT perfusion for penumbra imaging, CT angiogram for where the occlusion is - prox with penumbra can do thrombectomy
AHA stroke guidelines suggest CT perfusion not needed in first 4.5hr as thrombolysis decision can be made with CTH +/- CTA, however outside of this time is v useful to demonstrate a salvageable penumbra outside of the classical window
large art athero: Dual Antiplatelet – 1-3 month,Single antiplatelet – for life Control Vascular risk factors Carotid Surgery
cardioembolic: anticoag
small vessl disease: Antiplatelet Control Vascular risk factors BP, DM, Lipids, Smoking, Diet, Exercise, Alcohol
potential complications inc resistance to thrombo, secondary clots, vasoconstriction, haemorrhagic transformation
brocas: inf frontal gyrus, wernickes sup temoral gyrus; prosopagnosia from stroke damage to right fusiform gyrus in temp cortex
rationale for the different antiplatelet regime in stroke/TIA vs eg ACS
Highest risk of a second ischaemic stroke is within 14 days of a first stroke. Hence the traditional loading course of Aspirin before switching to clopidogrel. Beyond this and the risks (of general bleeding) outweigh benefits.
Now a loading course of DAPT (e.g. D1 - 300/300 asp/clopi then 75/75 for 20 days) results in lower rates of recurrent stroke, but higher risks of haemorrhagic transformation (amongst other forms of bleeding). Remember that with ischaemic strokes, the infarcted capillary bed becomes friable and prone to bleeding upon reperfusion, and the greater the infarct volume the greater the risk. Hence loading DAPT is not safe to use with medium to large ischaemic strokes. But you can use it in small strokes
don’t have to load on clopi when swapping from aspirin as aspirin effect on plts is irreversible and plt turnover takes a week, so by the time this has happened the normal dose clopi will have had time to take effect
stroke risk factors (4 modifiable, 3 not) and subtypes (4 causes of lacunar, 5 types of lacunar, PACS v TACS, POCS 5sx), 3 inds for hemicraniectomy; secondary prev strats for large vessel, small vessel, embolic
smoking, DM, hypertens/lipidaemia, AF are modifiable stroke risk factors; non-modifiable age, sex, genetics
small embolism can cause lacunar stroke, but more likely atheroma from bigger art blocking, intrinsic small vessel disease, or atheroma
within the perforating artery; lacunar intrinsic small ves dis often hyalinosis of the arterioles (collagen/fibrous lined on histo)
lacunar strokes: pure motor hemiparesis = internal capsule/corona radiata, basal pons/medulla - dysarth/dysphagia can be part of this
pure sensory numbness if thalamus, pontine tegmentum, corona radiata; ataxic hemiparesis (unilat weakness + ataxia 0 weak leg, ataxic arm);
sensorimotor syndrome (hemiparesis of face/arm/leg with ipsi sensory impairment); dysarthria with clumsy hand syndrome (weak/clumsy hand)
all generally internal capsule/corona radiata, basal pons
- best recovery, lowest risk of recurrence
PACS motor +/sensory, plus one of homonymouss hemianopia or higher function eg dysphasia (or higher function alone); TACS all three
POCS: ataxia, diplopia, cortical blindness, isolated homonymous hemianopia, LMN cranial nerves
2nd prevention: large vessel: endarterectomy, dual antiplat, HTN control etc; small vessel single antiplatelet, cardioembolic (AF etc)
anticoag
hemicraniectomy if MCA territory, NIHSS >15, dec consciousness, infarct of >/=50% MCA
patho of infarct, cerebral amyloid angiopathy vshypertension vs global hypoperfusion, embolic shower, vasculitis stroke; ?carotid dissection when; TIA mx; CAA or hypertens bleed more likely to recur? 6 other causes of intraceb bleeds)
initially hypereosinophil, shrunken, vacuoles; then 5-10 days after neuts, macros, gliosis, liquefactive necrosis (dark macroscopically), months-years get glionic cavity (hole where tissue gone), haemosiderin staining (orange/brown over cavity); if dark with structure still its subacute, chronic once atrophied cavity etc; in acute may also see oedema, evidence of herniation/coning
watershed infarcts most likely global hypoperfusion ie cardiac arrest (oft bilat); lobar with BG sparing may be cerebral amyloid angiopathy;
hypertensive/arteriosclerosis will show ganglionic but not cerebral; severe vasculitis may look similar (if eg they have autoimmune disease)
myxoma and IE can cause too! (may get TACS/PACS as thromboembolic)
embolic shower if many small infarcts scattered throughout, consider embolic causes (inc fat embolism if after major trauma)
ipsi stroke + contra partial horners = ?carotid dissection (esp if younger); headache in 2/3 of cases
TIA: 300mg aspirin asap, TIA clinic within 24hrs, imaging not if resolved, consider MRI after TIA clinic unless think other diagnosis (eg
on anticoagulant); after confirmed TIA secondary prevention (as for after stroke eg thromboembolic, small or large vessel)
cerebral amyloid angiopathy underlies 10-20% of intracerebral bleeds (esp lobar bleeds), inc’d risk of recurrence as opposed to hypertension
related ICB
other causes eg aneurysm, AVM, tumour, alcohol/cocaine, coagulopathies (DIC, leukaemia (thrombocytopenia), thrombophilia
syndromes
stroke scores - rosier, NIHSS, MRS
all on MDCalc
rosier - recognising stroke vs stroke mimics, primarily for use in ED; score >0 means stroke possible
NIHSS - stroke severity, needs modifying if eg prior neurology (NIHSS website can help with this), assesses various modalities; levels of stroke severity on the NIHSS are categorised as: 0: no stroke * 1–4: minor stroke * 5–15: moderate stroke * 16–20: moderate/severe stroke * 21–42: severe stroke.
MRS - modified rankin scale, measures the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability; it is compared over time to check for recovery and degree of continued disability; is a common standard for assessing functional outcomes; correlates with physiological indicators such as stroke type, lesion size and neurological impairment
paediatric stroke
Use the FAST (‘Face, Arms, Speech Time’) criteria to determine stroke in children and
young people, but do not rule out stroke in the absence of FAST signs.
Do not apply the Recognition of Stroke in the Emergency Room (ROSIER) scale for
identifying stroke in children and young people.
Undertake urgent brain imaging of children and young people presenting with one or
more of the following symptoms:
- Acute focal neurological deficit
- Aphasia
- Reduced level of consciousness (age-appropriate Glasgow Coma Scale (GCS) less
than 15 or AVPU (‘Alert, Voice, Pain, Unresponsive’) less than A) at presentation
Consider urgent brain imaging for children and young people presenting with the
following symptoms which may be indicative of stroke:
- New onset focal seizures
- New onset severe headache
- Altered mental status including transient loss of consciousness or behavioural
changes
- New onset ataxia, vertigo or dizziness
- Sudden onset of neck pain or neck stiffness
- Witnessed acute focal neurological deficit which has since resolved
Ensure that a cranial computerised tomography (CT) scan is performed within one hour of arrival at hospital in every child with a suspected stroke. This should include:
- computerised tomography angiography (CTA) (covering aortic arch to vertex), if
the CT scan does not show haemorrhage OR
- CTA limited to intracranial vascular imaging, if haemorrhagic stroke (HS) is demonstrated.
Initial scan images should be reviewed on acquisition and if necessary transferred
immediately to the regional paediatric neuroscience centre for review.
Provide MRI within 24 hours if initial CT is negative and stroke is still suspected
Use the PedNIHSS and age-appropriate GCS or AVPU to assess the child’s neurological
status and conscious level respectively.
Withhold oral feeding (eating and drinking) until the swallow safety has been established.
Maintain normal fluid, glucose and electrolyte balance.
Target oxygen saturations above 92%.
Treat hypotension.
Consider the cause and necessity of treating hypertension in HS on a case-by-case basis.
Children and young people with AIS should only receive blood pressure-lowering
treatment in the following circumstances:
- in patients who are otherwise eligible for intravenous (IV) thrombolysis but in
whom systolic blood pressure exceeds 95th percentile for age by more than 15%
- hypertensive encephalopathy
- end organ damage or dysfunction, e.g. cardiac or renal failure
Provide clinical assessment of a child’s body structures and functions and activities, by
members of the relevant hospital multidisciplinary team (MDT) (including occupational therapists, physiotherapists, speech and language therapists), as soon as possible during hospital admission (within 72 hours)
risk factors for arterial ischaemic stroke:
focal cerebral arteriopathy of childhood
moyamoya
arterial dissection
central nervous system (CNS) vasculitis
congenital cardiac disease
additional risk factors in children and young people with cardiac disease: Right to Left shunt, increased Lipoprotein(a) (Lp(a)), anticardiolipin antibody (ACLA),
combined prothrombotic disorders
sickle cell disease
genetic: Factor V Leiden (FVL), PT20210, MTHFR c677T,
protein C deficiency, increased lipoprotein(a) (Lp(a)), high homocystinuria (HCY)
acquired: antiphospholipid syndrome
- trisomy 21
- neurofibromatosis
- malignancy and long-term effects of treatment for malignancy (especially cranial
radiotherapy)
- auto-immune diseases, e.g. systemic lupus erythematosus
- illicit drugs and other recreational drugs (e.g. cocaine)
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- haematological investigations, including full blood count, iron status (e.g. iron,
ferritin, total iron binding capacity) and haemoglobinopathy screen
- biochemistry tests, including total plasma homocysteine, alpha galactosidase,
fasting blood sugar, fasting cholesterol, and Lipoprotein(a)
- lupus anticoagulant and ACLA, and discuss beta 2GP1 testing with haematology if
necessary
- cardiac evaluation: electrocardiogram (ECG), echocardiogram (to identify structural lesions and R to L shunts)
- cerebrovascular imaging from the aortic arch to vertex, with CTA or MRA at the time of CT or MRI respectively
- transcranial Doppler in patients with SCD
Clinically evaluate all patients for history of prior infection (especially Varicella zoster virus
(VZV)), immunisation, dysmorphic features, neurocutaneous stigmata, autoimmune
disease and evidence of vascular disease in other organ systems
Prescribe and deliver 5mg/kg of aspirin up to a maximum of 300mg within 24 hours of diagnosis of AIS in the absence of contraindications (e.g. parenchymal haemorrhage).
After 14 days reduce dose of aspirin to 1mg/kg to a max of 75mg.
Delay administering aspirin for 24 hours in patients where thrombolysis has been given
Aspirin should not be routinely given to children and young people with SCD presenting with AIS.
In children and young people with cardiac disease presenting with AIS, make a
multidisciplinary decision (including haematologists, paediatric neurologists and
cardiologists) regarding the optimal antithrombotic therapy
off label use of tissue plasminogen activator (tPA) could be considered in children
presenting with AIS who are more than eight years of age and may be considered for
children aged between two and eight years of age on a case-by-case basis when the
following criteria have been met:
- AIS has occurred as defined by:
o an acute focal neurological deficit consistent with arterial ischaemia AND
o Paediatric National Institute of Health Stroke Scale (PedNIHSS) more than or equal to 4 and less than or equal to 24 AND
o treatment can be administered within 4.5 hours of known onset of symptoms
AND intracranial haemorrhage has been excluded:
o CT and CTA demonstrates normal brain parenchyma or minimal early ischaemic change AND CTA demonstrates partial or complete occlusion of the intracranial artery
corresponding to clinical or radiological deficit
OR MRI and MRA showing evidence of acute ischaemia on diffusion weighted imaging plus partial or complete occlusion of the intracranial artery corresponding to clinical or radiological deficit
PROVIDING that there are no contraindications
in sickle cell disease:
Treat children and young people with SCD and acute neurological signs or symptoms
urgently with a blood transfusion, to reduce the HbS to less than 30%, and increase the
haemoglobin concentration to more than 100–110g/l. This will usually require exchange
transfusion.
Provide a small top up transfusion to bring Hb to 100g/l to improve cerebral oxygenation
if the start of the exchange is likely to be delayed by more than six hours
Prioritise this over thrombolysis
Discuss any impairment of conscious level or decline in PedNIHSS in a child with AIS with
a neurosurgical team.
Consider decompressive hemicraniectomy in children and young people with MCA
infarction under the following circumstances:
- neurological deficit indicates infarction in the MCA territory
- surgical treatment can be given less than or equal to 48 hours after the onset of stroke
- a decrease in the level of consciousness to a score of 1 or more on item 1a of the PedNIHSS
- PedNIHSS score of more than 15
- while not validated in children, signs on CT of an infarct of at least 50% of the
MCA territory with or without additional infarction in the territory of the anterior
or posterior cerebral artery on the same side
Patients with acute AIS causing a disabling neurological deficit (NIHSS score of 6 or more) may be considered for intra-arterial clot extraction with prior IV thrombolysis, unless
contraindicated, beyond an onset-to-arterial puncture time of five hours if:
- PedNIHSS score is more than six
- a favourable profile on salvageable brain tissue imaging has been proven, in which
case treatment up to 12 hours after onset may be appropriate
paeds stroke - haemorrhagic and venous
haemorrhagic risk factors:
AVM
cavernous malformations, especially Zabramski type 1 & 2 cerebral arterial aneurysms moyamoya
severe platelet disorders/low platelet count all severe inherited bleeding disorders anticoagulation severe vitamin K deficiency
amphetamines cocaine
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Haematological investigations: coagulation screen including activated partial thromboplastin time (aPTT),
prothrombin time (PT), fibrinogen (ideally by Clauss method) (taken by a
free-flowing venous sample), full blood count (FBC), haemoglobinopathy
screen.
discuss any abnormality of these haematological tests with a paediatric
haematologist so that they can advise on further testing including specific
clotting factor assays.
establish whether the parents are consanguineous as there are some rare
severe recessive bleeding disorders that cannot be ruled out with a normal
blood count and coagulation screen.
- Imaging investigations: discuss the child’s case in a neurovascular MDT to plan further
investigations to identify/exclude underlying vascular malformation and to
plan any interventional treatment; such investigations may include noninvasive angiography such as CTA or MRA
Discuss coagulation management options with the haematology team if the child/young
person has a known underlying inherited or acquired bleeding disorder; treat the child
without delay with the relevant coagulation factor replacement
Transfer children and young people with an underlying inherited bleeding disorder (such
as severe haemophilia) who have an intracerebral bleed in HS to a Paediatric Haemophilia
Comprehensive Care Centre (CCC) as soon as possible.
Consider Nimodipine (mean starting dose 1mg/kg every four hours) to prevent the effects of vasospasm in children and young people with subarachnoid haemorrhage
acute hemiplegia (5 causes (10 (inc 3 risk factors for one);4;1;4 inc commonest cause in kids;3) 8ix)
stroke ofc - thromboembolic, hypertensive, arteritis, atheromatous, traumatic; also venous thrombosis (dehydrated, polycythaemia, protein C def), SLE, PAN, sickle cell, moya moya
vascular malformation/bleed such as AVM, aneurysm, angioma, bleeding disorder - look for eg HTN
migraine - may have associated sensory changes, dysarthria/dysphasia, oft FH, key is evolving over minutes
SOL - SDH, EDH (trauma commonest cause of hemiplegia in children and dont forget NAI), abscess (inc spread from OM), tumour (sudden bleed into one may give acute hemiplegia)
cerebral disease (meningitis which may be sec to vein/artery thrombosis), encephalitis, post-ictal state
do urgent CT head and then consider FBC, clotting, blood cultures, EEG, CT angiography/CT perfusion, get BM, autoimmune screen - and put out a stroke call
neurocritical care (3 components in skull and icp link, sign of herniation, 3 things to monitor and how often, icp and cpp targets, 8 options to manage raised icp)
blood, csf, brain tissue are 3 components in skull; as volume of one increases others must decrease as cranial comp is rigid, once this ability is exhauted icp rapidly rises
autoreg maintains cbf over variety of MAP, but these mechanisms lost after injury and cbf then determined directly by cerebral perf pressure which is map - icp
icp raises, brain herniates and compresses CNIII giving unilateral fixed/sluggish and dilated pupil; CT needed and immediate lowering of icp, or surgery
GCS and pupil size/reactivity should be monitored every hour, if pt sedated then invasive icp monitoring may be needed
keep icp under 20mmHg and CPP between ~50mmHg with vasopressors and fluid as well as supportive care (maintain airway, normocarbia, VTE prophy, protect against infections)
high icp can be managed by raising head of bed to 30deg, controlling any seizures, sedation, drainage of csf, osmotherapy with mannitol/hypernat, if refractory then optimise hyperventilation, hypothermia, decompressive craniectomy are options
central fever (how common, 2 reasons why and 3 areas damage might be, 6 features, 13 causes of extreme hyperpyrexia)
seen in almost 70% of neurocritically ill patients
inflammatory markers causing fever may be triggered by extreme physiologic stress in acute neurologic injury; brain injury may also lead to the disruption of the mesencephalic-diencephalic mechanisms responsible for the inhibition of thermogenesis: damage may be in hypothalamus, midbrain, or pons
diagnosis of exclusion. CF occurs early, typically within 72 hours of admission after acute brain injury. All the cultures are negative and the chest radiograph is normal. Fever is disproportionately high and persistent without diurnal variation; tends to be sustained and resistant to antipyretics; also tend to see relative bradycardia
note that extreme hyperpyrexia, defined as fever ≥41.1℃ (106°F), is usually noninfectious. Examples include CF, drug fever, malignant hyperthermia, transfusion reactions, adrenal insufficiency, thyroid storm, neuroleptic malignant syndrome, heat stroke, acalculous cholecystitis, mesenteric ischemia, acute pancreatitis, deep vein thrombosis, and pulmonary embolism
indications for urgent CT after head injury (7:4:8:6 + monitoring)
within 1 hr if any of:
-a GCS score of 12 or less on initial assessment in the emergency department
-a GCS score of less than 15 at 2 hours after the injury on assessment in the emergency department
-suspected open or depressed skull fracture
-any sign of basal skull fracture (haemotympanum, ‘panda’ eyes, cerebrospinal fluid leakage from the ear or nose, Battle’s sign)
-post-traumatic seizure
-focal neurological deficit
-more than 1 episode of vomiting
within 8 hrs if some loc or amnesia + one of:
->65yo
-bleeding/clotting disorder (inc anticoag)
-dangerous mechanism of injury (a pedestrian or cyclist struck by a motor vehicle, an occupant ejected from a motor vehicle or a fall from a height of more than 1 m or 5 stairs)
-more than 30 minutes’ retrograde amnesia of events immediately before the head injury.
if <16yo then within 1hr if:
-suspicion of non-accidental injury
-post-traumatic seizure
-on initial emergency department assessment, a GCS score of less than 14 or, for babies under 1 year, a GCS score (paediatric) of less than 15
-at 2 hours after the injury, a GCS score of less than 15
-suspected open or depressed skull fracture, or tense fontanelle
-any sign of basal skull fracture (haemotympanum, ‘panda’ eyes, cerebrospinal fluid leakage from the ear or nose, Battle’s sign)
-focal neurological deficit
-for babies under 1 year, a bruise, swelling or laceration of more than 5 cm on the head.
or if more than 1 of:
-loss of consciousness lasting more than 5 minutes (witnessed)
-abnormal drowsiness
-3 or more discrete episodes of vomiting
-dangerous mechanism of injury (high-speed road traffic accident as a pedestrian, cyclist or vehicle occupant, fall from a height of more than 3 m, high-speed injury from a projectile or other object)
-amnesia (anterograde or retrograde) lasting more than 5 minutes (it will not be possible to assess amnesia in children who are preverbal and is unlikely to be possible in children under 5)
-any current bleeding or clotting disorder.
if only one of above then observe for 4 hrs and do CT if GCS falls, vomits again, or has more abnormal drowsiness
raised ICP 7 mx, 2 structures at risk in base of skull fractures and SAH 6 mx; 1/3 of pt dev delayed what + how that presents x2; if BP raised what agent to use, why not alternative, what is target; reversal agents (2 for warfarin, 1 for doac, 1 for antiplatelet and follow up); VTE prophylaxis things x2
Raised ICP: raise head, O2, hypernat, hypervent to drive down co2; inotropes/fluids, hypothermia, decompressive craniectomy
base of skull fracture: ICA and CNVII at risk
SAH: treat hydroceph or haematoma mass effect; coil or clip (former through vessels, latter open head), bed rest, analgesia, prophylactic nimodipine 60mg 4-hrly and keep well hydrated
Around a third of patients develop symptomatic vasospasm (SAH big risk factor hence nimodipine) with feature of delayed cerebral ischaemia:
– Reduction in GCS
– New focal neurological deficit
If BP raised use labetalol to keep sys <160mmHg, not GTN as can cause cerebral vasodilation -> worsen ICP
For bleeds, inc spontaneous intracerebral bleeds, need to reverse anticoag: vit K for warfrain (but as acts via synthesis takes up to 24hrs to work so also give beriplex, give antidotes to DOAC if available and 1 dose of desmopressin for antiplatelets (may need to fluid restrict afterwards for 24hrs)); IPC for VTE prophy, aim for D5 LMWH switch
shaken baby syndrome (triad, controversy why)
triad of retinal haemorrhages, subdural haematoma, and encephalopathy. This is caused by the intentional shaking of a child (0-5 years old). The diagnosis of shaken baby syndrome has often made the headlines due to the controversy amongst physicians as to whether the mechanism of injury is definitely an intentional shaking of a child. This has often resulted in difficulty for the courts to convict suspects
neonatal head swellings - 4 types, what they are and telling them apart; for first 2 how long they last, when they appear, and relation to periosteum; space 3rd occurs in and how it appears
A cephalhaematoma can often be confused with a caput succedaneum. Distinguishing features of a cephalhaematoma are that they usually develop after birth and do not cross the suture lines of the skull as the blood is confined between the skull and periosteum. It resolves within a few months of birth.
Caput succedaneum is an extraperiosteal collection of blood therefore can cross over the suture lines and can be present at birth. It resolves within a few days of birth.
Subaponeurotic haemorrhages are a serious condition caused by bleeding in the potential space between the periosteum and subgaleal aponeurosis. Typically there is a boggy swelling that grows insidiously and is not confined to the skull sutures. The neonate may present with haemorrhagic shock.
