NEUROLOGY Flashcards
Recap - Outline the main roles of the
a) Frontal lobe
b) Temporal Lobe
c) Parietal Lobe
d) occipital lobe
Frontal - decision making, movement, executive function, personality.
Temporal - hearing (primary auditory cortex), memory and language, smell, facial recognition
Parietal - Sensory info
Occipital lobe - Vision
Recap - What are the main responsibilities for the
a) Brainstem
b) Cerebellum
brainstem - controls Heart and breathing rate, Blood pressure and GI function, as well as consciousness
Cerebellum - Muscle coordination, and balance
What are a collection of cell bodies in the CNS called?
What about the PNS?
Central nervous system (CNS) = brain and spinal cord
Collections of cell bodies in the CNS are called nuclei (singular = nucleus)
Peripheral nervous system (PNS) = nervous system outside the CNS
12 pairs of cranial nerves: head and neck*
31 pairs of spinal nerves
Collections of cell bodies in the PNS are called ganglia (singular = ganglion)
Key Tracts of brain - outline the course of the Dorsal column pathway (DCML).
What does it convey, and what 2 things can it be split into?
Touch, proprioception, vibration
Sensory primary axons ascend in the ipsilateral dorsal columns: either
Cuneate fasciculus – info from the UL
Gracile fasciculus – info from the LL
Synapse with 2nd neuron in the cuneate (UL) or gracile (LL) nucleus
Axons decussate in the medulla then ascend
Synapse with 3rd neuron in thalamus
Axons project to the somatosensory cortex
Lesions in the cord: ipsilateral loss of / impaired fine touch and proprioception
Recap - what are the two arteries that supply the brain?
Internal carotid
Vertebral arteries
What does the internal carotid artery branch off to supply?
branches off to create the Anterior cerebral artery, as well as posterior communicating artery to join the circle of Willis
After this the ICA continues on as the Middle cerebral artery, which supplies the lateral portions of the cerebrum.
What does the posterior cerebral artery go on to supply? What is it a branch of?
Supplies occipital lobe, posteromedial temporal lobes, midbrain, thalamus,
It is the terminal branch of the basilar arteries,
What does the middle cerebral artery supply?
· MIDDLE CEREBRAL ARTERY—(huge artery) supplies majority of lateral surface of the hemisphere and deep structures of anterior part of cerebral hemisphere.
What does the anterior cerebral artery supply?
· ANTERIOR CEREBRAL ARTERY (supplies and runs over Corpus Callosum and supplies Medial aspects of Hemispheres (anteromedial aspects of the cerebrum)
After entering the cranium through the foramen magnum, what branches does the vertebral artery give off? What do the 2 vertebral arteries then go on to do?
Give off Spinal arteries, supply the entire length of spine
Gives off The Posterior Inferior cerebellar artery - supplies cerebellum
also gives off a menigeal branch
But after this two vertebral arteries converge to form the basilar artery
What arteries branch off the basilar artery?
Superior cerebellar artery (SCA)
Anterior inferior cerebellar artery (AICA) - Both to supply the cerebellum
The Pontine arteries
What are the Two types of:
a) Strokes the in brain
b) Ischaemic events in the brain
Two kinds of stroke are ischaemic (85%) and haemorrhagic (15%)
The two types of ischaemic events in the brain are a Cerebral infarction (an ischaemic stroke) or a Transient ischaemic attack (TIA)
a TIA is not considered to be an actual stroke
Define what a stroke is:
a clinical syndrome, caused by cerebral infarction or haemorrhage, typified by rapidly developing signs of focal and global disturbance of cerebral functions lasting more than 24 hours or leading to death”
It is also referred to as a cerebrovascular accident
Define what an ischaemic stroke is
Reduction in cerebral blood flow due to arterial occlusion or stenosis. Typically divided into lacunar (affecting blood flow in small arteries), thrombotic and embolic
What are the different types of origin of ischaemic strokes?
Thrombus formation or embolus, for example in patients with atrial fibrillation
Atherosclerosis/Atherothromboembolism e.g. from carotid artery
Shock
Vasculitis
What is a Lacunar stroke? What happens in it. (it is a type of ischaemic stroke)
Lacunar stroke - Involves the Lenticulstriate arteries, small branches directly of the middle cerebral artery - more vulnerable to hypertension
—> Under high blood pressure they undergo Hyaline arteriosclerosis (where proteins are forced into the intima wall)
Damaged brain forms cysts - look like lakes under microscope hence name lacunar
What are the clinical manifestations of a lacunar stroke
Depends on the area affected
One of:
Sensory loss
Weakness (unilateral)
Ataxic hemiparesis
Dysarthria
Motor speech problems
Can happen in:
Internal capsule
Basal ganglia
Thalamus
Pons
Outline the pathology behind an ischaemic stroke of atherosclerotic origin
Basically formation of atherosclerotic plaque
Irritants damage the endothelium, damage becomes a site for atherosclerosis
A plaque forms, made of fats, cholesterol, proteins, calcium and immune cells encased in a fibrous cap.
If cap ruptures, (interestingly smaller plaques are more dangerous as they have weaker caps that are more prone to being ruptured), then
Soft core is thrombogenic and platelets adhere to the exposed collagen, creating a clot, Known as an Atherothromboembolism
Outline the pathology behind an ischaemic stroke of emboli origin.
Blood clot from elsewhere in the body, typically from atherosclerosis or from the heart
Cardiac emboli from AF, MI or infective endocarditis 🡪 blood stasis, forming a blood clot.
Only emboli in the systemic circulation/aka left side of heart can cause an embolic stroke.
Emboli in right side of heart will go to the lung, *unless a patient has a Septal defect- they can travel through the septal defect and go up to brain
Outline the pathology behind an ischaemic stroke due to shock. What are watershed infarcts
A rapid drop in blood pressure/perfusion to brain means that areas in the brain furthest from arterial blood supply - Known as Watershed zones Can undergo infarction.
Watershed infarcts are unique ischemic lesions which are situated along the border zones between the territories of the major cerebral arteries.
Causes of ischaemic strokes - Where are the “Watershed zones” of the brain?
- Cortical border zone infarction: border of ACA/MCA and MCA/PCA
- Internal border zone infarction: borders of penetrating MCA branches,orborders of the deep branches of the MCA and ACA (resulting in deep white matter infarction)
Name some risk factors for a stroke
- Hypertension
- Age: the average age for a stroke is 68 to 75 years old
- Smoking
- Diabetes
- Hypercholesterolaemia
- Atrial fibrillation
- Vasculitis
- Family history
- Haematological disease: such as polycythaemia, Sickle cell anaemia
- Medication: such as hormone replacement therapy or the combined oral contraceptive pill
What are the clinical manifestations of a stroke in the anterior cerebral artery?
1. Lower limb weakness and loss of sensation to the lower limb.
2. Gait apraxia (unable to initiate walking).
3. Incontinence.
4. Drowsiness.
Decrease in spontaneous speech.
Contralateral hemiparesis (weakness of one side of the entire body) and sensory loss with lower limbs > upper limbs
What are the clinical manifestations of a stroke in the middle cerebral artery?
Contralateral hemiparesis with upper limbs > lower limbs
Facial drop
sensory loss with upper limbs > lower limbs
Homonymous hemianopia
Hemineglect syndrome: if affecting the ‘non-dominant’ hemisphere; patients fail to be aware of items to one side of space
Aphasia: if affecting the ‘dominant’ hemisphere (the left in 95% of right-handed people) as Brocas/Wernickes areas supplied by MCA)
Aphasia is the medical term for full loss of language, while dysphasia stands for partial loss of language.
What is locked in syndrome? A stroke effecting which artery would lead to this, and what part of the brain is affected in this?
- A condition whereby the patient is fully aware but cannot move or communicate verbally due to almost complete paralysis - All voluntary muscles are generally affected, except for vertical eye movements and blinking
It may be caused by a stroke affecting thebasilar artery, thusdenying blood to the pons
What is a homonymous hemianopia?
a visual field defect involving either the two right or the two left halves of the visual fields of both eyes.
What are the clinical manifestations of a stroke in the Posterior cerebral artery?
Contralateral homonymous hemianopia with macular sparing
1. Visual field defects.
2. Cortical blindness.
Contralateralloss of pain and temperature due to spinothalamic damage
Visual agnosia - An inability to recognise or interpret visual information
Prosopagnosia - An inability to recognise a familiar face.
What are the clinical manifestations of a ischaemic stroke in the vertebral basilar arteries?
- Cerebellarsigns
- Reduced consciousness
- Quadriplegiaorhemiplegia
quadriplegia,
disturbances of gaze and vision,
lockedin syndrome (aware, but unable to respond
What are the clinical manifestations of a stroke in Weber’s syndrome (midbrain infarct; branches of posterior cerebral artery)
(midbrain infarct) Oculomotor palsy and contralateral hemiplegia
What are the clinical manifestations of a stroke in Lateral medullary syndrome (posterior inferior cerebellar artery occlusion)
Ipsilateral facial loss of pain and temperature
Ipsilateral Horner’s syndrome
(decreased pupil size, a drooping eyelid and decreased sweating on the affected side of the face)
Ipsilateral cerebellar signs
sudden vomiting and vertigo
Contralateral loss of pain and temperature
What is the ROSIER scale? What is it used for?
Recognition of Stroke in the Emergency Room (ROSIER) scale is a variation of FAST (Face, Arm, Speech, Time) and is used to differentiate acute stroke from stroke-mimics
A stroke is possible if the score is > 0 and requires an urgent non-contrast CT head. Once hypoglycaemia has been excluded, assess the following:
What is the first line investigation to do for a stroke, what would you see?
CT scan ASAP
Distinguishes ischaemic from haemorr
hypoattenuation (darkness) of the brain parenchyma
loss of grey matter-white matter differentiation, and sulcal effacement
hyperattenuation (brightness) in an artery indicates clot within the vessel lumen
What are some other investigations you would do for a Stroke
- ECG:assess for AF, MI
-
Bloods:
- Screen for risk factors includingHba1c, lipids, clotting screenand rule out stroke mimics such ashypoglycemia and hyponatraemia
- In younger patients, consider ESR, autoantibody and thrombophilia screen (ESR raised in vasculitis)
- CT angiogram (CTA):identifies arterial occlusion and should be performed in all patients who are appropriate for thrombectomy
- MRI head:MRI is an alternative to non-contrast CT head; MRI is more sensitive but CT is safer and easier to obtain
What is the management for an Ischaemic stroke?
Maintain stable blood glucose levels, hydration status and temperature
Blood pressure should not be lowered too much during a stroke because this risks reducing the perfusion to the brain.
- Thrombolysis: alteplase given if < 4.5 hours of symptom onset and haemorrhage excluded on imaging
Aspirin 300mg for 2 weeks
Prophylaxis - Lifelong clopidogrel (75mg, an Antiplatelet)
What is the function of Alteplase? What is it?
Tissue plasminogen activator that rapidly breaks down clots and can reverse the effects of a stroke if given in time.
Plasminogen is inactive form of enzyme plasmin
What would you give in the management of a stroke in someone with AF?
Warfarin/DOAC, it’s superior to aspirin in Atrial fibrillation / mural thrombus
Warfarin blocks one of the enzymes (proteins) that uses vitamin K to produce clotting factors. This disrupts the clotting process, making it take longer for the blood to clot
DOAC - eg rivaroxaban inhibit Thrombin
What are some differentials for a stroke/ what are some stroke mimics
- Stroke mimics e.g.
- Hypoglycaemia
- Hyponatraemia
- Hypercalcaemia
- Uraemia
- Hepatic encephalopathy
- Brain tumours
- Seizures
- Complicated migraine
What is average age for a stroke?
In what populations is it highest in?
- Stroke is the third leading cause of mortality in the US and the UK
- The average age for a stroke is 68 to 75 years old
- Stroke rates are higher in Asian and black African populations than in Caucasians
- M>F
What is a TIA?
