Neurology_Adams

Neurology_Adams. Embolic occlusion limited to one of the distal branches of the superior division, perhaps the most common stroke seen in clinical practice, produces a more circumscribed infarct that further fractionates the above-described syndrome. With occlusion of the ascending frontal branch, the motor deficit is limited to the face and arm with little or no weakness of the leg, and the latter, if weakened at all, soon improves. With left-sided lesions, there is dysfluent and agrammatic speech and normal comprehension (Broca aphasia). Embolic occlusion of the left rolandic branch alone results in sensorimotor paresis with severe dysarthria but little evidence of aphasia. A cortical– subcortical branch occlusion may give rise solely to a brachial monoplegia or hand weakness that simulates a problem in the peripheral nervous system. Embolic occlusion of ascending parietal and other posterior branches of the superior division may cause no sensorimotor deficit but only a conduction aphasia (see Chap.


Neurology_Adams

Neurology_Adams. the peripheral nervous system. Embolic occlusion of ascending parietal and other posterior branches of the superior division may cause no sensorimotor deficit but only a conduction aphasia (see Chap. 22) and ideomotor apraxia.


Neurology_Adams

Neurology_Adams. There are many other limited stroke syndromes or combinations of the aforementioned deficits relating to small regions of damage in the frontal, parietal, or temporal lobes. Among these are the Gerstmann syndrome and various forms of agnosia (in some patients, these may be in the territory of the inferior division of the MCA discussed below). Most of these are discussed in Chap. 21, which details the result of lesions in particular parts of the cerebrum. As indicated earlier, the distal territory of the middle cerebral artery may also be rendered ischemic by failure of the systemic circulation, especially if the carotid artery is stenotic; this situation may simulate embolic branch occlusions. Inferior division Occlusion of the inferior division of the MCA is slightly less frequent than occlusion of the superior one, but again is nearly always the result of embolism. The usual result in left-sided lesions is a


Neurology_Adams

Neurology_Adams. Wernicke aphasia, which generally remains static for days or weeks after which some improvement can be expected. In less-extensive infarcts that are the result of selective distal branch occlusions (superior parietal, angular, or posterior temporal), the deficit in comprehension of spoken and written language may be especially severe. As with superior division stroke, there may be mutism at the outset but the two are differentiated by a severe receptive language deficit with inferior division infarction. After a few months, the deficits usually improve, often to the point where they are evident only in self-generated efforts to read and copy visually presented words or phrases. With either rightor left-hemispheric lesions, there is usually a superior quadrantanopia or homonymous hemianopia and, with right-sided ones, a left visual neglect and other signs of amorphosynthesis may be apparent (Chap. 21). Rarely, an agitated confusional state may be a prominent feature of nondominant


Neurology_Adams

Neurology_Adams. and, with right-sided ones, a left visual neglect and other signs of amorphosynthesis may be apparent (Chap. 21). Rarely, an agitated confusional state may be a prominent feature of nondominant hemispheral lesions and sometimes of dominant ones. Some of the syndromes applicable to the angular gyrus and the supramarginal gyrus may occur in strokes within this division, depending on the distributions of the vessels in an individual.


Neurology_Adams

Neurology_Adams. This artery, through its cortical branches, supplies the anterior three-quarters of the medial surface of the frontal lobe, including its medial-orbital surface, the frontal pole, a strip of the lateral surface of the cerebral hemisphere along its superior border, and the anterior four-fifths of the corpus callosum. Most strokes are of the embolic variety, far less often atherosclerotic, and occasionally due to other processes such as vasospasm or vasculitis. Deep branches, arising near the circle of Willis (proximal and distal to the anterior communicating artery) supply the anterior limb of the internal capsule, the inferior part of the head of the caudate nucleus, and the anterior part of the globus pallidus (Figs. 33-6 and 33-7).


Neurology_Adams

Neurology_Adams. The largest of these deep branches is the artery of Heubner (“recurrent artery of Heubner”; Fig. 33-8). This artery, which may, in fact, be up to four small vessels, shares its territory of supply with anteriorly placed lenticulostriate arteries that emanate from the middle cerebral artery. Strokes in this territory cause infarction of the head of the caudate and adjacent white matter. In the past, this was a common stroke syndrome from meningovascular syphilis.


Neurology_Adams

Neurology_Adams. The clinical picture of anterior cerebral artery stroke will depend on the location and size of the infarct, which, in turn, relates to the site of the occlusion (proximal or distal to the anterior communicating artery), the pattern of the circle of Willis, and the other ischemia-modifying factors mentioned earlier. Well-studied cases of infarction in the territory of the anterior cerebral artery are not numerous; hence the syndromes have not been completely elucidated (see Brust for a review of the literature and a description of developmental abnormalities of the artery).


Neurology_Adams

Neurology_Adams. Occlusion of the stem of the anterior cerebral artery, proximal to its connection with the anterior communicating artery (the A1 segment in neuroradiologic parlance) is usually well tolerated, because adequate collateral flow is provided by the anterior or cerebral artery of the opposite side. Maximal disturbance occurs when both arteries arise from one anterior cerebral stem, in which case there is infarction of the anterior and medial parts of both cerebral hemispheres resulting in paraplegia, incontinence, abulia and nonfluent aphasic symptoms, and frontal lobe personality changes (see Chap. 21).


Neurology_Adams

Neurology_Adams. Complete infarction as a result of occlusion of one anterior cerebral artery distal to the anterior communicating artery (A2 segment) results in a sensorimotor deficit of the opposite foot and leg and, to a lesser degree, of the shoulder and arm, with sparing of the hand and face (the distribution of which is shown in the MRI of Fig. 33-7). This is the complement of the superior division middle cerebral artery pattern. The motor disorder is more pronounced in the foot and leg than in the hip and thigh. Sensory loss, when it occurs, is mainly of the discriminative modalities but it may be mild or absent. The head and eyes may deviate to the side of the lesion. Urinary incontinence, a contralateral grasp reflex, and paratonic rigidity (gegenhalten) of the opposite limbs may be evident. With a left-sided occlusion, there may be a “sympathetic apraxia” of the left arm and leg or involuntary misdirected movements of the left arm (alien arm or hand), as described in Chaps. 3 and 21.


Neurology_Adams

Neurology_Adams. Language disturbances, particularly transcortical motor aphasia (see Chap. 22), may occur with anterior cerebral artery territory stroke. Disorders of behavior that may be overlooked in cases of anterior cerebral artery occlusion; they are abulia, or a slowness and lack of spontaneity in all reactions, muteness or a tendency to speak in whispers, and distractibility. Branch occlusions of the anterior cerebral artery produce only fragments of the total syndrome, usually a spastic weakness or associative sensory loss in the opposite foot and leg.


Neurology_Adams

Neurology_Adams. With occlusion of penetrating branches of the ACA, typified by occlusion of Heubner’s artery, the anterior limb of the internal capsule and caudate is usually involved. In a series of 18 cases of unilateral caudate region infarcts collected by Caplan and associates, a transient hemiparesis was present in 13. Dysarthria and either abulia or agitation and hyperactivity were also common. Stuttering and language difficulty occurred with two of the left-sided lesions and visuospatial neglect with three of the right-sided ones. Alexander and Schmitt cited cases in which occlusions of the proximal artery (ACA), which included the Heubner artery, resulted in right hemiplegia (predominant in the leg) with grasping and groping responses of the right hand and buccofacial apraxia that were accompanied by a diminution or absence of spontaneous speech, agraphia, and a limited ability to name objects and compose word lists but with a striking preservation of the ability to repeat spoken and written


Neurology_Adams

Neurology_Adams. by a diminution or absence of spontaneous speech, agraphia, and a limited ability to name objects and compose word lists but with a striking preservation of the ability to repeat spoken and written sentences (i.e., transcortical motor aphasia). With bilateral caudate infarctions, a syndrome of inattentiveness, abulia, forgetfulness, and sometimes agitation and psychosis was observed. Transitory choreoathetosis and other dyskinesias (we have seen two cases of ballismus) have also been attributed to ischemia of the caudate and anterior basal ganglia, occurring sometimes under conditions of prolonged standing and exercise (Caplan and Sergay; Margolin and Marsden).


Neurology_Adams

Neurology_Adams. This is a long, narrow artery that springs from the internal carotid, just distal to the origin of the posterior communicating artery. It supplies the internal segment of the globus pallidus and posterior limb of the internal capsule and several contiguous structures including (in most patients) the optic tract (Figs. 33-6 and 33-9). It then penetrates the temporal horn of the lateral ventricle, where it supplies the choroid plexus and anastomoses with the posterior choroidal artery. This being a small caliber branch, most strokes in this territory are due to in situ atherosclerosis of the type that occurs in diabetics but occlusion of the orifice of the vessel by an embolus is possible and it is a known complication of clipping of an aneurysm at the upper reaches of the carotid artery.


Neurology_Adams

Neurology_Adams. Only a few complete clinicopathologic studies have been made of the distinctive syndrome caused by occlusion of this artery. It was found by Foix and colleagues to consist of contralateral hemiplegia, hemihypesthesia, and homonymous sectorial hemianopia as a result of involvement of the posterior limb of the internal capsule and white matter posterolateral to it, through which the geniculocalcarine tract passes, and the lateral geniculate nucleus. There has been considerable discussion regarding the vascular anatomy supply of the lateral geniculate; several authors have suggested that the anterior choroidal artery supplies the lateral and medial portions of the nucleus and a lesion there causes a homonymous quandrantopias in the upper and lower fields but sparing a sector that lies along the equator (cleverly called “quadruple quadrantanopia”). The complimentary stroke in the lateral geniculate is one from occlusion of the posterior (lateral) choroidal artery, which supplies the


Neurology_Adams

Neurology_Adams. the equator (cleverly called “quadruple quadrantanopia”). The complimentary stroke in the lateral geniculate is one from occlusion of the posterior (lateral) choroidal artery, which supplies the middle segment of the nucleus and gives rise a sectorial defect lying along the equatorial visual field (see Frisen et al, and Osborne et al). This combination of extensive unilateral motor, sensory, and visual impairment in an individual with well-preserved language and cognition distinguishes this stroke syndrome from the more common ones involving the major cerebral arteries. Decroix and colleagues reported 16 cases (identified by CT) in which the lesion appeared to lie in the vascular territory of this artery. In most of their cases, the clinical syndrome fell short of what was expected on anatomic grounds or had additional features.


