Neuro Flashcards
function of the frontal lobe
voluntary movement on the contralateral side of the body dominant hemisphere (left) controls speech and writing
function of the parietal lobe
language control and maths
primary sensory area
proprioception
function of the temporal lobe
primary auditory cortex
understanding spoken word and sounds
function of the occipital lobe
primary visual and visual association cortex
where is Broca’s area located
inferior frontal gyrus in the frontal lobe
what is the function of Broca’s area
motor production of speech
what artery is Broca’s area supplied by
middle cerebral artery
where is Wernicke’s area located
posterior temporal lobe
what is the function of Wernicke’s area
understanding the spoken word
what is the blood supply to Wernicke’s area
middle cerebral artery
what is the primary motor cortex
region in the cerebral cortex involved in planning, control and execution of voluntary movements
where is the primary motor cortex located
precentral gyrus
what is the primary somatosensory cortex
region of the cerebral cortex involved in touch and sensation
where is the primary somatosensory cortex located
postcentral gyrus
where is CSF produced
lateral ventricles by the choroid plexus
outline the flow of CSF
lateral ventricle –> 3rd ventricle via the interventricular foramen
3rd ventricle –> 4th ventricle via the cerebral aqueduct
4th ventricle –> subarachnoid space medially via the foramen of Magendie and laterally via the foramen of Luschka
returns to the venous system via arachnoid villi into the superior sagittal sinus
what is the corpus callosum
commissural fibres of white matter that connect the right and left hemispheres together
what is the function of the corpus callosum
links functionally similar areas of the 2 hemispheres together
what are the components of the brain stem
midbrain
pons
medulla oblongata
what are the three divisions of the midbrain
tectum
tegmentum
cerebral peduncles
what is the tectum composed of
superior and inferior colliculi
what is the function of the superior colliculi
sensitive to visual changes
what is the function of the inferior colliculi
sensitive to auditory events
what is the tegmentum composed of
periaqueductal gray, red nucleus and substantia nigra
what is the blood supply to the midbrain
basilar artery
which cranial nerves originate from the pons
trigeminal (V)
abducens (VI)
facial (VII)
vestibulocochlear (VIII)
blood supply of the pons
pontine branches of the basilar artery
what is the role of the medulla oblongata
- houses the ascending and descending nerve tracts along with brainstem nuclei and is the place where decussation of most nerve fibres occurs
- contains the autonomic cardiovascular and respiratory centres
blood supply to the medulla
posterior inferior cerebellar artery
anterior spinal artery
branches of the distal vertebral artery
contents of the olfactory foramen
olfactory nerve
contents of optic canal
optic nerve and opthalmic artery
contents of superior orbital fissure
CN3, 4, V1 (opthalmic branch), 6 and superior opthalmic artery
contents of the foramen rotundum
V2 (maxillary branch)
contents of the foramen ovale
V3 (mandibular branch)
contents of the foramen spinosum
middle meningeal artery
contents of the internal acoustic meatus
CN7, CN8, labrinthyne arteries and vein
contents of the jugular foramen
jugular vein, CN9, 10, 11
contents of the hypoglossal canal
hypoglossal nerve
contents of foramen magnum
spinal cord and vertebral arteries
what are the three layers of the meninges
dura mater
arachnoid mater
pia mater
function of the meninges
provide a supportive framework for the cerebral and cranial vasculature and with CSF protect the CNS from mechanical damage
what does the dura mater consist of
outer endosteal layer
inner meningeal layer
what does the arachnoid mater consist of
subarachnoid cisterns full of CSF
what does the pia mater form
the blood brain barrier and is closely adherent to the underlying nervous tissue
what is the function of the blood brain barrier
prevents unwanted molecules getting out of the blood and into the brain
arterial blood to the brain arrives within the skull via two pairs of vessels…
internal carotid arteries
vertebral arteries
how do the internal carotid arteries enter the skull
through the carotid canal
how do the internal carotid arteries interact
they interconnect to the form the circle of willis
how much of the brain’s blood supply is supplied by the internal carotid arteries
80%
how much of the brain’s blood supply is supplied by the vertebral arteries
20%
how to the vertebral arteries interact
fuse to form the basilar artery
what does the anterior cerebral arteries supply
anteromedial aspect of the cerebrum back to the parietal lobe
olfactory cortex
corpus callosum
internal capsule
what does the middle cerebral arteries supply
most of the lateral portions of the cerebrum
part of the internal capsule
basal ganglia
what does the posterior cerebral arteries supply
medial and lateral sides of the cerebrum posteriorly
occipital lobe
posteromedial aspect of the parietal lobe
what is the venous drainage of the brain
cerebral veins first drain into dural venous sinuses and then into the internal jugular vein
how many cervical, thoracic, lumbar and sacrum vertebrae
7, 12, 5, 5
name of cervical vertebrae C1 and C2
C1 : atlas
C2 : axis
what is the nucleus pulposus
soft, semi-fluid core of the intervertebral disc
what is the annulus fibrosus
outer later of the intervertebral disc
10-12 concentric layers of collagen
what is the conus medullaris
spinal cord tapers to a cone towards the end
what is the cauda equina
nerves from the lower part of the cord, lumbar and sacral nerves hang obliquely downwards
what is the filum terminale
fibrous strands extending from the conus medullaris to the coccyx
what part of the spinal tract contains the ascending and descending nerve fibres
outer part of the spinal cord in the white matter
what does the inner part of the spinal tract contain
grey matter than contains nerve cell bodies
name the two ascending spinal tracts
- spinothalamic
2. dorsal column-medial lemniscus
what is an upper motor neurone
neurons of the motor cortex and descending pathways involved
synapse of neurons not muscle cells
what is a lower motor neurone
neurons that synapse directly onto muscle cells and stimulate their movement
what sensation does the spinothalamic tract convey
pain
temperature
crude touch + pressure
outline the spinothalamic tract
- nerve endings (from nociceptors and mechanoreceptors) in the body send info down axon
- spinothalamic tract enters the spinal cord at Lissauer’s fasciculus and ascends 1-2 layers within
- synapses onto cell body in dorsal horn of grey matter
- axon from this neurone crosses over in ventral white commissure
- axon ascends via spinothalamic fasciculus
- axon ascends through brain stem and synapses onto the thalamus
- thalamus sends projections to the post central gyrus of the cortex
what sensations does the dorsal medial lemniscal column carry
proprioception
fine touch
vibration
outline the DCML
- first order neurone periphery enters the spinal column
- upper limb (T6 and above) ascends up the lateral fasciculus cuneatus
- lower limb (below T6) ascends up the medial fasciculus gracilis - fibres ascend up the dorsal column in respective fasciculi to either the cuneate or gracilis nuclei at the medulla
- fibres synapse with second order neurons
- second order neurons decussate at internal arcuate fibres to travel in the medial lemniscus and ascend to the ventral posterolateral nucleus in the thalamus
- synapse with third order neurons at the thalamus and travel to the sensory cortex
function of the corticospinal tract
a motor tract that conveys axial and limb voluntary motor control to generate muscle movements
outline the corticospinal tract
- upper motor neurons begin in the pre-central gyrus (primary motor cortex) and run as separate neurons (corona radiate)
- neurons converge and leave the cortex, descending through the internal capsule
- neurons pass through the midbrain, Pons and peduncles into the medulla
- 75% of fibres decussate at the level of the pyramids and descend down the lateral corticospinal tract –> synapse with a LMN –> innervate the limbs
- Remaining 25% of fibres descend down the anterior corticospinal tract and decussate as they leave the anterior white commissure –> synapse with a LMN –> innervate axial muscles
what is significant about the area postrema
only area that lacks a blood brain barrier. toxins enter here to alert the brain of a presence and induce vomiting to remove toxins
two types of summation
temporal and spatial
types of synapse
electrical and chemical
function of the somatic nervous system
innervates skeletal muscle cells
neurotransmitter in somatic nervous system
acetylcholine
what does the autonomic nervous system innervate
smooth muscle, cardiac muscle, glands, GI neurons
how many neurons is the autonomic nervous system made up of
2 neurons in series (pre and post ganglionic)
1st neuron has cell body in the CNS
this synapses with a neuron outside CNS in an autonomic ganglion
describe the sympathetic nervous system including neurons and neurotransmitters
- fight or flight response
- neurons leave CNS from thoracic and lumbar regions
- sympathetic ganglia
- preganglionic fibre (myelinated)–> acetylcholine – nictonic receptor –> postganglionic fibre (non-myelinated) –> noradrenaline –> adrenergic receptor
which cranial nevers are parasympathetic
CN3, 7, 9, 10
describe the parasympathetic nervous system including neurons and neurotransmitters
- neurones leave brainstem and sacral portion of spinal cord
- rest or digest
- single myelinated preganglionic fibre –> acetylcholine –> nicotinic receptor –> non-myelinated postganglionic fibre –> acetyl choline –> muscarinic receptors
what is substance P
peptide neurotransmitter involved in pain transmission and is a vasodilator
what is a stroke
rapid onset of neurological deficit caused by a vascular lesion and is associated with infarction of the central nervous tissue
what are the two types of stroke
ischaemic and haemorrhagic stroke
what is an ischaemic stroke
ischaemia of brain tissue caused by a lack of blood supply which leads to infarction and death of neural tissue resulting in loss of functionality
what is a haemorrhagic stroke
primary intracerebral haemorrhage
aetiology of an ischaemic stroke
cerebral infarction due to am embolism or thrombosis
cardiac emboli (AF, endocarditis)
atherothromboembolism (e.g from carotids)
aetiology of a haemorrhagic stroke
intracerebral or sub-arachnoid haemorrhage
primary : hypertensive, lobar haemorrhages due to amyloid deposition
secondary : anticoagulants, mets
name 5 risk factors for stroke
hypertension diabetes smoking and alcohol hyperlipidaemia obesity heart disease
signs of an ACA territory stroke
main symptoms are focused around the leg because of the homonculus
- leg weakness
- sensory disturbance in the legs
- gait apraxia
- incontinence
- drowsiness
- akinetic mutism
signs of a MCA territory stroke
- contralateral arm and leg weakness
- contralateral sensory loss
- hemianopia (caused by damage to the optic radiations)
- aphasia
- dysphagia
- facial droop
signs of a PCA territory stoke
patients mainly experience visual problems
- contralateral homonymous hemianopia
- prosopagnosia
- only time a headache is associated with a stroke!
