Neurovascular Disorders I PDF - 3B Aug 2023

Reynaldo B. Sta. Mina, Jr., M.D. NEUROVASCULAR DISORDERS I MED 7721 (CLINICAL NEUROLOGY) *This is the first of a two-part presentation (Neurovascular Disorders I and II).  CONTENTS ▪ Learning Objectives ▪ Clinico-Anatomic Correlati...

Reynaldo B. Sta. Mina, Jr., M.D. NEUROVASCULAR DISORDERS I MED 7721 (CLINICAL NEUROLOGY) *This is the first of a two-part presentation (Neurovascular Disorders I and II).  CONTENTS ▪ Learning Objectives ▪ Clinico-Anatomic Correlation  Anterior Cerebral Artery ▪ Stroke and Its Features  Middle Cerebral Artery ▪ Epidemiology  Internal Carotid Artery ▪ Risk Factors for Stroke  Posterior Cerebral Artery  Basilar Artery ▪ Acute Onset  Long Circumferential Vertebro-Basilar Branches ▪ Focal Involvement of the CNS  Long Penetrating Paramedian Vertebro-Basilar Branches  Short Basal Vertebro-Basilar Branches ▪ Lack of Rapid Resolution  Lacunar Infarction ▪ Vascular Cause ▪ Etiology  Anterior Circulation  Vascular Disorders  Posterior Circulation  Cardiac Disorders ▪ Ischemia  Hematologic Disorders  Cryptogenic Stroke ▪ Thrombosis ▪ YouTube Video Links ▪ Embolism ▪ Clinical Cases ▪ Pathophysiology  Injury Mechanisms ▪ Main Reference  Survival and Repair Mechanisms ▪ Related Readings ▪ Pathology  Large Artery Occlusion  Small Artery Occlusion *Clinical findings, Investigative studies, Differential diagnosis, Prevention, Treatment, Complications, Rehabilitation, Prognosis, as well as Intracerebral hemorrhage are discussed in Neurovascular Disorders II, a separate slide presentation.  LEARNING OBJECTIVES ▪ To learn what stroke is as a ▪ To understand the pathology neurologic disorder, and its key and pathophysiology of stroke, features specifically that of ischemia, thrombosis and embolism ▪ To understand the epidemiology of stroke including the etiologies ▪ To understand the clinico- and the risk factors for it anatomic correlations related to stroke, specifically the different arterial territories and the ▪ To review the anatomy of the syndromes they cause when cerebral circulation and its obstructed or ruptured relationship to the important parts of the brain WHAT IS STROKE? A neurologic syndrome with four key features: ▪ ACUTE ONSET ▪ FOCAL INVOLVEMENT OF CNS ▪ LACK OF RAPID RESOLUTION ▪ VASCULAR ETIOLOGY ACUTE ONSET ▪ Abrupt or sudden ▪ Neurologic deficits may be  maximal at onset  may be progressive (over seconds to hours, or occasionally days) ▪ STROKE IN EVOLUTION (PROGRESSING STROKE)  Actively progressing as a direct consequence of the underlying vascular disorder (but not because of associated cerebral edema) or has done so in recent minutes. FOCAL INVOLVEMENT OF THE CNS ▪ Focal symptoms and signs ▪ Correlate with the area of the brain supplied by the affected blood vessel. ▪ ISCHEMIC STROKE  More predictable pattern because affected blood vessel interferes with neurologic functions dependent on that region and producing a more or less stereotyped pattern of deficits. ▪ HEMORRHAGIC STROKE  Less predictable pattern because complications such as increased intracranial pressure, cerebral edema, compression of brain tissue and blood vessels, or dispersion of blood through the subarachnoid space or cerebral ventricles can impair brain function at sites remote from the hemorrhage. ▪ GLOBAL CEREBRAL ISCHEMIA (usually from cardiac arrest) and SUBARACHNOID HEMORRHAGE  More diffuse effect  Produce global cerebral dysfunction  Term “stroke” is not usually applied ▪ HISTORY AND NEURO EXAM  Help to localize the lesion  Laterality: Left or right  Anterior or posterior circulation LACK OF RAPID RESOLUTION ▪ Neurologic deficits persist are usually permanent. ▪ In contrast, some ischemic events may temporary.  TIA (TRANSIENT ISCHEMIC ATTACK)  Symptoms and signs resolve completely after brief periods (usually within 1 hour) without evidence of cerebral infarction  RECURRENT TIA  STEREOTYPIC  Identical clinical features  Caused by thrombosis or embolism arising from the same site within the cerebral circulation.  NONSTEREOTYPIC  Differ in character from event to event  Recurrent emboli from distant (eg, cardiac) or multiple sites. VASCULAR ETIOLOGY ▪ 90% - ISCHEMIA (due to occlusion)  35% large artery occlusion  25% small artery occlusion  20% cardiac embolism  15% unknown causes (cryptogenic)  5% other processes (eg inflammation) ▪ 10% - HEMORRHAGE (due to rupture) ▪ May be difficult to distinguish the two by history and neurologic examination, but CT scan or MRI permits definitive diagnosis. RISK FACTORS FOR STROKE  ARTERIAL SUPPLY OF THE BRAIN (Anterior and Posterior Circulation) ARTERIAL TERRITORIES OF THE BRAIN  ARTERIAL TERRITORIES (Lateral, Medial and Inferior Aspects)  ANTERIOR (CAROTID) CIRCULATION ▪ Consists of the internal carotid artery and its branches:  Anterior choroidal  Anterior cerebral (ACA)  Middle cerebral artery (MCA)  Posterior communicating artery  Other branches (ophthalmic artery, superior and inferior hypophyseal arteries, etc) ▪ Supplies most of the cerebral cortex and subcortical white matter, basal ganglia, and internal capsule. ANTERIOR CEREBRAL ARTERY (ACA) MIDDLE CEREBRAL ARTERY (MCA)  POSTERIOR (VERTEBROBASILAR) CIRCULATION ▪ Supplies the brainstem, cerebellum, thalamus, and portions of the occipital and temporal lobes. ▪ Consists of the paired vertebral arteries, the basilar artery, and their branches:  Posterior inferior cerebellar artery (PICA)  Anterior inferior cerebellar artery (AICA)  Superior cerebellar artery (SCA)  Posterior cerebral artery (PCA) – gives off thalamoperforate and thalamogeniculate branches.  CIRCLE OF WILLIS MAJOR CEREBRAL ARTERIES The anterior and posterior cerebral circulations arise anterior and posterior to the posterior communicating arteries, respectively. CIRCLE OF WILLIS ANTERIIOR COMMUNICATING (ACom) ANTERIOR CEREBRAL (ACA) INTERNAL CAROTID (ICA) POSTERIOR COMMUNICATING (Pcom) POSTERIOR CEREBRAL (PCA) CIRCLE OF WILLIS  ARTERIAL SUPPLY OF THE MIDBRAIN BASILAR ARTERY 1. PARAMEDIAN BRANCHES – supply the oculomotor (III) nucleus and red nucleus (RN) 2. POSTERIOR CEREBRAL ARTERY - a larger branch that courses laterally around the midbrain on each side, giving off: A. BASAL BRANCH - supplies the cerebral peduncle (CP; also called crus cerebri) B. DORSOLATERAL BRANCH - supplies the spinothalamic tract (ST) and medial lemniscus (ML).  