Neurology_Adams

Neurology_Adams. With right-sided lesions, there may be a left spatial neglect and constructional apraxia; slight disorders of speech and language may accompany left-sided lesions. Hupperts and colleagues have discussed the controversy regarding the effects of occlusion of the artery and in particular the variability of its supply to the posterior paraventricular area of the corona radiata and adjacent regions. They concluded, also from a survey of CT images, that there was no uniform syndrome attributable to occlusion of the vessel and that in most cases its territory of supply was overlapped by small surrounding vessels. It may be remembered that for a time, in order to abolish the tremor and rigidity of unilateral Parkinson disease, the anterior choroidal artery was being surgically ligated without these other effects having been produced.


Neurology_Adams

Neurology_Adams. Despite the small caliber of the vessel and its blood supply of deep structures, the most common cause of occlusion of this vessel is embolic (Leys and colleagues). In approximately 70 percent of individuals, both posterior cerebral arteries are formed by the bifurcation of the basilar artery and thin posterior communicating arteries join this system to the internal carotid arteries. In 20 to 25 percent, one posterior cerebral artery arises from the basilar in the usual way, but the other arises from the internal carotid, a persistent fetal pattern of circulation (“fetal PCA”); fewer than 5 percent have the unusual configuration in which both arise from the corresponding carotid arteries. Most strokes in this territory are embolic in origin, either cardioembolic or from a thrombus in a more proximal vessel, but some individuals are predisposed to atherosclerosis in the proximal posterior cerebral artery.


Neurology_Adams

Neurology_Adams. The configuration and branches of the proximal segment of the posterior cerebral artery (P1 segment) are illustrated in Figs. 33-8, and 33-10. The interpeduncular branches, which arise just above the basilar bifurcation, supply the red nuclei, the substantia nigra bilaterally, medial parts of the cerebral peduncles, oculomotor and trochlear nuclei and nerves, reticular substance of the upper brainstem, decussation of the superior cerebellar peduncles, medial longitudinal fasciculi, and medial lemnisci. The P1 portion of the posterior cerebral artery is the segment that arises from the terminus of the basilar artery proximal to the ostium of the posterior communicating artery. It gives rise to the interpeduncular branches, which are variable and complex. As pointed out by Percheron (whose name is often applied to the largest of these vessels), the arterial configuration of the paramedian mesencephalic arteries varies considerably: in some cases, two small vessels arise symmetrically,


Neurology_Adams

Neurology_Adams. name is often applied to the largest of these vessels), the arterial configuration of the paramedian mesencephalic arteries varies considerably: in some cases, two small vessels arise symmetrically, one from each side; in others, a single artery arises from one posterior cerebral stem (proximal P1), which then bifurcates. In the latter case, one posterior cerebral stem, through a small artery, supplies the medial thalamic territories on both sides, and an occlusion of this artery produces a bilateral butterfly shaped lesion in the medial parts of the diencephalon. These are elaborated and illustrated by Castaigne et al.


Neurology_Adams

Neurology_Adams. The thalamoperforate branches (also called paramedian thalamic arteries) arise slightly more distally from the stem, nearer the junction of the posterior cerebral and posterior communicating arteries (P2 segment of the artery) and supply the inferior, medial, and anterior parts of the thalamus. The thalamogeniculate branches arise still more distally, opposite the lateral geniculate body, and supply the geniculate body and the central and posterior parts of the thalamus. Medial branches emerging from the posterior cerebral artery as it encircles the midbrain, supply the lateral part of the cerebral peduncle, lateral tegmentum and corpora quadrigemina, and pineal gland. Posterior choroidal branches run to the posterosuperior thalamus, choroid plexus, posterior parts of the hippocampus, and psalterium (decussation of deep white matter fornices).


Neurology_Adams

Neurology_Adams. Most importantly, the terminal or cortical branches of the posterior cerebral artery supply the inferomedial part of the temporal lobe and the medial occipital lobe, including the lingula, cuneus, precuneus, and visual Brodmann areas 17, 18, and 19 (see Figs. 33-6, 33-10, and 33-11). Occlusion of the posterior cerebral artery produces a profusion of clinical because both the upper brainstem, which is replete with important structures, and the inferomedial parts of the temporal and occipital lobes lie within its supply. The site of the occlusion and the arrangement of the circle of Willis will, in large measure, determine the location and extent of the resulting infarct. For example, occlusion proximal to the posterior communicating artery may be asymptomatic or have only transitory effects if the collateral flow is adequate from the Circle of Willis (see Figs. 33-2, 33-10, and 33-11).


Neurology_Adams

Neurology_Adams. In older series of posterior cerebral artery strokes, such as the one by studied by Milandre and coworkers, the causes were mainly atherosclerotic. Our experience has differed in that the proportion of presumed embolic occlusions has been far greater than that of other causes. For convenience of exposition, it is helpful to divide the posterior cerebral artery syndromes into three groups: (1) proximal (involving interpeduncular, thalamic perforant, and thalamogeniculate branches), (2) cortical (inferior temporal and medial occipital), and (3) bilateral. Proximal PCA Syndromes (See Figs. 33-10 and 33-11)


Neurology_Adams

Neurology_Adams. The thalamic syndrome of Dejerine and Roussy (see also Chap. 7) follows infarction of the sensory relay nuclei in the thalamus, the result of occlusion of thalamogeniculate branches. Occlusion of the small vessels supplying these territories from in situ atherothrombosis or embolic occlusion of the posterior cerebral artery is the most common cause. There is both a deep and cutaneous sensory loss, usually severe in degree, of the opposite side of the body, including the trunk and face, sometimes accompanied by a transitory hemiparesis. A homonymous hemianopia may be conjoined. In some instances, there is a dissociated sensory loss—pain and thermal sensation being more affected than touch, vibration, and position—or only one part of the body may be anesthetic. The characteristic feature is always sensory loss that includes the entire hemibody up to the midline. After an interval, sensation begins to return, and the patient may develop pain, paresthesia, and hyperpathia in the affected


Neurology_Adams

Neurology_Adams. always sensory loss that includes the entire hemibody up to the midline. After an interval, sensation begins to return, and the patient may develop pain, paresthesia, and hyperpathia in the affected parts. The painful paresthetic syndrome may persist for years. There may also be distortion of taste, athetotic posturing of the hand, and alteration of mood. Mania and depression have occasionally been observed with infarction of the diencephalon and adjacent structures, but the data are usually incomplete.


Neurology_Adams

Neurology_Adams. Central midbrain and subthalamic syndromes are a result of occlusion of the interpeduncular branches (Percheron vessel) of the posterior cerebral artery. The clinical syndromes include palsies of vertical gaze, stupor, or coma. Syndromes of the paramedian arteries, including the proximal posterior cerebral artery, have as their main feature a third-nerve palsy on the side of the lesion combined with contralateral hemiplegia (Weber syndrome), contralateral ataxic tremor (Claude syndrome), or contralateral ataxia and hemiplegia (Benedikt syndrome), as summarized in Table 33-5.


Neurology_Adams

Neurology_Adams. Anteromedial-inferior thalamic syndromes follow occlusion of the thalamoperforant branches. Here the most common effect is an extrapyramidal movement disorder (hemiballismus or hemichoreoathetosis or less often, asterixis). Deep sensory loss, hemiataxia, or tremor may be added in various combinations. Hemiballismus is usually a result of occlusion of a small branch to the subthalamic nucleus (of Luys) or its connections with the pallidum. Occlusion of the paramedian thalamic branches to the mediodorsal nucleus is a recognized cause of an amnesic (Korsakoff) syndrome; this simulates but is less common than infarction of the hippocampi from occlusion of the medial temporal branch of the posterior cerebral artery as noted below. Cortical Syndromes of the Posterior Cerebral Artery


Neurology_Adams

Neurology_Adams. Occlusion of branches to the temporal and occipital lobes gives rise to a homonymous hemianopia as a result of involvement of the primary visual receptive areas (calcarine or striate cortex) or of the converging geniculocalcarine fibers. The hemianopia may be incomplete and involve the upper quadrants of the visual fields more than the lower ones (see Chap. 12). Macular, or central, vision is often spared (macular sparing) because of collateral blood supply of the occipital pole from distal branches of the middle (or rarely anterior) cerebral arteries. Other features seen in a few instances are visual hallucinations in the blind parts of the visual fields (Cogan) or metamorphopsia and palinopsia (Brust and Behrens). Occipital infarcts of the dominant hemisphere may cause alexia without agraphia, anomia (amnesic aphasia), a variety of visual agnosias, and rarely some degree of impaired memory. The anomias, when they occur, are most severe for colors, but the naming of other visually


Neurology_Adams

Neurology_Adams. agraphia, anomia (amnesic aphasia), a variety of visual agnosias, and rarely some degree of impaired memory. The anomias, when they occur, are most severe for colors, but the naming of other visually presented material such as pictures, mathematical symbols, and manipulable objects may also be impaired. The patient may treat objects as familiar—that is, describe their functions and use them correctly—but be unable to name them. Color anomia (a form of “central achromatopsia”) and amnesic aphasia are more often present in this syndrome than is alexia. The defect in retentive memory is of varying severity and may or may not improve with the passage of time. These syndromes are described in Chaps. 21 and 22.


Neurology_Adams

Neurology_Adams. A complete proximal arterial occlusion leads to a syndrome that combines cortical and anterior-proximal syndromes in part or totally. As mentioned, the vascular lesion may be either an embolus or an atherosclerotic thrombus, but more often the former. These occur as a result of successive infarctions or from a single embolic or thrombotic occlusion of the upper basilar artery, especially if the posterior communicating arteries are unusually small or absent, or from global failure of circulation.


Neurology_Adams

Neurology_Adams. Bilateral lesions of the occipital lobes, if extensive, cause “cortical blindness” that is essentially bilateral homonymous hemianopia, sometimes accompanied by unformed visual hallucinations. The pupillary reflexes are preserved and the optic discs appear normal. Sometimes the patient is unaware of being blind and denies the problem even when it is pointed out to him (Anton syndrome). More frequently, the lesions are incomplete, and a sector of the vision, usually on one side, remains intact. When the visual remnant is small, vision may seemingly fluctuate from moment to moment as the patient attempts to capture the image in the island of intact vision, in which case hysteria may be incorrectly inferred. In bilateral lesions confined to the occipital poles, there may be a loss of central vision only (homonymous central scotomas). With more anteriorly placed lesions of the occipital pole, there may be homonymous paracentral scotomas, or the occipital poles may be spared, leaving the


Neurology_Adams

Neurology_Adams. vision only (homonymous central scotomas). With more anteriorly placed lesions of the occipital pole, there may be homonymous paracentral scotomas, or the occipital poles may be spared, leaving the patient with only central vision (bilateral central, or macular sparing). Horizontal or altitudinal field homonymous defects are usually a result of similar restricted lesions affecting the upper or lower banks of the calcarine sulci (essentially, quadrantanopia). The Balint syndrome (see Chap. 21) is an effect of bilateral occipitoparietal border-zone lesions.


