Session 10

Question 1

Define stroke

Answer 1

Stroke, a ‘cerebrovascular accident’, is a ‘serious life threatening condition that occurs when the blood supply to part of the brain is cut off’. The symptoms and signs persist for more than 24 hours

Question 2

Define transient ischaemic event

Answer 2

Transient ischaemic attacks (TIAs), sometimes colloquially called ‘mini strokes’, have similar clinical features of a stroke but completely resolve within 24 hours

Question 3

What are the different types of stroke and how common is each?

Answer 3

o Ischaemic (85%) 

Thromboembolic

o Haemorrhagic (10%) 

Intracerebral (rupture of a vessel in brain parenchyma) 

Subarachnoid

o Other (15%) 

Dissection (separation of walls of artery, can occlude branches) 

Venous sinus thrombosis (occlusion of veins causes backpressure and ischaemia due to reduced blood flow) 

Hypoxic brain injury (e.g. post cardiac arrest)

Question 4

How are strokes managed?

Answer 4

o Two main principles 

Are they within the window for thrombolysis (<4 hours)? 

Do a CT head to determine if it is a bleed (if bleed cannot proceed with thrombolysis)

o Acute imaging of stroke 

CT

• Ischaemic area of brain not visible early on (as infarct becomes more established the ischaemic area will become hypodense)
• A bleed will show up as a bright white area, maybe with mass effect 

MRI

• Sometimes performed
• Ischaemia shows up as a high signal area

Question 5

How would a anterior cerebral artery (ACA) infarct present?

Answer 5

Contralateral weakness in lower limb 

Lower limb affected much worse than upper limb and face 

Contralateral sensory changes in same pattern as motor deficits (sensory homunculus in similar arrangement as motor homunculus) 

Urinary incontinence due to paracentral lobules being affected

• Paracentral lobules are essentially the most medial part of the motor/sensory cortices and supply the perineal area 

Apraxia

• Inability to complete motor planning (e.g. difficulty dressing oneself even when power is normal)
• Often caused by damage to left frontal lobe 

Dysarthria / aphasia

• A very unusual sign in ACA infarcts compared with MCA infarcts
• May be related to frontal lobe damage 

Split brain syndrome / alien hand syndrome (both rare)

• Caused by involvement of corpus callosum which is normally supplied by the ACA

Question 6

How would a middle cerebral artery (MCA) infarct present?

Answer 6

As MCA supplies a large area of brain these stroke can have very widespread effects and are associated with an 80% mortality if the main trunk of the MCA is affected due to resulting cerebral oedema

Haemorrhagic transformation can occur if the vessels in the infarcted area break down 

MCA can be occluded at three main points

• Proximal (main stem, before the lenticulostriate arteries come off)
  
  • In this case, all branches of MCA will be affected including lenticulostriates and distal branches to cortical areas
  • Contralateral full hemiparesis (face, arm and leg affected) 
    
    • Because the internal capsule has been affected which carries fibres to face, arm and leg so even though the MCA supplies the face and arm area of the motor homunculus, this is irrelevant
  • Contralateral sensory loss 
    
    • Probably in the distribution of primary sensory cortex supplied by MCA (i.e. face and arm), but could involve larger areas if sensory fibres in internal capsule affected
  • Visual field defects 
    
    • Usually contralateral homonymous hemianopia without macular sparing
      
      • Due to destruction of both superior and inferior optic radiations as they run through (superior) temporal and parietal lobes
      • More distal occlusions may affect one radiation alone causing quadrantanopias
  • Aphasia 
    
    • Global if dominant (usually left) hemisphere affected)
      
      • Therefore, cannot understand or articulate words
  • Contralateral neglect 
    
    • Usually in lesions of right parietal lobe (can be caused by occlusions of more distal branches as well) 
    • Essentially an issue with not ‘acknowledging’ that the usually left side of space or even your own body exists. Visual fields normal 
    • Other features
      
