Neurology_Adams

Neurology_Adams. A frequent clinical problem arises in an elderly patient with atrial fibrillation who is at risk of falling from any of a number of causes including the stroke itself. In a review of selected administrative database records, Gage and colleagues concluded that the overall risk of inducing cerebral hemorrhage in older patients with atrial fibrillation treated with warfarin was lower than the risk of recurrent stroke. In those patients who had hemorrhages while receiving warfarin, they were, however, more likely to be fatal. Of course, decisions about anticoagulation must be tailored to the conditions of the individual patient.


Neurology_Adams

Neurology_Adams. For patients with atrial fibrillation of recent onset, an attempt should be made to restore normal sinus rhythm by the use of electrical cardioversion or a trial of antiarrhythmic drugs. If these fail, prophylactic anticoagulant therapy is recommended. Before attempting cardioversion of more long-standing atrial fibrillation, anticoagulation for several days or longer is advisable to reduce emboli.


Neurology_Adams

Neurology_Adams. Anticoagulant therapy may also be desirable for at least several weeks in patients with acute myocardial infarction, especially if the left side of the heart is involved. No guidelines have been established in these circumstances; the new common use of one or more platelet aggregation inhibitor drugs after myocardial infarction may preclude the concurrent use of warfarin. In cerebral embolism associated with bacterial endocarditis, anticoagulant therapy should be used cautiously because of the danger of intracranial bleeding, and one proceeds instead with antibiotics. Generally, we have not anticoagulated these patients.


Neurology_Adams

Neurology_Adams. Aspirin has proved to be the most consistently useful drug in the prevention of thrombotic and possibly, embolic strokes but its effects have been small in large trials both for primary prevention and for reducing the risk of a recurrent stroke. The acetyl moiety of aspirin combines with the platelet membrane and inhibits platelet cyclooxygenase, thus preventing the production of thromboxane A2, a vasoconstricting prostaglandin, and also prostacyclin, a vasodilating prostaglandin. One currently favored approach, based in part on the WARSS trial, is to simply administer aspirin in all cases of acute stroke. This approach is further endorsed by the WASID trial comparing aspirin (1,300 mg/d) to warfarin for treatment of intracranial arterial stenosis on the basis that warfarin was no better at preventing strokes while aspirin was associated with fewer gastrointestinal hemorrhages and a lower overall death rate. Confirmation of this approach was given by the IST and CAST trials that


Neurology_Adams

Neurology_Adams. at preventing strokes while aspirin was associated with fewer gastrointestinal hemorrhages and a lower overall death rate. Confirmation of this approach was given by the IST and CAST trials that established a modest reduction in mortality and stroke recurrence if aspirin was given within 48 h of stroke. Whether low doses of aspirin (50 to 100 mg) or high doses (1,000 to 1,500 mg) provide equivalent protection is still uncertain.


Neurology_Adams

Neurology_Adams. In patients who cannot tolerate aspirin, the platelet aggregate inhibitor clopidogrel or a similar drug can be substituted (see below). Ticlopidine and clopidogrel are considered, on the basis of clinical trials, to be equivalent to or marginally more effective than aspirin for the prevention of stroke. Furthermore, both drugs have potential side effects; ticlopidine may produce neutropenia and clopidogrel may cause thrombotic thrombocytopenic purpura. Dipyridamole in high doses has not been as well tolerated by many of our patients because of dizziness induced by peripheral vasodilatation.


Neurology_Adams

Neurology_Adams. The combined use of dual antiplatelet drugs (with aspirin) given for days or weeks after the stroke has generally been shown to be slightly superior to aspirin alone in secondary stroke prevention, but with an increased risk of cerebral hemorrhage in some trials. In most large trials, the incremental benefits of adding one of these drugs to aspirin has been of the order of 1 to 3 percent (see the ESPRIT study and Bhatt et al and Sacco et al, a trial that failed to show benefit for the addition of extended release of dipyridamole to aspirin). A study with over 5,000 patients from China, the CHANCE trial reported by Wang and coworkers, did demonstrate a reduction in stroke recurrence during the first 90 days after the first minor stroke or TIA by adding clopidogrel to aspirin, either 75 mg or 300 mg, and no increase in major systemic or intracranial hemorrhages. When the use of dual antiplatelet agents was extended to larger, non-Asian, populations, the POINT trial (Johnston et al),


Neurology_Adams

Neurology_Adams. mg or 300 mg, and no increase in major systemic or intracranial hemorrhages. When the use of dual antiplatelet agents was extended to larger, non-Asian, populations, the POINT trial (Johnston et al), there was an excess of major systemic hemorrhages (not cerebral hemorrhages) compared to aspirin alone and somewhat less reduction in rates of stroke compared to the CHANCE trial but treatment was nevertheless effective in reducing 90-day recurrent stroke risk. The overall risk-benefit ratio for stroke reduction versus major system hemorrhage was judged to be favorable. These two antiplatelet trials enrolled patients with minor stroke or TIA that was considered to be high risk for subsequent stroke as gauged by ABCD2 score. Therefore, it applies to patients who are not planned to have thrombolysis, thrombectomy or anticoagulation. One consideration in the understanding hemorrhage rates is that the first trial used dual antiplatelet drugs for only 3 weeks, whereas the latter trial


Neurology_Adams

Neurology_Adams. thrombolysis, thrombectomy or anticoagulation. One consideration in the understanding hemorrhage rates is that the first trial used dual antiplatelet drugs for only 3 weeks, whereas the latter trial continued dual therapy for 90 days, which may have explained the divergence in hemorrhage rates.


Neurology_Adams

Neurology_Adams. In trials comparing aspirin to anticoagulation for secondary stroke prevention in atrial fibrillation, anticoagulation has still been superior (see ACTIVE Writing Group). These studies notwithstanding, the therapeutic effectiveness of aspirin is still rather slight and the addition of clopidogrel to aspirin in patients who were not deemed suitable for warfarin reduces strokes over several years of observation but increases the risk of major bleeding so that the combination cannot be endorsed (ACTIVE Investigators). Moreover, in each of the trials, a significant number of subsequent ischemic strokes occurred even in patients while they were receiving aspirin.


Neurology_Adams

Neurology_Adams. In a trial of statins, the institution of high doses of drug reduced the incidence of subsequent stroke after a TIA or first stroke by 2 percent over 5 years (see Stroke Prevention by Aggressive Reduction in Cholesterol Investigators [SPARCL trial]). Other large studies with lower doses of statin drugs have not shown this effect. These findings with high doses have, at the moment, been adopted into routine practice. Recent guidelines encourage LDL concentrations of less than 70 mg/dL for secondary stroke prevention. Early anticoagulation after an acute stroke carries an uncertain risk of hemorrhagic transformation of an ischemic infarct. In particular, patients with very large cerebral infarcts that have a component of deep (basal ganglionic) tissue damage, especially in those patients who are also hypertensive, there may be a risk of anticoagulant-related hemorrhage into the acute infarct—“hemorrhagic conversion” (Shields et al).


Neurology_Adams

Neurology_Adams. When there is a compelling reason after an embolic stroke in a non-fibrillator to anticoagulate a patient for secondary stroke prevention (e.g., mechanical heart valve, known left ventricular thrombus, hypercoagulable state, and perhaps patent foramen ovale with deep venous thrombosis), opinions vary about the use and precise timing of instituting an anticoagulant. In a patient with atrial fibrillation who has had a recent embolic stroke, the concern for risk of hemorrhagic transformation of the ischemic area has led to the practice of a delay of up to several weeks in starting treatment. Many practitioners will start anticoagulation in the acute phase under these circumstances if the stroke is small. Details pertaining to anticoagulation in atrial fibrillation can be found earlier under “Anticoagulants for the Primary Prevention of Strokes from Atrial Fibrillation.”


Neurology_Adams

Neurology_Adams. While anticoagulation is established as a treatment for primary and secondary prevention of embolic strokes with atrial fibrillation, the situation with other strokes, including those presumed to be embolic strokes, is not clear (called “embolic stroke of uncertain source”). For example, a trial conducted by Hart and colleagues (2018) showed that rivaroxaban was not more effective than aspirin for the prevention of a second stroke after a stroke that was presumed to be embolic, but not due to atrial fibrillation or extracranial vascular disease.


Neurology_Adams

Neurology_Adams. For warfarin, in the past, there had been a concern for the theoretical risk of transient hypercoagulability when starting the drug (due to upregulation of protein S); this, and a desire to institute anticoagulation rapidly, led to a strategy of “bridging” with heparin or a low-molecular-weight heparin while awaiting the effects of warfarin to be evident. This risk has seemingly not had clinical significance. On the basis of the aforementioned trials of acute anticoagulation that showed only a 1 to 2 percent frequency of early recurrent stroke, most clinicians have eschewed the “bridging” approach. The view that opposes heparin or a similar bridging anticoagulant is based also on a retrospective study by Hallevi and colleagues, supported by a meta-analysis reported by Whiteley and coworkers, that found higher rates of symptomatic and serious bleeding in the brain or systemically with the bridging strategy.


Neurology_Adams

Neurology_Adams. A common problem in general medicine is that of the need to discontinue warfarin in patients with atrial fibrillation who must undergo an invasive diagnostic procedure or surgery. Little guidance can be offered except that a randomized trial conducted by Douketis and colleagues suggested that foregoing interim anticoagulation with low-molecular weight heparin was non-inferior to foregoing this bridging treatment.


Neurology_Adams

Neurology_Adams. Anticoagulation for prevention of recurrent stroke with atherosclerotic disease There had been a notion that warfarin is of some value in the first 2 to 4 months following the onset of an ischemic stroke due to atherosclerotic disease. However, the results of controlled studies have indicated that there is no reason to favor warfarin in comparison to aspirin in cases of atherothrombotic stroke. This was amply shown in the Warfarin-Aspirin Recurrent Stroke Study (WARSS; not including cardioembolic stroke) reported by Mohr and colleagues (2001); over 2 years the recurrent stroke rate was about 16 percent in both groups, and, surprisingly, the rate of cerebral hemorrhage was similar (near 2 percent). Similarly, for the special case of TIA or stroke that is shown to be because of intracranial atherosclerosis, Chimowitz and colleagues in the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial have suggested that warfarin provided no benefit over aspirin in preventing subsequent


Neurology_Adams

Neurology_Adams. atherosclerosis, Chimowitz and colleagues in the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial have suggested that warfarin provided no benefit over aspirin in preventing subsequent cerebrovascular events but warfarin had more risk as commented below. The WASID trial exposed not so much the deficiency of warfarin in prevention of stroke as much as the difficulties in its use, as pointed out by Koroshetz.