ARTERIAL SUPPLY OF THE PONS BASILAR ARTERY 1. PARAMEDIAN BRANCHES - supply the abducens (VI) nucleus and medial lemniscus (ML). 2. ANTERIOR INFERIOR CEREBELLAR ARTERY A. BASAL BRANCH – supplies the descending motor pathways in the basis pontis (BP) B. DORSOLATERAL BRANCH – supplies the trigeminal (V) nucleus, vestibular (VIII) nucleus, and spinothalamic tract (ST)  ARTERIAL SUPPLY OF THE MEDULLA VERTEBRAL ARTERY 1. PARAMEDIAN BRANCHES – supply the descending motor pathways in the pyramid (P), the medial lemniscus (ML), and the hypoglossal (XII) nucleus. 2. POSTERIOR INFERIOR CEREBELLAR ARTERY A. BASAL BRANCH – supplies the olivary nuclei (ON) B. DORSOLATERAL BRANCH - supplies the trigeminal (V) nucleus, vestibular (VIII) nucleus, and spinothalamic tract (ST)  ISCHEMIA ▪ Deprives neurons, glia, and vascular cells of glucose and oxygen. ▪ Leads to death of brain tissue (INFARCTION) within the ischemic CORE, where flow is typically less than 20% of normal. ▪ MILD:  Cardiac arrest with rapid reperfusion  Selective vulnerability of certain neuronal populations ▪ MORE SEVERE:  Selective neuronal necrosis  Most or all neurons die but glia and vascular cells are preserved. ▪ COMPLETE/PERMANENT:  Stroke without reperfusion  Pannecrosis → affecting all cell types and resulting in chronic cavitary lesions. ▪ INCOMPLETE:  20-40% of normal blood flow  As in the ischemic border zone or penumbra  Cell damage is POTENTIALLY REVERSIBLE and cell survival may be prolonged. However, unless blood flow is restored by recanalization of the occluded vessel or collateral circulation from other vessels, reversibly damaged cells begin to die as well, and the infarct expands. ▪ DEATH OF PENUMBRAL TISSUE is associated with a worse clinical outcome. ▪ BRAIN EDEMA is another determinant of stroke outcome. ▪ Ischemia leads to VASOGENIC EDEMA as fluid leaks from the intravascular compartment into brain parenchyma. ▪ Edema is usually MAXIMAL approximately 2 to 3 DAYS after stroke and may be sufficiently severe that it produces a MASS EFFECT that causes HERNIATION (displacement of brain tissue between intracranial compartments) and death. ▪ Two pathogenetic mechanisms can produce ischemic stroke—THOMBOSIS and EMBOLISM. However, the distinction is often difficult or even impossible to make on clinical grounds.  THROMBOSIS ▪ Occlusion of  Large cerebral arteries (especially the internal carotid, middle cerebral, or basilar)  Small penetrating arteries (as in lacunar stroke)  Cerebral veins  Venous sinuses ▪ Symptoms typically evolve over minutes to hours. ▪ Thrombotic strokes are preceded by TIAs, which tend to produce similar symptoms because they affect the same territory.  EMBOLISM ▪ Produces stroke when cerebral arteries are occluded by the distal passage of clot from the heart, aortic arch, or large cerebral arteries.  EMBOLI IN THE ANTERIOR CIRCULATION most often occlude the middle cerebral artery or its branches, because most hemispheric blood flow is through this vessel.  EMBOLI IN THE POSTERIOR CIRCULATION usually lodge at the apex of the basilar artery or in the posterior cerebral arteries. ▪ Embolic strokes often produce neurologic deficits that are MAXIMAL AT ONSET. ▪ When TIAs precede embolic strokes, especially those arising from a cardiac source, symptoms typically vary between attacks because different vascular territories are affected. PATHOPHYSIOLOGY OF FOCAL CEREBRAL ISCHEMIA ▪ Complex ▪ Evolves over time ▪ Affects the brain non-uniformly; and targets multiple cell types. ▪ Several potentially important underlying mechanisms, some of which operate early and others later in the course of stroke. ▪ Some mechanisms contribute to ischemic injury, whereas others promote tissue survival or repair.  INJURY MECHANISMS ENERGY FAILURE ▪ Neurons rely on oxidative metabolism to generate adenosine triphosphate (ATP) for their high energy demands. ▪ Reduction of blood flow interferes with the delivery of two key substrates for this process—oxygen and glucose—causing ATP levels to fall. ▪ Cells can compensate to a limited extent by generating ATP via glycolysis but, without prompt reperfusion, they cease to function and eventually die. ▪ Like other ischemic injury mechanisms, energy failure is most pronounced in the ischemic core and less so in the surrounding penumbra. ION GRADIENT FAILURE ▪ A major use of cellular energy is the maintenance of transmembrane ion gradients. ▪ With energy failure, these are dissipated. Na+/K+-ATPase, which accounts for the majority of neuronal energy expenditure and is responsible for maintaining high intracellular K+ concentrations, fails to do so. ▪ K+ leaks from cells and depolarizes adjacent cells, activating voltage-gated ion channels and neurotransmitter release. ▪ Extracellular K+ and neurotransmitter glutamate trigger cortical spreading depression, leading to further neuron and astrocyte depolarization. ▪ This consumes additional energy and may extend the infarct. CALCIUM DYSREGULATION ▪ Intracellular Ca2+ is normally maintained at low levels, but ischemic elevation of extracellular K+ causes membrane depolarization and triggers influx of extracellular Ca2+ into neurons. ▪ Catabolic enzymes are activated, mitochondrial function is compromised, and cell death pathways are mobilized. EXCITOTOXICITY AGAINST NEURONS ▪ Excitotoxicity refers to the neurotoxic effects of excitatory neurotransmitters, especially glutamate. ▪ Ischemia promotes excitotoxicity by stimulating neuronal glutamate release, reversing astrocytic glutamate uptake, and activating glutamate receptor- coupled ion channels. ▪ Influx of Ca2+ through these channels contributes to Ca2+ dysregulation and activates neuronal nitric oxide synthase, generating potentially neurotoxic nitric oxide. OXIDATIVE & NITROSATIVE INJURY ▪ Some toxic effects of ischemia are mediated by highly reactive oxidative and nitrosative compounds, including superoxide and nitric oxide, which act primarily during the reperfusion phase that follows ischemia. ▪ Their effects include inhibiting mitochondrial enzymes and function, damaging DNA, activating