Neurology

Stroke

Introduction

Introduction

  • Stroke medicine demands a detailed knowledge of the vascular and general anatomy of the brain. Identification of the artery that has occluded due to either thrombosis or embolism or bleed from can help to focus investigations, determine causality and help determine an appropriate treatment plan.
  • Stroke is fascinating where two opposing aetiologies - thrombosis and haemorrhage cause a similar clinical syndrome which can only reliably be distinguished by Imaging. Treatment reflects this.

Stroke terminology

  • Avoid the term CVA
    • Not an accident - many are preventable
    • Stroke is a universally understood term
  • TIA - traditionally clinical symptoms resolve within 24 hours. However newer imaging (MRI DWI) shows infarction in many of those with symptoms > 1 hour and less than 24 hrs
  • Stroke in evolution - Ongoing increasing symptoms over 24 hours.
    • Consider critical carotid artery stenosis
    • Capsular warning syndromes
    • Thrombotic strokes
  • Reversible Ischaemic Neurological defect - symptoms lasting for 24 hrs to 3 weeks. Used really pre modern imaging. Adds little to understanding of stroke. Consider strokes as a continuum from reversible ischaemia to full blown infarction and all in between. Small ischaemic episodes are a warning to prevent larger ones.
  • Important point
    • Ischaemic stroke is a continuum from mild ischaemia to infarction
    • If disabling symptoms still present when seen refer urgently for thrombolysis
    • If symptoms resolved then refer urgently to TIA service
    • Both TIA and small strokes have risk of large strokes so do all possible to prevent

Epidemiology

  • Incidence 200-300 strokes per 100,000 per annum
  • Prevalence is 800 per 100,000
  • Suspected stroke underreporting
  • Average death rate is 20-25%
  • Treatment of hypertension reduces strokes aged 40-60
  • Most strokes occur in the elderly

Aetiology

  • Ischaemic 80%
    • Embolic
    • Thrombotic
    • Venous infarcts
  • Haemorrhagic 10%
  • Subarachnoid 5%

Ischaemic Stroke

Thrombotic

  • Clinically thrombosis - may be a more stuttering course
  • Arterial thrombosis
    • Extracranial e.g. internal carotid artery
    • Intracranial e.g. MCA
  • Venous thrombosis (rare)
    • Cerebral venous sinus thrombosis

Embolic :  Embolic typically deficit maximal at onset

  • Cardiac
    • Left atrium
      • Clot
      • Myxoma
    • Mitral valve
      • Clot
      • Vegetation
    • Left ventricle
      • Thrombus
  • Artery to artery e.g. from aortic or carotid plaque
  • Systemic vein DVT via PFO/ASD

Vascular Anatomy

  • Left atrium - > Left ventricle -> Aorta -> Aortic arch
    • Inominate artery
      • Right common carotid -> Right internal carotid 2/3rds of supply
      • Right subclavian artery -> Vertebral artery 1/3rd of supply
    • Left common carotid -> Left internal carotid
    • Left subclavian -> Vertebral artery
  • Almost all arteries are paired except for the basilar artery and the anterior communicating
  • Notes
    • A patent foramen ovale or ASD or any right to left shunt can allow clot to pass from the deep veins of the legs to the left atrium and then into the systemic circulation

Anterior circulation

Internal Carotid artery

  • Cervical segment - within the neck. Associated with sympathetic supply.
  • Petrous segment - enters skull via foramen lacerum and runs forwards
  • Cavernous segment - enters the cavernous sinus and runs with the VIth nerve and gives off branch superior hypophysial to the posterior pituitary
  • Supraclinoid segment - pierces dura and then splits into anterior cerebral artery and middle cerebral artery

Branches

  • Ophthalmic artery
    • central artery to retina runs forward to supply the eye and scalp around the eye as well as frontal and ethmoidal sinuses.
    • Maxillary artery anastomoses provides some collateral flow if proximal occlusion
  • Posterior communicating artery
    • Joins anterior and posterior circulations
    • Closely associated with IIIrd nerve and provides some vascular support
    • Also supplies thalamus, hypothalamus and tail of caudate
  • Anterior choroidal artery
    • Passes posteriorly with branches to supply
      • Posterior limb of internal capsule
      • choroid plexus of lateral ventricle
      • optic tract and lateral geniculate body (hemianopia)
      • area of midbrain and globus pallidus and substantia nigra

    • Anterior cerebral artery (Medial surface of cerebrum. Arches around corpus callosum)
      • A1 Segment - from the bifurcation of the internal carotid to the anterior comm artery. Branches include
        • medial lenticulostriate artery (contributes to anterior limb of internal capsule and basal ganglia)
        • Anterior communicating artery connects both ACA and is a common site of aneurysms
        • recurrent artery of heubner supplies head of caudate and anteroinferior internal capsule
      • Pericallosal branch - is the continuation of A1 supplying medial surface of cerebral cortex and corpus callosum
        • orbitofrontal
        • polar frontal
        • callosomarginal
    • Middle cerebral artery
      • M1 segment from the bifurcation of the internal carotid passes laterally to the surface of the insula where it bifurcates.
        • Occlusion here results in massive infarction depending on collateral supply.
        • A clot may be seen in the artery "the hyperdense MCA sign" on Non contrast CT.
        • Lateral lenticulostriate artery (penetrating vessels)
          • Branch of at right angles to supply the Globus pallidus and putamen, posterior limb of internal capsule, head and tail of caudate, thalamus and Meyer's loop which includes some of the optic radiations can be caught
          • Arterial occlusion typically may cause lacunar type strokes and vulnerable to lipohyalinosis and occlusion
      • M2 segment within the sylvian fissure and branch. A clot here may result in a "dot"sign on CT. The artery branches into
        • M3 segments Upper division
          • prefrontal (frontal cortex)
          • precentral (primary motor and associated areas)
          • central (pre/post central gyri)
          • post central (primary sensory area)
          • parietal (posterior parietal)
        • M3 segments Lower division
          • middle temporal (mid temporal cortex)
          • temporoccipital (temporal and occipital cortex)
          • angular (angular and associated gyri)
          • R/L Subclavian artery

Posterior circulation

Vertebral artery - 1st branches of the subclavian arteries on either side then enter the transverse process at (C6) and ascends through the foramina in the transverse processes of the upper six cervical vertebrae to C1 where they enter the foramen magnum in front of the the medulla. Inside the the skull, the two vertebral arteries join to form the basilar artery.