Neurology_Adams

Neurology_Adams. The justification for, and excess risk of hemorrhage, when combining an antiplatelet agent with warfarin, has not been quantified. There seems to be relatively small risk if low-dose (81 mg) aspirin is included in a regimen of warfarin for atrial fibrillation. Beyond this statement, little can be said with authority but our personal experience, certainly tainted by the weaknesses engendered by the availability heuristic, is that subdural hematomas abound in elderly patients, with or without falls, who are on one or more agents. Even the relatively rapid reversal of anticoagulation with vitamin K and one of the clotting factor preparations or fresh plasma do little more than allow for safer surgery to remove intracerebral clots. Certain conditions such as chronic renal failure may confer a greater risk of cerebral hemorrhage with either drug, but the stroke risk from atrial fibrillation is also increased in comparison to patients with normal renal function as described in the


Neurology_Adams

Neurology_Adams. confer a greater risk of cerebral hemorrhage with either drug, but the stroke risk from atrial fibrillation is also increased in comparison to patients with normal renal function as described in the epidemiologic study by Olesen and colleagues.


Neurology_Adams

Neurology_Adams. Closure of Patent Foramen Ovale (PFO) The role of the patent foramen ovale as a cause of stroke that is otherwise cryptogenic, has been a matter of contention for decades. Certainly, in some instances, such as a young individual who has demonstrable clots in the venous system of the legs or pelvis or who has had a recent pulmonary embolism, this mechanism becomes an appealing explanation. As mentioned earlier in the chapter, several epidemiologic and other studies have demonstrated a statistical association between strokes in the presence of a PFO. It had also been a matter of some contention whether the size of the cardiac defect or the presence of an associated atrial septal aneurysm raise the risk of stroke. Even in younger patients, simply the discovery of a PFO with the use of echocardiography and injection of agitated saline or similar method that highlights the potential for movement of material from the right into the left atrium is not nearly proof of a causative mechanism.


Neurology_Adams

Neurology_Adams. Moreover, the value of anticoagulation, either alone or in comparison to closure of the PFO, has been uncertain. Three trials prior to 2014 suggested little or no benefit from closure of a PFO after stroke but three subsequent trials published in 2017 demonstrated substantial reductions in recurrent ischemic stroke with closure compared to antiplatelet or anticoagulant treatment (see Ropper 2017 for summary of these trials). It should be pointed out that the populations in the last three positive trials were restricted to younger patients and those with moderate to large shunts across the defect or atrial septal aneurysms.


Neurology_Adams

Neurology_Adams. Comments have already been made concerning the opening of an occluded carotid artery soon after a stroke. Here we discuss secondary stroke prevention in the patient who has had TIAs or minor stroke and who has passed the acute period. The segment of the vessels that most often lends itself to endarterectomy or stenting is the carotid sinus (the bulbous expansion of the internal carotid artery just above its origin from the common carotid) because this is the site where atherosclerotic narrowing occurs. Other sites suitable for surgical or endovascular management include the common carotid, innominate, and proximal subclavian arteries. As mentioned earlier in the chapter, carotid artery disease most often causes strokes and single or repetitive TIAs but may also result in a hemispheral hypoperfusion syndrome as a result of low blood flow distal to a severe stenosis.


Neurology_Adams

Neurology_Adams. Surgery and stenting are as yet applicable mainly to the group of patients with symptomatic carotid artery stenosis (the asymptomatic ones are discussed below) who have substantial extracranial stenosis but not complete occlusion, and, in special instances, in those with nonstenotic ulcerated plaques. In formerly collected cohorts, carotid stenosis accounted for less than 20 percent of all TIAs (Marshall); but from the perspective of interventional therapy, the term symptomatic encompasses both TIAs and large or small strokes ipsilateral to the stenosis, some of which may be evident only with cerebral imaging.


Neurology_Adams

Neurology_Adams. There is evidence that well-executed surgery or stenting in appropriately chosen cases arrests the TIAs and diminishes the risk of future strokes. These views initially received strong affirmation from two often-cited randomized studies—the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgery Trial (ECST). The conclusion reached in each of these studies was that carotid endarterectomy for symptomatic lesions causing degrees of stenosis greater than 70 to 80 percent in diameter reduces the incidence of ipsilateral hemispheral strokes and shows greater benefit with increasing degrees of stenosis. The results apply generally only if surgical complication rates are below 3 percent. These two trials differed in the method of estimating the degree of stenosis, but when adjustments are made, the results are comparable (Donnan et al, 1998). Further analysis of the North American trial by Gasecki and colleagues indicated that the risk of cerebral


Neurology_Adams

Neurology_Adams. of stenosis, but when adjustments are made, the results are comparable (Donnan et al, 1998). Further analysis of the North American trial by Gasecki and colleagues indicated that the risk of cerebral infarction on the side of the symptomatic stenosis is increased if there is a contralateral carotid stenosis but that operated patients (on the side of symptomatic stenosis) still had fewer strokes than those treated with medication alone. In those with bilateral carotid disease, the risk of stroke after 2 years was 69 percent, and if operated, 22 percent. As to the timing of endarterectomy, opinions have diverged but a meta-analysis reported by Rothwell and colleagues (2004) has suggested that the maximum benefit is accrued if surgery is performed within 2 weeks of a TIA or minor stroke.


Neurology_Adams

Neurology_Adams. Carotid angioplasty and stenting offer an alternative to carotid endarterectomy. Direct comparisons have been made in several organized trials, initially in patients who were too ill to undergo endarterectomy but subsequently, in a larger population of symptomatic patients. In one early trial reported by the CAVATAS investigators (Carotid and Vertebral Artery Transluminal Angioplasty Study), the incidence of minor (nonstroke) complications was lower in patients who had angioplasty and stenting than for surgery. Otherwise, the recurrent stroke rates were similar, 10 percent for both groups. A useful comparison between angioplasty and surgical endarterectomy has been made in the trial reported by Mas and associates (2006) and in the “SPACE” trial. While the first of these favored a surgical approach for severe symptomatic stenosis, the second gave equivalent results of approximately 6 percent combined stroke and death rates with either procedure. Subsequent trials, such as CREST (Brott


Neurology_Adams

Neurology_Adams. approach for severe symptomatic stenosis, the second gave equivalent results of approximately 6 percent combined stroke and death rates with either procedure. Subsequent trials, such as CREST (Brott et al, 2010), and SAPPHIRE (Yadav et al), both of which had approximately half of patients with asymptomatic carotid stenosis, gave similar results, namely that recurrent stroke rates are alike for endarterectomy and stenting. Longer term follow of the CREST trial patients indicated that the stroke rates between the two groups remained similar up to 10 years (approximately 7 percent of patients in each group had a stroke ipsilateral to the affected side of carotid disease).


Neurology_Adams

Neurology_Adams. In the final analysis, the relative benefits of surgery or medical treatment (anticoagulation or aspirin) depend mainly on the surgical risk—including on the record of the individual surgeon. If there is an established operative complication rate of less than 3 percent, then surgery can be recommended in symptomatic patients with carotid stenosis greater than 70 percent. This benefit extends to elderly patients and, indeed, it has been shown on a statistical basis to be most evident in patients older than age 75 (see the post hoc analysis of NASCET data by Alamowitch et al). A trial in patients with complete atherosclerotic occlusion of the cervical internal, using extracranial to intracranial arterial bypass (COSS, reported by Powers and associates), failed to demonstrate an advantage of surgery over medical therapy. Bypass of this type is discussed further below and the section on Moyamoya disease.


Neurology_Adams

Neurology_Adams. Before operation or stenting, the existence of the carotid lesion and its extent must be determined. CTA and MRA have emerged as a surrogate procedures to the previously used catheter based imaging (Fig. 33-19). Severe stenosis is also indirectly reflected in filling of the distal branches of the external carotid artery before the branches of the middle cerebral artery are opacified—a reversal of the usual pattern. Increasingly, the diagnosis of carotid stenosis is being initially made by less invasive methods, but with ultrasonography there is some difficulty in quantifying severe stenosis and in separating it from complete carotid artery occlusion.


Neurology_Adams

Neurology_Adams. Endarterectomy, in a small number of cases may be followed by a new hemiplegia or aphasia that becomes evident in the hours after the procedure, usually by the time the patient arrives in the recovery room. In these cases, surgeons prefer to return the patient to the operating room and open the artery, as discussed earlier on. An intimal flap at the distal end of the endarterectomy and varying amounts of fresh clot proximal to it are usually encountered; but after removal and repair of the vessel, the effects of the stroke, if one has occurred, are not usually improved. The postoperative care of carotid endarterectomy focuses on reversing reflex hypotension that is induced by exposing the carotid wall to high perfusion pressure. This phenomenon can be reduced by infiltrating the carotid sinus with anesthetic prior to the operation. An uncommon but rather striking hyperperfusion syndrome develops several days to a week after carotid endarterectomy. The features are headache, focal


Neurology_Adams

Neurology_Adams. sinus with anesthetic prior to the operation. An uncommon but rather striking hyperperfusion syndrome develops several days to a week after carotid endarterectomy. The features are headache, focal deficits, seizures, brain edema, or cerebral hemorrhage. These are thought to reflect autoregulatory failure of the cerebral vasculature in the face of abrupt restoration of normal blood pressure and perfusion. After a long period of autoregulatory compensation for a stenotic carotid artery, then a normal cerebral perfusion pressure may result in endothelial incompetence with leakage of water across the blood–brain barrier. Unilateral severe headache is the most common symptom and may be the only manifestation. On occasion, cerebral edema is so massive as to lead to death (Breen et al). Treatment is by control of hypertension; it is unclear whether antiepileptic medications are required if there has been a seizure as a component of the syndrome. We mention here that an identical syndrome of


Neurology_Adams

Neurology_Adams. is by control of hypertension; it is unclear whether antiepileptic medications are required if there has been a seizure as a component of the syndrome. We mention here that an identical syndrome of focal cerebral deficits and brain edema, perhaps with the exception of seizures, has been seen, rarely and with no explanation spontaneously, in migraineurs (not those who have had endarterectomy), including two patients under our care.