Sudden onset focal neurological deficit.
Older definition:
symptoms of a stroke that resolve within 24 hours.
New definition:
transient neurological dysfunction secondary to ischaemia without infarction.
Either time based or tissue based
DOES NOT CAUSES ACUTE INFARCTION
What are some risk factors for getting a TIA
- Increasing age
- Hypertension
- Smoking
- Obesity
- Diabetes
- Hypercholesterolaemia
- Atrial fibrillation
- Carotid stenosis
- Thrombophilic disorders e.g. antiphospholipid syndrome
- Sickle cell disease
What are the 5 main aetiologies that can lead to a TIA
Atherothromboembolism
From Carotid artery – main cause - listen for a carotid bruit
Cardioembolism
In Atrial Fibrillation
After an MI
Valve disease/prosthetic valve
Hyperviscosity: eg polycythaemia, sickle-cell anaemia, myeloma.
Vasculitis eg cranial arteritis, PAN, SLE, syphilis, etc.
Dissection: a rare cause of cerebral ischaemia from tearing of the intimal layer of an artery (typically carotid).This leads to an intramural haematoma that compromisescerebral blood flow.
What artery is commonly the route of a TIA?
90% = ICA
10% = Vertebral
What are the symptoms of a TIA in the internal carotid artery?
Depends on the site of the TIA:
ACA - weak/numb contralateral leg
MCA - weak/numb contralateral side of body, face drooping w/forehead spared, dysphasia (temporal)
PCA -Homonymous hemianopia: visual field loss on the same side of both eyes
Hemisensory loss
Amaurosis fugax
What are the symptoms of a TIA in the vertebral/ basilar arteries
Diplopia – double vision
Vertigo
Vomiting
Choking and dysarthria
Ataxia
Hemisensory loss
TIA scoring - what score can help stratify which patients are at a higher risk of a stroke following a TIA?
ABCD2 score – risk score of strokes (max score is 7)
A – Age – > 60 (1 point)
B – Blood pressure (at presentation), 140/90 or more (1 point)
C – Clinical features: Unilateral weakness (2 points), Speech disturbance without weakness (1 point)
D – Duration, 60 minutes or longer (2 points), 10-59 minutes (1 point)
D – Presence of diabetes (1 point)
High risk:
ABCD2 score of 4 or more, AF is present, More than TIA in one week or a TIA whilst on anti-coagulation
Low risk:
None of the above
Present more than a week after their last symptoms have resolved
What are the primary investigations for a TIA
The Face Arm Speech Time Test (FAST test): check for/ ask about facial weakness, arm weakness, speech difficulty
- ECG: rule out AF as an underlying cause
- Auscultation: listen for carotid bruit
- Bloods:
- PT time/INR - in case thrombolytic therapy is needed
- To exclude hypoglycaemia/hyponatraemia
- FBC – looking for polycythaemia
CT scan - Request an urgent CT scan of the head
Carotid doppler – look for stenosis
CT angiography – look for stenosis
What is the management for a TIA?
Immediate management
Immediate loading dose: Aspirin 300mg
Refer to specialist – to be seen within 24h of symptom onset
Antiplatelet therapy
Standard treatment is Aspirin 75mg daily
With modified-release Dipyridamole
OR Clopidogrel daily
What is the acute management for a TIA?
What procedure is done?
- Antiplatelet:initiallyaspirin 300mg - the first-line, immediate management, if aspirin not appropriate, give an Clopidergol
REFER TO STROKE SPECIALIST*
Carotid endarterectomy:surgical procedure to remove the blockage, Done within 2 weeks stenosis of > 70% on Doppler is an indication for urgent endarterectomy
What further managment can you provide for a TIA, after the acute antiplatelets?
A High intensity Statin - atorvastatin : 20-80 mg orally once daily
An anticoauglant for AF - eg A low molecular weight heparin eg dalteparin, or
A direct thrombin inhibitor or factor Xa inhibitor - rivaroxaban
Give aspirin 300mg OD for 2wks, then switch to clopidogrel 75mg OD.
What are the main complications of a TIA?
How can you distinguish between a TIA and a Stroke?
Increased risk of stroke
Increased risk of underlying CVD
You cant distinguish until after recovery
TIA Sx resolve usually within/<24 hours
Stroke Sx last more than 24 hours
What is a Haemorrhagic Stroke?
Ruptured blood vessel leading to reduced blood flow to the brain
What is seen in Wernicke’s Aphasia?
What artery is blocked in wernickes aphasia?
history of fluent, yet confused speech.
Wernicke’s aphasia can be caused by a blockage in the inferior division of the left Middle Cerebral Artery
Therefore, a patient with Wernicke’s aphasia will talk fluently. However, the content will not make sense.
What is seen in Brocas Aphasia?
What artery is blocked in Brocas aphasia?
causes non-fluent speech. Patients often have word-finding difficulties. However, comprehension remains intact.
Broca’s area is within the frontal lobe = often affected by infarction of the left superior division of middle cerebral artery.
What are the subtypes of haemorrhagic stroke?
Intracerebral: bleeding within the brain parenchyma
Subarachnoid: bleeding into the subarachnoid space, between the pia mater and arachnoid mater of the meninges
Intraventricular: bleeding within the ventricles; prematurity is a very strong risk factor in infants
An intracerebral haemorrhage that involves just the brain tissue is called an intraparenchymal haemorrhage, whereas if the blood extends into the ventricles of the brain which store cerebrospinal fluid, it’s called an intraventricular haemorrhage.
What are the main aetiologies of a primary haemorrhagic stroke?
Hypertension
- Arteriovenous malformations: blood vessels that directly connect an artery to a vein. Over time these abnormal vessels dilate and can rupture
- Vasculitis
- Vascular tumours - aka Haemangioma
Cerebral amyloid angiopathy: a degenerative disease where abnormal protein deposits in the walls of arterioles making them less compliant
Head trauma
Outline the 2 main ways that hypertension can lead to a haemorrhagic stroke
- Arteriosclerosis: stiffening of vessels prone to rupture
- Microaneurysms: called Charcot-Bouchard aneurysms, most likely to be found on small arteries
How can a haemorrhagic stroke be secondary to an ischaemic stroke?
Ischaemia causes brain tissue death.
If there is reperfusion, there’s an increased chance that the damaged blood vessel might rupture. Bleeding into dead tissue is called haemorrhagic conversion.
Outline the pathology that a haemorrhagic stroke leads to.
pool of blood which increases pressure in the skull and puts direct pressure on nearby tissue cells and blood vessels
downstream tissue from bleed are also deprived of oxygen-rich blood. Healthy tissue can die from both the direct pressure and the lack of oxygen
Increased ICP can also lead to
CSF obstruction, - Hydrocephalus
Midline shift
Tentorial herniation
Pathologies of Brain haemorrhages -define
Midline shift
Tentorial herniation
Midline shift is a shift of the brain past its centre line it is commonly associated with a distortion of the brain stem
Tentorial herniation is the movement of brain tissue from one intracranial compartment to another
Midline shift is often associated with high intracranial pressure (ICP), which can be deadly. In fact, midline shift is a measure of ICP; presence of the former is an indication of the latter.
What are some general clinical manifestations of a haemorrhagic stroke?
Similar to an ischaemic stroke - brain region specific
- Headache
- Weakness
- Seizures
- Vomiting
- Reduced consciousness
- Anterior or middle cerebral artery stroke: numbness and sudden muscle weakness.
- Broca’s area or Wernicke’s area stroke: slurred speech or difficulty understanding speech, respectively.
- Posterior cerebral artery stroke: vision disturbances.
What are some manifestations that can point to a haemorrhagic stroke, over ischaemic?
Pointers to haemorrhage:
Sudden loss of consciousness
Severe headache
Meningism- the clinical syndrome of headache, neck stiffness and photophobia, often with nausea and vomiting - can be caused by raised ICP
Coma
These are unreliable, a CT scan is needed for differentiation
What are the investigations for a intercranial haemorrhage?
Request an immediate non-contrast CT scan of the head - will see hyperattenuation (brightness), suggesting acute blood, often with surrounding hypoattenuation (darkness) due to oedema
- Angiography: visualise the exact location of haemorrhage
- Check FBC and clotting
What is the management for an intercranial haemorrhage?
- Consider intubation, ventilation and ICU care if they have reduced consciousness
- Correct any clotting abnormality - STOP ANTICOAGULANTS IF PT IS ON THEM
Correct severe hypertension but avoid hypotension
Craniotomy, or stereotactic aspiration
Drugs to relieve ICP - IV MANITOL
Treatment for intracerebral haemorrhagic stroke - How does mannitol work?
elevates blood plasma osmolality, resulting in enhanced flow of water from tissues, including the brain and cerebrospinal fluid, into interstitial fluid and plasma
Mannitol hinders tubular reabsorption of water and enhances excretion of sodium and chloride by elevating the osmolarity of the glomerular filtrate.
Treatment for intracerebral haemorrhagic stroke - outline what happens in
a) Craniotomy
b) Stereotactic Aspiration
- Craniotomy: part of the skull bone is removed to drain any accumulated blood and relieve pressure. Good for if the bleed is close to the surface of the skull
- Stereotactic aspiration: aspirate off blood and relieve intracranial pressure, guided by CT scanner. Good for bleeding that is located deeper in brain tissue
Normal physiology - name two things found in the subarachnoid space
Cerebral Spinal fluid
The Circle of Willis
Normal physiology - what artery is found above the dura?
What is found in the subdural space
Middle meningeal artery is in the extradural space above the Dura mata
Bridging veins are found within the subdural space
normal physiology - what are the two layers of dura mater, and what is in between them?
The dura mater is composed of two layers: the periosteal/endosteal layer and the meningeal layer. The dural venous sinuses are between these two layers
Define what a Subarachnoid haemhorrhage
Subarachnoid haemorrhage (SAH) is a type of intracranial haemorrhage characterised by blood within the subarachnoid space.
Space between arachnoid mater & pia mater
What is the typical age people will have a subarachnoid haemorrhage?
How many people die straight away/soon after?
Typical age 35-65
Make up 5% of strokes
~50% of people die straight away or soon after
10-20% more die from rebleeding within weeks
Half the survivors are left with significant disability
What are some risk factors for a subarachnoid haemorrhage?
Hypertension
Known aneurysm
Previous aneurysmal SAH
Smoking
Alcohol
increasing age
Family history
Polycystic Kidney Disease
Ehlers-Danlos syndrome & Marfan syndrome
Associated with Berry aneurysms
What are the 3 main causes of a Subarachnoid Haemorrhage?
- Trauma
-
Atraumaticcases are referred to asspontaneousSAH - often due to a saccular cerebral (Berry) Aneurysm - 70-80% of SAH cases
Arteriovenous malformation(AVM) - abnormal connections between artery and vein can dilate and cause rupture - 15% of SAH cases
Can be Idiopathic
How can Polycystic Kidney disease lead to increased likelihood of aneurysms and hence Subarachnoid haemorrhages?
Polycystin help regulates cell growth and division (proliferation), by allowing Ca2+ into cells
PKD means there is a reduction in polycystin, which means that the wall of the blood vessels get bigger and bigger, getting stretched, leading to aneurysm formation
Also PKD can also cause hypertension, which can further increase risk of subarachnoid haemorrhages
Where are Berry Anerusyms most likely to occur?
Arise at points of arterial bifurcation within the Circle of Willis; the junction between the anterior communicating and anterior cerebral arteries is the most common location
Most common in anterior half of brain
Outline the pathophysiology behind a subarachnoid haemhorrage.
Rupture of blood vessel - leads to a rise in ICP,
Pressure on healthy tissues can make them die, as well as brain tissue not getting blood it needs due to bleed - Ischaemia
Vessels being bathed in a pool of blood can cause vasospasm - will further reduce the supply of blood flow to the brain
Also can irritate the meninges, which can lead to scarring which can obstruct CSF outflow ==> Hydrocephalus
What are some symptoms of an subarachnoid haemhorrage?