      • • Tactile extinction (if touch each side simultaneously doesn’t feel the affected side) • Visual extinction (as with half clock face etc.)
      • • Anosognosia (literally does not acknowledge that they have had a stroke, so will confabulate to explain disability)
• Lenticulostriate artery(ies) occluded
  
  • AKA lacunar strokes
  • Cause destruction of small areas of internal capsule and basal ganglia
  • Essential distinguishing feature from, say, a proximal MCA infarct is that they do not cause cortical features (e.g. neglect or aphasia)
  • Types 
    
    • Pure motor (face, arm and leg affected equally, caused by damage to motor fibres travelling through internal capsule due to occlusion of lenticulostriate arteries) 
    • Pure sensory (face, arm and leg affected equally, caused by damage to sensory fibres travelling through internal capsule probably due to occlusion of thalamoperforator arteries and maybe also lenticulostriate) 
    • Sensorimotor (mixed, caused by infarct occurring somewhere at boundary between motor and sensory fibres) 
    • Many other syndromes have been recognised which you need to know less about
• More distal branches occluded
• MCA splits into a superior and inferior division 
  
  • Superior division essentially supplies lateral frontal lobe
    
    • Including primary motor cortex and Broca’s area
    • Occlusion will cause contralateral face and arm weakness and expressive aphasia if left hemisphere affected 
  • Inferior division essentially supplies lateral parietal lobe and superior temporal lobe
    
    • Including primary sensory cortex, Wernicke’s area and both optic radiations
    • Occlusion will cause contralateral sensory change in face and arm, receptive aphasia if left hemisphere and contralateral visual field defect without macular sparing (often homonymous hemianopia as both radiations damaged)
  • Occlusion of branches distal to superior/inferior division may produce even more specific effects, e.g. taking out Broca’s areas specifically with no motor deficit

Question 7

How would a posterior cerebral artery (PCA) infarct present?

Answer 7

Somatosensory and visual dysfunction typical

• Contralateral homonymous hemianopia (with macular sparing due to collateral supply from MCA)
• Contralateral sensory loss due to damage to thalamus

Question 8

How would a cerebellar infarct present?

Answer 8

Symptoms

• Nausea
• Vomiting
• Headache
• Vertigo / dizziness 

Ipsilateral cerebellar signs (remember DANISH) 

Possible ipsilateral brainstem signs since cerebellar arteries supply brainstem as they loop round to the cerebellum 

Possible contralateral sensory deficit / ipsilateral Horner’s (once again due to brainstem involvement)

Question 9

How do brainstem strokes present?

Answer 9

A huge number of named syndromes (not important to know specifics) 

A typical feature is that contralateral limb weakness is seen with ipsilateral cranial nerve signs

• This can be explained by damage to corticospinal tracts (above decussation of pyramids) and damage to cranial nerve nuclei on same side

Question 10

How would a basilar artery occlusion present?

Answer 10

 As this vessel supplies the brainstem (which contains many vital centres), occlusion can sometimes cause sudden death 

Occlusion of distal (superior) basilar artery

• Visual and oculomotor deficits (as basilar sends some branches to midbrain which contains oculomotor nuclei. Also, occlusion at this site can prevent blood flowing into PCAs affecting occipital lobes)
• Behavioural abnormalities
• Somnolence, hallucinations and dreamlike behaviour (as brainstem contains important centres for sleep regulation – reticular activating system etc.)
• Motor dysfunction often absent (if the cerebral peduncles can get blood from the PCAs which in turn are being filled by the posterior communicating arteries)

Proximal basilar occlusion (at level of pontine branches. Embolus in basilar artery can occlude pontine branches on each side)

• Can cause locked in syndrome
• Complete loss of movement of limbs however preserved ocular movement. Eyes still move because midbrain is getting supply from PCAs via posterior communicating arteries
• Preserved consciousness (maybe because midbrain reticular formation is still intact)

Question 11

What is the Bamford (Oxford) stroke classification?

Answer 11

o This is a clinical tool to quickly diagnose strokes

Question 12

What is normal intracranial pressure?