Neurology_Adams

Neurology_Adams. For intracranial internal carotid occlusion that extends into the siphon and distally, a transcranial (superficial temporal–middle cerebral) and has caused a stroke, anastomosis had been employed in the past. Although this operation is technically feasible, its therapeutic value has been questioned by the multicenter study of The EC/IC Bypass Study Group (1985), who found that it did not produce a reduction in TIAs, strokes, or deaths. That study was criticized for having a skewed patient selection and several smaller and uncontrolled trials have suggested that the procedure may benefit some patients. A later trial (SAMMPRIS reported by Chimowitz and colleagues, 2011) indicated worse outcomes with intracranial stenting compared to medical management. There may, nevertheless, be particular circumstances that justify its use; for example, when there are ongoing TIAs in relation to upright posture or with episodes of mild hypotension.


Neurology_Adams

Neurology_Adams. Bypass procedures and their derivatives such as temporal-pial synangiosis may be useful in reestablishing flow to a hemisphere when there has been progressive intracranial carotid stenosis. Testament to the success of the bypass procedure is the regression of symptoms and of the network of collateral vessels in moyamoya disease (see further on).


Neurology_Adams

Neurology_Adams. Finally, there is the problem of the asymptomatic bruit over a carotid artery or incidentally discovered carotid artery stenosis when ultrasound or another diagnostic procedure is performed. A bruit generally corresponds to the reduction in luminal diameter of the artery to 2 mm or less and, while found in a large proportion of patients with severe stenosis, it is not specific and is heard in up to 10 percent of older patients who have little or no stenosis. The population studies by Heyman and associates over 40 years ago shed some light on this. They found, not surprisingly, that cervical bruits in men constituted a risk for death from ischemic heart disease, and that the presence of asymptomatic bruits in men (but not in women) carried a slightly increased risk of stroke. Notably, the subsequent stroke often did not usually coincide in its angioanatomic locus and laterality with the cervical bruit so that asymptomatic stenosis is in the short term a general marker for


Neurology_Adams

Neurology_Adams. Notably, the subsequent stroke often did not usually coincide in its angioanatomic locus and laterality with the cervical bruit so that asymptomatic stenosis is in the short term a general marker for atherosclerosis more so than for a proximate stroke. Other investigators have reported similar findings. On the other hand, Wiebers and colleagues (1990) found that patients with asymptomatic carotid bruits who were followed for 5 years were approximately three times more likely to have ischemic strokes than an ageand sex-matched population sample without carotid bruits. All of these cohorts were studied prior to the epoch of aggressive risk factor reduction, particularly with statin drugs.


Neurology_Adams

Neurology_Adams. The appropriate step when a carotid bruit is found during a routine examination is probably to obtain ultrasonography in order to quantify the presence of and degree of stenosis and to make subsequent decisions cautiously based on the studies discussed below. We usually also obtain imaging of the brain to determine if there has been a stroke on the side of the carotid disease—this aids in decisions regarding therapy. A note is made here regarding the self-audible bruit, which occasionally indicates carotid stenosis, dissection, or fibromuscular dysplasia, but is usually of less consequence and in some instances is associated with an enlarged and superiorly located jugular bulb—a benign anatomic variant that can be discerned on CT (Adler and Ropper).


Neurology_Adams

Neurology_Adams. Many attempts have been made to clarify the role of correcting asymptomatic carotid stenosis by means of endarterectomy. The Asymptomatic Carotid Atherosclerotic Study (ACAS) found that the frequency of strokes could be reduced from 11 to 5 percent over 5 years by removing the plaque if there was a stenosis greater than 60 percent (in diameter). These conclusions have been tempered by a reanalysis of the ACAS data, in which almost half of the strokes were of lacunar or cardioembolic (Inzitari et al). Data from a European trial, encompassing 3,120 patients (MRC Asymptomatic Carotid Surgery Trial [ACST] Collaborative Group), have indicated that asymptomatic carotid stenosis of more than 70 percent carries a 2 percent annual risk of stroke over a 5-year period and that the risk is reduced to 1 percent with endarterectomy. It was concluded that endarterectomy may be justified for asymptomatic carotid stenosis of this degree in men (not so in women) but that an audited surgical risk below


Neurology_Adams

Neurology_Adams. 1 percent with endarterectomy. It was concluded that endarterectomy may be justified for asymptomatic carotid stenosis of this degree in men (not so in women) but that an audited surgical risk below 3 percent was required to obtain favorable results (just as for symptomatic carotid stenosis). However, all of these trials were conducted before the ubiquitous use of statin drugs, which seemingly stabilize carotid plaques. Several trials comparing endarterectomy to stenting, some of which were commented on earlier, included asymptomatic patients but there were too few on which to base conclusions and, as for symptomatic cases, they were performed before the epoch of aggressive risk factor management. In a trial involving asymptomatic patients with severe carotid stenosis (mean stenosis by diameter of 74 percent) who were not at high risk for surgical complications, comparing endarterectomy to stenting with a device that captured embolic material, 5-year stroke rates were approximately 7


Neurology_Adams

Neurology_Adams. of 74 percent) who were not at high risk for surgical complications, comparing endarterectomy to stenting with a device that captured embolic material, 5-year stroke rates were approximately 7 percent in both groups ACTI, reported by Rosenfield et al).


Neurology_Adams

Neurology_Adams. None of these trials clearly resolve the issue of whether to intervene in asymptomatic carotid stenosis. From these and other trials it can be inferred that it is uncertain if endarterectomy reduces the incidence of strokes in patients who have asymptomatic carotid stenosis with luminal narrowing that is less than 60 to 70 percent of normal diameter. For those with greater degrees of stenosis, the benefits are slight and may apply predominantly to older men. It is not clear if the presence of an ulcerated plaque or heavy calcification alters this view but it probably does not. These comments also apply to patients with asymptomatic carotid stenosis who are about to undergo major surgery such as cardiac bypass grafting, but adequate studies in this circumstance have not been performed. As already noted, any advice should be tempered by the surgical risk in a particular institution. Our usual practice with asymptomatic cases has been to start medical treatment with statin agents,


Neurology_Adams

Neurology_Adams. As already noted, any advice should be tempered by the surgical risk in a particular institution. Our usual practice with asymptomatic cases has been to start medical treatment with statin agents, accompanied by smoking cessation, aspirin therapy, and glucose control and to reevaluate the lumen of the internal carotid artery (using ultrasonography) at 6to 12-month intervals. If the stenosis is advancing or becomes narrowed to about 2 mm or less, or if there is an event that could be construed as a TIA referable to the stenotic side, then surgery or endovascular treatment is considered.


Neurology_Adams

Neurology_Adams. These comments reflect the guidelines for asymptomatic carotid stenosis set forth by the American Heart Association in 2011 but there must be a careful evaluation of the circumstances in each patient, particularly the medical risk of endarterectomy, and a recognition that residual lumen diameters and percent stenoses are measured in different ways by varying techniques, both in the above-described studies and in clinical practice. Course and Prognosis of Ischemic Stroke


Neurology_Adams

Neurology_Adams. Course and Prognosis of Ischemic Stroke It is a fair statement that no rules have yet been formulated that allow prediction of the early or late course of stroke. A mild paralysis may become a disastrous hemiplegia or the patient’s condition may worsen only temporarily. In cases of basilar artery occlusion, dizziness and dysphagia may progress in a few days to total paralysis and deep coma. Or, in both cases, the deficit may completely resolve. Anticoagulation and thrombolytic or endovascular therapy may alter the course but cerebral thrombosis is often progressive.


Neurology_Adams

Neurology_Adams. During the period 1970–1974 in Rochester, Minnesota, 94 percent of patients with ischemic strokes survived for 5 days and 84 percent for 1 month (Garraway et al, 1983a and b). The survival rate was 54 percent at 3 years and 40 percent at 7 years. These were significantly greater than had been the case during the period 1965–1969. These figures, which were gathered retrospectively, are comparable to more recent ones reported by Bamford and colleagues from patients who had strokes in the 1980s. The mortality rate following cerebral infarcts (no separation being made between thrombotic and embolic types) at the end of 1 month was 19 percent and at the end of 1 year, 23 percent. Of the survivors, 65 percent were capable of an independent existence. In every series, among long-term survivors, heart disease is a more frequent cause of death than additional strokes. It has been repeatedly pointed out that pneumonia as a result of disordered swallowing is a major determinant of survival;


Neurology_Adams

Neurology_Adams. heart disease is a more frequent cause of death than additional strokes. It has been repeatedly pointed out that pneumonia as a result of disordered swallowing is a major determinant of survival; further discussion regarding aspiration problems following stroke are found in later sections of the chapter.


Neurology_Adams

Neurology_Adams. Several other circumstances influence the early prognosis in cerebral infarction. In the case of very large infarcts in the middle cerebral artery territory, swelling of the infarcted tissue may occur, followed by displacement of central structures, transtentorial herniation, and death of the patient after several days. This can at times be anticipated by the sheer volume of the infarct and is usually evident on the CT or MRI scan within a day of the stroke. Smaller infarcts of the inferior surface of the cerebellum may also cause a fatal herniation into the foramen magnum. Milder degrees of swelling and increased intracranial pressure in both of these strokes may progress as gauged by imaging studies for 2 to 3 days but do not prove fatal. (See earlier under “Treatment of Brain Swelling [Edema] and Raised Intracranial Pressure After Ischemic Stroke.”)


Neurology_Adams

Neurology_Adams. In extensive brainstem infarction associated with deep coma caused by basilar artery occlusion, the early mortality rate approaches 40 percent but some of this is self-fulfilling as support is sometimes withdrawn. In any type of stroke, if coma or stupor is present from the beginning, survival is largely determined by success in keeping the airway clear, preventing aspiration pneumonia, controlling brain swelling, and maintaining fluid and electrolyte balance, as described further on. With smaller thrombotic infarcts, the mortality is 3 to 6 percent, much of it from myocardial infarction and aspiration pneumonia.