  • Posterior inferior cerebellar artery
    • Largest branch of the vertebral and supplies lateral medulla and lateral cerebellum).
    • Loops around medulla to the inferior surface of cerebellum.
    • Wallenburg's syndrome
  • Anterior spinal artery (ventral medulla)
    • Forms at the point where the arteries fuse
  • Posterior spinal artery (dorsal medulla)

Basilar artery forms at the lower border of the pons by fusion of the two vertebral arteries

  • Anterior inferior cerebellar artery supplies lateral pons and anteroinferior cerebellum)
  • Superior cerebellar artery - supplies lateral pons and superior surface of cerebellum)
  • 12 Pontine arteries penetrate to supply medial pons - are a number of small vessels which come off at right angles from either side of the basilar artery and supply the pons and adjacent parts of the brain
  • Internal auditory artery - a long slender branch, arises from near the middle of the artery; it accompanies the acoustic nerve through the internal acoustic meatus, and is distributed to the internal ear

Posterior cerebral artery (PCA) (embryologically originate from Internal carotid) passes laterally and is joined by the posterior communicating and then sweeps back around the cerebral peduncle to reach the tentorial surface of the occipital lobe.

  • Postero-medial ganglionic branches arise at the commencement of the posterior cerebral artery and with branches from the post comm artery pierce the posterior perforated substance, and supply the medial surfaces of the thalami and the walls of the third ventricle.
  • Posterior choroidal branches run forward beneath the splenium of the corpus callosum, and supply the tela chorioidea of the third ventricle and the choroid plexus
  • Postero-lateral ganglionic branches are small arteries which arise from the posterior cerebral artery after it has turned around the cerebral peduncle; they supply a considerable portion of the thalamus
  • Anterior temporal supplies uncus and the anterior part of the fusiform gyrus
  • Posterior temporal supplies inferior temporal gyri, calcarine, to the cuneus and gyrus lingualis and the back part of the convex surface of the occipital lobe
  • Parietooccipital to the cuneus and the precuneus.

Occlusion of Artery and Clinical findings

Internal carotid artery

  • Ipsilateral frontal and parieto-occiptal and temporal lobes
  • Ipsilateral cortical infarction depending on degree of collaterals and COW flow
  • Mimics an MCA infarction or less as ACA may get some collateral supply across anterior communicating artery
  • Ophthalmic artery
    • Eye Monocular blindness
  • Posterior communicating artery
  • Anterior choroidal artery (choroid plexus of lateral ventricle)
    • homonymous field defect
    • motor/sensory loss
  • Anterior cerebral artery
    • Contralateral face/arm/leg weak Leg > arm
    • C/L face/arm/leg weakness leg > arm
    • C/L sensory loss
    • No hemianopia
    • C/L contralateral gaze palsy
    • Expressive Dysphasia (D)
    • Visuospatial (ND)
    • Dyspraxia (D)
    • Neglect (ND) apathy
    • Abulia, disinhibition and euphoria.
    • Paracentral lobule infarction causes urinary incontinence
  • Middle cerebral artery
    • Proximal MCA artery M1
      • Infarction of the basal ganglia Internal capsule out towards the cortex. Damage worse the more proximal the occlusion as lenticulostriates to basal ganglia affected
      • C/L face/arm/leg weakness arm > leg
      • C/L sensory loss
      • C/L hemianopia
      • C/L contralateral gaze palsy
      • Dysphasia(D)
      • Visuospatial(ND)
      • Neglect (ND)
      • Dyspraxia (D)
    • Distal MCA
      • Lenticulostriate arteries may be spared
    • Superior branch of MCA
      • Frontal lobe infarction
      • face/arm weakness
      • Gaze paresis
      • Expressive dysphasia (D) and dyspraxia (D)
    • Posterior inferior branch of MCA
      • Parietal lobe with sensory loss
      • homonymous hemianopia
    • Lateral striate (lenticulostriate)
      • lacunar type infarcts of basal ganglia and internal capsule as mentioned below
  • Posterior cerebral artery occlusion P1 before posterior communicating artery branch causes infarcts in the
    • cerebral peduncle
    • thalamus
    • mediobasal temporal lobes and thalamus
    • occipital cortex and resembles MCA stoke with hemiparesis, sensory loss and hemianopia.
  • Posterior cerebral artery occlusion distal to posterior communicating artery branch
    • Hemianopia
    • Non Dominant (often right cortical side)
      • Spatial disorientation
      • neglect
      • prosopagnosia
  • Bilateral PCA occlusion
    • Altitudinal hemianopia, cortical blindness (blindness with preservation of pupillary light response ? Anton?s syndrome)
    • Bilateral thalamic stroke causes amnestic symptoms
  • Basilar artery occlusion
    • Headache, dizziness, vertigo, seizures, coma, quadriplegia
    • Locked in syndrome, IIIrd nerve lesion, limb weakness
    • Only vertical gaze remains intact and opening and closing eyelids
    • Consider thrombolysis
  • Top of the basilar artery occlusion
    • Usually embolic infarction of midbrain, thalamus, hypothalamus and mediobasal portions of the temporal and occipital lobes
    • IIIrd nerve palsy, Vertical gaze palsy, ataxia, sleepiness and even coma, impaired attention and memory.
  • Midbrain Weber syndrome
    • Anterior brainstem infarction
    • Contralateral hemiparesis
    • ipsilateral IIIrd nerve palsy
  • Benedikt syndrome
    • Paramedian midbrain (red nucleus)
    • Contralateral cerebellar dysfunction
    • Partial ipsilateral IIIrd nerve nucleus
  • Nothnagel syndrome
    • Dorsolateral midbrain lesion
    • Complete contralateral loss of sensation
    • Ipsilateral Horner's syndrome
    • Ipsilateral IIIrd nerve palsy Ispilateral cerebellar signs Basilar artery branches to
  • Medial Midbrain
    • ? IIIrd nerve palsy
    • C|L hemiparesis and hemiataxia or tremor
  • P1 segment of PCA supply.
    • Lateral Midbrain ? C|L hemisensory loss
    • Vertical gaze palsies
  • Pons - Millard-Gubler syndrome
    • Pontine lesion involving VIth and VII
    • Contralateral hemiparesis
    • Ipsilateral 6th and 7th
  • Posterior inferior cerebellar artery (or vertebral artery infarction)
    • Lateral Medulla - Dorsolateral infarction or Wallenburg syndrome
    • Horner's syndrome
    • IX nerve and X weakness
    • Dysphagia and hoarseness
    • Nystagmus and Cerebellar ataxia (spinocerebellar tracts) same side
    • Contralateral spinothalamic signs and Symptoms
    • Altered facial sensation.
    • Medial medulla ? Hypoglossal weakness same side, contralateral hemisensory Symptoms
    • Autonomic disturbance
    • Apnoea ?ondine?s curse?

