Management of Cerebrovascular Steno-Occlusive Disease

Management of Cerebrovascular Steno-Occlusive Disease

Contemporary multidisciplinary approach

Patients with steno-occlusive cerebrovascular disease are at risk of ischemic symptoms from haemodynamic insufficiency in the presence of reversible hypoperfusion, exhausted autoregulation and impaired vasodilatory reserve. Multidisciplinary management approach includes blood pressure management, antithrombotic therapy, treatment of underlying brain-body interactions targeted at optimising cerebral blood flow and oxygen delivery, and revascularisation procedures.

Benjamin Wai Yue Lo, Neurosurgeon & ICU Specialist

Patients with symptomatic stenoocclusive disease have a risk of recurrent stroke of at least 10-15 per cent within 5 years. Progressive atherosclerosis of internal carotid artery (ICA) or middle cerebral artery (MCA) is the most common cause of impaired distal cerebral perfusion with cerebral misery hypoperfusion (Figure 1, Table 1).

Cerebral Hypoperfusion & Collateral Circulation

In the setting of cerebral hypoperfusion, recurrent ischaemic events occur depending on the following factors: (1) amount of collateral cerebral circulation; (2) extent of haemodynamic impairment; (3) age; (4) cardiac status; (5) presence of metabolic syndrome of hypertension, hyperlipidemia and insulin resistance; (6) factors affecting coagulation, blood oxygen carrying capacity and delivery (such as anaemia and other haematology disorders, systemic infections and sepsis, renal and hepatic disorders).

In addition to the traditional cerebral ischaemic symptomatology pertaining to the affected vascular territory (Table 2), orthostatic symptoms, syncope, transient global amnesia, episodic limb shaking and watershed infarction are possible.

In states of misery perfusion, compensatory cerebral vasodilation is not possible as the cerebral autoregulatory capacity is exhausted and, as a result, cerebral blood flow decreases proportionally with cerebral perfusion pressure (Figure 1). Possible cerebral collateral circulation routes include: (1) contralateral internal carotid artery (ICA) through anterior communicating artery; (2) posterior circulation via posterior communicating artery; (3)

leptomeningeal or pial collaterals; (4) collateral circulation from external carotid artery (ECA) with retrograde flow and connections with ophthalmic artery, extracranial connections between ECA or vertebral artery (VA) branches and distal ICA; (5) collaterals through dural meningeal arteries to cortical arteries; (6) anterior cerebral artery (ACA)-posterior cerebral artery (PCA) connections via the limbic loop; and (7) anterior spinal artery collaterals with the vertebrobasilar circulation.

Medical management principles

Medical management strategies are essential to treatment of cerebral ischaemic events and prevention of recurrent strokes in face of cerebral hypoperfusion. These include: (1) cautious individualised blood pressure management (usually systolic blood pressure targets of 130-160 mmHg for those with severe bilateral carotid stenoses); (2) maintenance of fluid status to maintain appropriate plasma oncotic pressures for adequate cerebral perfusion; (3) anti-platelet and anticoagulant therapies (single anti-platelet agent and anticoagulant for those with embolic strokes or in the setting of cardiac arrthymias; dual anti-platelet therapy, with laboratory evidence of responsiveness to these agents, for those with atherosclerotic disease or perforator events), (4) statin, and (5) glycaemic control.

Treatment of underlying brainbody interactions are also essential, including attention to haemodynamic stability, cardiac status, optimising cerebral oxygen delivery with avoidance of anaemia, goal-directed therapy for sepsis, optimisation of renal perfusion and avoidance of coagulopathy and encephalopathy due to underlying multi-systemic involvement, particularly renal or hepatic impairment.

Identification of surgical candidate

For patients with symptomatic severe (> 70 per cent) carotid stenosis, carotid endarterectomy or angioplasty/ stenting is considered. Thrombectomy is considered for patients with embolic strokes to large size cerebral vessels. For patients who have been medically optimised but are still at risk of ischaemic symptoms of haemodynamic insufficiency due to ICA/MCA stenosis/ occlusion in the setting of hypotension or orthostasis, one can identify candidates with reversible hypoperfusion, exhausted autoregulation and impaired vasodilatory reserve. Consideration of extracranialintracranial bypass procedure can be reliably made to identify patients who have reasonable chances of augmentable flow-induced long-term cerebral blood flow re-organisation (collateral shift) while preventing future hypoperfusion events. Identification of these candidates is made after blood pressure management, antithrombotic therapy and treatment of underlying brainbody interactions targeted at optimising cerebral blood flow and oxygen delivery.