Neurology_Adams

Neurology_Adams. As for the eventual prognosis of the neurologic deficits, some improvement is the rule. The patient with a lacunar infarct usually fares well but may take months to improve to the maximum extent. With other small infarcts, recovery may start within a day or two, and restoration may be complete or nearly complete within a week. In cases of severe deficit, there may be little significant recovery; after months of assiduous efforts at rehabilitation, the patient may remain bereft of speech and understanding, with the upper extremity still useless and the lower extremity serving only as an uncertain prop during attempts to walk. Between these two extremes there is every gradation of recovery. Measurement of central motor conduction by magnetic stimulation has been somewhat predictive of motor recovery but is not widely used for clinical work. If clinical recovery does not begin in 1 or 2 weeks, the outlook is poorer for both motor and language functions. Constructional apraxia,


Neurology_Adams

Neurology_Adams. of motor recovery but is not widely used for clinical work. If clinical recovery does not begin in 1 or 2 weeks, the outlook is poorer for both motor and language functions. Constructional apraxia, uninhibited anger (with left and rarely with right temporal lesions), nonsensical logorrhea and placidity, unawareness of the paralysis and neglect (with nondominant parietal lesions), and confusion and delirium (with nondominant temporal lesions) all tend to diminish and may disappear within a few weeks. A hemianopia that has not cleared in a few weeks will usually be permanent, although reading and color discrimination may continue to improve. In lateral medullary infarction, difficulty in swallowing may be protracted, lasting 8 weeks or longer, yet relatively normal function is finally restored in nearly every instance. Aphasia, dysarthria, cerebellar ataxia, and walking may improve for a year or longer, but for all practical purposes it may be said that whatever motor and language


Neurology_Adams

Neurology_Adams. restored in nearly every instance. Aphasia, dysarthria, cerebellar ataxia, and walking may improve for a year or longer, but for all practical purposes it may be said that whatever motor and language deficits remain after 5 to 6 months will be permanent.


Neurology_Adams

Neurology_Adams. Characteristically, the paralyzed muscles are flaccid in the first days or weeks following a stroke; the tendon reflexes are usually unchanged but may be slightly increased or decreased. Gradually spasticity develops, and the tendon reflexes become brisker. The arm tends to assume a flexed adducted posture and the leg an extended one. Function is rarely if ever restored after the slow evolution of spasticity; however, the use of botulinum toxin may help considerably in relieving the spasticity. Conversely, the early development of spasticity in the arm or the early appearance of a grasp reflex may presage a favorable outcome. In some patients with extensive temporoparietal lesions, the hemiplegia remains flaccid; the arm dangles and the slack leg must be braced to stand. The physiologic explanation of this remains obscure. If the internal capsule is not interrupted completely in a stroke that involves the lenticular nucleus or thalamus, the paralysis may give way to


Neurology_Adams

Neurology_Adams. The physiologic explanation of this remains obscure. If the internal capsule is not interrupted completely in a stroke that involves the lenticular nucleus or thalamus, the paralysis may give way to hemichoreoathetosis, hemitremor, or hemiataxia, depending on the particular anatomy of the lesion. Bowel and bladder control usually returns; sphincteric disorders persist in only a few cases. Physical therapy should be initiated early in order to prevent pseudocontracture of muscles and capsulitis at the shoulder, elbow, wrist, knuckles, knee, and ankle. These are frequent complications and often a source of pain and added disability, particularly of the shoulder. Occasionally, atrophy of bone and pain in the hand may accompany the shoulder pain (shoulder–hand syndrome). An annoying dizziness and unsteadiness often persists after damage to the vestibular system in brainstem infarcts.


Neurology_Adams

Neurology_Adams. Seizures are a relatively uncommon sequel of thrombotic strokes in comparison to embolic cortical infarcts, which have been followed by seizures in up to 10 percent of patients in some report, far fewer in our experience. The EEG in these cases of seizure does not normalize, even months after the stroke, and shows sharp activity over the region of the infarct (see further on for treatment of seizures after stroke).


Neurology_Adams

Neurology_Adams. Many patients complain of fatigability and are depressed, possibly more so after strokes that involve the left frontal lobe (Starkstein et al); other studies implicate an infarct on either side of the brain. The explanation of these symptoms is uncertain; some are certainly expressions of a reactive depression. Several small series have suggested that prophylactic treatment with antidepressants reduce the incidence of depression as described in the review by Chen and colleagues, but the routine administration of these medications has not found its way into general practice. Only a few patients develop serious behavior problems or are psychotic after a stroke, but paranoid trends, confusion, stubbornness, and peevishness may appear, or an apathetic state ensues. Large lesions affect concentration as well as synthetic and executive mental functions in rough proportion to their size; these global mental changes are independent of any disturbances in language function.


Neurology_Adams

Neurology_Adams. When multiple infarcts occur over a period of months or years, special types of dementia and gait failure may develop. In some, the major lesions involve the white matter and spare, relatively, the cortex and basal ganglia; the lesions may be lacunar or larger infarctions. This disorder, referred to in the past as arteriosclerotic dementia and Binswanger subcortical leukoencephalopathy, probably represents the accumulation of multiple white matter infarcts and lacunes (see further on and Babikian and Ropper). The white matter that is destroyed tends to lie in the border zones between the penetrating cortical and basal ganglionic arteries. Large patches of subcortical myelin loss and gliosis, in combination with small cortical and subcortical infarcts, are evident with brain imaging. This process and the histologically similar but biologically unique inherited condition of white matter termed CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarct and


Neurology_Adams

Neurology_Adams. imaging. This process and the histologically similar but biologically unique inherited condition of white matter termed CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy) are discussed further on.


Neurology_Adams

Neurology_Adams. In all but the most seriously ill patients, beginning within a few days of the stroke the paralyzed limbs ideally should be carried through a full range of passive movement several times a day. The purpose is to avoid contracture (and capsulitis), especially at the shoulder, elbow, hip, and ankle. Soreness and aching in the paralyzed limbs should not be allowed to interfere with exercises to the extent possible. Patients should be moved from bed to chair as soon as the stroke is completed and blood pressure is stable. Prophylaxis for deep venous thrombosis with compression boots or anticoagulation is appropriate if the patient cannot be mobilized. An assessment for swallowing difficulty should be made early during recovery and dietary adjustments on the insertion of a nasogastric tube made if there is a risk of aspiration. Nearly all hemiplegic patients regain the ability to walk to some extent, usually within a 3to 6-month period, and this should be a primary aim in rehabilitation.


Neurology_Adams

Neurology_Adams. if there is a risk of aspiration. Nearly all hemiplegic patients regain the ability to walk to some extent, usually within a 3to 6-month period, and this should be a primary aim in rehabilitation. The presence of deep sensory loss or anosognosia in addition to hemiplegia, are the main limiting factors. A short or long leg brace is often required. By teaching patients with cerebellar ataxia new strategies, balance and gait disorders can be made less disabling. As motor function improves and if mentality is preserved, instruction in the activities of daily living and the use of various special devices can help the patient become at least partly independent at home. Whatever little research is available on the effectiveness of stroke rehabilitation suggests that a greater intensity of physical therapy does indeed achieve better scores on some measures of walking ability and dexterity. In a randomized trial, Kwakkel and colleagues achieved these results by applying an additional 30 min/d


Neurology_Adams

Neurology_Adams. therapy does indeed achieve better scores on some measures of walking ability and dexterity. In a randomized trial, Kwakkel and colleagues achieved these results by applying an additional 30 min/d beyond conventional physical therapy of focused treatments to the leg or arm, 5 d/week, for 20 weeks. Other studies have demonstrated clearly the undesirable effects of immobilizing a limb in a splint after a stroke.


Neurology_Adams

Neurology_Adams. Experimental work in monkeys and limited data from patients suggest that improvement can be obtained by restraining the normal limb and forcing use of the sound limb. In a randomized trial, Wolf and colleagues (2006) were able to demonstrate a benefit from this form of “constraint therapy” by forcing the patient to wear a mitt on the good hand while engaging in persistent exercises with the hemiplegic limb for more than 90 percent of their waking time through 2 weeks. This may reflect functional expansion of the cortical motor representation into adjacent undamaged cortical areas, indicating the potential for some degree of reorganization that corresponds to clinical recovery. A related approach, “mirror therapy” confronts the patient with a mirror that creates an illusion of moving the paretic side when the good side is activated. The Cochrane meta-analysis of 14 such studies indicates a modest benefit in motor recovery and a more prominent benefit for relief of pain and quality of


Neurology_Adams

Neurology_Adams. paretic side when the good side is activated. The Cochrane meta-analysis of 14 such studies indicates a modest benefit in motor recovery and a more prominent benefit for relief of pain and quality of life improvement (Thieme and colleagues).


Neurology_Adams

Neurology_Adams. The neural substrates of improvement after stroke are just beginning to be studied. Considerable clinical experience and physiologic data such as those reported by Luft and colleagues have demonstrated that the injured brain has some degree of plasticity; remodeling of brain tissue and reorganization of neural function may occur with training even months after large strokes. Speech and language therapy is particularly valuable in identifying the risk of aspiration as noted above. Specific therapy should be given in appropriate cases and certainly improves the morale of the patient and family. Further comments on such treatments can be found in Chap. 22. GENERALIZED BRAIN ISCHEMIA AND HYPOXIA (SEE ALSO CHAP. 39)


Neurology_Adams

Neurology_Adams. This constitutes a special type of infarction that follows cardiac arrest and other forms of prolonged hypotension or hypoxia. The most typical configuration, seen with imaging, is of widespread cortical infarction affecting also the deep nuclei, that is, the most metabolically active regions of the cerebral hemispheres. An important distinction is drawn between the concept of end-arterial distribution, the site of distal embolization, and the area of lowest flow between two or more end territories, which is compromised in any form of globally returned blood flow. In extreme cases of hypotension, there is global infarction of the brain accompanied by the clinical syndrome of brain death. In the case of reduced blood flow to the cerebral hemispheres, there is a tendency for regional infarctions to occur in the areas of lowest blood flow that lie between the major surface arteries, referred to metaphorically as a watershed infarction (which may not be apt as a watershed is a region of


Neurology_Adams

Neurology_Adams. to occur in the areas of lowest blood flow that lie between the major surface arteries, referred to metaphorically as a watershed infarction (which may not be apt as a watershed is a region of water collection).


Neurology_Adams

Neurology_Adams. Pure hypoxia-anoxia without hypotension produces another type of damage in areas susceptible to reduced oxygen delivery, mainly affecting the hippocampi; a Korsakoff syndrome results. Most often, ischemic and hypoxic states coexist and produce complex patterns of cerebral damage. This topic is discussed fully in Chap. 39. The special problem of cerebral ischemia during cardiac surgery with the use of a bypass pump is discussed further on in the section “Stroke with Cardiac Surgery.”


