Neuro Flashcards
State the function of astrocytes
regulate the chemical content of the extracellular space
Envelope synaptic junctions in the brain.
State the function of oligodendrocytes
insulate axons within the CNS
Myelin speeds propagation of nerve impulses down axon
contribute to several axons
State the function of schwann cells
insulate axons in PNS
Myelin speeds propagation of nerve impulses down axon.
contribute to only one axon
State the function of microglia
remove debris left by dead or degenerating neurones and glial cells. Phagocytic.
Migrate into brain from the blood.
May be involved in remodelling synaptic connections.
Describe the structure of afferent neurones
from PNS to CNS
cell body in dorsal root ganglia
Describe the structure of efferent neurones
from CNS to PNS
cell bodies within the CNS derived from the ventral spinal cord
Describe the structure of interneurones
found exclusively within the CNS
Connection between afferent and efferent neurons. Form connections only with other neurons.
Which lobes of the brain does the central sulcus separate?
frontal
parietal
Which lobes of the brain does the lateral fissure separate?
frontal and parietal
temporal
Which lobes of the brain does the transverse fissure separate?
occipital
cerebellum
Which lobes of the brain does the longitudinal fissure separate?
right and left frontal and parietal
Where is the precentral gyrus found?
anterior to the central sulcus
Where is the postcentral gyrus found?
posterior to the central sulcus
Where is the parahippocampal gyrus found?
inferior to the hippocampus
where is the anterior commissure found?
inferior to the septum pellucidum
Superior to the hypothalamus
describe the location of the septum pellucidum
inferior to the corpus callosum
anterior and superior to the fornix
describe the location of the cingulate gyrus
superior to the corpus callosum
describe the location of the corpus callosum
inferior to cingulate gyrus
superior to fornix
describe the location of the fornix
surrounds thalamus
inferior to corpus callosum
describe the location of the hippocampus
inferior to fornix and thalamus
superior to parahippocampal gyrus and brain stem
Posterior to amygdala
describe the location of the thalamus
surrounded by fornix
superior to hippocampus
describe the location of the hypothalamus
anterior to fornix and thalamus
superior to pituitary gland
describe the location of the pituitary gland
inferior to hypothalamus
state the layers of the meninges
periosteal dura meningeal dura arachnoid mater (subarachnoid space) pia mater
describe the location of the uncus
superior anterior to parahippocampal gyrus
describe the location of the calcarine sulcus
medial surface of the occipital lobe
divides the visual cortex (aka calcarine cortex) into two.
describe the location of the parieto-occipital sulcus
between parietal and occipital lobes of cortex
describe the location of the pineal gland
inferior to thalamus
superior to cerebellum and cerebral aqueduct
describe the location of the optic chiasm
superior to pituitary gland
where is the vermis found in the cerebellum?
centrally
where are the tonsils found in the cerebellum?
lateral to the inferior vermis
State where the spinal cord enlarges
cervical
lumbar
What is the conus medullaris?
lower end of the spinal cord
State the location of the conus medullaris?
L1/2
What is the cauda equina?
spinal nerves and nerve roots
L2-S5
What is the filum terminale?
connective tissue
stretches from apex of conus medullaris to the coccyx
What is the lumbar cistern?
subarachnoid space between the conus medullaris of spinal cord and inferior end of subarachnoid space and dura mater (about vertebral level S2);
occupied by the posterior and anterior roots constituting the cauda equina, the filum terminale, and cerebrospinal fluid;
What is the clinical significance of the lumbar cistern?
site for lumbar puncture and spinal anaesthesia
What is the notochord?
How is it formed?
solid rod of cells running down the midline
formed from prenotochordal cells migrating through primitive pit
How is neurulation initiated?
ectodermal cells above the notochord differentiate to become the neural plate
How is the neural tube formed?
neural plate thickens
lateral edges rise up
midline depresses (forms neural groove)
lateral edges fuse in midline
Where does fusion of the neural folds begin?
How does it spread?
cervical region
cephalo-caudally
Why are neuropores formed?
last parts of neural tube to fuse anteriorly and posteriorly
Which neuropore closes first?
anterior (day 25)
posterior (day 28)
What fails to develop in anencephaly?
What is the result?
failure of anterior neuropore closure
absence of cranial structures, including brain
What fails to develop in spina bifida?
failure of posterior neuropore to close
can occur anywhere from base of skull to sacrum
vertebral arch incompletely formed or absent
Where along the spine is spina bifida most common?
lumbosacral region
Describe spina bifida occulta
overlying skin intact
bony vertebral arch defect
no visible external overlying sac
no protusion of spinal cord or membranes
Describe spina bifida cystica
both vertebral defect and visible cystic mass
Describe a meningocoele
cystic swellng of dura and arachnoid mater
protrudes through vertebral arch defect
no spinal neural tissue present within sac
Describe myelomeningocoele
cystic swellng of dura and arachnoid mater
protrudes through vertebral arch defect
spinal neural tissue forms part of the sac
Describe rachischisis
cystic swellng of dura and arachnoid mater
spine lies widely open
neural plate has spread out on to the surface
Which form of spina bifida is most common?
spina bifida occulta
then myelomeningocoele
How can a neural tube defect be detected in a fetus?
raised maternal serum α-fetoprotein
USS
How can neural tube defects be prevented?
Increased folic acid intake pre-conceptually (3 months) and in first trimester
State in general terms how the neuroectoderm tube forms the developed neural tissues
lumen = ventricular system
cranial dilations = brain
caudal tail = spinal cord
Why does the cauda equina form?
at 3 months of fetal development, the spinal cord and vertebral column are the same length
but after this, the spinal column grows faster
the spinal roots need to elongate to exit at their original intervertebral foramina
What are the three primary brain regions?
- forebrain (prosencephalon),
- midbrain (mesencephalon)
- hindbrain (rhombencephalom)
In what week do the three primary brain regions form?
week 4
In what week do the five secondary brain regions form?
week 5
State which primary brain region each of the secondary brain regions developed from
prosencephalon -> telencephalon and diencephalon
mesencephalon -> mesencephalon
rhombencephalon -> metencephalon and myelencephalon
What does the telencephalon develop into?
cerebral hemispheres
What does the diencephalon develop into?
thalamus
What does the mesencephalon develop into?
midbrain
What does the metencephalon develop into?
pons
cerebellum
What does the myelencephalon develop into?
medulla oblongata
Why do flexures form in the neural tube?
cranial end of the neural tube develops rapidly
exceeds available space
folds up
Where is the cervical flexure found?
spinal cord hindbrain junction
Where is the cephalic flexure found?
in the midbrain region
Which secondary brain region lumen does the lateral ventricle develop from?
telencephalon
Which secondary brain region lumen does the third ventricle develop from?
diencephalon
Which secondary brain region lumen does the cerebral aqueduct develop from?
mesencephalon
Which secondary brain region lumen does the fourth ventricle develop from?
metencephlon and myelencephalon
How does hydrocephalus develop in newborns?
blockage of ventriular system
impaired absorption of CSF
What are the symptoms of hydrocephalus?
What are the signs?
irritability
vomiting
impaired conscious level
dis-junction of sutures
dilated veins
rapid increase in head circumference
How is hydrocephalus treated?
shunt
Describe the organisation of the neural tube from inside to out
neuroepithelial layer
intermediate layer = neuroblasts
marginal layer = processes
How is dorsal and ventral patterning of the neural tube achieved?
roof and floor plates
State the dorsal and ventral patterns of the neural tube
roof = alar plate = sensory
floor = basal plate = motor
Where do the neural crest cells originate from?
lateral border of the neuroectoderm tube
What transition do the neural crest cells undergo?
displaced and enter mesoderm
epithelial to mesenchymal transisition
Give examples of where the neural crest cells are used in development
adrenal medulla
schwann cells
c cells
thyroid gland
Why are the neural crest cells vulnerable to environmental insults such as alcohol?
complex migratory pattern
What is Hirschprung’s Disease?
failure of neural crest cells to migrate to intestine
affected segment of colon fails to relax
obstruction occurs
State the functions of an anstrovyte
structural support provide nutrition for neurones remove neurotransmitters maintain ionic environment help form BBB
Why do neurones require a constant source of glucose?
cannot store or produce glycogen
Describe how astrocytes provide a direct source of glucose or lactate to neurones
glycogen in astrocyte converted to lactate
transport of lactate from astrocyte to neuron via MCT1 and MCT2 lactate transporters across interstitial space
lactate converted to pyruvate
used in respiration
Why do astrocytes have transporters specific for neurotransmitters?
remove neurotransmitter after an action potential
extracellular conc remain low
prevents toxicity of neurotransmitter
prevents spread of neurotransmitter to other receptors
Why do astrocytes have a very negative resting membrane potential?
high intracellular K+ conc
due to removal of K+ after an action potential
What is the function of oligodendrocytes?
myelination in CNS
What is the function of microglia?
immune system
APC
phagocytosis
Where to microglial cells originate from?