Chignon’s are birth traumas that occur after use of a ventouse device during delivery
additional CT head indications for kids
As adults + Loss of consciousness lasting more than 5 minutes (witnessed)
Amnesia (antegrade or retrograde) lasting more than 5 minutes
Clinical suspicion of non-accidental injury
If under 1 year, presence of bruise, swelling or laceration of more than 5 cm on the head
Dangerous mechanism of injury (high-speed road traffic accident either as pedestrian, cyclist or vehicle occupant, fall from a height of greater than 3 m, high-speed injury from a projectile or an object)
head injury (12 causes of coma, 6 signs of skull fracture (inc 1 suggests mid fossa and 1 suggests post fossa), risk of open skull fractures, 5 reasons for secondary injury after head trauma, where do coup and contre-coup injuries tend to fall; CPP and cushing reflex (inc when it might be masked and how quickly it can progress), 3 things that can persist for months after even minor head injury), prognosis for amnesia of diff lengths
open/penetrating or closed/concussional
causes of coma: head injury, CVA, SAH, epilepsy, cerebral tumour/abscess or meningitis; alcohol, CO, barbiturates/aspirin/opiates; hyper/hypoglyc; uraemia; encephalopathy (hepatic, hypertensive, metabolic disease); toxaemia
signs of skull fractures: nasal bleeding, orbital haematoma, CSF rhinorrhoea, CN injuries, if mid fossa then maybe bleeding from ear or csf otorrhoea; bruising behind ear/suboccipital region (Battle’s sign) suggests post fossa; open fractures inc basal skull fractures have risk of meningitis
brain injury may be traumatic or secondary (from hypoxia, hypercapnia, hypotension, intracranial bleeding, or infection); coup and contre-coup injuries w/ coup often front or temp lobes and contre-coup occipital, be aware of both
cerebral perfusion pressure = MAP - ICP so raised ICP will dec perfusion and this leads to the Cushing reflex: irreg breathing, bradycardia and (sys) hypertension in head trauma cases (unless trauma elsewhere causing an overriding hypotension); note this reflex may progress to death within minutes, so brady + hyper = manage quickly
persistent headaches, dizziness, concentration problems may be problem for months after even a minor head injury, will go with time
amnesia even of a few hours can carry good prognosis, if days/weeks then full recovery less likely
management of head injury - 5 things to find in history, examination inc what to def make note of and what to assume, how pupil response will evolve as pressure builds and what else might cause the same sign; why might they be pyrexic
history: mechanism of injury, condition of pt immediately afterwards (GCS, limb movements, pupils and vitals if poss); any change in condition since; how pt was before the injury inc were they drunk? diabetic? do they have false eye or chronic glaucoma (explaining abnormal pupil responses)
always assume cervical spine injury and immobilise until CT or good x-ray proves otherwise, and do ABCDE and a full secondary survey; note GCS
raising pressure from haematoma or oedema on one side will pressure CNIII on that side causing ipsi pupil to dilate and lose light reactivity but consensual constriction intact until compression of the other CNIII by continuing inc in pressure; bilat fixed dilated pupils is thus a poor sign; local trauma from skull base fractures might sometimes produce the same thing; pupil dilation can thus be false localising sign
injury to brainstem can cause pyrexia >40deg as temp reg centre damaged
meningitis - inflammation due to broadly what 3 things; 5 common bacti, 5 common viruses, 1 fungal and 1 parasitic cause, 9 sx/signs, 2 ways babies may look and sign on examination, 4 things to examine, 2 key meningitis signs, 4 base blood bottles to send, one to consider, one imaging, how bacti/virus/TB LP looks (appearance, pressure, wcc, protein, glucose)
inflamed meninges secondary to infection, autoimmune antibodies or paraneoplastic processes
Infections may be secondary to: Bacteria e.g. Neisseria meningitides (‘meningococcal’ = most common), Streptococcus pneumoniae (‘pneumococcal’ = 2nd), Haemophilus influenza b, Listeria monocytogenes, Group B streptococcus (high risk in newborns)
Viruses e.g. Enteroviruses (Echo/Coxsackie), Herpes Simplex Virus (2>1), VZV, HIV; Fungal causes e.g. Cryptococcus; Parasites e.g. Amoeba
Typically patients present with a headache
◦ Fever is usually present
◦ +/- Photophobia
◦ +/- Confusion/altered mental state
◦ +/- Vomiting
◦ +/- Neck pain or stiffness
◦ Altered neurology may have led to their presentation e.g. altered speech/weakness on one side/reduced
hearing
◦ If a non-blanching rash is present this is severe – it indicates septicaemia; seizures also late feature
In children they may not be able to describe the above, but parents may describe them as being ‘’irritable’’
or ‘’drowsy’’. On examination, if <6 months, they may have a bulging fontanelle
on examination:
◦ AMTS + GCS
◦ Neurological examination – any focal neurological changes (loss of
power/coordination/speech/sensation/hyperreflexia)?
◦ Check fundi for any signs of increased intracranial pressure (papilloedema)
◦ Other systems – look for possible causes of the meningitis and look for any signs of bacteraemia/sepsis e.g. non-blanching (petechial) rash – can be elicited by pressing on the rash and seeing if it blanches or not (parents may have done the ’tumbler test’)
◦ Key signs of meningism are:
◦ Brudzinski’s sign = forced flexion of the neck causes reflex flexion of the hips, if meningism is present
◦ Kernig’s sign = with the knees and hips flexed at 90 degrees, subsequent extension of the knees causes resistance, due to pain in the back/neck
bloods (4 bottles: FBC, culture, lab glucose for comparison to csf, baseline biochem), pcr/viral cultures, CT head
bacterial: turbid/cloudy csf with high opening pressure, wcc, neutrophils esp, protein, and low glucose (<0.4 ratio csf:blood)
viral: clear csf with normal opening pressure, wcc <1000 with more lymphocytes, normal/high protein, normal glucose
TB: very thick/turbid with normal/high opening pressure, more lymphocytes than neuts, high protein, low/very low glucose
meningitis treatment (bacti - inc initial prim care mx, pen allergic alternative, viral/TB/fungi, prophylaxis)
urgent transfer to hospital, in community give benzylpenicillin IM:
◦ <1 year of age — 300 mg
◦ Children 1–9 years of age — 600 mg
◦ Adults and children 10 years of age or older — 1200 mg
in hospital: Ceftriaxone IV + Dexamethasone (to reduce inflammation), then guided by cultures
◦ If Penicillin allergic – check the severity of the reaction – if severe (e.g. anaphylaxis) = Chloramphenicol (N.B. supply issues)
◦ If <3 month or ≥60 years old or immunocompromised/pregnant or Listeria suspected = add in Amoxicillin cover too
◦ If possibly viral in nature/signs of encephalitis = Aciclovir is added in
◦ Close contacts may need prophylactic antibiotic treatment cover – typically this is with either: rifampicin or ciproflox
If a more unusual cause:
◦ TB = needs TB meds = ‘RIPE’ quadruple therapy for 2 months (Rifampicin, Isoniazid, Pyrazinamide and
Ethambutol) followed by Rifampicin and Isoniazid for a further 10 months (12 months total treatment)
◦ Cryptococcus = Amphotericin B and Flucytosine (IV) and then oral Fluconazole
also: If you’re treating empirically for suspected bacterial meningitis (either contracted abroad or from a patient who has spent extended duration abroad in recent history or have had prolonged or multiple exposure to antibiotics (within the past 3 months)) and you haven’t yet identified the causative organism, you need to take into account the possibility of penicillin-resistant Streptococcus pneumonia and add vancomycin. this is because because in the UK Pneumococcal penicillin resistant is exceedingly rare, whereas around many other parts of the world it is common enough that you can’t afford to not cover for it in the case of meningitis. This is largely driven by the over-use of penicillin-based antibiotics (both by prescribers and over-the-counter). once cultures and sensitivities are back you can stop the vanc
carcinomatous meningitis - what are leptomeninges, which cancer (inc commonest source), 6 ways to present, 4 CSF findings (and major ddx), 3 MRI findings, 2 mx and contra to one option
dissemination of malignant cells from the primary tumor sites to leptomeningeal (ie arachnoid/pia) layers of the CNS. Can occur in the advanced stage of any cancer, solid as well as hematological malignancies (5-8% solid, 5-15% haem, and B-cell lymphoma commonest source). It is a rare complication with a dismal prognosis
may present with raised ICP sec to obstructing or non-obstructive hydrocephalus (depending on where block is), meningeal irritation causing a meningitis, metabolic depression of cortex due to glucose/O2 being used by cancer cells giving encephalopathy, seizures depending on site involved, often temporal lobe seizures giving deja vu, stereotypical movements, euphoria, hallucinations, and amnesia
posterior fossa involvement can give cerebellar signs and CN involvement
if spinal cord involved can give segmental numbness, dysesthesia, pain, and lower motor neuron pattern limb weakness, or even cauda equina
CSF: pleocytosis (esp lymphocytes), high protein, low glucose, positive cytology (differential may be eg chronic fungal infection)
MRI: findings may include hydrocephalus and leptomeningeal enhancement of the brain in the T1 weighted image with contrast. T2/FLAIR hyperintensities may be seen in the subarachnoid space. The cerebral convexities, cerebellar folia, basal cisterns, and ventricular ependymal regions are the common areas that display enhancement or nodular deposits in CM. linear and nodular leptomeningeal enhancements may occur along the nerve roots in cord involvement
Appearance similar to infectious or inflam meningitis, hence need for cytology
depending on performance status, palliative care may be recommended; however, if for active rx then intrathecal chemo (+/- radio and systemic chemo); note intrathecal chemo cannot be done if VP shunt in situ as toxic drugs then straight into other part of body
encephalitis (onset time, what to exclude in history, 10 sx/signs (inc one more common in meningoencep, one in autoimmune), 6 things to examine, 8ix, most common viral cause, 3 bacti causes, 2 parasitic causes, 2 autoimmune causes, 3 mx approaches
The patient may either have self-presented or may have been brought in by a concerned relative, partner or friend
◦ May have had an onset over a few days – weeks, can be faster
◦ Try to exclude drug use in history
key poss features:
◦ Headache/prodromal symptoms (e.g. GI upset)
◦ Fever
◦ Confusion
◦ Drowsiness
◦ Altered behaviour
◦ Psychosis/hearing voices
◦ +/- Vomiting
◦ +/- Photophobia
◦ Stiffness in the neck/meningism indicates that this may be a meningoencephalitis
◦ Autonomic dysfunction may be present (more commonly in autoimmune cases)
◦ Seizures may occur
on examination:
◦ They may have an altered mental state
(labile emotions/psychosis may be present)
◦ GCS
◦ Full neurological examination
◦ Any meningeal irritation present
(Brudzinski’s and Kernig’s tests)?
◦ Check for any signs of a seizure/head injury that may otherwise explain their behaviour
◦ Full examination to exclude other infections as a possible cause for fevers/confusion etc.
bloods and cultures (consider toxicology screen of blood and urine to rule out drugs causing altered mental state)
CT head; LP (if no virus can check for anti-NMDAr antibodies); EEG; MRI
key causes:
◦ Viral = most commonly HSV
◦ Bacterial = may a complication of meningitis causes, Lyme disease, Syphilis etc
◦ Parasitic/protozoal = Toxoplasmosis, malaria etc
◦ Autoimmune = NMDA-receptor Abs, ADEM
treatments:
◦ Aciclovir if viral (cover with this until proven not viral)
◦ If autoimmune = may need steroids/IVIg/plasmapheresis
◦ If driven by a malignancy (e.g. ovarian teratoma (NMDAR), small cell lung cancer (Hu)) = remove the tumour
encephalitis (6 sx, what CT/MRI might show, what EEG might show, 3 other ix)
Meningitis triad
Reduced GCS + focal neurological deficits (ophthalmoplegia, dysphasia, hemiparesis)
Fever, vomiting, seizures
Diffuse oedema, esp in temporal lobes on CT/MRI
CSF microscopy, culture & biochem
PCR, Acute & convalescent serology
Slow-wave changes on EEG
autoimmune encephalitis - sx onset time and ddx if longer (what to ask family), 3 sx and how they may change, 3 broad Ab types, what first is normally linked to and relative rx responsiveness, 4 crtieria needed for diagnosis (and 2 ddx if unilat imaging), 5 additional tests after, how many are Ab negative, 10 abs to test for and which fluids to send
encephalitis caused by various different autoantibodies; classically presents with the subacute onset (<3mo -> if longer then this consider neurodegen disease, although some antibodies can give a longer course - ask careful history to family for subtle changes) of short-term memory deficits, seizures or psychiatric symptoms, these may be fluctuating ie sometimes normal and then odd behaviour
various types of autoimmune encephalitis antibodies can be categorized into three groups: intracellular paraneoplastic Ab, cell-surface or synaptic Ab, and with Ab of unclear significance. Intracellular paraneoplastic antibody is frequently associated with systemic tumors (in more than 90% of cases). These patients are less responsive to immunotherapy because the antibody causes neuronal damage. Cell-surface or synaptic Ab is variably associated with systemic tumors, and patients with these Ab are more responsive to immunotherapy.
For the diagnosis of definite autoimmune limbic encephalitis, all four of the following criteria have to be met: subacute onset, bilateral brain abnormalities on T2-weighted fluid-attenuated inversion recovery (FLAIR) MRI highly restricted to the medial temporal lobes (may see unilateral high signal in some cases but consider stroke and tumour), cerebrospinal fluid (CSF) pleocytosis or EEG with epileptic or slow-wave activity on the temporal lobe, and reasonable exclusion of alternative causes. Although detection of auto-Abs is the best diagnostic method for autoimmune encephalitis, there are many Ab-negative probable autoimmune encephalitis cases. Then depending on type consider workup for systemic tumours -> SCLC, ovary, breast are commonest (CT CAP +/- pelvis MRI and USS breast/testes + relevant bloods should pick up most, consider CT PET if >65yo)
Although about half of all autoimmune encephalitis series are Ab-negative cases, the detection of auto-Abs is a confirmatory diagnostic test, panel includes anti-NMDAR, AMPA1, AMPA2, LGI1, CASPR2, DPPX, GABAR B1; send blood and CSF as some will show up better/only in one or the other; also send the intracellular Abs Hu, Ma2 and GAD
Naegleria fowleri - what it is, what it causes, how it infects inc incubation period, 2 things leading to destruction of brain, how does csf look, why culture can be negative, 3 ways to pick it up, main mx and what can buy time
amoeba found in freshwater that is usually contaminated with soil
infection with N. fowleri leads to amebic meningoencephalitis. Infection occurs when warm freshwater enters nasal passages and makes its way through the cribriform plate into the central nervous system. The incubation period can last anywhere from 1-14 days
N. fowleri elicits a significant innate immune response; combination of the intense immune response and virulence of this organism lead to the significant destruction of brain parenchymal tissue
should be suspected in patients with meningoencephalitis or meningitis when a recent history of freshwater exposure is present. Cerebrospinal fluid (CSF) analysis can be similar to that in bacterial meningitis with glucose being low to normal, elevated proteins, and polymorphonuclear cells. CSF pressures are elevated
Identification of N. fowleri can be missed on gram stains and cultures as the fixation procedure destroys them.
Visualization can be achieved on wet mounts and stains like H&E; Antigen detection by immunohistochemical staining techniques can be performed on CSF or tissue sample, along with PCR and cultures
v high doses of amphotericin B is main mx; therapeutic cooling has been used to buy time for mx to work
rasmussens encephalitis (what it is, who it is commonest in, what cell type involved, 5 features of first phase, second phase inc when, what EEG and MRI will show, definitive way to dx, 4 mx in first phase and mx in second inc what often ineffective and downsides x2 of main mx strategy (and when you’d possibly avoid this and why)
very rare, chronic inflammatory neurological disease that usually affects only one hemisphere. It most often occurs in children under the age of 10 but can also affect adolescents and adults
chronic inflammation of the brain, with infiltration of T lymphocytes
Frequent and severe seizures (often focal but may be mixed or generalised)
Encephalitis
Progressive loss of neurological functions including motor skills, speech, and eventual hemiparesis +/- hemianopia
Children with RE frequently enter a second phase of permanent, but stable, neurological deficits after eight to 12 months
dx can be made clinically, EEG will usually show the electrical features of epilepsy and slowing of brain activity in the affected hemisphere, and MRI brain scans will show gradual shrinkage of the affected hemisphere with signs of inflammation; brain biopsy definitive but not always needed
steroids, IVIg, plasmapharesis, tacrolimus; in chronic phase try to control remaining sx; standard AEDS often not effective, so surgery to disconnect affected half which can give further weakness and hemianopsia (but in v young children plastic brain can take over many or all lost features); may avoid if left side affacted as would lose speech centre
meningitis rash, LP for kids when (x3), dex when and when not
non-blanching rash indicates the infection has caused disseminated intravascular coagulopathy (DIC)
NICE recommend lumbar puncture as part of the investigations for all children:
Under 1 months presenting with fever
1 – 3 months with fever and are unwell
Under 1 years with unexplained fever
Steroids are also used in bacterial meningitis to reduce the frequency and severity of hearing loss and neurological damage. Dexamethasone is given 4 times daily for 4 days to children over 3 months if the lumbar puncture is suggestive of bacterial meningitis - not if signs of men septicaemia
pitu apoplexy (what it is most commonly into, 7 sx/signs + 3 from a complication, 5 ix, mx x3
pitu apoplexy: usually into pitu adenoma which usually hasnt been diagnosed
sudden headache +/- worsening visual field defect or double vision, then acute panhypopitu, notably adrenal crisis; oft nausea and vomiting, sometimes meningism, may have dilated pupils due to CNIII compression
adrenal crisis: hypotens, hypogly, abdo pain
generally idiopathic, though low incidence
CTH, MRI, LP (rule out SAH/mening), basic bloods inc pitu tests, visual field testing
treat adrenal crisis with hydrocortisone, refer to neurosurg (+ urgent ophtho review to assess visual fields)
*if seeing a sag MRI in exam quite likely due to pitu adenoma
menigococcal disease in children
fever, n&V, lethargy, irritability, toxic appearance, anorexia, myalgia, arthralgia, headache, difficulty breathing; sometimes chills, sore throat, abdo pain, diarrhoea
specifics: non blanching rash, stiff neck, crt up, cold extremities, shock, leg pain, bulging fontanelle, photophobia, kernigs sign pos (cant extend knee when hip flexed), seizures, focal neuro deficit
children oft present with the non specific signs eg look like urti, fever, vomiting, irritability; may have seizures; so take into account speed of progression, parental concern, overall severity, and transfer to sec care if any doubt
rash may be petechial or purpural: examine whole body, inc palms/soles/conjunctiva/palate (esp if darker skin); disease can be advanced before rash appears; rapidly evolving rash risk factor for fatal outcome; risk of meningococcal disease high is rash spreading, evolves to purpura, signs of meningitis or shock
consider other causes of petechiae, purpura; sah; aseptc, viral, fungal, drug induced meningitis; encephalitis; sepsis
if septic or rash present: emergency admission, single iv/im benzypenicillin 300mg if <1yo, 600 if 1-9, 1200 if >9yo, withhold this if history of penicillin allergy
non nonblanching rash: admit but no antibiotic unless hospital admission going to be delayed; if cant exclude them having this but no spec signs, still admit to sec care for full investigation
bact men is notifiable disease, hpu will give advice what to do with contacts: proph if living together for 7days+, or exposed to large dose of resp droplets around time of admission
4-6wk review after hospital discharge with paediatrician
meningitis mx kids (abx choice <3mo inc why different, older, steroids when, 3 other things)
Antibiotics
< 3 months: IV amoxicillin (or ampicillin) + IV cefotaxime - note no ceftriaxone if <3mo as it displaces bilirubin from albumin binding sites, resulting in higher levels of bilirubin that accumulate in the tissues
> 3 months: IV cefotaxime (or ceftriaxone)
- Steroids
NICE advise against giving corticosteroids in children younger than 3 months
dexamethsone should be considered if the lumbar puncture reveals any of the following:
frankly purulent CSF
CSF white blood cell count greater than 1000/microlitre
raised CSF white blood cell count with protein concentration greater than 1 g/litre
bacteria on Gram stain - Fluids
treat any shock, e.g. with colloid - Cerebral monitoring
mechanical ventilation if respiratory impairment - Public health notification and antibiotic prophylaxis of contacts
ciprofloxacin is now preferred over rifampicin
meningeal irritation signs and exam (inc how to properly test for neck stiffness and how to elicit Kernigs sign)
Meningism (inflammation or irritation of the meninges) can lead to increased resistance to passive flexion of the neck (neck stiffness) or the extended leg (Kernig’s sign). Patients may lie with flexed hips to ease their symptoms. Meningism suggests infection (meningitis) or blood within the subarachnoid space (subarachnoid haemorrhage
absence of all three signs of fever, neck stiffness and altered mental state virtually eliminates the diagnosis of meningitis in immunocompetent individuals
put patient supine: Neck stiffness
* Place your hands on either side of the patient’s head, supporting the occiput.
* Flex the patient’s head gently until their chin touches their chest.
* Ask the patient to hold that position for 10 seconds. If neck stiffness is present, the neck cannot be passively flexed and you may feel spasm in the neck muscles.
* Flexion of the hips and knees in response to neck flexion is Brudzinski’s sign.
Kernig’s sign * Flex one of the patient’s legs to 90 degrees at both the hip and the knee, with your left hand placed over the medial hamstrings
Extend the knee while the hip is maintained in flexion. Look at the other leg for any reflex flexion. Kernig’s sign is positive when extension is resisted by spasm in the hamstrings. Kernig’s sign is absent with local causes of neck stiffness, such as cervical spine disease or raised intracranial pressure.
interpreting csf data (rbcs/wbds due to 3 broad things, how to tell using ratio based on blood; wcc, rbc and protein range in premie/neonate/infant/child inc what kind of wcc present, glucose compared to blood; polymorph/lymph/protein/glucose count in bacti vs partially treat infection vs TB vs viral; history and csf findings if cerebral abscess and what might have similar history (+how to tell from abscess in the LP), a cause of isolated csf lymphocytosis, how might herpes and mumps look in csf)
rbcs and wbcs can be due to bloody tap/ivh, or inflam; in blood white:red is 1:500/600, if white cells inc’d then suggests some inflam component
csf should always be clear; white cells 0-100 in premie, 0-15 in neonate, 0-10 in infant and 0-5 in child; low or no polymorphs (so wcc all lymphocytes); red cells 0-1000 in premie, 0-500 in neonate, absent in infant or older; protein 1-4 in premie, 0,3-2 in neonate, 0,2-1 in infant, 0.2-0.4 in child; glucose always 2/3 of blood
polymorphs up to 50,000 in bacti, 1000 if partially treated or TB, few in viral; lymphocytes few in bacti, up to 1000 in partially treated, viral, TB; protein raised in bacti and TB most, a little in others; TB glucose v low, bacti low, partially treated or viral normally normal
cerebral abscess can be sterile but may see protein and lymphocytes; this and TB both have long history of several weeks fever, headache, non-specific symptoms and both give sterile culture with raised protein, but TB will have low glucose
leukaemia can cause csf lymphocytosis (check blood film!)
herpes encephalitis oft haemorrhagic so bloodstained csf, glucose low in 20% of cases
mumps meningitis has low glucose
reasons for raised protein (7), oligoclonal bands (6) in CSF
protein: GBS, spinal block, meningitis, cerebral abscess, neurosyphilis, SDH, cerebral malignancy
oligoclonal bands: MS, sarcoidosis, SLE, SSPE, SAH, neurosyphillis
csf microbiology (3 likeliest bacti meningitis in neonates, 9 after neonatal period (inc which is likely if shunt in situ), which is most likely to cause neuro sequelae, which is most improved by dex)
in neonates: GBS, e coli, listeria
after neonatal: neisseria, strep pneum, staph aureus, epidermidis (esp if indwelling prosthesis like a shunt), HiB, pseudomonas, klebsiella, TB, salmonella
pneumococcalis most likely to cause neuro sequelae (but all can), HiB meningitis sequelae most reduced by dexamethasone
skull x rays (1:1:2:1:3:3:2)
look for fracture, intracranial calcification, enlarged/destroyed sella turcica (raised icp or tumour), craniosynostosis, punched out lesions (due to histiocytosis, leukaemia, neuroblastoma), wormian bones (clediocranial dysostosis, hypothyroidism, down syndrome), increased density (oestopetrosis, hair on end appearance of beta thal)
11 causes of intracranial calcification inc characteristic appearance of 4)
choroid plexus calcification
intracranial bleed
infection (toxoplasmosis causes diffuse [triad of hydroceph, bilat chorioretinitis, intracran calcification], CMV causes perivent, also TB menin, cerebral abscess, cysticercosis)
TS (perivent and subependymral esp around foramen of munro, may look like candle dripping into ventricles)
sturge-webe syndrome (tram line on plain x ray with linear parallel calcification commonest in parieto-occipital, usually not if <2yo)
hypo/hyperparathyroid
tumours (craniopharyngioma, astrocytoma + others)
SDH and EDH
4 features of raised ICP on SXR
copper beating of skull, widening of sutures, thinning of the vault, and erosion of clinoid processes/sella turcica
rough ED headache guide - 3 stage process, 7 red flags and non head ddx to consider, 4 things in history, 4 minimum exam things, 2 ix, 3 initial mx and 3 for next few days + 2 longer term; 2 things meaning LP not needed for SAH, alternative if can’t get LP (what it picks up)
- red flags?