Neurology_Adams

Neurology_Adams. This is a segmental, nonatheromatous, noninflammatory arterial disease of unknown etiology, largely occurring in middle-aged women. It is uncommon (0.5 percent of 61,000 arteriograms in the series of So et al) but is being reported with increasing frequency because of improved arteriographic techniques. In our experience, it has often been an incidental finding in asymptomatic individuals undergoing vascular imaging for other reasons. Approximately 10 percent of cases have been reported to be familial and a connection to a variant in the phosphatase and actin regulator 1 gene (PHACTR1) has been found in some patients.


Neurology_Adams

Neurology_Adams. First described in the renal artery by Leadbetter and Burkland in 1938, fibromuscular dysplasia is now known to affect other vessels including cervicocerebral ones. The internal carotid artery is involved most frequently, followed by the vertebral and cerebral arteries. The radiologic picture is of a series of transverse constrictions, giving the appearance of an irregular string of beads or a smooth tubular narrowing; it is observed bilaterally in the carotid arteries in up to75 percent of cases. Usually only the extracranial part of the artery is involved. A single transverse web that occupies a portion of the carotid lumen is probably a variant of the fibromuscular condition or could conceivably represent an entirely different static congenital process. In the series of Houser and colleagues, 42 of 44 patients were women and most were older than 50 years of age. All of the patients reported by So and coworkers were women, ranging in age from 41 to 70 years. Cerebral ischemia may be


Neurology_Adams

Neurology_Adams. 42 of 44 patients were women and most were older than 50 years of age. All of the patients reported by So and coworkers were women, ranging in age from 41 to 70 years. Cerebral ischemia may be associated with the process but the rate of this complication has not been established; our impression is that it is low. In the study by Corrin and colleagues, among 79 untreated asymptomatic patients followed for an average of 5 years, 3 had a cerebral infarct 4 to 18 years after the initial diagnosis. Also, between 7 and 20 percent of affected individuals are found to have intracranial saccular aneurysms (rarely a giant aneurysm), which may be sources of subarachnoid hemorrhage, and up to 12 percent develop arterial dissections, as described below.


Neurology_Adams

Neurology_Adams. The narrowed arterial segments show degeneration of elastic tissue and irregular arrays of fibrous and smooth muscle tissue in a mucous ground substance. Interspersed dilatations are a result of atrophy of the coat of the vessel wall. There is atherosclerosis in some and small degrees of arterial dissection in others. Usually vascular occlusion is not present, though there may be marked stenosis. Schievink and colleagues have summarized the pathology of this disease. In some instances the mechanism of the cerebral ischemic lesion is unexplained, but is presumed to be from small thrombi in the pouches or in relation to intraluminal septa.


Neurology_Adams

Neurology_Adams. The disease is not amenable to endarterectomy. So and colleagues have recommended excision of the affected segments of the carotid artery if ischemic neurologic symptoms are related to them, and conservative therapy if the fibromuscular dysplasia is an incidental and asymptomatic arteriographic finding. It is now possible to dilate the affected vessel by means of endovascular techniques and several case reports have suggested that benefit is achieved at lower risk than with surgical excision. Intracranial saccular aneurysms, which may accompany this disease as noted above, should be sought by arteriography, CT, or MRA and obliterated if their size warrants. It is not known if anticoagulation or antiplatelet therapy confers protection from stroke but the latter is often implemented. Dissection of the Cervical and Intracranial Arteries


Neurology_Adams

Neurology_Adams. Dissection of the Cervical and Intracranial Arteries It has long been appreciated that the process formerly known as Erdheim medionecrosis aortica cystica, the main cause of aortic dissection, may independently involve or extend into the common carotid arteries, occluding them and causing massive infarction of the cerebral hemispheres. Examples of such occurrences were cited by Weisman and Adams in 1944 in their study of the neurology of dissecting aneurysms of the aorta, and Chase and colleagues gave the clinicopathologic details of 16 cases they studied. The principal neurologic features in both series were syncope, hemiparesis, or coma. The frequency of cerebral stroke with aortic dissection has varied from 10 to 50 percent and that of spinal stroke has been approximately 10 percent (see Chap. 44).


Neurology_Adams

Neurology_Adams. In more recent years, more attention has been drawn to the occurrence of spontaneous or traumatic dissection of the internal carotid artery, not necessarily associated intrinsic disease of the vessel walls, as an important cause of nonatherosclerotic stroke in young adults. Many large series of such cases have been reported in separate studies by Ojemann and colleagues (1972) and by Mokri and coworkers (1986 and 1988). Although the disease is overrepresented in women, it occurs frequently in men, typically in their late thirties or early forties for either sex. It is a spontaneous event or arises in relation to a whiplash injury, bouts of violent coughing, or direct trauma to the head or neck, which need not be severe—for example, being struck in the neck by a golf or tennis ball. We have encountered cases that occurred during pregnancy and immediately after delivery. Indeed, it is questionable if most cervical arterial dissections are truly “spontaneous,” as many can be connected to


Neurology_Adams

Neurology_Adams. encountered cases that occurred during pregnancy and immediately after delivery. Indeed, it is questionable if most cervical arterial dissections are truly “spontaneous,” as many can be connected to some strenuous event but a relation to trauma is often only presumed. Three of our patients over the years had a carotid dissection that was manifest as a hemiplegia days after blunt head injury that did not involve the neck.


Neurology_Adams

Neurology_Adams. A small number of patients have fibromuscular disease as discussed above. The Ehlers-Danlos and Marfan syndromes, osteogenesis imperfecta, Loeys-Dietz syndrome (transforming growth factor [TGF]-b receptor mutation), and α1-antitrypsin deficiency are also associated with an increased risk of vascular dissection. One of these conditions should be suspected if multiple extracranial vessels are involved in spontaneous dissections or if there is joint and skin laxity or widespread vascular tortuosity (neck and thoracic trauma or aortic arch dissection are more common causes of multiple extracranial dissections).


Neurology_Adams

Neurology_Adams. A few patients with carotid dissection have had preceding unilateral cranial or facial pain lasting days, followed by stroke in the territory of the internal carotid artery. The pain is aching, may fluctuate in severity, and is centered most often in and around the eye on the side of the dissection; less often, it is in the frontal or temporal regions, angle of the mandible, or high anterior neck over the carotid artery. Rapid and marked relief of the pain after the administration of corticosteroids in a young person may be a helpful diagnostic feature (see below). Neck pain over a site of dissection is usually present as well; however, it may be absent, particularly if the dissection originates near the base of the skull.


Neurology_Adams

Neurology_Adams. The ischemic manifestations consist of transient attacks in the territory of the internal carotid, followed frequently by the signs of hemispheral stroke, which may be abrupt or evolve smoothly over a period of minutes to hours or over several days in a fluctuating or stepwise fashion. A unilateral Horner syndrome is often present. A cervical bruit, sometimes audible to the patient, amaurosis fugax, faintness and syncope, and facial numbness are less common symptoms. Most of the patients described by Mokri and colleagues (1986) had one of two distinct syndromes: (1) unilateral headache associated with an ipsilateral Horner syndrome, essentially the Raeder syndrome, or (2) unilateral headache and delayed focal cerebral ischemic symptoms. One lesson is that a painful Horner syndrome is usually due to an underlying structural lesion. Some patients have evidence of involvement of one or more of the vagi, spinal accessory, or hypoglossal nerve on the side of a carotid dissection; these


Neurology_Adams

Neurology_Adams. due to an underlying structural lesion. Some patients have evidence of involvement of one or more of the vagi, spinal accessory, or hypoglossal nerve on the side of a carotid dissection; these nerves lie in close proximity to the carotid artery and are nourished by small branches from it.


Neurology_Adams

Neurology_Adams. In most cases, dissection of the internal carotid artery can be detected by ultrasonography and confirmed by MRI and CTA, which show a double lumen (Fig. 33-20) within the vessel on axial MRI sections. Arteriography by any method, including by conventional angiography usually reveals an elongated, but variable length, irregular narrow column of dye, usually beginning 1.5 to 3 cm above the carotid bifurcation and extending to the base of the skull, a picture that has been called the string sign. There may be a characteristic tapered occlusion or an outpouching at the upper end of the string. It is the site and the shape of the occlusion that are helpful in identifying dissection. Less often the dissection is confined to the midcervical region, and occasionally it extends into the intracranial carotid or even the middle cerebral artery or involves the opposite carotid artery or the vertebral and basilar arteries. Axial images of the T-1 and of fat-saturated MRI shows the false lumen


Neurology_Adams

Neurology_Adams. carotid or even the middle cerebral artery or involves the opposite carotid artery or the vertebral and basilar arteries. Axial images of the T-1 and of fat-saturated MRI shows the false lumen well and is often depended on for diagnosis of small dissections.


Neurology_Adams

Neurology_Adams. The pathogenesis of spontaneous carotid dissection is at present uncertain. In most reported cases, cystic medial necrosis has not been found on microscopic examination of the involved artery. It seems likely that some cases, even beyond those with known disorders of connective tissue and with fibromuscular dysplasia, are associated with genetic alterations that weaken the media of vessels. In some, there has been disorganization of the media and internal elastic lamina, but the specificity of these changes is in doubt, as Ojemann and colleagues (1972) noted similar changes in some of their control cases. In a small proportion of cases there are the changes of fibromuscular dysplasia, as noted earlier. Several groups have found structural collagen abnormalities in the skin biopsies of patients with dissection. A more thorough study of these vessels is needed.


Neurology_Adams

Neurology_Adams. Dissection of these arteries may originate in the neck and extend into the intracranial portion of the vessel or remain isolated to either of these segments as noted below. In both instances there is a tendency to form pseudoaneurysms, mostly with the intracranial type, and in the latter there is a risk of rupture through the adventitia leading to a subarachnoid hemorrhage. Rapid and extreme rotational movement of the neck is the most common identifiable cause of vertebral artery dissection, as in turning the head to back up a car or with chiropractic manipulation. Extending the neck to have one’s hair washed, swinging a golf club, and direct neck trauma have also been precipitants. Forceful coughing may also cause dissection, as it may in the carotid vessels. There is no clear female predominance (as there may be in carotid dissection) but the previously cited intrinsic weaknesses of the vascular wall from Ehlers-Danlos disease and fibromuscular dysplasia are risk factors.