Investigational adjuncts

In addition to clinical findings on presentation and with monitoring (Table 2), other adjunctive investigations are useful in identifying such surgical candidates. CT perfusion scans demonstrate ischaemic penumbra of increased time-to-peak (TTP, time between first arrival of CT contrast intracranially and its peak concentration), increased mean transit time (MTT, average time for blood to travel through a volume of brain), with relatively preserved cerebral blood volume (CBV) due to vasodilation and recruitment of collateral flow, and decreased cerebral blood flow (CBF). As reference, an infarcted core shows increased TTP, increased MTT, decreased CBV and decreased CBF. SPECT (single photon emission computerised tomography) scan with acetazolamide (DiamoxTM) is used to identify patients with haemodynamic insufficiency who exhibit reversible hypoperfusion and decreased cerebrovascular reactivity when challenged with acetazolamide (Figure 3a-c). In those who are in the misery perfusion stage of haemodynamic insufficiency, they are already maximally

vasodilated and dysautoregulated. In this regard, they cannot further vasodilate in response to increased carbon dioxide tension from diuretic acetazolamide, a carbonic anhydrase inhibitor.

Quantitative MR angiography (q-MRA)’s non-invasive optimal vessel analysis (NOVA) is also essential to quantify and measure blood flow through large vessels of the Circle of Willis (Figure 3b). Together with formal cerebral angiography, it can be used to estimate pial and collateral flow. It gives reasonable estimates of augmentable flow to ensure appropriate blood velocity ranges after bypass, and also in anticipation of longer term collateral shift, cerebral blood flow re-organisation.

Surgical procedure

Direct superficial temporal artery (STA) [donor] and middle cerebral artery (MCA) M4 cortical branch [recipient] bypass is generally preferred. Meticulous attention to blood pressure control, maintenance of intravascular volume and depth of anaesthesia are essential to avoid cerebral hypoperfusion during these cases with underlying steno-occlusive disease. Intraoperative end-to-side anastomoses are performed using 10-0 nylon sutures with indocyanine green (ICG) and intra-operative angiographic confirmation of anastomotic patency. Individualised blood pressure goals with gradual liberalisation of these parameters are done post-operatively with continuation of antithrombotic agents to maintain anastomotic patency and to avoid reperfusion-related injury.

Conclusion

For patients who have been medically optimised but still at risk of ischemic symptoms of haemodynamic insufficiency due to steno-occlusive cerebrovascular disease, one can identify candidates with reversible hypoperfusion, exhausted autoregulation and impaired vasodilatory reserve. Consideration of extracranial-intracranial bypass procedure can be reliably made to identify patients who have reasonable chances of augmentable flow-induced long-term cerebral flow re-organisation while preventing future hypoperfusion events. Identification of these candidates are made after medical optimisation, including blood pressure management, antithrombotic therapy and treatment of underlying brain-body interactions targeted at optimising cerebral blood flow and oxygen delivery.

Figure 1. Stages of Cerebral Hypoperfusion.

Table 1. Cerebrovascular mean flow velocities.

Artery

ICA Siphon

Normal Mean Flow Velocity [MFV] (cm/s)

< 70

MCA M1-M2 < 80

ACA A1 < 80

BA < 50

VA

PCA < 60

< 50

ICA = internal carotid artery, MCA = middle cerebral artery, ACA = anterior cerebral artery, BA = basilar artery, VA = vertebral artery, PCA = posterior cerebral artery.

Arterial Stenosis (50 per cent)

ICA Siphon, ACA (A1)

MCA M1-M2

BA-VA-PCA Mean Flow Velocity [MFV] (cm/s)

< 90

< 100

< 70

Table 2. Stroke Syndromes Carotid

asymptomatic bruit TIAs (transient ischemic attacks): transient monocular blindness, weakness, numbness, speech/language disturbance sudden deficit in MCA and/or ACA territory progressive or stepwise hemispheric deficits (watershed infarction)

MIDDLE CEREBRAL ARTERY (MCA) STROKE SYNDROMES MCA - entire territory

contralateral gaze palsy, hemiplegia, hemisensory loss, spatial neglect, hemianopsia (left) global aphasia

MCA – deep

contralateral hemiplegia, hemisensory loss (left) transcortical motor (non-fluent aphasia, intact repetition) and/or sensory (receptive) aphasia lacunar syndromes - pure motor hemiparesis, sensorimotor stroke

MCA – parasylvian

contralateral weakness and sensory loss of face and hand (left) conduction aphasia, apraxia, Gerstmann's syndrome (dys-/ a-graphia, dys-/a-calculia, finger agnosia, left-right disorientation) (right) constructional dyspraxia

