N. M. Bornstein

Triggering risk factors for ischemic stroke A case-crossover study

Background: While vascular risk factors for stroke are well established, little is known about factors that may precipitate the acute event. In this study the authors investigated the association between exposure to seven potential triggers during waking hours and acute onset of ischemic stroke. Methods: In a case-crossover study, 200 consecutive stroke patients were interviewed 1 to 4 days after the event using a validated questionnaire. Reported exposure to potential triggers including negative and positive emotions, anger, sudden posture changes as response to a startling event, heavy physical exertion, heavy eating, and sudden temperature changes during a 2-hour hazard period prior to stroke onset were compared to the same period during the preceding day and to average exposures in the last year. Results: Seventy-six patients (38%) reported exposure to at least one of the study triggers during the 2-hour hazard period. For all factors combined, the OR was 8.4 (95% CI 4.5 to 18.1). The OR for negative emotions was 14.0 (95% CI 4.4 to 89.7), for anger 14.0 (95% CI 2.8 to 253.6), and for sudden changes in body posture in response to a startling event 24.0 (95% CI 5.1 to 428.9). It is important to interpret the reported ORs as estimates of a short-term 2-hour period relative risk and not as cumulative risks. Conclusions: Negative emotions, anger, and sudden changes in body posture in response to a startling event appear to be independent triggers for ischemic stroke.

Prognostic implications of admission inflammatory profile in acute ischemic neurological events

Anuk T, Assayag EB, Rotstein R, Fusman R, Zeltser D, Berliner S, Avitzour D, Shapira I, Arber N, Bornstein NM. Prognostic implications of admission inflammatory profile in acute ischemic neurological events. Acta Neurol Scand 2002: 106: 196–199.

Parkinsonism in Patients with Lacunar Infarcts of the Basal Ganglia

Forty-five patients with CT findings of lucanar infarcts in the basal ganglia (LIBG) were included in this study. The patients were divided into those with lacunes in the caudate nucleus, lentiform nucleus or both caudate and lentiform nuclei. Linear measurements of ventricular spaces were also performed. Clinical evaluation disclosed parkinsonism in 17 patients (38%), strokes with contralateral hemiparesis in 14 (31%), while 9 (20%) had both parkinsonism and hemiparesis. The location and number of infarcts did not correlate with the clinical presentation. We conclude that LIBG are commonly associated with parkinsonism and that CT studies may help in the delineation of vascular parkinsonism.

Mechanical ventilation in stroke patients ; Is it worthwhile ?

We assessed the therapeutic efficacy and outcome of mechanical ventilation (MV) in patients with acute respiratory failure (ARF) following ischemic stroke (IS) or intracerebral hemorrhage (ICH), retrospectively graded by patients with IS (n = 881) and ICH (n = 108) admitted to our service during 11 years, according to the severity of their clinical state and to whether we employed MV.Outcome was recorded in terms of survival and duration of MV and compared with patients with neuromuscular (NM) diseases. We found a very high in-hospital mortality in stroke patients who were treated with ventilation (90.5% for IS and 87.5% for ICH) compared with NM patients (29%). We conclude that MV in stroke patients with ARF is not life-saving, and its use should be considered only after considering other potentially important factors. NEUROLOGY 1996;47: 657-659

Activated polymorphonuclear leukocytes and monocytes in the peripheral blood of patients with ischemic heart and brain conditions correspond to the presence of multiple risk factors for atherothrombosis.

Objective: Risk factors like hypertension, diabetes mellitus, dyslipidemia and smoking contribute to the pathogenesis of atherothrombosis. We investigated whether the multiplicity of risk factors for atherothrombosis is associated with leukocyte activation. Methods: We examined the availability of CD11b/CD18 antigen on the surface of peripheral blood polymorphonuclear leukocytes and monocytes in patients with acute ischemic heart and brain conditions. Results: There was a highly significant (p < 0.00001) increment in the availability of the CD11b/CD18 antigen on the surface of the polymorphonuclear leukocytes in patients with multiple (2 or more) vascular risk factors [mean fluorescence intensity (MFI) ± SD, 210 ± 102] as opposed to individuals with none or 1 risk factor for atherothrombosis (MFI 159 ± 73). Similar results were observed on the monocytes: 309 ± 151 and 235 ± 97, respectively (p < 0.00001). Conclusion: The multiplicity of risk factors for atherothrombosis is associated with the up-regulation of CD11b/CD18 antigen on the surface of peripheral blood polymorphonuclear leukocytes and monocytes, suggesting the presence of an increased inflammatory response and leukocyte activation in these individuals.

Interleukin‐6 as an early predictor for one‐year survival following an ischaemic stroke/transient ischaemic attack

Background Early biomarkers for survival in an acute ischaemic stroke/transient ischaemic attack might serve as a useful tool for the clinician. Several studies have highlighted the role of inflammatory biomarkers as an early signal for acute ischaemic stroke prognosis. Aims This study examines the potential advantage of using high-sensitivity interleukin-6 as a possible biomarker at the early stages of acute stroke for identifying patients at a high risk for 12-month mortality. Methods Inflammatory biomarkers and neurological scores were determined in 250 patients following mild to moderate acute ischaemic stroke within 24 h of hospital admission. Outcome data on mortality were collected after 12 months. The signal detection methodology was used to identify subgroups that were at a high risk for 12-month mortality. Results Twelve months following the event, 234 of the 250 stroke patients survived. Signal detection identified predictors that distinguished individuals likely to die from those with a better recovery prediction. Plasma interleukin-6 concentration emerged as the optimal predictor, with a cut point of 6·47pg/ml, χ2 (I, N = 250) = 20·5, P<0·001. Interleukin-6 above 6·47 pg/ml during the acute phase predicted subsequent non-survival (P = 0·006, odds ratio 8·0). Conclusions This study demonstrates the clinical potential of using high-sensitivity interleukin-6 as an early signal for acute ischaemic stroke survival and suggests a clear cut point for patients at a high risk who might benefit from closer clinical surveillance and/or administration of therapeutic interventions.