ion channels, causing covalent modification of proteins, and triggering cell death pathways. CELL DEATH CASCADES ▪ Ischemic cell death occurs most rapidly in the infarct core and more slowly in the penumbra and during reperfusion. ▪ Rapid cell death involves necrosis, in which cells and organelles swell, membranes rupture, and cellular contents spill into the extracellular space, whereas more delayed (programmed) cell death (eg, apoptosis) predominates in the penumbra and during reperfusion. INFLAMMATION ▪ Cerebral ischemia triggers an inflammatory response that involves both resident and blood-borne cells of the innate immune system. ▪ Resident immune cells include astrocytes and microglia, and blood-borne immune cells include neutrophils, lymphocytes, and monocytes. ▪ Adaptive immune responses emerge later in the course. ▪ Molecular mediators of ischemia-induced inflammation include adhesion molecules, cytokines, chemokines, and proteases. ▪ Although the early inflammatory response to ischemia exacerbates injury, subsequent inflammatory events may be neuroprotective or contribute to repair. SURVIVAL AND REPAIR MECHANISMS COLLATERAL CIRCULATION ▪ The FIRST LINE OF DEFENSE against ischemia is collateral circulation, which, if adequate, can bypass an arterial occlusion. ▪ The cerebral circulation contains numerous collateral pathways, accounting for the observation that patients with total occlusion of a major vessel are sometimes asymptomatic. ▪ However, this is not always the case, especially when occlusion is abrupt. ▪ Collateral routes for cerebral blood flow during arterial occlusion include the following:  Bilateral vertebral artery occlusion—anterior spinal artery  Common carotid artery occlusion—contralateral common carotid artery via ipsilateral external carotid artery or vertebral artery via ipsilateral occipital artery  Internal carotid artery occlusion—ipsilateral external carotid artery via ophthalmic artery or circle of Willis  Middle cerebral artery occlusion—ipsilateral anterior or posterior cerebral artery via leptomeningeal anastomoses INHIBITORY NEUROTRANSMITTERS ▪ Enhanced tonic inhibition mediated through extrasynaptic GABAA receptors may mitigate excitotoxic injury early in the course of stroke. ▪ However, persistent inhibition may impair recovery. TRANSCRIPTIONAL HYPOXIA RESPONSE ▪ Hypoxia activates transcription of proteins that promote cell survival and tissue recovery, including glycolytic enzymes, erythropoietin, and vascular endothelial growth factor. ▪ Other cytoprotective proteins induced after ischemia include antiapoptotic proteins, growth factors, and heat-shock proteins. NEUROGENESIS ▪ Cerebral ischemia stimulates neurogenesis and some new neurons migrate to ischemic brain regions. ▪ Here they may promote survival and repair by releasing growth factors, suppressing inflammation, or other effects. ANGIOGENESIS ▪ Ischemia also stimulates capillary sprouting to enhance local blood supply. ▪ The impact of this process (angiogenesis) in the acute phase of stroke is uncertain, but it may help to protect against subsequent ischemic episodes. ISCHEMIC TOLERANCE ▪ Ischemia may provide paradoxical protection against subsequent ischemia through ischemic tolerance, in which mild ischemia preconditions brain tissue and confers relative ischemia resistance. ▪ Ischemic tolerance involves extensive changes in gene expression and numerous molecular mediators. REPAIR MECHANISMS ▪ Most patients recover to some extent after stroke, reflecting a capacity for spontaneous post-ischemic repair and the brain’s innate plasticity. ▪ Plastic changes occur in the peri-infarct region and at remote sites, such as the contralateral cerebral hemisphere, and include changes in gene expression, increased neuronal excitability, axonal sprouting, synaptogenesis, somatotopic reorganization, and formation of new neuronal circuits.  PATHOLOGY LARGE ARTERY OCCLUSION ▪ On gross inspection, a recent infarct from large artery occlusion is a swollen, softened area of brain that usually involves both gray and white matter. ▪ Microscopy shows acute ischemic changes in neurons (shrinkage, microvacuolization, dark staining), destruction of glial cells, necrosis of small blood vessels, disruption of nerve axons and myelin, and accumulation of interstitial fluid. ▪ Perivascular hemorrhages may be observed. ▪ Depending on the interval between infarction and death, cerebral edema may also be present. ▪ Edema is maximal during the first 2-3 days after stroke and can cause subfalcine herniation of the cingulate gyrus across the midline or of the temporal lobe below the tentorium (transtentorial or uncal). In the chronic phase, the infarct site appears as a cavitary lesion.  Large vessel (left middle cerebral artery) ischemic stroke in the acute and chronic phases. Acutely, there is discoloration of the Over time, necrotic brain tissue gives way ischemic tissue, edema, mass effect, and, in to a cavitary lesion. this case, herniation of the cingulate gyrus across the midline. SMALL ARTERY OCCLUSION ▪ Infarcts from small artery occlusion rarely cause death, so only chronic lesions are usually found at autopsy. ▪ These include lacunes, or small cavities up to ~15 mm in diameter, usually located in subcortical white (eg, internal capsule) or deep gray (eg, basal ganglia or thalamus) matter; white matter (including periventricular) lesions showing punctate or confluent myelin rarefaction, gliosis, and axonal loss; and microbleeds. ▪ Small vessel occlusion may be associated with atherosclerosis, lipohyalinosis (collagenous thickening and inflammation of the vessel wall), or fibrinoid necrosis (vessel-wall destruction with perivascular inflammation). CLINICO-ANATOMIC CORRELATION ▪ Infarction in the distribution of different cerebral arteries produces distinctive clinical syndromes, which can facilitate anatomic and etiologic diagnosis and help guide treatment. SIGNS AND SYMPTOMS OF HEMISPHERIC DYSFUNCTION  Aphasia  Apraxia  Loss of ability to execute or carry out skilled movement and gestures, despite having the physical ability and desire to perform them  Agnosia  Inability to process sensory information.  