- probably migraine, maybe tension, maybe cervicogenic, are you unable to convince yourself it’s these?
- if yes to above -> neuro r/v may be helpful, not necessarily same day
red flags: thunderclap (SAH, apoplexy), recurrent or progressive severe (CVST -> remember sertraline incs risk, HTN -> PRES type picture), altered mental status or fever (encephalitis, start aciclovir asap), visual changes or 6th nerve palsy (CVST, IIH, raised ICP), positional (CSF leak, consider SDH so scan), new neuro signs, pregnant (CVST)
also don’t forget to consider acute glaucoma
ask about FH, ask if catamenial, ask about opioid/triptan/analgesia use, ask about sleep hydration and caffeine + elicit drugs; ask about factors influencing migraine prophylaxis choice eg plans for pregnancy, ideas re: weight gain, do they have vasovagals, on other meds
examination: minimum limbs, eye movements, acuity + fundoscopy
ix: CT if red flag, CTV if think CVST
mx (assuming red flags ruled out ie treating as possible migraine) -> hydrate them well, couple of bags would be okay; triptan +/- NSAIDs (naproxen a good option or high dose aspirin 900mg if old enough) acutely, if nausea present or quite bad give metoclopramide too (helps as migraines reduce gastric motility, thus you need a prokinetic to improve gastric emptying and so absorption of your oral meds - it also has a role in reducing pain independent of this too; prochlorperazine is an alternative that may be more effective); then home with NSAIDs over next few days, tell them to rest and the lingering headache should resolve, and safety net; if can’t control in ED using above get neuro input; also d/c with plan for next one (eg NSAIDs, triptans, maybe antiemetic) and advise them to speak to GP re: prophylaxis
re: CTH, if within 6 hours of onset for SAH and read by neuroradiologist then >99% sensitivity, if negative then no need for LP; if either of above not true and neg then need delayed LP to rule out; alternative if can’t get LP is MRI (picks up haemosiderin from chronic or previous bleeds
child with stiff neck - be alert to what sign and 3dd for this; 8 other dd)
be alert to meningism (stiff neck, pos kernig + brudzinski) -> (meningitis, SAH, pitu apoplexy), tonsillitis (or other jaw or salivary gland infection), otitis media, upper lobe pneumonia, torticollis, JCA, dermatomyositis, neck lump, presentation of a neuromuscular disease
child presents with headache and vomiting, may have been seen previously and given antibiotics, normal glucose and protein in csf and mixed white cell pleocytosis - 3ddx
most likely partially treated meningitis but don’t forget viral meningitis or brain abscess; latex agglut studies can identify cell walls of killed bacti
raised icp in absence of mass (3 sx BIH, how and why ventricles and sulci look and implication for LP, cause x7 (and overall), main risk, mx x4)
may be benign intracranial hypertension, which presents with headache, vomiting, and poss diplopia (6th nerve palsy)
csf pressure distributed evenly meaning normal appearing ventricles and sulci (or often slit like but pressure still evenly distributed)
due to impaired absorption at the arachnoid villi; LP has low risk of coning as no pressure gradient
90% of time is idiopathic but also tetracyclnes, steroids, obesity, cushings, addisons, following acute OM
main danger is visual loss as blind spot enlarges
treat causes (eg weight loss), acetazolamide or csf drainage (though therapeutic tap not advised anymore as just accumulates again), shunt may be required
idiopathic intracranial hypertension (pseudotumor cerebri) - measure what first and cutoffs to exclude what; what else to confirm/assess (inc 6 things), then 3 further ix; 8 ddx to exclude, when to advise weight loss, initial mx if vision threatened/not threatened; 4 ways to mx headache and what may cause remission; acute headache if shunt present mx, if vision worsening and shunt present mx, acute headache if no shunt and no vision changes
first: Blood pressure must be measured to exclude malignant hypertension, as defined as a diastolic blood pressure greater than or equal to 120 mm Hg or systolic blood pressure greater than or equal to 180 mm Hg
patients should have papilloedema confirmed and an assessment made of the imminent risk to their visual function. The following should be recorded in the presence of papilloedema:
visual acuity
pupil examination
intraocular pressure (to exclude hypotony, a rare cause for disc swelling)
formal visual field test (perimetry)
dilated fundal examination to grade the severity of the papilloedema and exclude ocular causes for disc swelling.
Where possible, document the fundus picture with drawings and document key findings on the optic nerve head (hyperaemia, haemorrhages, cotton wool spots, obscuration of the vessels and so on). Photographs and/or optical coherence tomography (OCT) imaging are useful
then within 24 hours should have MRI head and venography (CT or MR)
then do LP and record opening pressure (>25)
need to also exclude other secondary causes of raised intracranial prssure: FBC (polycthemia or anaemia), CKD (U&Es), OSA (history/sats monitoring), sle (inflam markers), TFTs (high or low function), hypopara (vit D levels, bone profile, PTH, Mg), cushings addisons and adrenal insuff (U&Es and BM as first clue + history)
mx:
if BMI >30 weight management advice should def be given
if vision threatened then lumbar drain and refer to surgery (CSF diversion)
if vision not threatened consider acetazolamide - LP relief temporary as fluid replaced so serial LP not recommended
can manage headache short term with paracetamol/NSAIDs but medication overuse is a big problem
topiramate may have a role, and sometimes triptans and migraine prophylaxis - assessment by neurologist is helpful
long term weight loss >15% may cause remission
acute headache if have shunt: meningitis? LP and treat; no meningitis but vision worsening: shunt reviison; no vision threatened either, may be eg medication overuse, evaluate and treat but exclude genera ddx for acute headache
acetazolamide side effects
metabolic acidosis; nephrolithiasis; paraesthesia
increased urine output
leucopenia, thrombocytopenia, anaemia, tinnitus or reduced hearing, skin blistering, electrolyte abnorms giving cramps or dizziness
it is a sulfonamide and so can inhibit CYP enzymes
migraine (sx w and w/o aura (inc definition of aura and how long before migraine sx and how long they then last), 3 common phobias associated, ppl who tend to get and when less common, when is rare for first one to occur, 7 triggers inc effects of pregnancy, 12 kinds of aura + timecourse of these vs TIA or seizure and how long they last for overall)
periodic, usually unilat, usually pulsatile headaches; may be migraine with or without aura
former is disturbance of neurological function then after a few minutes or hours hemicranial (bilat in 1/3 cases) headache, nausea, vomiting lasting for hours to day or more; latter is unheralded onset over minutes of hemicranial headache, sometimes generalised but rarer, with or without nausea and vomiting, and following same temporal pattern as with aura; photophobia, sonophobia, and often osmophobia attend both types; movement of head intensifies; pt often likes to sleep in darkened quiet room; hemicranial and pulsatile characteristics are most defining of migraine
more common in women, sometimes in children but usually adolescents through to middle age; less common as get older; be cautious saying it’s migraine if first time having it pt is >30yo (although it still can be)
may sometimes or exclusively occur in premenstrual period; sometimes migraines occur for first time in first trimester, but usually pregnancy reduces migraine frequency
tyramine, alcohol, jarring of head, strong sensory stimuli, excess or withdrawal from caffeine have been implicated as triggers
visual aura may be flashes of light, scintillating scotoma,and zigzag fortification spectra; sometimes vision may blur or shimmer, these hallucinations moving across visual field and leaving homonymous scotoma in wake sometimes
other aura less common but may be numbness/tingling of lips, face, hand on one or both sides, confusion, weakness in one arm or leg, aphasia or dysarthria, dizziness, unstable gait, drowsiness; if one symptom follows another or eg tingling spreads this is over minutes rather than instant as in tia or over seconds as in seizure; aura usually lasts for 30mins
migraine variants (crash (vs eg SAH), missing triad inc in elderly, brainstem aura (8sx, imaging to exclude 2ddx) familial hemiplegic, trauma triggered 5 ways it may look and 2ddx); stroke risk
may be bilat or not that pulsatile;
sometimes crash migraines occur with abrupt and severe pain resembling a thunderclap headache but usually will find the peak of pain took minutes to evolve rather than being very rapid but CSF and imaging needed to truly distinguish this migraine from SAH
any 2 out of the 3 main things of aura, headache (yes really), GI upset may be absent; eg oft in advancing age only the aura occurs, and that with dec freq; migraine w/o headache is fully possible; sometimes sudden transient blindness or hemianopia with only mild headache can occur
migraine with brainstem aura: often kids with FH of migraine, visual aura over most of visual fields, some of vertigo, incoordination, tingling in hands and feet, dysarthria lasting 10 to 30 mins then headache, usually occipital; may faint or become v confused when headache about to begin; imaging to exclude disease of basilar a and brainstem; rec attacks makes diagnosis clearer and imaging w/ associated stroke risk less neccessary
familial hemiplegic migraine: episode of unilat paralysis in children, sometimes massive unilat brain swelling
cranial trauma may precipitate migraines in ppl prone to getting them; some children and teens may, after mild head injury, lose vision, have severe headache, or be plunged into state of confusion lasting hours or days; another version has abrupt onset unilat paralysis or aphasia after virtually every minor head injury, may see in eg athletes or sporty ppl, with no headache or visual disturbances; subdural haematoma and carotid a dissection should also be considered; will often see FH of migraine but not always
migraine and aura seems to double risk of stroke esp if also eg smoke or on ocp
treatment of migraine (beginwhen, mild headache analgesia x2, severe x2 inc modes of admin and how to time them; when not to give these 2 x3 and why; x2 mx if these fail; 8 prophylaxis medications + 3 other things to advise; NICE guidance on acute mx step 1 (inc alt for CYP) and 2nd line x4; NICE guidance prophylaxis (when, effective in how many, 2 main options inc when to favour one (x2 reasons why) and what if these measures fail; supplement for proph and proph in menstrual migraine pts)
treatment of acute attack should begin during prodrome
for mild headaches, paracetamol, NSAIDs may control pain; worth trying a few diff combos to see what works best and using high-ish doses if needed
for severe attacks can use sumatriptan (naratriptan or others) or dihydroergotamine; if given subcut then ineffective if given during the aura, give at onset of headache instead; oral and nasal sprays on other hand should be given during aura if poss
these drugs cause cerebral hypertension so dont use if poorly controlled hypertension or cerebral/coronary/peripheal artery disease or if on other sympatheticomimetic drugs due to risk of vasospasm or haemorrhage
in refractory cases corticosteroid may be used iv or po, and failing that narcotics to provide restful sleep until it passes
propranolol can be used as prophylaxis, 10-20mg po tds titrating dose up; atenolol may also be tried from 40-160mg/d; side effects inc fatigue etc so not first choice
topiramate or amitriptyline 10, 20mg nightly may be tried; verapamil, nifedipine, indomethacin worth trying too if those fail; botox injection into sensitive muscles like temporalis can also help
avoiding triggers and limiting caffeine may be helpful
acupuncture worth trying too
Acute treatment
first-line: offer combination therapy with an oral triptan and an NSAID, or an oral triptan and paracetamol
for young people aged 12-17 years consider a nasal triptan in preference to an oral triptan
if the above measures are not effective or not tolerated offer a non-oral preparation of metoclopramide (caution in young ppl due to acute dystonia risk) or prochlorperazine and consider adding a non-oral NSAID or triptan
Prophylaxis
prophylaxis should be given if patients are experiencing 2 or more attacks per month. Modern treatment is effective in about 60% of patients.
NICE advise either topiramate or propranolol ‘according to the person’s preference, comorbidities and risk of adverse events’. Propranolol should be used in preference to topiramate in women of child bearing age as it may be teratogenic and it can reduce the effectiveness of hormonal contraceptives
if these measures fail NICE recommend ‘a course of up to 10 sessions of acupuncture over 5-8 weeks’
NICE recommend: ‘Advise people with migraine that riboflavin (400 mg once a day) may be effective in reducing migraine frequency and intensity for some people’
for women with predictable menstrual migraine treatment NICE recommend either frovatriptan (2.5 mg twice a day) or zolmitriptan (2.5 mg twice or three times a day) as a type of ‘mini-prophylaxis’
Mg supplements also help to reduce migraine intensity
Pizotifen can also be used as a prophylactic agent
acute and prophylactic mx of migraine in CYP
prescribe ibuprofen oral solution (OS)
(10 mg/kg) as an initial treatment option
For adolescents with migraine, clinicians should prescribe naproxen and a nasal triptan
Clinicians should offer an alternate triptan, if 1 triptan fails to provide pain relief, to find the most effective agent
Consider giving ondansetron to all even in absence of nausea
If oral meds not tolerated then IV metoclopramide or prochlorperazine + IVF + non-oral NSAID and triptan if not given
Explain to parents that metoclop/prochlor and oral triptans not licensed in kids and explain risks, document if they consent
Clinicians must not prescribe triptans to those with a history of ischemic vascular disease or accessory conduction pathway disorders
Advise them to take triptan at start of headache not during aura
Advise re: medication overuse headache
prophylaxis: riboflavin and Mg supplements, and choose between topiramate, propranolol, and pizotifen; can r/v and adjust these
also note that there is a probable relation between colic and migraine, therefore, migraine and colic as 2 pain syndromes may have a common pathophysiology; continued research is needed
cluster headache (usual pt; usual pattern of attacks; 8 sx lasting how long, possibly how do the eye sx arise; 3 acute and 1 proph mx + mx if intractable, 2 triggers)
usually adult men (5:1 m to f) age 20-50
months at a time with nothing then several a day for several days is usual pattern; occurring around night time is most common but can be at other times
severe unilat pain deep in and around eye, usually nonthrobbing; often radiate to forehead, temple, cheek
blocked nostril, rhinorrhoea, lacrimation, miosis, flush of cheek for 15-180 mins; sometimes ptosis which may become permanent after repeated attacks; ipsilat temp artery may become enlarged and tender during attack; most patients pace or rock on spot with hand to head
linked to circadian rhythm with parts of SCN seeming to be active on pet scan before attack and stimulation of hypothalamus is experimental treatment to stop the headaches
ICA wall may expand during attack, compromising the symp plexus on the ica leading to the horner syndrome symptoms; this seen in pt coincidentally having arteriogram but not yet replicated
100% O2 for 15 mins at start of attack may abort it; at start of attack give subcut or nasal sumatriptan, can give subcut injection up to 2x a day
verapamil may be used to terminate a cluster of headaches and is main form of prophylaxis
partial section of trigeminal nerve may be attempted if intractable or block with LA
alcohol or smoking may trigger an attack!
first bout needs specialist confirmation (and may neuroimage to exclude other causes)
tension headaches (2 sx, distribution pattern, and time t onset plus how long they last, age arises and common conditions seen along with, mx - for simple and more severe/prolonged, 4 non-medical things that help, 6 things that may cause/trigger); nice acute mx x3, prophylaxis x2
bilat and may be frontal, tempotal, or occipitonuchal or diffuse across cranium; dull aching or tightness/pressure; may be interpreted as waves or throbbing, but isnt pulsatile ie related to the pulse; nausea, photo and phonophobia, unilat, pulsatile main ways to tell migraine from this, also the onset of these is more gradual and may persist for days, weeks, months, even years; one of few headache types persistent throughout the whole day (sometimes)
more likely to arise in middle age and coincide with anxiety, fatigue, depression
not more than 2 in 1000 pts with persistent tension headache will be found to have eg intracranial tumour; 1/3 will have symptoms of depression
sometimes chronic daily headache may dev pulsatile quality, blurring distinction with migraine a little
persistent muscle contraction unclear if related as some emg studies dont show this
simple analgesia for brief or mild headaches; persistent, severe, or freq respond best to drugs for dep or anxiety eg amitriptyline at night; stronger analgesics not helpful; massage and meditation can help, yoga and exercise too
usually lasts 30mins to several hours
squinting, poor posture, skipping meals, dehydration, lack of physical activity, strong sensory experiences can act as triggers
acute treatment: aspirin, paracetamol or an NSAID are first-line
prophylaxis: NICE recommend ‘up to 10 sessions of acupuncture over 5-8 weeks’
low-dose amitriptyline is widely used in the UK for prophylaxis against tension-type headache. The 2012 NICE guidelines do not however support this approach ‘…there was not enough evidence to recommend pharmacological prophylactic treatment for tension type headaches. The GDG considered that pure tension type headache requiring prophylaxis is rare
SDH 5 sx and headache gets worse when and effect on cognition; postconcussion syndrome 6sx and 2 mx; whiplash injuries pain distribution x4 (2:2)
subdural haematoma will be dull, steady, unilat, with drowsiness, confusion, hemiparesis, may get worse when lying down or on one side; headaches in this case inc in freq or sev; may have fluctuating cognition
also postconcussion syndrome: dizziness, tiredness, nervousness, irritability, problems concentrating or some confusion, the headache may resemble a tension type one and needs reassurance, get pt active, maybe treatment for dep or anxiety
whiplash injuries can give bilat or unilat retroauricular or occipital pain
headache and brain tumour (how common as heralding sx, how pain is, how vomiting is inc when early, where pain is if supratentorial, what bilat pain suggests and 4 other features of this thing)
headache actually infreq as sign of brain tumour, particularly as a heralding symptom
usually deep, nonthrobbing (not always), aching or bursting; positional changes may worsen it; unexpected projectile vomiting may occur in late stages, or early stages if in post fossa; supratentorial tumours give pain felt anterior to interauricular circumference of skull; if pain bilat suggests rising icp due to tumour; greatly raised icp may also cause vomiting, transient blindness, leg weakness leading to collapse, and loc
giant cell arteritis (age distribution, pain features, how a’s feel and what sx you get in severe cases, 3 non headache sx, why aching in limbs and how common also have this, specific but not sensitive sign, mx strat and what to do if mx doesn’t help; 2 reasons for same day optho ax and how these problems treated; otherwise who assesses and how soon after diagnosis, 3 initial ix and 2 to follow this
almost always >55yo
intense throbbing or non throbbing headache, sometimes with stabbing pains, may dev rapidly; usually unilat, sometimes bilat, usually localised to site of temp a’s; these a’s often thickened and tender; jaw claudication in extreme cases
often feel unwell, may have lost weight, be running fever; esr up, crp up; aching of prox limbs in 50% cases reflecting concurrent polymyalgia rheumatica
masticatory claudication is specific but not sensitive sign
predisolone 40-60mg po od over several weeks down to 10-20mg po od for months or years if needed to prevent relapse; if doesnt improve within a few days of starting then question diagnosis; esr and crp should return to normal; biopsy the temporal a
If there is new visual loss (transient or permanent) or double vision:
Arrange an urgent (same day) assessment by an ophthalmologist.
Depending on the clinical situation, the specialist may advise one-off high dose corticosteroid treatment in primary care while the person awaits transfer to ophthalmology.
Acute or intermittent visual loss due to GCA is usually treated with intravenous glucocorticoid therapy; if this is not possible, 60–100 mg oral prednisolone may be given for up to 3 consecutive days.
For all other people with suspected GCA:
Urgently discuss with a specialist and refer using a fast track local GCA pathway.
Specialist assessment (usually a rheumatologist) should be on the same working day if possible, and in all cases within 3 working days.
Suspected GCA should be immediately treated with glucocorticoids.
Discuss the need for initiation of glucocorticoid treatment in primary care with the specialist — the standard initial dose for active GCA without visual symptoms is 40–60 mg oral prednisolone per day.
Consider arranging the following blood tests to support diagnosis unless there is evidence of critical ischaemia (such as visual loss or diplopia) or no immediate access to phlebotomy but do not delay referral while waiting for results:
Full blood count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR).
Diagnosis will be confirmed in secondary care with investigations such as ultrasound and biopsy.
low pressure headache (trigger, 2 sx relieved by what, what other way can it present)
when csf pressure falls, eg after 5% of lp cases; vertical traction on cerebral blood vessels ensues; pain and vomiting nearly always relieved by assuming supine position; neck pain may be prominent or only feature
sexual headaches (2 benign types, 2x serious ddx, 2 mx of chronic benign)
may be tension type building up during sexual excitement, or may be explosive type at point of orgasm, almost like a ruptured aneurysm
often on several consecutive sessions
indomethacin may be helpful if chronic, but usual mx is reassurance
ofc exertion of sex may lead to carotid dissection, MI, aneurysm rupture etc so be cautious before saying it’s benign
thunderclap headache - 9 causes, 3 common places for blood to be on CT, how often is it negative and what if it is, how long to wait to perform this test and what to do it confirms SAH
sudden severe headache like being kicked in the head; often benign though and idiopathic
may be crash migraine, sah, cvt, cerebral vasospasm, hypertension, pitu apoplexy, cocaine and adrenergic drugs
Confirmation of SAH:
Computed tomography (CT) head
Acute blood (hyperdense/bright on CT) is typically distributed in the basal cisterns, sulci and in severe cases the ventricular system.
CT is negative for SAH (no blood seen) in 7% of cases.
Lumbar puncture (LP)
Used to confirm SAH if CT is negative.
LP is performed at least 12 hours following the onset of symptoms to allow the development of xanthochromia (the result of red blood cell breakdown).
Xanthochromia helps to distinguish true SAH from a ‘traumatic tap’ (blood introduced by the LP procedure - another way to tell is to see a >30% decrease in RBC count from pot 1 to pot 3 (you my need to specifically ask lab to give you these results)).