Why is this important?
mesoderm
other glial cell are ectodermal
why is the CNS described as immune privileged?
specialised immune function
regulated inflammatory response
T cells are able to enter CNS but their inflammatory response is limited
so that inflammatory expansion is limited (rigidity of skull)
What forms the BBB?
tight junctions between endothelial cells
basement membrane surrounding capillaries
end feet of astrocyte processes
Describe the structure and action of the tight junction of the BBB
bound by clodin and occluding proteins
prevent hydrophilic molecules from entering the CSF
State the main categories of neurotransmitter, giving examples
amino acids - glutamate, GABA
biogenic amines - NA, ACh
peptides - somatostatin, neuropeptide P
What is the main excitatory amino acid?
glutamate
State the three main types of ionotropic glutamate receptors
AMPA
NMDA
kainate
What change does glutamate binding to AMPA receptors cause?
increases Na+ and K+ permeability
initial fast DEPOLARISATION
What change does glutamate binding to NMDA receptors cause?
increases Na+, K+ and Ca2+ permeability
DEPOLARISATION
How do ionotropic glutamate receptors allow more APs to fire?
depolarisation
EPSP
Why does the cell membrane need to be depolarised in order for the NMDA receptor to open?
at resting potential the channel is blocked by an Mg2+ ion
What needs to occur for the NMDA channel to open?
glutamate binds
depolarisation of membrane
glycine binds as co-agonist
What is Long Term Potentiation?
increased synaptic strength in the long term
What causes long term potentiation?
activation of NMDA receptors
Ca2+ entry
phosphorylation and insertion of additional AMPA receptors in postsynaptic membrane
What is the main inhibitory neurotransmitter in the brain?
GABA
What is the main inhibitory neurotransmitter in the brainstem and spinal cord?
glycine
How do GABA(A) and glycine receptors cause inhibition?
integral Cl- ion channels
HYPERPOLARISATION
IPSP
decreased AP firing
What is the mechanism of action of barbiturates and benzodiazepines?
bind to GABA(A) receptors
enhance inhibitory response
leads to sedation and anti-anxiety actions
What is the role of GABA(B) receptors?
modulation
State the major biogenic amines
ACh
dopamine
NA
serotonin (5-HT)
State the main action of ACh in the CNS
excitatory neurotransmitter at nicotinic and muscarinic receptors
present on presynaptic terminals to enhance the release of other neurotransmitters
Where do ACh neurones originate?
basal forebrain
pontomesencephalotegmental cholinergic complex
Which areas of the brain do ACh neurones originating in the basal forebrain innervate?
hippocampus
neocortex
Which areas of the brain do ACh neurones originating in the pontomesencephalotegmental cholinergic complex innervate?
dorsal thalamus
parts of forebrain
What actions are ACh receptors involved in?
arousal
memory
learning
motor control
Describe the link between cholinergic neurons and Alzheimer’s disease
degeneration of cholinergic neurones in the nucleus basalis is associated with Alzheimer’s disease.
Which areas of the brain have a high concentration of dopamine receptors?
substantia nigra in midbrain
ventral tegmental area of midbrain
Where do the dopaminergic neurons of the substantia nigra project axons into?
What is their function?
striatum
initiating voluntary movement
What causes Parkinson’s disease?
degeneration of dopaminergic neurons that being in the substantia nigra
What disorder can too much dopamine in the CNS lead to?
schizophrenia
Which neurotransmitters does amphetamine cause the release of?
dopamine
noradrenaline
How is Parkinson’s treated?
L-DOPA
crosses BBB
aromatic amino acid decarboxylase (AADC) converts L-DOPA to dopamine
Carbidopa given at same time
inhibits AADC so conversion does not occur in periphery
Where are noradrenaline containing neurones found in the brain?
locus coeruleus in brainstem
Where in the brain do noradrenaline containing neurones innervate?
cerebral cortex, thalamus hypothalamus, olfactory bulb, cerebellum, midbrain spinal cord
What is the function of noradrenaline containing neurones?
behavioural arousal
mood
Where are serotonin containing neurones found in the brain?
raphe nuclei in the midline of the brainstem
What is are dopamine containing neurones involved in the control of?
sleep/wakefulness
mood
How is knowledge of serotonin used in treatment of depression and anxiety disorders?
SSRIs (Serotonin Selective Reuptake Inhibitors)
increases serotonin at synapse
Which paired arteries supply the brain?
vertebral arteries
internal carotids
Where do the internal carotid arteries arise?
bifurcation of common carotid
C4
Describe the course of the carotid arteries
carotid sheath
enter brain via carotid canal of temporal bone
pass anteriorly through cavernous sinus
State the branches that the internal carotid arteries give rise to distal to the cavernous sinus
What does the ICA then continue as?
ophthalmic artery
posterior communicating artery
anterior cerebral
middle cerebral artery
What structures does the anterior cerebral artery supply?
medial surfaces of frontal and parietal lobes
What structures does the middle cerebral artery supply?
lateral portions of cerebrum
Describe the course of the vertebral arteries
arise from subclavian arteries medial to anterior scalene
ascends through transverse foramen of cervical vertebrae
enter cranium via foramen magnum
State the branches of the vertebral artery within the cranial vault
meningeal branch
anterior spinal arteries
posterior spinal arteries
posterior inferior cerebellar
How do the vertebral arteries terminate?
converge
form basilar artery
How does the basilar artery terminate?
bifurcates
forms posterior cerebral arteries
What structures does the posterior cerebral artery supply?
inferior surface of brain
occipital lobes
State the components of the circle of willis
anterior cerebral arteries anterior communicating artery internal carotid arteries posterior communicating arteries posterior cerebral arteries
In disease states, what is the benefit of the circle of willis?
anastomoses can provide collateral circulation
if arteries have become progressively blocked
however, if the block happens suddenly, collateral supply would be inadequate
Describe the blood supply of the spinal cord
anterior spinal artery - formed from branches of the vertebral arteries
two posterior spinal arteries - arise from the vertebral artery
lower than cervical: extra support from segmental and radicular arteries
What is a stroke?
acute development of a neurological deficit,
due to a disturbance in the blood supply of the brain.
What are the main causes of cerebrovascular accident?
thrombosis
embolism
hypoperfusion (due to systemically low BP)
haemorrhage - accumulation of blood within cranial cavity
What is an aneurysm?
dilation of an artery, which is greater than 50% of the normal diameter
What is spinal cord infarction?
the death of nervous tissue in the spinal cord
resulting from an interruption of the arterial supply.
What are the causes of spinal cord infarction?
vertebral fractures vertebral dislocations vascular disease atheroma external compression (eg. abdominal tumour)
What are the signs and symptoms of spinal cord infarction?
muscle weakness
paralysis
loss of relfeces
Where are the dural venous sinuses found?
between the periosteal and meningeal layers of the dura mater
Where do the dural venous sinuses drain into?
internal jugular vein
Which dural sinuses are found in the flax cerebri?
Where do they meet?
straight
superior
inferior
confluence of sinuses (posterior)
Describe the course of the venous blood from the confluence of sinuses
transverse sinuses continue bilaterally
curves into sigmoid sinus
joins to internal jugular vein
how does blood enter the cavernous sinus?
How does blood drain from the cavernous sinus?
from ophthalmic veins
via the superior or inferior petrosal sinuses to the internal jugular vein
What is Cerebral venous sinus thrombosis?
presence of a thrombus within one of the dural venous sinuses
occludes venous return
deoxygenated blood accumulates in brain parenchyma
venous infarction
also CSF accumulates as it can no longer drain
What are the symptoms of Cerebral venous sinus thrombosis?
headache
nausea
vomiting
neurological defects
How is a Cerebral venous sinus thrombosis treated?
anticoagulation
What is the role of the veins of the cerebrum?
carrying blood from the brain tissue
depositing it in the dural venous sinuses
How are cerebral veins divided into superficial and deep groups?
deep = emerge from transverse fissure superficial = in subarachnoid space. pierce meninges to drain blood into venous sinuses
state the three layers of the meninges
dura mater
arachnoid mater
pia mater
Describe the dura mater
lies directly beneath the skull
thick, tough, inextensible
periosteal layer
meningeal layer
What is a dural reflection?
meningeal layer of the dura mater folds inwards
partitions the brain, and divide the cranial cavity into several compartments
Describe the blood supply and innervation of the dura mater
middle meningeal artery and vein
trigeminal nerve
What is an extradural haematoma?
What is the common cause?
Arterial blood collects between the skull and periosteal layer of the dura.
The causative vessel is usually the middle meningeal artery, tearing as a consequence of brain trauma
What is a subdural haematoma?
What is the common cause?
Venous blood collects between the dura and the arachnoid mater.
damage to cerebral veins as they empty into the dural venous sinuses.
Describe the arachnoid mater
middle layer of the meninges,
lies directly underneath the dura mate
consists of layers of connective tissue
avascular.
What does the subarachnoid space contain?
CSF
How does CSF re-enter the circulation from the subarachnoid space?
arachnoid granulations = projections of arachnoid mater into the dura
enters dural venous sinuses
Meningitis causes cerebral oedema, raising ICP.
What are the life-threatening effects of this?
cranial herniation = parts of the brain forced out of the cranial cavity
reduced cerebral perfusion
How does a fracture of the skull vault lead to a haematoma formation?
disruption of dura and blood vessels
Why does CSF rhioorrhoea occur?
