Alan Z. Segal

Apolipoprotein E Genotype and the Risk of Recurrent Lobar Intracerebral Hemorrhage

BACKGROUND Recurrent lobar intracerebral hemorrhage is the hallmark of cerebral amyloid angiopathy. The factors that predispose patients to early recurrence of lobar hemorrhage are unknown. One candidate is the apolipoprotein E gene, since both the epsilon2 and the epsilon4 alleles of apolipoprotein E appear to be associated with the severity of amyloid angiopathy. METHODS We performed a prospective, longitudinal study of consecutive elderly patients who survived a lobar intracerebral hemorrhage. The patients were followed for recurrent hemorrhagic stroke by interviews at six-month intervals and reviews of medical records and computed tomographic scans. RESULTS Nineteen of 71 enrolled patients had recurrent hemorrhages during a mean follow-up period of 23.9+/-14.8 months, yielding a 2-year cumulative rate of recurrence of 21 percent. The apolipoprotein E genotype was significantly associated with the risk of recurrence. Carriers of the epsilon2 or epsilon4 allele had a two-year rate of recurrence of 28 percent, as compared with only 10 percent for patients with the common apolipoprotein E epsilon3/epsilon3 genotype (risk ratio, 3.8; 95 percent confidence interval, 1.2 to 11.6; P=0.01). Early recurrence occurred in eight patients, four of whom had the uncommon epsilon2/epsilon4 genotype. Also at increased risk for recurrence were patients with a history of hemorrhagic stroke before entry into the study (two-year recurrence, 61 percent; risk ratio, 6.4; 95 percent confidence interval, 2.2 to 18.5; P<0.001). CONCLUSIONS The apolipoprotein E genotype can identify patients with lobar intracerebral hemorrhage who are at highest risk for early recurrence. This finding makes possible both the provision of prognostic information to patients with lobar hemorrhage and a method of targeting and assessing potential strategies for prevention.

Fever in subarachnoid hemorrhage: Relationship to vasospasm and outcome

Objective: To investigate the causes of fever in subarachnoid hemorrhage (SAH) and examine its relationship to outcome. Background: Fever adversely affects outcome in stroke. Patients with SAH are at risk for cerebral ischemia due to vasospasm (VSP). In these patients, fever may be both caused by, and potentiate, VSP-mediated brain injury. Methods: The authors prospectively studied patients admitted to a neurologic intensive care unit with nontraumatic SAH, documenting Hunt–Hess grade, Fisher group, Glasgow Coma Score, bacterial culture data, daily transcranial Doppler mean velocities, and maximum daily temperatures. Patients were classified as febrile (temperature above 38.3 °C for at least 2 consecutive days) or afebrile (no fever or isolated episodes of temperature above 38.3 °C). VSP was verified by either transcranial Doppler or angiographic criteria. Rankin scale scores on discharge were dichotomized into good (0 to 2) or poor (3 to 6) outcomes. Results: Ninety-two consecutive patients were studied. Thirty-eight patients were classified as febrile. No source for infection was found in 10 of 38 (26%) patients. In a multivariate analysis, three variables independently predicted fever occurrence: ventriculostomy (OR, 8.5 [CI, 2.4 to 29.7]), symptomatic VSP (OR, 5.0 [CI, 1.03 to 24.5]), and older age (OR, 1.75 per 10 years [CI, 1.02 to 3.0]). Poor outcome was related to fever (OR, 1.4 per each day febrile [CI, 1.1 to 1.88]), older age (OR, 1.64 per 10 years [CI, 1.04 to 2.58]), and intubation (OR, 21.8 [CI, 5.6 to 84.5]). Conclusion: Fever in SAH is associated with vasospasm and poor outcome independently of hemorrhage severity or presence of infection.

