CEREBRAL BLOOD FLOW, ITS

AUTOREGULATION , CLINICAL RELEVANCE

ANDROLE OF

COLLATERALS IN ISCHEMIC STROKE

By-Varun Kumar Singh 18/12/2015

OVERVIEW

• CEREBRAL BLOOD SUPPLY(ARTERIAL AND VENOUS)• AUTOREGULATION MECHANISM AND ITS CLINICAL

IMPORTANCE• CEREBRAL COLLATERALS AND ITS SIGNIFICANCE IN

ACUTE ISCHEMIC STROKE

AORTIC ARCH1.Innominate artery (IA) /

Brachiocephalic trunk• Rt subclavian artery (SCA)- Right

vertebral artery • Rt common carotid artery (CCA)

2.Left Common Carotid Artery (CCA)

3.Left Subclavian Artery (SCA) • Left Vertebral Artery (VA)

Major Arteries1.INTERNAL CAROTID--TWO IN NO.• ARCH OF AORTA-

BRACHIOCEPHALIC-INTERNAL +EXTERNAL CAROTID AT SUPERIOR BORDER OF THYROID CARTILAGE(C3-C4)

• ENTER THE BRAIN-CAROTID CANAL

2. VERTEBRAL ARTERIES-TWO IN NO.• FROM 1st PART OF SUBCLAVIAN

ARTERY.• TRAVERSE FROM C6 TO C1 –

FORAMAN MAGNUM• UNITES TO FORM BASILAR

ARTERY AT THE LOWER BORDER OF THE PONS

INTERNAL CAROTID ARTERY• Four segments:

– Cervical (extracranial)– Petrous (extracranial)– Cavernous (intracranial)– Cerebral /Supraclinoid (intracranial)

• Branches (proximal to distal) – Meningohypophyseal trunk – Ophthalmic artery (OA)– Superior hypophyseal artery– Posterior communicating artery (PComA)– Anterior choroidal artery (AChA)– Anterior cerebral artery (ACA) – Middle cerebral artery (MCA) (continuation of the ICA)

Cervical segment– From the bifurcation of CCA

– Enters the skull through carotid canal in petrous part of temporal bone

– No branches

– Persistent embryonic vessels may give rise to ECA – ICA anastomoses

PETROUS SEGMENT

-Extends from base of skull to the petrous apex

-Ascending , Genu, Horizontal

-Enters cranial vault via foramen lacerum.

-Branches : Carotico tympanic A & A of pterygoid canal

CAVERNOUS SEGMENT• S- shaped course in sinus

referred to as CAROTID SIPHON• Passes through cavernous sinus• In proximity to CN III, IV, V1, V2

and VI• Ascending sympathetic fibres

surround artery• Branches supply posterior lobe

of pituitary and adjacent meninges

(Meningohypophyseal Artery)

SUPRACLINOID SEGMENT

• Begins after penetration of dura

• Continues until bifurcation into ACA & MCA

SUPRACLINOID SEGMENT

• Three Branches:

1.Ophthalmic A

2.Posterior Communicating A 3.Anterior Choroidal A

OPHTHALMIC ARTERY

1st intradural branch of ICA

Supplies globe, orbit, frontal and ethmoidal sinuses, & frontal scalp

Central retinal A, Long & Short posterior ciliary branches

Branches of Ophthalmic A anastamose with Maxillary A branches - potential for collateral flow in cases of proximal carotid occlusion

POSTERIOR COMMUNICATING A

• Branches enters the base of brain between infundibulum and optic tract

• Supply anteromedial thalamus and walls of third ventricle

ANTERIOR CHOROIDAL A• Branch of supraclinoid segment of ICA close to

its terminal bifurcation

• Passes backward along the optic tract and around the cerebral peduncle as far as the lateral geniculate body

• Enters the inferior horn of the lateral ventricle

ANTERIOR CHOROIDAL A

• Supplies the choroid plexus of lateral ventricle

• Branches to optic tract, hippocampus, tail of caudate nucleus, medial and intermediate portions of globus pallidus, posterior 2/3 of internal capsule along with retro and sublenticular part, middle third of cerebral peduncle and outer part of lateral geniculate body