Stroke classifications

TOAST trial ( Trial of Org 10172 in Acute Stroke Treatment (TOAST).)

  • large-artery atherosclerosis
  • cardioembolism
  • small-vessel occlusion
  • stroke of other determined aetiology
  • stroke of undetermined aetiology

Oxford community stroke project

  • Oxford community stroke project - provides a useful classification which can help determine prognosis
  • Total anterior circulation stroke - 40% death within 30 days Clinically all 3 of these are present
    • Higher dysfunction e.g dysphasia (left hemisphere, visuospatial and neglect (left hemisphere)
    • Homonymous hemianopia
    • Weakness/sensory loss in at least 2/3 of face, arm, leg.
  • Partial anterior circulation stroke (PACS) Clinically all 2 of these are present
    • Higher dysfunction e.g dysphasia (left hemisphere, visuospatial and neglect (left hemisphere)
    • Homonymous hemianopia
    • Weakness/sensory loss in at least 2/3 of face, arm, leg
    • less than 10% death within 30 days in small cortical infarcts
  • Lacunar stroke 20-40%
    • occlusion of small perforating arteries which branch of the MCA at right angles to supply the internal capsule and other deep structures
    • Clinically differentiated from PACS by the absence of cortical features e.g. apraxia, dysphasia etc Less than 3% death within 30 days
    • Hypertension - small vessels affected. In situ thrombosis, embolism unlikely
    • Lacunar syndromes
      • Pure motor (damage to posterior limb of internal capsule)
      • Pure sensory (thalamus)
      • Sensorimotor (thalamus and posterior limb of internal capsule)
      • Ataxic (variable)
      • Dysarthria and Clumsy hand (pons)
    • Small lacunae < 15 mm in size. Seen in the
      • corona radiata
      • basal ganglia
      • internal capsule
      • thalamus
      • pons
  • Posterior circulation stroke

    • More subtle in its milder forms but overall reasonably good prognosis
    • Watch out for the rare but often quoted "top of the basilar" syndrome
    • May be due to small vessel disease or embolism via the vertebral arteries
    • Vertebrals and their branches supply the Brainstem, occipital lobes, thalami
    • Dizziness, Vertigo, Diplopia, Nausea, Vomiting, Nystagmus
    • Cerebellar signs, Altered consciousness, Horner's syndrome, Bulbar signs - impaired swallow, Chorea, hemiballismus
  • Once a CT scan has been done the patient can be assessed as either a TACS becomes either a TACI (infarct) or a TACH (bleed)

Pathophysiology

  • The most important concept is that without a blood supply neurones only remain viable for 2-3 minutes. A time span that is beyond any therapeutic revascularistion modality. In practice however there is often a collateral supply and so there may well be a core of neurones that will not survive but a surrounding penumbra of cells which will continue to exists with some cellular dysfunction but are potentially viable especially if the blood supply can be improved.
  • Penumbra - This concept of penumbra of "stunned" cells is vital to the rational of current treatments. The penumbra is not a fixed but a dynamic entity. It can vary with arterial oxygenation, cerebral perfusion pressure, spontaneous or thrombolytic or mechanical reperfusion processes and other physiological parameters. Penumbra can be seen with modern imaging both with CT and MR.
  • Stages of dysfunction as cerebral blood flow falls
    • Reduction of evoked potentials
    • Arrest of cortical unit activity
    • Suppression of evokes potentials
    • Disturbance of tissue water content
    • Development of cytotoxic oedema
    • Increased extracellular potassium
    • Increased cortical impedance
  • Macroscopically
    • Occluded vessel soon leads to neuronal cell death and dysfunction. There is cytotoxic cell death and eventual swelling and oedema. There may be secondary haemorrhage (more so with embolic strokes) which leads to local pressure effects, ischaemia and neuronal dysfunction and raised ICP
  • Collaterals
    • Be aware that the COW has several variants and there may be collateral vessels
    • Right and left circulation connect via anterior communicating and posterior cerebral arteries
    • Leptomeningeal branches can also provide supply and all of these can change the stroke pattern
  • Pathology
    • More proximal occlusions lead to greater volumes of infarction
    • Extent of collatoralisation
    • Variations in structure of circle of willis can help reduce infarct size
    • Systemic effects - blood oxygenation, blood pressure, neuronal activity e.g. seizures