Neurology_Adams

Neurology_Adams. The dissection most commonly originates in the C1-C2 segment of the vessel, where it is mobile but tethered as it leaves the transverse foramen of the axis and turns sharply to enter the cranium. The symptoms, mainly vertigo, are fragments of the lateral medullary syndrome, often with additional features referable to the pons or midbrain, particularly diplopia and dysarthria. The clinical manifestations in our experience have fluctuated over minutes and hours, quite unlike the usual vertebrobasilar TIA.


Neurology_Adams

Neurology_Adams. Less-common strokes include artery-to-artery embolism to the posterior cerebral territory or, a syndrome that has come to our attention several times in the past few years, a centrally placed infarction of the cervical spinal cord with bibrachial weakness, presumably from occlusion of the anterior spinal arteries. Another interesting but rare association with dissection has been the reversible cerebral vasoconstriction syndrome (RCVS). Mawet and colleagues reported on 20 cases they extracted from their experience but could not determine which process occurred first and could only speculate as to the relationship. Dissection of the vertebral artery was a more common association with RCVS than was carotid artery dissection.


Neurology_Adams

Neurology_Adams. The diagnosis of vertebral dissection should be suspected if persistent occipitonuchal pain and vertigo or related medullary symptoms arise following one of the known precipitants—such as chiropractic manipulation of the neck, head trauma, or Valsalva straining or coughing activities—but it may otherwise escape detection until the full-blown medullary or cerebellar stroke is established. The stroke may follow the inciting event by several days or weeks or even longer, obscuring the relationship. Axial MRI images, particularly the T1-weighted sequences, show a double lumen in the dissected vessel, as described for carotid artery dissection earlier, and skillful ultrasound investigation documents the same. Some patients will be found to have evidence of spontaneous or traumatic dissection of multiple extracranial vessels; this also occurs as a consequence of dissection of the aortic arch from chest trauma.


Neurology_Adams

Neurology_Adams. No generally agreed upon method has been devised to detect the infrequent instance of subarachnoid hemorrhage from dissection. Lumbar puncture is not routinely performed. CT is probably adequate for this purpose but it must be acknowledged that it, too, is not often obtained, except in cases of strong suspicion that the dissection has extended into the subarachnoid space, as evidenced by lower cranial-nerve palsies.


Neurology_Adams

Neurology_Adams. Once a stroke has occurred, even though embolic in most cases, prompt reopening of the artery can at times prove beneficial; this is currently performed by endovascular techniques. Most neurologists take the approach that warfarin, if used, may be discontinued after several months or a year, when angiography or MRA shows the lumen of the carotid artery to be patent, or at least reduced to no more than 50 percent of the normal diameter, and smooth walled. Despite numerous publications demonstrating the ability of skilled operators to reopen a dissection by endovascular methods, acute intervention has not been studied in a way that allows a judgment regarding its value. Of both therapeutic and diagnostic value is the relief of pain afforded by corticosteroids in cervical and intracranial dissections, as mentioned earlier. Pseudoaneurysms in the cervical portions of the vessels generally do not require specific treatment; the series of 38 cases collected by Benninger and colleagues is


Neurology_Adams

Neurology_Adams. dissections, as mentioned earlier. Pseudoaneurysms in the cervical portions of the vessels generally do not require specific treatment; the series of 38 cases collected by Benninger and colleagues is instructive in that none of the aneurysms ruptured during several years of followup and one had a delayed ischemic strokes.


Neurology_Adams

Neurology_Adams. The study by Mokri and colleagues (1988) reported a complete or excellent recovery in 85 percent of patients with the angiographic signs of cervical artery dissection; mainly, these were patients who had fluctuating ischemic symptoms but without stroke and more recent series report comparable results. The outcome in cases complicated by stroke is far less benign. Approximately 25 percent of such patients succumb and most others remain seriously impaired. If early recanalization of the occluded artery is observed (as determined by ultrasonography), there may also be good functional recovery. Local pseudoaneurysms form in a small proportion of patients and generally do not require surgical repair; they also do not preclude cautious anticoagulation. Subarachnoid hemorrhage from transmural rupture is mostly a complication of vertebral artery dissection discussed below.


Neurology_Adams

Neurology_Adams. Dissections of intracranial arteries are far less common than extracranial ones and they present in several unusual ways. A number of times we have misinterpreted the arteriographic appearance of a short segment of narrowing of the basilar or proximal middle cerebral arteries, assuming these changes to represent embolism or arteritis when in fact they proved to be dissections of the vessel wall. In the case of purely intracranial dissection of the middle cerebral or basilar arteries, there is usually no preceding trauma, but a few patients have had minor head injuries, extreme coughing, or other recently Valsalva-producing events (e.g., after childbirth)—or they had used cocaine. The typical picture is of fluctuating symptoms referable to the affected circulation and severe cranial pain on the side of the occlusion—retroorbital in the case of middle cerebral dissection, occipital in the case of basilar dissection, occipital combined with supraorbital in the case of vertebral


Neurology_Adams

Neurology_Adams. pain on the side of the occlusion—retroorbital in the case of middle cerebral dissection, occipital in the case of basilar dissection, occipital combined with supraorbital in the case of vertebral dissection (see above). A few patients have had sudden strokes that suggested embolic infarction, and a small number present with subarachnoid hemorrhage. There has been very little pathological verification of these cases and the diagnosis is presumed from the luminal configuration on imaging studies but is hard to prove.


Neurology_Adams

Neurology_Adams. Treatment of Cervical Artery Dissection As an overall comment pertaining to dissection, treatment is primarily with anticoagulation or antiplatelet agents for several weeks or months and followed up with some form of arteriography. The choice between aspirin and warfarin has not been clarified as the rate of stroke is low, in the range of 5 percent or less, and remains so with either agent (Georgiadis and colleagues). If the dissection has produced complete occlusion of the vessel, the role of anticoagulation is less clear. Endovascular revascularization has been attempted with mixed results. Similarly, tandem lesions, meaning carotid dissection and a downstream intracranial embolus, have been treated with stenting and either thrombolysis of thrombectomy but again, the results are hard to judge.


Neurology_Adams

Neurology_Adams. An issue pertaining to treatment is in establishing the presence of dissection into the subarachnoid space of the intracranial compartment and the risk of subarachnoid hemorrhage. For carotid dissection, such extensions would seem to present a risk of subarachnoid hemorrhage if the lesion reaches beyond the cavernous sinus. Within the sinus, any bleeding would create a cavernous-carotid fistula, which is not usually fatal. In vertebral dissection, this question arises when the false lumen extends into the foramen magnum, beyond the dural entry of the vessel.


Neurology_Adams

Neurology_Adams. Although there are no data to determine the proper approach to acute treatment in these circumstances that entail a risk of a subarachnoid hemorrhage, in general we do use heparin and warfarin for a brief period, followed by aspirin, because of the greater concern for embolus, unless there is existing subarachnoid blood on a CT scan or if there is a pseudoaneurysm within the intracranial portion of the dissection (see Metso et al). Some stroke specialists have suggested that a lumbar puncture be performed before initiating anticoagulation but this has not usually been our practice.


Neurology_Adams

Neurology_Adams. Moyamoya is a Japanese word for a “haze,” “puff of smoke”; it has been used to refer to an extensive basal cerebral rete mirabile—a network of small anastomotic vessels at the base of the brain around and distal to the circle of Willis, seen in carotid arteriograms, associated with segmental stenosis or occlusion of the terminal intracranial parts of both internal carotid arteries (Fig. 33-21). This form of cerebrovascular disease is predominant in, but not limited to the Japanese. The authors have periodically observed such patients, as have others, in the United States, Western Europe, and Australia. Certain hemoglobinopathies, particularly sickle cell anemia, may cause a vasoocculsive condition equivalent to moyamoya disease, possibly because of sickling of red blood cells in the vasa vasorum of the supraclinoid carotid artery. An association between moyamoya, Down syndrome, and certain human leukocyte antigen (HLA) types favors a hereditary basis (Kitahara et al). A familial


Neurology_Adams

Neurology_Adams. vasa vasorum of the supraclinoid carotid artery. An association between moyamoya, Down syndrome, and certain human leukocyte antigen (HLA) types favors a hereditary basis (Kitahara et al). A familial component has long been suspected but can be established in only 10 percent of cases, possibly in an autosomal dominant pattern with incomplete penetrance due to a site on chromosome 17q that has been implicated as one possible locus. Also, a rare condition in either Asians or Europeans of atherosclerotic occlusion of the distal intracranial carotid arteries can cause deep collateral vessels to enlarge and simulate moyamoya. In this way, moyamoya can be considered either a radiologic pattern or a disease process.


Neurology_Adams

Neurology_Adams. Nishimoto and Takeuchi reported on 111 cases that were selected on the basis of the two main radiologic criteria. The condition was observed mainly in infants, children, and adolescents (more than half the patients were younger than 10 years of age, and only 4 were older than age 40 years). All of their patients were Japanese, in whom the disease seems disproportionately prevalent; both males and females were affected, and 8 were siblings. The symptom that led to medical examination was usually a sudden weakness of an arm, leg, or both on one side. The symptoms tended to clear rapidly but recurred in some instances. Headache, convulsions, impaired mental clarity, visual disturbance, and nystagmus were less frequent. In older patients, subarachnoid hemorrhage was the most common initial manifestation. Other symptoms and signs were speech disturbance, sensory impairment, involuntary movements, and unsteady gait. Characteristics noted in other series have included prolonged TIAs (this


Neurology_Adams

Neurology_Adams. manifestation. Other symptoms and signs were speech disturbance, sensory impairment, involuntary movements, and unsteady gait. Characteristics noted in other series have included prolonged TIAs (this accords with our experience), characteristically induced by hyperventilation or hyperthermia, parenchymal rather than subarachnoid hemorrhages (most situated in the basal ganglia or thalamus), and an unusual “rebuildup” EEG phenomenon in which high-voltage slow waves reappear 5 min after the end of hyperventilation.