What is a complication of this?
fracture of frontal sinus or cribriform plate
dura (normally adheres to periosteum) tears
CSF leaks out
infections
What are the functions of CSF?
protection - cushions the brain
bouyancy
chemical stability
Where is CSF produced?
ependymal cells of choroid plexus in ventricles
What is the embryological derivative of the ventricles?
neural tube
Name the paired ventricles
left ad right lateral ventricles
How are the lateral ventricles connected to the third ventricle?
foramen Monro
Describe the location and anterior projections of the third ventricle
between the left and right thalamus
supra-optic recess - above optic chiasm
infundibular recess - above optic stalk
How is the third ventricle connected to the fourth ventricle?
cerebral aqueduct
Describe the location of the fourth ventricle
within the brainstem
a the junction between the pons and medulla
Where does the fluid drain into from the fourth ventricle?
central spinal canal - bathes the spinal cord
subarachnoid cisterns - bathes the brain. between arachnoid mater and pia mater.
How is the chemical composition of the CSF controlled?
plasma is filtered by the epithelial cells of the choroid plexus
What is hydrocephalus?
abnormal collection of CSF within the vetricles
Describe communicating non-obstructive hydrocephalus and what causes it
Abnormal collection of CSF in the absence of any flow obstruction in the ventricles
functional impairment of the arachnoid granulations, such as fibrosis of the subarachnoid space following a haemorrhage
Describe non-communicating obstructive hydrocephalus and what causes it
Abnormal collection of CSF, with flow obstructed within the ventricular system.
The most common site of obstruction is the cerebral aqueduct, connecting the third and fourth ventricles.
Describe hydrocephalus ex vacuo and what causes it
ventricular expansion, secondary to brain atrophy.
neurodegenerative conditions, such as Alzheimer’s disease.
How is hydrocephalus treated?
reversal of cause
shunt, draining fluid into right atrium or peritoneum
Describe the features of first order sensory neurons
sensory receptors in dermis
How many neurones make up the somatosensory ascending tracts?
three:
primary - sensory receptors
secondary
tertiary
What modality do Merkel discs detect?
vibration
pressure
texture
What modality do Mesissner’s Corpuscles detect?
light touch
vibration
What modality do Riffini Corpuscles detect?
temperature
What modality do Pacinian Corpuscles detect?
vibration
pressure
How is information about the intensity and duration of a stimulus encoded by the primary afferent?
frequency - faster rate of action potential = stronger stimulus
activation of neighbouring cells - activation of neighbouring cells = stronger stimulus
Describe the difference between tonic and phasic receptors
tonic = respond continuously in presence of adequate stimulus
phasic = adapt to stimulus, so action potential frequency decreases during a maintained stimulus
What is acuity?1
the precision by which a stimulus can be located
What determines acuity?
size of the receptive field
lateral inhibition
convergence and divergence
What is a receptive field?
area of receptors innervated by the same sensory neuron.
small receptive field = greater acuity
Describe lateral inhibition
primary afferent neurones (with receptive field centre closest to point of stimulation) synapse with inhibitory interneurons in the spinal cord
inhibition of adjacent second order neurons
action potential from second order neurons whose receptive fields are to the periphery of the stimulus are more strongly inhibited
What is two point discrimination?
minimal distance required to perceive two simultaneously applied skin indentations
What is two point discrimination determined by?
density of receptors
size of neuronal receptive field
What is convergence between primary and secondary neurons?
How does this affect acuity?
when multiple primary afferents synapse onto one secondary neuron
decreases acuity
What is divergence between primary and secondary neurons?
How does this affect acuity?
one primary neuron splits to synapse with multiple secondary neurons
causes amplification
What modalities does the DCML ascending tract carry?
fine touch
conscious proprioception
In the DCML ascending tract, where are the cell bodies of primary neurons found?
dorsal root ganglion
In the DCML ascending tract, where are the cell bodies of tertiary neurons found?
thalamus
In the DCML ascending tract, where does decussation occur?
medulla
Where does the DCML ascending tract terminate?
sensory cortex
In the DCML ascending tract, describe the route of the first order neurones
neurons from lower limb travel in the fasciculus gracilis (medial part of dorsal column)
neurons from upper limb travel in fasciculus cuneatus (lateral part of dorsal column)
In the DCML ascending tract, describe the route of the secondary neurones
travel from medulla oblongata in contralateral medial lemniscus to the thalamus
In the DCML ascending tract, describe the route of the tertiary neurones
from the ventral posterolateral nucleus of the thalamus
through the internal capsule
to the sensory cortex
What can cause a spinal cord lesion affecting the DCML?
vitamin 12 deficiency tabes dorsalis (syphilis)
What modalities does the lateral spinothalamic tract carry?
pain
temperature
What modalities does the anterior spinothalamic tract carry?
crude touch
pressure
In the spinothalamic tracts, where are the cell bodies of primary neurons found?
dorsal root ganglion
In the spinothalamic tracts, where are the cell bodies of secondary neurons found?
dorsal horn - substantia gelatinosa
In the spinothalamic tracts, where are the cell bodies of tertiary neurons found?
thalamus
In the spinothalamic tracts, where does decussation occur?
spinal cord - via the vental white commissure
In the spinothalamic tracts, where does the tertiary neuron terminate?
sensory cortex
In the spinothalamic tracts, describe the route of the secondary neurones
from substantia gelatinosa decussate via ventral white commissure ascend in contralatrral anerior or lateral spinothalamic tract depending on modality medial to lateral = C,T,L,S synapse at thalamus
In the spinothalamic tracts, describe the route of the tertiary neurones
from the ventral posterolateral nucleus of the thalamus,
through the internal capsule,
terminating at the sensory cortex.
What will damage to the lateral spinothalamic tract in the spinal cord cause?
complete loss of pain and temperature sensation on opposite side
How does sacral sparing of sensation occur?
sacral and lumbar fibres lie dorsolateral to the thoracic and cervical fibres in the spinothalamic tract
so an expanding tumour or lesion in the grey matter will affect the thoracic and cervical fibres first
so the sacral and lumbar fibres have intact pain and temperature still present initially,
What is Brown-Séquard syndrome?
(one sided lesion) of the spinal cord
involves both the anterolateral system and the DCML pathway:
• DCML pathway – ipsilateral loss of tactile sensation and proprioception
• Anterolateral system – contralateral loss of pain and temperature sensation.
Where are the cell bodies of primary neurons of the pathways of unconscious sensation found?
dorsal root ganglion
Where are the cell bodies of secondary neurons of the pathways of unconscious sensation found?
spinocerebellar = spinal grey matter cuneocerebellar = accessory cuneate nucleus in brainstem
Describe the tertiary neuron of the pathways of unconscious sensation
there are none!!!
Describe the decussation of the pathways of unconscious sensation
anterior spinocerebellar decussates once in cord and again in pons
posterior spinocerebellar and cuneocerebellar DO NOT
Describe the course of the second order neurons of the spinocerebellar tracts
anterior = Decussate in spinal cord, travel in anterior spinocerebellar tract on CONTRALATERAL side, decussate in pons to terminate in the cerebellum
posterior = ascend on IPSILATERAL side in posterior spinocerebellar tract. terminate in the cerebellum
If the anterior spinocerebellar tract is damaged in the spinal cord, what will happen?
loss of proprioception and co-ordination in the contralateral side
If the posterior spinocerebellar tract is damaged in the spinal cord, what will happen?
in loss of proprioception and co-ordinated movement on the ipsilateral side.
Describe the course of the first order neurons of the cuneocerebellar tract
cell body in dorsal root ganglion
ascend on ipsilateral side in the fasciculus cuneatus
synapse in brain stem in accessory cuneate nucleus
Describe the course of the second order neurons of the cuneocerebellar tract
begin in accessory cuneate nucleus
travel in the cuneocerebellar tract
terminate in the cerebellum.
Describe the ascending tract from the trigeminal nerve of the face
Cell bodies from the first order neurones lie in the trigeminal ganglion
their central processes synapse in the trigeminal nucleus of the pons.
Second order neurones can then ascend to the thalamus
third order neurons ascend to the cerebral cortex.
What is a nociceptor?
free dendritic nerve endings that respond to noxious stimuli which would cause injury if they persisted
Describe nociceptive afferent C-fibres
Small in diameter
Unmyelinated with slow conduction
Associated with dull, aching pain
Activated by all three noxious stimuli, so are polymodal
Describe nociceptive afferent Aδ-fibres
Myelinated so faster conduction velocity Larger diameter Associated with sharp pain Mechano-heat fibres activated by chemical stimuli
What are the three noxious modalities?
chemical
mechanical
temperature
Where do first order nociceptive afferent fibres terminate?
dorsal horn of spinal cord
A delta fibres in lamina I and V
C fibres in lamina II
Where do first order nociceptive afferent fibres synapse with second order nociceptive afferent fibres?
laminae I and V of the dorsal horn
If nociceptive afferents synapse in lamina II of the dorsal horn (substantia gelatinosa), what occurs?
synapse onto cell bodies of inhibitory neurons
inhibitory neurons run into lamina I and V
inhibit transmission between first and second order nociceptive afferents
How is output from the substantia gelatinosa regulated?
Gate Control Theory
non-noxious stimuli (from Aalpha and ABeta fibres) increase inhibitory output, reducing transmission between first and second order nociceptive afferents
Noxious stimuli cause decreased inhibitory output, increasing transmission between first and second order nociceptive afferents
Describe the course of the nociceptive second order afferents
ascend the spinal cord in the anterior and lateral spinothalamic tracts
terminate in the thalamus, brain stem, limbic system and frontal cortex.
