Darius G. Nabavi

Effect of a Novel Free Radical Scavenger, Edaravone (MCI-186), on Acute Brain Infarction

Edaravone, a novel free radical scavenger, demonstrates neuroprotective effects by inhibiting vascular endothelial cell injury and ameliorating neuronal damage in ischemic brain models. The present study was undertaken to verify its therapeutic efficacy following acute ischemic stroke. We performed a multicenter, randomized, placebo-controlled, double-blind study on acute ischemic stroke patients commencing within 72 h of onset. Edaravone was infused at a dose of 30 mg, twice a day, for 14 days. At discharge within 3 months or at 3 months after onset, the functional outcome was evaluated using the modified Rankin Scale. Two hundred and fifty-two patients were initially enrolled. Of these, 125 were allocated to the edaravone group and 125 to the placebo group for analysis. Two patients were excluded because of subarachnoid hemorrhage and disseminated intravascular coagulation. A significant improvement in functional outcome was observed in the edaravone group as evaluated by the modified Rankin Scale (p = 0.0382). Edaravone represents a neuroprotective agent which is potentially useful for treating acute ischemic stroke, since it can exert significant effects on functional outcome as compared with placebo.

Factors influencing in-hospital mortality and morbidity in patients treated on a stroke unit

Objective: To determine the extent that demographics, clinical characteristics, comorbidities, and complications contribute to the risk of in-hospital mortality and morbidity in acute stroke. Methods: Data of consecutive patients admitted to 14 stroke units cooperating within the Berlin Stroke Register were analyzed. The association of demographics, clinical characteristics, comorbidities, and complications with the risk of in-hospital death and poor outcome at discharge was assessed, and independent attributable risks were calculated, applying average sequential attributable fractions. Results: In a 3-year period, 16,518 consecutive patients with ischemic or hemorrhagic stroke were documented. In-hospital mortality was 5.4%, and 45.7% had a poor outcome (modifed Rankin Scale score ≥3). In patients with length of stay (LOS) ≤7 days, 37.5% of in-hospital deaths were attributed to stroke severity, 23.1% to sociodemographics (age and prestroke disability), and 28.9% to increased intracranial pressure (iICP) and other complications. In those with LOS >7 days, age and stroke severity accounted for 44.1%, whereas pneumonia (12.2%), other complications (12.6%), and iICP (8.3%) contributed to one-third of in-hospital deaths. For poor outcome, attributable risks were similar for prestroke disability, stroke severity, pneumonia, and other complications regardless of the patients LOS. Conclusions: Approximately two-thirds of early death and poor outcome in acute stroke is attributed to nonmodifiable predictors, whereas main modifiable factors are early complications such as iICP, pneumonia, or other complications, on which stroke unit treatment should focus to further improve the prognosis of acute stroke.

Pneumonia in acute stroke patients fed by nasogastric tube

Background: Aspiration pneumonia is the most important acute complication of stroke related dysphagia. Tube feeding is usually recommended as an effective and safe way to supply nutrition in dysphagic stroke patients. Objective: To estimate the frequency of pneumonia in acute stroke patients fed by nasogastric tube, to determine risk factors for this complication, and to examine whether the occurrence of pneumonia is related to outcome. Methods: Over an 18 month period a prospective study was done on 100 consecutive patients with acute stroke who were given tube feeding because of dysphagia. Intermediate outcomes were pneumonia and artificial ventilation. Functional outcome was assessed at three months. Logistic regression and multivariate regression analyses were used, respectvely, to identify variables significantly associated with the occurrence of pneumonia and those related to a poor outcome. Results: Pneumonia was diagnosed in 44% of the tube fed patients. Most patients acquired pneumonia on the second or third day after stroke onset. Patients with pneumonia more often required endotracheal intubation and mechanical ventilation than those without pneumonia. Independent predictors for the occurrence of pneumonia were a decreased level of consciousness and severe facial palsy. The NIH stroke scale score on admission was the only independent predictor of a poor outcome. Conclusions: Nasogastric tubes offer only limited protection against aspiration pneumonia in patients with dysphagia from acute stroke. Pneumonia occurs mainly in the first days of the illness and patients with decreased consciousness and a severe facial palsy are especially endangered.

The association between migraine and juvenile stroke : a case-control study

Background.—Several studies suggest an association between migraine and juvenile stroke. Because of some shortcomings, we designed another case‐control study of a homogenous group of patients with juvenile cerebral ischemia. This study is part of a larger German epidemiological research project on the association of migraine with cerebrovascular disease.