As well as xanthochromia, CSF findings consistent with subarachnoid haemorrhage include a normal or raised opening pressure
Referral to neurosurgery to be made as soon as SAH is confirmed
LP guidelines
Indication for lumbar puncture procedure:
Suspected meningitis/encephalitis- for diagnosis
As part of neuro-metabolic investigations
For diagnosis of Benign (Idiopathic) Intracranial Hypertension (BIH)
Intrathecal chemotherapy
Contraindication for lumbar puncture procedure:
Signs suggesting raised intracranial pressure
reduced or fluctuating level of consciousness (Glasgow Coma Scale score less than 9 or a drop of 3 or more)
relative bradycardia and hypertension
focal neurological signs
abnormal posture or posturing
unequal, dilated or poorly responsive pupils
papilloedema
abnormal ‘doll’s eye’ movements
Shock
Extensive or spreading purpura
After convulsions until stabilised
Coagulation abnormalities
coagulation results (if obtained) outside the normal range
platelet count below 100 x 109/litre
receiving anticoagulant therapy
Local superficial infection at the lumbar puncture site
Respiratory insufficiency (lumbar puncture is considered to have a high risk of precipitating respiratory failure in the presence of respiratory insufficiency)
headaches from disease processes - mening and what other infections, BP and headache relationship inc tumour, headaches and seizures, 5 more headache dd (not normal ones) and 4 Ortho/rheum ones
meningitis - fever, stiff neck (get them to do chin to chest then look high up); headache can also occur in less serious infections, esp viral eg flu; neck pain and stiffness often accompanies this; sah and meningitis suspected but there wont be meningism
headache can raise bp, but if bp >200/120 or so then that can cause headache; can be malignant hypertension or eg tyramine food straight after maoi; also phaeochromocytoma
headaches maybe after 50% of seizures
generally also fevers, hypercapnia (chronic lung disease, usually in morning), withdrawal, acute severe anaemia, hypothyrodism etc
facet arthropathy, C2 dorsal root entrapment, hypertrophy of post long lig, RA of atlantoaxial region may give headaches
idiopathic facial pain syndromes - most common thing, 6 non-neuro ddx, 3 neuro classes 2:2:1(mx and why can this nerve carry this problem), ix should be had at first presentation
most common reason is dental problems so start by ruling that out
may be non-neurological in which case you may see signs of related disease: GCA, glaucoma, chronic sinusitis, poet-herpetic neuropathy, malignancy, central pain
if neurological + episodic 3 classes based on time and sx:
1-120s may be trigeminal neuralgia or SUNCT/SUNFA and need NaV block
unilat +/- lacrimation, salivation, rhinorrhoea, sweating think cluster headaches or paroxysmal hemicrania (15-180 mins vs 2-30mins)
if 4-72 hours with sensitivity to noise/light or nausea then can be V2 distribution migraine: try triptans, then migraine prophylaxis + regular mag and B2 supplements, if not working move to anti CGRP therapy
pain for the above may be felt in the upper teeth/jaw, even bridge of nose, rarely also mandible; generally V2 migraines don’t have aura and facial CH have less trigeminal autonomic sx
persistent idiopathic facial pain is a bit like a chronic form of trigeminal neuralgia without the attacks of obvious cause
note that V2 most commonly carries trigeminal neuralgia, but can carry primary headaches (migraines) as it innervates parts of the middle cranial fossa (as does V3 making V3 migraines also possible)
everyone with these conditions should have MRI at first presentation to pick up other causes eg maligancy
trigeminal autonomic cephalgias - what are they, 5 egs; for second eg 2 sx and 3 ways to diff from CH, for 4th eg which nerve distribution, each attack how long and 3 ways they cluster, how long is symptomatic period and how often, how long are remissions, 2 common autonomic sx and which are rarer, what can trigger (and how to differentiate from which common ddx), 2 key diagnostic/mx things for the 4th/5th eg, how to differentiate these two
group of primary headache disorders characterized by unilateral head pain that occurs in association with generally prominent ipsilateral cranial autonomic features
include cluster headache (CH), paroxysmal hemicrania (PH), hemicrania continua, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and its close relative, short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA)
Paroxysmal hemicrania (PH), like CH, is characterized by strictly unilateral, brief, excruciating headaches that occur in association with cranial autonomic features. PH differs from CH mainly in the higher frequency and shorter duration of individual attacks; unlike CH, PH responds in a dramatic and absolute fashion to indomethacin; Typically, patients have more than five attacks daily, although the frequency of attacks shows a considerable fluctuation, ranging between one and 40 daily. The attacks occur regularly throughout the 24-h period, without a preponderance of nocturnal attacks as in CH.
for SUNCT: pain is usually maximal in the ophthalmic distribution of the trigeminal nerve; attacks are stabbing, burning, prickling, lasting for 5–240 s, and have one of three different types of attack profiles: They can occur as single short-lasting stabs; longer-lasting groups of repetitive stabs; or a serrated pattern; Symptomatic periods generally last from a few days to several months, and occur once or twice annually. Remissions typically last a few months, although they can range from 1 week to 7 years; attacks are virtually always accompanied by both ipsilateral conjunctival injection and lacrimation. Ipsilateral nasal congestion, rhinorrhoea, eyelid edema, ptosis and facial redness or sweating are less commonly reported; majority of patients can precipitate attacks by touching certain trigger zones within trigeminal innervated distribution and, occasionally, even from an extratrigeminal territory - note similarity to trigeminal neuralgia (autonomic features and V1 instead of V2/3 help to differentiate)
a full diagnostic work-up for SUNCT/SUNA must include a brain MRI scan with dedicated trigeminal views and a trial of indometacin to exclude indometacin-responsive headaches
Note although the 2 present similarly, the key difference is that a person with SUNCT must have both eye redness and tearing on the same side as the pain compared to SUNA which may have only one or neither symptom but will often have other cranial autonomic symptoms.
hemicrania continua - 4 characteristics of pain and where normally felt, 3 features of exacerbation, 3 diagnostic criteria, pathognomic feature (and why this works x2)
present with a continuous unilateral headache that is present for months. It is mild-to-moderate in severity, dull in character, and often does not affect physical activity. It is commonly located in the first division of the trigeminal nerve involving the frontal and periorbital regions, but other extra-trigeminal areas may also be involved
often has superimposed fluctuating headache exacerbations, which may last for a few minutes to days with a frequency ranging from more than 20 attacks daily to one attack in 4 months; moderate-to-very severe in intensity and throbbing or stabbing in character - may become restless migrainous features of photophobia, phonophobia, nausea, and/or vomiting may occur during exacerbations; Like other TACs, HC is associated with ipsilateral cranial autonomic symptoms, especially during exacerbations. Still, these autonomic symptoms are generally less prominent than other TACs, including cluster headache (CH) and paroxysmal hemicrania (PH). The cranial autonomic features may include forehead sweating, lacrimation, conjunctival injection and swelling, ptosis, miosis, a feeling of foreign body sensation in the eye, nasal congestion, rhinorrhea, and/or aural fullness
criteria: unilat, for 3mo+ w exacerbations, either or both of autonomic signs or agitation (/movement worsens), and responds to indomethacin
complete response to indomethacin is one of the pathognomonic features of hemicrania continua; proposed that indomethacin is more effective than other NSAIDs, probably due to the highest central nervous system penetration, central serotonergic effects etc
trigeminal neuralgia (sx and common age range, 5 causes, imaging and mx x8 + acute x1 + PRN x1, glossopharyngeal neuralgia pain distribution and vagus involvement
common in middle age+; stabbing pains usually of a few seconds to a few minutes, both day and night, for several weeks or months at a time; may be triggered by shaving, brushing teeth, cold wind, yawning; no sensory or motor loss usually
atypically but not infreq may get itching or sensitisation of the face
usually idiopathic but can be due to 5th CN involvement in MS (bilat often), aneurysm of basilar a, tumour in cerebellopontine angle; somtimes by compression by branch of basilar a: mri angiography shows, and surgery to separate relieves; this not most cases though
carbamazepine 600-1200mg od works in 70-80% of ppl, half become tolerant over years; oxcarbazepine and lamotrigine as alternatives; others inc gabapentin, pregabalin, phenytoin, valproic acid may be used; short course of steroid can be used during a flare of attacks or eg to cover while uptitrating/switching meds and a large pulse of eg dex can be used if pt presents in crisis with frequent severe attacks; baclofen PRN can be used as an adjuvant for relief during an attack
rarely can get glossophayrngeal neuralgia, resembles the above but pain in throat and tonsillar fossa, often provoked by swallowing, yawning, talking etc; pain may localise to ear or radiate from throat to ear so auricular branch of vagus nerve; vagus pain afferents trigger bradycardia and even syncope; tumours may also cause by compression but this even rarer; treat as for trigeminal
tmj pain - commonest reason, joint examination, other cause, ix and 2 mx
often due to disruption of the bite and may have deviation of mandible to affected side and clicking sounds from joint when moving it; jaw may lock in open or closed position
jaw opening limited, tenderness and crepitations over joint; headache in front of ear radiating over temple and face; may also be involved in joint disease like RA
palpating joint from eam may reproduce pain, this gives confidence in the diagnosis; MRI to show joint effusion
adjust bite by dental specialist and maybe amitriptyline at night
medication overuse headache - how common, headache freq and criteria x3, 4 common causes, headache character, initial mx x2 then once problem solved, another med that helps, 2 long term strats
3rd most common after migraine and tension is drug misuse headache; caused by taking painkillers or triptans regularly, usually for headaches but sometimes eg back pain, this much less common and generally not seen
headache will happen most days, sometimes every day; must be present at least 15 days of the month, developed while using medication; diagnosis only confirmed if headache resolves or reverts to previous pattern within 2mo of stopping the medication
codeine, triptans, ergotamine (rarely used) are the most common causes, nsaids less so but can
constant dull headache, spells where gets worse; usually worse in the morning or after headache
stop the medicine and maybe replace with less provocative one eg replace codeine with ibuprofen
once headaches back to normal can resume taking the original medicine but beware overuse; in meantime things may get worse before they get better, and giving antiemetic may help
avoid taking the medicine on more than 2 days a week, maybe consider prophylaxis
reversible cerebral vasoconstriction syndrome - 7 sx and possible trigger, 6 associations, 7 ddx, 2 first ix then 3 optional follow ons including finding but thing to be cautious about, 9 ix you can do after that, 2 mx
present with symptoms of recurrent sudden-onset most intense headache peaking immediately to maximal intensity over seconds to minutes (thunderclap); generally b/l; may present with vomiting, photophobia, phonophobia, confusion, and blurred vision; may be accompanied by seizures, FNS or stroke; headaches may be trigger by valsalva manoeuvre
Up to two-thirds of RCVS cases are associated with an underlying condition or exposure, particularly vasoactive or recreational drug use (SSRIs, sympathomimetic decongestants, adrenaline (inc phaeochromocytoma), cocaine, cannabis), pre-eclampsia
subarachnoid hemorrhage, ischemic stroke, pituitary apoplexy, cerebral artery dissection, meningitis, PRES (25% of kids with RCVS have PRES too), and spontaneous cerebrospinal fluid leak
CTH and LP ?SAH first ix
if NAD may proceed to eg CT angio, formal angiography, or MRA; string-of-beads sign supports RCVS diagnosis but note imaging can be normal in first week of sx
If the clinical and radiological findings are inconclusive or the underlying cause is still missing, routine blood tests, urinalysis, urine vanillylmandelic acid and 5-hydroxyindoleacetic acid levels, serum and urine toxicology screens, ESR, CRP, infectious and rheumatological panel tests, and CSF examination are indicated
mx inc trigger avoidance, calcium channel blockers such as nimodipine and verapamil are used to relieve the headache acutely and can work as prophylaxis
concerning headaches, (5 things) gliomas (3 types)
concerning headache features: Constant
Nocturnal
Worse on waking
Worse on coughing, straining or bending forward
Vomiting
Gliomas are tumours of the glial cells in the brain or spinal cord. There are three types to remember (listed from most to least malignant):
Astrocytoma (glioblastoma multiforme is the most common)
Oligodendroglioma
Ependymoma
post traumatic seizure (control early why? favoured drug? 4 other trauma associated things)
Common following any form of acute brain injury
* Important to control early before they become more
frequent or evolve into status epilepticus
– Levetiracetam is now the favoured anti-convulsant in
most circumstances (in adults can load on valproate if keppra not working)
– Tend to avoid benzodiazepines
hydrocephalus may be part of trauma: In the acute setting this is usually managed with an external ventricular drain
hyponat (SIADH, fluid restriction maybe contra so eg hypertonic saline); maybe hypernat if diabetes insipidus
cerebral contusions: Often multiple and bilateral
– Contre-coup (opposite site of impact)
– Predominantly frontal and temporal lobes
* Higher velocity injuries associated with deeper
contusions (including brainstem)
raised ICP (8 sx, coning 3 sx, 2ix); cause besides sol (inc 2sx, 6 risk factors, 2 mx, specific signs for each sinus of cavernous transverse straight, 2 ix, low index of suspicions when; 4 risk factors for abscess and ix for cause; how tumour shows on MRI and how to ix it further
raised ICP: dull headache, worse when lying down/on waking; maybe pulsatile tinnitus; maybe diplopia (CNVI), valsalva things might bring
on; papilloedema, scotoma/enlarged blind spot, UMN signs; coning (CNIII, coma, resp arrest); need imaging, LP if safe
tumour or sol*, but also CVST: progressive headache etc, seizures; risk factors smoking, COCP, cancer, pregnancy, dehydration, hyperviscous
give anticoag, manage sequelae; if cavernous then CNIII-VI, proptosis maybe, in transverse sinus maybe tinnitus; straight sinus may give
motor deficits or mental status changes; do CT, MR venogram; low index of sus if progressive/seizures, headache fits
abscess may be from neurosurg, parameningeal infection, cranial trauma, haemat spread (maybe multi abscesses - consider echo)
T1 with contrast enhances tumour, on T2 can see oedema around the tumour which will be dark like brain (not as dark as abscess); biopsy and
histo of the mass
4 cluster headache mimics and differentiating first 2 from CH
CH picture but w/o red eye - maybe carotid artery dissection? MRI can help; CAD can give horners, signs eg CNXII palsy
GCA: artery wall thickened due to lymphocyte/histiocyte infiltration, narrowing lumen so distal ischaemia; maybe multinuc giant cells too
GCA may see dipolopia, jaw claudication, tender temples, beading/enlarged artery; systemically unwell; high dose steroids, biopsy asap
also in CH picture consider trigem neuralgia and the autonomic cephalgias, sinusitis
childhood brain tumours (how common, where are most of them, commonest subtype; 4 general sx, 4 if under 4 and 6 if under 2, 1 from post fossa (inc 5 sx of this), midbrain and brainstem 3sx, 1 sx from occipital and frontal; how to ix if suspect, 3 mx inc what to wait for, ix to follow up; monitor for what x2, 3 other long term risks of mx
most common solid tumours in children; 70-80% infratentorial (glial tumours, medullablastoma) or midline (germinoma (pineal), craniopharyngioma); 43% of childhood brain tumours are astrocytomas
headache, n&v, abnormal gait; worsening, headache oft worse on waking; seizures at any age poss
<4yo oft macrocephaly, n&v, irritability, lethargy
<2yo non specific vomiting, irritability, failure to thrive, maybe hyperreflex, CN palsies, macroceph
post fossa tumours gives hydrocephalus (morning headache, vomiting, ataxic unsteady gait, double vision, papil); squint, CN palsies, pyramidal signs from brainstem or central brain tumours (and involvement from post fossa)
occipital lobe maybe visual deficits, frontal maybe behavioural changes
if suspect, esp if new CNS changes in child, very urgent MRI; then biopsy
surgical resection, chemo (usually inc vincristine), radiotherapy can be used but try to wait until 5yo or so; 6mo’ly MRI for 2 yrs after then annualy
long term intellectual decline (esp if irradiated), esp attention span and reaction times, so monitor for this; GH def common, intellectual disability, risk of second tumour 10-20 yrs down line esp if radiotherapy used
brain and CNS cancers (8 symptoms, why to think of high vs low grade, commonest type in adults; 4 common high grade and 5 common low grade; 2 mx strat inc preferred radiation for mets vs PCL/medulloblastomas; which type is chemo most important; 3 other mx things; 2 common acute problems, 1 subacute problem (inc when and 2x sx)
progressive subacuteCNS sx (seizures, headache (oft worse in morning), nausea, drowsiness, visual change, personality change, dysarthria, upper/lower limb defects) - 2ww MRI of brain
new abnormal cerebellar or other central neuro function in kids - 48hr appt referral
benign often not as SOL, so think of high grade (aggressive) and low grade
adults: mets from elsewhere 10x more common than prim tumours;
high grade prim inc gliomas, glioblastoma multiforme, medulloblastomas, prim cerebral lymphomas; low grade meningiomas, acoustic neuromas, neurofibromas, pitu/pineal tumours, craniopharyngiomas; resection if poss; if not external beam therapy can be curative, is preferred option for mets; whole brain irradiation for PCL, medulloblastomas; CNS lymphoma has intrathecal and iv chemo, other types chemo less important; platinum types for medulloblasts
analgesics, steroids, anticonvulsants; bleeding into tumour, hydrocephalus can occur raising icp to life threatening levels w brain herniation; subacute encephalopathy (somnolence, headaches) 1-16 wks after radiotherapy
posterior fossa tumours
60% of paeds brain tumours are in post fossa
Posterior fossa tumors (PFTs) include medulloblastomas, atypical teratoid/rhabdoid tumors, pilocytic astrocytomas, ependymomas, and brainstem gliomas
Paediatric low-grade gliomas (LGGs) are the most frequent brain tumours diagnosed in
children and young adults, accounting for approximately 40% of all reported cases; NF1 and TSC are linked to these accounting for around 20% between them
astrocytomas and other gliomas make these up; pilocytic astrocytoma is the most common type of astrocytoma diagnosed in children and these are seen in cerebellum 60% of time with next commonest area the optic pathway; slow growing with gradual symptom onset usually
- Features of raised intracranial pressure – headaches, vomiting, cranial nerve palsies,
papilloedema, macrocephaly, ataxia, reduced consciousness. - Tumours of the floor of the 3rd ventricle / hypothalamus – diencephalic syndrome
- Tumour of the cerebral hemispheres – seizure activity
- Tumours of the cerebellum – ataxia, incoordination
- Tumours of the brainstem – long tract motor / sensory signs, cranial nerve palsies including
hearing loss. - Tumours of the suprasellar area – visual and endocrine anomalies (delayed/ precocious puberty, diabetes insipidus, anomalous weight gain / loss, short stature)
assess visual acuity and fields as appropriate (modified techniques for young kids)
MRI
Excluding a secreting germ cell tumour (serum AFP and b-HCG) is an important consideration in suprasellar lesions detected on imaging. Likewise, for suprasellar lesions involving the hypothalamic-pituitary axis, baseline pituitary function tests including the assessment of salt/water balance are advised before any surgical intervention is undertaken.
surgery for 80% and sent for histopath, biopsy if can’t resect
chemo if not managed surgically - usually vincristine and carboplatin +/- radiotherapy (generally avoid giving radiotherapy treatment to children under the age of 10 or with NF1)
proton beam therapy occasionally performed - manchester and UCLH only have these
then follow up scans for recurrence
Medulloblastomas are the most common malignant brain tumours of childhood, most often presenting as midline masses in the roof of the 4th ventricle with vast majority arising from cerebellum and most of these from the vermis; they are a small round blue cell tumour; Treatment typically consists of surgical resection, radiation therapy, and chemotherapy; growth of these very cellular tumours is often rapid and accounts for their relatively rapid clinical onset. Typically, presentation occurs over a few weeks with features that are dominated by symptoms of raised intracranial pressure as a result of obstructive hydrocephalus; they are all considered at least grade 4; As CSF seeding is common at presentation, imaging with contrast of the whole neuraxis is recommended to identify drop metastases and leptomeningeal spread
ependymoma usually arises from the floor of the 4th ventricle and typically squeezes out the foramen of Luschka; Although medulloblastomas project into the fourth ventricle, unlike ependymomas they do not usually extend into the basal cisterns; Enhancement is significantly greater in medulloblastomas compared with ependymomas, and greater still in astrocytomas
specific CNS tumours (pitu 14 sx, 3 ix, 4 mx; pineal tumours 4 types, 9 signs, 2 mx; meningiomas grading and how fast, arise from where, if in spine syndrome can cause and if in sella turcica, 1ix and 3mx; acoustic neuroma from where, how fast, how threatens life, genetic risk factor, environmental risk factor, 6 sx, 2ix and 3mx; GBM how common, ix findings, 3mx)
pitu - symptoms from hormones eg acromegaly, gigantism (kids), cushings, high prolactin; if nonfunctioning, visual field loss may be first symptom; headaches worse in morning, maybe sudden severe pitu apoplexy, hydroceph, squint; hypopitu also poss eg low libido, ed, oliomenorrhoea or in kids delayed puberty, diabetes insipidus rarely (note: these may follow pitu removal surgery too); pitu function tests, visual field mapping, MRI; transsphen surg, radiotherapy if incompletely resected; bromocriptine in prolactin secreting tumours; radiotherapy if rec
pineal - germinomas, teratomas, pineocytomas, pineoblastomas; morning headache, n&v, hydrocephalus -> death; vertical gaze palsy ie cant move eyes up and down +/- CNIII paralysis; mydriasis, convergence, unequal pupils; maybe cerebellar signs; surgery, stereotactic radiotherapy
meningiomas - grades I, II, III (inc aggresiveness), arise from dura mater and slow growing; present as other tumours but if in spine then brown sequard syndrome, panhypopitu if in sella turcica; MRI; conservative management if small and in elderly pt; surgical excision, radiotherapy as for pitu or if high grade/anaplastic
acoustic neuroma - from CNVIII schwann cells; low grade slow growing, life threatening eventually through mass effect; neurofibro is risk factor, radiation as kid for adenoids/tonsils also; consider if unilat hearing loss/tinnitus (progressive or acute), impaired facial sensation (affect trigem, may also give facial pain), unexplained balance issues; earache, ataxia; audiology for hearing loss, MRI; small + good hearing then watch and wait, active treatment if growth detected; surgery, maybe stereotactic radiotherapy
glioblastoma multiforme - most common and aggressive primary brain tumour, has ring enhancement, surgery, radiotherapy, and chemo (temozolomide)
papilloedema - 4 fundo findings, 7 causes
following features may be observed during fundoscopy:
venous engorgement: usually the first sign
loss of venous pulsation: although many normal patients do not have normal pulsation
blurring of the optic disc margin
elevation of optic disc
loss of the optic cup
Causes of papilloedema
space-occupying lesion: neoplastic, vascular
malignant hypertension (will see other hypertensive retina signs, note raised ICP can also cause hypertension as part of Cushing triad in which case you wouldn’t see hypertensive retina changes)
idiopathic intracranial hypertension
hydrocephalus
hypercapnia
Rare causes include
hypoparathyroidism/hypocalcaemia
vitamin A toxicity
glia (overall function and ratio to neurons, oligodends function, astrocytes functions x4, microglia and ependymal cells roles; what % of cells in brain macroglia inc how many of each)
provide a stable environment for the neurons, which they outnumber (2-10x as many)
oligodendrocytes myelinate neurons (1-30 internode regions)
astrocytes maintain homeostasis as part of BBB and regulate CSF composition by taking up K (high K permeability from high conc of K channels) from repetitive AP firing (most numerous, have end feet that interact with capillary endothelial cells), separate cells to insulate neuronal groups from each other, high affinity uptake of glutamate, converting it to glutamine then transferring back to neurons (also other NTs)
microglia phagocytose debris and play a role in inflammation and ependymal cells form a columnar epithelium lining the ventricles and forming CSF, with cilia to help circulate the CSF
80% of all cells in brain are macroglia, 1/2 astro and 1/2 oligo
hydrocephalus in child - causes 6:4:1
increased amount of csf, normally under inc’d pressure and so dilates ventricles
can be obstructive (non-communicating), dec’d csf absorption (communicating), inc’d csf production
obstructions can result from tumours, and congen abnorms eg dandy walker cyst (deficiency of cerebellar vermis and 4th ventricl foramina + cystic dilatation of 4th ventricle), arnold-chiari malform (small post fossa, downward displacement of cerebellar tonsils and medulla into foramen magnum, oft associated with spina bifida), aqueduct stenosis (x linked or sporadic -> x linked form oft has overlapping fingers and/or adducted thumbs so if this plus large head consider hydroceph, tho sporadic majority of cases), aneurysm of vein of galen (obstruction at level of aqueduct), achondroplasia
dec’d absorption due to meningitis/encephalitis (inc intrauterine toxoplasmosis/CMV), intravent/intracranial bleeds, sagittal sinus thrombosis, arachnoid villi hypoplasia
inc’d production rare, usually choroid plexus papilloma
septo-optic dysplasia (what it is, 3 features, commonest pattern and 5 other common features; what ix to show and what 2 other ix needed)
congenital condition usually diagnosed at birth but sometimes not until adolescence
will have 2 or 3 out of:
optic nerve hypoplasia (causing serious visual impairment)
absent or small septum pellucidum or corpus callosum giving dev delay and some movement or coordination problems
hypopituitarism
commonest pattern is GH deficiency and visual impairment; often will have sleep disturbances, ASD behaviour, and tendency to weight gain; may also present with seizures or cerebral palsy
MRI will show, need bloods for pitu function and an ophthalmological assessment
septum pellucidum cysts
Cavum septum pellucidum (CSP) is a common incidental finding, defined as a midline cerebrospinal fluid (CSF) space delimited superiorly by the crus of the fornices and inferiorly by the tela choroidea of the third ventricle. It is anatomically distinct from cavum vergae (CV) which is a CSF space extending posteriorly to the columns of the fornix. However, CSP and CV cysts are used interchangeably in the literature and may co-exist in many cases
CSP normally exists in the fetal period but begins to close from the posterior part starting the 6th month of gestation). It remains as a small slit but usually becomes to close
completely around the 2nd month of birth as brain develops
They are usually asymptomatic but may present with symptoms related to obstructive hydrocephalus
where symptomatic/causing hydrocephalus, neurosurgeons can remove the cyst
Septum pellucidum itself cannot cause epilepsy because it does not consist of pyramidal cells, and is in the wrong place, however it is observed more frequently in people who have epilepsy - it is thought that the same dev problems leading to the epilepsy might also lead to the leaflets not fusing properly
neonatal uss (through what structure, 4 grades of IVH and where the bleed is, when most common and common complication; PVL appearance, when, association; hydranencephaly what it is and physical finding may see; porencephaly what it is and after what; lenticulostriate vasculopathy what it is and 5 associatsions plus risk of what
through ant fontanelle
IVH grade 1 confined to germinal matrix, 2 extension with blood in LV, grade 3 similar but ventricles now dilated, grade 4 has parenchymal involvement
the bleed is in subependymal matrix antlat to lat ventricles, 90% in first 4 days of life; posthaemorrhagic hydroceph in up to 40%
perivent leucomalacia where isodense lesions become echolucent cysts, usually after 2nd week of life, associated with cerebral palsy
also may see hydranencephaly where brain above thalamus replaced with csf, dies soon after birth (may also see transilluminated skull to demonstrate this)
porencephaly is cystic cavities in one cerebral hemisphere which may be continous with lat ventricle, commonly after intraparenchymal h+
lenticulostriate vasculopathy: hyperechogenic linear or branching tubular streaks in the thalami or basal ganglia; association with TORCH infections, esp CMV, perinatal hypoxia-ischaemia IEM, FAS, and cr abnorms; higher risk of IVH
MRI scans for neuro (what colour is CSF in T2 scan; lissencephaly inc 4 sx; 2 gyrus size abnorms; shiczencephaly meeaning; what to look for in EDH; what to look for with SOL; 6 features of raised ICP; hydrocephalus mimic
T1 more for anatomy, T2 more for pathology and CSF is white in T2
may see lissencephaly (smooth brain, due to problem with neuronal migration, get microceph, microphthalmia, seizures, severe dev delay)
macrogyria or microgyria
schizencephaly (symmetrical clefts in hemisphere from cortex to ventricle)
EDH (look for bubbles in this as evidence of skull fracture
sol inc any midline shift?