Risks factors for ischaemic stroke

  • Increasing Age
  • Male sex
  • Race
  • Family History
  • Previous stroke
  • Hypertension
  • Smoking
  • Diabetes
  • Dyslipidaemia (High cholesterol increases Ischaemic stroke)
  • Sickle cell anaemia
  • Atrial fibrillation
  • Obesity
  • Excess Alcohol
  • Prothrombotic disorders
    • Hyperhomocystinaemia
    • Antiphospholipid antibodies
    • Factor V Leiden
    • Prothrombin G20210 mutation
    • Protein C/S deficiency
    • Antithrombin II deficiency
    • Oral Contraceptive
  • Internal Carotid artery stenosis
  • Embolic
    • Atrial fibrillation
    • LV thrombus
      • Myocardial infarction
      • Cardiomyopathy
    • Endocarditis - septic emboli
    • LA thrombus
    • LA myxoma
    • Mechanical valve replacement
    • Tissue valve replacement
    • PFO
    • Atrial septal aneurysm
    • ASD
  • Migraine with aura
  • Carotid/Vertebral Arterial dissection
  • Cocaine
  • Connective tissue
  • Moyamoya syndrome
  • Mitochondrial diseases
  • Inflammatory vasculitis e.g. PAN
  • Takayasu's disease
  • Cardioembolism (AF, MI, Dilated CMP, Endocarditis)

Ischaemic Stroke Investigations

  • FBC - polycythaemia
  • ESR (temporal arteritis)
  • Coagulation screen (clotting + platelets) (Bleed or lysis)
  • Urea+electrolytes, Cholesterol, Glucose
  • CXR
    • cardiomegaly, enlarged LA
    • lung cancer with cerebral metatases acting as a stroke mimic
  • ECG
    • Look for AF
    • Hypertensive changes
    • Recent MI
    • Cardiomyopathy
  • CRP ? vasculitis, endocarditis
  • Carotid dopplers in those for endarterectomy or where dissection is suspected looking for carotid stenosis or dissection.
  • Echocardiogram
    • Suspected endocarditis or cardiomyopathy or LV thrombus suspected or myxoma.
  • MRI/MRA may be done when diagnosis is unclear
    • Metastases
    • Demyelination, normal early CT and stroke diagnosis questioned.
  • Thrombophilia in those under 45
    • Protein C and S
    • Antithrombin III etc )
    • ANA, dsDNA, ANCA
    • Anticardiolipin abs
  • TOE for PFO/ASD in those under 50
  • 24 hr tape for PAF
  • Alpha galactosidase ? Fabry?s disease
  • Homocysteine