Neurology_Adams

Neurology_Adams. With bilateral lesions that involve the inferomedial portions of the temporal lobes, including the hippocampi and their associated structures, the impairment of memory may be severe, causing the Korsakoff amnesic state. In several of our patients, a solely left-sided infarction of the inferomedial temporal lobe impaired retentive memory. Bilateral mesiotemporal-occipital lesions also cause a lack of recognition of faces (prosopagnosia). These and other effects of temporal and occipital lesions are discussed in Chaps. 12 and 22.


Neurology_Adams

Neurology_Adams. The vertebral arteries are the chief arteries of the medulla; each supplies the lower three-fourths of the pyramid, the medial lemniscus, all or nearly all of the retroolivary (lateral medullary) region, the restiform body, and the posteroinferior part of the cerebellar hemisphere through the posterior inferior cerebellar arteries (Figs. 33-2 and 33-12). The relative sizes of the vertebral arteries vary considerably and in approximately 10 percent of cases, one vessel is so small that the other is essentially the only artery of supply to the brainstem. The dominant vertebral artery can usually be identified by the convexity of the basilar artery, which swings in a direction away from the dominant vertebral artery. This may be helpful to the clinician in identifying that the dominant vertebral artery is occluded. If there is no collateral flow from the carotid system via the circle of Willis, occlusion of one functional vertebral artery is equivalent to occlusion of the basilar artery


Neurology_Adams

Neurology_Adams. artery is occluded. If there is no collateral flow from the carotid system via the circle of Willis, occlusion of one functional vertebral artery is equivalent to occlusion of the basilar artery (see below). The posteroinferior cerebellar artery (PICA) is usually a branch of the vertebral artery but can have a common origin and form a loop with the anteroinferior cerebellar artery (AICA) from the basilar artery. It is necessary to keep these anatomic variations in mind in considering the effects of vertebral artery occlusion.


Neurology_Adams

Neurology_Adams. The vertebral artery is assigned four numerical segments for convenience of explication. They are: V1, from the origin to the first entry into the cervical transverse foramen (usually C6 as noted); V2, from the transverse foramen to the uppermost foramen (at C1); V3 from this site to the dural penetration at the foramen magnum; and V4 from the dural entry to the junction with the opposite vertebral artery and the origin of the basilar artery.


Neurology_Adams

Neurology_Adams. The vertebral arteries may be occluded by atherothrombosis in their intracranial portion or at their origin at the subclavian artery or the arch of the aorta. Because the vertebral arteries have a long extracranial course and pass through the transverse processes of the cervical vertebrae, entering at C6 to proceeding rostrally to the C1 vertebrae before entering the cranial cavity, they are subject to trauma, spondylotic compression, and a variety of other vertebral diseases. With the exception of arterial dissection, in our experience the other causes of vascular occlusion in this list happen only infrequently. We rarely see convincing examples of spondylotic occlusion but several such cases have been reported. Extreme extension of the neck, as experienced by people who are having their hair washed in salons, or during yoga positions, may give rise to transient symptoms in the territory of the vertebral artery.


Neurology_Adams

Neurology_Adams. Dissection of the vertebral artery declares itself by cervicooccipital pain ipsilateral to the dissection and deficits of brainstem function. One’s attention is drawn to the diagnosis of vertebral dissection where there have been vigorous and protracted bouts of coughing or trauma to the neck or head. Dissection of the extracranial vessels is discussed in more detail further on. Examples of posterior circulation stroke in children have been reported in association with odontoid hypoplasia and other atlantoaxial dislocations, causing the vertebral arteries to be stretched or kinked in their course through the transverse processes of C1-C2 (Phillips et al).


Neurology_Adams

Neurology_Adams. The results of acute vertebral artery occlusion are quite variable and there may be no symptoms if an artery is occluded extracranially and there is adequate flow from the opposite vertebral artery or other collateral supply. Occlusion of a vertebral artery low in the neck is usually compensated by anastomotic flow to the upper part of the artery via the thyrocervical, deep cervical, and occipital arteries or by reflux from the circle of Willis. In a configuration in which one vertebral artery is occluded just proximal to the origin of its PICA branch, and the opposite vertebral artery is open and sufficient in size, there may be no symptoms because the PICA is still filled by retrograde flow through its vertebral artery. If the occlusion of the artery is so situated as to block the posterior inferior cerebellar artery supplying the lateral medulla and inferior cerebellum (PICA), a characteristic syndrome results with vertigo being a prominent symptom (see “Lateral Medullary


Neurology_Adams

Neurology_Adams. Syndrome” described further on). If the subclavian artery is blocked proximal to the origin of the left vertebral artery, exercise of the arm on that side may draw blood from the right vertebral and basilar arteries, retrograde down the left vertebral and into the distal left subclavian artery—sometimes resulting in the symptoms of basilar insufficiency. This phenomenon, described in 1961 by Reivich and colleagues, was referred to by Fisher (1961) as the subclavian steal. Its most notable features are vertigo and other brainstem signs coupled with transient weakness on exercise of the left arm. There may also be headache and claudication or pain of the arm.


Neurology_Adams

Neurology_Adams. Less often, occlusion of the vertebral artery or one of its medial branches produces an infarct that involves the medullary pyramid, the medial lemniscus, and the emergent hypoglossal fibers; the resultant syndrome consists of a contralateral paralysis of arm and leg (with sparing of the face), contralateral loss of position and vibration sense, and ipsilateral paralysis and later atrophy of the tongue. This is the medial medullary syndrome (Fig. 33-13). A more limited lesion, from occlusion of one spinal artery arising from the vertebral artery, gives rise to a contralateral hemiplegia (rarely a quadriplegia) that spares the face. When the vertebral branch to the anterior spinal artery is blocked, flow from the other (corresponding) branch is usually sufficient to prevent infarction of the cervical cord, but we and others have described solely pyramidal infarction with hemiplegia or quadriplegia that spares the face (Ropper et al).


Neurology_Adams

Neurology_Adams. Known also as the Wallenberg syndrome (who described a case in 1895), this common stroke is produced by infarction of a wedge of lateral medulla lying posterior to the inferior olivary nucleus (see Figs. 33-2, 33-12, and 33-13). The complete syndrome, as outlined by Fisher and colleagues (1961) comprises (a) symptoms derived from the vestibular nuclei (vertigo, nystagmus, oscillopsia, vomiting); (b) spinothalamic tract (contralateral or, less often, ipsilateral impairment of pain and thermal sense over half the body); (c) descending sympathetic tract (ipsilateral Horner syndrome—miosis, ptosis, decreased sweating); (d) issuing fibers of the ninth and tenth nerves (hoarseness, dysphagia, hiccough, ipsilateral paralysis of the palate and vocal cord, diminished gag reflex); (e) utricular nucleus (vertical diplopia and illusion of tilting of vision and rotation of the vertical meridian, rarely so severe as to produce upside down vision); (f) olivocerebellar, spinocerebellar fibers,


Neurology_Adams

Neurology_Adams. nucleus (vertical diplopia and illusion of tilting of vision and rotation of the vertical meridian, rarely so severe as to produce upside down vision); (f) olivocerebellar, spinocerebellar fibers, restiform body and inferior cerebellum (ipsilateral ataxia of limbs, falling or toppling to the ipsilateral side, and the sensation of lateropulsion); (g) descending tract and nucleus of the fifth nerve (pain, burning, and impaired sensation over ipsilateral half of the face); (h) nucleus and tractus solitarius (loss of taste); and rarely, (i) cuneate and gracile nuclei (numbness of ipsilateral limbs). Fragmentary syndromes are more frequent, especially at the onset of the stroke. These subsyndromes consist mainly of vertigo but may include and ptosis, toppling and vertical diplopia, hoarseness and disequilibrium, or other combinations short of the entire syndrome. While vertigo is the most frequent feature, it alone, is not usually an indication of lateral medullary infarction. The smallest


Neurology_Adams

Neurology_Adams. disequilibrium, or other combinations short of the entire syndrome. While vertigo is the most frequent feature, it alone, is not usually an indication of lateral medullary infarction. The smallest infarctions we have encountered gave rise only to symptoms of lateropulsion and mild ipsilateral limb ataxia and in one case with a very small region of pontomedullary infarction on MRI, vertigo, and associated gait difficulty.


Neurology_Adams

Neurology_Adams. The eye signs of lateral medullary infarction are also varied and quite interesting. Nystagmus is almost invariable. Direction-changing nystagmus (with different positions of gaze) is a useful feature that suggests brainstem forms of nystagmus (see Chap. 13). There may be a fragment of an internuclear ophthalmoplegia or a skew deviation (hypotropia on the side of the stroke). There may be hypometric saccades toward the side of the lesion and hypermetric saccades in the opposite direction.


Neurology_Adams

Neurology_Adams. The entire lateral medullary syndrome, one of the most striking in neurology, is usually caused by infarction, with only a small number of cases being the result of hemorrhage, demyelination, or tumor. Although it has traditionally been attributed to occlusion of the PICA, as mentioned earlier, careful studies have shown that most cases are due to vertebral artery occlusion by atherothrombosis; in the remainder, either the posterior inferior cerebellar artery or one of the lateral medullary arteries is occluded by atherothrombosis. Embolism to the PICA is a less-frequent cause. The inferior cerebellum may be affected in isolation if the embolus travels distal to the medullary branches of the PICA, causing vomiting, vertigo, and ataxia with occipitonuchal headache but without Horner syndrome, hiccoughs, palatal paralysis, and other features of medullary infarction.


Neurology_Adams

Neurology_Adams. In recent years, we have had experience with patients who initially have considerable recovery from lateral medullary infarction in the first days and weeks but experience sudden death from respiratory or cardiac arrest, even in the absence of cerebellar swelling or basilar artery thrombosis. Cases of this nature have been reviewed by Norrving and Cronqvist. The related and important issue of cerebellar swelling after vertebral artery or PICA occlusion and the need for surgical decompression is discussed later in the chapter.