ANTERIOR CEREBRAL ARTERYThree segments:

A1 –Horizontal/Pre communicating segmentMedial lenticulostriate

branches

A2-Vertical/Post communicating segment

From its connection to the AComA to its bifurcation into the pericallosal and callosomarginal arteriesRecurrent artery of HeubnerOrbitofrontalFrontopolar

A3- distal ACA / cortical branchesPericallosalCallosomarginal

ACA SUPPLY• Medial and orbital surface of frontal lobe• Medial surface of the parietal lobe as far as the

parietooccipital fissure• Genu and Anterior 4/5th of the corpus callosum• A longitudinal 2 cm wide strip of superior surface of

the frontal & parietal lobes next to the central sulcus

• Anterior parts of Basal Ganglia & Anteroinferior parts of Internal Capsule

ACA Supply

RECURRENT ARTERY OF HEUBNER• Also called medial striate artery

• Give few branches to orbital cortex, passes through anterior perforated space to join deep branches of MCA

• Supplies lower part of head of caudate, lower part of frontal pole of putamen, frontal pole of globus pallidus, frontal half of anterior limb of internal capsule, and anterior portions of external capsule and lateral ventricle

Infarct in Heubner artery territory

MIDDLE CEREBRAL ARTERYFour segments:• M1- horizontal / sphenoidal

segment:The stem of MCA 5-15 lenticulostriate branches

• M2- insular segment:Runs deep in sylvian fissure and along insula ; Superior & Inferior divisions

• M3- opercular segment: Follows the curvature of operculum and ends as terminal branches of MCA

• M4- cortical branches:Terminal segment as it emerges from the sylvian fissure

Middle cerebral ArteryM1- Horizontal segment•Lateral Lenticulostriate•Temporoparietal artery•Frontobasal artery

M2- Insular segment

M3- Opercular segment•Opercular segment branches•Operculofrontal artery

M4- Cortical branches•Lat Orbitofrontal•Pre rolandic•Rolandic•Ant. parietal•Post. parietal•Angular •Temporopolar•Ant temporal•Middle temporal•Post. temporal

MCA SUPPLY

• Most of the convex surface of the brain, except the frontal (ACA)and occipital(PCA) poles & the superior rim of the convex surface(ACA)

• Lenticulostriate arteries (Artery of cerebral hemorrhage) supply

-All of the putamen except for its anterior pole -Upper part of head of caudate N and all of its body -Lateral part of globus pallidus -Posterior part of anterior limb, genu and anterior

third of posterior limb

Posterior cerebral artery P1Segment (Precommunicating/mesencephalic) short segment from the basilar tip to the PComA

– Mesencephalic br. – Cr. Nv. Nuclei 3 - 6

– Thalamoperforating arteries - diencephalon and midbrain

P2 or ambient segment runs in the ambient cistern from the PComA to

the posterior aspect of the midbrain– Thalamogeniculate br.– Medial posterior choroidal arteries– Lateral posterior choroidal arteries

P3 or quadrigeminal segment runs within the quadrigeminal cistern behind the

brainstem– Hippocampal artery– Antetior, middle, and posterior temporal

arteries– Parieto-occipital artery– Calcarine artery– Posterior pericallosal artery

P4 –DISTAL SEGMENT

POSTERIOR CEREBRAL ARTERY

PCA SUPPLY

-Uncus-Medial and inferior surface of temporal lobe

(Temporal pole- MCA)-Thalamus, midbrain-Cuneus and splenium of corpus callosum-Medial surface of occipital lobe including entire

visual cortex

VERTEBRAL ARTERY• V1(EXTRAOSSEOUS): Segmental cervical muscular

and spinal branches - passing into spinal canal via intervertebral foramina and reinforce blood supply of spine and vertebrate.

