Mehmet Akif Topcuoglu

Reversible Cerebral Vasoconstriction Syndromes: Analysis of 139 Cases

OBJECTIVES To compare the clinical, laboratory, and imaging features of patients with reversible cerebral vasoconstriction syndromes evaluated at 2 academic centers, compare subgroups, and investigate treatment effects. DESIGN Retrospective analysis. SETTING Massachusetts General Hospital (n = 84) or Cleveland Clinic (n = 55). PATIENTS One hundred thirty-nine patients with reversible cerebral vasoconstriction syndromes. MAIN OUTCOME MEASURES Clinical, laboratory, and imaging features; treatment; and outcomes. RESULTS The mean age was 42.5 years, and 81% were women. Onset with thunderclap headache was documented in 85% and 43% developed neurological deficits. Prior migraine was documented in 40%, vasoconstrictive drug exposure in 42%, and recent pregnancy in 9%. Admission computed tomography or magnetic resonance imaging was normal in 55%; however, 81% ultimately developed brain lesions including infarcts (39%), convexity subarachnoid hemorrhage (34%), lobar hemorrhage (20%), and brain edema (38%). Cerebral angiographic abnormalities typically normalized within 2 months. Nearly 90% had good clinical outcome; 9% developed severe deficits; and 2% died. In the combined cohort, calcium channel blocker therapy and symptomatic therapy alone showed no significant effect on outcome; however, glucocorticoid therapy showed a trend for poor outcome (P = .08). Subgroup comparisons based on prior headache status and identified triggers (vasoconstrictive drugs, pregnancy, other) showed no major differences. CONCLUSION Patients with reversible cerebral vasoconstriction syndromes have a unique set of clinical imaging features, with no significant differences between subgroups. Prospective studies are warranted to determine the effects of empirical treatment with calcium channel blockers and glucocorticoids.

Effects of Stroke Localization on Cardiac Autonomic Balance and Sudden Death

BACKGROUND AND PURPOSE Stroke has been shown to alter autonomic function. The purpose of this study was to show the differential effects of stroke localization on autonomic function parameters assessed by heart rate variability (HRV). METHODS To determine the differential effect of ischemic stroke localization on autonomic cardiac innervation, we evaluated 62 patients with ischemic stroke and 62 age- and sex-matched controls. The localization of the infarct was determined by CT and MRI. Power spectrum analysis of HRV was performed. Myocardial necrosis was ruled out by echocardiography and creatine kinase myocardial isoenzymes measurements. RESULTS All stroke patients had significantly decreased low frequency, high frequency, and standard deviation of all relative risk intervals values (P<0.001). However, patients with right-middle cerebral artery (R-MCA) and insula lesions had significantly lower power spectrum analysis values compared with all other localizations (P<0.001). In addition, 5 patients with R-MCA insular lesions died suddenly compared with 2 patients with left-middle cerebral artery insular lesions during hospitalization. Both sympathetic- and parasympathetic-controlled HRV were decreased in patients with ischemic stroke. The most pronounced decrease was found in the territory of R-MCA insular cortex, which suggests that cardiac autonomic tone may be regulated by insula and that these patients are more prone to cardiac complications such as arrhythmias and sudden death due to autonomic imbalance. CONCLUSION We conclude that stroke in the region of insula (especially the right) leads to decreased HRV and to increased incidence of sudden death.

Relationship between hyperglycemia and symptomatic vasospasm after subarachnoid hemorrhage.