raised icp (loss of differentiation between grey and white matter due to oedema, loss of gyri, reduced space between skull and brain, poss compression of ventricles, flattening of sella turcica, and distension of optic nerve sheath)
cerebral atrophy (with compensatory ventricular enlargement, may look like hydroceph)
blocked shunt (4 shunt types, 5 things may see, commonest cause, other organ involved and 3 sx of this + ix finding
ventriculo-atrial or ventriculo-peritoneal shunt in situ for hydrocephalus - there are also other types like ventriculo-pleural, lumboperitoneal but these less common
child may be generally unwell or have fever, headache, vomiting, papilloedema
often due to infection (staph epidermidis, corynebacterium); neurosurgeons to manage
if also hypertension, haematuria, splenomegaly may be shunt nephritis (due to staph epidermidis), C3/4 will be low
looking after kid with VP shunt
Symptoms that are typical of
shunt dysfunction include
* Drowsiness
* Headache
* Vomiting
* Irritability
child may complain of headache or nausea and may vomit, often in the morning.
Babies may have symptoms such as increasing head size, tense bulging fontanelle,
a high pitched cry, irritability, sun-setting eyes or distended scalp veins.
Other symptoms that may be particular to the child could include seizures and
cranial nerve palsies, such as a squint
Often children only have a drop in their level of consciousness in the latter stages and so any patient with a shunt who has a reduced level of consciousness should be treated as a medical emergency
CT brain scan and shunt series X-rays should be obtained in a timely manner.
A shunt series for a VP shunt comprises of an AP and lateral skull and neck
X-ray, AP chest X-ray and AP abdominal X-ray so the whole shunt tubing can
be followed throughout its course. If the child has a VA or VPleural shunt then
abdominal x-ray is not required. It should be remembered that 15% of shunt
blockages do not produce a change in the scan appearance
Make these images available to neurosurgery team and discuss with them
Minimum of hourly observations: pulse rate, respiratory rate, blood pressure, neurological observations and continuous oxygen saturation monitoring
Where there is a clinical deterioration or reduced conscious level then the child may require urgent intubation and ventilation for transfer directly to neurosurgical theatres or to
Paediatric Intensive Care - will need to liaise with neurosurgery and transport teams; if stable can still transfer to neurosurgery urgently but not emergently; If the CT scan is not diagnostic of shunt dysfunction but the child remains clinically unwell then transfer may still be appropriate after discussion with on-call neurosurgery team
If Shunt is blocked or disconnected then child to go to theatres for revision of VP shunt as soon as possible
If the child is pyrexial, WCC is raised and remains symptomatic of shunt dysfunction
then CSF tap from shunt reservoir - done by neurosurgeons or under their direction.
If CSF has a raised WCC then for removal of VP shunt, insertion of EVD and commencement of antibiotics.
If no change on scan and the child remains symptomatic then ICP monitoring to be considered. If ICP raised then VP shunt
may need to be revised
If investigations are all within normal limits, the
child may need Neurology review
ventricular system (general anatomy inc where 3rd/4th lie and how they connect; recess into pitu stalk (from where, what 3 sub-components), 4 components of lat vents
set of fluid filled cavities with lateral ventricles in the cerebral hemispheres the largest and communicating with 3rd ventricle in the midline around the hypothalamus which connects to the 4th ventricle via the cerebral aqueduct in the midbrain; the 4th lies deep to the cerebellum and communicates with the subarachnoid spaces around the brain; floor of 3rd ventricle has infundibular recess into the pituitary stalk with supraoptic (above chiasm), suprapineal and pineal (into pineal stalk) recesses; lat divided into ant horn (frontal lobe) post horn (occipital lobe) inf horn (temporal lobe) and body
csf (production- where and structure details, resorption - where and into what, 3 functions of CSF, pressure inc what is considered raised, how it is formed, comp relative to plasma (3 things lower and 1 higher))
continuously produced by choroid plexus (capillary beds embedded in ependymal cells, largest and most obvious in lateral ventricles), with transport through cells required as ependymal cells connected by tight junctions
also continually resorbed into the venous system from the subarachnoid space via the arachnoid granulations, primarily into the sagittal sinus
the brain floats in CSF and this cushions it against mechanical stress from impacts and prevents it collapsing under its own weight; CSF also provides metabolites to the brain and removes waste to the venous system
normally under pressure of 7-18mmHg (measured via lumbar puncture, >25 often considered raised)
pressure gradient filters plasma from caps to choroid interstitium; basolateral exchange of Na for H+ and Cl for HCO3 (CA in interstitium) with apical Na/K/Cl cotransport (both directions) and HCO3/Na cotransport establishing osmotic pressure, water drawn into ventricle lumen through aquaporins; similar comp to plasma but lower protein, glucose and higher Cl (and ofc no cells!), same comp as brain ECF
ventricular system (inc foramina)
two large lateral ventricles develop from the cavity within the cerebral vesicles and connect via the inter-ventricular foramen of Munro with the 3rd ventricle on the midline in the diencephalon (thalamus etc); cavity of the midbrain narrows during development to form the cerebral aqueduct which connects the 3rd and 4th ventricles in the hindbrain with its roof formed by the cerebellum; the 4th ventricle is continuous with the central canal of the spinal cord and the subarachnoid space via the foramina of Magendie (median) and Luschka (lateral, paired); plexi of capillaries wrapped in choroid epithelium (ependymal cells and pia mater) form CSF from blood in the ventricles which then escapes via the foramina of Magendie/Luschka into the subarachnoid space around the brain/spinal cord
hydrocephalus (what it is, 3 fetal risk factors, 3 congen and 5 acquired obstructive causes, 5 reasons for non obstructive, 5 ways infants present, 8 ways adults present, 2 other things that might come from it) and microcephaly (3 coocurring features, 14 causes)
hydrocephalus - inc in csf volume occupying ventricles; maternal hypertension, preeclamp, alcohol use are risk factors
cogen eg agenesis or atresia of foramen of munro, or lusckha/magendie foramina, congen toxoplasmosis, other malforms; acquired from infection (eg exudate block foramina of l/m), h+ after eg injury, tentorial herniation, intravent haematoma, ventricular pineral and post fossa tumours
communicating if thickening of leptomeninges or involvement of arachnoid granulations eg meningitis, sah, choroid plexus papilloma; inc’d csf visc from high protein count; venous sinus thrombosis
infants present with inc’g head circ (or is in 98tj percentile), tense fontanelle, dilated scalp veins, setting sun sign, inc limb tone; older children/adults may have headache, papill, 6th nerve palsy, unsteady gait from leg spasticity, blurred vision, cognitive decline, n&v, neck pain
epilepsy, learning/dev disorders may come from it
microcephaly - smaller than normal head, oft have intellectual disability, poor motor/speech function, seizures; genetic, fas, stroke, congen CMV rubella varicella zika toxoplasmosis; maternal radiation, phenylketonuria, malnutrition, hypothyroid, placental insuff, gest diabetes poorly controlled
vertebral column anatomy (how many vertebrae, structure of a standard vertebra, atlas and axis features x2; general shape and movements of vertebra at different levels, syndrome where cervical might be fused)
33 vertebrae formed from intersegmental somite fusion; 7c,12t,5l,5s,3-4c; bodies are weight bearing parts linked by discs and ligaments with an arch forming foramina which unite to form vertebral canal, continuous with cranial cavity through foramen magnum; pedicles are pillar like extensions with 2 laminae meeting in midline; spinous process projects posteriorly, transverse laterally from each side, sup/inf articular processes from where pedicles join laminae (also where tps come off)
atlas/axis special with atlas no body as it becomes dens of axis, no IV disc between them; sacrum is fused vertebrae with 4 pairs of anterior/posterior sacral foramina for ant/post sacral rami; in spine movement between individual vertebrae is small but can add up
coccyx has no canal or arches; cervical has large triangular foramen, small body with uncovertebral processes, bifid spinous processes, transverse foramina in transverse processes and tubercles for scalene muscles; facets in oblique plane and can do flexion, extension, lateral flexion and rotation; thoracic have circular foramen, demifacets in body for ribs, long spinous processes which point down, articular facets for ribs in tps, facets in arc of a circle, rotation limited by thoracic cage; lumbar have small triangular foramen, large and thick body, thick and oblong sp, large lateral tps, interlocking vertical and sagittal facets, does flexion, extension and lateral flexion; space between adjacent laminae in lumbar region allowing for lumbar puncture; lumbar vertebra may fuse with sacrum and cervical may fuse in klippel-feil syndrome
vertebral column joints (how many, type, how many discs total)
typical vertebra has 6: 4 synovial and 2 symphyses: IV disk is secondary cartilaginous (each body has layer of hyaline cartilage) with anulus fibrosus (collagen and fibrocartilage lamellae arranged concentrically to limit vertebral rotation) and nucleus pulposus at centre, gelatinous to absorb compressive force, 23 in total; zygapophyseal joints synovial between articular processes
ligaments in vert column (8 types)
ant/post longitudinal from skull to sacrum either side of bodies
ligamentum flava between laminae of adjacent vertebrae to resist separation in flexion
supraspinous ligament along tips of sp from C7 to sacrum; before this ligamentum nuchae sheet like structure in midsagittal plane from external occipital protuberance to foramen magnum with apex at C7 continuous with suprapinous ligament
interspinous ligament between adjacent sp blending with ligamentum flava and supraspinous
capsular ligaments for joints
intertransverse ligaments thin and membranous in l region, irregular and often replaced by muscle in c region, cordlike and connected with deep muscles of back in t region
spinal cord and nerves (inc where cord and sac end, where widest diameters, where roots emerge relative to vertebrae, epineurium formation)
from foramen magnum to lower border of L1 where it tapers to cone shaped ending, conus medullaris which is attached to end of dural sac at S2 by stalk of pia mater and nerves from L2 down passing as cauda equina; diameter not uniform with enlargements at C5-T1 and L1-S3 corresponding with limbs, small central canal in cord with longitudinal vessels descending on its surface and segmental spinal arteries from vertebral, deep cervical, posterior intercostal and lumbar arteries; spinal nerve roots from ventral and dorsal horns, make mixed spinal nerve in intervertebral foramen with covering of all 3 meningeal layers that fuse with epineurium as nerves emerge; 8 C roots and 7 verterbra, after this root emerges below corresponding vertebra; dura mater, arachnoid mata, subarachnoid space then pia mater; epidural space between dura mater and vertebral periosteum contains loose connective tissue, venous plexuses, lymphatics; subarachnoid contains CSF and extends to terminate at lumbar cistern at S2, facilitating lumbar puncture
spine loading and the vertebral disc (why more strain in disc and how structure of disc functions as shock absorber; why herniate backwards; role of zygapophyseal joints)
load to spine stresses stiff vertebral body and relatively elastic disc so strain more easily produced in disc; even at rest pressure within nucleus pulposus >0 to provide preload mechanism for resistance to applied forces, when hydrostatic pressure rises exerts pressure on anulus fibrosus whose concentric fibres bulge and experience tensile forces, transferring the force to slow application of force and thus act as shock absorber; annular fibres thinner posteriorly with less strictly arranged collagen hence herniation backwards; zygapophyseal joints help resist shear forces
spinal cord afferent systems - 2 main pathways inc routes and where they terminate
one pathway for tactile sensation/proprioception, one for nociception and thermal sensation; the latter carried by afferents through dorsal roots, terminating in dorsal horn close to entry; after at least one relay, projection cells send axons across ventral commisure to contralateral anterolateral white matter where they ascend, fibres terminating in medulla, pons, midbrain and several parts of thalamus; this anterolateral ascending system also called spinothalamic tract
axons of tactile system (propioception and touch) enter spinal cord and ascend in ipsilateral dorsal columns without synaptic relay (though do give branches to spinal cord); terminate at rostral end of spinal cord in gracile and cuneate (dorsal column) nuclei; axons from these cross midline and ascend in large tract of fast conducting fibres (medial leminiscus, found in medial brainstem); hence this system is is dorsal column medial meniscus system; fibres project to thalamus from where 3rd order neurons project to somatosensory cortex in postcentral gyrus of parietal lobe
spinal cord cross sectional anatomy (white matter columns, contents of each, and what is in medial ventral horn; grey matter subdivisions inc what is later 2 and what does it contain, what overlies it, what are in deeper layers of dorsal horn; what and where are largest neurons in spinal cord; what layer is in centre of cord)
white matter: 3 basic columns/bundles/fasciculi: dorsal, ventral and lateral; anterolateral system runs ventrally in lateral column; dorsal column can be subdivided at high thoracic/cervical levels into lat cuneate and medial gracile divisions (fibres from upper/lower limbs respectively); dorsolateral column has many descending motor fibres, as does the ventral column; in ventral horn, motor neurons for axial muscles are more medial
grey matter can be divided into layers: Rexed’s laminae; these represent functional specialisations; most important is layer 2, substantia gelatinosa which is critical for processing noxious information and thus a therapeutic target; overlying this is Lissauer’s tract which contains afferent axons carrying pain/temp that travel up or down the cord to an adjacent segment before entering the dorsal horn; deeper layers of dorsal horn (IV/V) have relay neurons with axons crossing midline in ventral commisure for anterolateral system; largest cells in spinal cord are motorneurons projecting to muscles, found in groups in ventral horn; major region in centre of cord (lamina VII) has interneurons for local processing ie reflexes
cross sectional anatomy of brainstem (3 gross components and along dorsal surface what you see, what you’ll seein terms of sensory pathways at caudal central and rostral levels of medulla (inc what nucleus is prominent), what you’ll see in upper pons, sections through lower and upper midbrain)
medulla, pons and midbrain; from dorsal surface can see thalamus on top at either side with sup/inf colliculi inferior to it; inf to these are sup/mid/inf cerebellar peduncles; inf to this are cuneate swelling/tubercle and gracile swelling/tubercle (former lat, latter med)
section through caudal medulla can see dorsal columns, anterolateral tract and between them the prominent spinal nucleus of the trigeminal nerve; this and the tract of CNV are continuous with and homologous to substantia gelatinosa and Lissauer’s tract; section more rostrally in medulla (at level of sensory decussation) can see gracile and cuneate nuclei, medial leminiscus arching from them to midline where sensory decussation is; lateral to ML is prominent spinal trigeminal nucleus with overlying fibre tract; section through upper/rostral medulla, all ascending sensory fibres have terminated so tactile pathway represented by ML in midline; still large trigeminal sensory nucleus though not as clear as at lower levels
section through upper pons reveals ML dorsally and more lateral; along ventral midline is groove for basilar artery; section through midbrain has prominent tectum (roof) formed by colliculi, which is dorsal to narrow aqueduct running through midbrain to link 3rd/4th ventricles; in lower midbrain, IC is visible either side, with ML more lateral and joined by fibres of anterolateral tract (so sometimes called spinal leminiscus); section through upper midbrain is similar but with sup colliculi visible instead
thalamus (what it is and function served, which nuclei more concerned with sensation and motor coordination) and internal capsule (what it is and contains)
major route to cerebral cortex, relaying info from medulla, cerebellum and brainstem and other areas of hemisphere; has many component nuclei, some that project specifically to defined areas and others with more extensive/diffuse projections; ventral nuclei concerned specifically with sensory relay/motor coordination;
internal capsule is massive white matter tract linking cortex to thalamus that also contains descending fibres and fibres running between nuclei of thalamus and different cortical regions
afferent pathways overall (routes inc level of gracile cuneate fasciculi starting, and 2 types of second order neurons in spinothalamic pathway, 5 places those neurons terminate and 2 places descending modulation comes from)
fine touch/prop: primary sensory axons enter dorsal root and ascend in dorsal columns, no synapse and so very long; above mid thoracic level each dorsal column has medial gracile fasciculus for lower body fibres and lat cuneate fasciculus for upper body fibres; in dorsal column nuclei second order neurons arise, sending axons in ribbon like ML that decussates across midline, reaching thalamus to synapse onto third order neurons that project to primary SSC by internal capsule
thermal/pain: primary afferent bifurcating into short ascending/descending branches running in Lissauer’s tract for about a spinal segment and giving branches that enter/synapse in dorsal horn, principally in substantia gelatinosa (pale, jelly like appearance and containing unmeyelinated fibres, small cell bodies and processes); this first synapse allows modulation/gating of pain by eg endogenous opioid peptides; second order axons arise on same side of body as stimulus; diversity of second order neurons: some in lamina V also have input from tactile system and called wide dynamic range neurons; another group in lamina I are nociceptor specific; axons from both groups cross midline in ventral commisure below central canal and ascend contralaterally in anterolateral white matter (not a distinct tract though major component with fibres terminating in thalamus called spinothalamic tract); from thalamus, 3rd order neurons ascend via internal capsule to processing areas; many fibres of anterolateral system also terminate in brainstem, esp in reticular formation, where they influence level of arousal through actions on symp system (medulla) and other ascending systems; considerable modulation of this system by descending pathways from higher centres like raphe nuclei in reticular formation of medulla and periaqueductal grey of midbrain
lesions of primary SCC don’t lead to pain loss; lesions in other areas did; some project to primary SCC helping with localisation of pain; others to insula (seems to be major relay station for pain processing); also anterior part of cingulate gyrus (medial part of frontal lobe, esp important for affective part of pain perception
motor control (3 cortical areas and their roles, pyramidal paths including 2 output tracts, general function of cerebellum, difference in cerebellar and extra pyramidal sx)
motor areas of cerebral cortex: PMC (executing movements once planned and prepared in other areas), premotor cortex (externally guided movements eg response to visual stimulus, postural adjustments to prep for movements) and supplementary motor area (internally triggered movements eg remembered sequences + coordinating hemispheres)
main route from brain to spinal cord is corticospinal tract with axons from motor cortex running in internal capsule, cerebral peduncles, pons, emerge as medullary pyramids and continue as crossed lateral and uncrossed ventral corticospinal tracts in spinal cord; damage can give paresis/paralysis; motor structures prominent on ventral surface of brainstem and in cross section
cerebellum involved in motor co-ordination and learning and humans is esp large, reflecting use of tools, dexterity and speech; cerebellum connects with other structures via cerebellar peduncles; cerebellar cortex one of best understood parts of brain in terms of connectivity; damage to cerebellum can result in ataxia; brains originally evolved to control movement; cerebellar disease often worsens on movement and extra pyramidal often improves
corticospinal and corticobulbar system (combined form what, function of each, axons of what neurons form which layer form, what pathway do these neurons take, what percent of spinal fibres decussate and where (continuing as what); 5 targets for corticobulbar system)
collectively the two pyramidal tracts
corticobulbar tract is equiv of corticospinal tract for nerves innervating musculature of head and neck
motor areas of cortex in frontal lobe, anterior to central sulcus; axons of pyramidal neurons in layer V of motor cortex form corticospinal tract and run in internal capsule which forms cerebral peduncles; after emerging as medullary pyramids, corticobulbar fibres leave to innervate motoneurons of CNS (but not the ones controlling eye movements);
90% of corticospinal fibres cross midline at base of pyramids and continue as lateral corticospinal tract, with uncrossed ventral corticospinal tract also continuing into spinal cord; descending corticospinal tract massive in humans: over 1mil axons enter spinal cord either side
corticobulbar fibers exit at the appropriate level of the brainstem to synapse on the lower motor neurons of the cranial nerves. In addition to endings in these motor neurons, fibers of the corticobulbar tract also end in the sensory nuclei of the brainstem including gracile nucleus, cuneate nucleus, solitary nucleus, and all trigeminal nuclei
motor pathways (route from IC, where medulla becomes cord, side distribution of corticobulbar fibres, which nuclei aren’t innervated by these fibres and why, what structure is lateral to pyramids and what do they provide, structure deep to peduncles (and structure deep to this), why CPs much larger than pyramids, how many cross and where they descend, where they terminate x2
in midbrain, fibres from internal capsule form cerebral peduncles; cortical fibres hard to spot in pons, some pass through as corticospinal/bulbar tracts and corticopontine fibres terminate; in medulla, medullary pyramids are emerging corticospinal fibres which decussate with motor decussation marking boundary between medulla and spinal cord; corticobulbar fibres leave tract at various points to synapse with motor nuclei in medulla and pons, many distribute bilaterally (trigeminal motor nucleus in pons, facial motor nucleus, nucleus ambiguus); eyes not as need to move consensually so controlled directly by brainstem; inferior olives either side of pyramids, associated with climbing fibre input to cerebellum
CPs are massive bundles of white matter on ventral midbrain; just deep to this are dopaminergic neurons of substantia nigra and deep to this are red nuclei; most fibres in CPs terminate in pons onto neurons that project as mossy fibres into cerebellum, thus peduncles larger than pyramids
upper medulla ventrally has medullary pyramids and deep/lateral to them inf olivary nuclei; in lower medulla is motor decussation (85% cross and continue contralaterally, almost all other descending ipsilaterally, mainly in medial part of ventral funiculus and most of these will cross midline before terminating); in spinal cord can see dorsolateral area containing lateral corticospinal tract containing crossed fibres from contralateral cortex, and ventral area containing ventral corticospinal tract containing uncrossed fibres from ipsilateral cortex
most terminate on spinal interneurons to influence both motor and sensory processing and in most mammals this is main route for movement control; primates also have direct cortico-motoneuronal connections, esp the large corticospinal fibres; this latter connection especially common for distal muscle control (ie intrinsic foot/hand muscles); this connection esp developed in great apes and esp humans, underlying our dexterity
brainstem motor centres (vestibulospinal moves where and does what, reticulospinal does what, rubrospinal does what (gets input from where, where is red nuclei main output destination), cross sectional anatomy in spinal cord location of the motor tracts and general function; 3 main cranial nerve motor nuclei; which 2 pathways trigger automatic postural responses, lesions of these tracts thus lead to what, what causes decerebrate and decorticate posturing and why the latter mainly affects arms differently)
gives rise to other descending pathways which are smaller and less obvious as their fibres mingle with ascending/descending ones
vestibulospinal tracts descend in ventral columns of spinal cord, arising in vestibular nuclei of dorsal medulla and acting mainly on extensor/antigrav limb muscles and proximal neck/trunk muscles to maintain posture/equilibrium; reticulospinal originate from cells of reticular formation of pons/medulla and send fast conducting axons through length of spinal cord, involved in posture too; rubrospinal tract fibres from red nuclei of midbrain are numerous in mammals, nuclei large in humans but sends few fibres to spinal cord, mainly involved in big upper limb movements (flexion); receiving input from cerebellar nuclei and areas of cortex; besides rubrospinal, red nucleus majority output mainly to inf olivary nucleus; thought to be involved in motor skills learning
ventral system involved in posture and contains ventral corticospinal (some decussate, meaning both sides innervated by neurons from both sides so lesions often masked) as well as med/lat reticulospinal and lat vestibulospinal tracts; meanwhile dorsolat system is for appendicular muscles and contains lateral corticospinal and rubrospinal tracts
also cranial nerve motor nuclei: trigeminal, facial, nucleus ambiguus
Two major descending systems carrying signals from the brainstem and cerebellum to the spinal cord can trigger automatic postural response for balance and orientation: vestibulospinal tracts from the vestibular nuclei and reticulospinal tracts from the pons and medulla. Lesions of these tracts result in profound ataxia and postural instability.
