Vessel Wall Enhancement on Black-Blood MRI Predicts Acute and Future Stroke in Cerebral Amyloid Angiopathy.

BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) is a known risk factor for ischemic stroke though angiographic imaging is often negative. Our goal was to determine the relationship between vessel wall enhancement (VWE) in acute and future ischemic stroke in CAA patients. MATERIALS AND METHODS: This was a retrospective study of patients with new-onset neurologic symptoms undergoing 3T vessel wall MR imaging from 2015 to 2019. Vessel wall enhancement was detected on pre- and postcontrast flow-suppressed 3D T1WI. Interrater agreement was evaluated in cerebral amyloid angiopathy-positive and age-matched negative participants using a prevalence- and bias-adjusted kappa analysis. In patients with cerebral amyloid angiopathy, multivariable Poisson and Cox regression were used to determine the association of vessel wall enhancement with acute and future ischemic stroke, respectively, using backward elimination of confounders to P < .20. RESULTS: Fifty patients with cerebral amyloid angiopathy underwent vessel wall MR imaging, including 35/50 (70.0%) with ischemic stroke and 29/50 (58.0%) with vessel wall enhancement. Prevalence- and bias-corrected kappa was 0.82 (95% CI, 0.71-0.93). The final regression model for acute ischemic stroke included vessel wall enhancement (prevalence ratio = 1.5; 95% CI, 1.1-2.2; P = .022), age (prevalence ratio = 1.02; 95% CI, 1.0-1.05; P = .036), time between symptoms and MR imaging (prevalence ratio = 0.9; 95% CI, 0.8-0.9; P < .001), and smoking (prevalence ratio = 0.7; 95% CI, 0.5-1.0; P = .042) with c-statistic = 0.92 (95% CI, 0.84-0.99). Future ischemic stroke incidence with cerebral amyloid angiopathy was 49.7% (95% CI, 34.5%-67.2%) per year over a total time at risk of 37.5 person-years. Vessel wall enhancement-positive patients with cerebral amyloid angiopathy demonstrated significantly shorter stroke-free survival with 63.9% (95% CI, 43.2%-84.0%) versus 32.2% (95% CI, 14.4%-62.3%) ischemic strokes per year, chi-square = 4.9, P = .027. The final model for future ischemic stroke had a c-statistic of 0.70 and included initial ischemic stroke (hazard ratio = 3.4; 95% CI, 1.0-12.0; P = .053) and vessel wall enhancement (hazard ratio = 2.5; 95% CI, 0.9-7.0; P = .080). CONCLUSIONS: Vessel wall enhancement is associated with both acute and future stroke in patients with cerebral amyloid angiopathy.

Neurology Academic Advisory Committee: a strategy for faculty retention and advancement.

Major effort and expense are devoted to faculty recruitment. Subsequent direction, support, and guidance of faculty members for retention and academic advancement are often inconsistent and ineffective. Individual mentorship is widely endorsed as an important element in advancement but often does not occur or is uneven in its pragmatic benefit. We formed a Departmental Academic Advisory Committee to provide individualized advice and guidance about career development and institutional promotion, retention, and tenure procedures. To assess the effectiveness of this process, a survey was sent to faculty members. A 100% response rate was achieved. The results of the survey demonstrated high levels of acceptance by faculty members and described benefits experienced by faculty, including better understanding of promotion and tenure policies and specific actions taken to achieve professional goals. An academic advisory committee can be a valuable adjunct to individual mentorship and to meetings with department chairs to enhance faculty satisfaction and advancement of neurology faculty members.

Silent infarction as a risk factor for overt stroke in children with sickle cell anemia: a report from the Cooperative Study of Sickle Cell Disease.

OBJECTIVE: To determine whether children with homozygous sickle cell anemia (SCD) who have silent infarcts on magnetic resonance imaging (MRI) of the brain are at increased risk for overt stroke. METHODS: We selected patients with homozygous SCD who (1) enrolled in the Cooperative Study of Sickle Cell Disease (CSSCD) before age 6 months, (2) had at least 1 study-mandated brain MRI at age 6 years or older, and (3) had no overt stroke before a first MRI. MRI results and clinical and laboratory parameters were tested as predictors of stroke. RESULTS: Among 248 eligible patients, mean age at first MRI was 8.3 +/- 1.9 years, and mean follow-up after baseline MRI was 5.2 +/- 2.2 years. Five (8.1%) of 62 patients with silent infarct had strokes compared with 1 (0.5%) of 186 patients without prior silent infarct; incidence per 100 patient-years of follow-up was increased 14-fold (1.45 per 100 patient-years vs 0.11 per 100 patient-years, P =.006). Of several clinical and laboratory parameters examined, silent infarct was the strongest independent predictor of stroke (hazard ratio = 7.2, P =.027). CONCLUSIONS: Silent infarct identified at age 6 years or older is associated with increased stroke risk.