Neurology_Adams

Neurology_Adams. Postmortem examinations of cases of moyamoya have yielded a reasonably clear picture of the intracranial distal carotid lesion. The adventitia, media, and internal elastic laminae of the stenotic or occluded arteries were normal, but the intima was greatly thickened by fibrous tissue. No inflammatory cells or atheromata were seen. In a few cases, hypoplasia of the vessel with absent muscularis has been described. The profuse rete mirabile consists of a fine network of vessels over the basal surface of the brain (in the pia-arachnoid), which, according to Yamashita and coworkers, reveals microaneurysm formation because of weakness of the internal elastic lamina and thinness of the vessel wall. The latter lesion is the source of subarachnoid hemorrhage. Thus one part of the symptomatology is traced to the distal carotid stenosis and another to the rupture of the vascular network. Opinion is divided as to whether the basal rete mirabile represents a congenital vascular malformation


Neurology_Adams

Neurology_Adams. is traced to the distal carotid stenosis and another to the rupture of the vascular network. Opinion is divided as to whether the basal rete mirabile represents a congenital vascular malformation (i.e., a persistence of the embryonal network) or a rich collateral vascularization secondary to a congenital hypoplasia, acquired stenosis, or occlusion of the internal carotid arteries early in life.


Neurology_Adams

Neurology_Adams. Treatment The treatment of moyamoya is far from satisfactory. Certain surgical measures have been employed, including transplantation of a vascular muscle flap, omentum, or pedicle containing the superficial temporal artery to the pial surface of the frontal lobe temporal pial synangiosis with the idea of creating neovascularization of the cortical convexity. These measures have reportedly reduced the number of ischemic attacks, but whether they alter the natural history of the illness cannot be stated. Anticoagulation is considered risky in view of the possibility of cerebral hemorrhage, but there have not been systematic studies. The reader is referred to a review of the clinical features and surgical treatments by Scott and Smith.


Neurology_Adams

Neurology_Adams. This entity was mentioned briefly in the discussion of the course and prognosis of atherothrombotic infarction and as a cause of dementia in Chaps. 20 and 38 but it has appeared in the literature with decreasing frequency. The term has come to denote a widespread degeneration of cerebral white matter having a vascular causation and observed in the context of hypertension, atherosclerosis of the small blood vessels, and multiple strokes. Hemiparesis, dysarthria, TIAs, and typical lacunar or cortical strokes are admixed in many cases. The process has been associated with a particular radiologic appearance that reflects confluent areas of white matter signal change. The term leukoaraiosis describes the imaging appearance of hypointense periventricular tissues, presumably damaged by chronic ischemia. It is likely that leukoaraiosis exist in a continuum with Binswanger disease and many elderly individuals who have these changes show cognitive impairment as discussed below. Whether multiple


Neurology_Adams

Neurology_Adams. It is likely that leukoaraiosis exist in a continuum with Binswanger disease and many elderly individuals who have these changes show cognitive impairment as discussed below. Whether multiple discrete lacunes in the deep white matter constitute Binswanger disease may be a semantic issue, but we adhere to the notion that the former is characterized by a more widespread ischemic and gliotic change in the deep white matter.


Neurology_Adams

Neurology_Adams. Dementia, a pseudobulbar state, and a gait disorder, alone or in combination, are the main features of Binswanger cases. They have been attributed to the cumulative effects of the ischemic changes producing white matter degeneration. It is likely that the pathologic basis of such a clinical entity is arteriolar sclerosis but surprisingly, as pointed out in Fisher’s review (1989), the lumens are open. Yet another problem is to distinguish such a state from deficits produced by the cumulative effect of numerous larger lacunes, which have for a century been known to cause the aforementioned syndromes of dementia, gait disturbance, and a pseudobulbar syndrome. From time to time, imaging studies of the brain disclose large regions of white matter change or the occurrence of multiple infarctions in the absence of hypertension, and it is not clear how such cases should be classified. Some prove to be areas of demyelination or metabolic dysmyelination; others are mitochondrial disorders, and


Neurology_Adams

Neurology_Adams. in the absence of hypertension, and it is not clear how such cases should be classified. Some prove to be areas of demyelination or metabolic dysmyelination; others are mitochondrial disorders, and perhaps some are related to the familial CADASIL syndrome or Susac syndrome discussed below. Fabry disease also enters into the differential diagnosis of multiple small infarctions in the cerebrum that may coalesce into areas of white matter damage. Readers may consult the reviews on the subject by Babikian and Ropper, by Caplan (1995), and the mentioned review by CM Fisher.


Neurology_Adams

Neurology_Adams. A process with an imaging appearance of large confluent cerebral white matter changes, somewhat similar to Binswanger leukoencephalopathy, has been identified as an autosomal dominant familial trait linked in several families to a missense mutation on chromosome 19. In the past, it had been described under a number of names, including hereditary multiinfarct dementia. The acronym CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is now applied. In these patients recurrent small strokes beginning in early adulthood culminate in a subcortical dementia (see Chap. 20). Migraine headaches, often with neurologic accompaniments, may precede the strokes by several years, and varied TIAs that are attributed, probably incorrectly, to the migraine. On the other hand, some individuals display few clinical changes while yet others are demented or have strokes that simulate lacunes. We are unable to comment on the encephalopathy and coma


Neurology_Adams

Neurology_Adams. migraine. On the other hand, some individuals display few clinical changes while yet others are demented or have strokes that simulate lacunes. We are unable to comment on the encephalopathy and coma accompanied by fever described by Schon and colleagues that has been attributed to this condition.


Neurology_Adams

Neurology_Adams. The familial nature of the process may not be appreciated because genetic penetrance is not complete until after 60 years of age. On MRI, clinically unaffected family members may show substantial changes in the white matter well before strokes or dementia arises (Fig. 33-22). A syndrome of early alopecia and lumbar spondylosis with the white matter changes typical of CADASIL has been identified as a recessively inherited disease (cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy [CARASIL]) and is discussed separately below.


Neurology_Adams

Neurology_Adams. The MRI and CT appearance is of multiple confluent white matter lesions of various sizes, many quite small and concentrated around the basal ganglia and periventricular areas. Lesions anterior to the temporal horns of the lateral ventricles are particularly characteristic of the entity. When the affected regions are asymmetrical and periventricular, they are difficult to distinguish from the lesions of multiple sclerosis. In the autopsy cases studied by Jung and colleagues, numerous partially cavitated infarctions were found in the white matter and basal ganglia. Small vessels in the regions of these infarctions, 100 to 200 mm diameters, contained basophilic granular deposits in the media with degeneration of smooth muscle fibers. Attribution of the white matter lesions to these vascular changes presents the same problems as in Binswanger disease, particularly in view of patency of most of the many small vessels in the examined material. Nevertheless, CADASIL is probably the main


Neurology_Adams

Neurology_Adams. changes presents the same problems as in Binswanger disease, particularly in view of patency of most of the many small vessels in the examined material. Nevertheless, CADASIL is probably the main cause of sporadic instances of what otherwise passes for Binswanger disease; the anterior temporal changes, however, are typical of the former. Also, migraine headaches are not a component of Binswanger disease.


Neurology_Adams

Neurology_Adams. The responsible mutation is a missense change on chromosome 19 of the NOTCH 3 gene, in the same locus as the gene for familial hemiplegic migraine, and has been characterized by Joutel and colleagues; this provides a diagnostic test that can be performed on the blood or skin. The gene may now be sequenced in commercial laboratories. The diagnosis can also be confirmed by finding eosinophilic inclusions in the arterioles of a skin biopsy (osmophilic with electron microscopy).


Neurology_Adams

Neurology_Adams. An entirely different vasculopathy with widespread white matter signal change has been reported in Japan. Migraine is not a component of the syndrome, and the NOTCH gene, implicated in CADASIL, is normal. Inheritance is as a recessive trait (hence, CARASIL) from a mutation in the HTAR1 gene (see Hara et al). The result is fragmentation and duplication of the internal elastic lamina of cerebral vessels with narrowing of their lumens. As intriguing from this mutation is an associated osteoid growth that causes severe lumbar stenosis and alopecia. An interesting mutation of the COL4A1 gene for type 4 collagen leads to familial small vessel disease and intracerebral hemorrhage in mice and humans (Gould et al). More often, as in the cases described by Verreault and colleagues, there are numerous white matter infarctions that are not explained by hypertension and similar lesions may be found in family members by MRI.


Neurology_Adams

Neurology_Adams. Under the terms HERNS (hereditary endotheliopathy, retinopathy, nephropathy, and strokes) and CRV (cerebroretinal vasculopathy), rare dominantly inherited conditions have been described that cause subcortical white matter degeneration, presumably on a microvascular occlusive basis. Ocular symptoms and retinopathy are the main features and the neurologic aspects. Awareness of these vascular forms of white matter degenerations adds to the list of inherited leukoencephalopathies discussed in Chap. 37 and the action of the implicated genes reveals novel mechanisms of damage to small cerebral vessels. As indicated in Table 33-2 in an earlier section, ischemic necrosis of cerebral tissue can occur in utero. The resulting stroke is usually referred to as congenital hemiplegia but there are heterogeneous causes and in most instances, the underlying vascular disease cannot be discerned. The adjacent ventricular region tends to expand into the stroke cavity and may cause a porencephalic cyst.


Neurology_Adams

Neurology_Adams. Acute hemiplegia in infants and children is a rare but well-recognized phenomenon. In a series of 555 consecutive postmortem examinations at the Children’s Medical Center in Boston (now Boston Children’s Hospital), there were 48 cases (8.7 percent) of occlusive vascular disease of the brain (Banker). The occlusions, studied neuropathologically, were both embolic (mainly associated with congenital heart disease) and thrombotic, and the latter were actually more common in veins than in arteries.


Neurology_Adams

Neurology_Adams. Similarly, stroke is not an uncommon event in young adults (ages 15 to 45 years), accounting for an estimated 3 percent of cerebral infarctions in typical series. In terms of causation, this group is also remarkably heterogeneous. Among 144 such patients, more than 40 possible etiologies were identified by H.P. Adams and colleagues. Nevertheless, most of the strokes could be accounted for by three categories, more or less equal in size: (1) atherosclerotic thrombotic infarction (usually with a recognized risk factor); (2) cardiogenic embolism (particularly in the past association with rheumatic heart disease, infective and noninfective endocarditis, paradoxic embolism through patent foramen ovale and other cardiac defects, and prosthetic heart valves); and (3) one of several nonatherosclerotic vasculopathies (arterial trauma, dissection of the carotid artery, moyamoya, lupus erythematosus, drug-induced vasculitis). Hematologically related disorders—use of oral contraceptives


Neurology_Adams

Neurology_Adams. vasculopathies (arterial trauma, dissection of the carotid artery, moyamoya, lupus erythematosus, drug-induced vasculitis). Hematologically related disorders—use of oral contraceptives (discussed further on), the postpartum state, and other hypercoagulable states—were the probable causes in 15 percent patients. The presence of antiphospholipid or anticardiolipin antibodies (lupus anticoagulant) explains some of these cases and is discussed further in the section on “Stroke as a Complication of Hematologic Disease”; the majority of these patients are women in their thirties without manifest systemic lupus erythematosus.