Physical or vascular damage to the brainstem disconnecting the red nucleus (midbrain) and the vestibular nuclei (pons) may cause decerebrate rigidity, which has the neurological sign of increased muscle tone and hyperactive stretch reflexes. Responding to a startling or painful stimulus, both arms and legs extend and turn internally. The cause is the tonic activity of lateral vestibulospinal and reticulospinal tracts stimulating extensor motoneurons without the flexion input from rubrospinal and corticospinal tracts.
Damage above the red nucleus level may cause decorticate rigidity (so eg cerebrum, internal capsule, thalamus). Responding to a startling or painful stimulus, the arms flex and the legs extend. The cause is disinhibition of the red nucleus, via the rubrospinal tract, counteracting the extensor motorneuron’s excitation from the lateral vestibulospinal and reticulospinal tracts. Because the rubrospinal tract only extends to the cervical spinal cord, it mostly acts on the arms by exciting the flexor muscles and inhibiting the extensors, rather than the legs -> which extend due to loss of corticospinal flexor input
low back pain- commonest reasons, when to suspect fracture x2 and imaging to get, prolapsed disc what worsens pain, 9 further dd, 2 complications, red flags for CA, malignancy, infection, AAA, fracture (inc 2 things making fracture less likely), 1 thing making mechanical cause less likely)
mechanical back pain most common but diagnosis of exclusion
vertebral fracture if onset coincides with injury or if bony tenderness, LXR -> CT
prolapsed disc, straight leg test
renal colic from loin to groin, micro haematuria in 95% cases; pyelonephritis; renal cancer; symptomatic aortic aneurusm: shock and sudden pain if noncontained bleed, pain if contained bleed, rapidly growing w/o rupture hurt due to stretching of the a wall; beware esp in those >55, and often they present with what seems to be left sided renal colic due to bleed contained in left retroperitoneal space, but may have abdo tenderness; abdo uss to rule out as exam alone often doesnt pick up
bony mets - constant, chronic, unremitting, worse at night - needs myeloma screen and MRI, may present with fracture
pancreatitis relatively common but usually abdo pain radiating to back, check serum amylase
discitis, osteomyelitis, epidural abscess
prostatitis often has severe pain in lower back and perineum, prostate exam v tender, sometimes fevers and rigors, often associated uti
many of above can cause cauda equina or spinal cord compression
red flags for cauda equina: saddle area paraesthesia, urinary retention or incontinence, faecal incontinence
red flags malignancy - constant pain inc at rest and night
red flags infection - fever, constant pain inc at rest
aaa red flags - abdo pain, sudden onset or cv collapse, >55yo
fracture red flags - history of trauma w/ pain starting soon after; fractures unlikely if pain free after accident then pain devs, or if no bony tenderness
mechanical cause unlikely if pain not made worse by movement
fasciculations- suggestive of damage where, and 7 more common dd
anterior horn cell damage (ie LMN)
werdnig-hoffman disease, poliomyelitis, syringomyelia, cervical spondylosis, denervation of a nerve root, hyponat, hypomag/calc
neurological consequences of B12 def x4 (inc what 2 tracts most affected by SACD)
SACD (pyramidal tracts and dorsal column), periph neuropathy, optic neuritis, dementia/personality changes
B12 deficiency-> required for what 2 processes, 2 main systems affected by deficiency and are both always affected?; 4 main areas of nervous system affected and signs/sx from each; 3 things to check the level of, how do B12 and folate interact and which is more commonly deficient; 2 key co-factors and how to interpret their levels inc functional vs true deficiency; how does nitrous effect and why does B12 supplementation not matter; link between metformin and B12 deficiency
required for DNA synthesis and myelin sheath formation; deficiency usually results in megaloblastic anemia (due to impaired hematopoiesis) and/or neurologic manifestations (due to myelin damage). A minority of patients have neurologic findings alone; therefore, the lack of hematologic abnormalities (eg, macrocytosis) does not exclude the diagnosis. Neurologic abnormalities generally arise because of damage to the following:
Dorsal columns, leading to impaired vibratory sensation/proprioception and sensory ataxia (gait impairment that worsens when the eyes are closed [positive Romberg sign])
Lateral corticospinal tracts, leading to positive Babinski sign
Myelinated peripheral nerves, leading to lower extremity paresthesias
Myelinated fibers in the brain, leading to neuropsychiatric manifestations (eg, irritation, mood changes)
Workup begins with a serum vitamin B12 level, but methylmalonic acid and homocysteine levels may be required if results are inconclusive -> raised MMA can indicate deficiency if borderline, or as some ppl show signs with normal levels, or can have functional/uptake related deficiency without true deficiency, so MMA and HC raised if deficient at tissue level even if not in serum
it’s more common to have a folate deficiency than B12 but a folate deficiency can give a functional B12 deficiency due to the two being co-factors in the methylation cycle. The same is true vice versa, and B12 should always be checked as well before supplementing folate if folate found to be low
Homocysteine is consumed in folate aspect & MMA in B12 aspect of methylation cycle. Raised levels = not enough of B12/folate in respective arm of the cycle. However, since they are co-factors, it’s possible to have a true deficiency in one (measurably low serum) and a functional deficiency in the other (normal serum but high levels of the substrate (MMA/homo)) as the process of both is impaired by the absence of one; hence raised levels of MMA is very sensitive for B12 deficiency
it’s a false reassurance if a patient tells you they use NO2 but supplement B12, as the nitrous doesn’t interfere with absorption of B12 but impairs one of the enzymes involved in the methylation cycle which utilises that B12. So clinically the symptoms are of B12 deficiency and often serum B12 is adequate, it’s just that it can’t be used
also note 30% of patients on metformin develop clinically significant vitamin B12 deficiency after ≥5 years of treatment. The mechanism is not entirely elucidated but may be in part due to metformin altering calcium homeostasis in the gastrointestinal tract, thereby impairing calcium-dependent vitamin B12 absorption
5 causes of absent ankle jerks with extensor plantar response
a mixture of umn and lmn signs seen in
B12 def, werdnig-hoffman disease, friedreich ataxia, conus medullaris lesion, taboparesis
babinski sign vs foot tapping
foot tapping (hold foot slightly off floor, rapidly tap toes up and down) as much higher sensitivity for UML than babinski - babinski maybe 37% where this is >90%, and will look abnormal due to spasticity
however, babinski still has a place as it is more specific, with abnormal foot tapping also a type of dysdiadochokinesia
werdnig-hoffman disease (aka, 2x sx in fœtus, 2x sx in baby, relation to age and progression; 11 general sx; 2 features of late onset form and what 2ix are and might show)
aka SMA type 1, is an AR disease with prog destruction of ant horn cells
variable presentation may start in intrauterine life (reduced fetal movements, polyhydramnios) or after (breathing difficulties inc cyanosis, poor feeding); earlier onset, quicker decline in function; see prox muscle weakness, hypotonia, muscle wasting, facial diplegia, flaccid quadriplegia, loss of reflexes (unlike myotonic dystrophy), bulbar palsy, abdominal see-saw breathing, and bell shaped chest; fasciculations and resp failure, up to death
milder form starts in late childhood, prox leg weakness progressing over years with normal mental function; emg may show spont fasciculations and biopsy may show atrophy; treatment supportive
acute paraplegia - how spinal cord trauma evolves over time, 3 common reasons for cord compression, 9 other ddx for acute paraplegia
remember that trauma to spinal cord will first show spinal shock with predominantly LMN signs slowly replaced by UMN (which will include loss of sphincter tone and urinary retention or incontinence if at high enough level)
cord compression caused by tumour, abscess, bone (trauma)
also consider transverse myelitis (oft after viral illness like chickenpox and treated with steroids), discitis, GBS, hysterical paraplegia, MS, SACD, sagittal sinus thrombosis, anterior spinal art thrombosis, friedreich ataxia
infectious causes of radiculopathy and myelitis
Clinical Indications Suspicious of an Infectious
Myelopathy:
Fever
Confusion
Meningism
Rash (lyme, zoster)
Lymphadenopathy
Causes:
HSV, VZV, CMV, EBV, HHV 6/7
Flaviviruses
Influenza A
Measles, mumps
Enteroviruses including polio
Mycoplasma
Borellia
Treponema
TB
Rarely fungi and parasites
Blood culture and serology, CSF culture, microscopy, viral PCR and serology
Poliomyelitis, or gray matter myelitis, is usually caused by infection of anterior horn of the spinal cord by the enteroviruses (polioviruses, enteroviruses (EV) 70 and 71, echoviruses, coxsackieviruses A and B) and the flaviviruses (West Nile, Japanese encephalitis, tick-borne encephalitis). On the other hand, transverse myelitis or leukomyelitis, or white matter myelitis, are often caused by the herpesviruses and influenza virus.
VZV, HSV, and lyme among others can also cause an infectious radiculopathy/radiculitis
friedreich ataxia - tracts affected, inheritance pattern, 8 features and what x2 happens in middle age
degen of dorsal tracts, lat corticospinal tracts and spinocerebellar tracts
AR inheritance
1-15yo cerebellar ataxia first of lower then upper limbs; broad-based gair, spasticity of legs with upgoing plantars; dorsal column changes inc absent ankle jerks
scoliosis and pes cavus common; cardiomyopathy giving arrhythmias and heart failure; optic atrophy; dementia and death in middle age
6 causes of pes cavus
idiopathic
friedreich ataxia
duchenne
spina bifida
CMT
tethered spinal cord syndrome
tethered cord syndrome (how conus medullaris moves over time, 4 egs of causes, spina dysraphism, sx worsened x2, what may overlie dysraphism, 5 sx and 2 ix, mx and what influences success
at 3mo in utereo conus medullaris at end of spinal cord, but descends to L3 due to differential growth, then L1/2 after a few months
interference in growth may tether the spinal cord, eg myelomeningocele, tight filum terminale syndrome, diastematomyelia, intradural lipoma etc
occult spina dysraphism in 15-30% of pop, with spinous process absent in a vertebra
sx usually after period of growth and exacerbated by exercise
hypertrichosis may overly the dysraphism; weakness of legs or sensory problems may occur as well as eg club foot or pes cavus, incontinence; uss or ideally MRI to diagose; urodynamics to assess urinary dyfunction
untethering to treat, more succesful the earlier it’s done
child w continuous burning sensation in a part of body, poss also hyperaesthesia, doesnt correlate to distribution of a periph nerve; may be history of trauma eg fracture in area of the pain, and pain may worsen on movement - condition, 2 other short and 2 long term features, mechanism, 3x mx
reflex sympathetic dystrophy, may also have autonomic features eg sweating, erythema; long term get skin atropy and disuse atrophy
initial injury provokes hyperactive autonomics
physiotherapy, sympathetic blockade, may improve w time
descending pathways and pain (why modulate, 3 main centres of descending input and what x3 inputs to these areas from above, how does the main area work (pathway), what things can placebo work for, organisation of PAG and impact of naloxone on placebo
pain is heavily modulated, allowing it to be integrated with other systems like skin reflexes, attention, emotion and autonomics
descending systems located in periaqueductal grey (PAG) matter of mid brain, the raphe nuclei and other nuclei of the rostral medulla; electrical stim of PAG can produce sufficient analgesia for abdo surgery though other, non-painful sensations left intact; PAG thought to control nociceptive gate in dorsal horn by integrating inputs from cortex, thalamus and hypothalamus; morphine induced analgesia blocked using naloxone (opiate antagonist) introduced into PAG, can also block electrical analgesia; bilateral transection of dorsolateral funinculus blocks both this and morphine induced analgesia; many PAG neurons excite serotonin neurons in rostroventral medulla which inhib neurons in laminae 1/2/5
placebo analgesia (non-analgesic gives analgesia) when subject told it’s a painkiller; placebo effect also works for diabetes, cough, asthma, MS, ulcers and parkinsonism; pain modulation thought to be targeted to whole body, recently suggested opioid modulation can be targeted (volunteers have capsaicin applied to distal limbs, asked to report pain intensity, placebo cream applied with placebo analgesia only on treated part; naloxone intravenous infusion abolished placebo response suggesting it is mediated by one of endogenous opioid systems; attentional mechanisms can be directed to specific parts of body, with argument that spatial specific organisation retained by endogenous opioid systems and indeed rats found to have somatotropic PAG, stimulating different areas producing analgesia in different cutaneous regions
neuropathic pain relief (7 drugs inc mechanism)
SNRIs like duloxetine and TCAs like amitryptiline provide pain relief in neuropathic pain, presumably by descending inhib modulation from locus coeruleus via NA; gabapentin (GABA analogue developed as epilespy drug) has no activity at GABAr, but can block neuropathic pain in some patients (not acute pain), appears to decrease PM CaV a2d1 subunit localisation (upregulated in some neuropathic pain to inc Ca current) thus gabapentin decreases CaV current density and decreases spinal NT release with pregabalin a successor with better pharmacokinetics; lidocaine acts by blocking NaVs, providing anaesthesia via local application by preventing spontaneous peripheal neuron discharge associated with neuropathic pain, carbamazepine and lamotrigine also NaV blockers used as anti-epileptics and neuropathic pain relief
vertebral fracture (7 causes, sx inc of rotary injury, mx)
usually from violent impact eg fall or jump from height or vehicle accident; osteoporosis often the cause, esp in older ppl, or bone weakness due to hyperparathroidism, prolonged corticosteroid use, osetomalacia, myeloma, carcinoma met to the bone
pain usually immediate but may be delayed up to days after; all lumbar movements limited, spasm of lower lumbar muscles, radiographic appearance
high impact rotary injury can break transverse process and tear paravert muscle giving limited movements, deep tenderness, local haematoma, and poss bleeding into retroperitoneal space giving groin pain, prox leg weakness and loss of patellar reflex, and grey turner sign
body fractures usually need bed rest and analgesia
herniated disc (usually what age, most common 3 levels, likely mechanism of injury, 5 findings, 4 things that might exacerbate pain, posture you might see, differentiate this foot drop from peroneal nerve injury, reflex lost in S1 but not L5, which give diminished knee jerk, ix and when to do, resolves over how long, 4 mx
usually in 3rd/4th decade where nuc pulp still gelatinous
L5-S1 most common, then L4-5, L3-4, L2-3, and finally L1-2 quite rarely
flexion injury likely cause of herniation but pt often wont recall a particular trauma; sneeze, lurch, or trivial movement may be enough if sufficient degen of post long ligs and ann fib; nuc impinges on root or roots giving radicular pain
typical picture: sacroiliac pain radiating into buttock, post thigh and calf (sciatica), maybe feet, stiff spinal posture, some of paraesthesia, weakness, reflexes may be lessened in affected root
straight leg raise should provoke pain, as often will dorsiflexion of foot or even great toe; if other leg straight raise provokes pain then specific but not sensitive for herniated disc
flexion of head and neck can exacerbate as should coughing
if inconsistencies in these tests suspect psych component or muscle injury
antalgic posture (sciatic scoliosis) is maintained; limp with knee slightly flexed and brief cautious weight bearing, going up/downstairs esp hard
foot inversion will be weak, unlike foot drop due to peroneal nerve damage which spares inversion as this controlled by tibial nerve; S1 achilles reflex lost, whereas not in L5
L3 and 4 give diminished knee jerk
clinical pic should be enough, MRI to confirm esp if persistent symptoms
some bed rest although sciatica tends to resolve within 3-6 months
NSAIDs, if not add codeine, if together dont work can try amitryp; still no luck can consider referral for surgery
chronic sciatica (12 causes)
besides disc herniation may get entrapment due to spondylotic spurs, cysts of synovium due to facet joint degen; this is not uncommon and cyst can be removed if pain intractable; may also get cyst like dilatation of perieural sheath compressing sacral roots where they penetrate the dura
endometriosis of the nerve at the sciatic notch may give premenstrual sciatica; uterine traction on nerve can give sciatica during each pregnancy
nerve damage from DM, herpes zoster, infarction, retroperitoneal mass; sometimes lumbosacral plexus neuritis; also tumours affecting sciatic nerve
also oa or other degen cause narrowing of canal compressing lumbar or sacral roots - flucutating ache often precipitated by prolonged sitting, standing, walking, rest relieves pain
neoplastic and infectious back pain (5 cancers commonly met to spine, 2 features and 2 complications), 4 infectious causes of back pain
BBKPT commonest mets to spine (breast, bronchus, kidney, prostate, thyroid) also pancreas; constant dull pain unrelieved by rest and worse at night, often interrupting sleep; may become radicular if met extends lat; may cause fracture of vert body, esp suspicious if in young or middle aged person;
tuberculous infection giving kyphotic deformity common in developing countries
spinal epidural abscess needs surgical drainage, otherwise paraplegia and poss sepsis; often from blood, osetomyelitis, ivdu, sometimes lp or epidural; low grade fever, leucocytosis, persistent severe localised pain intensified by percussion; may become radicular
discitis
reflex roots (big 5) and dermatome roots (inc angle of jaw, middle finger, nipples, umbilicus, middle of foot, lat border of foot)
Reflex Root
Triceps C7/8
Supinator C5/6
Biceps C5/6
Knee L3/4
Ankle S1/2
Dermatome Root
Angle of the Jaw C2
Middle Finger C7
Nipples T4
Umbilicus T10
Middle of foot L5
Lateral border of
foot S1
degenerative cervical myelopathy (5 sx, progression speed, main ix, mx)
Typically presents with
– Neck pain
– Sensory symptoms in both hands
– Unsteadiness and falls
– Upper limb weakness, eg. difficulty opening bottles or using a mobile phone
– Can get bladder involvement
– Gradual progression
* Abnormalities on examination can be mild and presentation can be asymmetrical
MRI to ix
* Treatment is surgical when indicated, and avoiding falls
spinal cord infarct (prominent feature and why, area spared, how initial imaging looks, radiology hard to tell from what, 4 classic features, how long spinal shock lasts, 5 ix, can occur after what, 2 mx)
(ant horn syndrome): Not common; about 1% of all strokes
* Pain is often a prominent feature, presumably because of involvement of the spinothalamic tracts
* Dorsal columns are typically spared
* Initial imaging may be normal, as in stroke
* Radiologically it can be difficult to differentiate from inflammatory lesions
* Classic presentation is of weak floppy legs with a sensory level to pinprick but preserved JPS and VS, with bladder and bowel involvement
* Spinal shock (floppy legs with absent reflexes) can last several days
* Further investigations may include a thrombophilia screen,
vascular imaging from aorta to carotids as well as echo,
rheumatological and vasculitic (including syphilis) investigations.
CSF is often examined. Often no cause found.