Stroke in patients with cancer Incidence and etiology

Objective: To assess the incidence and type of strokes in patients with cancer at Memorial Sloan–Kettering Cancer Center. Methods: Retrospective review of all ischemic strokes diagnosed by a neurologist and confirmed by neuroimaging between February 1997 and April 2001 was conducted. Age, gender, cancer diagnosis and stage, and vascular risk factors were recorded. NIH Stroke Scale and modified Rankin Scale scores were calculated retrospectively. Stroke etiology was assigned independently by two neurologists using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Results: Ninety-six patients with a confirmed stroke were identified. The median age was 67, and 61.5% were men. The distribution of vascular risk factors was comparable with that seen in large stroke trials. Lung cancer (30%) was the most common primary tumor followed by brain and prostate cancer (9% each). Strokes were embolic in 52 (54%) and nonembolic in 44 (46%). Eleven of 12 tested patients had an elevated d-dimer level, but in only 3 patients could a definitive diagnosis of nonbacterial thrombotic endocarditis be made. The median survival was 4.5 months (95% CI 2.8 to 9.5) from the diagnosis of stroke; 25% of patients died within 30 days. Treatment had no effect on survival. Conclusions: Embolic strokes are the commonest cause of stroke in patients with cancer, due partially to hypercoagulability, whereas atherosclerosis accounted for only 22% of stroke in this population. Outcome was primarily determined by the underlying malignancy and the patient’s neurologic condition.

A pilot study of drug-induced hypertension for treatment of acute stroke

The aim of this pilot study was to determine whether the use of induced hypertension in acute stroke is feasible and associated with neurologic improvement. Phenylephrine was used to raise the systolic blood pressure in patients with acute stroke by 20%, not to exceed 200 mmHg. Of 13 patients treated, 7 improved by 2 points on the NIH Stroke Scale. No systemic or neurologic complications were seen. The authors conclude that induced hypertension in acute stroke is feasible and likely safe and can improve the neurologic examination in some patients.

Cerebrovascular Reserve and Stroke Risk in Patients With Carotid Stenosis or Occlusion A Systematic Review and Meta-Analysis

Background and Purpose— Impairments in cerebrovascular reserve (CVR) have been variably associated with increased risk of ischemic events and may stratify stroke risk in patients with high-grade internal carotid artery stenosis or occlusion. The purpose of this study is to perform a systematic review and meta-analysis to summarize the association of CVR impairment and stroke risk. Methods— We performed a literature search evaluating the association of impairments in CVR with future stroke or transient ischemic attack in patients with high-grade internal carotid artery stenosis or occlusion. We included studies with a minimum of 1-year patient follow-up with baseline CVR measures performed by any modality and primary outcome measures of stroke and/or transient ischemic attack. A meta-analysis with assessment of study heterogeneity and publication bias was performed. Results were presented in a forest plot and summarized using a random-effects model. Results— Thirteen studies met the inclusion criteria, representing a total of 1061 independent CVR tests in 991 unique patients with a mean follow-up of 32.7 months. We found a significant positive relationship between impairment of CVR and development of stroke with a pooled random effects OR of 3.86 (95% CI, 1.99–7.48). Subset analysis showed that this association between CVR impairment and future risk of stroke/transient ischemic attack remained significant regardless of ischemic outcome measure, symptomatic or asymptomatic disease, stenosis or occlusion, or CVR testing method. Conclusions— CVR impairment is strongly associated with increased risk of ischemic events in carotid stenosis or occlusion and may be useful for stroke risk stratification.

Gabapentin as a novel treatment for postherpetic neuralgia

We report a case of postherpetic neuralgia that was dramatically responsive to the antiepileptic drug gabapentin (neurontin). This agent may prove a safe and effective alternative to current therapy, such as carbamazepine or amytriptilline. Our case highlights the severe morbidity that can otherwise result from postherpetic neuralgia and its treatment, particularly in the elderly. A 77-year-old right-handed woman with rheumatic heart disease, on warfarin for atrial fibrillation and prosthetic mechanical aortic and mitral valves, presented in August 1994 with a left occipital hemorrhagic stroke. Three months before admission, she developed herpetic zoster in the right T4 dermatome that was complicated by severe burning postherpetic neuralgia. Ten days before admission, she became oversedated on oral narcotic analgesics and fell backward out of a chair, suffering bilateral rim occipital subdural hematomas. Because of the hemorrhage, her warfarin dose was decreased. On August 7, the patient presented …

Stroke as a complication of cardiac catheterization: Risk factors and clinical features

The authors aimed to delineate the risk factors and radiologic pattern of stroke complicating cardiac catheterization. Twenty-two cases were matched with three control subjects. Stroke was significantly associated with severity of coronary artery disease and length of fluoroscopy time (OR 1.96 and 1.65). The use of MRI with diffusion weighting allowed the identification of multiple asymptomatic lesions and a subset of lacunar-type infarcts (23%), which most likely occurred on an atheroembolic basis.