Neurology_Adams

Neurology_Adams. The branches of the basilar artery may be instructively grouped as follows: (1) paramedian, 7 to 10 pairs, supplying a wedge of pons on either side of the midline; (2) short circumferential, 5 to 7 pairs in number, supplying the lateral two-thirds of the pons and the middle and superior cerebellar peduncles; (3) long circumferential, 2 on each side (the superior and anterior inferior cerebellar arteries), which run laterally around the pons to reach the cerebellar hemispheres (see Figs. 33-2, 33-12, and 33-14 through 33-16); and (4) several paramedian (interpeduncular) branches at the bifurcation of the basilar artery and origins of the posterior cerebral arteries supplying the high midbrain and medial subthalamic regions. These interpeduncular and other short proximal branches of the posterior cerebral artery were described earlier in the chapter.


Neurology_Adams

Neurology_Adams. Basilar artery occlusion, typically because of local thrombosis that is superimposed on a preexisting atherosclerotic plaque, can arise in several ways: (1) occlusion of the basilar artery itself, usually in the lower or middle third at the site of an atherosclerotic plaque; (2) occlusion of both vertebral arteries as mentioned earlier, which produces the equivalent of basilar artery occlusion if the circle of Willis is inadequate; and (3) occlusion of a single vertebral artery when it is the only one of adequate size. When there is embolism, the clot usually lodges at the terminal bifurcation of the basilar (“top-of-the-basilar syndrome” as detailed by Caplan 1980) or in one of the posterior cerebral arteries, as the clot, if small enough to pass through the vertebral artery, easily traverses the length of the basilar artery, which is of greater diameter than either vertebral artery. Also, atherothrombosis may involve a branch of the basilar artery rather than the trunk (basilar


Neurology_Adams

Neurology_Adams. traverses the length of the basilar artery, which is of greater diameter than either vertebral artery. Also, atherothrombosis may involve a branch of the basilar artery rather than the trunk (basilar branch occlusion).


Neurology_Adams

Neurology_Adams. The syndrome of basilar artery occlusion (Fig. 33-2), as delineated by Kubik and Adams, reflects the involvement of a large number of bilateral structures: corticospinal and corticobulbar tracts; cerebellum, middle and superior cerebellar peduncles; medial and lateral lemnisci; spinothalamic tracts; medial longitudinal fasciculi; pontine nuclei; vestibular and cochlear nuclei; descending hypothalamospinal sympathetic fibers; and the third through eighth cranial nerves (the nuclei and their segments within the brainstem). Thus the complete syndrome comprises bilateral long tract signs (sensory and motor) with variable cerebellar, cranial nerve, and other segmental abnormalities of the brainstem.


Neurology_Adams

Neurology_Adams. Another important syndrome, the result of occlusion of the distal end of the basilar artery, usually from embolus, consists of coma from infarction of the high midbrain reticular activating system. This “top of the basilar” artery occlusion is characterized by transient loss of consciousness, oculomotor disturbances (roving eye movements or eyes looking downward and inward with inability to reflexly elicit upward movements), hemianopia, bilateral ptosis, and pupillary enlargement with preserved reaction to light. Spontaneous recanalization of the vessel may occur, but in a delayed fashion, after the infarct has been established. MRI demonstrates one of several characteristic patterns of central midbrain, bilateral posterior thalamic, typically in the shape of a butterfly, and more variably, unior bilateral posterior cerebral artery territory infarction as discussed below.


Neurology_Adams

Neurology_Adams. Yet another configuration, the result of occlusion of the midbasilar artery, gives rise to the locked-in syndrome, in which the patient is mute and quadriplegic but conscious, reflecting interruption of descending motor pathways in the base of the pons but sparing of the reticular activating system (“locked-in” syndrome; see Chap. 16). Horizontal eye movements are obliterated but vertical ones and some ability to elevate the eyelids are spared. The pupils become extremely small but retain some reaction to light. Midbasilar disease may also cause coma if the posterior communicating arteries are inadequate to perfuse the distal basilar artery territory.


Neurology_Adams

Neurology_Adams. In the presence of the full syndrome of basilar occlusion with coma, quadriplegia, and ophthalmoplegia, it is usually not difficult to make the correct diagnosis. The aim should be, however, to recognize basilar insufficiency long before the stage of total deficit has been reached. The early manifestations (in the form of TIAs) occur in many combinations, described in detail further on.


Neurology_Adams

Neurology_Adams. Occlusion of branches at the bifurcation (top) of the basilar artery results in a remarkable number of complex syndromes that include, in various combinations, somnolence or coma, memory defects, akinetic mutism, visual hallucinations, ptosis, disorders of ocular movement (convergence spasm, paralysis of vertical gaze, retraction nystagmus, pseudoabducens palsy, retraction of upper eyelids, skew deviation of the eyes), an agitated confusional state, and visual field defects. These have been summarized by Petit and coworkers and Castaigne and associates and categorized as paramedian thalamic, subthalamic, and midbrain syndromes, and by Caplan (1980) as parts of the “top of the basilar” syndrome as noted above. Limited, small infarctions on one side of the brainstem are usually due to occlusion of small penetrating vessels that originate in the basilar artery. Emboli coursing through the basilar artery can also occlude the mouths of several small penetrating vessels and cause larger


Neurology_Adams

Neurology_Adams. of small penetrating vessels that originate in the basilar artery. Emboli coursing through the basilar artery can also occlude the mouths of several small penetrating vessels and cause larger heterogeneous infractions. A larger infarction in the territory of one circumferential vessel may be due to an embolus or result from an atherosclerotic plaque in the parent basilar artery. The clinical distinction is made by the rapidity of onset and the presence of risk factors such as atrial fibrillation for embolus or diabetes and hypertension for small vessel occlusion.


Neurology_Adams

Neurology_Adams. The main signs of occlusion of the superior cerebellar artery, the most rostral circumferential branch of the basilar, are ipsilateral cerebellar ataxia of the limbs (referable to middle and superior cerebellar peduncles); nausea and vomiting; slurred speech; and loss of pain and thermal sensation over the opposite side of the body (spinothalamic tract). Static tremor of the ipsilateral upper extremity, an ipsilateral Horner syndrome, and palatal myoclonus have also been reported.


Neurology_Adams

Neurology_Adams. With occlusion of the anterior inferior cerebellar artery (AICA), the extent of the infarct is extremely variable, as the size of this artery and the territory it supplies vary inversely with the size and territory of supply of the PICA. The principal findings are vertigo, vomiting, nystagmus, tinnitus, and sometimes unilateral deafness; facial weakness; ipsilateral cerebellar ataxia (inferior or middle cerebellar peduncle); an ipsilateral Horner syndrome and paresis of conjugate lateral gaze; and contralateral loss of pain and temperature sense of the arm, trunk, and leg (lateral spinothalamic tract) as shown in Fig. 33-15. The tinnitus, if present at all, may be overwhelming, called “screaming” by some of our patients. If the occlusion is close to the origin of the artery, the corticospinal fibers may also be involved, producing a hemiplegia; if distal, there may be cochlear and labyrinthine infarction. Cerebellar swelling did not occur with AICA territory infarction in the 20


Neurology_Adams

Neurology_Adams. fibers may also be involved, producing a hemiplegia; if distal, there may be cochlear and labyrinthine infarction. Cerebellar swelling did not occur with AICA territory infarction in the 20 collected by Amarenco and Hauw but it has been a more common occurrence in our material.


Neurology_Adams

Neurology_Adams. The most characteristic manifestation of all these basilar branch strokes is the “crossed” cranial nerve and long tract sensory or motor deficit reflecting a unilateral segmented infarction of the brainstem. These syndromes, which may involve any of cranial nerves III through XII, are listed in Table 33-5 and discussed in Chap. 44. Although the finding of bilateral neurologic signs strongly suggests brainstem involvement, the signs may also be limited to one side of the body.


Neurology_Adams

Neurology_Adams. Distinguishing capsular from pontine hemiplegia It is often not possible to distinguish a hemiplegia of pontine origin from one of deep cerebral origin unless there is an associated cranial nerve palsy to triangulate the lesion to a specific part of the brainstem. In both, the face, arm, hand, leg, and foot are affected because of the location of the descending motor fibers into a small segmental region in both structures. With brainstem lesions, as with cerebral ones, a flaccid paralysis gives way to spasticity after a few days or weeks, and there is no satisfactory explanation for the occurrence in some cases of spasticity from the onset of the stroke. There is also may be a combined hemiparesis and ataxia of the limbs on the same side. With a hemiplegia of pontine origin, however, the eyes may deviate to the side of the paralysis, that is, the opposite of what occurs with supratentorial lesions. The pattern of sensory disturbance may also be helpful. A dissociated sensory deficit


Neurology_Adams

Neurology_Adams. eyes may deviate to the side of the paralysis, that is, the opposite of what occurs with supratentorial lesions. The pattern of sensory disturbance may also be helpful. A dissociated sensory deficit over the ipsilateral face and contralateral half of the body usually indicates a lesion in the lower brainstem, while a hemisensory loss including the face and involving all modalities indicates a lesion in the upper brainstem, in the thalamus, or deep in the white matter of the parietal lobe. When position sense, two-point discrimination, and tactile localization are affected relatively more than pain or thermal and tactile sense, a cerebral lesion is suggested; the converse indicates a brainstem localization. Bilateral motor and sensory signs are almost certain evidence that the lesion lies in the brainstem. When hemiplegia or hemiparesis and sensory loss are coextensive, the lesion usually is situated supratentorially. Additional manifestations that strongly favor a brainstem site are


Neurology_Adams

Neurology_Adams. in the brainstem. When hemiplegia or hemiparesis and sensory loss are coextensive, the lesion usually is situated supratentorially. Additional manifestations that strongly favor a brainstem site are vertigo, diplopia, cerebellar ataxia, a Horner syndrome, and deafness. The numerous brainstem syndromes illustrate the important point that the cerebellar pathways, spinothalamic tract, trigeminal nucleus, and sympathetic fibers can be involved at different rostral-caudal levels so that “neighboring” phenomena are required to identify the exact site of the infarction.


Neurology_Adams

Neurology_Adams. A myriad of proper names have been applied to the brainstem syndromes, as noted in Tables 33-5 and 44-1. Many of them were originally described in relation to tumors, trauma, and other nonvascular diseases. The diagnosis of vascular disorders in this region of the brain is not greatly facilitated by knowledge of these eponymic syndromes; it is much more profitable to be closely familiar with the anatomy of the brainstem. To recapitulate, the principal syndromes to be recognized are the full basilar, vertebral–PICA, posteroinferior cerebellar, anteroinferior cerebellar, superior cerebellar, pontomedullary, and medial medullary. Figures 33-12 through 33-16, supplied originally by C.M. Fisher and used in previous editions of this book. Other syndromes can usually be identified as fragments or combinations of the major ones.