* Can occur after aortic aneurysm repair (artery of Adamkiewicz)
* Treatment is with aspirin; rehabilitation via spinal injuries unit
syringomyelia (age at presn, assoc, sx progression x3 and usual spared area, mx, rule out what), neuromyelitis optica (antibodies against what/where, 3 areas affected and sx from this, x2 short term management and x3 long term), thoracic meningioma (imaging vs clinical finding, contrast enhancement, mx)
Syringomyelia: Prevalence 8-10 per 100,000
- Typically presents in 20s and 30s
- Congenital, usually associated with Arnold
Chiari malformation
- More usually presents with suspended sensory loss (arms > legs); cape distribution and typically spares dorsal columns
- As the syrinx expands, it can affect motor function (hands first, spreading proximally)
- Can extend into the brainstem
- Treatment is surgical decompression
- Need to make sure there is no associated lesion eg. tumour
neuromyelitis optica: Aquaporin IV antibodies; targets astrocytes (foot processes so often see along BBB), not oligodendrocytes
- Longitudinally extensive transverse myelitis
- Also affects the optic nerves and area postrema (loss of vision with colours appearing faded and nausea/vomiting respectively)
- Treat with steroids and consider plasma exchange
- In longer term, immunosuppression
with azathioprine, mycophenolate or
rituximab
thoracic meningioma: Tend to be slow growing, hence fairly significant
radiological cord compression with often mild clinical findings
- Like cerebral meningiomas, typically enhance uniformly
- Can be removed surgically
cauda equina syndrome (6 sx, 1 ix, 1 mx, 2 causes, 3 ddx) and AV fistula (between what levels, 4sx, 2 mx)
cauda equina: back pain with lower motor neurone syndrome (with loss of reflexes)
* Multiple roots compressed, with variable weakness
* Red flags include saddle anaesthesia, bilateral radicular
pain, impaired bladder/bowel/sexual function
* Requires urgent MRI and neurosurgical intervention
* Don’t forget other causes, such as prostate mets (bones) and epidural abscesses + back pain with urinary retention due to pain and opiates (which can also cause
constipation, another cause of urinary retention)
spinal AV fistula: >80% between T6 and L2
- Typical combination of slowly
progressive walking problems, sensory symptoms and sphincter involvement
- Often get combo of upper and lower motor neurone involvement
- Treatment is to identify the site of the fistula and attempt to embolise it.
Surgery may also be considered
spinal pathology ddx - 14
Congenital: syringomyelia (suspended sensory loss, dorsal columns oft spared,motor involvement later)
– Degenerative: cervical myelopathy, lumbar canal stenosis
– Functional: important differential, especially in context of pain
– Infective: eg. varicella zoster, syphilis
– Inflammatory: MS, Neuromyelitis optica
– Metabolic: vitamin B12 deficiency and subacute combined degeneration of the cord (posterior and posterolateral columns)
– Traumatic: cauda equina
– Tumour: spinal meningioma (slow growing), lymphoma (quick growing)
– Vascular: spinal cord infarct (dorsal columns usually spared), dural AV fistula
autonomic dysreflexia - cause, 3 step process, 5 sx, 2 mx
clinical syndrome occurs in patients who have had a spinal cord injury at, or above T6 spinal level. Briefly, afferent signals, most commonly triggered by faecal impaction or urinary retention (but many other triggers have been reported) cause a sympathetic spinal reflex via thoracolumbar outflow. The usual, centrally mediated, parasympathetic response however is prevented by the cord lesion. The result is an unbalanced physiological response, characterised by extreme hypertension, flushing and sweating above the level of the cord lesion, agitation, and in untreated cases severe consequences of extreme hypertension have been reported, e.g. haemorrhagic stroke.
Management of autonomic dysreflexia involves removal/control of the stimulus and treatment of any life-threatening hypertension and/or bradycardia.
brown-sequard syndrome is what injury, 3 areas affected, 3 sx; subacute combined degen of cord 4 causes, 3 areas affected, 3 sx; friedrichs ataxia resmbles what + other feature; anterior spinal artery occlusion 2 areas affected, 2 sx; syringomyelia 2 areas affected, 2 sx; tabes dorsalis cause, area affected, 1 sx
Brown-Sequard syndrome (spinal cord hemisection)
1. Lateral corticospinal tract
2. Dorsal columns
3. Lateral spinothalamic tract
1. Ipsilateral spastic paresis below lesion
2. Ipsilateral loss of proprioception and vibration sensation
3. Contralateral loss of pain and temperature sensation
Subacute combined degeneration of the spinal cord (vitamin B12 & more rarely vit E, cu, folate deficiency)
1. Lateral corticospinal tracts
2. Dorsal columns
3. Spinocerebellar tracts
1. Bilateral spastic paresis
2. Bilateral loss of proprioception and vibration sensation
3. Bilateral limb ataxia
Friedrich’s ataxia Same as subacute combined degeneration of the spinal cord (see above)
In addition cerebellar ataxia → other features e.g. intention tremor
Anterior spinal artery occlusion
1. Lateral corticospinal tracts
2. Lateral spinothalamic tracts
1. Bilateral spastic paresis
2. Bilateral loss of pain and temperature sensation
Syringomyelia
1. Ventral horns
2. Lateral spinothalamic tract
1. Flacid paresis (typically affecting the intrinsic hand muscles)
2. Loss of pain and temperature sensation
Neurosyphilis (tabes dorsalis)
1. Dorsal columns
2. Loss of proprioception and vibration sensation
spinoreticular and spinomesencephalic tracts - projection from where to where, function of former
former projects from laminae VII/VIII and terminating in reticular formation and thalamus to promote arousal and automatic responses to pain; some of these axons don’t cross midline; latter projects from laminae I and V via anterolateral quadrant of spinal cord to mesencephalic reticular formation and periaqueductal grey
mechanoreceptors in skin - 4 main types and what structure theyre in, how they respond to mechanical stim and what determines which kind of stim they respond best to; where RA2 are and role; what RA1 respond best to and the utility of rapid adaptation; general difference in response between RA and SA; why is amplitude encoded by number of fibres rather than frequency of firing for RA; SA1 role and how encode stimulus magnitude; SA2 role
4 principle mechanoreceptive systems innervating glabrous skin of hand: slowly adapting type 1 (end in merkel cells), rapidly adapting type 1 afferents that end in Meissner’s corpuscles, rapidly adapting type 2 pacinian corpuscles and slowly adapting type 2 afferents (end in Ruffini endings); all respond to mechanical stim by producing depol receptor pot, and type of stim they respond best to determined by accessory structures (like lamellae in pacinian corpuscles)
RA2; pacinian corpuscle is concentric layers of cellular membranes alternating with fluid filled spaces, and distributed widely (inc periosteum of bones, connective tissue in muscles, and mesentery) and extremely sensitive, responding to 10nm of skin motion at 200Hz; sense pressure and higher freq vibration; play role in perceiving edges of objects held in hand etc
RA1; receptive fields averaging 3-5mm in diameter and respond best to low freq (10-40hz) vibration; perceive slip between skin and object eg in feedback signals for grip control; rapid adapting hence eg stop feeling your clothes
rapidly adapting receptors respond only to onset of stimulus whereas slowly adapting receptors give tonic response to constant stimulus; rapid adaptors respond to low freq sinusoidal mechanical stim with single AP for each phase of stim, treating each period as new stimulus; this is phase-locking and intensity of sinusoidal stim must thus be encoded by number of active sensory fibres rather than freq of firing; number of active fibres is linearly related to amplitude of vibration
SA1; small, highly localised receptive fields that innervate skin densely and give linear response to indentation up to 1500 microns; can resolve points, edges, curvature and spatial detail of 0.5mm; firing rate can encode perceived stimulus magnitude
SA2 detect skin stretch
nociceptor sensitisation - hyperalgesia vs allodynia, common eg of allodynia, 3 egs of excitatory agents, 2 that enhance responsivness without direct excitation, 2 vasodilating factors released by nociceptor terminals when stimulated
property of nociceptors: if stimulus great enough to cause tissue damage, response to subsequent stim increases thus hyperalgesia to previous painful stim and allodynia to previously innocuous stim; allodynia example is taking shower when sun-burned, hot water suddenly painful when normally not; excitatory agents such as ATP (from damaged cells) bradykinin and acid released by anaerobic metabolism during anoxia or metabolic overload)
second class of sensitising agents don’t directly excite nerve terminals, instead enhance responsiveness to excitatory stimuli eg prostaglandins, NGF; the previous 3 examples excite and sensitise
stimulated nociceptor terminals release factors such as calcitonin gene related peptide CGRP and subtance P, vasodilatory peptides both directly and indirectly (mast cell degranulation via SP), inducing neurogenic inflam
SMA - inheritance and general path; what kind of neuron affected; type 1 onset when and progression, type 2 onset when and prognosis, type 3 onset when + progression + which muscles less affected; type 4 onset when; general mx
Spinal muscular atrophy (SMA) is a rare autosomal recessive condition that causes a progressive loss of motor neurones, leading to progressive muscular weakness.
Spinal muscular atrophy affects the lower motor neurones in the spinal cord
SMA type 1 has an onset in the first few months of life, usually progressing to death within 2 years.
SMA type 2 has an onset within the first 18 months. Most never walk, but survive into adulthood.
SMA type 3 has an onset after the first year of life. Most walk without support, but subsequently lose that ability.
Respiratory muscles are less affected and life expectancy is close to normal.
SMA type 4 has an onset in the 20s.
no cure, generally supportive
onc emergencies - spinal cord compression (5 common sources, ix, 3 mx), SIADH (onc cause inc commonest cancer), leukostasis (generally what cancer, 10 sx, 2 mx and complication), raised ICP (general onc reason, 3 linked cancer, 4 sx, ix, 4 mx)
spinal cord compression - spinal mets, esp breast, kidney, thyroid, lung, prostate; dexameth as soon as suspect, get total length MRI imaging, urgent surgical or radiotherapy treatment
SIADH - consider when pt with cancer presents with hyponat; ADH from tumous, esp small cell LC
leukostasis - in pt with AML/ALL 5-30% of time, infants esp affected; very high wcc, fever, papilloedema, focal neuro deficits(inc headache, dizziness, confusion, lethargy), retinal H+, RVT, MI, limb ischaemia, DIC, resp failure - dyspnoea, hypoxia; cytoreduction w chemo or leukophoresis; high risk of tumour lysis syndrome
raised ICP - cranial mets affect 1/4 of pts who die of cancer; lung, breast, melanoma most common to met here; headache, n&v, behaviour changes, seizures, other signs of raised icp; urgent MRI, dexameth, mannitol, irradiation or surgery
metastatic spinal cord compression mx - initial 5 things, 2 definitive options
high dose steroids: dex 16mg/d PO stat
Urgent MRI + consult neurosurgeons.
Analgesia, catheter, laxatives, bed rest
Definitive management
Surgical decompression appropriate if one site, limited disease, histology needed, skeletal instability.
Most pt: urgent radiotherapy - initially induces oedema so things worsen before get better.
root compression vs cauda equina syndrome
compression of single nerve root
- pain
- Straight leg raise replicates pain
- Pain radiates neck/back in dermatomal distribution
- weakness/reflexes limited to specific myotome / Absent
- numbness ditto
- bladder normal
- imaging not required
Compression of cauda equina (bundle of nerve roots below spinal card termination at L2)
- Severe lower back pain
- Bilateral radicular pain
- weakness/reflexes Severe, bilateral, multiple nerve roots
- numbness ditto
- Incontinence/ dysfunction
- Lax anal tone on PR
- Perianal anaesthesia
- Urgent MRI
4 poor prognostic features in spina bifida
hydroceph, incontinence, paralysis of legs, lumbar kyphosis
7 causes of pes cavus
friedreich ataxia, duchenne, spina bifida, tethered cord syndrome, CMT, idiopathic, and familial
notochord embryo layer and what it is, what is remnant in adults, what is its function; what is neural plate and what is the first step in neurolation; different protein expression in neural plate cells and surroundings; where do neural crest cells come from; 12 structures derived from the neural crest; when do cranial and caudal neuropores close and where does tube closure start; 2 egs of defect from failure to close tube; 2 important nutrients for this process
notochord is dense cell rod that forms along midline axis from mesoderm, its remnant in adults the nucleus pulposus; produces proteins like SHH to induce specialisation of ectoderm to form midline floorplate of neural tube
ectoderm thickens into neural plate which folds inwards to become a groove, then a tube in neurolation; neural groove cells express N-cadherin (lateral ectoderm E-cadherin) which helps keep two populations separate; 2 lips of groove come together and fuse in midline to give neural tube with overlying ectoderm to internalise the neural tube; cells at leading edge of lip break away and migrate into surrounding tissues as neural crest cells, cranial ones give rise to face bones/teeth/thymus/parathyroid/thyroid/sensory cranial neurons/PS ganglia/heart valves and trunk crest cells give rise to melanocytes, sensory neurons, symp ganglia/nerves, chromaffin cells of adrenal medulla; cranial neuropore closes in 4th week and caudal 2 days later
closure of tube spreads cranially/caudally from thoracic region with defects affecting 1:300 to 1:5000 live births depending on geographical region; anencephaly (head defect) fatal, failures in spinal cord closure vary in severity eg spina bifida; ~50% defects may be prevented with folic acid supplements, cholesterol also important as involved in processing hedgehog proteins
patterning the CNS
neural tube is midline ectoderm dorsal to notochord, specified to form neural tissue, neural plate folds to complete the tube; defects give neural tube defects (1 in 500 births) eg spina bifida; ant/post (rost/caud) patterning of tube to regionalise (forebrain, midbrain, hindbrain, spinal cord) with regions subdivided as complexity increases; HOX genes control this by encoding tfs; signalling centres arise that secrete factors that influence fate of nearby tissue: eg mid/hindbrain boundary (isthmus) devs at caudal expression boundary of a tf and secretes FGF8 to induce special fates in dorsal neural tissue, leading to dev of tectum rostrally and cerebellum caudally; neural tissue ventral to isthmus generates substantia nigra and motot CN III/IV
notochord acts as signalling centre in ventral midline, inducing neural floorplate via Shh; floorplate then acquires signalling properties, inc Shh expression, and patterns D-V axis via Shh conc (highest conc floorplate, lower induces motor neurons and suppresses dorsal spinal cord phenotypes; other genes subdivide lat/dorsal regions; for radial axis, neural tube initially organised as neuroepithelium with multipotent stem cells dividing ventricular zone, these generating neurons and radial glia which provide scaffold for neuroblast migration (for inside out dev of cerebral cortex); in mammals, neuronal stem cells disappear (prob differentiate into astrocytes) except in specialised locations (hippocampus, olfactory bulb); productions of neurons ceases in infancy in most regions of mammalian brain and neurons are post-mitotic
neural tube defects - 2 cranial, 1 spinal (3 subtypes); 4 risk factors; for first cranial what is absent, diagnosed when, usual mx, prognosis; for second 2 subtypes, 2 sx; how common is first subtype of spinal and what is it, how common and what is second type + 5 sx and association, when to suspect 3rd subtype x3 and ix to get and 4 sx; 8 mx for all 3 subtypes, when usually picked up
cranial: anencephaly, encephalocele (meningocele),
spinal: spina bifida (occulta, meningocele, myelomeningocele)
inadequate folate, sod val, carbamazepine, FH are risk factors
anencephaly - cranial vault absent, prenatal diagnosis, termination; otherwise 75% stillborn, rest die shortly after
cephalocele - brain matter deviates through defect in skull eg meninges in meningocele, brain matter too in encephalocele; seizures. intellectual impairment, or other disturbance
spinal meningocele: meninges outside spinal canal, normal exam, 5% cases spina bifida cystica
myelomeningocele: 80-90% spina bifida cystica cases, disturbed bladder/bowel control inc obstruction + chronic pyeloneph, sensory loss to level of lesion, motor weakness below lesion, hydrocephalus, associated with
chiaria II malformation
spina bifida occulta -often incidental finding but if naevus, hairy patch, sinus then MRI spine indicated; may give asym lower motor neuron weakness, diminished reflexes and tone; can get spasticity and impaired bladder control
keep newborn warm, defect covered with sterile saline dressing in prone position, close defect promptly; shunt for hydroceph if myelomeningocele; post fossa decompression for CM if sympt; physio, occupational therapy, wheelchairs or walking aids etc
usually picked up on anomaly scan (18-21 weeks)
brachial plexus anatomy (which upper limb nerve not through plexus, formed by what nerve roots, 5 regions and where each is, how cords are formed, best way to image)
distributes almost all upper limb nerves except accesory nerve
formed by union and division of roots of C5-T1
roots between scalenus ant/med, trunks cross post triangle of neck, divisions at apex of axilla deep to clavicle, cords deep to pec minor and named according to relation with 2nd part of axillary artery, terminal branches relate to 3rd part of artery; roots, trunks (up,mid,low) divisions, cords branches; up/mid trunk ant divs to lat cord, low trunk ant div to med cord, all post divs to post cord; imaged with MRI due to multiplanar arrangement and tissue contrast difference
branches of BP- before divisions: first to what muscles/function, second marks what point, third along and to what muscle, 4th to what muscles; 3 branches from lat cord and which can be good to block/when, 5 branches from medical cord, 5 from post cord inc 3 times axillary nerve damaged
before divisions: dorsal scapular from C5 to levator scapulae and rhomboids giving elevation/retraction of shoulders; nerve to subclavius C5/6 to subclavius, marks Erb’s point where C5/6 unite; long thoracic nerve C5/6/7 passes through cervicoaxillary canal and along serratus anterior innervating each of its digitations to help control scapula protraction and rotation; suprascapular nerve C5/6 from upper trunk along post triangle, deep to trap, through suprascapular notch to supra.infraspinatus and acromioclavicular joint
branches from lat cord: lateral pec nerve C5,6,7 pierces clavipectoral fascia to reach clavicular pec major, forming ansa pectoralis loop around axillary artery with med pec nerve, block during orthopaedic shoulder procedures (like dislocation) can reduce spasm from pec major so reduce pain; musculocutaneous; lat cord median nerve
branches from med cord: med pec nerve C8/T1 between axillary artery/vein to pec minor, through to pec major sternocostal head; medial cutaneous nerve of arm T1 sensory supply to skin of lower arm to medial epicondyle; medial cutaneous nerve of forearm C8/T1 sensory supply to skin of lower arm, medial forearm, branches into volar/anterior and ulnar/posterior; medial head of median nerve, ulnar nerve
branches from post cord: upper subscapular nerve C6 to upper part of subscapularis, thoracodorsal nerve C6,7,8 to lat dorsi, lower subscapular nerve C6,7 lower part of subscapularis and teres major; axillary nerve C5/6 ant branch closely related to surgical neck, main deltoid innervator and some cutaneous innervation; radial nerve; axillary nerve may be damaged in dislocation, crutch compression, fracture of cervical neck giving square shoulder deformity, loss of abduction from 15 to 90 degrees and loss of sensation
ulnar nerve - 4 initial steps in course, 2 initial branches to where, main nerve terminal branches innervate what; which spinal levels, distal injuries give what (2 muscles affected and 2 joint positions), ulnar paradox is what; 2 bones forming guyons canal; where is autonomous sensory area; 2 ix of palsy
runs on medial aspect of arm close to coracobrachialis and pierces medial intermuscular septum to lie posteriorly in groove between olecranon and medial epicondyle; enters ant forearm comp by passing between heads of FCU
midforearm gives palmar cutaneous branch to supply skin on medial palm, dorsal cutaneous branch winds around ulna deep to FCU to supply dorsal aspect of ulnar one and a half fingers
main nerve continues with ulnar artery to wrist, dividing into deep/superficial branches: sup to PB, palmar skin of ulnar 1.5 digits via digital branches deep trhough palm to terminate in adductor pollicis
C8/T1, distal injury gives claw hand (MCP extended, IP flexed in ulnar two fingers) as interossei and lumbricals paralysed (except what median nerve does); ulnar paradox as lesion at or above elbow also paralyses ulnar FDP so less deformity but greater functional loss; guyon’s canal between pisiform and hook of hamate, fibrooesseous tunnel in which nerve may be compressed although rarer than carpal tunnel; autonomous sensory area is palmar tip of little finger
can suspect clinically, otherwise nerve conduction studies and electromyography can prove problem
musculocutaneous nerve - roots, pierces/supplies which muscle, then 2 other muscles supplied and cutaneous innervation
C5,6,7, pierces and supplies coracobrachialis then into arm between biceps and brachialis, supplying both; just proximal to elbow becomes lateral cutaneous nerve of forearm which gives ant/post branches and innervates lateral forearm to wrist; frequent variations including interconnecting with median nerve
median nerve - roots, relationship with artery to ACF, passes between which muscle to enter forearm, 3 important branches then where nerve ends up; proximal lesions features x4; distal lesion sx x2 and area spared, mx x3; why pregnant women at risk; martin-gruber anastomosis; 2 ix if palsy
C5-T1, runs anteromedially with brachial artery then crosses anterior to artery to lie medial to it at the cubital fossa; passes between heads of PT
gives ant int branch after PT which passes along IM and innervates forearm flexors
palmar cutaneous branch to skin over thenar eminence superficial to FR so spared in carpal tunnel
recurrent branch to thenar muscles affected in carpal tunnel
gives digital branches to thumb, index, middle and radial half of ring fingers (palmar plus nailbeds) with tip of index finger for autonomous testing
proximal lesions manifest like carpal tunnel but inability to flex index/middle fingers, distal phalanx of thumb (both due to losee of forearm flexors), weakness and wasting in thenar eminence, ulnar deviation
distal lesion from carpal tunnel syndrome giving pain and paraesthesia, thenar wasting, skin over thenar spared; managed by night splints to prevent wrist flexion, steroid injections, surgery to divide FR, pregnant women at risk due to fluid retention
martin-gruber anastomosis is communicating nerve branch between ulnar/median nerves in forearm which can serve as conduit for alternative innervation, exacerbating or attenuating problems and leading to false conclusions about injury to nerve, study found it in 27% of 50 cadavers, matching another study (found it in 23%)
evaluate lesions with nerve conduction studies and electromyography
radial nerve - roots, proximal muscle supplied, runs in what feature in arm, perforates what prior to division; course of deep branch; superficial innervates what muscles and skin; additional sensory branch and its territory; 3 features of lesion; 2 features pointing to proximal lesion and where this might occur; what is saturday night palsy
C5-T1, supplies triceps and runs with profunda brachii in spiral groove, perforates lateral intermuscular septum and passes anteriorly to divide into superficial and deep branches in lateral vicinity of cubital fossa
deep passes between heads of supinator to emerge as post int and innervates the forearm extensors in posterior compartment
superficial deep to brachioradialis and lateral to radial artery, curves around radius and pierces deep fascia to give sensory branches to dorsum of hand: thumb/index/middle/radial half of ring up to DIP joint; autonomous testing zone is dorsal aspect of first web space
posterior cutaneous nerve of arm branch supplies lateral arm proximal to elbow and much of the back of the arm and forearm
lesion gives wrist drop (inability to extend wrist, fingers, thumb); power grip weakness as synergism between flexors/extensors needed; dorsum of hand sensation loss
proximal injury in eg axilla suggested by wrist drop and loss of active elbow extension + greater sensory loss; saturday night palsy when person falls asleep with arm across back of chair giving wrist drop
brachial plexus lesions - erbs palsy where, motion needed and eg, 3 movements lost so position of arm; klumpkes palsy level, mechanism and eg x2, 4 sx; 2ix
Erb’s palsy, upper trunk C5,6, excessive downwards traction on limb in eg difficult delivery; shoulder abduction, elbow flexion, supination lost so arm hangs by side with forearm pronated and elbow extended
Klumpke’s palsy C8/T1 from hyperabduction of shoulder in eg breech delivery, catching yourself if you fall, gives wasting/paralysis of intrinsic muscles of hand, possible claw hand, numbness in C8/T1, may be crying/painful in babies
as always NCS/EMG can help, otherwise clinical diagnosis
how long do erbs/klumpkes palsy take to resolve and what other intervention is important?