what are the signs that would point to a posterior circulation stroke?
- motor deficits - hemiparesis, tetraparesis and facial paresis
- dysarthia and speech impairment
- visual disturbances
- vertigo, nausea and vomiting
- locked in syndrome - aware but cannot respond
what is the management plan in ischaemic strokes?
- FAST - important to recognise quickly!
- diagnose a stroke clinically
- CT head (ensure that it is ischaemic not haemorrhagic)
- thrombolytic treatment
- risk management treatment
what is the thrombolytic treatment used in acute stroke management
IV alteplase
must give within 4 1/2 hours!!
what are 3 contraindications for giving thrombolytic treatment in the acute management of stroke?
haemorrhage active bleeding warfarin or heparin aneurysm pregnant
what is an alternative therapy for ischaemic stroke and when would you use this?
clot retrieval
use if the clot is in one of the large arteries of the brain
what is the treatment for haemorrhagic stroke?
stop anticoagulants if on any
control BP with beta blocker
surgical - clipping or coiling
what are the 4 risk management treatments used in acute stroke?
- antiplatelets - 300mg aspirin for 2 weeks then lifelong clopidogrel
- statin
- AF treatments if found to have AF (NOACs, warfarin)
- antihypertensives
name three primary preventative measures used to stop a stroke ever happening
- treat hypertension
- treat diabetes
- treat hyperlipidemia
- quit smoking
- exercise
- treat cardiac disease
what treatment is used post-stroke for re-enablement?
physiotherapy
speech and language therapists (swallowing and speech)
occupational therapists for home modification
what complications can arise after a stroke related to immobility?
- pressure sores
- aspiration pneumonia
- constipation
what is the definition of a transient ischaemic attack?
an ischaemic (usually embolic) neurological event with symptoms lasting less than 24 hours (but they are often much less than this e.g 30 mins)
what is the pathophysiology behind TIAs
inadequate cerebral blood supply leading to ischaemia –> hypoxia of brain tissue –> transient loss of function with resolution but possible remittance
aetiology of TIAs (name three causes)
atherothromboembolism
cardioembolism (mural thrombosis post MI or in AF)
hyperviscosity (polycythaemia, sickle cell)
clinical presentation of a TIA depends on what?
depends on which area of the brain has become ischaemic
clinical presentation of a TIA affecting the anterior circulation
- amaurosis fugax (fleeting loss of vision in one eye) if the retinal artery is occluded
- hemiparesis
- hemisensory loss
- aphasia
clinical presentation of a TIA affecting the posterior circulation
- diplopia, vertigo, vomiting
- hemianopic visual loss
- hemisensory
- ataxia
what tests would you do to investigate a TIA
bloods - FBC for polycythaemia - glucose for hypoglycaemia Carotid doppler +/- angiography CT head ABCD2 score to assess their risk of having another stroke in the next two days
what are the categories in an ABCD2 score and what points to a patient to be at a particularly high risk for a stoke?
Age > 60 = 1 point Blood pressure > 140/90 = 1 point Clinical features - unilateral weakness = 2 points - speech disturbance w/o weakness = 1 point Duration of symptoms - symptoms lasting > 1hr = 2 points - symptoms lasting < 1hr = 1 point Diabetes = 1 point
A score over 6 strongly predicts a stroke within the next week
What is the treatment for a TIA?
- antiplatelet medication : aspirin 300mg for 2 weeks then 75mg clopidogreal lifelong
- cardiovascular risk factors controlled
- statin if high cholesterol
- carotid endarterectomy (recommended in patients where their internal carotid artery is > 70% and operative risk is acceptable).
what can you not do if you have had a TIA?
drive for 1 month
What is the pathophysiology behind a subarachnoid haemorrhage
spontaneous rupture causes a rapid release of arterial blood into the subarachnoid space causing an increased intracranial pressure and possibly a cerebrovascular accident
aetiology of subarachnoid haemorrhage
Most commonly caused by a berry aneurysm rupture
common sites are at bifurcations like:
- posterior communicating and internal carotid
- anterior communicating and ACA/MCA
congenital arteriovenous malformations
What are 4 risk factors for developing a subarachnoid haemorrhage?
hypertension
smoking
alcohol misuse
polycystic kidney disease
symptoms of a subarachnoid haemorrhage
- THUNDERCLAP HEADACHE –> sudden onset very severe
- nausea
- loss of consciousness/collapse
- seizures
- coma may follow
- may be a preceding sentinel headache
Signs of a subarachnoid haemorrhage
- neck stiffness
- kernig’s sign (unable to extend patient’s leg at the knee when thigh is flexed - takes 6 hours to develop)
- retinal bleeds
what investigations would you do in a suspected subarachnoid haemorrhage ?
- CT HEAD - seen as a star shaped lesion due to blood filling in gyro patterns around the brain and ventricles
- Lumbar puncture if the CT is negative but the history is very suggestive of a SAH
If you need to do a lumbar puncture for a SAH what is very important to consider when taking it and why?
Must make sure that it is done over 12 hours after the headache onset to allow the breakdown of RBCs
what does a positive sample from a lumbar puncture show when investigating subarachnoid haemorrhage?
Xanthochromic sample (yellow due to bilirubin) confirms diagnosis. As this differentiates between old blood from SAH vs a bloody tap.
What is the treatment of a subarachnoid haemorrhage?
- resuscitation if needed
- refer to neurosurgery immediately (endovascular coiling (preferred where possible) or surgical clipping)
- IV fluids
- Nimodipine is a Ca2+ antagonist that reduces vasospasm
what is the pathphysiology of a subdural haematoma?
rupture of bridging veins between the cortex and venous sinuses that causes an accumulating haematoma between the dura and arachnoid space. Causes a rise in intracranial pressure and can shift midline structures away from the clot.
consequence of a subdural haematoma if left untreated?
eventual tentorial herniation and coning
aetiology of a subdural haematoma
- Majority from head injury (can be minor and up to 9 months previous)
what group of people are most susceptible to subdural haematomas
elderly as brain atrophy makes bridging veins vulnerable
risk factors for subdural haematomas
falls (epileptics, alcoholics)
anticoagulation
symptoms of a subdural haematoma
- fluctuating level of consciousness +/- insidious physical/intellectual slowing
- sleepiness
- headache
- personality change
signs of a subdural haematoma
- increased ICP (headache, reduced GCS, papilloedema)
- localizing neurological symptoms
- seizures
What investigations would you do in a suspected subdural haematoma?