Neurology_Adams

Neurology_Adams. As one might surmise, small penetrating branches of the cerebral arteries may become occluded, and the resulting infarcts may be so small or so situated as to cause no symptoms whatsoever. As the softened tissue is removed by macrophages, a small cavity, or lacune, remains. Early in the twentieth century, Pierre Marie referred to the condition as état lacunaire (the lesions were first described by Durant-Fardel in 1843). He distinguished these lesions from a fine loosening of tissue around thickened small vessels that enter the anterior and posterior perforated spaces, a change to which he gave the name état criblé (cribriform change). Pathologists have not always agreed on these distinctions, but we have adhered to the view of Fisher that lacunes are usually caused by occlusion of small arteries, 50 to 200 μm in diameter, and the cribriform state, to mere thickening of vessels and fraying of the surrounding tissue—that is, dilated perivascular spaces (Virchow-Robin spaces) that do


Neurology_Adams

Neurology_Adams. arteries, 50 to 200 μm in diameter, and the cribriform state, to mere thickening of vessels and fraying of the surrounding tissue—that is, dilated perivascular spaces (Virchow-Robin spaces) that do not have a corresponding neurologic disease.


Neurology_Adams

Neurology_Adams. In almost all clinical and pathologic material, there has been a strong relationship between the lacunar state and chronic hypertension, but also diabetes and hyperlipidemia. Sacco and colleagues (1991), in a population-based study in Rochester, Minnesota, found that 81 percent of patients with lacunar infarctions were also hypertensive. There appear to be three mechanisms for lacunar infarction but variants of atherothrombosis are foremost. The first, and traditionally most characteristically tied to lacunes, is a local type of fibrohyalinoid arteriolar sclerosis that involves the orifice or proximal part of a small penetrating blood vessel (lipohyalinosis as described below). The second is atherosclerosis of a large trunk vessel that occludes the origin of these same small vessels. This is prone to involve several adjacent vessels and cause, at times, larger lacunes or the atherosclerosis extends from a trunk vessel into a smaller one. Third is the entry of small embolic material


Neurology_Adams

Neurology_Adams. is prone to involve several adjacent vessels and cause, at times, larger lacunes or the atherosclerosis extends from a trunk vessel into a smaller one. Third is the entry of small embolic material into one of the vessels. The relative frequency of these three pathologies is not known, but the first seems to be most common and occurs without pathologic change in the trunk vessel of the circle of Willis whereas the embolic type is least frequent. When Fisher (1975) examined a series of such lesions in serial sections, from a basal parent artery up to and through the lacune, he was able to confirm a lipohyalin degeneration of the vessel wall and occlusion in the initial course of small vessels in most cases. In some, lipohyalinotic changes had resulted in false aneurysm formation, resembling the Charcot-Bouchard aneurysms, another hypertension-related change that underlies brain hemorrhage (see further on). In a series of 1,042 consecutive adults whose brains were examined postmortem,


Neurology_Adams

Neurology_Adams. the Charcot-Bouchard aneurysms, another hypertension-related change that underlies brain hemorrhage (see further on). In a series of 1,042 consecutive adults whose brains were examined postmortem, Fisher (1965b) observed one or more lacunes in 11 percent but that certainly reflected the lack of adequate treatment of hypertension and hyperlipidemia of that time. He found 4 to 6 and sometimes up to 10 to 15 lacunes in any given brain specimen. In recent years, better treatment of hypertension has greatly reduced this number and the overall frequency of lacunar infarction, at least as judged by MRI.


Neurology_Adams

Neurology_Adams. Lacunes are situated, in descending order of frequency, in the putamen and caudate nuclei, thalamus, basis pontis, internal capsule, and deep in the central hemispheral white matter. The cavities range from 3 to 15 mm in diameter, and whether they cause symptoms depends entirely on their location.


Neurology_Adams

Neurology_Adams. Lacunar strokes tend to evolve quickly but not typically as suddenly as an embolus, for example. These clinical aspects are discussed extensively in the earlier section “Lacunar TIA.” In broad terms, the essential feature of these deep strokes is the striking absence of cortical deficits; that is, seizures, aphasia or amnesia (except in limited circumstances of small thalamic infarction), agnosia, apraxia, dysgraphia, alexia, and a number of cognitive changes. Multiple deep strokes can result in a dementia of the type discussed in Chap. 20. Furthermore, because of the small size of the strokes, certain clinical syndromes that might be expected to result from deep lesions, such as hemianopia, also do not occur. Fisher, in several papers (1965a, 1967, 1979) and in an iconic review 1965b, delineated the most frequent symptomatic forms of lacunar stroke: 1. Pure motor hemiplegia 2. Pure sensory stroke 3. Clumsy hand–dysarthria 4. Ipsilateral hemiparesis–ataxia


Neurology_Adams

Neurology_Adams. A lacune in the territory of a lenticulostriate artery, that is, in the internal capsule or adjacent corona radiata, usually causes a highly characteristic syndrome of pure motor hemiplegia involving the opposite face, arm, hand, leg, and foot in approximately equal measure. A lacune situated in the ventral pons causes an identical syndrome as discussed in an earlier section (Fig. 33-17). Most often the symptoms begin abruptly but not as rapidly as in embolic infarction, or evolve over several hours; in rare instances the neurologic deficit evolves stepwise and relatively slowly, exceptionally over as long a period as 2 to 3 days. Our experience has tended toward the shorter time frame, with most patients reporting that the full deficit is present not instantaneously but within minutes. Recovery, which may begin within hours, days, or weeks, is sometimes nearly complete even in the face of a severe initial stroke. However, many patients are left with some degree of clumsiness or


Neurology_Adams

Neurology_Adams. Recovery, which may begin within hours, days, or weeks, is sometimes nearly complete even in the face of a severe initial stroke. However, many patients are left with some degree of clumsiness or slowness of movement of the affected side.


Neurology_Adams

Neurology_Adams. The motor disorder may take the form of a hemiparesis of the face and arm or arm and leg, or predominantly arm and proximal leg weakness; these fragmented patterns are indicative of a lesion located higher than the internal capsule, in the centrum semiovale. In these cases, the stroke simulates an embolic stroke affecting the cortex. A lacune of the lateral thalamus or (less often of the deep parietal white matter) is the cause of hemisensory defect involving the limbs, face, and trunk extending to the midline with no motor or language difficulty, a pure sensory stroke. Partial sensory syndromes involving only parts of the hemibody are less frequent than in motor lacunar strokes. The incidence, course, and outcome are much the same as in a pure hemiplegia.


Neurology_Adams

Neurology_Adams. As mentioned, in the ventral pons, the lacunar syndrome may be one of pure motor hemiplegia, mimicking that of internal capsular infarction except at times for relative sparing of the face and the presence of an ipsilateral paresis of conjugate gaze in some cases; or there is another highly characteristic lacunar syndrome of a combination of dysarthria and clumsiness of one hand. This “clumsy hand–dysarthria” stroke is usually located in the paramedian midpons or in the posterior portion of the internal capsule opposite the affected limb. Occasionally, a lacunar infarction of the pons, midbrain, internal capsule, or parietal white matter gives rise to a hemiparesis with ataxia on the same side as the weakness (Fisher, 1965a; Sage and Lepore). Some of the brainstem syndromes may blend with basilar branch syndromes.


Neurology_Adams

Neurology_Adams. There are many other less frequent lacunar configurations but they can be identified by their similarity to one of the archetypal syndromes; they tend to affect one limited system or are fragments of a typical syndrome. Indeed, Fisher (1982) described 20 such variant types and several “miscellaneous” patterns. Some of these are difficult to accept, such as pure motor hemiparesis with confusion and loss of memory, but we have encountered many of the others, admittedly infrequently, including pure dysarthria, hemiballismus, virtual locked-in syndrome from bilateral lacunes in the base of the pons, and pure motor hemiplegia with sixth nerve palsy.


Neurology_Adams

Neurology_Adams. Some strokes that carry the term “lacune” are simply the result of larger deep cerebral infarctions along the lines of the striatocapsular stroke discussed earlier. In order to retain its clinical utility, the term lacune is probably best applied to small deep lesions that are the result of occlusion of a correspondingly small vessel and not to those strokes that result from occlusion of the orifices of several adjacent small vessels and are typically from larger atheromas in a parent vessel.


Neurology_Adams

Neurology_Adams. Multiple lacunar infarcts involving the corticospinal and corticobulbar tracts are a common cause of pseudobulbar palsy in clinical practice (trailed in frequency by amyotrophic lateral sclerosis and infiltrating tumors). Undoubtedly, an accumulation of lacunes deep in both hemispheres can give rise to gait disorders and also to mental dulling sometimes referred to as multiinfarct dementia (see further on and Chap. 20). The main differential diagnostic considerations are normal-pressure hydrocephalus (see Chap. 29) and the common degenerative brain conditions that affect the frontal lobes and basal ganglia (see Chap. 38). Finally, it should be emphasized that what appears initially to be a lacunar syndrome may be the initial component or warning sign of a large deep territory infarction in the middle, posterior cerebral, or basilar arteries.


Neurology_Adams

Neurology_Adams. As mentioned earlier, MRI is more reliable than CT in demonstrating the lacunes. Initially, lacunes are seen on the MRI as deep oval or linear areas of T2, fluid-attenuated inversion recovery (FLAIR) and, especially, diffusion-weighted signal abnormality; later they become cavitated. Representative lacunar infarctions are shown in Fig. 33-17. The EEG, while little used for this purpose nowadays, may be helpful in a negative sense; in the case of lacunes in the pons or the internal capsule, there is a notable discrepancy between the unilateral paralysis or sensory loss and the negligible electrical changes over the affected hemisphere and, even with lacunes of the deep cerebrum, any EEG changes are disproportionately mild in comparison to the deficit.