• V2 (FORAMINAL): -In foramina transversaria of

C6-C2 -meningeal/muscular/spinal

branches

VERTEBRAL ARTERY• V3 (EXTRASPINAL): Posterior meningeal artery

• V4(INTRADURAL):– Anterior and posterior spinal arteries(Two anterior

spinal A join to supply lower medulla, cervicomedullary junction and upper spinal cord)

– Perforating branches to medulla

– PICA: Arises from distal Vertebral Artery, supply medulla and cerebellum

BASILAR ARTERY

• Forms at pontomedullary junction from two vertebral artery

• Ends at the upper border of pons• Major 5 branches

1.The pontine arteries 2. The labyrinthine 3. The anterior inferior cerebellar artery4. The superior cerebellar artery5.The posterior cerebral

BASILAR ARTERY1.The pontine arteries 2. The labyrinthine -the internal ear.- often arises as a branch of the anterior

inferior cerebellar artery.3. The anterior inferior cerebellar artery-the anterior and inferior parts of the

cerebellum - A few branches pass to the pons and the

upper part of the medulla oblongata.4. The superior cerebellar artery-arises close to the termination of the

basilar artery-supply superior surface of the

cerebellum, pons, the pineal gland, and the superior medullary velum.

5.The posterior cerebral

• Medulla-Vertebral Pons – Basilar Midbrain- Basilar and proximal Posterior

cerebral Artery

• Two vertebral artery are rarely the same size. Left is most often dominant; Right can be smaller or completely atretic

• SCP-SCA, ICP-PICA, MCP-AICA and SCA

CIRCLE OF WILLIS-In the interpeduncular

fossa at the base of the brain.

-It is formed by the anastomosis between the two internal carotid arteries and the two

vertebral arteries

VARIATIONS IN THE CIRCLE OF WILLIS

Anteroinferior part-medial lenticulostriate arteries

Superior part of head and body of caudate nucleus, lentiform nucleus- Lateral lenticulostriate arteries

Thalamus and tail of caudate- by thalamogeniculate and posterior choroidal artery

VENOUS DRAINAGE OF THE BRAIN

The characteristic features of venous drainage of the brain are:

• The venous return in the brain does not follow the arterial pattern

• The veins of the brain are extremely thin-walled due to absence of muscular tissue in their walls

• The veins of the brain possess no valves• The veins of the brain run mainly in the subarachnoid space• The cerebral veins, generally enter obliquely into the dural

venous sinuses against the flow of blood in the sinuses to avoid their possible collapse following an increased intracranial pressure as they are thin walled

SINUSES OF THE DURA MATER.

(1) Postero-superior at the upper and back part of the skull. 1 Superior Sagittal (Convex or attached margin of falx cerebri)2 Straight sinus3 Inferior Sagittal (free or inferior margin of falx cerebri)4 Two Transverse. 5 Occipital

(2) Antero-inferior at the base of the skull. 1 Two Cavernous2 Two Superior Petrosal3 Two Intercavernous 4 Two Inferior Petrosal5 Two sphenoparietal

VENOUS DRAINAGE OF BRAIN

• Anterior cerebral vein + Deep middle cerebral Vein + Striate veins = Basal Vein of Rosenthal

• Thalamostriate vein + Choroidal vein = Internal cerebral vein

• Internal cerebral vein + Basal Vein of Rosenthal = Great vein of Galen

• Great vein of Galen + ISS = Straight sinus

• Superior cerebral vein drain to SSS

• SSS + straight sinus + Occipital sinus = Transverse sinus(Attached margin of tentorium cerebelli)

• Inferior cerebral vein drain to superficial middle cerebral vein terminates to cavernous sinus

• SSS connects to superficial middle cerebral vein by Troland’s vein AND Transverse sinus to superficial middle cerebral vein by vein of Labbe’

• Cavernous sinus (drain to transverse and IJV via superior and inferior petrosal sinus.

VENOUS DRAINAGE OF BRAIN

VENOUS DRAINAGE OF BRAIN

CEREBRAL BLOOD FLOW AUTOREGULATION

• Neurons produce energy (ATP) almost entirely by oxidative metabolism of substrates including glucose and ketone bodies, with very limited capacity for anaerobic metabolism.