Neurology_Adams

Neurology_Adams. Despite the attention they have received recently as a cause of strokes in the juvenile and young adult period, the frequency of inherited deficiencies of naturally occurring anticoagulant factors as a cause of stroke is low.


Neurology_Adams

Neurology_Adams. Table 33-7 summarizes the main inherited prothrombotic clotting defects. They predispose primarily to cerebral venous thrombosis. Most arise from partial protein deficiencies as a result of heterozygous mutations in the genes encoding proteins in the clotting cascade (antithrombin III, proteins S and C) and from those that disturb clotting balance (resistance to activated protein C, or factor V Leiden mutation, and prothrombin mutations as well as excess factor VIII) (see discussion by Brown and Bevan). When homozygous, these mutations may be associated with devastating neonatal hemorrhagic conditions. In some series that report cases of strokes in youth, such as the one reported by Becker and colleagues, up to half of stroke cases had one of these disorders, the most common being the factor V Leiden mutation, but others have found this mutation to be much less frequent, which is more consonant with our experience. Nevertheless, in children with unexplained stroke, particularly venous


Neurology_Adams

Neurology_Adams. V Leiden mutation, but others have found this mutation to be much less frequent, which is more consonant with our experience. Nevertheless, in children with unexplained stroke, particularly venous ones or if there is a family history of stroke in early life, and especially if there has been a previous thrombosis or if the strokes are recurrent, it is advisable to carry out an extensive hematologic investigation, including testing for antiphospholipid antibody (an acquired defect), as described in the later section on “Antiphospholipid Antibody (Hughes) Syndrome.” Establishing a diagnosis of a prothrombotic clotting gene variant has further significance because strokes are prone to occur in the setting of additional risks, such as the use of oral contraceptives and smoking. In adults, the evaluation for inherited clotting defects is less fruitful. Furthermore, it should be kept in mind that the levels of proteins C and S and of antithrombin are temporarily depressed after stroke, so


Neurology_Adams

Neurology_Adams. evaluation for inherited clotting defects is less fruitful. Furthermore, it should be kept in mind that the levels of proteins C and S and of antithrombin are temporarily depressed after stroke, so that any detected abnormalities must be confirmed months later and in the absence of anticoagulation.


Neurology_Adams

Neurology_Adams. Persistent cerebral ischemia and infarction may occasionally complicate migraine in young persons as discussed in Chap. 9. Wolf and colleagues identified a prolonged aura in young women with an established history of migraine as a risk for strokes, most of which occurred in the posterior circulation. The combination of migraine and oral contraception is particularly hazardous, as detailed below. Despite the common occurrence of mitral valve prolapse in young adults, it is probably only rarely a cause of stroke (see previous comments). Stroke because of either arterial or venous occlusion occurs occasionally in association with inflammatory bowel disease in young persons. Evidence points to a hypercoagulable state during exacerbations of the enteritis but a precise defect in coagulation has not been identified. Meningovascular syphilis and fungal and tuberculous meningitis and other forms of chronic basal meningitis are also considerations in this age group; the strokes are usually of


Neurology_Adams

Neurology_Adams. not been identified. Meningovascular syphilis and fungal and tuberculous meningitis and other forms of chronic basal meningitis are also considerations in this age group; the strokes are usually of the lacunar type, resulting from inflammatory occlusion of small basal vessels.


Neurology_Adams

Neurology_Adams. Sickle cell anemia is a rare but important cause of stroke in children of African ancestry; acute hemiplegia is the most common manifestation but all types of focal cerebral disorders have been observed. The pathologic findings are those of infarction, large and small; their basis is assumed to be vascular obstruction associated with the sickling process. The association of sickle cell anemia with the moyamoya syndrome was mentioned earlier and surveillance for the development of supraclinoid stenosis may be undertaken by transcranial Doppler. Exchange transfusions have prevented or retarded the formation of moyamoya and the report by RJ Adams and colleagues indicates that the procedure may reduce the risk of stroke if the arteriopathy is detected. Intracranial bleeding (subdural, subarachnoid, and intracerebral) and cerebral venous thrombosis may also complicate sickle cell anemia, and—probably because of autosplenectomy—there is an increased incidence of pneumococcal meningitis.


Neurology_Adams

Neurology_Adams. and intracerebral) and cerebral venous thrombosis may also complicate sickle cell anemia, and—probably because of autosplenectomy—there is an increased incidence of pneumococcal meningitis. Treatment of the cerebral circulatory disorder, based presumably on sludging of red blood cells, is with intravenous hydration and transfusion. Cerebral venous sinus thrombosis in young children and neonates from various causes represents a special problem, difficult to diagnose, and with a poor prognosis (see deVeber et al).


Neurology_Adams

Neurology_Adams. Certain hereditary metabolic diseases (homocystinuria and Fabry angiokeratosis) and the mitochondrial disorder MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) may give rise to strokes in children or young adults; investigation of these causes is undertaken if the aforementioned clotting disorders have been excluded or if there is a family history. Figure 33-23 demonstrates an example of stroke related to MELAS.


Neurology_Adams

Neurology_Adams. Overall, in children and young adults with ischemic stroke, the main diagnoses to be considered are carotid and vertebral dissection, drug abuse (mainly cocaine), thrombosis induced by contraceptive estrogens (see below), antiphospholipid antibody syndrome, and cardiac disease including patent foramen ovale (PFO). Migraine might be added to this list, but it is a diagnosis by exclusion in these circumstances and CADASIL, albeit rare, should also be considered if migraine headaches and TIAs precede a stroke. Inherited prothrombotic states—such as those caused by the various clotting factor deficiencies discussed above, Fabry disease, moyamoya, and Takayasu arteritis—arise in the younger age group and require exploration if clinical circumstances suggest one of these processes on the basis of unusual TIAs (orthostatic, hyperventilation, or fever induced), Down syndrome, or strong family history of strokes in youth. Oral Contraceptives, Estrogen, and Cerebral Infarction


Neurology_Adams

Neurology_Adams. The early studies of Longstreth and Swanson and of Vessey and associates indicated that women who take oral contraceptives in the childbearing years—particularly if they are older than 35 years of age and also smoke, are hypertensive, or have migraine—are at increased risk of cerebral infarction. Stroke in these cases is usually a result of arterial occlusion, occurring in both the carotid–middle cerebral and vertebrobasilar territories and sometimes to occlusion of cerebral veins. In most of the reported fatal cases, the thrombosed vessel has been free of atheroma or other disease. The vascular lesion underlying cerebral thrombosis in women taking oral contraceptives was studied by Irey and colleagues. It consists of nodular intimal hyperplasia of eccentric distribution with increased acid mucopolysaccharides and replication of the internal elastic lamina. Similar changes have been found in pregnancy and in humans and animals receiving exogenous steroids, including estrogens. These


Neurology_Adams

Neurology_Adams. mucopolysaccharides and replication of the internal elastic lamina. Similar changes have been found in pregnancy and in humans and animals receiving exogenous steroids, including estrogens. These observations, coupled with evidence that estrogen alters the coagulability of the blood, suggest that a state of hypercoagulability is the important factor in the genesis of contraceptive-associated infarction.


Neurology_Adams

Neurology_Adams. Mainly at increased risk of stroke are women taking high-dose (0.50-mg) estrogen pills; in recent years, lowering the estrogen content has substantially reduced, but not eliminated, this risk. The use of progestin-only pills or of subcutaneously implanted capsules of progestin has not been associated with stroke as far as can be currently determined (Petitti et al). The epidemiologic study reported by Lidegaard and colleagues puts the risk of hormonal contraception in perspective; in a large cohort of Danes, the risks of thrombotic strokes and myocardial infarction over 15 years was very low with estradiol-containing compounds but it increased with age and with the dose of estradiol. It has also become apparent that mutations of the prothrombin gene are more frequent in patients who have cerebral venous thrombosis while on oral contraceptive pills than they are in the general population. Martinelli and associates propose that these genetic abnormalities account for 35 percent of


Neurology_Adams

Neurology_Adams. have cerebral venous thrombosis while on oral contraceptive pills than they are in the general population. Martinelli and associates propose that these genetic abnormalities account for 35 percent of idiopathic cases of cerebral vein thrombosis; and they have contended that contraceptives increase this risk 20-fold.


Neurology_Adams

Neurology_Adams. Stroke in Pregnancy and the Postpartum Period


Neurology_Adams

Neurology_Adams. In addition to the eclamptic-hypertensive state, there is an increased incidence of cerebrovascular events during pregnancy and the postpartum period. The risk of both cerebral infarction and intracerebral hemorrhage appears to be mainly in the 6-week period after delivery rather than during the pregnancy itself (Kittner et al). Fisher (1971) reviewed the literature and analyzed 12 postpartum, 9 puerperal, and 14 contraceptive cases, as well as 9 patients receiving estrogen therapy; arterial thrombosis was demonstrated in half of these cases. Most of the focal vascular lesions during pregnancy were a result of arterial occlusion in the second and third trimesters and in the first week after delivery. Venous occlusion tended to occur 1 to 4 weeks postpartum. In Rochester, New York, the incidence rate of stroke during pregnancy was 6.2 per 100,000, but it doubled with each advance in age from 25 to 29, 30 to 39, and 40 to 49 years (Wiebers et al 1985). Included in most past series are


Neurology_Adams

Neurology_Adams. rate of stroke during pregnancy was 6.2 per 100,000, but it doubled with each advance in age from 25 to 29, 30 to 39, and 40 to 49 years (Wiebers et al 1985). Included in most past series are cases with cardiac disease, particularly valve-related embolism. It is perhaps surprising that subarachnoid hemorrhage is not more frequent during the Valsalva activity of childbirth. Carotid artery dissection may also be encountered late in pregnancy or soon after delivery.