Answer 12

Determined by volume of blood, brain and CSF all enclosed within a rigid box

Values (wide range, can be difficult to define normality precisely) 

• Adults 5-15 mmHg 
• Children 5-7 mmHg 
• Term infants 1.5-6mmHg 
• A good rule of thumb is that a pressure >20 mmHg is raised

Question 13

What is the Monro-Kellie doctrine?

Answer 13

• Any increase in the volume of one of the intracranial constituents (brain, blood or CSF) must be compensated by a decrease in the volume of one of the others
• In the case of an intracranial mass (e.g. brain tumour), the first components to be pushed out of the intracranial space are CSF and venous blood, since they are at the lowest pressure

Question 14

What is cerebral perfusion pressure? How can changes in intracranial pressure and mean arterial pressure affect this and what is the possible consequence?

Answer 14

• CPP = mean arterial pressure (MAP) – ICP
• Normal CPP >70 mmHg • Normal MAP ~90mmHg
• Normal ICP ~10 mmHg
• If MAP increases then CPP increases, triggering cerebral autoregulation to maintain cerebral blood flow (vasoconstriction)
• If ICP increases then CPP decreases, triggering cerebral autoregulation to maintain cerebral blood flow (vasodilatation)
• If CPP <50 mmHg then cerebral blood flow cannot be maintained as cerebral arterioles are maximally dilated
• ICP can be maintained at a constant level as an intracranial mass expands, up to a certain point beyond which ICP will rise at a very rapid (exponential) rate
• Damage to the brain can impair or even abolish cerebral autoregulation

Question 15

What is Cushing’s triad?

Answer 15

 Cushing’s triad aka Cushing’s response aka Cushing’s reflex

• A rise in ICP will initially lead to hypertension as the body increases mean arterial pressure to maintain cerebral perfusion pressure
• The increase in MAP is detected by baroreceptors which stimulate a reflex bradycardia via increased vagal activity (which can cause stomach ulcers as a dangerous side effect)
• Continuing compression of the brainstem leads to damage to respiratory centres causing irregular breathing

Question 16

What are the causes of raised intra cranial pressure

Answer 16

Too much blood within cerebral vessels (rare)

• Raised arterial pressure
  
  • Malignant hypertension
• Raised venous pressure
  
  • SVC obstruction (e.g. external compression by a lung tumour) 

Too much blood outside of cerebral vessels (haemorrhage)

• Extradural
• Subdural
• Subarachnoid
• Haemorrhagic stroke
• Intraventricular haemorrhage

Too much CSF

• Hydrocephalus
  
  • Congenital (more common than acquired types) 
    
    • Obstructive
      
      • Neural tube defects
      • Aqueduct stenosis
      • Frequently part of a larger syndrome 
    • Communicating (i.e. drainage of CSF not impaired)
      
      • Increased CSF production
      • Decreased CSF absorption 
    • Clinical signs
      
      • Bulging head with head circumference increasing faster than expected
      • Sunsetting eyes (due to direct compression of orbits as well as involvement of oculomotor nerve as it exits midbrain) 
    • Management
      
      • Can be treated in acute setting by tapping the fontanelle with a needle
      • Medium term drainage can be achieved by external ventricular drain (EVD)
        
        • Allows continuous pressure monitoring
        • Can be at risk of infection due to direct communication between brain and outside world
        • Requires inpatient monitoring so not good as a long term solution
        • Used if shunt fails or contraindicated
      • Long term drainage by ventricular shunts
        
        • Essentially, a tube is placed from the ventricular system into the peritoneum (V-P) or right atrium (V-A)
        • V-P shunts performed most commonly
        • Tube is tunnelled under skin
        • A one way valve is incorporated to prevent backflow into ventricle
        • Extra length of tubing is provided to allow growth before revision is required o V-P shunts vulnerable to infection (e.g. if abdominal infection, can track back up to brain) or kinking
        • Most shunts will require revision
  • Acquired 
    
    • Meningitis 
    • Trauma 
    • Haemorrhage (e.g. post subarachnoid haemorrhage) 
    • Tumours (e.g. compressing cerebral aqueduct)