over time, usually before end of 1st year; physio to prevent contractures developing - they will do specific movements and also assess using toronto score, if scores low (poor mobility) or only marginal improvement will refer for surgery, often if little improvement by 3-4mo or adequate function not back by 9mo - surgery will include removal of scar tissue/neuroma and nerve grafting (often using small sensory nerves from legs)
lumbar plexus - located where, nerve roots, 4 early nerves and their targets; comon ways for 2 nerves to be injured; 2 other nerves and their relation to psoas, final nerve
within or posterior to psoas major, by anterior rami of L1-4, some of L4 joins L5 to form lumbosacral trunk
iliohypogastric L1 to innervate genital and hypogastric regions
ilioinguinal L1 to conjoint tendon, skin at root of penis/clitoris, anterior scrotum, mons pubis, labia majora
genitofemoral L1,2 pierces psoas, lies on it, with femoral branch L1 to upper anterior thigh and genital branch L2 to cremasteric muscle and areas supplied by ilioinguinal
lateral femoral cutaneous L2,3 across iliacus and enters thigh medial to ASIS beneath IL
open repair of inguinal hernia may damage and laparoscopic repair entrap the ilioinguinal nerve, some surgeons say gives less pain but conjoint tendon denervated; meralgia paraesthetica entrapment of lat fem cut nerve as it passes beneath IL giving numbness/pain in outer aspect of thigh with restrictive clothing and weight gain common causes
L2-4 give femoral nerve and obturator nerve, femoral lateral to psoas and obturator medial to it
L4/L5 form lumbosacral trunk to connect to sacral plexus
femoral nerve - what levels, small first branch, 5 branches from ant division, posterior supplies branches to what 3 structures; saphenous nerve function; injury to femoral nerve cause eg and consequence, 2 other clinical relevances
from posterior divisions,L2-4, gives small branch to iliacus (hip flexor), ant division gives anterior, intermediate, medial femoral cutaneous nerves to medial thigh and around knee and branches to pectineus/sartorius (hip flexors); posterior division branches to quads/joints with hip joint from branch to rectus femoris and knee joint vastus intermedius
gives saphenous nerve that innervates anteromedial leg/ankle
penetrating trauma like knife, surgery on groin or hip, can paralyse knee extensors and give difficulty walking/standing due to injury to femoral nerve; anaesthestised in FIB, saphenous vein harvest may damage saphenous nerve giving pain or numbness in that distribution
obturator nerve - root origins, 4 things innervated, general function
from ant divisions, L2-4; gives a/p divisions after passing through obturator canal; skin of medial aspect of thigh, adductor longus/brevis/magnus, gracilis, obturator externus
in general can say it innervates medial compartment of thigh with role being hip adduction
sacral plexus - what forms it, related to what muscle, 9 branches
lumbar plexus insufficient to innervate entire lower limb, lumbosacral trunk and ant rami S1-4 form sacral plexus: trunk joins S1 which joins S2-4 on piriformis
sup glut L4-S1 to med/min glut and tensor fascia latae above piriformis
inf glut below, L5-S2 to glut max, if injured in post hip replacement gives glut max lurch when trunk extends on heel strike to compensate for weak hip extension
direct L5-S2 branches to piriformis
nerve to obturator internus L5-S2 and quadratus femoris L4-5,S1
post femoral cutaneous nerve to skin of post thigh/perineum, medial to sciatic and may be damaged in post approach to hip, S2,3
pudendal, coccygeal and sciatic (from origin onwards can be thought of bundle of tibial and peroneal nerves)
sciatic nerve and branches - root origin, divides where, general function of tibial nerve x2, course of the common fibular including two branches and their targets 1:2, include in all the function of innervated compartment; sural nerve branches from what, role, used in what test and what sparing means; other 2 major sensory innervation of lower leg; sciatic may be injured in what and precaution to avoid, 3 other ways it may be injured; tarsal tunnel syndrome affects what, where, common in who/why
L4 to S3, through greater sciatic foramen, enters thigh deep to hamstrings, divides at variable distance, usually mid-thigh into tibial/common fibular (peroneal) nerves but you can think of it as being these two nerves bundled throughout
tibial nerve innervates post comp leg (toe flexion, inversion, plantarflexion), gives med/lat plantar nerves to intrinsic foot muscles, sole and toes; common fibular is smaller, winds laterally round head of fibula gives sup branch to lateral leg comp (foot eversion), deep branch to ant comp (dorsiflexion and inversion), dorsal intrinsic foot muscles
sural made of branches from tibial and fibular, innervates skin of posterolateral leg, foot and ankle, often used for biopsy if nerve biopsy indicated (will lose distal sensation), spared in GBS and some other autoimmune diseases, helping to differentiate from a length dependent process which won’t spare; common fibular innervates some anterolateral leg, superficial fibular does much of dorsum of foot
injured in intramuscular buttock injection, top right quadrant to avoid this; post hip dislocation/surgery may injure, penetrating trauma esp when emerges from buttock before passing deep to hamstrings; tarsal tunnel syndrome affects tibial nerve post to medial malleolus, more common in athletes due to chronic sustained overuse, much rarer than carpal tunnel syndrome
lower limb myotomes - movements and their myotomes x8
Hip L2/3 flex/adduct/med rot, L4/5 extend,abduct, lat rot; Knee L3/4 extend, L5/S1 flex; ankle L4/5 dorsiflex, S1/2 plantarflex; foot L4 invert, L5/S1 evert
NMJ: where is the motor endplate usually, axon to muscle fibre ratio, what is a motor unit, what is the synaptic cleft, what are junctional folds and active zones, 2 major constituents of the cleft, NT release to [Ca] ratio, what is the synaptic delay and where is the site of longest delay
motor axons emerge from bundle in nerve and split into branches, each forms a motor endplate with a single muscle fibre, usually near the middle; normally one axon to one fibre; motor unit is group of muscle fibres innervated by one motor neuron; fibre (1-2micron diameter) separated by synaptic cleft (50-70nm); every 1-2 microns, transverse invagination of synaptic membrane called junctional fold with thickenings above in presynaptic membrane called active zones where thousands of NT vesicles cluster, each about 50nm in diameter; cleft filled with mucopolysaccharide gel and layer of extracellular material called basal lamina
AP opens VG Ca channels, causes vesicles to fuse; visualised in freeze-fracture EM; vesicle [NT] 100-200mM, ~10^4 per vesicle; release prop to [Ca]ext^4, suggesting cooperative mechanism; synaptic delay between AP arrival and start of postsynaptic response: in frogs shown to be ~1ms, maybe ~-0.75 in ppl, most in presynaptic terminal before release with ACh diffusing across cleft in ~10microsecs and postsynaptic response taking <100microsecs to begin
end plate potentials - time constant and faster decay in what kind of neurons, how does EPSP timecourse compare to EPSC and what explains the difference, what are MEPPs and what do they correspond to and what influences MEPP frequency, what is the quantal content of an AP, how does EPP decay and what does this mean for AP generation
curare used to block AP to observe EPP, with time constant of 10s of ms, and faster decay with larger fibre diameter; voltage clamp at negative potential and then presynaptic nerve stimulated shows at muscle an endplate current which rises to a peak in <1ms and has TC of ~1ms, representing sum of currents through thousands of nAChRs; EPSP much slower as time needed to charge/discharge muscle membrane capacitance
spontaneous MEPPs (<1mV), shown by measuring response to artificially applied ACh that one MEPP corresponds to a quantum of ~10,000 ACh molecules; occurred even when TTX blocked presynaptic APs; MEPP frequency changed decreased with decreased [Ca]ext and other factors affecting vesicle release; proposed that quantum = one vesicle and probabilistic chance of release; quantal content is mean number of quanta released during an AP
recording near endplate shows upstroke of EPP in AP, moving recording electrode 5mm away and EPP not observed; curare treated muscle to make EPP subthreshold shows it decays exponentially with distance due to cable properties of muscle, no regenrative inwards current so EPP fades as endplate current leaks across PM; restricts region over which EPP can initiate an AP to that area immediately around the endplate
3 proteins in trans-SNARE complex and funtion, what inserts to prevent spontaneous fusion, how do tetanus and botulinum toxins work, how does Ca lead to vesicle fusion
synaptobrevin, syntaxin and SNAP-25 form four-helix bundle (trans-SNARE complex) that holds vesicle close to PM; complexin inserts into complex to prevent spontaneous fusion (note, synaptobrevin may be cleaved by tetanus toxin in inhib spinal interneurons and some botulinum toxins target all 3 in motor neurons to block vesicle fusion); Ca binds to synaptotagmin which displaces complexin resulting in fusion
neuron capacitance and eqpot (why is nerve membrane a capacitor and what is the time constant (inc numeric value for motor neuron, how does capacitance limit response speed, what drives passive movement of solute across PM, what is the eqpot, 3 factors that influence, why is theoretical one rarely reached and what equation combines different ones
dielectric separating charge hence capacitor, shown experimentally with time taken to charge/discharge capacitance as changing Em if current applied; R is about 1 megaohm, capacitance about 2000 picofarads for mammalian motorneuron, so time constant (time to change Em by ~63%) is ~2ms; capacitance limits speed of response to stimuli that change Em by delaying depolarisation
eqpot: driving force for passive, uncoupled movement of solute is electrochemical energy difference for that solute either side of PM, with chemical force based on diffusion and electrical force based on developing Em; when the forces balance such that there is no net flux, Eqpot is reached; larger conc diff needs larger balancing Em, raising temp gives greater energy to ions so greater balancing Em; higher charge for ion means more strongly affected by voltage diff so less Em needed; theoretical usually not achieved as perm to more than 1 ion, GHK combines Em factoring in perms
propagating APs (triggered at what part of axon, change from what kind of signal to what other kind, how to observe spatial decay of current and 2 factors that contribute to this including why current leaks out of cell and how this justifies action potentials, 2 ways myelination improves conduction, how conduction velocity relates to diameter for myelinated and un myelinated fibres, metabolic cost of APs verse alternative, why do small diameter myelinated neurons conduct slower than unmyelinated
AP triggered at axon hillock by synaptic inputs, with change from analogue (continually variable) input at hillock to digital AP pulse
blocking VG channels in axon and depolarising it allows observation of spatial decay of current due to electrotonic spread along path of least R, determined by transmembrane and longitudinal resistance; axoplasm has high R and PM low, causing current to leak out of cell, APs exist as passive flow is unable to carry information far
Ions don’t carry this current, rather entry of ions causes chain of ionic rearrangement driven by electrostatic forces which gives an impression of flow; large I with small PM C gives fast initial depolarisation, simply increasing Na current metabolically expensive as Na has to be pumped out; larger diameter neurons have lower longitudinal R, eg giant squid axons
myelination increases PM R 300x to reduce current leakage so length constant increases (sheath can be 1/4 of axon diameter), saltatory conduction between nodes every 0.1-2mm; myelination reduces PM C 300x too so Em can change more rapidly (these numbers based on number of layers and R in series add directly and C in series as sum of reciprocal), though may be offset by smaller nodal currents; velocity prop to diameter for myelinated, sqrt of diameter for unmyelinated; APs less metabolically expensive too as less ions move so less pumping needed; small diameter myelinated nerves conduct slows than unmyelinated as axon very narrow, giving high R
6 nerve types
Aalpha (motor) 80-120m per s; Abeta (sensory mechanoreceptors) 35-75 m per s; Agamma (motor fibres to intrafusal muscle spindles) 12-30 m per s; Adelta (nociceptive/cold receptors) 5-30 m per s; B (pregang autonomic) 3-15 m per s; unmyelinated type C (nociceptive/warm) <2m per s
length constant of neuron - velocity equation, how to calculate length constant, 2 variables that change with demyelination and how this results in failure to conduct impulses
V decays exponentially V=Voe^(-x/lambda) with lambda the length constant, due to electrotonic currents; lambda = sqrt(membrane R/ longitudinal R); multiple sclerosis with loss of myelin giving paralysis/altered sensation as PM R falls and PM C rises until cannot propagate far enough to reach next node of ranvier and nerve doesn’t conduct
Na and K channels in AP (NaV open when, close when, what follows closure; what is absolute vs relative refractory period and what is its function; how is inactivation achieved; KaV gating, kinetics of above; how does probability of either channel opening vary with Em; what segment senses voltage; how does depol to threshold trigger AP and how does repol/hyperpol occur)
Na: open at a threshold voltage; time dependent closure after ~1ms with a period of inactivation lasting ~1ms giving absolute refractory period; gradual deinactivation when threshold raised as less Na channels available is relative refractory period; these periods ensure APs conduct in one way; stretch of aa at N terminus of Na channel can block the pore giving inactivation
K channels: purely VG, open on depolarisation and close on hyperpolarisation; no obvious threshold and very slow to respond due to the kinetics of their pore opening/closing (4 separate events: colder temps, much slower than Na)
probability that a channel is open varies with Em according to a Boltzmann distribution, if voltage sensing part of channel is +ve then probability of channel opening increases from 0 to 1 in a sigmoid fashion as Em becomes more positive (Em on x axis, prob on y); total current carried by an ion is equal to total number of channels, current through individual channel (conductance x difference between Em and Eeqpot) and probability that the channel is open at that Em; S4 segment in Na, Ca and K channels has Arg/Lys residues every third residue which acts as a voltage sensor
depolarisation to threshold has enough Na channels open to cause +ve feedback cycle of Na channel openings until ~1ms when they close; slower K channels start to open allowing repolarisation, which overshoots (hyperpolarises) as the channels are slow to close
many neurons show reduction in firing freq over time; firstly due to Na channel inactivation, and secondly the open K channels clamp the Em towards Keq (-105mV) which takes it further from threshold
GABA and glycine increase what conductance, 2 receptors glut binds to (what ions they are permeable and which part of EPSC they mediate), GABA a vs b; location of main shunting channel synapses
GABA and glycine bind to gated Cl channels, increased Cl conductance opposing EPSPs as Ecl in neurons is near resting potential
glutamate binds to AMPA receptors permeable to Na and K which mediate fast part of EPSC; and to NMDA receptors which allows Na/Ca through, glycine required to co-activate this and does the slow part of EPSC; inhibition by ionotropic GABAa and metabotropic GABAb, GABAa shunt and hyperpolarise, GABAb inhibits both pre and post synaptically
some inhibitory synapses are closer to AP trigger zone and so may shunt excitatory current to prevent AP generation
distribution of Cl across PM, donnan product rule, how Cl transport influences Eqpot, 2 situations where Cl transport is in opposite direction and effect of this on Cl current including how this might become pathological; 2 ways Ca excreted and how this makes Ca a good messenger; how to draw an equivalent circuit for PM
[Cl]i is low giving a negative Eqpot; Cl- is primarily distributed passively such that the nernst potential is approximately equal to Em, leading to the donnan product rule where Ek=Ecl and thus (by cancelling, taking antilogs and cross multiplying) [K]o . [Cl]o = [K]i . [Cl]i; there is also secondary active transport with Cl extrusion coupled to K efflux via KCC2 and Na dependent influx of bicarbonate via NDCBE. both these processes lower the [Cl]i such that Ecl is more negative than the resting potential. in developing neurons and adult olfactory receptor neurons, inwards Na/K coupled Cl transport via NKCC1 raises [Cl]i such that opening Cl channels at the Em allows an excitatory outwards flow of Cl ions; in certain types of epilepsy/chronic pain syndrome, expression pattern of Cl cotransporters reverts to the immature state so GABA has a depolarising effect leading to abnormally high levels of excitation
[Ca]i is very low and has a positive Eqpot; it is powerfully extruded via ATP driven Ca pump and secondary Na/Ca exchange via NCX, sometimes also utilising the outwards K gradient NCKX to give more powerful extrusion; thus in most cells [Ca]i is <100nM which allows use of Ca as an intracellular messenger as small fluxes cause large concentration changes, often Ca stores are released from ER after stimulation and taken back up by pumps; most neurons have relatively few ca pumps and are more reliant on Na/Ca exchange
equivalent circuit for PM: 4 parallel circuits for each ion containing battery of Eion, resistor representing conductance of that ion and carrying a current for the ion with total current the sum of each individual with Iion = gion (E - Eion)
NT release
Ca entry through VG Ca channels serves to transduce electrical activity into chemical response at the synapse, and Ca is used due to its low [Ca]i at the Em; within immediate vicinity of Ca channel, ten or hundreds of micromolar [Ca] can be attained; quantal release of NT via vesicles occurs with synaptotagmin serving as a Ca sensor and snare proteins fusing the vesicles: vesicle docks, is primed by association between v-SNARE and t-SNARE and then Ca dependent fusion occurs, releasing contents into synaptic cleft
NTs (main excitatory inc 3 egs of receptors and how many of last, main brain inhibitory inc 2 receptors and what type they are, main spine inhib and its receptor; eg of bioactive amine and 2 receptor types, main catecholamine and where associated, DAr subtypes, subtypes for 5HT and associated with where, histamine receptor subtypes, receptor subtypes for ATP and adenosine; neuropeptides tend to have what kind of role and are released with what, what kind of receptor subtype, and 3 egs of gaseous transmitters)
amino acids like glutamate, main CNS excitatory and acting via ionotropic like AMPA/NMDA and metabotropic like mGluR1 to mGluR5; GABA (main brain inhibitory) acting via iono GABA-A and metabo GABA-B; glycine (spinal cord inhibitory) acting only via iono glycine receptor
bioactive amines such as Ach acting via nictotinic (iono) and muscarinic (metabo), catcholamines like NA acting via metabo alpha/beta receptors and associated with locus coeruleus; dopamine (DA) acting via metabo D1-like and D2-like, via cAMP cascades in substantia nigra; serotonin (5-HT) acting via iono 5-HT3 and metabo 5-HT1/2/4 and associated with raphe nucleus; histamine (H) acting via metabo H1/2/3/4
ATP and adenosine act at non-cholinergic non-adrenergic autonomic synapses via purinergic receptors such as P1/P2Y metabo and P2X iono for ATP with roles in vascular, apoptosis, cytokines etc and A1/2/3 metabo with cardiovascular roles for adenosine
extremely diverse range of neuropeptides which have NT, modulatory and hormonal roles and are often co-released with more traditional NTs eg VIP with Ach; they act via diverse set of metabotropic receptors and include eg opioids, pituitary, secretins, insulins, tachykinins, somatostatins, gastrins etc
gaseous transmitters such as NO acting metabotropically via guanylyl cyclase as endothelium derived relaxing factor, and possible roles also for CO and H2S
basis of sensory receptors - stimulus results in generation of what, leading to change in what; short vs long receptors; 3 egs of each; 2 examples of direct transduction, what are indirect based on; what must long receptors have that short dont
a stimulus results in a graded receptor current dependent on stimulus strength, which subsequently generates a graded receptor potential and depolarises the site of impulse initiation, which varies its rate of AP generation in response to magnitude of depolarisation, an exception is the retinal photoreceptors which hyperpolarise in light; long receptors send afferent axons to CNS and fire APs and short receptors without an axon synapse with a second order neuron for conduction to the CNS, these often generate a graded potential instead of spikes giving a graded change in NT release and graded generator potential in the second order cell modulating rate of spike firing; cutaneous, cranial and olfactory receptors are long, taste, hearing and vision are short
transduction mechanisms: direct in mechanoreceptors with opening of stretch-sensitive channels coupled to cytoskeleton or more complex structures in the case of hearing; cations then enter and depolarise the receptor; other receptors that use a direct mechanism include salt receptors in the tongue; most others use indirect second messenger cascade (taste, smell, sight etc), similar to metabotropic synapse transmission; long receptors must have AP, short don’t
spread of synaptic input (3 parts of neuron that receive input from axon, excit and inhib input to which parts of cortical pyramidal cells, how does AP propagate and how does its potential decay
axosomatic (input to soma), axodendritic (axon to dendrites), axo-axonic (axon to axon)
cortical pyramidal cells receive type 1 (excitatory input) to dendritic shaft (mostly) and spines, and type 2 (inhibitory) to the soma
AP propagates via local circuit currents, the potential of which undergoes exponential decay with a length/space constant; dendritic tree can be imagined as split into passive cable segments into which current is injected by synaptic receptors when activated, and VG Na/Ca conductances in many neurons can boost the decaying passive dendritic current
AP initiation (where, why here, main thing determing how much a given synapse influences the soma and another factor influencing attenuation)
specialised region called axon hillock, which has the lowest threshold; shown by cortical slice of pyramidal cell with current clamp (so voltage varies freely), AP always recorded first at soma regardless of whether you stimulate dendrites or soma, in many neurons the AP then propagates actively back into the dendritic tree
axon hillock has lowest threshold due to exceptionally high conc of VG Na channels as well as sensitive channels and turns graded receptor potentials into train of all-or-none APs; hillock Em must change by 10mV vs 30mV for cell body
an individual synapse will influence the soma based on how far it is away on dendritic tree (due to space constant) and are also more strongly attenuated along small dendrites as space constant varies with square root of neuron diameter
spike trains - different spike pattern if depol axon vs soma, what at soma allows this to happen, what is it called and how does it work to achieve its goal, how is burst firing triggered and stopped; when do thalamic relay neurons show bursting, how is threshold for intrinsic bursting reached and what happens at other membrane potentials
depolarising an axon by injecting current gives a rate of firing related extremely steeply to the magnitude of injected current (ie does not fire or fires very rapidly), whereas depolarising the soma gives a rate of firing that is a graded function of the current such that magnitude of stimulus is encoded in the frequency of the spike train; a requirement for this is an additional K conductance which inactivates on maintained depolarisation, and voltage clamp experiments using a Na channel blocker (TTX) show a component of K current that inactivates and can be inactivated if the cell is held at a depolarised potential before the strongly depolarising clamp step,
inactivating current is known as the A current; after each AP Ia remains inactivated and Ik remains high which holds the membrane at a negative potential, Ia then activates which prevents Em being raised to threshold before inactivating again, allowing threshold to be approached and another AP to fire, thus Ia serves to space out APs in the spike train
many CNS neurons fire in bursts, and some cortical pyramidal cells show intrinsic bursting even when stimulated continuously; bursting occurs when low threshold VG Ca channels are activated: T (transient) channels have a threshold of -65mV and inactivate moderately slowly (20-50ms) to terminate the burst; thalamic relay neurons exhibit bursting when relatively hyperpolarised as in sleep as T channels can recover form inactivation and fire another bust of 2-5 APs, threshold for the T channels is reached by a hyperpolarisation activated inwards current Ih comprising Na and K; at more depolarised potentials the T channels are permanently inactivated and the relay neuron repeatedly fires single spikes in tonic mode