Perfusion Mapping Using Computed Tomography Allows Accurate Prediction of Cerebral Infarction in Experimental Brain Ischemia

Background and Purpose— We have developed a dynamic CT method to measure absolute cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). In this study we evaluated the ability of CT-derived functional maps to detect infarction in a rabbit model of focal cerebral ischemia. Methods— Sequential dynamic CT studies were performed at 2 different slices in 5 control rabbits and another 8 after induction of focal cerebral ischemia. The size of critically ischemic tissue was correlated to size of infarction measured by postmortem 2,3,5-triphenyltetrazolium chloride staining. In the control rabbits, short-term variability of the parameters was assessed by ANOVA analysis. Results— In 7 of 8 animals of the ischemia group, cerebral infarction was visible on 2,3,5-triphenyltetrazolium chloride staining, constituting 16.7±10.6% of the ipsilateral hemisphere. Good agreement of CBF functional maps with tissue specimens was found with respect to size and location of infarction. Best prediction of infarction was found for thresholds of CBF <10 mL/100 g per minute (mean size, 17.5±13.4%;r =0.95) and MTT >6 seconds (mean size, 15.6±13.5%;r =0.85), with regression slopes close to unity. CBV maps were less predictive of occurrence of infarction, especially in cases of small infarction. The short-term variability of CBF, CBV, and MTT in the control group was 10.9%, 15.2%, and 19.9%, respectively. Conclusions— Functional CT measurements of absolute CBF and MTT early after onset of ischemia allow prediction of the size and location of cerebral infarction with good accuracy.

Quantitative assessment of cerebral hemodynamics using CT : Stability, accuracy, and precision studies in dogs

PURPOSE The limited clinical availability of currently used methods to measure regional cerebral blood volume (CBV) and cerebral blood flow (CBF) represents an important restriction. We undertook this study to evaluate a new dynamic CT method to measure CBV and CBF in normal and ischemic tissue. METHOD A total of 21 dynamic CT studies were performed in seven male beagles. The contrast enhancement curves of the carotid arteries and of various brain regions were deconvolved to obtain CBV and CBF. The stability of the deconvolution method employed was assessed by comparing three data sets obtained by analyses of one, two, and four regions of interest (ROIs), all covering the entire brain area. The accuracy of CT-derived CBF was analyzed for normal (n = 5 studies) and ischemic (n = 7 studies) brain tissue using fluorescent microspheres. Repetitive CT studies were performed to evaluate the precision of the CT measurements. RESULTS The stability of the deconvolution method was high with variabilities of 2.3% (CBV), 5.9% (CBF), and 8.9% (mean transit time), respectively. The correlation between the CT and the microsphere measurements was good for both normal and ischemia studies (r > 0.78, slope > 0.9). The variability of the CT CBF (30.6%) was higher than that of the CT CBV (12.3%) measurements. CONCLUSION Our novel dynamic CT method is stable with respect to the sizes of ROIs used, allowing for accurate measurements of CBV and CBF in both normal and ischemic tissue. Further studies are necessary to evaluate the variability of this method under controlled physiologic conditions.

Monitoring cerebral perfusion after subarachnoid hemorrhage using CT.

Abstract The aim of this prospective study was to assess the feasibility and diagnostic relevance of repetitive dynamic (contrast-enhanced) CT measurements of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) in the first 3 weeks after aneurysmal subarachnoid hemorrhage (SAH). In 15 patients with SAH, 59 dynamic CT studies including 944 regions of interest (ROI) were analyzed. The results were correlated with the clinical course and time after the event and the occurrence of vasospasm. Values for the entire series were 33.8 ± 19.3 ml/100 g/min (CBF), 3.3 ± 1.3 ml/100 g (CBV), and 7.3 ± 3.9 s (MTT). Significant differences in CBF and CBV were found between ROI in grey and white matter, with time after the event, between patients with significant and absent or minor vasospasm, and between patients with and without a presumed vasospasm-related infarct.

Cerebral and Systemic Embolization During Left Ventricular Support With the Novacor N100 Device