Neurology_Adams

Neurology_Adams. The main objective in these forms of ischemic cerebrovascular disease is the amelioration of the existing deficit and the prevention of future stroke. It is now a major goal of general medicine to reduce the incidence of stroke in the general population by the control of modifiable risk factors. In addition to reduction of known risk factors such as hypertension, smoking, and glucose control in diabetics, the widespread use of cholesterol-lowering statin medications has been shown in some studies to reduce stroke incidence (“primary prevention”) and recurrence of stroke (“secondary prevention”). The use of anticoagulants to prevent stroke in patient with atrial fibrillation is a component of primary prevention. Although the risk of recurrent stroke is dependent on the underlying mechanism, some insight has been gained by the study of a cohort of patients with mild stroke or what have been considered to be “high-risk” TIAs in the modern era by Amarenco and colleagues (2016 and 2018).


Neurology_Adams

Neurology_Adams. some insight has been gained by the study of a cohort of patients with mild stroke or what have been considered to be “high-risk” TIAs in the modern era by Amarenco and colleagues (2016 and 2018). They estimated recurrence rates of approximately 4 percent at 90 days, 5 percent at a year and another 6 percent between the end of the first year and the fifth year. The treatment of stroke may be divided into three broad parts: management in the acute phase by measures to restore the circulation and arrest the pathologic process, physical therapy and rehabilitation, and measures to prevent further strokes and progression of vascular disease.


Neurology_Adams

Management in the Acute Phase

Neurology_Adams. Management in the Acute Phase


Neurology_Adams

Neurology_Adams. With the inception of thrombolytic agents for stroke and the advances in endovascular procedures for thrombectomy, acute stroke treatment has evolved to emphasize rapid restoration of perfusion through occluded cerebral vessels. The steps in the process are now dominated by rapidly determining the patient’s eligibility for intravenous and intra-arterial revascularization treatment and the timing of these steps has been derived from a series of randomized clinical trials. The current practice is to use intravenous thrombolysis within 3 h if there is no intracranial hemorrhage on CT and with additional qualifications, up to 4.5 h of stroke onset (Hacke et al, 2008). If vascular imaging performed during or after intravenous thrombolysis treatment shows large vessel occlusion (distal internal carotid or proximal middle cerebral arteries), the patient is eligible for endovascular thrombectomy or thrombolysis. If vascular imaging at that point shows no proximal arterial occlusion, no


Neurology_Adams

Neurology_Adams. carotid or proximal middle cerebral arteries), the patient is eligible for endovascular thrombectomy or thrombolysis. If vascular imaging at that point shows no proximal arterial occlusion, no endovascular procedure is undertaken. Beyond 4.5 h (“outside the window”), intravenous thrombolysis is not used. If there is a large vessel occlusion and the patient is seen between 4.5 and 6 h of stroke onset, endovascular treatment is undertaken based on several trials including SWIFT-PRIME (see Saver et al). Beyond 6 h after stroke onset, and extending to at least 18 h and probably to 24 h, including if the patient awakens from sleep with a stroke (“last seen well”) and there is large vessel occlusion demonstrated by vascular imaging, endovascular treatment is possible but only of advanced imaging demonstrates a mismatch between the size of the infarction (diffusion volume) and a region of hypoperfused ischemic, but not yet infarcted tissue (perfusion defect). This has created a notion that


Neurology_Adams

Neurology_Adams. demonstrates a mismatch between the size of the infarction (diffusion volume) and a region of hypoperfused ischemic, but not yet infarcted tissue (perfusion defect). This has created a notion that imaging demonstration of perfusion defects could be a better gauge than the time interval from onset of symptoms for predicting response to treatment. There are also clinical and laboratory features that preclude various of these steps, as noted below. Medical systems have had to adapt to the resource requirements to carry out these therapies.


Neurology_Adams

Neurology_Adams. Tissue plasminogen activators (recombinant tPA) convert plasminogen to plasmin. These drugs were shown to be effective in the treatment of stroke decades after the demonstration that they were effective for coronary artery occlusion. Alteplase and tenecteplase are the main genetically engineered forms of plasminogen activators. Tenecteplase has a higher fibrin specificity and longer duration of action compared to alteplase. In the following discussion, we use “tPA” to represent all tissue plasminogen activators.


Neurology_Adams

Neurology_Adams. The benchmark study organized by the National Institute of Neurological and Communicative Disorders and Stroke (see the NINCDS and Stroke rtPA Stroke Study Group in the references) provided evidence of benefit from intravenous tPA. Treatment within 3 h of the onset of symptoms led to a 30 percent increase in the number of patients who remained with little or no neurologic deficit when examined 3 months after the stroke; this benefit persisted when assessed 1 year later in the study by Kwiatkowski and associates. Two aspects are notable: the benefits extended to all types of ischemic strokes, including those caused by occlusion of small vessels (lacunes), and improvement was not apparent in the days immediately following treatment, only when patients were examined at 3 months.


Neurology_Adams

Neurology_Adams. We make a comment here about the historically important, seminal NIH study, in which tPA was administered in a dose of 0.9 mg/kg, 10 percent of which was given as an initial bolus, followed by an infusion of the remainder over 1 h. A dose of 90 mg was not exceeded, this being lower than the dose used for myocardial infarction. The relative improvement in neurologic state came at the expense of a 6 percent risk of symptomatic cerebral hemorrhage and 4 percent of insignificant hemorrhages seen on imaging, that is, a lower rate than in most previous studies but twice the expected rate without thrombolysis (some of the hemorrhages were into the area of infarction and did not cause symptomatic worsening). Patients were excluded from the study if they had massive infarctions (encompassing more than two-thirds of the territory of the middle cerebral artery), had high scores on a clinical stroke scale that was devised for the National Institutes of Health (NIH) study (available at:


Neurology_Adams

Neurology_Adams. more than two-thirds of the territory of the middle cerebral artery), had high scores on a clinical stroke scale that was devised for the National Institutes of Health (NIH) study (available at: http://www.ninds .nih.gov/doctors/NIH_Stroke_Scale.pdf and from other sources) had uncontrolled hypertension, were more than 80 years of age, or had recently received anticoagulants (except aspirin). Further analysis of the NINCDS trial revealed that patients who were treated earliest within the 3-h time frame had more benefit than those treated later; indeed, the administration of tPA in the time between 2.5 and 3 h after the stroke was of less value. One trial has suggested that a lower dose of tPA (0.6 mg/kg) is non-inferior to the standard dose in a population of predominantly Asian patients (Anderson et al 2016).


Neurology_Adams

Neurology_Adams. For tenecteplase, doses of 0.25 mg/kg or 0.4 mg/kg have been used for thrombolysis and achieved comparable results. The trial reported by Logallo comparing tenecteplase at the higher dose to alteplase showed no difference between groups in clinical outcomes but other trials, such as the one by Parsons et al and by Campbell et al showed an improved rate of revascularization before thrombectomy, in the latter of 22% compared to 10% with alteplase using a lower dose of 0.25 mg/kg.


Neurology_Adams

Neurology_Adams. Attempts to establish that patients with a longer duration of ischemic symptoms benefit from thrombolysis by tPA have varied in success but have favored an effect up to 4.5 h as noted below. In some patients with basilar artery occlusion and coma of brief duration and those without extensive thrombosis, prompt tPA treatment has at times also resulted in an overall improvement in neurologic function, but there were numerous exceptions. Adapted from guidelines issued by the American Heart Association are the generally agreed upon inclusion and exclusion criteria for the use of intravenous tPA as shown in Table 33-6. Intracranial and systemic bleeding is, of course, the great concern and a minor but interesting point is that some patients, who had been receiving angiotensin-converting enzyme inhibitors for the treatment of hypertension, seem to display angioneurotic edema as a side effect of tPA.


Neurology_Adams

Neurology_Adams. Generally excluded from thrombolysis are those patients in whom the deficit is either very small (e.g., hand affected only, dysarthria alone, minor aphasia), rapidly improving, or more importantly, is so large as to implicate almost the entire territory of the middle cerebral artery. Many centers have expanded their practices beyond the confines of the initial NIH study, treating patients older than age 80 years and some with large strokes. Also ambiguous is the treatment with tPA of patients with acute stroke in whom the referable cerebral vessels are entirely patent. Often, the patency of the vessel is not known. Public health education should increase the numbers of stroke patients who seek early attention and thus raise the proportion who are eligible for tPA treatment.


Neurology_Adams

Neurology_Adams. Thrombolytic substances injected intraarterially (thrombolysis), or mechanical lysis for disruption or removal of an intravascular clot (thrombectomy) can in some instances restore blood flow of the middle cerebral and basilar arteries. There is an incidence of reocclusion of the treated vessel. The more recent approaches involve the use of a device that retrieves clots from the intravascular lumen. Whereas the initial trials were conducted in patients up to 6 h after stroke, more recently this window has been extended to 16 to 24 h with proper patient selection. The main criteria for selection of patients for thrombectomy in these trials have been: the presence of occlusion of the intracranial internal carotid, middle, or anterior cerebral arteries, and a mismatch between the extent of the stroke deficit and the volume of ischemic but not yet infarcted tissue, as judged either clinically or by imaging criteria (Albers et al, Kidwell et al, and Nogueira et al). The rate of symptomatic


Neurology_Adams

Neurology_Adams. stroke deficit and the volume of ischemic but not yet infarcted tissue, as judged either clinically or by imaging criteria (Albers et al, Kidwell et al, and Nogueira et al). The rate of symptomatic intracranial hemorrhage has been similar to that for intravenous thrombolysis, approximately 6 percent. As all of these trials have enrolled patients with anterior circulation strokes, the problem of reversing the neurologic deficit from acute basilar artery thrombosis by the use of thrombectomy is being studied.


Neurology_Adams

Neurology_Adams. This refers to the opening of an occluded carotid artery immediately after a stroke with the intention of improving the clinical outcome; the issue of endarterectomy for the prevention of future strokes is another matter and is taken up in a later section. In past decades, there had been limited experience with immediate surgical removal of a clot from the carotid artery or the performance of a bypass to restore function. Ojemann and colleagues (1995) operated on 55 such patients as an emergency procedure; 26 of these had stenotic vessels and 29 acutely thrombosed vessels. Of the latter, circulation was restored in 21, with an excellent or good clinical result in 16. In 26 patients with stenotic carotid arteries, an excellent or good result was obtained in 19. Usually several hours will have elapsed before the diagnosis is established. If the interval is longer than 12 h, opening the occluded vessel is usually of little value and may present additional dangers. In any case, this


Neurology_Adams

Neurology_Adams. have elapsed before the diagnosis is established. If the interval is longer than 12 h, opening the occluded vessel is usually of little value and may present additional dangers. In any case, this approach has been largely supplanted by the above-described endovascular techniques, for which the results have been generally poor. Reoperation because the vessel has closed or caused an embolus immediately after carotid endarterectomy is a special circumstance in which rapid removal of a clot or repair of an intimal tear is performed more or less routinely and is also mentioned in a later section. This subject is reviewed again further on.