-
Headache
- Severe, sudden onset
- Occipital
- ‘Thunderclap’ headache
- Meningism: photophobia and neck stiffness - due to Meningies irritation
- Vision changes
- Nausea and vomiting
- Speech changes
- Seizures
- Weakness
- Confusion
- Coma
What are some signs of a Subarachnoid haemhorrhage?
- Neck stiffness
- Budzinski’s Sign - Flexion of neck = Flexion of Knees
- Kernig sign - Knee cannot be fully extended with hip flexed at 90 degrees
- Focal neurological deficit - eg if affecting Posterior cerebral artery - Oculomotor palsy
- Increased BP
Papilledema
What are some differentials for a subarachnoid haemorrhage?
Migraine
Meningitis
Corticol vein thrombosis
Carotid/vertebral artery dissection
What investigations would you do for a subarachnoid haemorrhage?
urgent Non Contrast CT head
ASAP
Detects >95% of SAH in first 24 hours - Subarachnoid and/or intraventricular blood, hyperdense areas in the subarachnoid space
“Star” shaped sign
ECG - Arrhythmias and ischaemic changes, Prolonged QTc, ST segment/T-wave abnormalities.
Lumbar puncture – if CT normal but SAH still suspected
Findings - RBCs or xanthochromia (yellow pigmentation due to degradation of haemoglobin to bilirubin)
Electrolytes - Moderate hyponatraemia
ABG – to rule out hypoxia
What is the non surgical management for a subarachnoid haemorrhage?
Immediately refer to neurosurgeon
Nimodipine - Ca2+ antagonist, (CCB) Reduces vasospasm and therefore cerebral ischaemia
Re-examine CNS often
IV fluids -Maintain cerebral perfusion
Ventricular drainage for hydrocephalus
If features of raised intracranial pressure: consider intubation with hyperventilation, head elevation (30°) and IV mannitol
What is the surgical management for a subarachnoid haemorrhage?
first-line endovascular coilingof the aneurysm -reduces blood circulation to the aneurysm inserting one or more microsurgical detachable platinum wires, into the aneurysm until there is no more blood flow occurring. Usually enter through leg.
Second-line issurgical clippingvia craniotomy - opening in the skull is created to reach the aneurysm. Then small metal clip on the neck (opening) of the aneurysm to obstruct the flow of blood.
What is the 6 month prognosis for a subarachnoid haemorrhage?
At 6 months, 25% of patients are dead and 50% are moderately to severely disabled.
Importantpredictors of 30-day mortalityinclude age, level of consciousness on admission and the amount of blood visible on CT.
What is the difference between Haematoma and haemorrhage?
A hematoma is when some blood that has seeped out of blood vessels collects under the skin. A hemorrhage is active bleeding from a broken blood vessel.
Therefore a haemorrhage can cause a haematoma.
Define what an Extradural/ Epidural Haemorrhage is.
A bleed ABOVE the dura mater, between the outer endosteal of the dura and the skull.
What is the epidemiology of a extradural haematoma?
Mostly in young people
Rare in small children, Due to plasticity of skull
Rare in >60s, as Dura is more tightly adherent to skull
More common in males
What are some general risk factors for an extradural haematoma? What is the most common cause of it?
- Head injury
- Hypertension
- Aneurysms
- Ischaemic stroke can progress to haemorrhage
- Brain tumours
- Anticoagulants such as warfarin
HEAD INJURY IS BY FAR THE MOST COMMON CAUSE
Where is the most common site for an extradural haematoma? Why is this?
The most common site where the frontal, parietal, temporal and sphenoid bones join together, CALLED THE PTERION ===>
This section of the skull is relatively thin and it’s located right above the middle meningeal artery.
Outline the pathophysiology behind what happens in an extradural haematoma.
Once a meningeal artery is torn, blood will pool between the skull and the external layer of the dura mater, separating it from the inner surface of the skull.
This blood cannot cross the suture lines where the dura mater adheres more tightly
A large epidural haematoma can cause a midline shift = displacement of the whole brain towards the opposite side of the skull.
When there’s active bleeding, it’s called a haemorrhage, and the collection of blood that results is called a haematoma.
Define what a lucid interval is, as sometimes seen in an extradural haematoma.
lucid interval which is when several hours pass before the onset of symptoms, if blood is accumulating slowly. Here patient will have mild/little symptoms just after trauma and then decline
What can a rise in ICP lead to in an Extradural haematoma? What are the two types of this
Can cause brain to herniate =
Either a Supratentorial herniaton, as cerebrum is Pushed against skull or tentorium, can lead to an ischaemic stroke
or Infratentorial herniation, as cerebellum is pushed up against brainstem - can affect consciousness, resp and heart rate.
What are the clincal manifestations of an extradural haematoma?
Characteristic history, Head injury
- Reduced GCS: loss of consciousness after the trauma due to concussion
- There might be a lucid interval after initial trauma if there is a slower bleed. This is followed by rapid decline.
- Headaches
- Vomiting
- Confusion
- Seizures
- Pupil dilation if bleeding continues
- May be focal neurological symptoms e.g. muscle weakness, hemiparesis, abnormal plantar reflex (upgoing plantar) or sensory problems
What investigations would you do for a extradural haematoma?
CT scan – shows biconvex hyperdense haematoma that is adjacent to the skull:
Blood forms rounded/biconvex shape as the tough dural attachments to the skull keep it more localised - Don’t cross suture lines
Skull X-ray – may be normal or show fracture lines crossing the course of the middle meningeal artery
Skull fracture increases the extradural haemorrhage risk so do an urgent CT on anyone with suspected skull fracture
What is the management of an extradural haematoma?
Refer to neurosurgeon -
- Clot evacuation
- Craniotomy: part of the skull bone is removed in order to remove accumulated blood below.
- Followed by ligation of the vessel.
- Consider intubation, ventilation and ICU care if they have reduced consciousness
- Correct any clotting abnormality
-
Correct severe hypertension but avoid hypotension
Stabilise patient – ABCDE management
IV mannitol – to reduce ICP
Look at this picture
What is a subdural haematoma?
A subdural haematoma (SDH) is a collection of blood that forms in the subdural space, the space between the dura mater and the arachnoid mater, due to Rupture of the bridging veins
normal physiology - describe the venous drainage of the brain, in respect the meningeal layers involved.
Deoxygenated blood drains into superficial cerebral veins, or bridging veins, that sit in the subarachnoid space (along with cerebral arteries)
- These veins travel through the arachnoid mater, pass through the subdural space and penetrate the inner layer of the dura mater to drain into the Dural venous sinuses located between the two layers of the dura mater. (the inner meningeal layer and the outer endosteal layer)
- Eventually the blood in the venous sinuses drain into the internal jugular vein and returns to the heart.
What two things make up the Leptomeninges? What is found between them?
- The pia and arachnoid maters, are also called leptomeninges.
- Between the leptomeninges, there’s the subarachnoid space, which houses cerebrospinal fluid. CSF is a clear, watery liquid which is pumped around the spinal cord and brain, cushioning them from impact and bathing them in nutrients.
What are the main causes for a subdural haematoma?
Rupture of bridging veins, usually caused by:
- Brain atrophy: in the elderly the brain shrinks in size which means that the bridging veins are stretched across a wider space where they are largely unsupported
- Alcohol abuse: caused the wall of the veins to thin out, and make them more likely to break.
-
Trauma/ injury e.g.
- Falls
- Shaken baby syndrome
- Acceleration-deceleration injury: speeding on the road and then suddenly slamming the brakes
What are some risk factors for a subdural haematoma?
- Head injury
- Brain atrophy
- Alcohol abuse
- Hypertension
- Aneurysms
- Ischaemic stroke can progress to haemorrhage
- Brain tumours
- Anticoagulants such as warfarin
Epileptics, as they can hit their head when having a siezure
Outline the pathophysiological course of a subdural haematoma.
bridging veins are under low pressure = bleeding can be slow = delayed onset of symptoms.
Weeks/months later, haematoma starts to autolyse, (broken down by own enzymes) = increase in oncotic pressure so Water sucked in, haematoma enlarges.
Gradual rise in ICP over weeks, as haematoma grows
A large subdural haematoma on one side of the skull can cause a midline shift, or can cause brain to herniate
How can a subdural haematoma be classified?
An acute subdural haematoma causes symptoms within 2 days, a subacute subdural haematoma causes symptoms between 3 and 14 days, and a chronic subdural haematoma causes symptoms after 15 days.
What are some clinical manifestations of a subdural haematoma
- Reduced GCS: loss of consciousness right after the injury or in the ensuing days to weeks as the haematoma increases in size.
- Headaches
- Vomiting
- Seizures
- Sometimes there can be focal neurological symptoms e.g. muscle weakness, unequal pupils, hemiparesis or sensory problems
Confusion
May fluctuate
Insidious physical & intellectual slowing
Personality change
Unsteadiness
They often cannot remember the traumatic injury as it was long ago
What is the investigations for a Subdural haemorrhage?
- Immediate NON CONTRAST CT head to establish the diagnosis. Shows clot and midline shift.
Bleeding is between the dura and arachnoid so subdural haematomas follow the contour of the brain and form a crescent-shape and cross suture lines. This is different to an epidural haemorrhage!
Check FBC and clotting
What would you see on a non contrast CT head for someone with a
Acute Subdural haematoma
Chronic subdural haematoma
Acute on chronic haematoma
- Acute subdural haematoma: hyperdense mass = looks “more white” than the surrounding healthy brain tissue
- Chronic subdural haematoma: hypodense masses = “less white” than the surrounding brain tissue.
- Acute on chronic bleeding: combination of hyperdense and hypodense, seen in individuals who have a rebleed in the bridging veins after a chronic haematoma has already formed.
What is the management of subdural haematoma?
IV mannitol - reduce ICP
Burr hole / Craniotomy to relieve pressure
Craniotomy a large opening in the skull is created to evacuate the haematoma and relieve the associated mass effect.
What is Amaurosis Fugax
A classical syndrome of painless short-lived monocular blindness.
It is a term usually reserved for transient visual loss of ischaemic origin.
Management will depend on cause.
What is the aetiology of amararosis fugax?
temporary reduction in the retinal, ophthalmic or ciliary blood flow leading to temporary retinal hypoxia.
The most common cause of amaurosis fugax is atherosclerotic embolism, leading to a narrowing of either the carotid or retinal artery
Can also be caused by inflammation of the optic nerve (optic neuritis), nervous system (e.g. in multiple sclerosis) or in head injury.
Individuals older than 60 years of age that have had multiple episodes of transient monocular blindness could also be investigated for giant cell arteritis, which is characterized by inflammation of the large vessels of the scalp, neck, and arms.
What is meningitis?
Meningitis describes inflammation of the leptomeninges (the arachnoid and pia mater) and usually occurs due to a bacterial, viral, or fungal infection.
What is the most common cause of meningitis?
What is the most common form of chronic meningitis?
Viral infection is most common
Then bacterial infection
Can also be caused by fungal/parasite infection, as well as
Autoimmune (aka Lupus)
Medication injected into CSF (Intrathecal therapy)
Fungal infection is the most common form of chronic meningitis
What are the most common bacterial causes of meningitis in neonates?
Escherichia coli
Group B Streptococcus (Streptococcus agalactiae)
Listeria monocytogenes
only group where both Streptococcus Pneumoniae or Neisseria Meningitidis aren’t in the most common top 3
What are the most common bacterial causes of meningitis in infants
Neisseria meningitidis
Haemophilus influenzae (but less common now due to vaccination)
Streptococcus pneumoniae
if in doubt, just say Streptococcus Pneumoniae or Neisseria Meningitidis)
What are the most common bacterial causes of meningitis in young adults
Neisseria meningitidis
Streptococcus pneumoniae
if in doubt, just say Streptococcus Pneumoniae or Neisseria Meningitidis)
What are the most common bacterial causes of meningitis in the elderly
Streptococcus pneumoniae
Neisseria meningitidis
Listeria monocytogenes
if in doubt, just say Streptococcus Pneumoniae or Neisseria Meningitidis)
Outline the classification of the two most common bacterial causes of Meningitis in adults
The two most common causes of meningitis in adults are both diplococci:
1. Neisseria meningitidis (gram Negative)
- Strep. Pneumoniae (gram Positive)
Alpha Haemolysis on Blood agar, and Optochin sensitive
What are the common causes of viral meningitis?