BACKGROUND Patients undergoing implantation of left ventricular assist systems (LVAS) are prone to thromboembolic complications. We analyzed the incidence, clinical findings, and outcome of neurologic and systemic thromboembolic events (TE) in patients with the Novacor N100 LVAS. In a subset of patients, transcranial Doppler sonography was used to detect microembolic signals. METHODS Thirty-six patients underwent implantation of a Novacor N100 LVAS for various reasons. The surgical procedure was elective in 18 patients and scheduled on an urgent or emergency basis in another 18 patients. The assist period lasted from 17 to 336 days (109 +/- 88 days); 22 patients were forwarded to heart transplantation after being supported for 140 +/- 87 days. RESULTS Clinical cerebral embolism was evident in 17 patients (47%). Thromboembolic events were singular in 8 and multiple in 9 patients; in the latter up to 10 TE occurred (mean +/- SD, 1.4 +/- 2 TE). Leading neurologic symptoms were unilateral hemiplegia in 11, as well as ocular symptoms and aphasia in 12 patients each. Noncerebral TE were detected in 4 patients, 2 of whom underwent an emergency operation for intestinal and iliac artery occlusion. The incidence of TE did not correlate strongly with the interval of LVAS support. Cerebral computed tomography confirmed lesions in 58% of patients. Transcranial Doppler sonography detected microembolic signals on 67% of all recordings, with the microembolic signals being more frequent on days with clinically manifest TE. The outcomes were good, as only 2 patients suffer from neurologic sequelae. CONCLUSIONS Thromboembolism is still a major threat for patients with LVAS implantation. Neurologic sequelae are frequent but have a favorable prognosis, and systemic complications occur considerably less often. Patient selection, adequate anticoagulation, and transcranial Doppler sonography may help to reduce the incidence of TE.

Improved Detection of Silent Atrial Fibrillation Using 72-Hour Holter ECG in Patients With Ischemic Stroke A Prospective Multicenter Cohort Study

Background and Purpose— Adequate diagnosis of atrial fibrillation (AF), including paroxysmal AF, is an important part of stroke workup. Prolonged ECG monitoring may improve the detection of paroxysmal, previously undiagnosed AF (unknown AF). Therefore, we evaluated systematic 72-hour Holter ECG monitoring to detect unknown AF for the workup of patients with stroke. Methods— Unselected survivors of a stroke or transient ischemic attack (TIA) without known AF were enrolled in a prospective, multicenter cohort study of 72-hour Holter ECG monitoring in 9 German secondary and tertiary stroke centers between May 2010 and January 2011. In addition to standardized workup of stroke pathogenesis according to the German Stroke Unit protocol, all patients underwent 72-hour Holter ECG monitoring directly after admission. All ECGs were centrally analyzed by 2 independent observers. We determined the proportion of unknown AF and compared the detection rates of 72- and 24-hour monitoring. Results— A total of 1135 patients were enrolled (mean age, 67 years [SD, 13.1 years], 45% women, 29% TIA). Unknown AF was detected in 49 out of 1135 patients (4.3%, [95% confidence interval, 3.4–5.2%]) by 72-hour ECG monitoring. Unknown AF was diagnosed in 29 patients (2.6%) within the first 24 hours of ECG monitoring, and in 20 more patients only by 72 hours of ECG monitoring. The number needed to screen by 72-hour ECG was 55 patients (95% confidence interval [35–123]) for each additional AF diagnosis. Patients with unknown AF were significantly older and had more often a history of previous stroke. Patients with unknown AF were equally distributed within categories of pathogenesis according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Conclusions— In unselected survivors of stroke or TIA, 72-hour ECG monitoring is feasible and improves the detection rate of silent paroxysmal AF.

Mild mechanical traumas are possible risk factors for cervical artery dissection

Background and Purpose: Cervical artery dissection (CAD) is a common cause of ischemic stroke in younger aged subjects. Retrospective studies suggest cervical manipulative therapy (CMT) and preceding infections as extrinsic risk factors for CAD. In a case-control study, we assessed a questionnaire with 7 mild mechanical traumas as potential trigger factors for CAD, including CMT and recent infections. Patients and Methods: Forty-seven consecutive patients with CAD were compared with 47 consecutive patients of similar age with ischemic stroke due to etiologies other than CAD. Patients underwent a standardized face-to-face interview. We assessed head or neck pain and recent infection <7 days before symptom onset, as well as the following mechanical trigger factors <24 h and <7 days prior to symptom onset: (1) heavy lifting, (2) sexual intercourse, (3) mild direct or (4) indirect neck trauma, (5) jerky head movements, (6) sports activity, and (7) CMT. Results:We found no association between any single one of the above risk factors and CAD. CMT (CAD, n = 10; non-CAD, n = 5) and recent infections (CAD, n = 18; non-CAD, n = 10) were more frequent in the CAD group but failed to reach significance. However, the cumulative analysis of all mechanical trigger factors revealed a significant association of mechanical risk factors as a whole in CAD <24 h prior to symptom onset (p = 0.01). Conclusion: Mild mechanical stress, including CMT, plays a role as possible trigger factor in the pathogenesis of CAD. CMT and recent infections alone failed to reach significance during the present investigation, presumably due to the relatively small sample size of the study cohort.