Often there is a loss of ability to recognize objects, persons, sounds, shapes, or smells while the specific sense is not defective nor is there any significant memory loss. ▪ Hemiparesis, hemisensory disturbances, and visual field defects (but these can also occur with posterior circulation strokes). SIGNS AND SYMPTOMS OF BRAINSTEM AND/OR CEREBELLAR DYSFUNCTION  Coma or altered consciousness  Drop attacks (sudden collapse without loss of consciousness)  Vertigo  Nausea and vomiting  Cranial nerve palsies  Ataxia  Crossed sensorimotor deficits that affect the face on one side of the body and the limbs on the other. ▪ Hemiparesis, hemisensory disturbances, and visual field deficits also occur (but these can also occur with anterior circulation strokes). CLINICAL SYNDROMES  ANTERIOR CEREBRAL ARTERY ANATOMY ▪ Supplies:  Parasagittal cerebral cortex, which includes portions of motor and sensory cortex related to the contralateral leg  Bladder inhibitory or micturition center  Anterior corpus callosum. CLINICAL SYNDROME ▪ Contralateral paralysis and sensory loss exclusively or primarily affecting the leg and foot. ▪ Other possible findings:  Abulia (apathy)  Disconnection syndromes such as the “alien hand” (involuntary performance of complex motor activity)  Transcortical expressive aphasia  Urinary incontinence  MIDDLE CEREBRAL ARTERY ANATOMY ▪ Supplies most of the remainder of the cerebral hemisphere (cortical branches) and deep subcortical structures. ▪ Cortical branches:  SUPERIOR DIVISION supplies:  Motor and sensory representation of the face, hand, and arm  Broca’s area of the dominant hemisphere  INFERIOR DIVISION supplies:  Visual radiations  Visual cortex related to macular vision  Wernicke’s area of the dominant hemisphere ▪ LENTICULOSTRIATE BRANCHES of the most proximal portion (stem) supply:  Basal ganglia  Motor fibers to the face, hand, arm, and leg as they descend in the genu and posterior limb of the internal capsule. Arterial supply of the primary motor and sensory cortex (lateral and coronal views). The middle cerebral artery supplies areas related to face and upper limb function, whereas the anterior cerebral artery supplies areas related to lower limb function. This explains why middle cerebral artery strokes affect the face and arm most severely, whereas anterior cerebral artery strokes affect the leg. ANATOMIC BASIS OF MIDDLE CEREBRAL ARTERY SYNDROMES Stroke in the distribution of the middle cerebral artery causes: HEMIPARESIS affecting primarily face and arm (due to involvement of the primary motor area) HEMISENSORY DEFICIT affecting primarily face and arm (due to involvement of the primary sensory area) GAZE PREFERENCE toward the affected hemisphere (due to involvement of the frontal eye field) APHASIA if the dominant hemisphere is affected (due to involvement of Broca area, Wernicke area, or both) HEMIANOPIA (due to involvement of the optic radiations leading to the primary visual area  MIDDLE CEREBRAL ARTERY SYNDROMES ▪ SUPERIOR DIVISION STROKE  Contralateral hemiparesis that affects the face, hand, and arm but spares the leg  Contralateral hemisensory deficit in the same distribution  No homonymous hemianopia  If the dominant hemisphere is involved, there is Broca’s (expressive) aphasia, which is characterized by impaired language expression with intact comprehension. ▪ INFERIOR DIVISION STROKE  Contralateral homonymous hemianopia that may be denser inferiorly  Impaired cortical sensory functions (eg, agraphesthesia and astereognosis) on the contralateral side of the body  Disorders of spatial thought (eg, anosognosia [unawareness of deficit], neglect of the contralateral limbs and contralateral side of external space, dressing apraxia, and constructional apraxia).  If the dominant hemisphere is involved, Wernicke’s (receptive) aphasia occurs and is manifested by impaired comprehension and fluent but often nonsensical speech.  With involvement of the nondominant hemisphere, an acute confusional state may occur. ▪ OCCLUSION AT THE BIRUFCATION OF MIDDLE CEREBRAL ARTERY  Combines the features of superior and inferior division stroke  Contralateral hemiparesis and hemisensory deficit involving the face and arm more than leg  Homonymous hemianopia  If the dominant hemisphere is affected, global (combined expressive and receptive) aphasia. ▪ OCCLUSION AT THE STEM OF THE MIDDLE CEREBRAL ARTERY  Occurs proximal to the origin of the lenticulostriate branches  Clinical syndrome similar to that seen after occlusion at the trifurcation.  Involvement of the internal capsule causes paralysis of the contralateral leg, so hemiplegia and sensory loss affect the face, hand, arm, and leg.  INTERNAL CAROTID ARTERY ANATOMY ▪ Arises at the bifurcation of the common carotid artery in the neck. ▪ In addition to the anterior and middle cerebral arteries, it also gives rise to the ophthalmic artery, which supplies the retina. CLINICAL SYNDROME ▪ Occlusion may be asymptomatic, or cause strokes of highly variable severity, depending on the adequacy of collateral circulation. ▪ Symptomatic occlusion results in a syndrome similar to that of middle cerebral artery stroke (contralateral hemiplegia, hemisensory deficit, and homonymous hemianopia, together with aphasia if the dominant hemisphere is involved). ▪ Monocular blindness is also common. ▪ Transient monocular blindness is also called “amarausis fugax.”  POSTERIOR CEREBRAL ARTERY ANATOMY ▪ Arises from the tip of the basilar artery ▪ Supplies:  Occipital cerebral cortex  Medial temporal lobes  Thalamus  Rostral midbrain  Posterior corpus callosum ▪ Emboli in the basilar artery tend to lodge at its apex and occlude one or both posterior cerebral arteries; subsequent fragmentation can produce asymmetric or patchy posterior cerebral artery infarction. CLINICAL SYNDROME ▪ Occlusion produces homonymous hemianopia affecting the contralateral visual field, except that macular vision may be spared. ▪ In contrast to visual field defects from infarction in the middle cerebral artery territory, those caused by posterior cerebral artery occlusion may be denser superiorly. ▪ With occlusion near the origin of the posterior cerebral artery at the level of the midbrain, ocular abnormalities may occur:  Vertical gaze palsy  Oculomotor (III) nerve palsy  Internuclear ophthalmoplegia  Vertical skew deviation of the eyes ▪ Involvement of the occipital lobe of the dominant hemisphere may cause:  Anomic aphasia (difficulty in naming objects)  Alexia without agraphia (inability to read without impairment of writing)  Visual agnosia (This is failure to identify objects presented in the left side of the visual field, caused by a lesion of the corpus callosum that disconnects the right visual cortex from language areas of the left hemisphere.  