Proximal extracranial vertebral artery disease in the New England Medical Center Posterior Circulation Registry.

OBJECTIVE: To describe the clinical features of patients with occlusive disease of the proximal (V1) segment of the vertebral artery. DESIGN AND PATIENTS: Patients with either occlusion or high-grade stenosis involving the V1 segment were chosen for study from the New England Medical Center Posterior Circulation Registry. The registry is a consecutive series of patients with signs and symptoms of posterior circulation ischemia seen at the New England Medical Center, Boston, Mass, during a 10-year period. Clinical features, radiographic findings, and patient outcome were reviewed. RESULTS: Of the 407 patients in the registry, 80 (20%) had V1 segment lesions. Patients could be classified into 5 groups: (1) V1 disease and coexistent severe intracranial occlusive disease of the posterior circulation (n=22); (2) V1 disease with evidence of artery-to-artery embolism (n=19); (3) suspected V1 disease with artery-to-artery embolism, but with other potential causes of stroke or less certain vascular diagnosis (n=20); (4) V1 disease associated with hemodynamic transient ischemic attacks (n=13); and (5) proximal vertebral arterial dissection (n=6). Hypertension, cigarette smoking, and coronary artery disease were common risk factors. Clinical features, location of infarct, and outcome differed between groups and reflected the presumed mechanisms of stroke. CONCLUSIONS: Occlusive disease involving the V1 segment of the vertebral artery is common in patients with posterior circulation ischemia, but is often associated with other potential mechanisms of stroke. However, in a series of patients seen at a tertiary referral center, occlusive disease of the V1 segment was the primary mechanism of ischemia in 9% of patients.

Intracranial vertebral artery disease in the New England Medical Center Posterior Circulation Registry.

We studied 75 patients with severe intracranial vertebral artery (ICVA) occlusive disease from the New England Medical Center Posterior Circulation Registry to learn the etiologies and locations of the vascular lesions, the location and patterns of related ischemia and infarctions, and the outcomes. All patients had neuroimaging and vascular studies. Thirty-nine percent of patients had bilateral ICVA lesions. Twenty-four percent also had basilar artery disease and 36% had associated extracranial disease. The most common site of lesions was the distal ICVA after the origin of the posterior inferior cerebellar artery (PICA). Twenty-five percent of patients had only proximal intracranial posterior circulation territory infarcts (medullary and PICA cerebellar); 32% had infarcts that involved other intracranial territories in addition to the proximal territory. We found more distal intracranial territory infarcts resulting mainly from embolism from ICVA lesions than reported previously; this occurred in 17% of all patients. The ICVA was a recipient site for emboli in 8% of patients. Thirteen percent of patients died during follow-up. The outcome was favorable in most surviving patients. Three-fourths of them had no deficit or only slight disability. The patients with distal territory infarcts due to emboli from the ICVA had the worst outcome.

Proximal intracranial territory posterior circulation infarcts in the New England Medical Center Posterior Circulation Registry.

We studied 91 patients with proximal intracranial territory posterior circulation ischemia from the New England Medical Center Posterior Circulation Registry to learn their distribution, underlying cardiovascular causes and longterm outcome. All patients had imaging and vascular studies. Six patients had proximal territory TIAs. Among 85 stroke patients, 52% had infarcts limited to the proximal territory, while 48% also had infarcts in other intracranial posterior circulation territories. Eighty-five percent of proximal territory infarcts were posterior inferior cerebellar artery (PICA) territory cerebellar infarcts and 30% were lateral medullary infarcts. One patient had a hemimedullary syndrome. Six patients had PICA territory cerebellar and lateral medullary infarcts. The most common vascular lesion in lateral medullary infarct patients was ipsilateral intracranial vertebral artery (ICVA) disease (38% isolated ICVA disease) and in PICA territory cerebellar infarcts, extracranial vertebral artery (ECVA) disease (29% isolated ECVA disease). Half of all lateral medullary infarcts were due to a hemodynamic mechanism, most often in situ thrombosis of an ICVA occlusive lesion. Half of all PICA territory cerebellar infarcts were due to intra-arterial embolism and one-fifth to cardiac origin embolism. Embolism was a more frequent cause of proximal territory posterior circulation infarcts than intrinsic ICVA disease. The etiological profiles of lateral medullary and PICA cerebellar infarcts were different. Seventeen percent of all patients died during follow-up (41 months) but mortality related to the acute stroke or new strokes was only 6 percent. The outcome was favorable in the surviving patients; 89% had no or only slight disability.