CT head
- shows clot +/- midline shift of structures
- crescent shaped collection of blood over 1 hemisphere
what is the treatment of subdural haematomas?
- reverse clotting abnormalities
- surgical removal of clot - emergency craniotomy and clot evacuation
- IV mannitol if increased ICP
what is the pathophysiology of an extradural haematoma?
traumatic skull fracture (usually temporal/parietal bone) leads to a rupture, typically in the middle meningeal artery and vein, causing blood to accumulate between the bone and the dura.
aetiology of an extradural haematoma
traumatic skull fracture, usually to the temporal and parietal bones
trauma to the temple
what are the clinical features of an extradural haematoma?
- beware the lucid interval pattern. this may last a few hours to days. progressive deteriorating consciousness after any head injury that initially produced no loss of consciousness. This is caused by a raising ICP.
- increasingly severe headache
- vomiting, confusion, seizures
- +/- hemiparesis with brisk reflexes and an upgoing plantar
- if bleeding continues the ipsilateral pupil dilates, coma deepens and bilateral limb weakness develops
complications from an extradural haematoma?
- brainstem compression causing deep and irregular breathing
what are the late signs in an extradural haematoma
bradycardia
increased blood pressure
what investigations would you do in a suspected extradural haematoma?
CT head
- shows a biconvex/lens-shaped haematoma because the tough dural attachments keep the bleed more localised
Skull Xray
- may be normal or may show fracture lines crossing the course of the middle meningeal vessels.
what is the treatment for an extradural haematoma?
- surgery for clot evacuation +/- ligation of the bleeding vessel
- IV mannitol if increased ICP + intubation and ventilation if patient unconscious
define epilepsy
condition that is defined by recurrent, unprovoked, epileptic seizures
what is the difference between epilepsy and epileptic seizures?
epilepsy is a chronic condition
an epileptic seizure is one event
what is the definition of an epileptic seizure?
paroxysmal event in which changes of behaviour, sensation or cognitive processes are caused by excessive hypersynchronous ( groups of brain cells depolarizing at exactly the same time) neuronal discharges in the brain
what is the definition of a non epileptic seizure?
paroxysmal event in which changes in behaviour, sensation and cognitive function caused by mental processes associated with psychosocial distress (situational)
what are 5 characteristics of an epileptic seizure
- stereotypical seizures (they are the same in each patient)
- positive ictal symptoms (seeing /hearing / feeling something that isn’t there)
- may occur from sleep
- typical seizure phenomena (lateral tongue bite, head turning)
- lasting for a relatively short amount of time (30-120 seconds)
- negative postictal symptoms (weakness)
- cyanosis
what are 3 characteristics of a non-epileptic seizure?
- rapid or slow postictal recovery
- prolonged duration (1-20 minutes)
- dramatic motor phenomena or prolonged atonia (loss of muscle strength)
- eyes/mouth closed
- ictal crying
- shaking
what is syncope?
paroxysmal event in which changes in the behaviour, sensation and cognitive processes are caused by an insufficient blood or oxygen supply to the brain
3 causes of syncope
low blood pressure
arrhythmia
blood loss
what are 5 features of syncope ?
- more likely to occur from standing
- rarely from sleep
- situational
- presyncopal symptoms (dizzy + lightheaded, seeing stars over visual field, washy noises - associated with the posterior aspects of the brain)
- Duration 5-30 seconds
- recovery within 30 seconds
what are the steps in diagnosing epilepsy (investigating transient loss of consciousness)
- is it a primary brain problem (disturbance of brain function) or a secondary brain problem (problem with blood circulation i.e syncope)?
- if a primary brain problem - is it an epileptic seizure of a non epileptic seizure? (injury during seizures and tongue biting are more suggestive of epilepsy) HISTORY - appreciate that this is difficult if you are going off of recollection and have no video.
- if deemed to be epilepsy what type of epilepsy is it?
what are the two main types of epilepsy?
- structural/metabolic epilepsy (focal epilepsy)
2. generalised (idiopathic) epilepsy
what is a focal seizure?
a seizure that originates from one part of the brain (they can gradually spread causing a secondary generalised seizure)
what are the three types of focal seizure
- partial seizures without impairment of consciousness (e.g Jacksonian seizures)
- partial seizures with impairment of consciousness (e.g psychomotor seizures)
- secondary generalised seizures
what features would you see in focal temporal lobe seizure?
- autonomic features (lip smacking, swallowing)
- manual movements (fumbling and fiddling)
- dysphagia
- Deja vu / jamais vu
- hallucinations of smell, taste or sound
- emotional disturbance
They are unconscious!
what features would you see in a focal frontal lobe seizure?
- awareness will be fully retained but they cannot control movement
- motor features: posturing or peddling movements
- Jacksonian march : spreading focal motor seizure with retained awareness
- usually from sleep
what features would you see in a focal parietal lobe seizure?
sensory disturbances - tingling, numbness
what is the first line treatment for focal seizures?
- carbamazepine
- lamotrigine
what is a common cause of focal epilepsy
hippocampal sclerosis - caused by prolonged febrile seizure in early life
aetiology of epilepsy
2/3 are idiopathic
structural : cortical scarring (head injury), developmental , hippocampal sclerosis
what investigations would you do in a presenting apparent seizure?
- thorough history, look for provoking causes
- consider an EEG - cannot exclude epilepsy and can give a false positive
- MRI : investigated for a structural lesion
- drug levels
- lumbar puncture if an infection was suspected
what is a generalised (idiopathic) seizure?
originates at some point within the brain but rapidly engaging bilaterally distributed networks leading to simultaneous onset of widespread electrical discharge with no localizing features
what are three types of generalised (idiopathic) seizure
- absences seizures
- myoclonic
- primary generalised tonic-clonic seizure
what is an absence seizure
- generalised seizure
- brief blank spells where consciousness is lost but no movement
- e.g may stop in middle of a sentence, when seizure has stopped may be able to re pick up the sentence
- presents in childhood
what are the features of myoclonic seizure?
- brief, quick, sudden jerk of a limb, face or trunk
what are the features of a tonic-clonic seizure ?
- loss of consciousness
- tonic phase - limbs stiffen, mouth and eyes open, limited movement
- clonic phase -individual spikes of electrical activity hitting the muscle so there are fast big jerky movements.
- negative post-ictal symptoms
what is the first line treatment for generalised (idiopathic) epilepsy?
- valproate
- lamotrigine
name three side effects of carbamazepine
dizziness drowsiness dry mouth nausea vomiting vision disorders
what is the mechanism of action of carbamazepine and lamotrigine?
- work on pre-synaptic excitability
- sodium channel blockers
- stop depolarization and stop the release of excitory neurotransmitters
what is the mechanism of action of pregabalin and gabapentin (two medications which can also be used to treat focal seizures)
- calcium channel blockers
- directly inhibit the presynaptic neurone
what is the mechanism of action of valproate ?
- targets and inhibits GABA transaminase (which normally degrades GABA)
- if this is inhibited GABA metabolism is reduced and GABAergic neurotransmission is increased
- inhibits presynaptic neurone
how do we use epileptic treatment and what is the potential progression?
- try to use as a monotherapy (try the lowest possible effective dose)
- if that doesn’t work consider alternative monotherapy or combinations of drugs that have different modes of action
- surgery
- electrostimulation
what are the surgical treatment options for epilepsy
- resective surgery - only for focal epilepsy - try to cut out the area of the brain where the seizure originates
- tractotomy - surgical severing of nerve tracts
what is electrostimulation (a potential treatment option for epilepsy)?
- vagal nerve stimulation
- sends electrical impulses to the brain through the vagus nerve which stops synchronization in the brain
- usually can just help reduce frequency
What is the pathology of Parkinson’s disease?
- loss of domaminergic neurons in the substantia nigra causing an alteration in neural circuits within the basal ganglia which regulates movement
- Lewy bodies in neurons (abnormal intracellular aggreagtes of protein)
- pale substantia nigra
aetiology of Parkinson’s ?
unknown often sporadic thought to have a genetic susceptibility which is triggered by the environment oxidative stress mitochondrial dysfunction
what are the three cardinal features of Parkinson’s disease?