Bilateral posterior cerebral artery infarction may result in:  Cortical blindness  Memory impairment (from temporal lobe involvement)  Inability to recognize familiar faces (prosopagnosia)  A variety of exotic visual and behavioral syndromes.  BASILAR ARTERY ANATOMY ▪ Arises from the junction of the paired vertebral arteries ▪ Courses over the ventral surface of the brainstem ▪ Terminates at the level of the midbrain, where it bifurcates to form the posterior cerebral arteries. ▪ Branches supply:  Occipital and medial temporal lobes  Medial thalamus  Brainstem  Cerebellum CLINICAL SYNDROMES ▪ Thrombosis  Occlusion of the basilar artery or both vertebral arteries is often incompatible with survival.  Causes bilateral symptoms and signs of brainstem and cerebellar dysfunction from involvement of multiple branch arteries.  Temporary occlusion of one or both vertebral arteries, leading to transient brainstem dysfunction, can also result from rotating the head in patients with cervical spondylosis.  Basilar thrombosis usually affects the proximal basilar artery, which supplies the pons.  Involvement of the dorsal pons (tegmentum) produces:  Unilateral or bilateral abducens (VI) nerve palsy  Impaired horizontal eye movement  Vertical nystagmus and ocular bobbing may be present  Pupils are constricted due to involvement of descending sympathetic pupillodilator fibers; but may be reactive.  Hemiplegia or quadriplegia is usually present  Coma is common.  CT or MRI brain scan will differentiate between basilar occlusion and pontine hemorrhage.  In some patients, the ventral pons (basis pontis) is infarcted and the tegmentum is spared.  Patients remain conscious but quadriplegic (LOCKED- IN SYNDROME).  Locked-in patients may be able to open or move their eyes vertically on command.  EEG further distinguishes the locked-in state from coma.  Stenosis or occlusion of the subclavian artery proximal to the origin of the vertebral artery can lead to the SUBCLAVIAN STEAL SYNDROME, in which blood is diverted from the vertebral artery into the distal subclavian artery with physical activity of the ipsilateral arm. The resulting brainstem ischemia can mimic basilar thrombosis; but is not predictive of stroke. ▪ Embolism  Emboli usually lodge at its apex.  Interruption of blood flow to the ascending reticular formation in the midbrain and thalamus produces immediate loss or impairment of consciousness.  Unilateral or bilateral oculomotor (III) nerve palsies are characteristic.  Hemiplegia or quadriplegia with decerebrate or decorticate posturing results from involvement of the cerebral peduncles in the midbrain. Thus, the TOP-OF- THE-BASILAR SYNDROME may be confused with midbrain damage caused by transtentorial uncal herniation.  Less commonly, an embolus may lodge more proximally, producing a syndrome indistinguishable from basilar thrombosis.  Smaller emboli may occlude the rostral basilar artery transiently before fragmenting and passing into one or both posterior cerebral arteries. In such cases, portions of the midbrain, thalamus, and temporal and occipital lobes can be infarcted. Patients may display visual (homonymous hemianopia, cortical blindness), visuomotor (impaired convergence, paralysis of upward or downward gaze, diplopia), and behavioral (especially confusion) abnormalities without prominent motor dysfunction. Sluggish pupillary responses are a helpful sign of midbrain involvement.  LONG CIRCUMFERENTIAL VERTEBRO-BASILAR BRANCHES ANATOMY ▪ The long circumferential branches of the vertebral and basilar arteries are:  Posterior inferior cerebellar artery (PICA)  Anterior inferior cerebellar artery (AICA)  Superior cerebellar artery (SCA) ▪ Supply the dorsolateral brainstem, including dorsolateral cranial nerve nuclei (V, VII, and VIII) and pathways entering and leaving the cerebellum in the cerebellar peduncles. CLINICAL SYNDROMES ▪ Occlusion of a circumferential branch produces infarction in the dorsolateral medulla or pons.  POSTERIOR INFERIOR CEREBELLAR ARTERY occlusion results in the LATERAL MEDULLARY (WALLENBERG) SYNDROME.  Ipsilateral cerebellar ataxia  Ipsilateral Horner syndrome  Ipsilateral facial sensory deficit  Contralateral impaired pain and temperature sensation  Nystagmus  Vertigo  Nausea or vomiting  Dysphagia, dysarthria and hiccup  Motor system is characteristically spared because of its ventral location in the brainstem.  ANTERIOR INFERIOR CEREBELLAR ARTERY occlusion  Leads to infarction of the lateral portion of the caudal pons and produces many of the same features.  Ipsilateral facial weakness, gaze palsy, deafness, and tinnitus are common.  Horner syndrome, dysphagia, dysarthria, and hiccup do not occur  SUPERIOR CEREBELLAR ARTERY occlusion  Causes lateral rostral pontine infarction  Resembles anterior inferior cerebellar artery lesions, but impaired optokinetic nystagmus (nystagmus evoked by tracking a moving object) or skew deviation (vertical dysconjugacy) of the eyes may occur, hearing is unaffected, and contralateral sensory loss may involve touch, vibration, and position as well as pain and temperature sense.  LONG PENETRATING PARAMEDIAN VERTEBROBASILAR BRANCHES ANATOMY ▪ Long penetrating paramedian arteries supply the medial brainstem, including the medial portion of the cerebral peduncle, sensory pathways, red nucleus, reticular formation, and midline cranial nerve nuclei (III, IV, VI, XII). CLINICAL SYNDROME ▪ Occlusion of a long penetrating artery causes paramedian infarction of the brainstem ▪ Results in contralateral hemiparesis if the cerebral peduncle is affected. ▪ Associated cranial nerve involvement depends on the level of the brainstem at which occlusion occurs.  