Too much brain

• Cerebral oedema
  
  • Four major pathophysiologies, but often multiple mechanisms at play in disorders such as stroke or trauma 
    
    • Vasogenic (breakdown of tight junctions) 
    • Cytotoxic (damage to brain cells) 
    • Osmotic (e.g. if ECF becomes hypotonic)
    • Interstitial (flow of CSF across ependyma and damage to blood brain barrier)

Something else

• Tumour
• Cerebral abscess
• Idiopathic
  
  • Idiopathic intracranial hypertension (IIH) 
    
    • Aka benign intracranial hypertension 
    • May present with headache and visual disturbance 
    • Usually obese middle aged females 
    • Poorly understood aetiology 
    • Diagnosis can be confirmed by raised opening pressure on an lumbar puncture
      
      • Make sure there are no signs of intracranial pathology before doing an lumbar puncture in a patient with suspected raised ICP as this can precipitate brain herniation! 
    • Treat with weight loss and blood pressure control

Question 17

What are the consequences of raised intracranial pressure?

Answer 17

Clinical features:

• • Headache
  
  • Constant
  • Worse in the morning
  • Worse on bending / straining
• Nausea and vomiting
• Difficulty concentrating or drowsiness
  
  • Effect on daily life
• Confusion
• Double vision
  
  • Problems with accommodation (early sign, pupillary dilatation a late sign)
  • Maybe effects on acuity
  • Visual field defects
  • Papilloedema (swelling of optic disc)
• Focal neurological signs
  
  • Depends on where lesion is
• Seizures 

Brain herniation (when ICP get very high, often preterminal)

• Tonsillar herniation aka coning
  
  • Cerebellar tonsils herniate through foramen magnum, compressing medulla
• Subfalcine herniation
  
  • Cingulate gyrus is pushed under the free edge of the falx cerebri
  • Can compress anterior cerebral artery as it loops over the corpus callosum
• Uncal herniation
  
  • Uncus of temporal lobe herniates through tentorial notch compressing adjacent midbrain
  • Can cause third nerve palsy and maybe even contralateral hemiparesis (due to compression of cerebral peduncle)
• Central downward herniation
  
  • Medial temporal lobe / other midline structures pushed down through tentorial notch
• External herniation through skull fracture or therapeutic craniectomy

Question 18

How is raised intracranial pressure managed?

Answer 18

Brain protection measures

• Airway and breathing
  
  • Maintain oxygenation and removal of CO2
• Circulatory support
  
  • Maintain MAP and hence CPP
• Sedation, analgesia and paralysis
  
  • Decrease metabolic demand
  • Prevents cough / shivering that might increase ICP further
• Head up tilt
  
  • Improves cerebral venous drainage
• • Temperature
  
  • Prevent hyperthermia
  • Therapeutic hypothermia may be beneficial
• Anticonvulsants
  
  • Prevent seizures, reduce metabolic demand
• Nutrition and proton pump inhibitors
  
  • Improved healing of injuries and prevent stomach ulcers due to increased vagal activity 

Other treatments

• Mannitol or hypertonic saline
  
  • Osmotic diuresis
• Ventricular drainage
• Decompressive craniectomy as a last resort

Question 19

Describe the epidemiology and risk factors for subarachnoid haemorrhage

Answer 19

▪ ~6% of all strokes

▪ Slightly more females 1.6:1

▪ Most are under 50

▪ 50% mortality, 60% suffer some longer term morbidity following the event

Risk factors (most as for vascular disease in general):

• Hypertension
• Smoking
• Excess alcohol consumption
• Predisposition to aneurysm formation
• Family history
• Associated conditions
  
  • Chronic kidney disease (resultant effect on vessel wall)
  • Marfan’s syndrome (effect on connective tissues of vessels)
  • Neurofibromatosis (unclear mechanism, if any link)
• Trauma
• Cocaine use

Question 20

What is the pathophysiology of of subarachnoid haemorrhage?