- Bradykinesia - slowness or absence of movement
- Tremor - at rest, unilateral
- Rigidity - causing pain
What is the clinical presentation of Parkinson’s Disease?
ALWAYS ASYMMETRICAL. SLOW GRADUAL PROGRESSION OVER TIME.
- Bradykinesia - slowness or absence of movement (e.g problems doing up buttons, smaller writing etc.)
- Tremor - at rest, unilateral
- Rigidity - caused by increased tone
- if you ask the patient to make repetitive movements over time there will be a decrease in amplitude and decrease in accuracy of the movement over time (usually starts off better)
- Small stepped wide gait with a stooped posture (shuffling)
- Problems initiating movement e.g walking
- Reduced arm swinging on one side
- Reduced facial expression
how do you diagnose Parkinson’s disease?
- Diagnosis is clinical
- can do a DaTSCAN which images the dopanergic terminals or the nigrostriatal neurons in the putamen
what are the three pharmacological supportive treatments used in managing Parkinson’s?
- L-Dopa (levodopa) (first line treatment!)
- Dopamine agonists (first line treatment in younger patients) e.g ropinirole
- Enzyme inhibitors
- catechol-o-methyl-transferase inhibitors (tolcapone)
- monoamino-oxidase-B inhibitors (selegiline)
usually a combination of these treatments
pharmacological mechanism of L-Dopa
- L-Dopa is the naturally occurring pre-cursor substance of dopamine
- tyrosine –> L-Dopa –> Dopamine
- acts at dopamine receptor to increase the amount in the brain
- must be given with a peripheral dopa-decarboxylase inhibitor like carbidopa so that the levodopa can cross into the brain
this combination drug : co-careldopa
what is the pharmacological mechanism of dopamine agonists
e. g ropinirole
- supports the action of L-Dopa
- works at the post synaptic dopamine receptors
what is the pharmacological mechanism of the enzyme inhibitors used in treatment of Parkinson’s?
- they decrease the naturally occurring breakdown of dopamine to increase the dopamine levels in the brain
what are the three preparations of L-Dopa and when are they used?
- dispersible L-Dopa : rapid acting can be used 1st thing in morning
- standard release - day time
- slow release - night
what motor complications can patients develop in late stage Parkinson’s?
- on-dyskinesias : hyperkinetic movements when drugs work
- off-dyskinesias : fixed, usually painful muscle
- freezing : unpredictable loss of mobility
along with pharmacological interventions what other management should be involved in Parkinson’s disease?
- MDT approach!
- physiotherapist and occupational therapist
monitor mood as depression is very common in Parkinson’s
how are headaches classified? Give some examples for each classification
primary (no underlying cause for the headache) and secondary headaches
painful cranial neuropathies and other face pains e.g trigeminal neuralgia
primary : migraine, cluster, tension type
secondary : meningitis, SAH, GCA, medication overuse
what is the difference between primary and secondary headaches regarding diagnosis?
primary headaches are syndromes diagnosed by the history and examination
in secondary headaches there will be an abnormal result i.e on a brain scan or blood test
red flags in a patient presenting with headache that need an urgent referral
- thunderclap headache - SAH
- seizure + new headache
- suspected meningitis or encephalitis
what is the clinical presentation of a tension type headache
- how many to diagnose
- time course
- characteristics
- 10 or more attacks occurring for less than 1 day a month
- headache lasts 30mins-7 days
- bilateral
- pressing/squeezing/tightening quality
- mild to moderate intensity
- not aggravated by routine physical activity
- NEED TO HAVE : no nausea or vomiting, only one of : photophobia and phonophobia
treatment of tension type headaches
- reassurance
- lifestyle advice : exercise, avoid triggers
- symptomatic treatment for episodes : aspirin, paracetamol
investigations for a suspected tension type headache
clinical diagnosis
what is the clinical presentation of a cluster headache?
- rapid onset of severe unilateral orbital/supraorbital and/or temporal pain lasting 15-180 minutes if untreated
- ipsilateral cranial autonomic features (red, swollen eye, lacrimation)
- unilateral pain
- sense of restlessness/agitation
- attacks have a frequency from 1 every other day to 8 a day
- often nocturnal
how do you diagnose cluster headaches?
at least 5 headaches fulfilling the clinical presentation
what is the treatment for cluster headache?
- 100% Oxygen for 15 minutes
Preventives - avoid triggers (e.g alcohol)
- corticosteroids e.g verapamil for short term
what is the clinical symptom of a medication overuse headache and what drugs can cause these?
- regular headache for more than 15 days of the month
- combination analgesics
treatment for medication overuse headache?
- withdraw the analgesic
- give aspirin / naproxen to help with the rebound headache
what is the clinical presentation of a migraine without aura?
- moderate - severe headache
- attacks last between 4 and 72 hours
- can be aggravated by routine physical activity
- pulsating
- unilateral
during the headache at least one of the following: - nausea and/or vomiting
- photophobia and phonophobia
list some potential triggers for migraines
CHOCOLATE Chocolate Hangovers Orgasms Cheese/caffeine Oral contraceptives Lie-ins Alcohol Travel Exercise
what is an aura, experienced in 20% of migraine patients
patients can see flashing lights / zig-zag lines
feel that part of their vision is blurry or lost part of their vision
what are the clinical presentations of migraines with auras?
aura has only of the following:
- fully reversible visual symptoms including positive and negative features
- fully reversible dysphasic speech disturbance
at least two of the following
- homonymous visual symptoms and/or unilateral sensory symptoms
- at least 1 aura symptom develops gradually over 5 mins or more
- each symptom lasts more than 5 and less than 60 minutes
how do you diagnose a migraine with aura ?
2 attacks fulfilling the clinical presentation
what investigations would you do in a suspected migraine?
- diagnosis is clinical
- can exclude other causes by doing CRP, ESR, CT/MRI /lumbar puncture if there are red flags present
pharmacological treatment of migraines to stop an attack
combination therapy - oral triptan + NSAIDs - oral triptan + paracetamol monotherapy - oral triptan - NSAID - aspirin - paracetamol
consider adding an anti-emetic
pharmacological and non-pharmacological preventative treatment of migraines
topiramate / propranolol (stay on for a few months and can titrate dose up, use if having attacks more than 5 days a month)
acupuncture 10 sessions (2nd line)
Amitriptyline (3rd line)
Botulinum toxin type A injections
- prophylaxis of chronic migraine
- need to have tried several oral drugs first
list some potential triggers for migraines
CHOCOLATE Chocolate Hangovers Orgasms Cheese/caffeine Oral contraceptives Lie-ins Alcohol Travel Exercise
what is an aura, experienced in 20% of migraine patients
patients can see flashing lights / zig-zag lines
feel that part of their vision is blurry or lost part of their vision
what are the clinical presentations of migraines with auras?
aura has only of the following:
- fully reversible visual symptoms including positive and negative features
- fully reversible dysphasic speech disturbance
at least two of the following
- homonymous visual symptoms and/or unilateral sensory symptoms
- at least 1 aura symptom develops gradually over 5 mins or more
- each symptom lasts more than 5 and less than 60 minutes
how do you diagnose a migraine with aura ?
2 attacks fulfilling the clinical presentation
what investigations would you do in a suspected migraine?
- diagnosis is clinical
- can exclude other causes by doing CRP, ESR, CT/MRI /lumbar puncture if there are red flags present
pharmacological treatment of migraines to stop an attack
combination therapy - oral triptan + NSAIDs - oral triptan + paracetamol monotherapy - oral triptan - NSAID - aspirin - paracetamol
consider adding an anti-emetic
pharmacological and non-pharmacological preventative treatment of migraines
topiramate / propranolol (stay on for a few months and can titrate dose up, use if having attacks more than 5 days a month)
acupuncture 10 sessions (2nd line)
Amitriptyline (3rd line)
Botulinum toxin type A injections
- prophylaxis of chronic migraine
- need to have tried several oral drugs first
what is the pathophysiology of trigeminal neuralgia
compression of the trigeminal nerve resulting in demyelination and excitation of the nerve resulting in erratic pain signalling
what are potential triggers for trigeminal neuralgia?
washing the affected area
shaving
eating
talking
name two potential causes of trigeminal neuralgia?