MCA - superior division

contralateral hemiplegia, hemisensory loss, gaze palsy, spatial neglect (left) Broca's aphasia

MCA - inferior division

contralateral hemianopsia or upper quadrantanopsia (left) Wernicke's aphasia (right) constructional dyspraxia

ANTERIOR CEREBRAL ARTERY (ACA) STROKE SYNDROMES

ACA - entire territory

contralateral hemiplegia abulia incontinence transcortical motor aphasia or motor and sensory aphasia limb dyspraxia

ACA – distal

contralateral weakness of leg, hip, foot, shoulder sensory loss in foot transcortical motor aphasia or motor and sensory aphasia limb dyspraxia

ACA – deep

lacunar syndromes - pure motor hemiparesis, sensorimotor stroke

ACA - anterior choroidal

hemiparesis, hemisensory abnormalities, hemianopia

MIDBRAIN STROKE SYNDROMES

Midbrain basis (Weber's syndrome)

PCA (posterior cerebral artery) branches, top of basilar CN (cranial nerve) 3 fascicles - ipsilateral 3rd palsy (ptosis, no eye adduction, no up/downgaze +/- dilated pupil)

Midbrain tegmentum (Claude's syndrome)

PCA (posterior cerebral artery) branches, top of basilar CN 3 fascicles - ipsilateral 3rd palsy red nucleus, superior cerebellar peduncle fibers - contralateral ataxia

Midbrain basis and tegmentum (Benedikt's syndrome)

PCA (posterior cerebral artery) branches, top of basilar CN 3 fascicles - ipsilateral 3rd palsy cerebral peduncle - contralateral hemiparesis red nucleus, substantia nigra, superior cerebellar peduncle fibers - contralateral ataxia, tremor, involuntary movements

PONS STROKE SYNDROMES

Medial pontine basis (dysarthria hemiparesis - pure motor hemiparesis)

basilar artery (paramedian branches), ventral territory corticospinal/bulbar tracts - contralateral face/arm/leg weakness, dysarthria

Medial pontine basis (ataxic hemiparesis)

basilar artery (paramedian branches), ventral territory corticospinal/bulbar tracts - contralateral face/arm/leg weakness, dysarthria pontine nuclei/pontocerebellar fibers - contralateral ataxia (occasional ipsilateral ataxia)

Medial pontine basis and tegmentum (Foville's syndrome)

basilar artery (paramedian branches), ventral and dorsal territories corticospinal and corticobulbar tracts - contralateral face/arm/ leg weakness, dysarthria facial colliculus - ipsilateral face weakness, ipsilateral horizontal gaze palsy

Medial pontine basis and tegmentum (Pontine wrongway eyes syndrome)

basilar artery (paramedian branches), ventral and dorsal territories corticospinal and corticobular tracts - contralateral face/arm/leg weakness, dysarthria abducens nucleus/paramedian pontine reticular formation - ipsilateral horizontal gaze palsy

Medial pontine basis and tegmentum (Millard-Gubler syndrome)

basilar artery (paramedian branches), ventral and dorsal territories corticospinal and corticobulbar tracts - contralateral face/arm/leg weakness, dysarthria CN7 fascicles - ipsilateral face weakness

Medial pontine basis and tegmentum (Other regions)

basilar artery (paramedian branches), ventral and dorsal territories medial lemniscus - contralateral decreased position and vibration sense medial longitudinal fasciculus - internuclear ophthalmoplegia (affected eye impaired adduction)

Lateral caudal pons (anterior inferior cerebellar artery - AICA)

middle cerebellar peduncle - ipsilateral ataxia vestibular nuclei - vertigo, nystagmus trigeminal nucleus and tract - ipsilateral facial decreased pain and temperature sense spinothalamic tract - contralateral body decreased pain and temperature sense descending sympathetic fibers - ipsilateral Horner's syndrome

Lateral caudal pons (Other regions)

labyrinthine artery - inner ear - ipsilateral hearing loss

Dorsolateral rostral pons (superior cerebellar artery - SCA)

superior cerebellar peduncle and cerebellum - ipsilateral ataxia other lateral tegmental structures (variable) - variable features of

AICA syndrome (lateral tegmental involvement)

MEDULLA STROKE SYNDROMES

Medial Medulla

paramedian vertebral artery (VA), anterior spinal artery (ASA) pyramidal tract - contralateral arm/leg weakness medial lemniscus - contralateral decreased position/vibration CN12 nucleus/fascicles - ipsilateral tongue weakness