Objective:To determine the relationship between blood glucose levels (mg/dL) and occurrence of symptomatic vasospasm (VSP) and clinical outcomes after aneurysmal subarachnoid hemorrhage. Design:Retrospective observational study of 352 patients with subarachnoid hemorrhage admitted within 48 hrs of ictus between January 1995 and June 2002. Setting:Neurointensive care unit. Patients:Adult patients admitted after subarachnoid hemorrhage. Interventions:None. Measurements and Main Results:Variables included age; Hunt-Hess classification score; Fisher group; insulin use; infectious disease status; history of diabetes mellitus; and blood glucose values. Poor clinical outcome was defined by a modified Rankin score ≥3, and hyperglycemia was defined by a blood glucose level >140 mg/dL. Mean daily blood glucose values were assessed from admission to development of VSP or day 14. Mean admission blood glucose value, mean inpatient blood glucose value, insulin use, infectious disease status, Hunt-Hess classification score, Fisher group, and history of diabetes mellitus were entered in a Cox proportional hazards model. VSP occurred in 103 (29.2%) of 352 patients. Mean admission blood glucose values (176.6 ± 40.3 mg/dL vs. 162.3 ± 47.8 mg/dL; p = .01) and mean inpatient blood glucose values (166.2 ± 24.7 mg/dL vs. 155.8 ± 29.7 mg/dL; p = .001) were significantly higher in patients with VSP. Mean inpatient blood glucose value (relative risk, 1.01; 95% confidence interval, 1.0–1.03; p = .04), Hunt-Hess classification score ≥3 (relative risk, 2.23; 95% confidence interval, 1.21–3.99; p = .02), and Fisher group score of 3 (relative risk, 1.28; 95% confidence interval, 1.15–3.1; p = .05) increased the risk for VSP. Hyperglycemia was associated with longer length of stay in the neurointensive care unit (14.5 ± 7.1 days vs. 11.6 ± 5.4 days; p < .001) and poor outcome at discharge (modified Rankin score ≥3: 58.9% vs. 18.8%; p < .001). Conclusions:Mean inpatient blood glucose value is associated with the development of VSP and may represent a target for therapy to prevent VSP and improve clinical outcomes.

Acute Ischemic Stroke Patterns in Infective and Nonbacterial Thrombotic Endocarditis A Diffusion-Weighted Magnetic Resonance Imaging Study

Background and Purpose— Although infective endocarditis (IE) and nonbacterial thrombotic endocarditis (NBTE) are associated with cardioembolic stroke, differences in the nature of these conditions may result in differences in associated stroke patterns. We compared patterns of acute and recurrent ischemic stroke in IE and NBTE, using diffusion-weighted MRI (DWI). Methods— Using ICD-9 diagnostic codes and medical record review, we identified 362 patients (387 episodes) with IE and 14 patients with NBTE. Thirty-five patients (with 27 episodes of IE, 9 NBTE) who underwent 36 initial and 29 follow-up DWI scans were selected for this study. DWI lesion size, number, and location were compared between groups and correlated with stroke syndromes and endocarditis features. Results— DWI was abnormal in all but 2 patients. Four acute stroke patterns were identified: (1) single lesion, (2) territorial infarction, (3) disseminated punctate lesions, and (4) numerous small (<10 mm) and medium (10 to 30 mm) or large (>30 mm) lesions in multiple territories. All patients with NBTE exhibited pattern 4, whereas those with IE exhibited patterns 1, 2, 3, and 4 (6, 2, 8 and 9 episodes, respectively). Seventy-five percent of patients with pattern 3 exhibited the clinical syndrome of embolic encephalopathy. Vegetation size, valve, and organisms had no correlation with stroke patterns. Conclusion— DWI has utility in differentiating between IE and NBTE. Patients with NBTE uniformly have multiple, widely distributed, small and large strokes, whereas patients with IE exhibit a panoply of stroke patterns.

Effect of clipping, craniotomy, or intravascular coiling on cerebral vasospasm and patient outcome after aneurysmal subarachnoid hemorrhage.