Stroke imaging

  • Acute stroke imaging concepts - one suggested system is the 4 P's
    • Parenchyma - look for blood and early signs of infarction
    • Pipes - look at head and neck vessels if possible and intracerebral vessels for thrombosis or dissection depending on modality
    • Perfusion - depending on modality assess cerebral blood volume and flow and mean transit time
    • Penumbra - assess for potentially salvageable tissue
  • Non contrast CT scan
    • Within 24 hours is standard and useful and will reliably exclude primary intracerebral haemorrhage
    • An urgent CT is indicated
      • Anticoagulant treatment, a known bleeding tendency
      • Depressed level of consciousness
      • Unexplained progressive or fluctuating Symptoms
      • Papilloedema
      • Neck stiffness or fever
      • Severe headache at onset
      • Indications for thrombolysis or early anticoagulation
    • Definitive distinctive changes may not occur until 6-8 hrs. In the meantime more subtle signs are seen
      • loss of grey-white matter differentiation - seen at the cortical surface due to localised changes such as cytotoxic oedema within the grey matter which has a higher metabolic requirement and so becomes oedematous quicker
      • sulcal effacement - suggests some increased oedema
      • loss of insular ribbon - similar to loss of grey white differentiation with localised cytotoxic oedema. Vascular supply here is more vulnerable due to poor collatoralisation and so this may show first
      • low density area/hypoattenuation - Hypoattenuation on CT is highly specific for irreversible ischaemic brain damage if it is detected within first 6 hours
      • hyperdense MCA sign or "dot sign" it may be normal is a sign of clot (thrombotic or embolic) (not a contraindication to lysis) but shows extent of possible infarct which depends also on collateral flow.
      • obscuration" of the lentiform nucleus (loss of the normal attenuation difference of the globus pallidus and/or putamen with respect to contiguous white matter structures
      • CSF space compression
    • After 12 hours
      • Cleary delineated wedge shaped hyodense region involving cortex and adjacement white matter related to the occluded artery anatomy and collatorals. May be some haemorrhagic transformation. Estimated HT is up to 40% in subacute period.
      • Lacunar infarcts seen deep within white matter and within the basal ganglia
      • Hypodensity is the main finding and is due to
        • Cytotoxic oedema initially
        • Vasogenic oedema secondarily
        • Best seen days 3-10
      • Fogging
        • Density of ischaemic tissue reaches same intensity as normal brain tissue and so evidence of infarction not seen
      • Late
        • Infarcted zone has density of CSF
      • MCA
        • Hypodense caudate suggests MCA occlusion proximally taking out lenticulostriate arteries
        • Depends on leptomeningeal anastomoses of ACA and PCA
    • NCCT false negatives
      • Infarcts when done early
      • Late haemorrhage after 7-10 days
    • NCCT false positives
      • Lacunar infarcts are common and most often asymptomatic but appear on scans done for a myriad of reasons so unless there is corresponding new neurology do not diagnose acute stroke but do treat for "stroke disease".
  • CT angiography
    • Allows visualisation of the pipes from aortic arch to circle of willis and so includes head and neck vessels and COW and its branches
    • Added value is the identification of vessel occlusion from carotid to COW branches. Extent of collaterals.
    • Can help to direct mechanical or systemic or intraarterial thrombolytic therapies
  • CT Perfusion
    • Assess perfusion in a CT slice following an injection of IV contrast an measuring the first pass as the contrast perfuses the brain. Modern scanners can take 10 and more images per second. Mutlislice scanners allows different slices to be taken simultaneously. A time density curve for each pixel can be generated.
    • Can calculate relative cerebral blood flow, relative cerebral blood volume, time to peak and mean transit time which can be displayed in a colour map
    • Volume of blood per unit of brain 4-5 ml/100 g
    • Flow to grey matter is 50-60 ml/100 g/min
    • Transit time is from arterial inflow to venous outflow.
    • Time to peak enhancement - beginning of contrast injection to the maximum contrast in the area under study
  • MRI
    • Standard MRI
      • Acute ischaemia
        • T2WI and FLAIR show increased signal which peaks at 7 days and may persist for a month
        • Diffusion weighted imaging
          • This the most sensitive sequence for acute ischaemia as it shows the restriction of diffusion (Brownian motion) of extracellular water due to imbalance caused by cytotoxic oedema within minutes.
          • It can remain bright for up to 3 weeks. Some of the bright area may be viable.
          • ADC map is initially low signal and then increases in signal later on
      • Chronic infarction
        • DWI shows decreased signal intensity
        • ADC shows increased ADC values
      • MRA
        • Investigation of Haemorrhage
          • AV Malformations
          • Aneurysms
          • AV fistulae
          • Vasculitis
        • Uses time of flight
      • Contrast enhanced MRA (CEMRA)
        • Mainly used for extracranial vessels
      • MRV
        • Investigation of CVT
      • MR perfusion
        • Multi-slice imaging without radiation
        • Perfusion weighted T2* images taken following a bolus of Gadolinium every 1-2 seconds for 1-2 minutes
        • Calculate
          • time to peak
          • mean transit time
          • relative cerebral blood flow
          • relative cerebral blood volume
  • Penumbra assessment
    • CT based studies
      • Penumbra assumed to have
        • increased mean transit time with decreased cerebral blood flow (> 60%) and normal or increased cerebral blood volume (80-100%)
        • increased mean transit time with marked reduction in CBF (> 30%) and moderately reduced CBV (> 60%)
      • Infarction - severely decreased CBF < 30% and CBV volume < 40% with increased mean transit time
      • CBF = CBV divided by mean transit time
      • Penumbra = Map of Cerebral blood volume - Map of Cerebral blood flow
      • Measurements are made after the passage of contrast is given through the cerebral circulation
  • ASPECTS scan
    • Assesses MCA infarction at two different axial slices and subtracts -1 from total of 10 for each area affected
    • Lentiform nucleus level - M1, M2, M3, Lentiform, Caudate nucleus, Internal capsule, Insular cortex
    • Centrum semiovale level - M4, M5, M6
    • A score of 0 suggests extensive MCA infarction and correlates inversely with NIHSS
  • Doppler
    • Carotid/Vertebral duplex
      • Identify stenosis - useful for those with symtomatic disease for consideration of endarterectomy or stenting
      • Occlusion - due to atheroma/embolism or dissection
    • Transcranial
      • Identifies MCA flow through a temporal bone window. Takes 30-60 minutes.
      • Reduced MCA flow with vasospasm post SAH
      • Emboli and microemboli seen following agitated saline in those with Right to left shunt
      • Bilateral TCD can help show emboli origin. Both sides show emboli if cardiac, one side if carotid

Management of Ischaemic stroke

  • Stroke Thrombolysis
    • Reduces combined end point of death and disability
    • Effectiveness falls of rapidly so must be delivered quickly and safely
    • 1 in 8 chance of significant recovery
    • 1 in 18 chance of symptomatic intracerebral haemorrhage

      Clinical contraindications

      • Determine when last normal or without stroke symptoms > 4.5 hrs
      • Non abrupt onset (symptoms come on ever days may suggest other pathology)
      • A seizure at onset is a contraindication
      • Exclude hypoglycaemia
    • Initial screen
      • Last normal and symptoms free greater than 4.5 hrs
      • Age 18 to 80 (those > 80 should be considered for a stroke trial)
      • GCS > 8
      • Must have persisting symptoms - face/arm/leg weakness or speech impairment or visual loss
      • No thunderclap headache (minor headaches seen with some ischaemic stroke) or meningism or concerns of SAH (will need CT and LP if suspected)
    • Indications
      • Stroke symptoms and signs giving an NIH score 4-25
    • Contraindications
      • Previous haemorrhagic stroke
      • Major surgery or trauma in past 3 months
      • Current / recent active internal bleeding - haematuria, melaena, haemoptysis, haematemesis
      • Upper Gastrintestinal bleeding in past 3 months
      • Aortic aneurysm
      • Pericarditis
      • Known bleeding disorder - Haemophilia, Severe liver disease
      • Pregnancy (needs pregnancy test to prove not pregnant if any doubt) or recent delivery 10 days
      • AV Malformation or berry aneurysm
      • Previous stroke and concomitant Diabetes
      • Previous stroke or head trauma in past 3 months
      • Lumbar puncture within past 1 week
      • Non compressible vessel puncture within 10 days
      • CPR within past 10 days
      • Bleeding, AVM or tumour or other pathology other than stroke on CT scan
      • Cancer with increased bleeding risk
      • Greater than 1/3rd MCA territory on CT scan
    • Blood contraindications
      • Warfarin or anticoagulant with INR > 1.4
      • Platelet count < 100
      • Glucose greater than 20 mmol/l or less than 2.7 mmol/l (correct)
      • Hb < 10 g/dl
    • Observation contraindications
      • BP > 185/10 mmHg (correct it carefully if possible)
      • GCS > 8
      • Previously not independent
      • NIHSS > 25