-Enteroviruses (echoviruses, Coxsackieviruses, polioviruses)- most common
-Mumps in countries without routine childhood immunisation
-Herpes simplex virus
What are the two ways in which bacteria infect the meninges, as seen in meningitis?
-
Direct spread:
Pathogen gets inside the skull or spinal column, and then penetrates the meninges, eventually ending up in the CSF. - either through overlying skin or up nose. Normally due to congenital defect like spina bifida, or acquired defect like a skull fracture - Haematogenous spread:Pathogen enters the bloodstream and moves through the endothelial cells in the blood vessels making up the blood-brain barrier and gets into the CSF
What are some signs of Meningitis?
- Kernig’s sign: extension of the knee when hip is flexed at 90 degrees causes neck pain
- Brudzinski sign: severe neck stiffness causes the hips and knees to flex when the neck is flexed
- Petechial or purpuric non-blanching rash: associated with meningococcal disease (N. meningitidis)
- Pyrexia
- Reduced GCS
What are some symptoms of meningitis?
FEVER
HEADACHE
NECK STIFFNESS – ‘MENINGISM’
Might not be able to touch chin to neck
Purpuric rash – only in BACTERIAL meningitis
Non-blanching plupurent rash = meningococcal septicaemia (meningitis caused by N. Menigitidis)
Photophobia and/or phonophobia
Papilloedema – swelling of optic disc on fundoscopy
Usually bilateral
What investigations do you do for meningitis?
INVESTIGATIONS AND TREATMENT SHOULD BE DONE IN PARALLEL
Treat first, investigate later – give IM benzylpenicillin
Assess GCS - if <8 then can’t maintain their own airway, 🡪 intubate
Blood cultures – BEFORE ANTIBIOTICS!!
Lumbar puncture - to obtain CSF - Diagnostic
Head CT – to exclude lesions e.g. tumour
Blood – blood cultures and PCR for S. pneumoniae and N. meningitidis.
Nose and throat swabs – are plated out onto blood and chocolate agar.
Stool – stool PCR can be used to detect enterovirus.
Serology – blood (to detect a convalescent rise in antibody).
What would you see on a Lumbar puncture for someone with bacterial meningitis?
CSF:
Appearance - Cloudy/Turbid
WCC - High neutrophils
Protein - High
Glucose - Low
Culture - bacterial organism
bacteria swimming in the CSF (cloudy) will release proteins (high) and use up the glucose (low). Immune response to bacteria is neutrophils
What would the results of an LP CSF sample analysis look like in Viral meningitis?
CSF:
Appearance - Clear
WCC - High Lymphocytes
Protein - Normal/Mildly raised
Glucose - Normal (2.8–4.2mmol/L., two thirds of blood glucose)
Culture - Negative
Viruses cant be seen (clear) don’t use glucose (normal) but may release a small amount of protein (normal/mild inc). Immune response to viruses are lymphocytes
Where is a lumbar puncture usually taken from?
What are some contraindications for a lumbar puncture?
Between L3/L4
Raised ICP
GCS <9
Focal Neurological signs
coagulopathy
Cardiovascular compromise (bradycardia and HTN),
Infection at the site of LP
What is the treatment for viral Meningitis?
Usually milder and so Supportive Tx
If HSV/VZV infection then Acyclovir
What is the treatment for bacterial meningitis in a hospital, for those <60 and not immunocompromised?
IV dexamethasone, ideally administered before or with the first dose of antibiotics once in hospital. Reduces mortality and likelihood of neurological sequelae.
ceftriaxone : 2 g intravenously every 12 hours
OR
cefotaxime : 2 g intravenously every 6 hours
What is the treatment for bacterial meningitis in a hospital, for those >60 or immunocompromised?
intravenous dexamethasone, ideally administered before or with the first dose of antibiotics once in hospital. Reduces mortality and likelihood of neurological sequelae.
ceftriaxone : 2 g intravenously every 12 hours
OR
cefotaxime : 2 g intravenously every 6 hours
AND (for Listeria monocytogenes cover)
amoxicillin : 2 g intravenously every 4 hours
What is the treatment for suspected meningitis w/ non-blanching rash present in the community?
Urgent/immediate IM Benzylpenicillin
Prior to immediate transfer to a hospital
What is the most common cause of fungal meningitis?
Cryptococcus Neoformans
Candida
Very rarely affects immune competent people
Once the pathogen causing meningitis has been identified, what antibiotic can you swith to for a
Meningococcal meningitis?
Pneumococcal meningitis?
Listeria Monocytogenes Meningitis?
Meningococcal meningitis - IV benzylpenicillin, or Cefotaxime
Pneumococcal meningitis - IV cefotaxime
Listeria Monocytogenes Meningitis - IV Amoxicillin and Gentamicin
What do you do as a GP if a patient presents to you w/ non blanching rash and you suspect meningococcal septicaemia?
What can you offer to families/close contacts of a relative with meningitis?
Give IM benzylpenicillin and do an immediate hospital referral
Can offer close contacts Ciprofloxacin
What is Encephalitis? Where does it most commonly affect?
infection of the brain leading to inflammation of the brain parenchyma
Most commonly affects frontal and temporal lobes of brain
What is the most common causes of Encephalitis?
Encephalitis is generally a viral infection and the viral causes are:
almost always Herpes simplex virus
but occasionally Varicella zoster virus (chickenpox), Parvoviruses, primary HIV, Mumps virus and Flaviviruses such as Japanese encephalitis virus and West Nile virus
What are some non viral causes of Encephalitis?
TB
Malaria
Neisseria meningitidis
- Fungal:
- Cryptococcus
- Parasitic:
- Toxoplasmosis - from cats
What are the symptoms of encephalitis?
Fever
Headache
Confusion
Seizures
Encephalopathy:
Behavioural changes
psychotic behaviour
mood changes
What are the signs of encephalitis?
- Pyrexia
- Reduced GCS
- Focal neurological deficit, such as:
- Aphasia
- Hemiparesis
- Cerebellar signs
- May also have signs of meningitis: meningo-encephalitis
What cell layer is the only output of the cerebellar cortex? Loss of it will lead to what?
The Purkinje cell layer - loss of the purkinje cells well due to cerebellar degradation will lead to ataxia
What investigations would you do for Encephalitis?
What is Diagnostic
- Blood tests:FBC, CRP, U&Es and blood culture
- Throat swab:culture for viral organisms
- HIV serology: now routinely tested in the emergency department
CT/MRI Head:
Shows evidence of unilateral encephalitis
Diagnostic - LP and CSF analysis, and PCR
CSF analysis:
Viraemia - increased lymphocytes, raised protein if viral aetiology
Consider PCR for confirmation
Cultures from CSF
What is the treatment of encephalitis?
Aim to start acyclovir within 30min of the patient arriving (10mg/kg/8h IV over 1h)
if HSV or VZV
Symptomatic treatment: eg phenytoin for seizures
What happens in multiple sclerosis?
Chronic progressive autoimmune, T-cell mediated inflammatory disorder of the CNS, against the myelin basic protein of oligodendrocytes
causes demyelination of CNS neurons (brain and spinal chord)
What are the risk factors for MS?
- Age: most commonly diagnosed in 20-40 year olds
- Female gender: MS is 3 times more common in females
- Smoking
- Vitamin D deficiency - due to lack of sunlight? so - Northern latitudes is also a risk factor
- Family history: HLA-DR2 is implicated
- Autoimmunity: patients often have a family history of other autoimmune disorders
- EBV infection: the virus with the greatest link to MS
Normal physiology - what does myelin do and what is it produced by in the CNS and PNS?
Myelin is the protective sheath that surrounds the axons of neurons, allowing them to quickly send electrical impulses.
This myelin is produced by oligodendrocytes in the CNS and by schwann cells in the peripheral nervous system
Outline the pathophysiology behind Multiple sclerosis. What happnes when the T cells get through the BBB, What is left behind on the myelin?
T Cells get through blood brain barrier, and get activated by Myelin = T cells can now change BBB (so has more receptors) to allow more immune cells to get through it
T cells release cytokines, damaging Oligodendrocytes, and B cells make antibodies and which allow macrophages to attack the oligodendrocytes,
Leaving behind areas of plaque/sclera on neurone
Pathophysiology behind MS - why do patients with this often get relapses?
regulatory T-cells can inhibit other immune cells, meaning at first there may be remyelination of damaged neurons - but over time this remyelination doesn’t keep up and permanent damage occurs.
A characteristic features of MS is that lesions vary in their location over time, meaning that different nerves are affected and symptoms change over time.
What is the most common type of Multiple sclerosis?
-
Relapsing-remitting:
- The most common pattern (85% of cases)
- Episodic flare-ups (may last days, weeks or months), separated by periods of remission. There isn’t full recovery after the flare-ups, so disability increases over time
- 60% of patients develop secondary progressive MS within 15 years
Briefly outline the other types of multiple sclerosis
-
Secondary progressive:
- Initially, the disease starts with arelapsing-remitting course, but then symptoms get progressively worse withnoperiods of remission
-
Primary progressive:
- Symptoms get progressively worse from diseaseonsetwithno periods of remission
- Accounts for 10% of cases and is more common inolder patients
-
Progressive relapsing:
- One constant attack but there are bouts superimposed during which the disability increases even faster
What are some symptom of multiple sclerosis?
EYES:
Optic neuritis - most common presentation of MS - It involves demyelination of the optic nerve and loss of vision in one eye - PAIN WHEN LOOKING SIDEWAYS
Double Vision - due to lesions with the sixth cranial nerve (abducens nerve).
Plaques in sensory pathways from skin - Numbness, tingling, sensory loss, paraesthesia (tingling, itching burning sensation)
Plaques in autonomic nervous system- Bladder incontinence, sexual dysfunction
-
Trigeminal neuralgia: stimulation to face causes pain
Cognitive decline - Poor concentration, critical thinking, depression
Charcot’s triad due to Cerebellar white matter demyelination
Symptoms of MS - what is Charcots Neurological Triad?
Dysarthria – due to plaques in brainstem
Difficult or unclear speech – can affect eating, talking, swallowing
Intention tremor – due to plaques along motor pathways
Muscle weakness and spasms
Tremors
Ataxia
Paralysis
Nystagmus – due to plaques in nerves of eyes
Loss of vision
Optic neuritis
Painful eye movements
Double vision
what is
Uhthoff’s Phenomenon
Lhermitte’s phenomenon
SEEN IN MS
Uhtoff’s phenomenon: worsening of symptoms following a rise in temperature, such as a hot bath/sauna/exercise
Lhermitte’s phenomenon: electric shock sensation on neck flexion (bending neck forward), caused by stretching the demyelinated dorsal column.
Uhtoff explained - Although the myelin sheath does regenerate, the new myelin is less efficient and temperature dependent - When exposed to high heat – conduction through new myelin drastically decreases
How is a diagnosis for Multiple sclerosis made?
Diagnosis - neurologist based on the clinical picture and symptoms suggesting lesions that change location over time.
Often using the McDonald Criteria. - looking for symptoms/signs which demonstrate dissemination in space (i.e. different parts of the CNS affected) and time.