Extra-cranial venous flow in patients with multiple sclerosis

INTRODUCTION Recently, a chronic state of impaired venous drainage from the central nervous system, termed chronic cerebrospinal venous insufficiency (CCSVI) was claimed to be a pathologic condition exclusively seen in patients with multiple sclerosis (MS), suggesting that cerebral venous congestion plays a significant role in the pathogenesis of MS. This hypothesis has gained enormous attention among patients and physicians but has been questioned since. METHODS Twenty seven patients with MS and 32 healthy controls underwent color extra cranial Doppler exam aimed to detect four parameters of abnormal venous flow: no Doppler-detected flow in the IJV or vertebral veins (VV), reflux in the internal jugular veins (IJVs), venous flow stenosis in the IJVz (cross sectional area <0.3 cm) or reverted postural control in the IJV. RESULTS Except for one healthy patient, blood flow direction in the IJVs was normal in all subjects. When aiming to detect at least one parameter of abnormal venous flow per subject, two parameters or three parameters no significant difference was found between subjects and controls (p = 0.707, 0.62, 0.849 respectively). CONCLUSION We found no evidence to suggest that MS patients have excess of CCSVI. In addition we failed to observe a typical venous flow pattern in MS patients. Until carefully designed controlled studies to investigate CCVSI have been completed, invasive and potentially dangerous endovascular procedures as therapy for MS should be discouraged.

Derivation and validation of the Prolonged Length of Stay score in acute stroke patients

Background: Length of stay (LOS) is the main cost-determining factor of hospitalization of stroke patients. Our aim was to derive and validate a simple score for the assessment of the risk of prolonged LOS for acute stroke patients in a national setting. Methods: Ischemic stroke (IS) and intracerebral hemorrhage (ICH) patients in the National Acute Stroke Israeli Surveys (NASIS 2004 and 2007) were included. Predictors of prolonged LOS (LOS ≥7 days) in the NASIS 2004 (n = 1,700) were identified with logistic regression analysis and used for the derivation of the Prolonged Length of Stay (PLOS) score. The score was validated in the NASIS 2007 (n = 1,648). Results: Median (interquartile range) LOS was 6 (3–10) days in the derivation cohort (42.3% prolonged LOS) and 5 (3–8) in the validation cohort (35.7% prolonged LOS). The derivation cohort included 54.8% men, 90.8% IS and 9.2% ICH, with a mean (SD) age of 71.2 (12.5) years. Stroke severity was the strongest multivariable predictor of prolonged LOS: odds ratio (95% confidence interval [CI]) increased from 2.6 (2.0–3.3) for NIH Stroke Scale score (NIHSS) 6–10 to 4.9 (3.0–8.0) for NIHSS 16–20, compared with NIHSS ≤5. Stroke severity and type, decreased level of consciousness on admission, history of congestive heart failure, and prior atrial fibrillation were used for the derivation of the PLOS score (c statistics 0.692, 95% CI 0.666–0.718). The score performed similarly well in the validation cohort (c statistics 0.680, 95% CI 0.653–0.707). Conclusion: A simple prolonged length of stay score, based on available baseline information, may be useful for tailoring policy aimed at better use of resources and optimal discharge planning of acute stroke patients.

The erythrocyte adhesiveness/aggregation test in the peripheral blood of patients with ischemic brain events.

We adopted a simple slide test and image analysis to determine the state of erythrocyte adhesiveness/aggregation in the peripheral blood of 45 patients with acute ischemic stroke, 30 with TIA and 27 matched controls. A highly significant (P=0.005) difference was noted between patients and controls regarding the degree of erythrocyte adhesiveness/aggregation while there was no significant difference for both erythrocyte sedimentation rate or fibrinogen concentrations. We suggest that our slide test might be a low cost and real time method to detect the increased erythrocyte aggregability in the peripheral blood of patients with acute ischemic neurological events. These findings might be relevant in view of recent studies that suggest a favorable effect of therapeutic interventions directed at the improvements of this hemorrheological aspect in individuals with ischemic vascular conditions.

Clinical consequences of aspirin and clopidogrel resistance: an overview.

The aim of this review is to introduce the concept of personalized medicine in secondary stroke prevention with antiplatelet medication. In the last years, many studies have been conducted regarding aspirin resistance and genotyping of clopidogrel metabolism. A review of the currently published data on this issue emphasizes the importance of focusing on the individualizing approach in antiplatelet therapy to achieve maximal therapeutic beneficial effect. However, many authors suggest that, before new information from ongoing trials become available, good clinical practice should dictate the use of low dose of aspirin that was shown to be effective in the prevention of stroke and death in patients with ischemic cerebrovascular disease, because higher doses do not have significantly better efficacy than lower doses in secondary stroke prevention, but lower‐dose aspirin is associated with less side effects. On the other hand, many factors are associated with clopidogrel resistance, and recent genetic studies showed that the CYP2C19*2 genotype (loss‐of‐function allele) is related to poor metabolism of clopidogrel, but larger studies are needed to definitively confirm or rule out the clinical significance of this genetic effect. The aim of personalized approach in secondary stroke prevention is to take the most appropriate medicine in the right dose in accordance with the clinical condition of the patient and associated risk factors.