- idiopathic
- secondary to a tumour
what is the clinical presentation of trigeminal neuralgia?
- pain occurring in one or more distributions of the trigeminal nerve with no radiation beyond the trigeminal distribution
- reoccurring in paroxysmal attacks from a fraction of a second to 2 mins
- electric shock like, stabbing, shooting or sharp
- severe intensity
- precipitated by innoculous (talking or chewing) stimuli to the affected side of the face
investigations in suspected trigeminal neuralgia
- MRI head to rule out any secondary cause e.g tumour
- diagnosis is clinical : at least three attacks unilateral face pain fulfilling the clinical presentation
what is the treatment for trigeminal neuralgia?
carbamazepine (anticonvulsant)
aetiology of multiple sclerosis?
unknown
believe that individual has to be genetically susceptible and be exposed to an environmental factor that triggers the illness (e.g EBV infection is shown to be associated)
2 facts about the epidemiology of multiple sclerosis?
- more prevalent in caucasians
- women > men
- peaks between 20-30 years old
- less likely the closer you live to the equator (vitamin D levels)
what is the pathophysiology of multiple sclerosis?
- chronic autoimmune inflammatory disorder of the CNS
- autoreactive T lymphocytes are activated
- can cross the BBB
- cause a cascade immune response
- results in damage to myelin
- myelin heals poorly with thinner, inefficient myelin and eventually causes axonal loss of oligodendrocytes
what are the pathological features of an active lesion in multiple sclerosis?
- hypercellular plaque edge due to infiltration of tissue with inflammatory cells
- demyelination breakdown products present
- extensive BBB disruption
what are the pathological features of a chronic, inactive lesion in MS?
- hypocellular plaque
- loss of axons and demyelination (no breakdown products)
- atrophy
what are the two types of demyelination seen in multiple sclerosis?
- macrophage mediated demyelination
2. antibody mediated demyelination
is myelin able to regenerate in multiple sclerosis?
some of the cells will survive
body is able to remyelinate but this myelin is thin and ineffective
these patients may recover fully but if you stress that axon by exposing it to heat you get impaired conduction (i.e in a hot shower or hot environment) (UHTOFF’S PHENOMENON)
what is the clinical presentation of multiple sclerosis?
DEMYELINATION
Diplopia
Eye movements are painful (optic neuritis)
Motor weakness (spastic and progressive)
nYstagmus
Elevated temperature worsens symotoms (uhtoff’s phenomenon)
Lhermitte’s sign (sudden sensation, like an electric shock, that passes down the back of the neck when flexed)
Intention tremor
Neuropathic pain (e.g trigeminal neuralgia, pins and needles)
Ataxia (trunk and limb)
Talking slurred (dysarthria)
Impotence
Overactive bladder (incontinence)
Numbness (decreased vibration sensation)
what are the symptoms of MS associated with?
the site where the CNS is affected e.g spinal cord - spastic weakness, optic nerves - optic neurtitis
what are the three clinical courses that MS can run?
- relapsing/remitting course
- secondary progressive
- primary progressive
can also have lesions in a preclinical setting - asymptomatic patients but have lesions which can be picked up on MRI
what is the most common type of MS?
relapsing / remitting
what is relapsing / remitting MS
clearly defined disease relapses with full recovery OR with sequelae and residual deficit (partial recovery). Periods between disease relapses are characterised by a lack of disease progression (they are stable between relapses).
what is secondary progressive MS
initial relapsing / remitting disease course followed by progression with or without occasional relapses, minor remissions or plateaus
what is primary progressive MS
disease progression from onset with occasional plateaus and temporary minor improvements allowed
what is the diagnostic criteria for MS?
clinical diagnosis
two or more CNS lesions disseminated in time and space (attacks occur at multiple sites with 30 or more days in between attacks)
investigations in suspected MS?
- MRI with contrast - active lesions are white
- CSF - Lumbar puncture (electrophoresis shows IgG bands - inflammatory proteins only seen in CSF not in serum)
- evoked responses - delayed response in visual, auditory , somatosensory and brainstem potentials
two differential diagnoses when investigating MS?
autoimmune : SLE
infectious : lyme disease, syphillis, AIDs
what is the treatment for an acute relapse/attack in MS?
Oral or IV methylprednisolone can speed up recovery from an acute exacerbation of MS
Does not alter overall prognosis
what are the disease modifying treatments used in MS?
treated aggressively in the relapse/remitting phase
- dimethyl fumerate oral BO
- monoclonal antibodies
- alemtuzumab (acts against T cells) IV
- natalizumab (acts against VLA-4 receptors that allow immune cells to cross the BBB) (this is treatment for highly active relapsing MS)
what can be used to manage symptoms in MS?
- spasticity : baclofen or gabapentin
- tremor : botulinum toxin type A injections
- urgency/frequency : intermittent self-catheterization
lifestyle advice for MS?
- regular exercise
- stop smoking
- avoiding stress
what is the definition of motor neuron disease?
a cluster of neurodegenerative diseases, characterized by a selective loss of neurons in the motor cortex, cranial nerve nuclei and anterior horn cells.
Upper and lower motor neurons can be affected
what is the main difference between MND and MS?
In MND there is no sensory loss or sphincter disturbance
what is the most typical type/clinical pattern of MND?
Amyotrophic lateral sclerosis (ALS)
- loss of motor neurons in motor cortex AND anterior horn of the cord so there are combine UMN and LMN signs
what is the aetiology of MND?
unknown
what differentiates MND from myasthenia gravis?
MND never affects eye movements
what is the second most common clinical pattern of MND, affected 10-20% of all MND?
Progressive Bulbar Palsy
- only affects cranial nerves IX-XII
what are the signs of LMN pathology?
EVERYTHING LOWERS
- reduced muscle tone
- muscle atrophy
- fasciculations
- depressed reflexes
what are the signs of muscle atrophy in MND affecting the following regions:
- bulbar
- upper and lower limbs
- resp muscles
- furrowing of tongue and fasciculations.
- upper and lower limb weakness. May have bilateral footdrop from wasing and weakness
- weak breathing muscles. diaphragm may be higher up in chest than it should be
Investigations in suspected motor neuron disease
- Neurophysiology : nerve conduction studies, electromyography (shows that problem is with LMN and not the muscles)
- MRI head and spine (looking for structural pathology)
- Blood tests (muscle enzymes - increasing creatinine kinase due to atrophy)
- Lumbar puncture (to exclude inflammatory causes)
what are the signs of UMN pathology?
EVERYTHING GOES UP
- increased muscle tone (affected limb is spastic)
- tendon reflexes go up (pathologically brisk)
- positive Babinski sign (plantar responses extensor)
- characteristic pattern of limb weakness
- upper limb : flexor muscles > extensor
- lower limb : flexor muscles < extensor
what may you observe if the patient has bilateral lesions of the UMN system?
pseudobulbar palsy emotional lability
- laugh longer/louder than normally would and may cry much more easily than normally would
clinical presentation of ALS?
- stumbling spastic gait
- foot drop +/- proximal myopathy
- weak grip (door handles don’t turn)
- weak shoulder abduction (hair washing is hard)
- UMN signs
- LMN signs
what is the diagnostic criteria for ALS / MND
- no diagnostic test
- definite MND : lower and upper motor neuron signs in 3 regions
what is the treatment for MND? What is its mechanism of action
Riluzole
inhibitor of glutamate release and NMDA receptor antagonist
what is meningitis?
inflammation of the meninges
what are the non-infective causes of meningitis?
- paraneoplastic
- drug side effects
- autoimmune (vasculitis/SLE can cause sterile meningitis)
how can infection enter the CSF and brain?
- via blood stream –> if bacteraemic can get seeding of infection into CSF
- extracranial infection –> colonisation in nasopharynx of causative bacteria / otitis media / sinusitis
- neurosurgical or trauma
what is the pathophysiology of meningitis?
- bacteria in CSF
- because CSF is sterile there are no WBC and the bacteria can replicate freely and rapidly
- Inflammation
- Blood brain barrier breaksdown
- neutrophils/lymphocytes enter the CSF
- more inflammation
- can cause brain swelling
what are the symptoms of meningitis?