• Without oxygen, energy-dependent processes cease leading to irreversible cellular injury if blood flow is not re-established rapidly (4 to 10 minutes under most circumstances)

REGULATION OF CEREBRAL BLOOD FLOW

Cerebral blood flow (CBF) is dependent on a number of factors that can broadly be divided into:

a. those affecting cerebral perfusion pressureb. those affecting the radius of cerebral blood vessels

• CBF = 50ml/100g/min (ranging from 20ml/100g/min in white matter to 70ml/100g/min in grey matter)

• Adult brain weighs 1400g or 2% of the total body weight.

• But CBF is 700ml/min or 15% of the resting cardiac output

1) CEREBRAL PERFUSION PRESSURE• Perfusion of the brain is dependent on the

pressure gradient between the arteries and the veins and this is termed the cerebral perfusion pressure (CPP)

• This is the difference between the mean arterial blood pressure (MAP) and the mean cerebral venous pressure

CPP = MAP – ICP

• MAP can be estimated as equal to: diastolic blood pressure + 1/3 pulse pressure, usually around 90mmHg

• ICP is much lower and is normally less than 13mmHg.

• An increase in CPP is usually the result of an increase in MAP, the contribution made by reducing ICP is minimal, apart from in pathological states when ICP is very high

• In a normal brain, despite the potential for changes in MAP (sleep, exercise etc.), CBF remains constant over a wide range of CPPs.

This is achieved by a process called autoregulation

2) THE RADIUS OF CEREBRAL BLOOD VESSELS

This is regulated by four primary factors:1. Cerebral metabolism2. Carbon dioxide and oxygen3. Autoregulation4. Other factors

CEREBRAL METABOLISM• Local or global increases in metabolic demand are

met rapidly by an increase in CBF and substrate delivery and vice versa

• These changes are controlled by several vasoactive metabolic mediators including hydrogen ions, potassium, CO2, adenosine, glycolytic and phospholipid metabolites and NO

CARBON DIOXIDE AND OXYGEN• At normotension, the relationship between partial

pressure of carbon dioxide in arterial blood (PaCO2) and CBF is almost linear and at a PaCO2 80mmHg CBF is approximately doubled.

• No further increase in flow is possible at this point as the arterioles are maximally dilated.

• Conversely at 20mmHg flow is almost halved and again cannot fall further as the arterioles are maximally vasoconstricted

• Arteriolar tone has an important influence on how PaCO2 affects CBF.

• Moderate hypotension impairs the response of the cerebral circulation to changes in PaCO2, and severe hypotension abolishes it altogether

• Oxygen has little effect on the radius of blood vessels at partial pressures used clinically

• Blood flow increases once PaO2 drops below 50mmHg.

• Hypoxia acts directly on cerebral tissue to promote the release of adenosine, and in some cases prostanoids that contribute significantly to cerebral vasodilatation.

• Hypoxia also acts directly on cerebrovascular smooth muscle to produce hyperpolarisation and reduce calcium uptake, both mechanisms enhancing vasodilatation.

• In adults under normal circumstances (ICP <10mmHg), CPP and MAP are very similar and

CBF remains constant with a CPP of 60-160mmHg

• The higher the ICP the more CPP deviates from MAP.

• Autoregulation is thought to be a myogenic mechanism, whereby vascular smooth muscle

constricts in response to an increase in wall tension and to relax to a decrease in wall tension

AUTOREGULATION

• At the lower limit of autoregulation, cerebral vasodilation is maximal, and below this level the vessels collapse and CBF falls passively with falls in MAP.

• At the upper limit, vasoconstriction is maximal and beyond this the elevated intraluminal pressure may force the vessels to dilate, leading to an increase in CBF and damage to the blood-brain-barrier.

OTHER FACTORS

• Blood viscosity: As viscosity falls, CBF increases. However, there will also be a reduction in oxygen-carrying capacity of the blood

• Temperature: CMRO2 decreases by 7% for each 1°C fall in body temperature and is paralleled by a similar reduction in CBF.