      Management

      • Urgent Non contrast CT and bloods
      • Repeat scan at 24 hours to look for haemorrhage
      • Withhold Aspirin, Clopidogrel, Heparin until after 2nd scan shows no haemorrhage
      • Avoid IM injections (except adrenaline if required), urinary catheter, NG tube unless vital medications, arterial blood gas.
      • Consent patient
      • Alteplase 0.9 mg/kg (max dose 90 mg) with 10% as initial bolus
      • Observations
      • Blood pressure
        • Measure every 15 mins during and for the first 2 hours after and then every 30 minutes for 4 hours. Then hourly for 18 hours
        • Consider labetalol IV 20 mg boluses if BP > 185/110 mmHg
        • Reassurance, quite area

      Complications

      • Anaphylaxis - treat with IV N-Saline, IV Hydrocortisone, IV Antihistamine and consider im Adrenaline if circulatory failure
      • Orolingual Angiooedema - usually involves tongue on same side as weakness and is seen moreso in those with ACE inhibitors. Treat with IV Hydrocortisone and IV Antihistamines and anaesthetic support for the airway which may be come compromised.
      • Intracranial haemorrhage - usually haemorrhagic transformation of the infarct. Separated into symptomatic (6%) and non symptomatic. Management is to stop alteplase. If acutely then cryoprecipitae may be given. If discovered on the day 1 CT then consider withholding antiplatelets agents and heparin for a short period. Discuss with neurosurgeons.
      • Extracranial haemorrhage - Stop alteplase, Give IV Colloids, Blood and consider cryoprecipitate and platelets if needed- take haematology advice. Involvement of specialist e.g. gastroenterologists for Upper GI bleeds
  • Mechanical clot extraction devices
    • Mechanical embolus removal in cerebral ischaemia (MERCI) device can corkscrew clot out of embolised vessels. Currently under research and no significant trial data.
  • Intraarterial thrombolysis
    • Requires formal cerebral angiography. Thrombolytic (urokinase) agent delivered directly to the artery blocked. Logistically needs at least 60mins to organise lab, insert catheter and pass catheter.
    • Has been used up to 6 hours when
      • usual thrombolysis has failed
      • after the 3-4.5 hour window
      • In carotid T occlusions - occlusions within the intracranial carotid where it forms the MCA and other branches. Some suggestion that it is superior to iv alteplase.
  • Antiplatelet therapy
    • Aspirin reduces further events by 13-25% in doses of 75-150 mg od. S/E GI haemorrhage and dyspepsia
    • Dipyridamole MR 200 mg bd reduces further events by 15% when combined with aspirin
    • Clopidogrel 75 mg od alone reduces vascular events by 10% more than aspirin alone S/E rash and diarrhoea
    • Warfarin without AF or proper indication is not recommended
    • Aspirin + Clopidogrel is generally not indicated in stroke disease
  • Dipyridamole
    • Dipyridamole MR 200 mg bd for at least 2 years
    • Side effects - headache
    • Combined aspirin + dipyridamole increases efficacy
  • Clopidogrel
    • Clopidogrel 75 mg od
    • May be used alone if aspirin intolerant
    • Greater efficacy than aspirin alone
  • Carotid endarterectomy
    • Carotid territory TIA or mild carotid territory stroke with good recovery
    • Indicated symptomatic disease + ICA stenosis > 70%
    • Surgery should be done within 2 weeks or sooner of symptom - treat as vascular emergency
    • Surgery generally not on asymptomatic patients unless very severe stenosis
    • Surgical expertise and general surgical care are important
  • Carotid angioplasty and stenting
    • Generally not better and possibly worse than CEA
  • Hypertension
    • Ignored for the first 7 days if < 200-210/100 mmHg
    • Exceptions
      • Aortic dissection
      • Preeclampsia
      • Hypertensive induced heart failure
      • Hypertensive encephalopathy
    • Rapid reductions should be avoided
    • Thiazides + ACEInhibitors advocated
  • Atrial fibrillation
    • Warfarin at 2 weeks if in AF or LV thrombus or Dissection (aspirin may suffice)
    • Use in AF CHADS score to ascertain risk
    • Target INR 2-3
    • Indications
      • AF reduces annual rate of stroke from 12% to 4%
      • Recent STEMI - large anterior with hypokinesis and poor LV or apical thrombus
      • Dilated CMP
      • Some cases of Valvular heart disease
      • Complicated PFO ? controversial
  • Dissection
    • Start Warfarin at 2 weeks if in AF or LV thrombus or Dissection (aspirin + clopidogrel may suffice)
  • LV thrombus
    • Start warfarin once risk of HT low
  • PFO closure
    • may be considered for patients with recurrent cryptogenic stroke
    • Evidence not clear. Antiplatelets may be sufficient
    • Evidence that warfarin without other indications should not be used
  • Simvastatin
    • Simvastatin 40 mg given after 24-48 hrs
  • Cerebellar stroke
    • Hydrocephalus can occur
    • Refer to neurosurgeons
  • Cerebellar Haemorrhage
    • Haematoma within confines of posterior fossa compresses aqueduct and can cause hydrocephalus
    • Refer to neurosurgeons for decompression. Clear benefit for surgery in those fit for surgery
  • Raised ICP
    • Seen with haemorrhage and infarction
    • Oedema maximal at day 2-3
    • Reduced GCS and Cheyne-stokes respiration
    • Late signs with hypertension and bradycardia
    • Nurse with head elevated at 30 degrees
    • Avoid 5% dextrose
  • Haemorrhagic transformation
    • Most often asymptomatic and unknown. Increased with thrombolysis
    • Confirmed by CT scan.
    • Considered avoiding antithrombotics for a period
  • Constipation
    • Ensure hydration, stool softeners, avoid opiates
  • Contractures
    • Passive physiotherapy
  • Pressure sores
    • Regular turns
    • Pressure relieving mattress
    • Nutritional needs
  • Aspiration pneumonia
    • Actively prevent by early swallowing assessment
    • NG tube and PEG feed if swallowing unsafe
    • Good positioning can help
    • Sitting out of bed is better for chest mechanics, expectoration and preventing atelectasis
  • Subluxed shoulder on weak side
    • Joint integrity depends on muscles which have been weakened by the stroke
    • Prevent by minimising weight through shoulder joint supported and avoid damage to rotator cuff
  • Deep vein thrombosis and Pulmonary embolism
    • Prevent by early mobilisation
    • Low dose clexane in selected patients
    • TED stockings not shown to work
  • Depression
    • Mood should be assessed
    • Consider antidepressants in selected patients with moderate to severe depression