Fever
headache
neck stiffness (may not be able to touch chin to chest)
Later:
- decreasing GCS
- petechial rash (non-blanching) if bacterial
what is meningism
- neck stiffness
- photophobia
- Kernig’s sign (pain and resistance on passive knee extension with hip fully flexed)
If a suspected meningitis patient arrived at a GP surgery what would be the management the GP should give?
IM Benzylpenicillin
Admit the patient
What is the immediate management steps for a patient in hospital with meningitis
- Assess GCS
- Blood culture
+ FBC, U&E, CRP, serum glucose + lactate - Broad spectrum antibiotics
- Lumbar puncture
- Steroids
what first line broad spectrum antibiotics would you give a patient with suspected meningitis innitially?
What type of antibiotics are these?
Why do we use these?
Ceftriaxone or cefotaxime
3rd generation cephalosporins
They are able to cross the blood brain barrier
what patients should you not give cephalosporins to ?
- if they are penicillin allergic leading to anaphylaxis)
- immunocompromised
- recent travel
what steroids should you give a patient with meningitis ?what does it do?
IV dexamethasone
helps to reduce brain swelling and reduce neurological sequele
what is the definitive investigation to diagnose meningitis
Lumbar puncture
when investigating meningitis what do you test the CSF for?
- microscopy : look for white or red blood cells
- gram stain : look for organisms
- culture : blood and chocolate agar plates
- protein
- glucose
- Viral PCR : looking for certain viruses
when is a lumbar puncture contraindicated in a patient with suspected meningitis ?
- abnormal clotting (platelets/coagulation)
- petechial rash
- raised ICP - look for papilloedema
what is the most common causative organism of meningitis?
And what type of bacteria is it?
What colour on staining would it be ?
is it an acute or chronic cause for meningitis?
Gram negative diplococci : Neisseria meningitidis
pink
acute
what group of people usually present with Neisseria meningitidis ? Why?
university students
5-10% of adults are carriers of the bacteria without symptoms
when go to uni and large groups of adults mix then some can become infected
what are three bacterial causes of acute meningitis?
what type of bacteria are they?
what colour would they be on staining?
- Neisseria meningitidis (gram negative diplococci ; pink)
- Streptococcal pneumoniae (gram positive diplococci ; purple)
- Listeria (gram positive rod ; purple)
- Group B streptococci (gram positive cocci ; purple)
Listeria can be a bacterial cause of acute meningitis, what group of people are more likely to present with this as the cause?
immunosuppressed
elderly
neonates
name three viral causes of acute meningitis ?
- enterovirus
- herpes simplex virus
- varicella zoster virus
bacterial causes of chronic meningitis ?
how would one of them stain?
- mycobacterium tuberculosis (green on phenol-auramine staining)
- syphillis
how does the CSF appear in bacterial meningitis?
cloudy (pus cells)
how does the CSF appear in viral meningitis ?
clear
how does the CSF appear in TB meningitis?
clear with a fibrin web
what are the risk factors for developing bacterial meningitis?
- student
- recent travel (e.g to Sub Saharan Africa)
- Immunosuppressed
what are the risk factors for developing viral meningitis
- near small children / a small child
what would you see in CSF microscopy for bacterial meningitis?
polymorph neutrophils
what would you see in CSF microscopy for viral and TB meningitis?
lymphocytes
what would protein level in CSF be like in a patient with meningitis?
High
what would the glucose level in CSF be like in a patient with bacterial meningitis
Low (use the glucose to reproduce)
What would the glucose level in CSF be like in a patient with viral meningitis?
Normal (virus does not need glucose to replicate)
what is a clinical presentation of viral meningitis?
- had a recent viral infection
- less severe
- no rash
what other step do you need to do if the patient has Neisseria Meningitidis?
- inform public health england
- identify close contacts (partners, sharing kitchen and household contacts in droplet range)
- give ciprofloxacin prophylaxis
what is encephalitis?
inflammation of the brain
aetiology of encephalitis
usually always viral
- herpes simplex
- varicella zoster
- other viral : measles, mumps, rubella, EBV
- other : rabies
- non-infective : autoimmmune, paraneoplastic
more common in the immunocompromised
clinical presentation of encephalitis?
- preceding flu-like illness (hours -days)
- altered GCS (confusion, drowsiness, coma)
- odd behaviour
- fever
- seizures
- memory loss
- focal neurological signs
- history of travel
as viral meningitis can progress to encephalitis the patient may have a history of meningism
what is the management of encephalitis?
- Bloods cultures, serum for viral PCR
- MRI of the head +/- EEG
(white areas = inflammation) - Lumbar puncture
- lymphocytic CSF
- high protein and normal glucose
- viral PCR
- HIV test
treatment of encephalitis?
mainly supportive - pain killers - fluids - nutritional support physio and neuro rehab
what pharmacological treatment can you give to patients with encephalitis where the cause is HSV or ZVZ
Aciclovir
what is the definition of dementia?
a set of symptoms including memory loss and a decline in the previous level of normal cognitive functioning including abilities problem solving or language. It is a gradual and progressive onset.
what are the 4 subtypes of dementia?
- Alzheimer’s disease
- Vascular dementia
- Lewy body dementia
- Fronto-temporal dementia
What is the clinical presentation of frontotemporal dementia?
- behavioural / personality change
- disinhibition
- emotional unconcern
what is the most common cause of dementia?
Alzheimer’s disease
what is the pathophysiology of Alzheimer’s disease?
- accumulation of beta amyloid peptide results in progressive neuronal damage
- cerebral cortex atrophy
- intracellular neurofibrillary tangles
- increase in number of extracellular amyloid plaques
- loss of neurotransmitter acetylcholine
- enlarged ventricles
name 2 areas of the brain that are most susceptible to neuronal loss in Alzheimer’s disease?
- hippocampus
- amygdala
- temporal neocortex
- subcortical nuclei
what is the aetiology of vascular dementia?
cumulative effect of many small strokes
what is the aetiology of Lewy body dementia?
Lewy bodies in the brainstem and neocortex
what is the aetiology of fronto-temporal dementia?
frontal and temporal atrophy with loss of over 70% of spindle neurons
name 3 risk factors for developing Alzheimer’s disease?
- 1st degree relative with AD
- Down’s syndrome
- depression
- loneliness
- smoking
what features differentiate depression from dementia?
Depression
- onset and decline often rapid with a trigger/life event
- subjective complaints of memory loss (obvious early on)
- patients are distressed / unhappy variability in cognitive performance - they ‘don’t know’ answers
Dementia
- vague, insidious onset
- unaware / attempt to hide problems
- mood may be labile, cognitive performance is consistent and answer all questions
what is the clinical presentation of Alzheimer’s disease?
- suspect in adults > 40 years old with:
- persistent, progressive and global cognitive impairment
- short term memory loss
- semantically empty speech (lacking detail)
- selective amnesia
- visuo-spatial skill affected
- anosognosia - a lack of insight into the problems endangered by the disease e.g missed appointments, mishandling of money
Later :
- irritability
- mood disturbance
- behavioural change (aggression)
clinical presentation of vascular dementia?
stepwise deterioration with short periods of stability, sudden onset
clinical presentation of Lewy body dementia?
- fluctuating cognitive impairment
- detailed visual hallucinations
clinical presentation of fronto-temporal dementia
- executive impairment
- behavioural/personality changes
- disinhibition
- episodic memory and spatial orientation are preserved until later stages
what are the investigations involved in diagnosing someone with Alzheimer’s disease
- take a history from the patient
- assess cognitive function 6CIT
- year? month? address? count 20-1?months of the year in reverse?repeat that address? - MMSE <17/30 = serious cognitive impairment
- blood tests - vitamin deficiencies, thyroid dysfunction
Specialised diagnostic tests - Structural MRI
- can see atrophy / shrinking of the hippocampal region - Amyloid imaging
- PET scan or CSF - FDG PET
- looks at glucose metabolism, in AD there is a loss of uptake of glucose
name three preventative measures for developing AD?
- healthy body weight
- healthy diet
- decrease alcohol consumption
- no smoking
- regular exercise
- engage in leisure activity (socially active)
- higher occupation (cognitively active)
- control vascular risk factors (e.g blood pressure control)
what pharmacological management can be used in treatment of AD?
- acetylcholinesterase inhibitors e.g donepezil or rivastigmine (they increase the amount of ACh in the synapse)
- antiglutamatergic treatment e.g memantine
(recommended in patients with severe disease)
name three features which differentiate dementia from delirium?