• Drugs: Cerebral metabolism can be manipulated (reduced) and consequently CBF ,cerebral blood volume and ICP is reduced.

Clinical implications

• Hyperventilation reduces the PaCO2 and causes vasoconstriction of the cerebral vessels and therefore reduces cerebral blood volume and ICP in patients with raised intracranial pressure, for example after traumatic brain injury.

• However if PaCO2 is reduced too much, it may reduce CBF to the point of causing or worsening cerebral ischaemia

• PaCO2 is therefore best maintained at level of 35-40mmHg to prevent raising ICP. This reactivity may be lost in areas of the brain that are injured.

Clinical implications

• Pressure autoregulation can be impaired in many pathological conditions including patients with a brain tumour, subarachnoid haemorrhage, stroke, or head injury.

• The reduction in CMRO2 with decrease in temperature is the factor that allows patients to withstand prolonged periods of reduced CBF without ischemic damage for example during cardiopulmonary bypass (Hypothermia helps to reduce excitatory neurotransmitter release, important to central nervous system protection)

Clinical implications

• Infusions of the barbiturate thiopentone are used to reduce cerebral metabolic rate and so decrease high ICP after head injury

• Anaesthetic drugs (volatile agents) cause a reduction in the tension of cerebral vascular smooth muscle resulting in vasodilatation and an increase in CBF(minimal with isoflurane)

•Arterial insufficiency due to thromboembolism, hemodynamic compromise, or a combination of these factors may lead to the recruitment of collaterals

•The arterial anatomy of the collateral circulation includes extracranial sources of cerebral blood flow and intracranial routes of ancillary perfusion

COLLATERALS IN CEREBRAL CIRCULATION

• It is commonly divided into primary or secondary collateral pathways

• Primary collaterals include the arterial segments of the circle of Willis,

whereas, the ophthalmic artery and leptomeningeal

vessels constitute secondary collaterals

• Interhemispheric blood flow across the anterior communicating artery and reversal of flow in the proximal anterior cerebral artery provide collateral support in the anterior portion of the circle of Willis

• Additional interhemispheric collaterals include the proximal posterior cerebral arteries at the posterior aspect of the circle of Willis.

• The posterior communicating arteries may supply collateral blood flow in either direction between the anterior and posterior circulations

• Anatomic studies note absence of the anterior communicating artery in 1% of subjects, absence or hypoplasia of the proximal anterior cerebral artery in 10%, and absence or hypoplasia of either posterior communicating artery in 30%

• The number and size of these anastomotic vessels are greatest between anterior and middle cerebral arteries, with smaller and fewer connections between middle and posterior cerebral arteries and even less prominent terminal anastomoses between posterior and anterior cerebral arteries.

• Distal branches of the major cerebellar arteries similarly provide collateral links across the vertebral and basilar segments of the posterior circulation

• Leptomeningeal and dural arteriolar anastomoses with cortical vessels further enhance the collateral circulation.

• Other collateral routes less commonly encountered in acute stroke are tectal plexus joining supratentorial branches of the posterior cerebral artery with infratentorial branches of the superior cerebellar artery

And the orbital plexus linking the ophthalmic artery with facial, middle meningeal, maxillary, and ethmoidal arteries

Extracranial arterial collateral circulation. Anastomoses from the facial (a), maxillary (b), and middle meningeal (c) arteries to the ophthalmic artery and dural arteriolar anastomoses from the middle meningeal artery (d) and occipital artery through the mastoid foramen (e) and parietal foramen (f)

Intracranial arterial collateral circulation in lateral (A) and frontal (B) views. Posterior communicating artery (a); leptomeningeal anastomoses between anterior and middle cerebral arteries (b) and between posterior and middle cerebral arteries (c); tectal plexus between posterior cerebral and superior cerebellar arteries (d); anastomoses of distal cerebellararteries (e); and anterior communicating artery (f)

• Moyamoya syndrome represents the ultimate example of excessive collateralization over a chronic time course, recruiting a wide range of leptomeningeal and deep parenchymal vessels

VENOUS COLLATERALS

• Venous collaterals augment drainage of cerebral blood flow when principal routes are occluded or venous hypertension ensues

• The anatomy of venous collateral circulation is highly variable, allowing diversion of blood through numerous routes when exiting the brain

Venous collateral circulation. Pterygoid plexus (a), deep middle cerebral vein (b), inferior petrosal sinus and basilar plexus (c), superior petrosal sinus (d), anastomotic vein of Trolard (e), anastomotic vein of Labbé (f), condyloid emissary vein (g), mastoid emissary vein (h), parietal emissary vein (i), and occipital emissary vein (j).