Cerebellar hemorrhagic infarction.

We investigated 17 patients with 26 cerebellar hemorrhagic infarcts for their vascular anatomy, stroke mechanisms, and clinical course. Sixteen infarcts involved the superior cerebellar artery, nine the posterior inferior cerebellar artery, and one the anterior inferior cerebellar artery territories. The infarcts involved the full territory of the supplying arteries in 19 of 26 infarcts (73%). Sixteen of 17 patients were stable or improving when the hemorrhagic infarction was detected. All but one patient had an imaging study at the time of presentation that was negative for blood; hemorrhagic infarction was detected on routine serial scans performed during the first 15 days. Nine of the 17 patients were on anticoagulants when the cerebellar hemorrhagic infarct was detected; anticoagulation was maintained in eight of them with no clinical worsening. The stroke mechanism in all patients was considered embolic from cardiac and intra-arterial sources. The causes, imaging findings, and consequences of hemorrhagic infarcts in the posterior circulation are similar to those in the anterior circulation.

Stroke with sensory symptoms mimicking myocardial ischemia.

OBJECTIVE: To report five stroke patients with sensory deficits including prominent chest discomfort mimicking angina. BACKGROUND: Chest wall sensory discomfort, as a part of unilateral sensory dysfunction, has seldom been recognized as a potential imitator of cardiac ischemia. METHODS: A retrospective review of stroke patients with sensory symptoms from the New England Medical Center Stroke Registry. RESULTS: As a part of an acute stroke that included unilateral sensory symptoms and signs, five patients had chest pain or discomfort, which prompted cardiac evaluation for potential coronary artery disease. In two patients, the primary presentation was chest discomfort. In the other three, chest discomfort was part of a more extensive stroke syndrome. The symptoms were described as "burning," "hot feeling," "flashes," "tightness," and "cold." In three patients, an MRI or CT scan showed an infarct in the thalamus, corona radiata, or lateral medulla. Cardiac evaluation was negative in all but one patient who had single vessel percutaneous transluminal coronary angioplasty without resolution of sensory symptoms. Chest discomfort fluctuated but persisted for months or years after presentation. CONCLUSION: Chest discomfort mimicking cardiac ischemia may be a prominent sensory symptom in acute stroke.

Brain edema after carotid surgery.

The postoperative hyperperfusion syndrome describes an abrupt increase in blood flow with loss of autoregulation in surgically reperfused brain. Reports described a spectrum of findings, including severe headache, transient ischemia, seizures, and intracerebral hemorrhage. Hypertension is common after carotid artery surgery and often plays a role in the pathophysiology. We now report five patients with severe white matter edema after carotid surgery, a finding not previously included in the hyperperfusion syndrome. Five to 8 days after carotid surgery and after hospital discharge, each patient developed hypertension, headache, hemiparesis, seizures, and aphasia or neglect due to severe white matter edema ipsilateral to the carotid surgery. One patient had a small hemorrhage within the edematous area. Hypertension was severe in four patients and moderate in one. The carotid artery was patent by ultrasound or angiography in each patient after surgery. Transcranial Doppler showed increased velocities ipsilateral to surgery in two patients and bilaterally in one. Computed tomographic abnormalities and neurologic signs resolved within 3 weeks in four of the five patients treated with antihypertensives and anticonvulsants. The fifth patient died from herniation secondary to massive edema. Brain edema with focal neurologic signs should be included as a serious but potentially reversible component of the postoperative hyperperfusion syndrome.

Longitudinal monitoring of intracranial arterial stenoses with transcranial Doppler ultrasonography.