Describe the course of the nociceptive third order afferents
from the thalamus, brain stem, limbic system and frontal cortex
to the cerebral cortex
Describe descending inhibitory control of pain
cortical stimulation of periaqueductal grey area in midbrain
neurons in periaqueductal grey stimulate nucleus raphe magnus in the medulla
neurons from nucleus raphe magnus stimulate inhibitory interneurons in the substantia gelatinosa of the spinal cord
reduces transmission between primary and secondary afferent nociceptive neurons.
Describe chronic pain
lasts for more than three months
persists after all possible healing has occurred
cause often unknown
How does tissue damage lead to pain?
tissue damage leads to detruction of cells and local leakage of contents
attraction of immune cells
release of further chemical mediators
substance P and 5-HT cause pain directly
other mediators potentuate the actions of pain mediators, as well as sensitising nociceptors
What is peripheral sensitisation?
noxious stimuli sensitise nervous system response by causing increased release of glutamate, excess NMDA receptor activation and increased second order neuron firing
at the same stimulus intensity, there is a greater pain intensity
nociceptive neurons have become hyperexcitable
What is hyperalgesia?
There is increased pain at normal threshold stimulation.
nociceptive afferents respond at a lower stimulus activity
This is the result of peripheral and central sensitisation.
What is allodynia?
pain is felt from stimuli which are not normally painful.
Pain which occurs at an area other than in the area stimulated.
What is central sensitisation?
Repeated stimulation increases spinal processing
of the same stimulus intensity, there is a greater pain intensity
What is neuropathic pain?
pain of neural origin
burning, tingling or shooting sensation
What are the symptoms of a peripheral nociceptive nerve injury?
Decreased threshold of Nociceptor activation
Increased receptive field
allodynia
hyperalgesia
prolonged post-stimulus sensations = hyperpathia
emergence of spontaneous activity
What is Complex Regional Pain Syndrome?
What is it caused by?
neuropathic disease of the extremities. diagnosis of exclusion
can be triggered by minor trauma, bone trauma, surgery, stroke or MI
What are the symptoms of Complex Regional Pain Syndrome?
- Continuous burning pain, hyperalgesia, allodynia
- Temperature and skin colour asymmetry
- Oedema, sweating changes
- Decreased range of motion, motor dysfunction, trophic changes
Describe the mechanism of action of opioids
act on MOP, DOP and KOP GPCR dopamine receptors centrally and peripherally close VOCC opens potassium channels inhibits cAMP formation reduces neurotransmitter release analgesia
What are some of the effects of opioids?
respiratory depression nausea and vomiting antitussive (preventing cough) constipation, itching, euphoria
State the names of some weak opioids
codeine
tramadol
dihydrocodeine
State the names of some strong opioids
morphine,
diamorphine
fentanyl,
oxycodone,
hydromorphone
Describe the steps of the WHO analgesics ladder
step one = non-opioids
step two = incorporate weak opioids
step three = adding strong opioids
What kind of pain are opioids poor at controlling?
neuropathic pain
What are adjuvant analgesics?
drugs that increase or aid the effect of the analgesia already being used
What is a lower motor neurone?
cell bodies in spinal cord or cranial nerve motor nuclei
act directly on muscle
What is a motor unit?
group of muscle fibres innervated by one motor neuron.
The muscle fibres are not a discrete group, but are distributed at random.
Describe S motor units
o Slow contracting o Very resistant to fatigue o Very small force o Oxidative metabolism o Well vascularised (so red)
Describe FR motor units
o Faster contracting
o Fatigue resistant
o Low force
o Oxidative and glycolytic
Describe FF motor units
o Fast contracting o Fast fatigue o High force o Glycolytic o Low vascularisation (so pale)
What are S fibres used for?
maintaining posture
What are FF fibres used for?
rapid motor movements
What is the force of muscle contraction affected by?
frequency of activation of motor units
number and type of motor units activated
What is a spinal reflex?
involuntary, unlearned, automatic reaction to a specific stimulus that does not require the brain,
What are the components of a reflex arc?
receptor afferent fibre integration centre (in spinal cord) efferent fibre effector
Describe the structure of muscle spindle
made of intrafusal skeletal muscle fibres
serve as proprioceptors that detect the amount and rate of change in length of a muscle
innervated by one sensory and one motor axon
Describe intrafusal fibres of muscle spindle
have contractile proteins (thick and thin filaments) at either end,
central region that is devoid of contractile proteins.
The central region is wrapped by the sensory dendrites of the muscle spindle afferent.
How is an action potential triggered in the muscle spindle afferent?
muscle lengthens and the muscle spindle is stretched
opens mechanically-gated ion channels in the sensory dendrites,
receptor potential that triggers action potentials
State the function of the two types of afferent fibre in the muscle spindle
The primary endings (1a)
- respond to muscle speed and the size of a muscle length change.
- fast conduction, because of their wide diameter and myelination.
- contribute both to movement and the sense of limb position.
Secondary endings (II)
- only sensitive to length and not to velocity
- contribute only to the sense of position.
- smaller axons and thus slower conduction speed
Describe the efferent innervation of the intrafusal fibres
the gamma motor neuron
When the extrafusal fibres have been stimulated to contract by alpha MN activation, the gamma MN is simultaneously excited.
This is known as alpha-gamma coactivation.
The gamma MN stimulates contraction in the two ends of the intrafusal fibre, readjusting its length and keeping the central region of the intrafusal fibre taut, to keep the muscle spindle afferent responsive.
What is the role of the efferent innervation of intrafusal fibres
to maintain muscle spindle sensitivity, regardless of muscle length.
What are Golgi tendon organs?
high-threshold receptors located at the junction of muscle and tendon
provide nformation about muscle tension.
Describe the structure of Golgi tendon organs
bare nerve endings of group 1b axons that invest a collagen matrix
sit at the junction between a muscle fibre and the tendon
How is an action potential triggered in the golgi tendon organ afferent?
When tension is created in the muscle, the collagen fibres distort and squeeze the mechanosensetive nerve endings, triggering an action potential.
Describe the stretch reflex
primary receptor = muscle spindle, afferent neurone = group 1a afferents
synapse = group 1a afferents synapse directly with alpha-motor neurones in the spinal cord to innervate the extrafusal muscle fibres
efferent neruone = alpha-motor neurones effect = contraction of the same muscle
Describe the inhibitory pathway in the stretch reflex
An excitatory synapse is also made with an inhibitory interneurone in the spinal cord,
this makes an inhibitory synapse with the alpha-motor neurones innervating the antagonistic muscle
Describe the flexion reflex
primary receptor = nociceptor
afferent neuron = myelinated afferent fibres (group 3 fibres) and unmyelinated afferent fibres (group 4 fibres).
Synapse = directly synapse with alpha-motor neurones in the spinal cord (normally polysynaptic so 3 or 4 interneurones are involved),
efferent neuron = alpha-motor neurones effect = contraction of ipsilateral flexor muscles. The net result is to withdraw the limb in response to the noxious stimuli.
Describe an alpha motor neuron
cell body in the ventral horn of the spinal cord
large diameter axon
Myelinated
60 m/s conduction velocity
innervate extrafusal fibres (the normal skeletal muscle fibres)
Describe a gamma motor neuron
- innervate the intrafusal fibres (found in muscle spindles)
- small diameter axon
- excitation leads to stimulation of intrafusal muscle fibres to contract in parallel with extrafusal fibres
What is an upper motor neuron?
- Cell body in cerebral cortex or brain stem
* Remain within CNS
State the names of the pyramidal descending tracts
corticospinal
corticobulbar
State the names of the extrapyramidal descending tracts
- Vestibulospinal
- Tectospinal
- Reticulospial
- Rubrospinal
- Olivospinal
State difference between the pyramidal and extrapyramidal descending tracts
pyramidal system has direct (monosynaptic) contact with lower motor neurones
pyramidal pass through the medullary pyramids
control voluntary movements
extra-pyramidal system has an indirect contact with the rest of the motor neurone pools.
do not pass through medullary pyramids
What is the function of the corticospinal tract?
control of voluntary movements
Where are the cell bodies of the upper motor neurons of the corticospinal motor tract found?
cerebral cortex
30% motor cortex,
30% premotor cortex and supplementary motor areas,
40% somatosensory cortex
Describe the course of the upper motor neurons of the corticospinal tract
pass through internal capsule
descend through midbrain, pons and medulla
descend in spinal cord to ventral horn of spinal level
State how fibres form either the lateral or anterior corticospinal tract and state their level of decussation
90% of fibres decussate to the contralateral side at the medulla = known as pyramidal decussation.
these fibres form the lateral corticospinal tract
terminate in the ventral horn
10% stay ipsilateral to form the anterior corticospinal tract
decussate in the spinal cord and then synapse with lower motor neurones
What is the function of the corticobulbar tract?
controlling muscles of facial expression, extra-oculuar muscles etc
mainly BILATERAL innervation
Where are the cell bodies of the upper motor neurons of the corticobulbar motor tract found?
cerebral cortex
30% motor cortex,
30% premotor cortex and supplementary motor areas,
40% somatosensory cortex
Describe the course of the upper motor neurons of the corticobulbar tract
descends through the internal capsule to the brainstem
decussate in brainstem
terminate on CONTRALATERAL cranial nerve motor nuclei in the midbrain, pons, and medulla
What is the function of the vestibulospinal tract?
balance and posture
State the source, decussation and termination of the vestibulospinal tract
arises from the vestibular nucleus
the fibres DO NOT decussate.
termination in the spinal cord
What is the function of the reticulospinal tract?
control of posture and rhythmic movements.
facilitate flexor and extensor spinal reflexes.