• Primary collaterals provide immediate diversion of cerebral blood flow to ischemic regions through existing anastomoses

• Secondary collaterals such as leptomeningeal anastomoses may be anatomically present, although enhanced capacity of these alternative routes for cerebral blood flow likely requires time to develop.

• Specific pathophysiological factors leading to the development of collaterals are uncertain, diminished blood pressure in downstream vessels is considered a critical variable

• Focal cerebral ischemia, a critical variable may lead to the secretion of angiogenic peptides with some potential for collateral formation

Factors determining functionality and patency of LMCs

• The incipient development of collaterals does not guarantee their persistence

• The efficacy of LMCs also depends upon age, duration of ischemia, and associated comorbidities.

• Hypertension may impair collateral development in the setting of carotid occlusion and therefore increase stroke risk.

• Chronic hypoperfusion due to arterial flow restrictions such as extracranial carotid or intracranial steno-occlusive disease promotes collateral development

• Hemodynamic fluctuations may influence the endurance of collaterals, possibly threatening cerebral blood flow.

• Similarly, distal fragmentation of a thrombus within the parent vessel may occlude distal branches supplying retrograde collateral flow from cortical arteries.

• The collateral circulation is also a critical determinant of Cerebral Perfusion Pressure in acute cerebral ischemia

• The hemodynamic effects of the collateral circulation may be important in maintaining perfusion to penumbral regions

• Deep parenchymal collaterals within the striatum may be less effective, allowing undissolved thrombus to be retained for longer periods of time

• These factors may be involved in the development of large subcortical infarcts with cortical sparing of the basal ganglia in middle cerebral artery occlusion and limited thalamic infarction in posterior cerebral artery occlusion

Diagnostic Evaluation• Numerous techniques, including xenon-

enhanced CT, SPECT, PET, CT perfusion, and MR perfusion, assess cerebral blood flow and thereby infer the status of collaterals

• CONVENTIONAL ANGIOGRAPHY remains the gold standard for collateral flow evaluation, given its high spatial resolution and the possibility of dynamic evaluation

Collateral bloodflow distal to an occlusion of the middle cerebral artery manifest as vascular enhancement (A, arrow) and FLAIR vascular hyperintensity (B, arrow)

Left ICA injection early (A) and late arterial phase.The left MCA is occluded. There is no filling of the vascular territory. Leptomeningeal collaterals (arrows) are now filling the MCA territory. The respective supply territories of the vessels are marked

Leptomeningeal collaterals (LMCs) also known as pial collaterals, are small arterial connections joining the terminal cortical branches of major (middle, anterior and posterior) cerebral arteries along the surface of the brain

• It remains dormant under normal conditions when blood flow from all major cerebral arteries is not impeded, but are recruited when one major artery is either chronically or acutely occluded.

• Their existence was first documented by Heubner in 1874. While trying to delineate the arterial territories in cadaveric brains, he observed that the injected product diffused in other arterial territories in the absence of Willis circle connections

• The presence of LMCs has also been associated with better outcomes, reduced infarct size, and faster recanalization

Ringelstein EB, Biniek R, Weiller C et al. Type and extent of hemispheric brain infarctions and clinical outcome in early and delayed middle cerebral artery recanalization. Neurology. 1992;42:289-298

• In PROACT II trial investigators analysed pial collateral formation on angiography and categorized them as full, partial,or none and found that presence of good collaterals influences NIHSS score at initial presentation and infarct volume on 24-hour CT scan in patients with MCA occlusion