OBJECTIVE:Although several recent studies have suggested that the incidence of vasospasm after aneurysmal subarachnoid hemorrhage is lower in patients undergoing aneurysmal coiling as compared with clipping, other studies have had conflicting results. We reviewed our experience over 8 years and assessed whether clipping, craniotomy, or coiling affects patient outcomes or the risk for vasospasm. METHODS:We included 515 patients with aneurysmal subarachnoid hemorrhage, identified prospectively from November 2000 to February 2003 (243 patients) and retrospectively from November 1995 to October 2000 (272 patients), by using International Classification of Diseases, 9th Revision, codes for subarachnoid hemorrhage. We classified patients as follows: clipping (413 patients), coiling (79 patients), and craniotomy (436 patients, including all 413 patients who underwent clipping plus 23 who underwent coiling as well as craniotomy for various reasons). We studied four outcome measures: total vasospasm, symptomatic vasospasm, poor outcome (modified Rankin score 3–6), and in-hospital mortality. To assess the risk of total vasospasm and symptomatic vasospasm, we performed multivariate regression analyses adjusting for age, Fisher grade, Hunt and Hess grade, aneurysm location (anterior versus posterior circulation), and aneurysm treatment modality. To assess the risk for poor outcome and in-hospital mortality, we adjusted for all the above variables as well as for total and symptomatic vasospasm. RESULTS:In the clipping group there was 63% total vasospasm and 28% symptomatic vasospasm; in the coiling group there was 54% total vasospasm and 33% symptomatic vasospasm; and in the craniotomy group there was 64% total vasospasm and 28% symptomatic vasospasm. In the multivariate analysis, age <50 years (P = 0.0099) and Fisher Grade 3 (P < 0.00001) predicted total vasospasm, and Fisher Grade 3 (P < 0.000001) and Hunt and Hess Grade IV or V (P = 0.018) predicted symptomatic vasospasm. Predictors of poor outcome were age ≥50 years (P < 0.0001), Fisher Grade 3 (P = 0.0072), Hunt and Hess Grade IV or V (P < 0.00001), symptomatic vasospasm (P < 0.0001), and coiling (P = 0.0314 versus clipping and P = 0.045 versus craniotomy). Predictors of in-hospital mortality were age ≥ 50 years (P = 0.0030), Hunt and Hess Grade IV or V (P = 0.0001), symptomatic vasospasm (P < 0.00001), and coiling (P = 0.008 versus clipping and P = 0.0013 versus craniotomy). There was no significant difference in total vasospasm or symptomatic vasospasm when patients who underwent clipping or craniotomy were compared with patients who underwent coiling. In patients with Hunt and Hess Grade I to III (“good grade”), clipping and craniotomy were associated with better outcome and less in-hospital mortality, but there was no difference in total vasospasm or symptomatic vasospasm versus coiling. In patients with Hunt and Hess Grade IV or V (“poor grade”), there was no difference in any outcome measure among the treatment groups. CONCLUSION:In a single-center, retrospective, nonrandomized study, performance of clipping and/or craniotomy had significantly better outcome and lower mortality at discharge than coiling in good-grade patients but had no effect on total vasospasm or symptomatic vasospasm in good- or poor-grade patients.

SSRI and statin use increases the risk for vasospasm after subarachnoid hemorrhage

Background: Use of medications with vasoconstrictive or vasodilatory effects can potentially affect the risk for vasospasm after aneurysmal subarachnoid hemorrhage (SAH). Methods: Using International Classification of Diseases–9 diagnostic codes followed by medical record review, the authors identified 514 patients with SAH admitted between 1995 and 2003 who were evaluated for vasospasm between days 4 and 14. The authors determined risks for vasospasm, symptomatic vasospasm, and poor clinical outcomes in patients with documented pre-hemorrhagic use of calcium channel blockers, beta-receptor blockers, ACE inhibitors, aspirin, selective serotonin reuptake inhibitors (SSRIs), non-SSRI vasoactive antidepressants, or statins. Results: Vasospasm developed in 62%, and symptomatic vasospasm in 29% of the cohort. On univariate analysis, the risk for all vasospasm tended to increase in patients taking SSRIs (p = 0.09) and statins (p = 0.05); SSRI use increased the risk for symptomatic vasospasm (p = 0.028). The Cochran-Armitage trend test showed that the proportion of patients taking SSRIs and statins increased significantly across three worsening categories (none, asymptomatic, symptomatic) of vasospasm. Logistic regression analysis showed that SSRI use tended to predict all vasospasm (O.R. 2.01 [0.91 to 4.45]), and predicted symptomatic vasospasm (O.R. 1.42 [1.06 to 4.33]). Statin exposure increased the risk for vasospasm (O.R. 2.75 [1.16 to 6.50]), perhaps from abrupt statin withdrawal (O.R. 2.54 [0.78 to 8.28]). Age < 50 years, Hunt-Hess grade 4 or 5, and Fisher Group 3 independently predicted all vasospasm, symptomatic vasospasm, poor discharge clinical status, and death. Conclusion: Selective serotonin reuptake inhibitor and statin users have a higher risk for subarachnoid hemorrhage–related vasospasm. Whether the underlying disease indication, direct actions, or rebound effects from abrupt drug withdrawal account for the associated risk warrants further investigation.