The natural history of intracranial arterial stenoses remains relatively unknown. To monitor the progression of these lesions over time, the authors reviewed transcranial Doppler (TCD) laboratory reports at five hospitals for patients with angiographically documented intracranial arterial stenoses along the internal carotid artery distribution, and at least two TCD studies conducted more than 2 months apart. Twenty-two patients (19 men and 3 women; mean age, 64 years) with 29 stenoses were identified. The findings were compared to reproducibility data obtained from 11 age-matched control subjects with repeat TCD studies. During a mean follow-up period of 21 months, peak systolic flow velocities corresponding to the areas of stenosis increased in 9 arteries with lesions, and new collateral flow patterns, indicating further hemodynamic compromise distal to the lesions, developed in 2; one of the latter also had increased corresponding velocities. Thus, 10 (35%) arteries with lesions had TCD evidence of progression. Flow velocities remained the same in 13 (45%) stenotic vessels and dropped in 2 (7%). Findings were considered inconclusive for 4 lesions (14%). These findings suggest that intracranial arterial stenoses are dynamic lesions, and that they can evolve and cause further reductions of the arterial diameters after relatively short periods of time. TCD can noninvasively detect their hemodynamic effects.

Neurologic complications of infectious mononucleosis.

A review of the neurologic complications of Epstein-Barr viral (EBV) infections is presented. EBV has been associated with a wide range of acute neurologic diseases in children. Encephalitis, meningitis, cranial nerve palsies, mononeuropathies, and many other neurologic ailments have been described since the confirmation of EBV as the etiology of infectious mononucleosis. It is important to recognize that EBV can cause a myriad of neurologic illnesses with or without the stigmata of infectious mononucleosis.

Transcranial Doppler validation pilot study.

The use of transcranial Doppler sonography (TCD) for the evaluation of patients with ischemic cerebrovascular disease remains controversial. This study was organized to gather preliminary data regarding the sensitivity and specificity of TCD when compared to cerebral angiography in detecting stenosing lesions and collateral flow patterns of the anterior cerebral circulation. Forty-two patients from six medical centers were prospectively enrolled. Each received cerebral angiography and TCD testing within 24 hours of each other. Based on TCD criteria established a priori, the results were first analyzed by a blinded investigator and then by computer. Computerized analyses were then repeated with modified criteria. Collateral flow through the anterior communicating and ophthalmic arteries was detected with sensitivities of 62% and 100%, and specificities of 98% and 92%, respectively. Internal carotid artery proximal and distal severe ( greater than 70%) stenoses were detected with sensitivities of 79% and 100% and specificities of 88% and 97%. Middle and anterior cerebral artery stenoses and middle cerebral artery occlusion were detected with specificities exceeding 98%; however, the data were insufficient to determine sensitivity. Computerized analyses did not permit improvement of sensitivity and specificity of the baseline criteria. The selected TCD criteria are highly specific in detecting intracranial stenoses and collateral flow patterns of the anterior circulation. The criteria have limited but acceptable sensitivity and specificity in detecting internal carotid artery origin severe stenoses, and are highly sensitive in detecting ophthalmic artery retrograde flow. A study with a larger sample is necessary to provide definitive guidelines for diagnosis.

Postoperative brainstem and cerebellar infarcts.

OBJECTIVE: To study the clinical features and causes of postoperative brainstem and cerebellar infarcts. METHODS: Two groups were studied. The 10 group 1 patients had cardiac (eight) or aortic (two) surgery. The 12 group 2 patients had noncardiac-nonvascular surgery, including orthopedic (five), gynecologic (four), and general (three). Patients were studied by stroke services at university hospitals in Boston (13), Charlottesville (three), Baltimore (three), and Mainz (three) during 2 consecutive years. RESULTS: Onset of strokes was immediately postoperative (six), during the first 48 postoperative hours (nine), and delayed 3 days or more (seven). Clinical syndromes were altered level of consciousness or cognition (15), vestibulocerebellar (four), and hemiparesis with focal brainstem signs (three). Infarction involved the brainstem (13), cerebellum (13), and posterior cerebral artery hemispheric territory (10). Causes: In group 1, five infarcts were due to cardiogenic embolism and three to embolism from the aorta. One patient had a postoperative pontine lacunar infarct and one developed an infarct in the territory of a known stenotic basilar artery. In group 2, one patient had vertebral artery injury from instrumentation, one had medical complications with severe hemorrhage and hypotension, and 10 most likely had position-related vertebral artery thromboses. CONCLUSIONS: Patients with postoperative brainstem and cerebellar infarcts present with altered consciousness or vestibulocerebellar syndromes. The major cause of brain infarcts after cardiac surgery is embolism from the heart and aorta. The causes of infarction after general surgery are less clear, but neck positioning during or after surgery may play an important role by promoting thrombi in compressed arteries that later embolize intracranially when neck motion becomes free.