State the source and decussation of the reticulospinal tract
The lateral reticulospinal tract fibres arise from the medulla
descend ipsilaterally to all levels of the spinal cord. DO NOT decussate
act to facilitate flexor spinal reflexes.
The medial reticulospinal tract fibres arise from the pons
descend ipsilaterally to all levels of the spinal cord. DO NOT decussate
They act to facilitate extensor spinal reflexes.
What is the function of the tectospinal tract?
aids the directing of head movements in response to visual and auditory stimuli.
State the source, decussation and termination of the tectospinal tract
arise from the tectum (superior and inferior colliculi) of the brainstem
DECUSSATE within the brainstem
terminate in neck and upper thoracic spinal cord
What is the function of the rubrospinal and rubrobulbar tracts?
control flexor tone in distal muscles and also the tone of facial muscles.
State the source, decussation and termination of the rubrospinal and rubrobulbar tracts
arise from neurones of the red nucleus, DECUSSATE in the midbrain
descend contralaterally in the spinal cord
terminate in contralateral spinal cord.
What is Amyotrophic Lateral Sclerosis?
progressive degenerative disease
the corticospinal tracts and ventral horn cells degenerate
often beginning with the lower limbs
What is Brown-Sequard Syndrome?
loss of sensation and motor function (paralysis and ataxia) that is caused by the lateral hemisection of the spinal cord.
presentation:
· Spastic paralysis of ipsilateral side (corticospinal tract)
· Loss of fine touch and proprioception to the ipsilateral side due to damage to fasciculus gracilis and cuneatus
· Loss of pain, temperature, and pressure sensation to the contralateral side due to damage to the spinothalamic tract.
What is Anterior Spinal Artery Syndrome ?
motor paralysis and impaired pain and temperature sensation due to ischaemia affecting the spinal cord by the anterior spinal artery, affecting the corticospinal tracts
What is Syringomyelia?
development of a cyst/cavity around central canal
this grows and spreads out over time, disrupting the spinothalamic tract as this decussates just ventral to central canal.
The result is reduced temperature and pain sensation at level of lesion, yet fine touch, proprioception and vibration are unaffected.
It can affect motor system as it extends
What are the functions of the cerebellum?
coordination
precision and timing of movement
motor learning
Name the anatomical lobes of the cerebellum
anterior lobe
posterior lobe
flocculonodular lobe
State how the anatomical lobes of the cerebellum are divided
primary fissure divides anterior and posterior
posterolateral fissure divides posterior and flocculonodular loves
Name the zones of the cerebellum
vermis
intermediate zone
lateral hemispheres
Name the functional divisions of the cerebellum
what parts of the cerebellum are these formed from?
cerebrocerebellum - lateral hemispheres
spinocerebellum - vermis and intermediate zone
vestibulocerebellum - flocculonodular lobe
What is the function of the cerebrocerebellum?
planning movements and motor learning
receives inputs from the cerebral cortex and pontine nuclei
sends outputs to the thalamus and red nucleus
regulates coordination of muscle activation
important in visually guided movements
What is the function of the spinocerebellum?
regulating body movements by allowing for error correction.
receives proprioceptive information
What is the function of the vestibulocerebellum?
controlling balance and ocular reflexes eg. fixation on a target.
receives inputs from vestibular system
sends outputs to the vestibular nuclei
What are the causes of cerebellar dysfunction?
stroke
trauma
tumours
ageing
What are the signs of cerebellar dysfunction
ataxia dysarthria scanning speech dysmetria (past-pointing) dysdiadochokinesia inability to learn new movements nystagmus abnormal gait wide stance loss of balance
Describe the function of the basal ganglia
regulate the amplitude and velocity of planned movement,
Name the basal ganglia
caudate nucleus putamen globus pallidus interna and externa substantia nigra subthalamic nucleus
Which structures together form the striatum?
caudate nucleus
putamen
Which structures together form the lenticular nucleus
putamen
globus pallidus
What is the effect on movement of the direct pathway through the basal ganglia?
acts to increase movement
Describe the direct pathway
- Excitatory signals from the cerebral cortex act to increase the release of inhibitory signals from the striatum (caudate nucleus + putamen) to the globus pallidus
- This means that less inhibitory signals are released from the internal segment of the globus pallidus
- So there is less inhibition at the thalamus.
More excitatory signals are sent from the thalamus to the cortex.
This stimulates movement.
How does the substantia nigra impact the direct pathway?
dopamine released
acts at D1 receptors
stimulates striatum
more inhibitory signals sent to globus pallidus interna
less inhibitory signals to thalamus
increased stimulation of cortex
stimulates movement
What is the effect on movement of the indirect pathway through the basal ganglia?
acts to inhibit movement
Describe the indirect pathway
- The cerebral cortex stimulates the striatum.
- This increases the inhibitory signals from the striatum, which act at the globus pallidus externa
- So less inhibitory signals are sent from the globus pallidus externa to the subthalamic nucleus.
- The decreased inhibition at the subthalamic nucleus leads to an increase in stimulatory signals sent to the globus pallidus interna from the subthalamic nucleus
- As the globus pallidus interna is stimulated, there are more inhibitory signals sent to the thalamus
- Less stimulation of the cerebral cortex.
so less movement
How does the substantia nigra impact the indirect pathway?
dopamine released
acts at D2 receptor
inhibits striatum
less inhibition of globus pallidus externa
more inhibition of subthalamic nucleus
less excitation of globus pallidus interna
less inhibition at thalamus
increases movement
Describe the pathogenesis of Parkinson’s disease?
degeneration of dopaminergic neurons of the substantia nigra, affecting the nigro-striatal pathway
How does Parkinson’s disease affect the direct pathway?
- Decreased stimulation of the striatum (less activation of D1 receptors)
- Decreased inhibition at the globus pallidus interna
- Increased inhibition from the globus pallidus interna at the thalamus
- Less excitation of the cerebral cortex
How does Parkinson’s disease affect the indirect pathway?
- Less inhibition at the striatum (less activation D2 receptors)
- Increased release of inhibitory signals from the striatum to the globus pallidus externa
- Decreased release of inhibitory signals from the globus pallidus externa to the subthalamic nucleus
- Increased excitatory signals sent from subthalamic nucleus to globus pallidus interna
- Increased inhibition from the globus pallidus interna at the thalamus
- Less excitation of the cerebral cortex
Describe the signs seen in Parkinson’s disease?
tremor at rest increased tone - lead pipe or cog wheel rigidity (tremor imposed on hypertonia) bradykinesia festinating gait taking more steps to turn reduced arm swing stooped posture hypomimia dysphonia
What is muscle tone?
The minimal muscle power that allows us to maintain our posture and minimal stiffness in our muscles
What creates muscle tone?
stretch reflex
when a muscle is stretched, muscle spindle afferent detect it
reflex contraction of muscles
What are some causes of LMN lesions?
peripheral neuropathy
radiculopathy
anterior horn cell damage
What causes peripheral neuropathy?
diabetes chronic alcohol abuse hypothyroidism vasculitis chemotherapy
What is radiculopathy?
compression or irritation of the nerves as they exit the spine.
can be due to mechanical compression by a disc herniation, an osteophyte, from osteoarthritis, or from thickening of surrounding ligaments.
What causes anterior horn cell damage?
motor neuron disease
poliomyelitis
What are the signs of a LMN lesion?
flaccid paralysis muscle atrophy hypotonia hyporeflexia fasciculations
Why does flaccid paralysis occur in LMN lesions?
denervation of muscles due to damage to the lower motor neurones
the muscle cannot be stimulated to contract
Why does atrophy occur in LMN lesions?
denervation
Why does hypotonia occur in LMN lesions?
failure of communication between α-motor neurones and muscles of that limb.
Why does hyporeflexia occur in LMN lesions?
loss of innervation to the muscles
loss of reflex arc
Why do fasciculations occur in LMN lesions?
denervation
individual motor units fire spontaneously
When can a lower motor neuron lesion not result in regeneration?
when the cell body of the neuron in damaged
axons cannot regenerate
When can a lower motor neuron lesion result in regeneration?
cell body intact
axon damaged
wallerian degeneration can occur
What is the pyramidal system responsible for?
fractionation of finger movements
What does the extrapyramidal system provide to the LMNs?
constant descending inhibition
what is the postural result of spastic paralysis?
in upper limbs, flexors are stronger than extensors
so overall flexion
in lower limbs, extensors are stronger than flexors
so overall extension
Where are the most common sites of UMN damage?
internal capsule
cerebral cortex
State the signs of UMN lesions
hyperreflexia hypertonia - rigidity or spasticity spastic paralysis muscle weakness Babinski sign clonus choreas hemiplegic gait
Why does hypereflexia occur in UMN lesions?
loss of the descending inhibition
loss of the inhibition of the spinal reflexes;
excessive action of the muscle reflexes
Why does hypertonia occur in UMN lesions?
loss of inhibition to lower motor neurones
reflex circuit no longer inhibited
What is spasticity in UMN lesions?
velocity dependent resistance to passive movement.