Occlusion in the midbrain results in ipsilateral oculomotor (III) nerve palsy, which may be associated with contralateral tremor or ataxia from involvement of pathways connecting the red nucleus and cerebellum.  Occlusion in the pons results in ipsilateral abducens (VI) and facial (VII) nerve palsies  Occlusion in the medulla results in hypoglossal (XII) nerve involvement  SHORT BASAL VERTEBROBASILAR BRANCHES ANATOMY ▪ Short branches arising from the long circumferential arteries penetrate the ventral brainstem to supply the brainstem motor pathways. CLINICAL SYNDROME ▪ The most striking finding is contralateral hemiparesis caused by corticospinal tract involvement in the cerebral peduncle or basis pontis. ▪ Cranial nerves (eg, III, VI, VII) that emerge from the ventral surface of the brainstem may be affected as well, giving rise to ipsilateral cranial nerve palsies. Sites of thrombotic and embolic occlusions in the vertebro-basilar circulation. (A) Thrombotic occlusion of the basilar artery. (B) Thrombotic occlusion of both vertebral arteries. (C) Embolic occlusion at the apex of the basilar artery. (D) Embolic occlusion of both posterior cerebral arteries.  LACUNAR INFARCTION ANATOMY ▪ Small vessel occlusion affecting penetrating arteries deep in the brain may cause infarcts in the putamen or, less commonly, the thalamus, caudate nucleus, pons, posterior limb of the internal capsule, or other sites. These are referred to as lacunar infarcts or lacunes. CLINICAL SYNDROMES ▪ Many lacunar infarcts are not recognized clinically and are detected only as incidental findings on imaging studies or at autopsy. ▪ In other cases, however, they produce distinctive clinical syndromes. ▪ Lacunar strokes develop over hours to days. ▪ Headache is absent or minor ▪ Level of consciousness is unchanged. ▪ Hypertension and diabetes predispose to lacunar stroke, but these and other cardiovascular risk factors may be absent. ▪ Prognosis for recovery from a lacunar stroke is good, but recurrent stroke is common. ▪ Although a variety of deficits can be produced, there are four classic and distinctive lacunar syndromes. Arterial supply of deep cerebral structures involved in lacunar infarction. The basal ganglia (caudate nucleus, putamen, and globus pallidus; light blue) and internal capsule are supplied by the anterior circulation (lenticulostriate branches of the middle and the anterior choroidal artery). The thalamus (dark blue) is supplied by the posterior circulation (thalamo-perforate and thalamogeniculate branches of the posterior cerebral artery). Descending motor fibers to the face (F), arm (A), and leg (L) and ascending sensory fibers from face (f), arm (a), and leg (l) are shown in the posterior limb of the internal capsule.  LACUNAR SYNDROMES  PURE MOTOR HEMIPARESIS  Hemiparesis affecting the face, arm, and leg to a roughly equal extent, without associated disturbance of sensation, vision, or language.  Lacunes are usually located in the contralateral INTERNAL CAPSULE or PONS.  May also be caused by internal carotid or middle cerebral artery occlusion, subdural hematoma, or intracerebral mass lesions.  PURE SENSORY STROKE  Hemisensory loss, which may be associated with paresthesia  Results from lacunar infarction in the contralateral THALAMUS.  May be mimicked by occlusion of the posterior cerebral artery or by a small hemorrhage in the thalamus or midbrain. ▪ SENSORIMOTOR STROKE  A small, deep infarct causes this lacunar syndrome's symptoms, which include a motor and a sensory deficit, as the name implies.  Results from a lesion in the THALAMUS AND ADJACENT POSTERIOR INTERNAL CAPSULE and LATERAL PONS ▪ ATAXIC HEMIPARESIS  Sometimes called ipsilateral ataxia and crural (leg) paresis, comprises pure motor hemiparesis combined with ataxia of the hemiparetic side and usually affects the leg predominantly.  Result from a lesion in the contralateral PONS, INTERNAL CAPSULE, or SUBCORTICAL WHITE MATTER. ▪ DYSARTHRIA-CLUMSY HAND SYNDROME  Consists of dysarthria, facial weakness, dysphagia, and mild weakness and clumsiness of the hand on the side of facial involvement.  Lacunes are located in the contralateral PONS or INTERNAL CAPSULE.  Infarcts or small intracerebral hemorrhages at a variety of locations can produce a similar syndrome.  Premonitory TIAs are unusual. ETIOLOGY 1. Vascular disorders 2. Cardiac disorders 3. Hematologic disorders VASCULAR DISORDERS ▪ ATHEROSCLEROSIS  Atherosclerosis of the large extracranial arteries in the neck and at the base of the brain and of smaller intracranial arteries is the most common cause of focal cerebral ischemia.  Within the cerebral circulation, the sites of predilection are:  Origin of the common carotid artery  Internal carotid artery just above the common carotid bifurcation and within the cavernous sinus  Origin of the middle cerebral artery  Vertebral artery at its origin and just above where it enters the skull  Basilar artery.  Pathogenesis of atherosclerosis:  Tends to occur at sites of low or disturbed blood flow, such as curvatures and branch points of large and medium-sized arteries.  Endothelial dysfunction which is thought to be an early step, allows adhesion and subendothelial migration of circulating monocytes and intramural accumulation of lipids.  Inflammation ensues  Engulfment of lipids by monocyte-derived macrophages produces lipid-laden foam cells, which contribute to an early atheromatous lesion, the fatty streak.  At this stage, growth and chemotactic factors released by endothelial cells and macrophages stimulate proliferation of intimal smooth muscle cells and migration of additional smooth muscle cells to the intima from the tunica media. These cells secrete extracellular matrix constituents, leading to the formation of a fibrous cap over the atherosclerotic plaque, in which a necrotic core develops.  In some cases, fractures in the cap lead to plaque rupture, a serious complication associated with the release of procoagulant factors and subsequent thrombosis. Possible outcomes include thrombotic occlusion of the vessel lumen or embolization.  