- dementia is insidious and progressive, delirium is acute and fluctuating
- dementia lasts months-years, delirium lasts hours - weeks
- dementia has normal consciousness and is a disorder, delirium has altered consciousness and can be due to stroke, metabolic or infective causes
name three types of primary brain tumour
- meningiomas (benign)
- germ cell tumours
- sellar region tumours
- gliomas
- schwannoma (tumour of cranial nerve roots - benign)
- Primary CNS lymphoma
what is the most common primary brain tumour
gliomas including astrocytomas (most common) and oligodendroglioma
what are more common primary or secondary brain tumours?
secondary metastatic brain tumours
what are the top 2 cancers than cause brain mets?
lung and brain
what gives a clue that the brain tumour is secondary not primary?
there are usually multiple mets and they have a rounded appearance with oedema surrounding them
how are brain tumours classified ?
1 by cell type (histological features) + molecular genetic features
2 grade using morphology into 4 grades of malignancy. to do this we look for mitotic activity, vascular proliferation and necrosis
what are gliomas?
tumours of the neuroepithelial cells
astrocytomas are the most common
what is the risk for grade II gliomas?
that they will go on and undergo anaplastic transformation into high grade malignant tumours
what are the 4 grades of malignancy as defined by the WHO classification of gliomas
I : benign paediatric tumour; pilocytic astrocytoma (characterised by rosenthal fibres present in children, cerebellum and are cystic)
II : premalignant tumour; diffuse astrocytoma (hypercellularity pleomorphism)
III ; anaplastic astrocytoma (proliferation, mitotic activity)
IV; glioblastoma (cellular necrosis, hypoxia within tumour. microvascular proliferation)
what are diffuse astrocytomas? and what is the difficulting with them when it comes to treatment?
tumour cells infiltrate diffusely into the brain so it is difficult to tell where the tumour ends
it is not curable by surgical resection
what is a medulloblastoma
cerebellum tumour
what is the aetiology of brain tumours?
- majority of causes are unknown
- childhood exposure to ionising radiation (more predisposed to developing a tumour)
- family history
- immunosuppression - more susceptible to CNS lymphoma
what are the symptoms of a brain tumour?
what features of each of these symptoms suggests a history more likely of a brain tumour
- headaches
- caused by raised ICP
- woken up by headache
- worse in the morning and when lying down
- associated with nausea and vomiting
- worse by coughing/sneezing - Seizures
- lower grade tumours more likely to present
- type and characteristics of the seizure depend on where the tumour is - Focal symptoms
- where in the lobes would give rise to the focal symptoms seen i.e loss of function of that area
what genetic factors are oligodendrogliomas associated with
1p19q co-deletion
IDH1 mutation
what are 3 features of an oligodendroglioma?
- calcification of tumour
- round uniform nuclei with cytoplasmic clearing
- in grade III can have vascular proliferation
what are the signs suggestive of a brain tumour
papilloedema Focal neurological deficit (rapidly progressing is a red flag!) - hemiparesis - hemisensory loss - visual field defect - dysphagia
what investigations would you do in a suspected brain tumour?
MRI head MR angiography sometimes necessary to define site or blood supply of the mass Brain biopsy (histology and molecular markers)
what tests are included in low grade protocol scanning or brain tumours?
- blood flow through mass
- MR spectroscopy - chemical composition of mass (do not want there to be high lactate peaks)
- serial scans to measure the rate of growth
- contrast dye to see if the tumour enhances
what is the treatment for a high grade glioma?
- treat the oedema surrounding the tumour with corticosteroids
- surgery : ideally resection - as much of the mass as possible
- radical radiotherapy
- chemotherapy
what is the treatment for a low grade glioma?
- surgery : early resection
- radiotherapy and chemotherapy
what is the pathophysiology of raised intracranial pressure?
- as volume of the lesion begins to increase initially there is a compensatory phase caused by a reduction in CSF volume so there is no rise in pressure
- then there is an exponential increase in pressure and lesion starts to press on adjacent structures
what are the three layers of the cerebellum?
- molecular layer - gray matter
- purkinje layer - single layer with large purkinje cells
- granular layer - white matter
what is cerebellar dysfunction usually caused by
loss of the purkinje cells
what are the signs of cerebellar ataxia?
DANISH Dysdiadochokinaesia Ataxia (limb, gait, truncal) Nystagmus Intention tremor Slurred speech (can be staccato speech) Hypotonia
what are the 4 main classifications of cerebellar ataxia?
- congenital
- diseases where ataxia is only one of the many features and may not be the main one
- familial ataxias (1/3)
- sporadic (acquired) ataxia
what are 4 subtypes of sporadic (acquired) ataxias?
- toxic : alcohol
- immune mediated ; gluten ataxia
- neurodegenerative ; multi-system atrophy
- idiopathic sporadic
- vascular
investigations in cerebellar ataxia?
what is pathognomonic sign of multi system atrophy?
MRI brain scan
- can exclude obvious structural problems
- hot cross bun sign
investigations in secondary brain tumours?
- MRI head
- CT/MRI abdomen and chest
aetiology of spinal cord compression
- disc prolapse
- secondary malignancy, spinal metastases (most commonly associated with lung, prostate, breast)
what is the clinical presentation of spinal cord compression
- progressive bilateral weakness of legs
- UMN signs below the level of the lesion
- LMN signs at the level of the lesion
- back pain
- sensory loss below the level of the lesion
investigations in suspected spinal cord compression
MRI spine
CXR of chest - primary lung malignancy
Bloods
Treatment for spinal cord compression
- dexamethasone
- surgical decompression
what is the pathophysiology of cauda equina syndrome
nerve root compression caudal to the termination of the spinal cord at L1/2
aetiology of cauda equina syndrome
herniation of lumbar disc (most commonly L4/5 + L5/S1)
tumour
trauma
Clinical presentation of cauda equina syndrome
major difference is that leg weakness is flaccid and areflexic
- bilateral sciatica - sensory loss/pain in the back of thigh/leg + lateral aspect of little toe
- bladder/bowel dysfunction (decreased sphincter tone)
- back pain
- saddle anaesthesia
investigations of cauda equina syndrome
MRI of spinal cord
Treatment of cauda equina syndrome
surgery for emergency pressure relief + conservative treatment
what is the pathophysiology of carpal tunnel syndrome?
inflammation of the carpal tunnel leads to entrapment of the median nerve at the wrist causing pain and loss of sensation
aetiology of carpal tunnel syndrome?
- anything causing swelling/compression of the tunnel
- rheumatoid arthritis
- local tumours (lipomas)
- myxoedema
clinical presentation of carpal tunnel syndrome
- aching pain in the hand and arm (especially at night)
- paraesthesia in thumb, index and middle fingers relieved by dangling hand over the edge of the bed and shaking (wake and shake)
- sensory loss
- weakness of abductor pollicis brevis +/- wasting of thenar eminence
investigations in carpal tunnel
- neurophysiological examination (nerve conduction studies)
- Phalen’s test - patient can only maximally flex wrist for 1 minute
- Tinel’s test - tapping on nerve at wrist induces tingling
what is the treatment for carpal tunnel
- splinting
- local steroid injections +/- decompression surgery
what muscles does the median nerve innervate
LLOAF
- 2x lumbricals
- opponens policis
- abductor pollicis brevis
- flexor pollicis brevis
what is a mononeuropathy
1 nerve involved
what are the 4 types of nerve fibre ? and are they myelination or not? are they large or small? what do they transmit?
large myelinated
A-alpha : proprioception
A-beta : light touch, pressure, vibration
small
A-gamma (myelinated) - pain and cold
C (unmyelinated) - pain and hot
how are polyneuropathies classified?
large fibre vs small fibre
chronic vs acute
axonal vs demyelinating
what are the three patterns of clinical presentation of chronic axonal polyneuropathies
- symmetrical sensorimotor
- asymmetrical sensory
- asymmetrical sensorimotor.
clinical presentation of a symmetrical sensorimotor polyneuropathy?
- long fibres are affected first
- tingling/pain in soles / fingertips
- if untreated becomes more proximal
- eventually motor symptoms develop after sensory to become sensorimotor
clinical presentation of an asymmetrical sensory polyneuropathy ?