Other causes for the symptoms need to be excluded
What investigations can point a diagnosis of Multiple Sclerosis
MRI with contrast - Active Lesions will take up contrasts, Old ones will not ==> Can also see Demyelinated Plaques, known as Dawson’s Fingers
Lumbar puncture with CSF electrophoresis = inflammatory proteins found in the CSF not serum eg Oligoclonal IgG bands = CNS inflammation
Evoked potentials – tests how long it takes impulses to travel
delayed, visual, brainstem, auditory, somatosensory potentials
E.g. stimulate optic nerve and measure time for impulse to go from eye to occipital cortex - measures visual evoked potential
As there is demyelination, conduction will be slower
Outline the McDonald Criteria
Criteria used to diagnose MS:
Uses symptoms/signs which demonstrate dissemination in space (i.e. different parts of the CNS affected) and time.
Diagnosis is based on:
- 2 or more relapses (disseminated in space and time AND EITHER
- Objective clinical evidence of 2 or more lesionsOR
- Objective clinical evidence of one lesionWITHa reasonable history of a previous relapse
- ‘Objective evidence’ is defined as an abnormality on neurological exam, MRI or visual evoked potentials
What is the management for Multiple sclerosis?
No cure
Acute attacks: (relapsing-remitting MS) – IV methylprednisolone 1000 mg intravenously once daily for 3 days
Plasma exchange: to remove disease-causing antibodies
Chronic
1st line (frequent relapse)
- Subcutaneous Interferon Beta
For spasticity
- Baclofen, and Botulinum toxin injections
Name any biological DMARDs that are used in MS
Beta Interferon and Monoclonal antibodes eg atemuzmab (anti-CD52), natalizumab
What is the management of MS, looking at symptom control?
Tremor – beta blocker
Mild to moderate muscle spasticity – oral medications e.g. diazepam, baclofen (GABA analogue that reduces Ca2+ influx)
Focal disabling muscle spasticity – peripheral nerve blocks, botulinum toxin - botox injections
Removal of trigger factors e.g. UTI, bed sores
Physical treatments e.g. physio, exercise to maintain strength.
Neuropathic pain – gabapentin
Depression - SSRIs
Normal Physiology - what are the two places where cell bodies of peripheral nerves are found?
For Peripheral nerves, - cell body is in the spine (spinal nerve)
Or brain (cranial nerve)
What is Guillain-Barre syndrome?
Guillain-Barré syndrome (GBS) is an autoimmune, rapidly progressive demyelinating condition of the peripheral nervous system, often triggered by infection
“Equivalent to MS for the PNS”
What bacteria/viruses can be known to trigger Guillain-Barre Syndrome?
What vaccine is associated with increased risk?
-
Infections:typically gastrointestinal or respiratory:
- Bacterial:e.g. Campylobacter jejuni (30%) and mycoplasma pneumoniae
- Viral:e.g. Zika virus, influenza, Epstein-Barr virus and cytomegalovirus
association with the influenza vaccination (uncommon)
Outline the pathophysiology behind Guillian-Barre Syndrome.
GBS is believed to be caused by‘molecular mimicry’
- Thought that infectious organisms have the antigens that resemble myelin gangliosides on Schwann cells (PNS) 🡪 autoantibody mediated damage to myelin sheath
- Processinvolves the production ofanti-ganglioside antibodies(anti-GMI is positive in 25% of patients)
- The demyelination occurs in patches along the length of the axon, so it’s called segmental demyelination
- Early on, there is remyelination but over time, there’s irreversible damage
What are some signs to note seen in Guillian-Barre Syndrome?
- Reduced sensation in affected limbs: sensory findings on examination are usually mild
-
Symmetrical weakness in lower extremities first, progressing to the upper limbs: proximal muscles often affected earlier than distal muscles
Autonomic dysfunction: e.g. tachycardia, hypertension, postural hypotension, urinary retention (in severe disease)
Respiratory distress: shortness of breath,
Ataxia with hyporeflexia (or areflexia) in affected limbs - (Absence of neurologic reflexes such as the knee-jerk reaction)
What are some symptoms of Guillian-Barre Syndrome?
- Tingling and numbness in hands and feet: often precedes muscle weakness
- Symmetrical, progressive, ascending weakness
- Unsteady when walking
- Back and leg pain: common at some point in disease course
- Facial weakness and speech problems,
- Double vision (due to Affected Cranial nerves)
Outline features of the diagnostic criteria for GBS
What are some blood tests would you do to investigate Suspected Gullian-Barre Syndrome?
Clinical Dx of Hx of recent infection with progressive weakness and areflexia, in >1 limb, near symmetry of symptoms.
-
Bloods:exclude other causes
- U&Es: electrolyte abnormalities resulting in neuropathic symptoms
- B12 and folate: deficiency associated with neurological features
- TFTs: to exclude hypothyroidism as a cause of weakness
- Anti-ganglioside antibodies: can be used to differentiate GBS variants, e.g. anti-GQ1b antibody in Miller-Fisher syndrome, or Anti GMI
What other investigations can aid to confirm the diagnosis of Guillain Barre?
Nerve conduction studies: findings will typically be suggestive of demyelination, e.g. reduced conduction velocity
Lumbar puncture for CSF:raised proteinwith normal WBC countis typical, although an initial normal protein level does not exclude GBS
Spirometry: to monitor respiratory function as 20% of patients require mechanical ventilation at some stage
What are the two options for management seen in Gullian-Barre syndrome?
-
IV immunoglobulins (IVIg):5 day treatment course commenced within the first 2 weeks of symptom onset,
Contraindicated in patients with IgA deficiency as can cause severe allergic reactions
OR
- Plasma exchange: 5 treatments of 2-3L over 2 weeks commenced within the first 4 weeks of symptom onset
Don’t do Both. No role for steroids
What is some additional management seen in GBS?
- Thromboprophylaxis:to prevent venous thromboembolism - eg a direct oral anticoagulant, unfractionated heparin, or a low molecular weight heparin
- Physiotherapy:for those with impaired mobility or motor disturbance
- Intensive care support:for those who develop ventilatory failure (20%), intensive care and mechanical ventilation may be required
What is classically seen in Parkinsonism?
This is the extrapyramidal triad of:
1 Tremor. Worse at rest; often ‘pill-rolling’ of thumb over fingers
2 Hypertonia/rigidity. - (is too much muscle tone. For instance, arms or legs are stiff and hard to move) Rigidity +tremor gives ‘cogwheel rigidity’, felt by
the examiner during rapid pronation/supination.
3 Bradykinesia. Cardinal sign (slowness of movement and speed (or progressive hesitations/halts)
Involves Postural instability or shuffling gait (1)
Expressionless face.
Marche à petit pas = Walk slowly
What things other than Parkinson’s disease can be known to cause parkinsonism?
What drugs can lead to Parkinsonism?
Some drugs
Drugs -
Antipsychotics eg haloperidol - blocks dopamine receptors
metoclopramide, - antisickness, a dopamine anatagonist
Wilson’s disease
Trauma - (dementia pugilistica) - seen in boxing
Encephalitis
Carbon monoxide
studies show smoking is protective for parkinson’s!!
Normal physiology - what does the part of the substantia nigra that is affected in Parkinson’s do normally?
SN is made of two parts - Pars Reticulata and Pars Compacta
The pars compacta sends messages to the striatum via neurons rich in the neurotransmitter dopamine, forming the nigrostriatal pathway, which helps to stimulate the cerebral cortex and initiate movement.
Forms part of the basal ganglia
In addition to simply initiating movements, the substantia nigra helps to calibrate and fine tune the way that movements happen.
Define Parkinson’s disease
Parkinson’s Disease (PD) is a neurodegenerative disorder characterised by loss of dopaminergic neurones within the substantia nigra pars compacta (SNPC) of the basal ganglia (nigrostriatal pathway)
What is the prevalence of PD? What age is the peak onset?
The second most common neurodegenerative disorder after alzheimers dementia
- It’s progressive, adult-onset disease, and it gets more common with age
- Prevalence of 1% in those aged 60-70 and up to 1-3% in those ≥80 years old
- M>F
Peak onset - 55-65 years
Mutations of what genes have been implicated?
What are some causes of secondary Parkinson’s
Idiopathic condition but potentially related to genetics
Mutation in Parkin Gene, PINK1
Mutation in alpha-Synuclein gene
Secondary causes of Parkinsonism;
Vascular parkinsonism
Infections – Encephalitis
Toxin induced – Carbon monoxide, drugs, Pesticides
studies show smoking is protective for parkinson’s!!
Outline the basic pathophysiology of parkinson’s
Neurodegenerative loss of dopamine secreting cells from the pars compacta of the substantia nigra that project to the striatum 🡪 reduced striatal dopamine levels,
This means that Subthalamic nucleus will be less inhibited, so it will inhibited the Thalamus more.
Less dopamine means the thalamus will be inhibited resulting in PROBLEMS INITAIATING
MOVEMENT
What is the histological hallmark seen in Parkinson’s?
eosinophilic inclusion bodies - consisting of misfoldedα-synucleinin the dopaminergic neurones of the Pars Compacta, calledLewy bodies.
What are some motor symptoms of Parkinson’s disease?
Bradykinesia (hypokinesia/akinesia) – slowness or absence of movement
Resting tremor
Rigidity – stiffness and Pain (20% initially present with pain), Increased tone in limbs and trunk
Postural instability - Impaired balance – especially when trying to turn
- Other features
- Micrographia (abnormally small, cramped handwriting)
- Hypomimia (reduced degree of facial expression)
Tremor is typically asymmetrical!
What are some non - motor symptoms of Parkinson’s Disease?
- Anosmia (smell blindness)
- Sleep disturbance: REM sleep is impaired
- Psychiatric symptoms
- Depression
- Anxiety
- Dementia: usually develops after motor symptoms, unlike in Lewy-body dementia
-
Constipation
Urinary incontinence not typical
What do you look for when making a clinical diagnosis of someone with Parkinson’s?
- PD is a clinical diagnosis: it should be suspected in a patient who has bradykinesiaand atleastoneofthe following:
- Tremor
- Rigidity
- Postural instability
Tremor is typically asymmetrical!
What investigations can help diagnose someone with parkinson’s?
- MRI brain:may help exclude other causes of neurological disease but should not be used to diagnose PD - show substantia nigra atrophy
- SPECT (DaT scan):single-photon emission computed tomography (SPECT) will show reduced dopamine uptake in the basal ganglia
name some things that should NOT be present in Parkinson’s disease, at the beginnning.
Incontinence
Dementia
Symmetry
Early falls
Tremor in action
if these are present, think of differentails……
name 2 differentials for Parkinson’s disease, what you may see in them and how you would treat them.
Normal pressure hydrocephalus – increase in CSF 🡪 enlarged ventricles
Will See Magnetic gait - inability to lift the feet off the floor - also incontinence, and dementia
Treatment = Surgical correction
Shunt from the ventricles to the peritoneum
Benign Essential Tremor
see next card for manifestations
Very common, can run in families
Treat with Beta-blockers
distinguish between the tremor of Parkinson’s disease and benign essential tremor.
Parkinson’s Tremor
Asymmetrical
Worse at rest
Improves with intentional movement
May have other Parkinson’s features
No Change with alcohol
Lower frequency (4-6 hertz)
Benign Essential Tremor
Symmetrical
Improves at rest
Worsens with intentional movement
No other Parkinson’s features
Improves Change with alcohol
Higher frequency (5-8 hertz)
What is some of the management of Parkinson’s disease?
1st line
carbidopa/levodopa (Co-careldopa): 100 mg orally
Most powerful drug
The higher the dose, the greater the risk of SE
What is the MOA of Parkinson’s disease drug, co-careldopa?
Increase amount of dopamine in CNS
Can’t give dopamine as it can’t cross the BBB
2 DRUGS LEVODOPA AND CARBIDOPA
Dopamine biosynthetic pathway:
Tyrosine 🡪 L-dopa 🡪 dopamine 🡪 dopamine receptor
L-dopa converted to dopamine under action of Dopa Decarboxylase in CNS
As Dopa Decarboxylase also exists outside the CNS, it is commonly combined with Carbidopa (Dopa Decarboxylase inhibitor) as it can’t cross into the CNS so it doesn’t affect dopamine production in CNS
This way the L-Dopa will only get converted into Dopamine in the CNS, not elsewhere in the body.