Low Cholesterol as a Risk Factor for Primary Intracerebral Hemorrhage: A Case-Control Study

We performed a case-control study to assess the relationship between primary intracerebral hemorrhage (ICH) and low serum cholesterol. Prospectively recruited, fully evaluated patients with ICH were compared to two independent control groups, one based in a primary care practice and one population-based. Low cholesterol was defined by the sex-specific lowest quintile of the primary care controls. The proportion of ICH cases with low cholesterol >3 months posthemorrhage was significantly greater than in controls (42 vs. 20% in either control group, p < 0.01). Subgroup analysis showed an overrepresentation of low cholesterols in probable hypertensive hemorrhage (47%, p < 0.05) but not in probable cerebral amyloid angiopathy (27%, p = 0.5). Low cholesterol increased the odds for hemorrhage 2.25-fold (1.12–4.50) after adjustment for age and apolipoprotein E genotype. These data confirm an increased risk for primary ICH associated with low cholesterol, a relationship that may apply specifically to hemorrhages from hypertensive vasculopathy.

Cardiogenic and aortogenic brain embolism.

Cardioaortic brain embolism is a potentially devastating condition that presents frequent diagnostic and therapeutic challenges. In this report, we review key aspects of the etiology, clinical presentation, diagnosis, prognosis, and treatment of cardiogenic and aortogenic stroke. Emphasis is on advances in diagnostic imaging capabilities and on recent literature addressing secondary prevention for specific cardioembolic sources, upon which diagnosis and prognosis primarily depend. While early evaluation with modern neuroimaging techniques offers to enhance diagnostic accuracy, additional study is required to define optimal utilization. Appropriate imaging of the heart and aorta is paramount to identifying potential sources of embolism. Secondary prevention for high-risk embolic sources generally involves anticoagulation, but immediate initiation of anticoagulation is not routinely indicated. Medium-risk sources have more modest or undefined risks and little randomized comparative evidence to guide management, but antiplatelet therapy is generally favored. One possible exception is patent foramen ovale, for which high-risk features may warrant anticoagulation or mechanical closure. Definitive recommendations for this and other findings await completion of ongoing clinical trials.

Using Quantitative CT Perfusion for Evaluation of Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage

BACKGROUND AND PURPOSE: DCI is a serious complication following aneurysmal SAH leading to permanent neurologic deficits, infarction, and death. Our aim was to prospectively evaluate the diagnostic accuracy of CTP and to determine a quantitative threshold for DCI in aneurysmal SAH. MATERIALS AND METHODS: Patients with SAH were prospectively enrolled in a protocol approved by the institutional review board. CTP was performed during the typical time period for DCI, between days 6 and 8 following SAH. Quantitative CBF, CBV, and MTT values were obtained by using standard region-of-interest placement sampling of gray matter. The reference standard for DCI is controversial and consisted of clinical and imaging criteria in this study. In a subanalysis of vasospasm, DSA was used as the reference standard. ROC curves determined the diagnostic accuracy by using AUC. Optimal threshold values were calculated by using the patient population utility method. RESULTS: Ninety-seven patients were included; 41% (40/97) had DCI. Overall diagnostic accuracy was 93% for CBF, 88% for MTT, and 72% for CBV. Optimal threshold values were 35 mL/100 g/min (90% sensitivity, 68% specificity) for CBF and 5.5 seconds (73% sensitivity, 79% specificity) for MTT. In the subanalysis (n = 57), 63% (36/57) had vasospasm. Overall diagnostic accuracy was 94% for CBF, 85% for MTT, and 72% for CBV. Optimal threshold values were 36.5 mL/100 g/min (95% sensitivity, 70% specificity) for CBF and 5.4 seconds (78% sensitivity, 70% specificity) for MTT. CONCLUSIONS: CBF and MTT have the highest overall diagnostic accuracy. Threshold values of 35 mL/100 g/min for CBF and 5.5-second MTT are suggested for DCI on the basis of the patient population utility method. Absolute threshold values may not be generalizable due to differences in scanner equipment and postprocessing methods.