Anterior inferior cerebellar artery territory infarcts. Mechanisms and clinical features.

Arterial lesions, mechanisms, territory, and clinical features of anterior inferior cerebellar artery (AICA) territory infarcts are only based on necropsy cases. To our knowledge, no large clinical series has been reported. We selected nine consecutive patients with AICA territory infarction confirmed by magnetic resonance imaging and angiography. Atherosclerosis was the only cause and all patients were hypertensive. Patients with pure AICA territory infarcts (n = 4) were diabetic and likely had basilar branch occlusion due to basilar artery plaques that extended into the AICA or microatheroma that blocked the AICA origin. These patients had no or had only recently had (1 day) prodromata. Patients with AICA plus infarct (n = 5) had basilar artery occlusion at the AICA and reconstitution of the distal basilar artery by collaterals through hemispheric anastomoses from the posterior inferior cerebellar arteries and posterior communicating arteries. All these patients except one had prodromata. In seven of nine patients, cranial nerve involvement indicated a lateral pontine lesion in the territory supplied by the AICA. Only two patients had the complete AICA syndrome, and none of the patients had isolated vertigo. The outcome was good in seven of nine patients. Isolated unilateral AICA infarcts should be regarded as most likely due to small artery atherosclerotic disease in diabetic patients. More widespread infarctions that include that AICA territory are due to basilar artery occlusive disease.

Intermittent downbeat nystagmus due to vertebral artery compression.

Downbeat nystagmus (DBN) uncommonly occurs as a transient phenomenon, and it rarely occurs in patients with cerebrovascular disease. We observed a patient with intermittent DBN and lightheadedness due to transient obstruction of his dominant vertebral artery when he turned his head to his left side. Surgical removal of an osteophyte at the site of the angiographically demonstrated lesion relieved his symptoms.

Embolism from vertebral artery origin occlusive disease.

We report 10 patients with severe occlusive disease of the vertebral artery (VA) origin in the neck with intra-arterial embolism to the posterior circulation. The VA lesions in seven patients were complete occlusions, and three patients had severe atherostenosis. All patients had strokes in the vertebrobasilar territory. The most frequent recipient sites of intra-arterial embolism were the intracranial VA-posterior inferior cerebellar artery region (8), and the distal basilar artery (BA) and its superior cerebellar and posterior cerebral artery branches (7). Two patients had pontine infarction due to BA embolism. The most common clinical signs were due to cerebellar infarction. Atherosclerotic disease of the VA origin has features in common with disease of the internal carotid artery origin. Both have similar risk factors and demography, and each can cause strokes by intracranial intra-arterial embolism.

Changing attentional demands in left hemispatial neglect.

Seven variations of a letter cancellation test were used to examine how varying attentional demands affect hemispatial neglect in patients with right hemisphere lesions. While the 14 targets always remained in the same location, the number of distractors (zero, nine, 28, or 82) as well as their complexity (one letter or nine different letters) were varied. The percentage of targets canceled in the left hemispace was linearly related to the number of distractors. There were no differences between the complexity conditions. In a second study, the same 14 targets were presented but the distractors (zero, 14, or 41) were all placed on the right. Increasing the number of distractors on the right increased neglect on both sides of the space. Taken together, these results suggest that, while the limited attentional resources of the left hemisphere are biased toward the right hemispace, the absence of contralateral attentional demands allows these resources to be directed ipsilaterally.

Effects of changes in stimulus contingency on visual extinction.

Left visual field (LVF) extinction during double simultaneous stimulation (DSS) is common in patients with right cerebral lesions. A postulate is that during DSS, the intact left hemisphere's limited attentional capacity is directed to right hemispace, resulting in LVF extinction. External cueing may help direct attention to the LVF and improve performance. In the present study, we varied patterns of unilateral stimulation preceding DSS in an attempt to redirect attention through expectancy. Nine patients (7 stroke, 2 tumor) with right hemisphere lesions each had 40 DSS trials with the distribution of unilateral stimulation trials systematically varied. Mean extinction percentages on DSS trials were 17% following 5 right unilateral trials, 30% following 1 right unilateral trial, 52% following 1 left unilateral trial, and 63% following 5 left unilateral trials. These findings indicate that the probability of extinction decreases following unilateral stimulation to the right visual field and increases following unilateral stimulation to the LVF. These results suggest that expectancy alters the attentional bias which mediates extinction.