Detected with quick movements
What is rigidity in UMN lesions?
sustained resistance throughout the range of movement.
Detected with slow movements
Why does spastic paralysis occur in UMN lesions?
muscle tone becomes very high
overall flexion of upper limb
overall extension of lower limb
What is a positive Babinski sign?
blunted instrument run along the sole of the foot laterally from heel to toe,
abduction of the toes and excessive dorsiflexion of the big toe.
What is a hemiplegic gait seen in UMN lesions?
extension at the hip, knee and ankle.
foot on the affected side will be plantar flexed and move in a semicircular fashion.
The upper limb will be flexed.
what is cortical localisation?
different areas of the cortex have a different histological structure and therefore different function
where is the somatosensory association area?
parietal lobe
posterior to central sulcus
where is the gustatory area?
frontal lobe
inferior to primary motor area
where is the olfactory cortex?
temporal lobe
superior
where is the primary visual cortex?
posterior occipital
where is the primary auditory cortex?
temproral lobe middle superior
where is the auditory association area?
superior temporal lobe
Where is Broca’s area?
posterior frontal
anterior to primary motor cortex
Where is Wernicke’s area?
superior temporal lobe
What are the functions of the frontal lobe?
motor expression of speech (left) behavioural regulation eye movements continence personality, mood
What are the functions of the parietal lobe?
sensory!
body image = right
awareness of external environment = right
calculation and writing = left
What are the functions of the temporal lobe?
hearing comprehension of speech = left olfaction memory emotion
What are the functions of the occipital lobe?
vision
What symptoms would be seen in a frontal lobe lesion?
loss of fine movements loss of complex chains of movement Broca's aphasia personality change apathy lack of ability to plan and sequence tasks disinhibition emotional lability
What are the functions of the dominant hemisphere?
comprehension and expression of speech
calculation and writing
NB dominant = left
What are the functions of the non-dominant hemisphere?
body awareness
visuospatial awareness
emotion
music
how are the two hemispheres able to pass information between them?
connections via corpus callosum and anterior and midbrain comissure
What are the symptoms of a parietal lobe lesion?
impairment of postural and tactile sensation
inability to write = agraphism
astereognosis = inability to identify an object by active touch of the hands
sensory and visual inattention
lower homonomous quadrantanopia
What are the symptoms of a dominant parietal lobe lesion?
Wernicke’s aphasia
• Gerstmann’s syndrome - characterized by:
o Dysgraphia/agraphia: deficiency in the ability to write.
o Dyscalculia/acalculia: difficulty in learning or comprehending mathematics.
o Finger agnosia: inability to distinguish the fingers on the hand.
o Left-right disorientation
What are the symptoms of a non-dominant parietal lobe lesion?
neglect of contralateral limb
spatial neglect
loss of three dimensional sense
geographical agnosia
What are the symptoms of a temporal lobe lesion?
disturbance of hearing and vision disturbance of language comprehension impaired long term memory altered personality upper homonomous quadrantanopia
What is the function of Wernicke’s area?
interpretation of written and spoken words
What is the function of Broca’s area?
formulation of laguage
describe the pathway for speaking a heard word
primary auditory area
wernicke’s area
broca’s area
motor cortex
describe the pathway for speaking a written word
primary visual area
wernicke’s area
broca’s area
motor cortex
Describe Wernicke’s aphasia
disorder of comprehension
fluent but unintelligible speech
NB: occurs when lesion affects dominant hemisphere
Describe Broca’s aphasia
poorly constructed sentences disjointed speech good comprehension (can carry out three stage command)
NB:occurs when lesion affects dominant side
Describe the symptoms of an extradural haematoma
Trauma to head Loss of consciousness Lucid interval recovery Progressive hemiparesis Rapid herniation Ipsilateral pupil dilation
What are the signs and symptoms of a subdural haematoma
Trauma Slow deterioration Headache Drowsiness Confusion Focal deficits
How can you tell on CT when the onset of a subdural haematoma was?
Acute - White
Chronic - denser and darker on CT - blood has clotted
Describe the signs and symptoms of a subarachnoid haemorrhage
Rapid onset severe headache - thunderclap
Vomiting
Coma
Neck stiffness
What causes subarachnoid haemorrhage?
Berry aneurysms
Malformations
Marfan’s
Ehlers danlos
What are the symptoms of a basal skull fracture?
Periorbital ecchymosis
Mastoid ecchymosis
CSF leakage
What is a coup and contracoup injury?
Brain bruising ( contusion) due to force
Coup - contusion at site of impact
Contracoup - contusion on opposite side of skull
What is diffuse axonal injury?
Acceleration and deceleration
Causes shearing, stretching and tearing at grey-White matter junction
Cell oedema
What are the signs and symptoms of diffuse axonal injury?
Instant loss of consciousness
Persistent vegetative state
What is coning?
Cerebellar tonsillar herniation through foramen magnum
Due to RICP
Increased P on brainstem
Brain stem death
Define stroke
Abrupt loss of cerebral function
Lasting >24hrs
Due to spontaneous haemorrhage or inadequate blood supply
Define a TIA
Focal deficit
Sudden onset
Resolves completely within 24hrs
What signs will a dominant cortical stroke cause?
Dysphasia
Dysgraphia
Dyslexia
What signs will a non dominant cortical stroke cause?
Visuospatial disorders
Neglect
What vessel is affected in a TACS?
ACA or MCA
What vessel is affected in PACS?
ACA
MCA
What vessel is affected in POCS?
PCA
What vessels are affected in LACS?
Small sub cortical vessels
What are the symptoms of a TACS and PACS?
Hemiparesis contra lateral to lesion
Hemianopia contra lateral to lesion
Disturbance of higher cortical function
TACS - all
PACS - 2/3
What are the signs of a POCS?
Cerebellar syndromes
loss of consciousness
Cranial nerve deficits - ipsilateral
What is the treatment for an ischaemic stroke?
Thrombolysis
Alteplase
Given within 3 hours any age
4.5 hours under 80
24 hrs later aspirin
Long term anti platelet, statins
What are the signs and symptoms of anterior spinal infarction?
Spinal shock - flaccid weakness, areflexia, loss of pain and temperature
Fine touch and proprioception and vibration sense remain
What can cause Parkinsonism?
Multiple system atrophy Wilson's disease Corticobasal degeneration Drug induced Encephalitis
What are the classical symptoms of Parkinson’s disease?
Tremor at rest
Bradykinesia
Rigidity
What signs show that Parkinson’s is the most likely cause?
Unilateral onset Rest tremor Progressive Persistent Asymmetry Good response to L-DOPA L- DOPA induced chorea Clinical course of 10 years or more Hallucinations Hyposmia
Describe the pathogenesis of PD
Destruction dopaminergic neurons in substantial Nigra pars compact
Reduction in dopamine action at striatum
More inhibition at thalamus
Slow movement
Describe the synthesis of dopamine
In cytosol
L-tyrosine -> l-dopa -> dopamine
Tyrosine hydroxylase
Dopa decarboxylase
Describe the degradation of dopamine
Monoamine oxidase in CNS
OR
COMT - catechol-o-methyl transferase in peripheries
Why can dopamine not be used as a treatment of PD?
It cannot cross BBB
Describe the mechanism of action of l-dopa
Crosses BBB
Taken up by dopaminergic cells in substantial Nigra
Converted to dopamine by dopamine decarboxylase
Why does l-dopa stop having an effect in the late stages of PD?
Needs dopaminergic neurones to remain
What is administered with L-DOPA?
Why?
Carbidopa - peripheral dopa decarboxylase inhibitor
More crosses BBB
Less peripheral effect
What are the disadvantages of L- dopa?
Loses efficacy
Causes involuntary movements
Motor complications - on/off, wearing off, dyskinesia, dystopia, freezing
What are the ADRs of l-dopa?
Nausea
Vomiting
Arrhythmias
Hypotension
What drugs can interact with l-dopa?
Vitamin b6 increases peripheral breakdown l-dopa
MAOIs plus l-dopa enhances catecholamine production and causes hypertensive crisis
Name some dopamine receptor agonists
Apomorphine
Bromocriptine
Ropinirole
Describe the mechanism of action of dopamine receptor agonists
Bind to dopamine receptors
Produce response in neurons
What are the advantages of dopamine receptor agonists?
Direct acting
Cause less dyskinesia
Neuroprotective (?)
What are the disadvantages of dopamine receptor agonists?
Less efficacy than l-dopa
Produce impulse control disorders
Psychiatric side effects
What are the symptoms of impulse control disorders?
Pathological gambling Hypersexuality Compulsive shopping Desire to increase dosage Punding- compulsive collecting, sorting or continually handling of objects
What are the ADRs of dopamine receptor agonists?
Sedation Hallucinations Confusion Nausea Vomiting Constipation
Name a monoamine oxidase B inhibitor
Selegiline
Describe the mechanism of action of monoamine oxidase B inhibitors
Inhibits breakdown dopamine
Enhances dopamine levels in brain
What happens if monoamine oxidase B inhibitors are used above recommended dose?