Answer 20

Usually occur following rupture of an aneurysm in the circle of Willis

• Aneurysm is a weakness in a vessel (usually artery) wall which can cause an abnormal bulge
• May be a genetic predisposition to aneurysm formation
• May be caused by haemodynamic effects at branch points in the circle of Willis (e.g. higher resulting flow rate in progressively smaller branches, turbulence)
• Most are berry aneurysms (as they look like berries). Common sites, making up 75% of all aneursyms:
  
  • Anterior communicating artery / proximal anterior cerebral artery (30%)
    
    • Can compress the nearby optic chiasm and may affect frontal lobe or even pituitary
  • Posterior communicating artery (25%)
    
    • Can compress the adjacent oculomotor nerve causing an ipsilateral third nerve palsy
  • Bifurcation of the middle cerebral artery as it splits into superior and inferior divisions (20%)

Bleeding into the subarachnoid space causes the following:

• • Early brain injury
  
  • Microthrombi
    
    • These may occlude more distal branches
  • Vasoconstriction
    
    • As a result of blood in the CSF ‘irritating’ cerebral arteries
  • Cerebral oedema
    
    • General inflammatory response to tissue hypoxia and extravasated blood
  • Apoptosis of brain cells
• Cellular changes
  
  • Oxidative stress
    
    • Maybe related to reperfusion?
  • Release of inflammatory mediators
• ▪ Can activate many pathways as well as activation of microglia
• o Platelet activation
• ▪ Formation of thrombi
• • Systemic complications
• o Sympathetic activation
• ▪ Early Cushing response
• o Myocardial necrosis
• ▪ Due to sympathetic activation
• ▪ Interestingly, SAH has typical ECG features
• o Systemic inflammatory response
• ▪ Can affect multiple systems

Question 21

What are the clinical features of subarachnoid haemorrhage?

Answer 21

▪ Thunderclap headache • Explosive in onset and severe, often reported as worst headache ever or even ‘like being hit on the head with a cricket bat’ • Diffuse pain • Can last from an hour to a week ▪ Frequently loss of consciousness and confusion ▪ Meningism • Neck stiffness • Photophobia • Headache ▪ May be focal neurology ▪ May be history of sentinel bleed (previous headache) ▪ May present as cardiac arrest (if intracranial pressure rises rapidly following bleed leading to profound Cushing response)

Question 22

What investigations would you do for a suspected subarachnoid haemorrhage and what would be the findings?

Answer 22

▪ CT head • Prominent filling of the basal cisterns in a five pointed ‘star’ pattern • Blood may be seen within the ventricles (maybe due to reflux from subarachnoid space) ▪ CT angiogram if bleed confirmed
• Will allow direct visualisation of bleeding aneurysm of aneurysm sac • Vital for planning surgery ▪ Lumbar puncture (LP) • Technique o Identify iliac crests (giving L4-L5 level) o Give local anaesthetic o Insert LP needle between spinous processes and through the supraspinous and interspinous ligaments o Feel give as pass through ligamentum flavum and dura o Remove needle stylet and collect CSF in sterile containers (allow to drip, don’t aspirate!) • LP findings in SAH o Increased opening pressure (as there is now additional volume in the subarachnoid space) o Frank blood or xanthochromia may be seen ▪ Xanthochromia is a yellow colouring of the CSF due to metabolism of haemoglobin to bilirubin within the subarachnoid space • Seen at least 12 hours post bleed • More specific than frank blood for SAH (helps exclude a bloody/traumatic tap) o High protein (blood constituents and haemoglobin) o White cells often not raised o Glucose not affected o High red cell count

Question 23

What is the treatment for subarachnoid haemorrhage?