Major risk factors for atherosclerosis leading to stroke include:  Systolic or diastolic hypertension  Elevated serum LDL cholesterol  Diabetes mellitus. ARTERIAL LESION IN ATHEROSCLEROSIS Endothelial injury permits entry of low- density lipoprotein cholesterol and circulating mononuclear cells into the vessel wall, where they form a fatty streak. The subsequent attachment of platelets and proliferation of smooth muscle cells within this lesion leads to production of a fibrous plaque, which may encroach on the arterial lumen or rupture to occlude the vessel and provide a source of emboli. In vivo imaging and histopathology of common carotid artery atheroma. Contrast-enhanced black blood MRI of an atherosclerotic common carotid artery (A) shows a narrowed lumen, thick fibrous cap, hemorrhagic necrotic core (NC), and focal calcification, as outlined in the schematic (B). The corresponding Movat pentachrome-stained endarterectomy section (C) shows the same features (*, calcification). ▪ HYPERTENSION  Commonly (but not universally) defined as systemic blood pressure >140 mm Hg systolic or >90 mm Hg diastolic  A major risk factor for stroke.  Screening and treatment for hypertension have had key roles in reducing stroke incidence in recent decades.  Blood pressure should be measured with the patient seated and relaxed for 5 minutes before three readings are taken at 1-minute intervals, and calculated as the average of the last two readings.  Values obtained in the clinic may be confounded by sampling error or patient anxiety, however, leading to spuriously low (masked hypertension) or high (white coat hypertension) readings.  24-hour ambulatory or automated unattended blood pressure measurement is sometimes used to improve diagnostic accuracy.  Chronic hypertension  Causes degenerative changes in the walls of small arteries and arterioles  Include lipohyalinosis (collagenous thickening and inflammation) and fibrinoid necrosis (degeneration with perivascular inflammation).  In the cerebral circulation, these effects are most pronounced in penetrating small arteries and arterioles of the subcortical white matter, basal ganglia, thalamus, pons, and cerebellum.  Hypertensive vascular disease predisposes to both ischemic and intracerebral hemorrhage. ▪ DIABETES  Type 1 and type 2 diabetes mellitus is associated with an increased risk of both ischemic stroke and intracerebral hemorrhage.  Diabetes affects large and medium-sized arteries, which exacerbates atherosclerosis, as well as small arteries and arterioles, such as those involved in lacunar infarction.  Treatment of diabetes is indicated to prevent other adverse effects.  Antihypertensive drugs and statins can reduce stroke risk in diabetic as in non-diabetic patients. ▪ VASCULITIS  Uncommon cause of stroke  Important to recognize because it is treatable.  Stroke can result from either primary central nervous system vasculitis or systemic vasculitis, and may be the earliest manifestation of the disease.  PRIMARY CNS VASCULITIS  Idiopathic inflammatory disease  Affects small arteries and veins in the brain and spinal cord  Can cause transient or progressive multifocal ischemia.  Clinical features include headache, hemiparesis and other focal neurologic abnormalities, and cognitive disturbances.  CSF may show elevated protein and lymphocytic pleocytosis  ESR is typically normal.  Diagnosis is by angiography, which shows focal and segmental narrowing of small arteries and veins, or brain biopsy.  Differential diagnosis includes reversible cerebral vasoconstriction syndrome.  GIANT CELL (TEMPORAL) ARTERITIS  Produces inflammatory changes that affect branches of the external carotid, cervical internal carotid, posterior ciliary, extracranial vertebral, and intracranial arteries.  Inflammatory changes in the arterial wall stimulate platelet adhesion and aggregation, leading to thrombosis or distal embolism.  Physical examination may show tender, nodular, or pulseless temporal arteries.  Laboratory findings include an increased ESR and evidence of vascular stenosis or occlusion on angiography or color duplex ultrasonography.  Definitive diagnosis is by temporal artery biopsy.  Should be considered in patients with transient monocular blindness or transient cerebral ischemic attacks—especially the elderly— because corticosteroid therapy can prevent its complications, notably permanent blindness.  SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)  Associated with a vasculopathy that involves small cerebral vessels and leads to multiple microinfarcts, but true vasculitis is absent.  Libman-Sacks endocarditis accompanying SLE may also be a source of cardiogenic emboli.  POLYARTERITIS NODOSA  Segmental vasculitis of small- and medium- sized arteries that affects multiple organs.  Transient symptoms of cerebral ischemia, including typical spells of transient monocular blindness, can occur.  SYPHILITIC ARTERITIS  Occurs within 5 years after primary syphilitic infection and may cause stroke.  Medium-sized penetrating vessels are typically involved, producing punctate infarcts in the deep cerebral white matter that can be seen on CT scan or MRI.  Treatment is important to prevent tertiary neurosyphilis (general paresis or tabes dorsalis).  AIDS  Associated with an increased incidence of TIAs and ischemic stroke.  In some cases, cerebrovascular complications are related to endocarditis or opportunistic infections, such as toxoplasmosis or cryptococcal meningitis. ▪ OTHER VASCULOPATHIES  FIBROMUSCULAR DYSPLASIA  Produces segmental medial fibroplasia of large (especially renal, carotid, and vertebral) arteries  Associated with arterial dissection and aneurysms.  Familial cases suggest autosomal dominant inheritance with incomplete penetrance.  Stroke is most common in children and young and middle- aged adults, especially females.  Characteristic “string-of-beads” appearance on angiography.  Symptomatic carotid artery disease is usually treated with antiplatelet drugs and intraluminal dilation of the affected vessel.  CAROTID OR VERTEBRAL ARTERY DISSECTION  May occur spontaneously or in response to minor trauma  Most common in middle age.  Results from medial degeneration followed by hemorrhage into the vessel wall, and causes stroke by occluding the vessel or predisposing to thromboembolism.  