- only sensory
- patchy distribution of symptoms, do not follow a specific nerve/root distribution
name 1 cause for an asymmetrical sensory polyneuropathy
- paraneoplastic
- gluten sensitivity or coeliac disease
what is the clinical presentation of asymmetrical sensorimotor polyneuropathy?
multiple mononeuropathies (mononeuritis multiplex) not specific pattern as multiple nerves are affected, not all at the same time
one cause of asymmetrical sensorimotor polyneuropathy?
vasculitis
aetiology of peripheral neuropathies ?
DAVID Diabetes Alcohol Vitamin deficiency (B12) Infective (HIV, hepatitis) Drugs
investigations in suspected peripheral neuropathies?
what does the neurophysiological examination show / identify?
- history
- clinical examination (reduced or absent tendon reflexes, sensory deficit, weakness and muscle atrophies)
- neurophysiological examination (nerve conduction studies identify the extent/severity of the peripheral neuropathy and type)
what difference would a nerve conduction study show between an axonal neuropathy and a demyelinating neuropathy?
axonal - reduced responses (amplitude decreased) of the potentials because of loss of axons
demyelinating - slow conduction velocities
what would be lost in a median nerve lesion at the wrist?
- precision grip (LLOAF muscles)
- sensory loss of radial 3.5 fingers and palm
what are the signs of an ulnar nerve lesion? (C7-T1)
When would the ulnar nerve be susceptible to damage
weakness/wasting of:
- interossei (cannot cross fingers in good luck sign)
- medial lumbricals (ulnar claw)
-hypothenar eminence
sensory loss over medial 1.5 fingers and the ulnar side of the hand
elbow trauma
what are the signs of radial nerve lesion ? (C5-T1)
what could cause damage to the radial nerve?
- wrist and finger drop
muscles involved: BEAST : brachioradialis, extensors, abductor pollicis longus, supinator, triceps
compression against the humerus
aetiology of brachial plexus mononeuropathy?
signs of brachial plexus mononeuropathy?
- trauma, radiotherapy, prolonged heavy rucksack
- pain/paraesthesia and weakness in affected arm in variable distribution
aetiology of phrenic nerve mononeuropathy?
signs of phrenic nerve mononeuropathy?
- lung cancer, myeloma, TB
- orthopnoea (shortness of breath) with raised hemidiaphragm on CXR
signs of lateral cutaneous nerve of the thigh mononeuropathy? (L2-L3)
meralgia paraesthetica - antero-lateral burning thigh pain from entrapment under the inguinal ligament
aetiology of sciatic nerve neuropathy? (L4-S3)
signs of sciatic nerve neuropathy?
- damaged by pelvic tumours or fractures to the pelvis/femur
- sensory loss below the knee laterally
- foot drop
aetiology of common peroneal nerve (L4-S1) neuropathy?
signs of common peroneal nerve neuropathy?
- often damaged as it winds round the fibular head from trauma or sitting cross legged
- foot drop
- weak ankle dorsiflexion
- sensory loss over dorsal foot
signs of tibial nerve (L4-S3) neuropathy?
inability to tiptoe (plantarflexion), invert foot or flex toes
sensory loss over sole
what does a left optic nerve lesion cause
left anopia (blindness in left eye)
what does an optic chiasm lesion cause
bitemporal hemianopia
what does a L optic tract lesion cause
contralateral (right) homonymous hemianopia
what does a lesion in the L Baum’s (parietal) loop cause
inferior right homonymous quadrantanopia
what does a lesion in the L Meyer’s (temporal) loop cause ?
superior right homonymous quadrantanopia
what are the signs of a third cranial nerve palsy?
ptosis
fixed dilated pupil (caused by the parasympathetic fibres of III damaged)
eye looks down and out
what are the signs of a IVth nerve palsy?
diplopia on looking down and in
signs of VIth nerve palsy?
horizontal diplopia on looking out
signs of Vth nerve palsy?
when open mouth the jaw deviates to the side of lesion
muscles of mastication affected
corneal reflex lost
signs of VIIth lesion
Bell’s palsy
face droop and weakness
forehead sparing (only bottom 2/3 are affected in UMN lesions)
signs of IX and Xth lesion?
when saying ah, uvula deviates away from the side of the lesion
gag reflex lost
sign of XIIth lesion?
tongue deviates to the side of the lesion
what are the three ‘clusters’ of cranial nerves?
- 3,4,5,6 all run in cavernous sinus
- 7,8 run through petrous part of the temporal bone through the internal acoustic meatus
- 9,10,11,12 all exit through jugular foramen
what is cavernous sinus syndrome?
combination of facial numbness and the eye on that side not moving +/- dilated pupil
what is the pathophysiology of myasthenia gravis?
autoimmune disorder
antibodies to nicotinic acetylcholine receptors on the post synaptic side of the NMJ
leads to less working post synaptic receptor sites leading to fewer action potentials firing, blocking the excitatory effect of ACh on the nicotinic receptors
both B and T cells are implicated
aetiology of myasthenia gravis?
associated with autoimmune disease (esp rheumatoid arthritis and SLE) thymic hyperplasia (under 50 + female) thymic atrophy/tumour (over 50 + male)
symptoms of myasthenia gravis?
slowly increasing or relapsing muscular fatigue
order that muscles are affected:
extra-ocular > bulbar > face > neck > limb girdle > trunk
name three things that can exacerbate myasthenia gravis?
pregnancy infection emotion exercise hypokalemia
signs of myasthenia gravis
ptosis diplopia dysphasia dysarthria myasthenic snarl on smiling
investigations in suspected myasthenia gravis
- serum antibodies : increased anti-ACh antibodies, muscle specific tyrosine kinase
- electromyogram : decremental muscle response to repetitive nerve stimulation
- ask patient to count to 50 - voice fades
- CT to exclude thymoma
treatment in myasthenia gravis?
- symptom control : anticholinesterase (pyridostigmine)
- immunosuppression : treat relapses with prednisolone
- thymectomy may be needed (esp in younger patients)
pathophysiology of Huntington’s disease ?
presence of mutant protein which causes loss of neurones in the striatum (caudate nucleus and putamen) of the basal ganglia, causing depletion of the GABA (inhibitory) and acetylcholine neurotransmitters
Less regulation of dopamine to the striatum causes increased movement
aetiology of Huntington’s disease?
- autosomal dominant inheritance
- CAG repear in the Huntington protein gene (HTT) on chromosome 4
- more than 35 CAG repeats = HD
- number of repeats can be indicative of age of onset and severity
- usually presents in middle age (30-40s)
what is the clinical presentation of HD?
Early - irritability and depression - personality change Later - chorea (jerky/twitching movements that become more pronounced as disease progresses) - dementia +/- fits - psychiatric problems
investigations into suspected Huntington’s?
Genetic diagnosis
MRI head shows striatum atrophy in moderate - severe disease
Treatment of Huntington’s disease?
- no cure
- counselling for patient and family
- treat chorea symptoms with benzodiazepines, sodium valproate
- treat depression with SSRIs like citalopram
- treat aggressive behaviour with antipsychotics like risperidone
- genetic counselling
what is the treatment for chronic peripheral polyneuropathies
always symptomatic - usually the damage that has been done to the nerve is not reversible
pain relief : amitryptilline, gabapentin, pregablin
cramps : quinine
balance : physiotherapy / walking aids
what is the pathophysiology of Guillain-Barre Syndrome?
acute inflammatory demyelinating polyneuropathy
demyelination and axonal degeneration due to a trigger causing antibodies to attack nerves
aetiology of GBS?
- presents a few weeks later post infection
- this trigger causes antibodies which attack the nerves
what are the common infections that can trigger GBS?
usually resp or GI tract
- campylobacter jejuni
- Cytomegalovirus
- Epstein Barr Virus
clinical presentation of GBS?
- rapid progressive symmetrical ascending (starts in toes) muscle weakness a few weeks post infection
- pain in back and limbs
- proximal muscles are more affected like the trunk, respiratory and cranial nerves (VII)
- sweating, increased pulse and BP changes
investigations into GBS?
nerve conduction studies - slow conduction
lumbar puncture - CSF has raised protein with normal WCC
monitor FVC for resp involvement
treatment of GBS?
IV immunoglobulin or plasma exchange
ventilation if resp muscles involved
major side effect of sodium valproate ?
teratogenic (disturbs development of fetus)