Ischaemic stroke notes

Small vessel disease

Introduction

  • Widely used term where disease is off the small arterioles < 800 um in diameter

Pathology

  • A more diffuse and gradual process slowly reducing brain function
  • There is white matter demyelination and a loss of axons and some scarring
  • Vessels occlude due to
    • occluding atheroma in the main arteries from which they branch
    • occlusion of the small arteries themselves - lipohyalinosis usually driven by hypertension

Clinical

  • Lacunar strokes
  • Vascular dementia
  • Gait apraxia
  • Parkinsonism

Investigations

  • Imaging
    • CT shows reduced intensity around the ventricles and there is Cerebral atrophy
    • MRI shows increased signal on T2 and FLAIR
  • Doppler and Echo have less importance as embolic cause is uncommon

Management

  • Treat as small vessel stroke

Cryptogenic stroke

Introduction

  • Many young strokes have no identifiable cause
  • Make sure stroke diagnosis correct - discuss with neurologists
  • Worth doing additional tests if aetiology unclear

Differential

  • Demyelination - ADEM and MS large areas can resemble Infarction on CT/MR

Aetiology

  • Unknown by definition

Investigations

  • Non contrast CT
  • MRI/MRA/MRV
  • Trans-oesophgeal Echo + Bubble study
    • Cardiomyopathy
    • Patent Foramen ovale
    • Endocarditis
    • Atrial myxoma
    • Occult mitral stenosis
    • Dilated Cardiomyopathy
  • Actively exclude carotid/vertebral dissection which may be clinically silent with MR
  • Thrombophilia screen
  • 24 hr tape (may need several) to look for AF
  • ESR and CRP
    • Vasculitis
  • LP - CSF pressure, protein, cells, lactate (MELAS)
  • Skin biopsy for CADASIL
  • Screen for Fabry's disease
  • Autoimmune screen
  • Haemorrhagic stroke
    • MRI/MRA - look for AVM, Cavernoma
    • Coagulation screen, platelets
    • Cocaine toxicology
    • MRV to exclude haemorrhagic venous infarcts
    • Screen for Sickle cell

Management

  • Different set of risks and aetiology to an older stroke. Be cautious as closure devices for young may be inserted at 20 into someone with longevity of 90 and so long term risks and benefits need considered. Evidence lacking.
  • Younger patients have a very different vascular profile than older and the standard secondary prevention may not be appropriate. Most would at least use Aspirin in ischaemic events.

Carotid dissection

Introduction

  • Always screen for it in a young person with an anterior circulation stroke

Aetiology

  • The clot can cause complete or subtotal occlusion of the carotid artery
  • Clot can form on the luminal intimal surface and embolise
  • Ehlers-Danlos Type IV or Fibromuscular dysplasia
  • May be precipitated by neck trauma

Clinical

  • Pain anywhere along carotid up into the face and behind the eye
  • Ipsilateral Horner's syndrome - mild ptosis, small pupil, enophthalmos
  • Ipsilateral Stroke findings if embolises or ICA occludes
  • Rarely dissection extends into intracranial vessels and lead to SAH symptoms

Investigations

  • MRI with fat suppression of neck shows crescent shaped intramural clot and may show infarction
  • Doppler may show occluded vessel

Management

  • Warfarin for 6 months or longer though poor evidence base
  • Aspirin + Clopidogrel may be an alternative
  • Lacking in absolute data

Vertebral dissection

Introduction

  • Always screen for it in a young person with a posterior circulation stroke

Aetiology

  • Dissection leads to luminal clot formation which can embolise
  • The clot can cause occlusion of the vertebral or distal embolisation
  • Ehlers-Danlos Type IV or Fibromuscular dysplasia
  • May be precipitated by neck trauma e.g. hairdressers, reversing

Clinical

  • pain anywhere along back of neck
  • posterior circulation stroke symptoms

Investigations

  • MRI with fat suppression of neck shows crescent shaped intramural clot
  • Doppler may show occluded vessel

Management

  • Warfarin for 6 months or longer though poor evidence base
  • Aspirin + Clopidogrel may be an alternative
  • Lacking in absolute data

Antiphospholipid syndrome

  • A rare cause of Stroke in younger people
  • Positive Anticardiolipin antibody (false +ve in elderly)
  • Lupus anticoagulants ? more specific but less common
  • Current consensus is treat as normal stroke

Cerebral venous thrombosis

Introduction

  • Headache, papilloedema and a normal CT exclude CVT
  • Think of as brain DVTs in terms of management
  • Look for underlying causes

Aetiology

  • May be seen with Procoagulant conditions
  • Localised infections e.g. sinusitis, mastoiditis

Anatomy of the thrombosis in order of occurrence

  • Superior sagittal sinus
  • Lateral sinuses
  • Straight sinus
  • Cavernous sinus

Aetiology

  • Venous thrombosis leads to increased venous pressure, oedema and venous infarction
  • Reduced CSF drainage with increased ICP
  • Congested oedematous haemorrhagic infarcts
  • Subarachnoid bleeding may be seen

Procoagulant conditions

  • OCP, Pregnancy, hyperviscosity syndromes, smokers
  • Malignancy, labour, dehydration, ecstasy,
  • Behcet's disease
  • Localised mastoid, ear or sinus infections

Differential

  • Idiopathic intracranial hypertension need to exclude CVST especially if male or non obese

Clinical

  • Headache
  • Cortical vein occlusion gives expected localising signs.
  • Dural sinuses ? raised ICP, Sudden headache
  • Declining consciousness, Coma, Seizure,
  • Neurological deficit like stroke, Papilloedema
  • VI nerve palsy

Investigations

CT

  • May be normal or may be wedge like (haemorrhagic) infarcts not corresponding to arterial territory
  • Increased contrast enhancement of falx and tentorium
  • Cord sign on non contrast CT due to fresh clot along falx
  • Subarachnoid blood may be seen
  • Empty delta sign on CT with contrast identifying clot
  • CT with contrast or MRV can show empty delta sign and absence of flow in lumen of sagittal sinus occluded by venous clot.