What are some common side effects of L-Dopa?
-
Dyskinesia:excessive involuntary movements related to levodopa use (excess dopamine)
- Dystonia: This is where excessive muscle contraction leads to abnormal postures or exaggerated movements.
- Chorea: These are abnormal involuntary movements that can be jerking and random.
- Athetosis: These are involuntary twisting or writhing movements usually in the fingers, hands or feet.
Excessive daytime sleepiness and sudden onset of sleep
What is the issue with using levodopa to treat PD?
Initially works well but soon the Px becomes resistant to it and the effects wear off.
Therefore want to only use it when Sx are bad enough to prevent early resistance.
Parkinson differentials -
When would you see Parkinson’s Dementia?
What about Lewy Body Dementia/w Parkinsonism?
Parkinson Sx THEN dementia - PARKINSON’S DEMENTIA
Dementia Sx THEN Parkinson’s - LEWY BODY DEMENTIA W PARKINSONISM
Define chorea
a movement disorder that causes sudden, unintended, and uncontrollable jerky movements of the arms, legs, and facial muscles.
Chorea is seen in many diseases and conditions and is caused by an overactivity of the chemical dopamine in the areas of the brain that control movement.
What is Huntington’s Chorea (HD)?
an autosomal dominant genetic neurodegenerative condition that causes a progressive deterioration in the nervous system
What is the inheritance pattern of Huntingtons disease?
What type of genetic disease is Huntington’s, as where is this mutation?
autosomal dominant - SOMEONE WITH HD HAS 50% OF PASSING IT ONTO CHILDREN
It’s a “trinucleotide repeat disorder” that involves a genetic mutation in the HTT gene on chromosome 4., that codes for the huntingtin protein.
Outline what is seen in the Huntingtin Protein of someone with HD.
ON CHROMOSONE 4
On the HTT gene - the base sequence of CAG (that codes for Glutamine) is repeated more than 35 times.
This means that patients have 36 or more glutamines in a row in the huntingtin protein.
pathophysiology of huntingtons - what do mutated HTT proteins go on to do in the brain?
Mutated proteins aggregate within the neuronal cells of the caudate and putamen (dorsal striatum) of the basal ganglia causing neuronal cell death.
Specific neurons that die are the GABAergic and cholinergic neurones in the corpus striatum = decreased ACh and GABA synthesis. Without this, levels of dopamine increase leading to excessive movement - Chorea
Define anticipation
What does this mean for people with huntingtons?
A phenomenon in which the signs and symptoms of some genetic conditions tend to become more severe and/or appear at an earlier age as the disorder is passed from one generation to the next.
Anticipation is where successive generations have morerepeatsin the gene, resulting in:
- Earlier age of onset
- Increased severity of disease
What is the penetrance of HD?
Full penetrance:
All genotypes of Huntington’s will express the phenotype
Why does anticipation occur in Huntington’s?
What is the phenomena known as?
The expanded CAG not only causes the HTT protein to be mutated, but also interferes with DNA replication itself
When copying the HTT gene, DNA polymerase can lose track of which CAG it’s on and so add extra CAGs.
This is called repeat expansion and happens more frequently in the production of sperm than egg.
Therefore symptoms tend to present progressively sooner when Huntington’s disease runs in men
REPEAT EXPANSION
What is the only cellular output later in the cerebellum? Degradation of it will lead to what?
The Purkinje cell layer - degradation of it will lead to ataxia
What is the pathophysiology of AD - how do Amyloid Beta plaques form?
Amyloid Beta Plaques:
• Amyloid Precursor Protein (APP) - A channel protein in neurons.
• If it is broken down by the Beta secretase enzyme, the fragment is not soluble and becomes sticky, and will clump together
• ==> get in the way of neurones and their signalling
==> Plaques can trigger immune response, leading to inflammation
What is the pathophysiology of AD - What are neurofibrillary tangles? (NFTs)
Beta amyloid plaque build-up outside the neurone, lead to kinase enzyme activation in Neuron
This leads to phosphorylation of the tau protein, that helps hold microtubules in cell together.
When Tau is phosphorylated it stops supporting microtubules and clumps with other Tau proteins, forming forming neurofibrillary tangles
Neurones with tangles and non-functioning microtubules can’t signal as well, and sometimes end up undergoing apoptosis
How is activities of daily living can be affected in early and then later stages of Alzheimer’s disease.
- Loss of independence: increasing reliance on others for assistance with personal and domestic activities
- Early stages: problems with higher level function (e.g. managing finances, difficulties at work)
- Later stages: problems with basic personal care (e.g. washing, eating, toileting) and motor function (e.g. walking, transferring)
‘Enduring’ doesn’t mean unfluctuating: cognition comes and goes, allowing poetic insights, as in Iris Murdoch’s poignant self-diagnosis: ‘I am sailing into the dark’.
What is frontal temporal dementia? What ages does it most likely affect?
Frontotemporal dementia is a neurodegenerative disorder characterised by focal degeneration of the frontal & temporal lobes.
- Typically affects patients at a younger age (< 65 years)
- The mean age of onset is 58 years old. The onset before 40 years old and after 75 years old is uncommon.
Rapid onset - Overall survival is 8-10 years from symptoms starting
outline the pathophysiology behind Frontal temporal dementia
3R isoforms of the tau protein get hyperphosphorylated. =====>As with AD, these can’t hold the tubulins together, and start clumping.
Affected Neurons won’t function well, and so neurons get damaged/undergo apoptosis
Large scale changes in brain -
- Brain atrophy: the gyri get narrower whereas the sulci get wider.
- The ventricles expand as the rest of the brain shrinks.
- The parietal and occipital lobes are spared.
What are some investigations to do for Frontal temporal dementia?
- Diagnosis based on cognitive assessment
- Imaging:
- MRI: exclude other pathology; indicates changes in the frontal and temporal lobes
- Definitive diagnosis: brain biopsy after a person has died
Outline the pathphysiology behind what happens in Lewy- Body Dementia
neurones contain a protein called alpha synuclein. In LBD, this gets misfolded in neurons
misfolded alpha-synuclein aggregates to form Lewy bodies that deposit inside neurones, particularly in the cortex and the substantia nigra.
As the disease progresses, more and more neurones accumulate Lewy bodies and die.
What is the two treatments you can give to alleviate symptoms of Lewy body dementia?
- Dopamine analogue e.g. levodopa: for Parkinson’s like motor symptoms
- Cholinesterase inhibitors e.g. donepezil: increases acetylcholine availability, used for Alzheimer’s-like cognitive symptom
Normal Physiology - how much of the hearts cardiac output goes to the brain?
What is unique about the brain’s metabolism?
Brain takes around 20-25% of CO
Neurons can only function in aerobic conditions.
- Neurons also don’t have long term energy stores, so they need a constant supply of glucose to keep working.
Outline the pathophysiology behind vascular dementia
Small vessel diseases eg Atherosclerosis, Ischaemic strokes, haemorrhage, amyloidosis = leads to lack of o2, and a gradual decrease in blood supply = chronic ischaemia
Tissue gets damaged = Liquefactive Necrosis
Brain necrosis leads to a loss of mental functions that are governed by that area.
Outline the percentage prevalence’s of each of the dementia subtypes.
Alzheimer’s - 60%
Vascular - 20%
Frontaltemporal dementia 10%
Dementia with Lewy bodies 5%
Young Onset Alzheimer’s 1-5%
Others 1%
Define and give some examples of primary headaches
No underlying cause relevant to headache: - syndromes based on symptoms
Migraine
Cluster
Tension
(Trigeminal Neuralgia)
What other features/things would make you always consider an immediate referral for a suspected secondary headache?
- Thunderclap headache ?SAH
- Seizure and new headache
- Suspected meningitis
- Suspected encephalitis
- Red eye ? acute glaucoma
- Headache + new focal neurology
– including papilloedema
– Other abnormal neuro exam or symptom (evidence = orange)
What things should be included in a physical examinatio, for a headache?
Fever
Altered consciousness
Neck stiffness/ Kernigs sign
Focal neurology signs
Fundoscopy
Check BP too
What kinds of things are seen in auras? What are auras?
An aura is a perceptual disturbance that can occur before or during a migraine.
It is usually experienced as a visual phenomenon, such as flashing lights, zigzag lines, or blind spots. Other types of auras may include sensory disturbances, such as tingling in the arms and legs, or speech and language problems.
What is the 4 diagnostic criteria for a migraine without aura?
4 diagnostic criteria
A – 5 attacks fulfilling B-D
B - attacks last 4-72 hours
C – Character, two of the following:
Unilateral, Pulsing, Moderate/severe, Aggravated by routine physical activity
D – during headache at least one of
Nausea and/or vomiting
Photophobia (light sensitive) and phonophobia (sound sensitive)
What is the diagnostic criteria for a migraine with aura?
3 diagnostic criteria
A – at least 2 attacks fulfilling B (character) and C (time)
B - > 1 reversible aura symptom - eg
- Visual – zigzags, spots
- Unilateral sensory – tingling, numbness
- Speech – aphasia
- Motor weakness – known as “hemiplegic migraine” so rule out stroke and TIA
C > 2 of the following 4:
-Aura symptoms spread gradually over 5 minutes and/or > 2 aura
symptoms occurring in successions
- Each aura symptom lasts 5-60 minutes
-followed within 60 minutes by headache
How are migraines diagnosed?
Clinical Dx unless pathology is suspected where you do tests to exclude DDx, investigating red flags:
CT/MRI red flags ie. Indications
- Worst/severe headache ie. Thunderclap
- Change in pattern of migraine
- Abnormal neurological exam
- Onset >50yrs
- Epilepsy
- Posteriorly located headache
Lumbar puncture indications
- Thunderclap headache
- Severe, rapid onset headache/ progressive headache/ unresponsive
headache
What is the mechanism of action of Triptans?
Why are they used for migraines?
5-HT receptor agonists (serotonin) that are used to abort migraines when they start to develop
So prevents peptide release that would lead to vasodilation, pain, neurogenic inflammation.
What are cluster headaches?
Cluster headaches are intensely painful, unilateral, periorbital headaches with associated autonomic dysfunction.
How long can a cluster headache last for?
How long can the periods of attack last, and how long can go inbetween?
Clusters of attacks may last for weeks/months before a pain free period follows which may last for years
What are some clinical manifestations seen in cluster headaches?
- Unilateral, periorbital or temporal headaches lasting 15 minutes to 3 hours
- Ipsilateralautonomicsymptoms:
- Lacrimation (teary eye)
- Conjunctival injection (red eye due to enlargement of conjunctival vessels)
- Nasal congestion
- Rhinorrhoea (nasal discharge)
- Nausea and vomiting
- Photophobia, with agitation and restlessness
Horner’s Syndrome
- Ptosis (eyelid drooping)
- Miosis (excessive constriction of the pupil of the eye)
- Anhidrosis (Decreased sweating on on half of face)
What is the management of cluster headaches in acute attacks?
Acute attacks
Analgesics are unhelpful
15L 100% O2 for 15 mins via non-rebreather mask
Triptans eg. Sumatriptan
Normal Physiology - what are the 3 branches of the trigeminal nerve?
Where does it exit the brain?
What are its functions?
Trigeminal nerve (CN5) has both motor and sensory functions and enters the brainstem at the level of the Pons.