Lose selectivity
Inhibits MAO type A which metabolises noradrenaline too
Name a COMT inhibitor
Entacapone
Describe the mechanism of action of COMT inhibitors
Reduce peripheral breakdown of dopamine
No therapeutic effect alone
Describe the ADRs of COMT inhibitors
Diarrhoea Postural hypotension Nausea Anorexia Dyskinesia Hallucinations Sleep disorders
Name an anticholinergic used in PD
Procyclidine
Describe the mechanism of action of anticholinergics used in PD
ACh may have antagonistic effect to dopamine
Anticholinergics may be able to treat tremor in some
No effect on bradykinesia
Describe the ADRs of anticholinergics in PD
Mood changes
Xerostomia
Visual probs
Interfere with peristalsis
Describe the mechanism of action of amantadine
Increases release dopamine in CNS
Blocks cholinergic receptors
Inhibits NMDA receptors
What are the disadvantages of amantadine in PD?
Poorly effective
Little effect on tremor
Define consciousness
Awake state in which one is fully aware of oneself and the environment
Ability to perceive and interpret stimuli
Ability to interact and communicate with others
What does consciousness require?
Function of:
Reticular system
Cerebral cortex
What part of the brain stimulated wakefulness in consciousness?
Reticular formation
What part of the brain stimulates awareness in consciousness?
Cerebral cortex
Where is the reticular formation located?
Centre of brainstem
What structures input into the reticular formation?
Cortex
Sensory system from body
Where does the reticular formation send outputs to?
Thalamus
Hypothalamus
Basal forebrain nuclei
Spinal cord
What neurotransmitter do the inter neurons projecting from the reticular formation use?
ACh
What neurotransmitter do neurones projecting from the basal forebrain nuclei going to the cortex use?
ACh
What neurotransmitter do neurones going from the hypothalamus to the cortex use?
Histamine
What neurotransmitter do neurones going from the thalamus to the cortex use?
Glutamate
Why do antihistamines cause drowsiness?
Less histamine transmitted from hypothalamus to cortex
Decreased wakefulness from reticular activating system
What causes impaired wakefulness?
Problems with reticular activating system
What causes impaired awareness?
Problems with cortex
What is the name for impaired wakefulness and awareness?
Coma
What conditions is impaired wakefulness, but normal awareness, seen in?
REM sleep
Lucid dreaming
What conditions is impaired awareness but normal wakefulness seen in?
Vegetative state
Acute confusional state
What can cause a diffuse decrease in cortical function?
Metabolic disturbance
What can damage the RAS?
RICP - compress brainstem
Lesion in brainstem
What are intracranial causes of reduced consciousness?
Haemorrhage Stoke Neoplasm RICP Infection Trauma Epilepsy
What are some extra cranial causes of reduced consciousness?
Hypoxia Electrolyte disturbances Metabolic disorder Sepsis Toxins Endocrine disorders
What are the signs of coma?
Absence of consciousness
No purposeful movement
No response to stimuli
GCS <8/15
Describe the signs of acute confusional state/delirium
Fluctuating arousal
Impaired awareness
Disorientation
Hallucinations
What are the first signs of impaired consciousness?
Change in behaviour or mood
Unsteady
Difficulty finding words
Slurred speech
Describe the AVPU scale
Alert
Voice - response to verbal stimulus
Pain - response to pain stimulus
Unresponsive
What is the AVPU score used for?
Emergency settings
Scoring less than A requires further investigation
Describe the GCS scale
Eye response 1 none 2 to pain 3 to speech 4 spontaneous
Verbal response 1 none 2 incomprehensible 3 inappropriate words 4 confused 5 orientated
Motor response 1 none 2 extensor response - decerebrate 3 flexor response - decorticate 4 flexion to pain 5 localises pain 6 obeys command
When is GCS used?
Used to see change in consciousness over time
Viewed as a pattern of change
What is declarative memory?
Naming objects, recognising places, remembering events
Stored in cortex
Assessed consciously
Rapidly learned and rapidly forgotten
What is nondeclarative memory?
Performance of motor skills
Difficult to form
Long lasting and performed without conscious recollection
Stored in cerebellum and basal ganglia
What neural changes are seen when memories are formed?
Synaptic changes
Neuroplasticity
What is memory consolidation?
What makes this more likely?
Memories committed from short term to long term
Emotion
Rehearsal and repetition
Association
What is the role of the hippocampus in memory?
Consolidation declarative memory
Integrates visual, auditory and somatosensory
Gives context and association to memories
What is long term potentiation?
Long lasting enhancement in signal transmission between two neurones
Due to synchronous stimulation
What is long term depression?
Weakening of synaptic strength
In infrequently used synapses
Causes gradual loss of memory
What is anterograde amnesia?
Cannot form new memories
What is retrograde amnesia?
Cannot remember previous memories
Describe dementia
Progressive decline of cognitive function
Memory declines
Intellect falls
What are the signs and symptoms of AD?
Progressive memory loss Aphasia Apraxia Agnosia Behavioural changes Depression
What is seen on MRI in AD?
Generalised atrophy - disproportionate in hippocampus
What are the histological markers of AD?
Neurofibrillatory tangles
Plaques
What are the neurofibrillatory tangles and plaques in AD made from?
NT - intracellular twisted hyperphosphorylated tau proteins
Plaques - amyloid deposition extracellular
What stimuli activate the reticular formation?
Sensory inputs from body
Visual inputs
Stimulation from cortex
How does visual stimulation reach the reticular formation?
Eye stimulates hypothalamus
Hypothalamus stimulates reticular formation - uses orexin as neurotransmitter
Describe non-REM sleep
Slow wave
Active body and inactive brain
Made of 4 stages
Describe REM sleep compared to non-REM sleep
active brain and inactive body
Will appear awake on EEG
Difficult to disturb from sleep
Muscle tone lost due to descending inhibition from glycinergic fibres from reticular formation
Eye movements and cranial nerve function preserved
Describe what is seen on EEG when awake
Beta waves - >14 Hz
What is seen on EEG when someone closed their eyes
Alpha waves - 8-13 Hz
Synchronous
Describe an EEG during stage 1 of sleep
Theta waves 4-7 Hz
Lower amplitude than alpha waves
What is seen on EEG in stage 2 and 3 of sleep?
Sleep spindles - almost fibrillation like. Due to thalamic activity
K complexes - tall
What is seen on EEG in stage 4 of sleep?
Delta waves - oscillations. <3.5 Hz
What is seen on EEG in REM sleep?
Beta waves!!!
What is narcolepsy?
What is thought to cause it?
Spontaneously falling asleep
Sleep paralysis - remain awake but unable to move
Loss of orexinergic neurones stimulating reticular formation leading to abnormal function cholinergic neurones
What is sleep apnoea?
Interruption of breathing during REM sleep, leading to aeousal from sleep
Caused by airway narrowing
Describe how an EEG is taken
Place 16-25 electrodes on head
Measure electrical activity
State the frequency of the waves seen during sleep on EEG
Alpha 8-13 Hz
Beta >14
Theta 4-7
Delta <3.5
What is cerebral perfusion pressure?
Difference between mean arterial pressure and intracranial pressure
Represents the pressure gradient driving cerebral blood flow
What is a normal ICP?
Between 5 and 15 mmHg
What causes venous pressure to change and increase ICP?
Raises in intrathoracic pressure
Due to breathing out, coughing, laughing, sneezing of straining
What are the components of the volume of the brain?
Brain
Arterial blood
Venous blood
CSF
What is meant by the brain being in a compensated state?
The CSF and venous volumes have decreased
ICP remains within normal limits
What is meant by the brain being in a decompensated state?
Brain has reached critical volume RICP ICP > CCP Cerebral perfusion is prevented Brain becomes ischaemic
How does the body attempt to compensate for brain ischaemia in RICP?
Cerebral vessels vasodilator
BP increase
Attempts to increase cerebral perfusion
But only raises ICP more!
How can blood cause RICP?
Venous sinus thrombosis - increased intravascular volume Extradural haematoma Subdural haematoma Subarachnoid haemorrhage Intracerebral haemorrhage
How does the brain cause RICP?
Tumour
Oedema- trauma, infarct, malignancy, infection, water intoxication
How does the CSF cause RICP?
Hydrocephalus
What causes hydrocephalus?
Increased production - choroid plexus papilloma
Disruption of flow - spina bifida, aqueduct stenosis, clot, space occupying lesion
Disruption of absorption by arachnoid granules
What are the signs and symptoms of RICP?
Headache Nausea and vomiting Uni ocular loss of vision CNIII nerve palsy CN vi nerve palsy Papilloedema Reduced GCS Loss of vestibule-ocular reflex Cushing's triad
Describe the headache seen in RICP
Generalised Bilateral Worse first thing in morning, on lying down, coughing, sneezing, bending forwards Wakes them up at night Relieved by sitting or standing
Why does CN III palsy occur in RICP?
Uncal herniation compresses
Why does CN vi palsy occur in RICP?
Long course through cranium
What is the vestibulo-ocular reflex?
Why is it lost in RICP?
Eyes normally look towards cold water placed next to ear and away from warm water placed next to ear
Brainstem death
What is cushing’s triad?
Irregular respiration
Bradycardia
Systolic hypertension
Why does Cushing’s reflex happen?