Roberts HC, Dillon WP, Furlan AJ et al. Computed tomographic findings in patients undergoing intra-arterial thrombolysis for acute ischemic stroke due to middle cerebral artery occlusion: Results from the PROACT II trial. Stroke. 2002;33:1557-1565

• Christoforidis et al22(2005) reviewed 65 patients retrospectively who underwent thrombolysis for acute ischemic stroke and reported that LMC formation before thrombolytic treatment predicted infarct volume and clinical outcome independent of other predictive factors

Christoforidis GA, Mohammad Y, Kehagias D et al. Angiographic assessment of pial collaterals as a prognostic indicator following intra-arterial thrombolysis for acute ischemic stroke. AJNR Am J Neuroradiol. 2005;26:1789-1797

• The presence of collateral sparing of penumbral region may also because of enhanced blood flow and retrograde collateral filling which allow thrombolytic access to distal aspects of the clot

Caplan LR, Hennerici M. Impaired clearance of emboli (washout) is an important link between hypoperfusion, embolism, and ischemic stroke. Arch Neurol. 1998;55:1475–1482

• The presence of leptomeningeal collaterals is also predictive of improved long-term clinical outcome in patients treated with and without thrombolysis for middle cerebral artery occlusion

• In chronic ischemic conditions, such as moyamoya syndrome and steno-occlusive carotid disease, adequacy of collaterals may be used to guide therapy

• The presence of collaterals on conventional angiography has been associated with a lower risk of hemispheric stroke and transient cerebral ischemia in patients with carotid stenosis

Henderson RD et al for the North American Symptomatic Carotid Endarterectomy Trial (NASCET) Group. Angiographically defined collateral circulation and risk of stroke in patients with severe carotid artery stenosis. Stroke. 2000;31:128–132

• Hypertension may impair collateral development in the setting of carotid occlusion and therefore increase stroke risk

• Several papers have found that the pre-morbid use of statins is associated with better collateral flow in patients with acute ischemic stroke

Hedera P et al. Stroke risk factors and development of collateral flow in carotid occlusive disease. Acta Neurol Scand. 1998;98:182–186

Lee M.J. et al. Role of statin in atrial fibrillation-related stroke: an angiographic study for collateral flow. Cerebrovascular diseases (Basel, Switzerland) 2014; 37:77-84.

Sargento-Freitas J et al. Preferential effect of premorbid statins on atherothrombotic strokes through collateral circulation enhancement. European neurology2012; 68:171-176

• Additionally, hemodynamic factors like arterial blood pressure, central venous pressure, intracranial pressure and distal micro-emboli can alter the functionality of the collateral flow

Liebeskind D.S. Collateral therapeutics for cerebral ischemia. Expert review of neurotherapeutics 2004; 4:255-265.

Two separate pathological processes have been identified after an arterial occlusion

1)Arteriogenesisis(development of functional collateral flow from pre-existing arterial anastomoses)

• This process starts immediately after the arterial occlusion

• Opening of the anastomoses induced by mechanical forces and involves endothelial cell activation, infiltration of inflammatory cells and subsequent inflammatory response leading to structural remodeling and increased diameter

2. Angiogenesisis • A much slower process that involves the proliferation of

endothelial cells and formation of new vessel

Temporal profile of development of LMCs in acute ischemic stroke

• Yamashita et al 29 (1996) used Xenon enhanced CT rCBF measurement with acetazolamide challenge in patients with ICA stenosis and demonstrated that LMCs develop to some extent immediately after occlusion and continue to

develop for some time

• The presence of secondary collateral pathways is usually a marker of impaired cerebral hemodynamics.

• Secondary collateral pathways that require time to develop are presumed to be recruited once primary collaterals at the circle of Willis are inadequate

By understanding the role of LMA in acute stroke, two avenues of research are opened.

• First, evaluation of collateral flow in the acute setting can improve the clinical results of revascularization treatments by helping identify patients who benefit best and possibly extending the currently accepted time window

• Second, a new generation of stroke treatments can be developed, with the aim to improve collateral flow.

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