Neurology_Adams

Neurology_Adams. The separate issue of the endovascular treatment of intracranial atherosclerosis is considered here for convenience. The risks of manipulating intracranial vessels are obvious, particularly those of the circle of Willis with no surrounding tissue because they are located within the subarachnoid space. In an attempt to determine if a stent and angioplasty would improve outcome in patients who had TIAs or minor strokes as a result of an intracranial stenosis, Chimowitz and colleagues (2011) reported that their trial was stopped early because of poor outcomes of the group who were treated by stent in comparison to medical management. The treatment of symptomatic intracranial atherosclerosis therefore remains problematic and is delegated to the antiplatelet drugs and lipid-lowering agents discussed further on.


Neurology_Adams

Neurology_Adams. Several considerations weigh in any discussion of the institution and choice of antiplatelet or anticoagulant treatment (meant here to denote the agents that alter the clotting cascade) for stroke. First is the distinction between anticoagulation to prevent the progression of an acute stroke and the prophylactic use of anticoagulation for the prevention of future strokes. Second, the pivotal issue in prevention of further strokes is whether the stroke or TIA is atherothrombotic or cardioembolic. As discussed further on, several studies point conclusively to a role for anticoagulation in stroke due to certain cardioembolic sources, particularly atrial fibrillation, while the indications in acute stroke are less certain.


Neurology_Adams

Neurology_Adams. Heparin treatment during an acute evolving stroke The two situations in which the immediate administration of heparin or an equivalent agent such as enoxaparin have drawn the most support from clinical practice are in basilar artery thrombosis with fluctuating deficits and in impending carotid artery occlusion from thrombosis or dissection. In these situations, the administration of heparin may be initiated while the nature of the illness is being clarified; the drug is then discontinued if contraindicated by new findings. Satisfactory clinical studies in support of this approach of acute anticoagulation have not been carried out and most authoritative writers find no evidence for the use of heparin in these situations (e.g., see Report of the Joint Stroke Guideline Development Committee authored by Coull et al). One fact seems fairly clear—that the administration of anticoagulants is not of great value for acute amelioration once the stroke is fully developed. Most clinical trials


Neurology_Adams

Neurology_Adams. authored by Coull et al). One fact seems fairly clear—that the administration of anticoagulants is not of great value for acute amelioration once the stroke is fully developed. Most clinical trials have too few such cases to evaluate the results of treatment.


Neurology_Adams

Neurology_Adams. Swanson has reviewed several trials evaluating heparin (including the International Stroke Trial and the TOAST study) and suggested that there was no net benefit from heparin in acute stroke because of an excess of cerebral hemorrhages. However, in these series there was a low incidence, estimated as 2 percent, of recurrent stroke in the first weeks after a cerebral infarction in the untreated groups. An early recurrent stroke rate this low almost precludes demonstrating a benefit from the use of heparin or heparinoid drugs. The issue of administering heparin or low molecular weight heparin subcutaneously in cases of recent cardioembolic cerebral infarction, particularly as a “bridge,” while waiting for the effects of an oral anticoagulant to be established is addressed further on. Heparin is also used by some practitioners in stuttering small vessel lacunar stroke but the effects are uncertain.


Neurology_Adams

Neurology_Adams. In the event heparin is used, and assuming tPA has not been used in the preceding 24 h, heparin may be given intravenously, beginning with a bolus of 100 U/kg followed by a continuous drip (1,000 U/h) and adjusted according to the partial thromboplastin time (PTT). Bleeding into any organ may occur when the PTT is greater than 3 times the pretreatment level. When the PTT exceeds 100 s, it is preferable to discontinue the infusion, check the blood clotting values, and then reinstitute the infusion at a lower rate based on the test results (rather than simply lower the infusion rate). In circumstances of fluctuating basilar artery ischemia, it is our practice to permit higher values of PTT.


Neurology_Adams

Neurology_Adams. The use of low-molecular-weight heparin (enoxaparin or nadroparin) given subcutaneously within the first 48 h of the onset of symptoms have uncertain benefit. In a limited trial, there was no increase in the frequency of hemorrhagic transformation of the ischemic region when compared to placebo treatment (Kay et al). Because the outcome measures in this study were coarse (death or dependence 6 months after stroke), further investigations of this approach need to be carried out. We can only infer that the use of low-molecular-weight heparins appears to be safe but there is no compelling evidence supporting their use in acute ischemic stroke. Treatment of Brain Swelling (Edema) and Raised Intracranial Pressure After Ischemic Stroke (See Also Chap. 34)


Neurology_Adams

Neurology_Adams. In the first few days following massive cerebral infarction, brain edema of the necrotic tissue may threaten life. Most often this occurs with a complete infarction in the territory of the middle cerebral artery, that is, encompassing the deep and distal vascular territory. Some degree of mass effect may be evident on a CT in the first 24 h. Additional infarction in the territory of the anterior cerebral artery (total carotid occlusion) worsens the situation. Clinical deterioration occurs usually on the third to fifth days, sometimes later, but may rarely evolve as quickly as several hours after the onset (Fig. 33-18). The clinical indicators of worsening—drowsiness, a fixed (but not necessarily enlarged) pupil, a Babinski sign on the side of the infarction (on the preserved side of the body), and changes in breathing pattern, as well as characteristic imaging signs—are all a result of secondary tissue shifts, as described in Chaps. 16 and 29 and are detailed in the studies of Hacke


Neurology_Adams

Neurology_Adams. body), and changes in breathing pattern, as well as characteristic imaging signs—are all a result of secondary tissue shifts, as described in Chaps. 16 and 29 and are detailed in the studies of Hacke and colleagues (1996), and Ropper and Shafran. Frank has shown that clinical deterioration is not always associated with an initial elevation of intracranial pressure (ICP). It is not clear if it is advisable, in selected cases, to measure the ICP directly before embarking on an aggressive medical regimen to lower the pressure.


Neurology_Adams

Neurology_Adams. The mechanism of this type of massive brains swelling is not known but may have to do with disruption of endothelial barriers in the infarcted regions and the passive transit of water and solutes into brain tissue. Presumably the main factor in swelling is edema rather than increased blood volume. That the size of the infarct is more important in the than reperfusion of a region was shown by Kimberly et al, who analyzed patients in one of the larger endovascular thrombectomy trials and found that successful reperfusion was associated with less edema. Intravenous mannitol in doses of 1 g/kg, then 50 g every 2 or 3 h, or hypertonic saline may forestall further deterioration, but most of these patients, once comatose, are likely to die unless drastic measures, such as hemicraniectomy, are taken. In such instances, controlled hyperventilation may be useful as a temporizing maneuver. Glucocorticoids are of little value; several trials have failed to demonstrate their efficacy.


Neurology_Adams

Neurology_Adams. In the past several decades, there has been the inception of hemicraniectomy as a means of reducing the mass effect and intracranial pressure in these extreme circumstances (see Schwab et al). One favored approach has been to perform hemicraniectomy early in the course of brain swelling, in the first 2 or 3 days, when the patient is drowsy but before coma supervenes. A pooled analysis of three randomized trials based on this premise has been given by Vahedi and colleagues. Excluding patients older than age 60 years, a total of 93 patients who were not fully alert could be analyzed. An advantage in survival was found favoring the group operated within 48 h. There has been controversy regarding the functional status of survivors and this involves the matter of the desirability of patients remaining with modified Rankin scale scores of 4, meaning they are dependent on others for their personal care. A controlled trial conducted in patients over age 60 has confirmed a beneficial effect of


Neurology_Adams

Neurology_Adams. with modified Rankin scale scores of 4, meaning they are dependent on others for their personal care. A controlled trial conducted in patients over age 60 has confirmed a beneficial effect of hemicraniectomy in preventing death from brain swelling after stroke. However, not surprisingly, the proportion of survivors with good functional outcomes in this older group was not as high as for younger patients.


Neurology_Adams

Neurology_Adams. One practice has been to wait for signs of deterioration, generally leading to operation on fewer than half of patients with large MCA territory strokes and, generally having operations from the third through fifth days. The family must understand the risks involved and the likelihood that the stroke deficits will persist so that approximately a third of surviving patients will be dependent for care. Hemicraniectomy combined with an overlying duraplasty is then undertaken if the patient is progressing from a stuporous state to coma and imaging studies show increasing mass effect. Whether anterior temporal lobectomy is of added benefit is not known, but it is now infrequently included. The value of surgical decompression has not been limited to patients with right-hemispheric strokes; those with mild or moderate of aphasia may also be appropriate candidates. After a protracted period of coma with bilaterally enlarged pupils or with evidence that the midbrain has been irrevocably


Neurology_Adams

Neurology_Adams. those with mild or moderate of aphasia may also be appropriate candidates. After a protracted period of coma with bilaterally enlarged pupils or with evidence that the midbrain has been irrevocably damaged, the procedure may be futile.


Neurology_Adams

Neurology_Adams. In the special case of large cerebellar infarctions, usually from occlusion of a vertebral artery, swelling may compress the lower brainstem within hours or days. This complication carries the risk of sudden respiratory arrest. Cerebellar swelling may occur with or without an associated lateral medullary stroke and the situation is comparable to medullary compression caused by cerebellar hemorrhage. Hydrocephalus usually develops as a prelude to deterioration and is manifest as drowsiness and stupor, increased tone in the legs, and Babinski signs; other sentinel signs of compression of the brainstem are gaze paresis, sixth nerve palsy, or hemiparesis ipsilateral to the ataxia (Kanis and Ropper). It is at times difficult to differentiate the effects of increasing hydrocephalus from those of brainstem infarction from thrombus propagation in the basilar artery (Lehrich et al). Surgical decompression of the infarcted and swollen tissue should be undertaken almost as soon as cerebellar


Neurology_Adams

Neurology_Adams. of brainstem infarction from thrombus propagation in the basilar artery (Lehrich et al). Surgical decompression of the infarcted and swollen tissue should be undertaken almost as soon as cerebellar edema becomes clinically apparent by the emergence of hydrocephalus or brainstem signs, as further swelling can be anticipated. A brief period of observation before committing to surgery is not unreasonable if the fourth ventricle and peribrainstem cisterns are open and the patient is awake. Mannitol may be used to prepare the patient for surgery or if a period of observation is anticipated but its value is not clear. As in the case of cerebellar hemorrhage, ventricular drainage alone is usually inadequate and, in any case, is unnecessary if the pressure is relieved by hemicraniectomy and resection of infarcted tissue.