Lateral Medulla (Wallenberg's syndrome)

posterior inferior cerebellar artery (PICA), vertebral artery (VA) inferior cerebellar peduncle, vestibular nuclei - ipsilateral ataxia, vertigo, nystagmus, nausea trigeminal nucleus, tract - ipsilateral facial decreased pain and temperature sense spinothalamic tract - contralateral body decreased pain and temperature sense descending sympathetic fibers - ipsilateral Horner's syndrome nucleus ambiguus - hoarseness, dysphagia nucleus solitarius - ipsilateral decreased taste

VERTEBRAL ARTERY (VA) STROKE SYNDROMES Subclavian Steal

asymptomatic sometimes vertebrobasilar (VB) TIAs (dizziness, slurred speech, faintness, imbalance)

Extracranial Vertebral Artery (VA)

asymptomatic sometimes VB TIAs

Intracranial Vertebral Artery (VA)

lateral medullary syndrome (Wallenberg's syndrome) medial medullary syndrome (tongue paralysis, contralateral hemiplegia) hemi-medullary infarction PICA infarction (dorsolateral medulla and lower half of cerebellum)

BASILAR ARTERY STROKE SYNDROMES

Basilar occlusion

often preceding TIAs at onset headaches, dizziness, paresthesia, confusion followed by CN palsies neuro-ophthalmologic abnormalities (such as vertical skew, oscillopsia, downbeat nystagmus), ataxia, quadriparesis/plegia, locked-in syndrome, coma

Lacunes

pure motor hemiparesis, dysarthria-clumsy hand, pure sensory stroke, sensorimotor stroke Paramedian and short circumferential arteries crossed syndromes with ipsilateral CN palsy contralateral motor, sensory or sensorimotor deficits neuro-ophthalmologic abnormalities, dysarthria, ataxia

Superior Cerebellar Artery (SCA)

limb ataxia, dysarthria, CN4 palsy (diplopia worse in downgaze),

Horner’s syndrome, contralateral thermoanalgesia

Anterior Inferior Cerebellar Artery (AICA)

limb and trunk ataxia, CN7 & 8 palsies, Horner’s syndrome, contralateral hemiplegia and hemisensory loss

Posterior Inferior Cerebellar Artery (PICA)

pseudovestibular syndrome, nystagmus, trunk and limb ataxia, lateral medullary syndrome

Top of Basilar Occlusion

abnormal pupils, convergence, vertical eye movements,

CN3 palsy, hemiplegia/quadriplegia, sensory loss, ataxia, hypersomnolence, inattention, abnormal behaviour, confusion, hallucinations, memory loss, visual defects, abnormal movements

Thalamic Infarcts

abulia, memory loss, dysphasia, dyspraxia (anterolateral infarction)

hypersomnolence, coma, abnormal vertical eye movements and convergence, disorientation, amnesia, dysphasia (anteromedial infarction) pure sensory stroke, sensorimotor stroke, Dejerine-Roussy syndrome (lateral infarction) visual field defects (dorsal and lateral geniculate body infarction)

POSTERIOR CEREBRAL ARTERY (PCA) STROKE SYNDROMES

PCA - deep and superficial territory

part of syndrome of top of basilar

PCA - deep territory

thalamopeduncular infarcts

PCA – superficial

cortical blindness visual field defects (homonymous hemianopia, altitudinal hemianopia, quadrantanopia) abnormal color vision, pallinopsia, micropsia visual agnosia, pure alexia, hemidyslexia, prosopagnosia, memory deficits, topographic disorientation, amnesic aphasia

Figure 3a. MR Angiogram showing left ICA functional occlusion. Figure 3b. Quantitative MRA showing decreased left MCA flow.

Figure 3c. SPECT showing slight reversible hypoperfusion after acetazolamide challenge (right).

Acknowledgement: Acknowledgement is made to Dr. David J. Langer for his expertise in this clinical area.

AUTHOR BIO

Benjamin W Y Lo is a neurosurgeon and ICU specialist. His clinical focus is cerebrovascular disorders. His research focus characterises brain-body interactions in neurocritical care patients with cerebrovascular disorders. Dr. Lo’s qualifications include FRCSC certification in neurosurgery (2009), FRCSC certification in critical care medicine (2011), MSc and PhD degrees in clinical epidemiology and biostatistics from McMaster University. His clinical experience includes working as neurosurgeon and ICU specialist at St. Michael’s Hospital, University of Toronto; Montreal Neurological Institute & Hospital, McGill University; and Northwell Health Lenox Hill Hospital, New York.