Megalencephaly and leukodystrophy with mild clinical course: a report on 12 new cases

Twelve patients with early infancy onset megalencephaly and leukodystrophy with a mild clinical course are reported. The neuroradiological, clinical, and genetic aspects of this recently recognized familial leukodystrophy syndrome were reviewed. Five were affected siblings, and all patients had consanguineous parents. Macrocephaly, a slowly progressive delay in motor development and mild mental deterioration constitute the clinical triad of the disease, showing characteristic age-related onset. The clinical findings outlined remarkably slight functional deterioration despite severe lesions on magnetic resonance imaging (MRI), especially in the initial period. Characteristically, mental function is preserved for years after onset of the motor deficit. The MRI lesions do not reflect the progress of disease. The disease probably has an autosomal recessive mode of inheritance even though no metabolic defect has been detected to date. In a more severe variant of the mentioned disease, there is more progressive and severe neurological dysfunction, including ataxia and spastic quadriparesis, leading to an inability to walk independently after 10 years of age. In mild variants, however, disease severity varies from macrocephaly with near-normal pyschomotor development to mild motor and/or mental dysfunction. Seizures were observed in both types but response to drugs was good. The 12 patients reported here confirm the specific and distinguishing clinical and radiological features of the previously reported 51 cases with this new syndrome, while adding some information regarding identification of the disease.

Antiplatelet resistance in stroke

Although the exact prevalence of antiplatelet resistance in ischemic stroke is not known, estimates about the two most widely used antiplatelet agents – aspirin and clopidogrel – suggest that the resistance rate is high, irrespective of the definition used and parameters measured. Inadequate antiplatelet responsiveness correlates with an increased risk of recurrent ischemic vascular events in patients with stroke and acute coronary syndrome. It is not currently known whether tailoring antiplatelet therapy based on platelet function test results translates into a more effective strategy to prevent secondary vascular events after stroke. Large-scale clinical trials using a universally accepted definition and standardized measurement techniques for antiplatelet resistance are needed to demonstrate whether a ‘platelet-function test-guided antiplatelet treatment’ strategy translates into improved stroke care. This article gives an overview of the clinical importance of laboratory antiplatelet resistance, describes the challenges for platelet-function test-guided antiplatelet treatment and discusses practical issues about the management of patients with aspirin and/or clopidogrel resistance.

Reversible cerebral vasoconstriction syndromes and primary angiitis of the central nervous system: clinical, imaging, and angiographic comparison.

Reversible cerebral vasoconstriction syndromes (RCVS) and primary angiitis of the central nervous system (PACNS) are invariably considered in the differential diagnosis of new cerebral arteriopathies. However, prompt and accurate diagnosis remains challenging. Here we compared the features of 159 RCVS to 47 PACNS patients and developed criteria for prompt bedside diagnosis. Recurrent thunderclap headache (TCH), and single TCH combined with either normal neuroimaging, border zone infarcts, or vasogenic edema, have 100% positive predictive value for diagnosing RCVS or RCVS‐spectrum disorders. In patients without TCH and positive angiography, neuroimaging can discriminate RCVS (no lesion) from PACNS (deep/brainstem infarcts). Ann Neurol 2016;79:882–894

The detrimental effect of aging on leptomeningeal collaterals in ischemic stroke.

BACKGROUND Aging is associated with decreased penumbral salvage in patients with ischemic stroke. Another critical factor that determines the fate of penumbra tissue is the degree of collateral circulation, which decreases significantly with aging in experimental models of stroke. In this study, we sought to identify whether these observations could be translated to humans and, therefore, analyzed the effect of patient age on extent of leptomeningeal collaterals in patients with ischemic stroke. METHODS Computed tomography angiography (CTA) source images were used to assess the degree of collateral circulation in a retrospective series of patients with proximal middle cerebral artery (MCA) occlusion. Bivariate and multivariate analyses were used to explore the relationship between patient age and degree of collateral circulation. RESULTS A total of 70 patients were included into the study. Older age (P = .005), history of hypertension (P = .036), higher admission National Institutes of Health Stroke Scale (NIHSS) scores (P = .013), and increased time to CTA (P = .013) were associated with inadequate collaterals in bivariate analyses. In multivariate analysis, older age (P = .008) and higher NIHSS scores (P = .032) remained as the only significant independent variables that were associated with inadequate collaterals. A 10-year increment in patient age increased the odds of inadequate collateral circulation by 1.87 (95% confidence interval: 1.18-2.97). CONCLUSION Our findings show that there is a significant interplay between patient age and adequacy of leptomeningeal collateral circulation in patients with proximal MCA occlusion. The relationship could contribute to adverse tissue outcome and thereby to unfavorable clinical outcome observed in elderly patients with ischemic stroke.