Brain ischaemia Increase in symp tone to vessels Increases BP Carotid detectors sense rise in BP Increase parasympathetic tone Bradycardia
What is decorticate posturing?
Lower limbs extended
Upper limbs flexed
Why does the decorticate response occur?
Destruction connection between cortex and thalamus
Isolates cortex from lower brain and spinal cord
What is decerebrate posturing?
Extension lower limb
Extension upper limbs
Extension head
Why does the decerebrate response occur?
Lower parts of brain and brainstem damaged
All descending inhibition lost
What is a hernia?
Protrusion of an organ or part of an organ into a region that does not normally contain it
Describe subfalcine herniation
Herniation occurs on same side as mass
Cingulate gyrus pushed under free edge falx cerebri
What are the consequences of subfalcine herniation?
Compresses anterior cerebral artery
Causes ischaemia medial parts frontal and parietal lobe
Describe uncal herniation
Uncus herniates through tentorial notch (edge of tentorium cerebelli)
What are the consequences of uncal herniation?
Compression CN III
Compresses cerebellar peduncles
Occludes cerebellar arteries
Describe tonsillar herniation
Cerebellar tonsils pushed through foramen magnum
What are the consequences of tonsillar herniation?
Brainstem compression - affects cardiac and resp control centres
Coma
Describe the phases of migraine
Well being
Prodromal symptoms - visual or sensory
Pain! Begins locally then becomes generalised
Feeling drained
What causes tension headaches?
Neurovascular irritation
Due to excessive tension on scalp muscles
What causes migraines?
Vasodilation and oedema in blood vessels
Stimulates nerve endings
What is temporal arteritis?
Also known as giant cell arteritis
Systemic immune mediated vasculitis
Chronic inflammation large arteries
What are the signs and symptoms of temporal arteritis?
Temporal headache - acute severe Myalgia Malaise Fever Visual disturbances on same side Jaw or tongue claudication Scalp tenderness Older than 50 Temporal artery abnormality - prominent, beaded, tender, pulse less
What is the main causative organism of meningitis?
Under 2 - E. Coli
2-5 - H. influenzae type B
5-30 - N. meningitidis
Over 30 - S. Pneumoniae
What is encephalitis?
Infection of neural parenchyma
What causes encephalitis?
What regions are affected?
Viral! Herpes - temporal lobe Polio - spinal cord Rabies - brain stem Cytomegalovirus
What are the symptoms of encephalitis?
Headache Confusion Fever Drowsiness Fatigue Seizures Tremors
Describe the function of the cones in the retina
Provide high acuity vision
Day vision
Colour vision
Describe the location of the cones in the retina
Concentrated at fovea
Describe the function of the rods of the retina
Specialised for night vision
Highly light sensitive
What three functional classes of cells are present in the retina?
Photoreceptors - rods and cones
Inter neurons - combine signals from the photoreceptors
Ganglion cells - output cells
What is a visual field?
Region of space that the eye can see whilst looking straight ahead
What part of the retina are images present in the left visual fields recognised by?
Nasal hemiretina of left eye
Temporal hemiretina of right eye
State the order of neurones after leaving the retina
Optic nerve Optic chiasm Optic tract Lateral geniculate ganglion Optic radiations
What fibres does the right optic tract contain?
Nasal fibres from left eye
Temporal fibres from right eye
Where is the lateral geniculate nucleus found?
In the thalamus
What fibres does the upper optic radiation carry?
Fibres from superior retinal quadrants
So vision from inferior visual quadrants
Describe the course of the superior optic radiations
Through parietal lobe
To visual cortex in occipital lobe
What fibres does the lower optic radiation carry?
Fibres from the inferior retinal fibres
So vision from the superior visual field quadrants
Describe the course of the lower optic radiation
Through temporal lobe
Pathway is called Meyer’s loop
To reach visual cortex in occipital lobe
Where is the primary visual cortex found?
Medial aspect of occipital lobe
Describe the steps in the light reflex
Light stimulates optic nerve
Synapses with interneurones in midbrain
Interneurones project bilaterally to edinger-westphal nucleus
Preganglionic parasympathetic neurones then travel to ciliary ganglion
Postganglionic fibres then innervate sphincter papillae
What is seen in accommodation of the eye?
Convergence of eye
Constriction of pupil
Lens becomes convex to increase refractive power
When is the accommodation reflex used?
When the eyes changes focus from distant to near
Why must the accommodation reflex involve the cortex?
Relates to analysis
Where in the visual pathway is the damage in complete loss of vision in one eye?
The optic nerve
What causes an optic nerve lesion?
Optic nerve glioma
Retinoblastoma in children
Optic sheath meningioma in middle aged
What part of the visual pathway is damaged in a bitemporal hemianopia?
Optic chiasm
What causes an optic chiasm lesion?
Pituitary adenoma
Anterior communicating artery aneurysm
Where in the visual pathway is damaged in a patient with left homonymous hemianopia
Loss of left field of vision
Right optic tract
What can cause damage to the optic tracts?
Stroke
Neoplasm
Trauma
Where in the visual pathway is the lesion in superior left homonymous hemianopia?
Right lower optic radiations
What causes damage to the lower optic radiations?
Damage to the temporal lobe
vascular occlusion In middle cerebral artery
Why does macular sparing occur in a posterior cerebral artery stroke?
Dual blood supply to occipital lobe
- posterior cerebral artery
- middle cerebral artery (normally supplies occipital pole representing macula)
What is an otic placode?
Thickened ectodermal patch on back of head
Goes on to form ear
How does the otic placode turn into the otic vesicle
Thicken
Invaginate
Sink below surface
Pinched off to form otic vesicle
Describe how the otic vesicle transforms into the inner ear
Saccule - cochlea
Utricle - semicircular canals
State the origins of the component of the middle ear
Tympanic cavity - first pharyngeal pouch
Malleus and incus - Meckel’s cartilage - 1st pharyngeal arch
Stapes - Reichert’s cartilage - 2nd pharyngeal arch
What does the first pharyngeal pouch turn into?
Distal end - tympanic cavity
Proximal end - Eustachian tube
State the innervation of the muscles of the middle ear. Why is this?
Tensor tympani - mandibular branch CN V - 1st pharyngeal arch
Stapedius - facial nerve - second pharyngeal arch
What does the external auditory meatus develop from?
1st pharyngeal cleft
What do the auricles develop from?
Auricular hillocks - proliferations within first and second pharyngeal arches
How do the ears move from the back of the head to the side?
Mandible grows and pushes them into place
What can be the cause of congenital deafness?
Middle ear deafness - 1st and second pharyngeal arch probs
Inner ear deafness - malformation organ of corti - commonly due to teratogenic agents
When does development of the eye begin?
Week 4
Describe formation of the eye from the forebrain
Optic vesicles (part of forebrain) grow toward lens placode in ectoderm Lens placode thickens, invaginates and pinches off. Sinks down into optic vesicle Optic vesicle stretches out to grasp lens placode
What is the choroid fissure?
Long slit running down stalk of optic vesicle
What does failure of closure of the choroid fissure result in?
Coloboma
The optic vesicles closes around the hyoid artery
What is the fate of this artery?
Degenerated dismally
Becomes central retinal artery proximally
What forms the ciliary body musculature and the extra ocular muscles?
Ciliary body - rim of optic vesicle
Extra ocular muscles - pre optic myotomes
What does the optic vesicle develop into?
Optic cup
Retina, iris, ciliary body
Why can retinal detachment occur?
Retina develops from two separate layers
Intraretinal space can open up again
What are congenital cataracts?
Opacity of lenses
Due to genetic defect or teratogen
What is congenital rubella syndrome?
When pregnancy woman gets rubella during first trimester Triad of symptoms in fetus: Sensorineural deafness Cataracts or retinopathy Congenital heart disease (PDA)
Define a partial seizure
Only affects one hemisphere of the brain
What is the difference between a simple and complex partial seizure?
Simple - no loss of consciousness
Complex - loss of consciousness
What are the symptoms of a partial seizure affecting the frontal lobe?
Abnormal head movements
Swearing/shouting out
Abnormal posturing
Repeated movements
Describe the features of a partial seizure affecting the parietal lobe
Abnormal sensations
Hallucinations
Difficulty understanding speech and language
Describe the features of a partial seizure affecting the temporal lobe
Deja vu
Strange taste/smell
Lip smacking
Swallowing or chewing
Describe the features of a partial seizure affecting the occipital lobe
Hallucinations
Disturbed vision
Eye pain
Nystagmus
What is a generalised seizure?
Affects both hemispheres
Describe a tonic-clonic seizure
Loss of consciousness Body stiffens Fall Limb jerking Loss of bladder control Post ictal period
Describe the difference between a clonic and myoclonic seizure
Clonic - jerking lasts two mins. Loss of consciousness
Myoclonic - jerking lasts fraction of second. No loss of consciousness. Happens early in morning
What are the main causes of secondary epilepsy?
Brain injury or hypoxia Pyrexia in children Alcohol Drugs Encephalitis Metabolic disturbances
What can generate an epileptic fit?
Increased excitatory activity
Decreased inhibitory activity
Loss homeostatic control
Spread neuronal hyperactivity
What is status epilepticus
Medical emergency
Continuous seizures without period of recovery
More than 30 mins
High risk mortality