MRI and MRV

  • Can show extent of infarcts, haemorrhage and evidence of venous thrombosis

CSF

  • Raised pressure and protein.
  • LP may help reduce CSF pressure

Prognosis

  • Deep vein thrombosis is worse
  • Males and right lateral sinus thrombosis also worse

Management

  • IV Heparin or S/C LMWH is reasonable even with evidence of haemorrhagic infarction
  • Warfarin for 3-6 months followed by antiplatelets. Prolonged warfarin course e.g. 12 months if idiopathic cause

Moyamoya

Introduction

  • Can cause ischaemic and haemorrhagic stroke

Aetiology

  • Rare in Europeans, mostly seen in Asians
  • Fragile arteries can bleed

Clinical

  • Affects young people.
  • Progressive intracranial artery stenosis and internal carotid artery occlusion.
  • May involve other parts of COW
  • Ischaemic stroke and haemorrhage
  • Seizures

Investigations

  • MRI and MRA should be performed for the diagnosis and follow-up
  • Angiography shows fragile collateral vessels give traditional ?puff of smoke? angiography appearance.

Management

  • Direct superficial temporal artery (STA) to middle cerebral artery (MCA) bypass is considered the treatment of choice

CADASIL

Introduction

  • Suspect when there is a family history of migraines or early dementia
  • Causes small vessel stroke disease

Aetiology

  • Autosomal dominant Cerebral arteriopathy
  • Subcortical infarcts leucoencephalopathy
  • Mutation on notch 3 gene on chromosome 19p13.1

Clinical

  • TIA and lacunar strokes
  • Migraine with aura
  • Epilepsy
  • Psychiatric disturbance
  • Dementia

Investigations

  • Eosinophilic deposits in tunica media of arteries in brain, skeletal muscle and skins
  • Skin biopsy for diagnosis.

Management

  • There is No specific treatment except to manage as Ischaemic stroke
  • Genetic counselling for family

MELAS

Aetiology

  • Maternally inherited disease of metabolism seen in those under 20
  • mitochondrial encephalopathy, lactic acidosis, and stroke like episodes syndrome
  • Mutation in maternally inherited mtDNA.

Clinical

  • Stroke like episodes in the young
  • Seizures, Hemiparesis, Hemianopia, Cortical blindness

Investigations

  • MRI ? basal ganglia calcification, Lactic acidosis.
  • Plasma and CSF lactate elevated, Genetics. Muscle biopsy ? red ragged fibres

Heparin induced thrombocytopenia (HIT)

Aetiology

  • Recent heparin exposure and falling platelets with venous or arterial thrombosis.

Clinical

  • Venous or arterial thrombosis
  • Thrombocytopenia.

Management

  • Stop all heparin and switch to alternatives

Management

  • See haematology section

Cerebral Vasculitis

  • Common with Polyarteritis nodosa, Rare with SLE
  • Takayasu's arteritis, Can be secondary to infections, drugs, lymphoproliferative disorders

Takayasu's arteritis

Introduction

  • Large vessel vasculitis of Aorta and arch vessels
  • Neurological disease if carotids or subclavian vessels affected

Aetiology

  • Autoimmune response to an aortic antigen has been suggested

Clinical

  • Age < 40 with absence of pulses and claudication
  • Stroke due to carotid artery or subclavian stenosis or occlusion
  • Aneurysms of head and neck vessels can occur
  • Systemic inflammatory symptoms e.g. malaise, weight loss
  • Difference in pulses of 30 mmHg suggests vessel stenosis on the lower pressure side

Investigations

  • ANCA negative
  • Elevated CRP and ESR > 50 mm/hr
  • Angiography shows narrowing or occlusion or aneurysmal dilatation
  • Detected by MRA or Angiography or USS.

Management

  • Steroids and Immunosuppression e.g. azathioprine, cyclophosphamide etc
  • Possibly a role for Anti-TNF treatments

Fabry disease

Introduction

  • Inherited or spontaneous gene mutation
  • Usually X linked recessive
  • Stroke is only one of many manifestations

Aetiology

  • Deficiency of alpha galactosidase in cell lyzosomes
  • Build up of glycosphingolipids

Clinical

  • Burning pains in the limbs "acroparaesthesia" starts in adolescence or before. Worse with exercise.
  • Purplish angiokeratomas on abdomen, umbilicus and genital areas
  • Corneal verticillata detectable by slit lamp examination
  • Decreased sweating
  • Cardiac - conduction abnormalities

Investigations

  • ESR may be elevated
  • ECG - non specific changes and conduction abnormalities
  • Proteinuria and progressive renal failure
  • MRI - may show small vessel stroke
  • a -Gal A activity may be measured in plasma, serum, and leukocytes
  • DNA analysis

Management

  • Management of neuropathic pain with usual therapies
  • Enzyme replacement in all males and symptomatic females is recommended and can reduce complications
  • Pacing if required
  • Renal replacement

Haemorrhagic strokes 15%

Types

  • Lobar haemorrhages
  • Deep bleeds
  • Subarachnoid haemorrhages