Carotid dissection may be accompanied by prodromal transient hemispheric ischemia or monocular blindness, jaw or neck pain, visual abnormalities that mimic those seen in migraine, or Horner syndrome.  Vertebral dissection may produce headache, neck pain, and signs of brainstem dysfunction.  Treatment is with antiplatelet drugs, sometimes combined with endovascular repair.  MULTIPLE PROGRESSIVE INTRACRANIAL ARTERIAL OCCLUSIONS (MOYAMOYA)  Produce bilateral narrowing or occlusion of the distal internal carotid arteries and adjacent anterior and middle cerebral artery trunks.  REACTIVE ARTERIOGENESIS leads to a fine network of collateral channels at the base of the brain, which can be seen by angiography.  May be idiopathic (moyamoya disease) or due to atherosclerosis, sickle cell disease, or other arteriopathies.  Most common in children and middle-aged adults  More common in females than males  Occurs in all ethnic groups  May be sporadic or inherited.  Children tend to present with ischemic strokes and adults with intracerebral, subdural, or subarachnoid hemorrhage.  Treatment includes antiplatelet drugs and surgical revascularization procedures. Carotid angiogram in moya moya. The middle cerebral artery and its branches are replaced by a diffuse capillary pattern that has been likened to a “puff of smoke”. (A) AP view. (B) Lateral view.  DRUG ABUSE  Especially involving cocaine, amphetamines, other stimulants (eg, phenylpropanolamine, ephedrine, or ecstasy), or heroin.  Intravenous drug users may develop infective endocarditis leading to embolic stroke  Stroke also occurs in drug users without endocarditis, including those who take drugs only orally, intranasally, or by inhalation. In these cases, stroke typically has its onset within hours of drug use.  Cocaine hydrochloride and amphetamines are most often associated with intracerebral hemorrhage, whereas stroke from alkaloidal (crack) cocaine use is usually ischemic  Proposed mechanisms include drug- induced endothelial dysfunction leading to a prothrombotic state, vasospasm, rupture of preexisting aneurysms or vascular malformations, and vasculitis.  Stroke has also been reported after use of synthetic cannabinoids.  MIGRAINE WITH (BUT NOT WITHOUT) AURA  Rare cause of ischemic stroke  Most common in women, patients less than 65 years old, smokers, and oral contraceptive users.  Both thrombotic and cardioembolic mechanisms have been proposed.  Migraineurs exhibit a higher incidence of subclinical white matter lesions in the posterior circulation, patent foramen ovale, and cervical artery dissection, but their relationship to clinical stroke is uncertain.  Sporadic or familial (autosomal dominant) hemiplegic migraine is associated with focal cerebral edema during attacks and with cerebellar atrophy, but not with stroke.  REVERSIBLE CEREBRAL VASOCONSTRICTION SYNDROME  Characterized by recurrent thunderclap headache (excruciating pain that reaches peak severity within 1 minute of onset), multifocal constriction of cerebral arteries and, in most cases, spontaneous resolution within 3 months.  Women are affected more often than men  Recent use of vasoconstrictor drugs, especially serotonergic antidepressants  Focal neurologic symptoms and signs, including hemiparesis, aphasia, visual disturbances and seizures  CT or MRI may show multiple lesions, including hemispheric borderzone infarctions, subarachnoid hemorrhage, intracerebral hemorrhage and vasogenic edema.  Angiography is abnormal bilaterally, with concentric smooth tapering and segmental dilatation the most frequent findings.  Cerebrospinal fluid is usually normal.  Treatment is with nimodipine (eg, 60 mg orally every 4-8 hours for 4-12 weeks)  Corticosteroids appear to be unhelpful and possibly harmful.  Differential diagnosis includes primary central nervous system vasculitis and aneurysmal subarachnoid hemorrhage, but neither produces recurrent thunderclap headache. Borderzone infarction or vasogenic edema on CT or MRI also argues against these diagnoses.  VENOUS SINUS THROMBOSIS  Uncommon cause of stroke.  Affects young women most often  May be associated with a predisposing condition, such as otitis or sinusitis, pregnancy and the puerperium, dehydration, cancer, oral contraceptive use, or coagulopathy.  Clinical features include headache, papilledema, impaired consciousness, seizures, and focal neurologic deficits.  CSF pressure is typically increased, and in cases of septic thrombosis, pleocytosis may occur.  CT scan may show edema, infarct, hemorrhage, or filling defect in the superior sagittal sinus (delta sign).  MRI with MR angiography (venography) is the most definitive diagnostic test.  Treatment is with anticoagulants and, for septic thrombosis, antibiotics.  RARE MENDELIAN DISORDERS  Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), due to mutations in the NOTCH3 gene, produces small-vessel strokes, migraine, encephalopathy, and seizures.  Both small- and large-vessel strokes can be seen with mutations in α-galactosidase A (Fabry disease, X-linked recessive); ATP- binding cassette, subfamily C, member 6 (pseudoxanthoma elasticum, autosomal recessive); neurofibromin (neurofibromatosis 1, autosomal dominant); and cystathionine β- synthase (homocystinuria, autosomal recessive).  Arterial dissection leading to stroke may complicate autosomal dominant mutations in the type 3 collagen α-1 chain (Ehlers–Danlos syndrome, type IV) or fibrillin-1 (Marfan syndrome). CARDIAC DISORDERS* ▪ Atrial Fibrillation ▪ Myocardial Infarction ▪ Prosthetic Heart Valves ▪ Dilated Cardiomyopathy ▪ Rheumatic Mitral Stenosis ▪ Infective Endocarditis ▪ Nonbacterial Thrombotic Endocarditis ▪ Atrial Myxoma ▪ Paradoxical Embolus HEMATOLOGIC DISORDERS** ▪ Hemoglobinopathies ▪ Hypercoagulable States ▪ Myeloproliferative Disorders ▪ Secondary Polycythemia *Previously discussed under Cardiovascular System II module **Previously discussed under Hematology/Immunology II module CRYPTOGENIC STROKE ▪ No specific cause can be identified. ▪ Patients tend to be younger, have less severe impairment, and experience fewer recurrences. ▪ Diagnosed when imaging excludes lacunar stroke based on lesion size or location, arteries supplying the affected region show