Three divisions:
Ophthalmic (exits Superior Orbital fissure)
Maxillary (Foramen Rotundum)
Mandibular (exits Foramen Ovale)
Function = General SENSATION of the FACE, SCALP, NOSE MOUTH AND FRONT OF TONGUE, MOTOR = OPEN and CLOSE OF MOUTH (MASTICATION) GENERAL SENSATION OF front 2/3 of tongue. also inervates tensor tympani for hearing
Overview of Primary Headache Features:
Outline the site and duration of
Migraine headaches
Tension Headaches
Cluster Headaches
Trigeminal Neuralgia
Duration:
MH - 4-72 hrs
TH - Minutes to dates
CH - 15-180 mins
TGN - Few seconds
Site:
MH - Unilateral
TH - Bilateral
CH - Retro-orbital/unilateral
TGN - unilateral V1/2/3 distribution
Overview of Primary Headache Features:
Outline the Character and severity of
Migraine headaches
Tension Headaches
Cluster Headaches
Trigeminal Neuralgia
Character:
MH - Throbbing
TH - Pressing/tight band
CH - Hot poker/boring
TGN - Electric shock/stabbing
Severity:
MH - Moderate-severe
TH - Mild to moderate
CH - Severe to very severe
TGN - Severe to very severe
Overview of Primary Headache Features:
Outline the treatment of
Migraine headaches
Tension Headaches
Cluster Headaches
Trigeminal Neuralgia
Acute Tx:
MH - Triptan
TH - Paracetamol
CH - Triptan/100% O2
TGN - Carbamazepine
Normal physiology - Neuroepithelial cells differentiate into Neurones and Glial cells.
What are the 4 main types of Glial cells?
Glial cells are the non neuronal cells of the CNS and PNS that do not produce electrical impulses
- Astrocytes - provide: physical support, repair, K+ metabolism neurotransmitter removal and maintenance of the BBB.
- Microglia - immune cells of the central nervous
- Oligodendrocytes - produce the myelin sheath insulating neuronal axons in CNS
- Ependymal Cells produce CSF and help with CSF homeostasis, brain metabolism, and the clearance of waste from the brain.
What is the most common Primary brain tumour? What is it’s appearance histologically?
Astrocytoma - specifically - Glioblastoma multiformeis the most common, an aggressive type of astrocytoma
- Histologically has pseudo-palisading pattern - peripheral tumour cells lined up around necrotic centre
- Grade IV (most malignant)
(90% of Primary brain tumours)
2nd Most common Paediatric cancer
Other primary brain tumours -
Outline some features of
Meningiomas
and
hemangioblastomas
(how they grow and hallmark histological appearance)
Meningiomas -
- Graded I through III, relatively slow growing.
- Histologically, they form nests of cells or a multinuclear syncytium of fused cells.
- Can cause calcifications called psammoma bodies.
Haemangioblastomas
- Derived from cells with blood vessel origins
- Can be anywhere, often found in cerebellum
- Typically grade I => Slow growing
- Histologically, there are often thin-walled capillaries that are arranged close to one another.
Name some causes of raised intercranial pressure
Brain tumours
Intracranial haemorrhage
Idiopathic intracranial hypertension
Abscesses or infection
How are Brain tumours classified into the WHO grade?
Characterised histologically
Cellularity
Mitotic activity
Vascular proliferation
Necrosis
In brief, what are some symptoms of a
Low grade (I-II) tumours
High grade (III-IV) tumours?
Low grade – typically present with seizures (can be incidental finding).
High grade – rapidly progressive neurological deficit. Symptoms of raised intracranial pressure.
What is seen in Cushing’s triad, and why does it occur due to raised ICP?
To maintain cerebral perfusion pressure!!
The body prioritises CPP (cerebral perfusion pressure) over pretty much everything else .
Increase in ICP = will lead to decrease in CPP
The body compensates by raising MAP to counteract the rise in ICP – hence hypertension
This may then lead to a reflex bradycardia based on the HTN, and breathing can become irregular due to brainstem compression
What is papilloedma?
Papilloedema is a swelling of the optic disc secondary to raised intracranial pressure. Papill- refers to a small rounded raised area (the optic disc) and -oedema refers to the swelling
Sheath around the optic nerve is connected with the subarachnoid space. Therefore it is possible for CSF under high pressure to flow into the optic nerve sheath.
What will you see on fundoscopy in someone with papilledema?
- Blurring of optic disc margin
- Elevated optic disc (look for the way the retinal vessels flow across the disc to see the elevation)
- Venous engorgement
- Peripapillary haemorrhage
Vessels are able to flow straight across a flat surface, whereas they will curve over a raised disc.
What are the common causes of secondary brain tumours?
Metastases from:
Non-Small Cell Lung Cancer (NSCLC)
Breast
Small Cell Lung Cancer (SCLC)
Melanoma
Renal Cell Carcinoma
Gastric Cancer
normal physiology - what is the main excitatory neurotransmitter in brain? What does it bind to, what does ion channel does it cause to open causing these ions to flow into the adjacent neurone?
glutamate,
NMDA is the primary receptor that responds to glutamate by opening ion channels that let Ca2+ ions in.
normal physiology - what is the main inhibitory neurotransmitter in brain? What does it bind to, what does ion channel does it cause to open causing these ions to flow into the adjacent neurone?
GABA, Gamma-aminobutyric acid
binds to GABA receptors that tell the cell to inhibit the signal by opening channels that let in chloride ions Cl-.
What are the different types of epileptic seizures?
Generalised seizures (affect both hemispheres)
Focal (affect one hemisphere/lobe)
What are the subtypes of generalised seizures?
Tonic Clonic
Absence
Tonic
Myoclonic
Atonic
Subtypes of generalised seizure - define
Tonic
Clonic
Tonic - Clonic
Tonic seizure: the muscles become stiff and flexed, which can cause the patient to fall, usually backwards
Clonic seizures: violent muscle contractions (convulsions).
Tonic-clonic seizures: there is loss of consciousness andtonic(muscle tensing) andclonic(muscle jerking) episodes. Typically the tonic phase comes before the clonic phase. There may be associated tongue biting, incontinence, groaning and irregular breathing.
Subtypes of generalised seizures - define
Myoclonic seizures
Absence seizures
Atonic seizures:
Myoclonic seizures: short muscle twitches. The patient usually remains awake during the episode.
Absence seizures:** impaired awareness or responsiveness, Patient becomes blank and stares into space before returning to normal. Motor abnormalities are either absent or very minor e.g. eyelid flutters or repetitive lip smacking
Atonic seizures:** aka drop attacks. The muscles suddenly relax and become floppy, which can cause the patient to fall, usually forward. These don’t usually last more than 3 minutes
**= common in children
What are the subtypes of Focal Seizures? What parts of the brain do they involve
Simple focal - The Focal region of cortex + NO basal ganglia/thalamus involvement
Complex focal The focal region of cortex + Basal ganglia and thalamus are involved.
What Happens in a Simple Focal Seizure?
No Loss of consciousness
The patient is awake and aware
Will have uncontrollable muscle jerking and may be unable to speak
What are the features of a Frontal lobe focal seizure?
motor and thought processing
Jacksonian march – seizure “marches” up or down the motor homunculus starting in face or thumb (primary motor cortex is in frontal lobe)
Post-ictal Todd’s palsy – paralysis of limbs involved in seizure for several hours
What is the management of status epilepticus?
ABCDE approach - secure airway and give oxygen.
IV bolus—to stop seizures: eg lorazepam 4mg (in hostpial)
Give 2nd dose of lorazepam if no response after 10–20min
Or Buccal Midazolam, or rectal diazepam (try cannulating a fitting person)
Then Phenytoin if second dose doesn’t work.
Get ITU/Anaesthetist help!!
What are the different causes of seizures, other than epilepsy?
VITAMIN DE:
Vascular - haemorrhage/infarcts
Infection - Encephalitis
Trauma
Alcohol -(if patient has seizures due to alcohol/alcohol withdrawal, give pabrinex)
Metabolic - Hypocalcaemia, Hypo/hypernatraemia, hypoglycaemia
Idiopathic - Epilepsy
Neoplasms - causing a lesion in brain
Dementia + Drugs (cocaine)
Eclampsia + everything else
Treatment of epilepsy - how does Lamotrigine and Carbamazepine work
Lamotrigine and Carbamazepine both inhibit voltage gated pre synaptic Na+ channels - therefore reduces pre synaptic excitability
Treatment of epilepsy - how does sodium valproate work?
inhibits an enzyme that leads to an increase in an inhibitor of GABA transaminase ==> Therefore GABA is broken down less
aka leads to an increase in GABA/inhibitory neurotransmission
What are some side effects of lamotrigine/what is it associated with?
What are some side effects of Carbamazepine?
Lamotrigine is associated with Stevens-Johnson syndrome, Toxic
Epidermal Necrolysis or Hypersensitivity syndrome. its a dermatological medical emergency, type IV hypersensitivity reaction
High levels of carbamazepine are associated with Blurred vision, nystagmus, unsteadiness and incoordination
Where does the spinal chord end? What is this known as?
ends at the level of the L1/L2 spinal vertebrae.
the terminal end of the spinal chord is known as conus medullaris.
Normal physiology - What is an upper motor neurone? Where can they be found? In clinical practise, where do they originate and where do thy terminate?
a neurone whose cell body originates in the cerebral cortex or brainstem and terminates within the brainstem or spinal cord.
basically used to describe descending motor neurons in corticospinal and corticobulbar tracts.
Both arise form pre-central gyrus,
Corticospinal terminate in the ventral horn of the spinal cord
Corticobulbar terminate in and motor nuclei of cranial nerves
Normal physiology - What is an lower motor neurone? where do they originate and where do thy terminate?
multipolar neuron which connects the upper motor neurone (UMN) to the skeletal muscle it innervates.
The cell body of a LMN lies within the ventral horn of the spinal cord or the brainstem motor nuclei of the cranial nerves.
The axon of a LMN exits the CNS terminates on the muscle fibres which it innervates. The combination of the LMN and these fibres is known as a motor unit.
Also known as a motor neuron
What are some causes of spinal chord compression
Vertebral body neoplasms (most common cause)
-
Spinal pathology
-
Disc herniation
- When centre of disc (nucleus pulposus) has moved out through the annulus (outer part of disc) resulting in pressure on nerve root and pain
-
Disc herniation
-
Disc prolapse
- When nucleus pulposus moves and presses against the annulus - can cause a bulge in the disc
- Primary spinal cord tumour e.g. glioma, neurofibroma
- Infection e.g. epidural abscess
- Haematoma
What are some Upper motor neurone signs?
Hypertonia - an abnormally high level of muscle tone or tension
Hyperreflexia - overactive or overresponsive bodily reflexes, twitching
Spasticity
Positive Babinski sign - extension of large toe when plantar surface of foot is stroked
What nerve roots make up the sciatic nerve?
Both anterior and posterior divisions of nerve root
L4,L5,S1 and S2
What two nerves makes up the sciatic nerve? What are these nerves made from?
The anterior division of L4,L5,S1 and S2 make up the Tibial nerve
The posterior division of L4,L5,S1 and S2 make up the common fibular nerve
Together these join to make the sciatic nerve.
What muscle does the sciatic nerve pass under as it leaves the hip?
Where does it split into tibial and common peroneal/tibial nerve?
It passes closely behind the Piriformis muscle , and becomes the tibial and common fibular/peroneal nerve at the popliteal fossa/lower thigh
What is Sciatica?
Sciatica refers to the symptoms associated with irritation of the sciatic nerve.
What are some causes of sciatica? (spinal and non spinal)
Spinal
Intervertebral disc herniation
Disc prolapses
Spinal stenosis - due to degenerative bone disease, or RA
Spondylolisthesis – vertebra becomes displaces and slips on top of one below
Non-spinal
Piriformis syndrome (spasming of piriformis)
Pregnancy
Trauma
What are the diagnostic investigations for sciatica?
Clinical Dx generally:
Can’t Do straight leg raise test without pain
May have:
XR
CT
MRI - if cauda equina suspected
What is the cauda equina?
It’s a nerve bundle formed by the lumbar, sacral and coccygeal nerves, as they travel down the spinal canal together to reach their corresponding openings.
Distal to level of termination of spinal cord at L1/L2.
Cauda equina syndrome caused by damage to the peripheral nerves at the cauda equina
What functions do nerves in teh cauda equina have?
nerves in the cauda equina carry motor innervation for the genitals, both internal and external anal sphincter, detrusor vesicae, and muscles of the leg. They are also responsible for skin sensations in these regions.