Answer 23

▪ ABC approach • Support airway if diminished conscious level • Give oxygen • Support circulation o Fluids o Maybe nimodipine to alleviate cerebral vasospasm ▪ Neurological observations • Looking for trends which may be suggestive of increasing intracranial pressure ▪ Neurosurgery • Decompressive surgery (craniectomy) • Coiling o Insertion of (frequently) a platinum wire into the aneurysm sac, which causes thrombosis of blood within the aneurysm itself o Performed by neuroradiologists • Clipping
o Placement of a spring clip around the neck of the aneurysm, causing it to lose blood supply and ‘shrivel up’ o Performed by neurosurgeons

Question 24

Describe the epidemiology and risk factors for meningitis

Answer 24

▪ Can be bacterial, viral or fungal or even non-infective (last two are very rare) ▪ Neonates • Typical organisms o E. coli o Group B streptococcus o Listeria monocytogenes • Children o Haemophilus influenzae type B (HiB vaccine given, ‘meningococcus’) o Neisseria meningitidis (vaccines given for some strains • Elderly o Streptococcus pneumoniae (vaccines now given) o Listeria monocytogenes ▪ Risk factors • CSF defects (e.g. spina bifida) • Spina procedures (e.g. surgery, lumbar puncture) • Endocarditis (as a focus of bacteraemia) • Diabetes (immunosuppression) • Alcoholism • Splenectomy (immunosuppression) • Crowded housing (students at risk)

Question 25

What are the clinical features for meningitis?

Answer 25

▪ The triad of ‘meningism’ with fever • Headache • Neck stiffness (nuchal rigidity) • Photophobia ▪ Associated symptoms • Flu-like symptoms • Joint pains and stiffness • Seizure • Meningococcal rash (non blanching) • Drowsiness • Patient may be in shock • Babies o Inconsolable crying / off feeds o Rigidity / floppiness o Bulging fontanelle (late sign)

Question 26

What is the pathophysiology of meningitis?

Answer 26

▪ Bugs which normally live in the nose gain entry to the circulation and cause a bacteraemia ▪ The bacteraemia causes damage to vessel walls in the brain and meninges, allowing pathogen to enter the subarachnoid space ▪ Once in the subarachnoid space pathogens multiply rapidly causing purulent CSF and severe meningeal inflammation ▪ Vasospasm of cerebral vessels can cause cerebral infarction ▪ Oedema of brain parenchyma can cause raised intracranial pressure ▪ Maculopapular rash seen in meningococcal septicaemia • Caused by microvascular thrombosis due to many factors, including o Sluggish circulation o Impaired fibrinolysis o Increased tissue factor expression in endothelial cells

Question 27

What investigations would you do for a suspected meningitis patient? What would their fndings be?

Answer 27

▪ Bloods including sepsis screen and PCR ▪ Maybe chest X-ray or mid stream urine if suspect a particular septic focus ▪ Lumbar puncture findings. Make sure you have blood results to compare with • Bacterial meningitis o Cloudy CSF o High protein (immune proteins etc.) o High white cells, primarily neutrophils (which phagocytose bacteria) o Low glucose as bacteria (and white cells) metabolise it • Viral meningitis o Maybe clear but can be cloudy (due to immune cells and proteins) o Protein level may be normal or raised (as above) o High white cells, primarily lymphocytes to mount an adaptive response o Normal glucose (>60% plasma)

Question 28

What is the treatment for meningitis?

Answer 28

▪ Supportive • Analgesia • Antipyretics • Fluids if shocked ▪ Medical • IV ceftriaxone • Dexamethasone to prevent hearing loss (due to swelling of vestibulocochlear nerve or effect on cochlea) • If viral o Aciclovir for Herpes
o Ganciclovir for CMV

Question 29

What are the possible complications of meningitis?

Answer 29

▪ Septic shock (due to bacteraemia)

▪ Disseminated intravascular coagulation (due to bacteraemia)

▪ Coma (due to raised ICP)

▪ Cerebral oedema (due to cerebral inflammation)

▪ Raised ICP

▪ Death (due to brain herniation, sepsis)

▪ SIADH (maybe direct effect on hypothalamus/pituitary?)

▪ Seizures (due to irritation of brain parenchyma)

▪ Hearing loss (due to swelling of vestibulocochlear nerve or cochlea itself. Perilymph is continuous with subarachnoid space) ▪ Intellectual deficits (due to direct brain damage)

▪ Hydrocephalus (due to interruption of CSF drainage pathways and effect on arachnoid granulations)

▪ Focal paralysis (maybe due to cerebral abscess)