Neurology_Adams

Neurology_Adams. The relative advantages of placing the seriously ill acute stroke patient in a special stroke unit have been the subject of much study. The outcome in these patients in terms of morbidity and mortality is improved, although the differences have been small and difficult to document. However, this organizational plan has not been widely implemented and instead protocols for rapid evaluation of stroke and the emergence of a specialty of stroke neurology have proliferated. If nothing else, this is the result of a general recognition that stroke, like myocardial infarction, requires special expertise and focus. Protocols to prevent excessive hypertension after thrombolytic treatment are best instituted in units that have staffing patterns that create familiarity with these and other protocols. As already emphasized, the prevention of aspiration and pneumonia is paramount by identifying those patients at risk. The patients at risk also benefit from systematic application of protocols. Also


Neurology_Adams

Neurology_Adams. As already emphasized, the prevention of aspiration and pneumonia is paramount by identifying those patients at risk. The patients at risk also benefit from systematic application of protocols. Also deserving attention is the prevention of venous thrombosis in the legs, pulmonary embolism, and coronary syndromes. Some units find it advisable to keep patients supine for the first hours or day after an ischemic stroke, mainly to prevent hypotension and cerebral hypoperfusion; this approach has not been studied systematically. When sitting and walking begin, special attention should be given to the maintenance of normal blood pressure. The rigid control of glucose after stoke has fallen in and out of favor based on various trials but it generally prudent to keep glucose within reasonably normal levels.


Neurology_Adams

Neurology_Adams. Despite conflicting evidence, current practice has encouraged the maintenance of euglycemia. Experimental models of ischemic stroke certainly support the avoidance of hyperglycemia. This is complicated by the high frequency of diabetes as a risk factor for stroke and the need to make decisions regarding glycemic control. Excessively tight control of glucose may not confer a benefit in the acute phase.


Neurology_Adams

Neurology_Adams. Several studies have confirmed the high prevalence of new or enhanced levels of hypertension immediately following an ischemic stroke and its tendency to decline over subsequent days even without medications. The treatment of previously unappreciated hypertension is preferably deferred until the neurologic deficit has stabilized. As suggested by Britton and colleagues, it is prudent to avoid antihypertensive drugs in the first few days unless there is active myocardial ischemia or the blood pressure is high enough to pose a risk to other organs, particularly the kidneys, or there is a special risk of cerebral hemorrhage as a result of the use of thrombolytic drugs.


Neurology_Adams

Neurology_Adams. Other forms of medical treatment In the past, treatment by hemodilution was popularized by the studies of Wood and Fleischer, who showed a high incidence of short-term improvement when the hematocrit was reduced to approximately 33 percent. That lowering blood viscosity improves regional blood flow in the heart had been known for some time, and a similar effect on the brain has been demonstrated by CBF studies. Earlier observations had shown a reduction in the overall neurologic deficit, but almost all larger randomized trials—which included patients in many settings who were treated at various times up to 48 h after stroke—failed to confirm any such benefit and the use of this treatment has been virtually abandoned. Therapies aimed at improving blood flow by enhancing cardiac output (aminophylline, pressor agents), by improving the microcirculation (mannitol, glycerol, dextran), or by use of a large number of vasodilating drugs (see below) have failed to show consistent benefits, but


Neurology_Adams

Neurology_Adams. pressor agents), by improving the microcirculation (mannitol, glycerol, dextran), or by use of a large number of vasodilating drugs (see below) have failed to show consistent benefits, but several are still under study. Normobaric and hyperbaric oxygen may reduce ischemic deficits temporarily but have no sustained effect. A trial in over 8,000 patients failed to demonstrate benefit of low dose supplemental oxygen in the acute setting (Roffe et al). Induced hypothermia limits the size of ischemic stroke, but it is technically difficult to administer and often has serious side effects. In the past, much attention was paid to head and body positioning in the acute phase of stroke but the sitting up position failed to confer an advantage over the supine position in a randomized trial (Anderson et al).


Neurology_Adams

Neurology_Adams. Calcium channel blockers of the types administered for cardiac disease increase CBF and to reduce lactic acidosis in stroke patients. However, several multicenter clinical trials that compared calcium channel blockers with placebo did not establish a difference in outcome in the two groups. There has also been interest, as noted earlier in this chapter, in drugs that inhibit excitatory amino acid transmitters and free-radical scavengers such as dimethyl sulfoxide (DMSO) and growth factors, but so far none of these has been successfully applied to humans.


Neurology_Adams

Neurology_Adams. Despite some experimental evidence that certain vasodilators, such as CO2 and papaverine, increase CBF, none has proved beneficial in carefully studied human stroke cases at the stage of TIAs, thrombosis in evolution, or established stroke. Vasodilators may actually be harmful, at least on theoretical grounds, because by lowering the systemic blood pressure or dilating vessels in normal brain tissue (the autoregulatory mechanisms are lost in vessels within the infarct); they may reduce the intracranial anastomotic flow. Moreover, the vessels in the margin of the infarct (border zone) are already maximally dilated. New discoveries regarding the role of nitric oxide in vascular control will probably give rise to new pharmacologic agents that will require evaluation. The metabolic stresses of ischemia and the production of destructive oxygen-free radicals were referred to earlier. Among the numerous “brain-sparing” agents that have been tried in an attempt to reduce the size of


Neurology_Adams

Neurology_Adams. of ischemia and the production of destructive oxygen-free radicals were referred to earlier. Among the numerous “brain-sparing” agents that have been tried in an attempt to reduce the size of infarction, certain ones have had erratic results in large randomized trials. Two trials, for example, gave initially promising results and later proved ineffective (Shuaib et al). These agents were of interest because they can be administered up to several hours after the stroke (continuing for 72 h). So far, the results of neuroprotective agents in stroke have been discouraging.


Neurology_Adams

Neurology_Adams. Primary and Secondary Prevention of Ischemic Stroke In addition to reduction in the well-known risk factors for vascular disease, certain measures have been shown to reduce the risk of a subsequent stroke and to prevent a first stroke. Many of these approaches have required large randomized trials, sometimes in selected populations, in order to demonstrate significant differences compared to no treatment or to various comparators. For this reason, it is often uncertain how to apply these findings to the individual patient but they have found their way into guidelines. Anticoagulants for the Primary Prevention of Strokes (See Table 33-3)


Neurology_Adams

Neurology_Adams. With regard to primary stroke prevention, convincing evidence favoring the efficacy of anticoagulants in the prevention of embolism in patients with atrial fibrillation came from the Boston Area Anticoagulant Trial for Atrial Fibrillation in 1990. Initially, patients younger than 65 years of age in this and other trials did not clearly benefit from long-term prophylactic anticoagulation unless there were additional cerebrovascular risk factors such as diabetes, hypertension, congestive heart failure, or cardiac valvular disease but newer studies have extended this age range for those with atrial fibrillation. (Those younger than 65 years old and without such additional features [formerly called lone fibrillators], constituting about one-third of adults with atrial fibrillation, have a low risk of stroke). In order to estimate the risk of stroke in atrial fibrillation, including age as a factor so as to address those younger than 65, two variants of what are termed CHADS scores have


Neurology_Adams

Neurology_Adams. risk of stroke). In order to estimate the risk of stroke in atrial fibrillation, including age as a factor so as to address those younger than 65, two variants of what are termed CHADS scores have been developed as summarized in Table 33-3.


Neurology_Adams

Neurology_Adams. Aspirin does not appear to afford the same degree of protective benefit as does anticoagulation for primary risk stroke reduction in atrial fibrillation, and some studies suggest if there are no other risk factors for stroke, there may be slightly better risk reduction for stroke with aspirin than with no treatment. For patients under age 65 and without other risk factors for stroke, reflected usually by a low CHADS score, aspirin may be reasonable preventive measure. The appropriate dose of aspirin has not been established but former trials of very large doses, for example, 1 g/d, conferred risk of bleeding.


Neurology_Adams

Neurology_Adams. A determination of prothrombin and partial thromboplastin activity is needed before therapy is started with warfarin, but if this is not feasible, the initial doses of anticoagulant drugs can usually be given safely if there is no clinical evidence of bleeding anywhere in the body and there has been no recent surgery. Warfarin, beginning with a dose of 5 to 10 mg daily, is relatively safe provided that the international normalized ratio (INR) is brought only to 2 to 3 (formerly measured as a prothrombin time between 16 and 19 s) and the level is determined regularly (an approximate plan is once a day for the first 5 days, then 2 or 3 times a week for 1 to 2 weeks, and finally once every several weeks).


Neurology_Adams

Neurology_Adams. Numerous drugs may alter the anticoagulant effects of the coumarins or add to the risk of bleeding—aspirin, cholestyramine, alcohol, carbamazepine, cephalosporin and quinolone antibiotics, sulfa drugs, and high-dosage penicillin being the most important ones. Hemorrhagic skin necrosis is a rare but dangerous complication. It is the result of a paradoxical microthrombosis of skin vessels and is liable to occur in patients with unsuspected deficiencies of endogenous clotting proteins (S and C). Although the disseminated form of skin necrosis occurs within days of initiating warfarin therapy, we have seen one patient with a form of this lesion following local skin injury after months on treatment.


Neurology_Adams

Neurology_Adams. The introduction of factor Xa inhibitors has offered an alternative to the vitamin K antagonist, warfarin, for primary risk reduction of strokes in patients with atrial fibrillation. In one study by Granger and coworkers that used apixaban for this purpose, there were slightly fewer strokes and fewer cerebral hemorrhages than with warfarin when the intended goal with warfarin was to keep the INR between 2 and 3. Dabigatran and rivaroxaban confer similar reductions in stroke to apixaban and warfarin in atrial fibrillation (c.f., Patel et al). These drugs have the advantage over warfarin of not requiring regular blood tests for the measurement of the INR and of having fewer drug interactions. However, although they have short half-lives compared to warfarin, they are still present for many hours after discontinuation and anticoagulation is not easily reversible should there be systemic or cerebral bleeding. Drugs that reverse the anticoagulant effect of these new drugs are available or


Neurology_Adams

Neurology_Adams. hours after discontinuation and anticoagulation is not easily reversible should there be systemic or cerebral bleeding. Drugs that reverse the anticoagulant effect of these new drugs are available or being developed. (We mention here that reversal the effect of warfarin with, for example, vitamin K, and even with clotting factors, is also not rapid).