Causes of cauda equina syndrome - what is spondylolisthesis? What pathophysiological effects will be seen as a result of spondylolisthesis?
Spondylolisthesis is where one of the bones in your spine, called a vertebra, slips forward
most commonly anterolisthesis (vertebra moves forward)
Slippage of one vertebra over the one below
Nerve root comes out ABOVE the disc therefore root affected will be the one BELOW the disc herniation
E.g. L4/L5 herniation 🡪 L5 nerve root compression
What are some symptoms/signs of cauda equina syndrome
Saddle anaesthesia
Less bladder and bowel control – increased tone of anal sphincter and muscle wall of bladder
Erectile dysfunction (or other sexual dysfunction)
Lumbosacral pain
Leg weakness – flaccid and areflexic
Paraplegia
Signs
Areflexia
Fasciculations
Loss of bowel/bladder control
Urinary retention
WILL SEE LOWER MOTOR NEURON SIGNS ONLY*
For each division of CN 5, outline function, what it innervates and whether its sensory or motor
V1 Ophthalmic, Sensory to forehead, middle nose, frontal and ethmoidal sinuses, and sensory to the cornea - hence responsible for the corneal reflex
V2 Maxillary, Sensory to Lower eyelid, Gums/teeth of upper jaw, Bony part of cheek
V3, Mandibular, Both
Sensory innervation to Mucosa of oral cavity/palate, General sensation to Ant. 2/3 of tongue, Soft part of cheek/mandible
Motor innervation to Muscles of mastication, Tensor Tympani
For CN 8, 9, outline its function, what it innervates, and whether it is sensory, motor or both
VIII, Vestibulocochlear, Sensory
Innervates Vestibular and cochlear, for hearing and balance
IX, Glossopharyngeal, Both
Parasympathetic Secretion from parotid gland
Taste to post. 1/3 of tongue, sensation from pharynx, salivation, parasympathetic from carotid vessels AND motor to stylopharyngeus muscle
Outline how you can get a homonymous quadrantanopia
- superior: lesion of the inferior optic radiations in the temporal lobe (Meyer’s loop)
- inferior: lesion of the superior optic radiations in the parietal lobe
- mnemonic = PITS (Parietal-Inferior, Temporal-Superior
so field defect is caused by lesion in opposite optic radiations - (aka Inferior homonymous quadrantanopia’s are caused by lesions of the superior optic radiations
Outline how you can get a Homonymous hemianopia
Homonymous hemianopia
lesion of optic tract (4)
Lesions of both optic radiations (7)
macula sparing: Homonymous hemianopia lesion of occipital cortex (8)
What are the symptoms of a CN4 palsy?
Diplopia (double vision) when looking down
“walking down stairs”
What are the symptoms of a CN5 palsy?
Loss of function of muscles of mastication - Jaw deviates to side of lesion
Loss of corneal reflex
Reduced sensation or dysasthesia over the affected area
What are the symptoms of a CN6 palsy?
What are some causes of CN6 Palsy?
Adducted eye
Raised ICP
MS
Wernicke’s Encephalopathy
Pontine Stroke
What are the symptoms of a CN6 palsy?
What are some causes of CN6 Palsy?
Adducted eye
Raised ICP
MS
Wernicke’s Encephalopathy
Pontine Stroke
What is Bells Palsy?
Neurological condition that presents with a rapid onset of unilateral facial paralysis -
Normally post viral infection
How can you tell if a bells palsy is an UMN or LMN lesion?
UMN injured, lower half on contralateral side is weak but forehead is not as it has contralateral and ipsilateral innervation (bilateral)
LMN - weakness of all the muscles on the ipsilateral side of the face
What are the signs of an Upper motor neuron (UMN) lesion, as seen in Motor Neurone disease
UMN – everything goes UP
Hypertonia
Rigidity + spasticity
Hyperreflexia
Extensor plantar responses (positive Babinski sign) stroke sole of foot, big toe goes up
Power:
Arms - Flexors > Extensors
Legs - Flexors < Extensors
If you see a patient with mixed upper and lower motor neurone signs, think Motor neurone disease!!
What are the signs of an lower motor neurone LMN lesion, as seen in Motor Neurone disease
Hypotonia
Flaccidity + muscle wasting
Hyporeflexia
Fasciculations
Babinski Reflex Negative - big toe goes down when stroking foot
Generally loss of power
If you see a patient with mixed upper and lower motor neurone signs, think Motor neurone disease!!
How can you diagnose motor neurone disease?
- Definite: LMN + UMN signs in 3 regions
- Probable: LMN + UMN signs in 2 regions
- Probable with lab support: LMN + UMN signs in 1 region, or UMN sign in more than 1 region + electromyography (EMG) shows acute denervation in more than 2 limbs
What investigations can you do to help diagnose Motor neurone disease?
- Electromyography:in MND there will be evidence of fibrillation potentials - due to denervation of muscles due to LMN dysfunction - ( EMG is a technique for evaluating and recording the electrical activity produced by skeletal muscles.)
- Nerve conduction studies:may show modest reductions in amplitude
- MRI spine:imaging can help exclude spinal pathology which may mimic MND, such as cervical cord compression and myelopathy
- Lumbar puncture: to exclude inflammatory causes
- Pulmonary function tests:patients with MND are at risk of respiratory failure
Blood tests e.g. raised Creatinine Kinase (due to muscle destruction),
What is Myasthenia Gravis?
(Latin for “Grave Muscle Weakness”), its a Type 2 hypersensitivity reaction/autoimmune disease against nicotinic acetylcholine receptors (AChR) in the NMJ
Normal physiology - outline what happens at a neuromuscular junction with between an α-motor neuron and a skeletal muscle fibre.
Action potential arrives at NMJ, causing opening of voltage-gated Ca2+ channels.
increase in intracellular Ca2+ causes vesicles containing acetylcholine (ACh) to release their contents into the synaptic cleft.
ACh activates nicotinic ACh receptors in the muscle fibres’ plasma membrane, resulting in an influx of sodium ions and depolarisation of the muscle fibre membrane potential.
Leads to generation of action potential in skeletal muscle fibre
Outline the pathophysiology behind Myasthenia Gravis
type II hypersensitivity reaction
B cells produce anti-AChR autoantibodies which interfere with the NMJ by binding to nicotinic AChR on muscle cells
When AChR are bound by the autoantibodies, they can’t be bound by ACh and don’t respond to “contract” signal from CNS
Results in muscle weakness
What autoantibodies are seen in Myasthenia Gravis?
What paraneoplastic syndrome is a risk factor with MG?
- anti-AChR autoantibodies (85%)
- Some people produce Muscle specific receptor tyrosine kinase (MuSK) antibodies which target proteins in muscle cells - (15%)
- Thymoma or thymic hyperplasia: 10-15% of patients have a thymoma, whilst up to 70% have thymic hyperplasia - thought that perhaps T cells made in thymus can lead to B cells creating autoantibodies
What are some signs/symptoms of MG?
Worse later in the day/on exertion
Lethargy
Muscle weakness that starts at head/neck and moves downwards
Weak eye muscles - diplopia, ptosis
Ptosis
Jaw fatigability - slurred speech/ chewing difficulties
- Dysphagia: difficulty swallowing
What is a Myasthenic crisis: ? What is the management
weakening of the respiratory muscles and is often provoked by infections or medications. Patients present with increasing shortness of breath, which can deteriorate into respiratory failure
Monitor forced vital capacity. Ventilatory support (ie BiPAP) may be needed. Treat with plasmapheresis (removes AChR antibodies from the circulation) or IV immunoglobulin and identify
and treat the trigger for the relapse (eg infection, medications).
What is Lambert Eaton Syndrome?
A NMJ syndrome which has similar Symptom to MG.
Autoimmunity against the voltage gated calcium channels
= less ACh release at the NMJ causing muscle weakness.
Pathophysiology of syncope - outline what happens in carotid sinus hypersensitivity and how it causes fainting, and what can cause this?
- variant of neurocardiogenic syncope.
This occurs when mild external pressure on the carotid bodies in the neck is enough to induce Parasympathetic response (seen in vasovagal)
Mild pressure could be due to shaving, neck turning, tight collar etc
Recap - What are the different functions of the different nerve fibre types?
A-alpha – proprioception
A-beta – light touch, pressure, vibration
A – delta – dull pain and cold
C – fibres – sharp pain and warmth
What are some causes of peripheral nerve disease?
DAVIDE:
Diabetes
Alcohol
Vitamin B12 Deficiency
Infective - Guillain Barre/Charcot Marie Tooth
Drugs - isoniazid
Every vasculitis
What is carpal tunnel syndrome?
Carpal tunnel syndrome (CTS) is a collection of symptoms and signs caused by compression of the median nerve in the carpal tunnel.
What are the sensory symptoms of carpal tunnel syndrome? Think, what sensory areas does the median nerve supply?
Numbness
Paraesthesia (pins and needles or tingling)
Burning sensation
Pain
Palmer aspects and full fingertips of:
Thumb
Index and middle finger
The lateral half of ring finger
hat are the motor symptoms of Carpal Tunnel Syndrome?
Numbness
Paraesthesia (pins and needles or tingling)
Burning sensation
Pain
Palmer aspects and full fingertips of:
Thumb
Index and middle finger
The lateral half of ring finger
Weakness of thumb movements
Weakness of grip strength
Difficulty with fine movements involving the thumb
Wasting of the thenar muscles (muscle atrophy)
Thenar Muscles
Flexor Pollicis Brevis
Abductor Pollicis
Opponens Pollicis
Tests for carpal tunnel syndrome - what is Phalen Test?
Phalen’s test - flex the wrists are far as possible and hold that position for a minute, this results in numbness in the areas of the hand innervated by the median nerve in people with carpal tunnel syndrome
Tests for carpal tunnel syndrome - what is Tinel’s Sign?
tap the transverse carpal ligament, this reproduces the symptoms of tingling or feelings of pins and needles in areas of the hand served by the median nerve
TOM TIP: I think of tapping a tin can (Tinel’s) to remember the difference between Phalen’s and Tinel’s test.
What is the classical presentation of a radial nerve palsy?
Wrist drop
(with elbow flexed and arm pronated?
What muscles are innverated by the radial nerve?
BEST:
Brachioradialis
Extensors of forearm
Supinator
Triceps
What is the classical presentation of an ulnar nerve palsy?
Claw hand (4th/5th fingers claw up)
Damage to what causes foot drop?
Common peroneal nerve palsy
What are the nerve roots for the common peroneal nerve?
L4-S1
(Branch off the Sciatic nerve)
What would be the clinical features of brown-Sequard syndrome?
(Ipsilateral Corticospinal) Ipsilateral (Same side) weakness and loss of motor function below the lesion.
(Ipsilateral DCML) Ipsilateral (Same side) loss of proprioception, 2-point discrimination and fine touch.
(Contralateral Spinothalamic) (opposite side) Contralateral loss of pain and temperature sensation 1-2 spinal segments below the lesion.
What are the classical features of Charcot-Marie-Tooth Syndrome?
High foot arches (pes cavus)
Distal muscle wasting causing “inverted champagne bottle legs”
Weakness in the lower legs, particularly loss of ankle dorsiflexion
Weakness in the hands
Reduced tendon reflexes
Reduced muscle tone
Peripheral sensory loss
What is Gower’s Sign?
an inability to lift the trunk without using the hands and arms to brace and push –
From the lying position, the patient rolls to the kneeling position, pushes on the ground with extended forearms to lift the hips and straighten the legs, so forming a triangle with hips at the apex and hands and feet on the floor forming the base.
The hands are then used to push on the knees and so lift up the trunk (climbing upon yourself).
What is the only cellular output later in the cerebellum? Degradation of it will lead to what?
The Purkinje cell layer - degradation of it will lead to ataxia
