Perfusion-CT guided intravenous thrombolysis in patients with unknown-onset stroke: a randomized, double-blind, placebo-controlled, pilot feasibility trial.

INTRODUCTION: Patients with unknown stroke onset are generally excluded from acute recanalisation treatments. We designed a pilot study to assess feasibility of a trial of perfusion computed tomography (PCT)-guided thrombolysis in patients with ischemic tissue at risk of infarction and unknown stroke onset. METHODS: Patients with a supratentorial stroke of unknown onset in the middle cerebral artery territory and significant volume of at-risk tissue on PCT were randomized to intravenous thrombolysis with alteplase (0.9 mg/kg) or placebo. Feasibility endpoints were randomization and blinded treatment of patients within 2 h after hospital arrival, and the correct application (estimation) of the perfusion imaging criteria. RESULTS: At baseline, there was a trend towards older age [69.5 (57-78) vs. 49 (44-78) years] in the thrombolysis group (n = 6) compared to placebo (n = 6). Regarding feasibility, hospital arrival to treatment delay was above the allowed 2 h in three patients (25%). There were two protocol violations (17%) regarding PCT, both underestimating the predicted infarct in patients randomized in the placebo group. No symptomatic hemorrhage or death occurred during the first 7 days. Three of the four (75%) and one of the five (20%) patients were recanalized in the thrombolysis and placebo group respectively. The volume of non-infarcted at-risk tissue was 84 (44-206) cm(3) in the treatment arm and 29 (8-105) cm(3) in the placebo arm. CONCLUSIONS: This pilot study shows that a randomized PCT-guided thrombolysis trial in patients with stroke of unknown onset may be feasible if issues such as treatment delays and reliable identification of tissue at risk of infarction tissue are resolved. Safety and efficiency of such an approach need to be established.

The Acute STroke Registry and Analysis of Lausanne (ASTRAL): design and baseline analysis of an ischemic stroke registry including acute multimodal imaging.

BACKGROUND AND PURPOSE: Stroke registries are valuable tools for obtaining information about stroke epidemiology and management. The Acute STroke Registry and Analysis of Lausanne (ASTRAL) prospectively collects epidemiological, clinical, laboratory and multimodal brain imaging data of acute ischemic stroke patients in the Centre Hospitalier Universitaire Vaudois (CHUV). Here, we provide design and methods used to create ASTRAL and present baseline data of our patients (2003 to 2008). METHODS: All consecutive patients admitted to CHUV between January 1, 2003 and December 31, 2008 with acute ischemic stroke within 24 hours of symptom onset were included in ASTRAL. Patients arriving beyond 24 hours, with transient ischemic attack, intracerebral hemorrhage, subarachnoidal hemorrhage, or cerebral sinus venous thrombosis, were excluded. Recurrent ischemic strokes were registered as new events. RESULTS: Between 2003 and 2008, 1633 patients and 1742 events were registered in ASTRAL. There was a preponderance of males, even in the elderly. Cardioembolic stroke was the most frequent type of stroke. Most strokes were of minor severity (National Institute of Health Stroke Scale [NIHSS] score ≤ 4 in 40.8% of patients). Cardioembolic stroke and dissections presented with the most severe clinical picture. There was a significant number of patients with unknown onset stroke, including wake-up stroke (n=568, 33.1%). Median time from last-well time to hospital arrival was 142 minutes for known onset and 759 minutes for unknown-onset stroke. The rate of intravenous or intraarterial thrombolysis between 2003 and 2008 increased from 10.8% to 20.8% in patients admitted within 24 hours of last-well time. Acute brain imaging was performed in 1695 patients (97.3%) within 24 hours. In 1358 patients (78%) who underwent acute computed tomography angiography, 717 patients (52.8%) had significant abnormalities. Of the 1068 supratentorial stroke patients who underwent acute perfusion computed tomography (61.3%), focal hypoperfusion was demonstrated in 786 patients (73.6%). CONCLUSIONS: This hospital-based prospective registry of consecutive acute ischemic strokes incorporates demographic, clinical, metabolic, acute perfusion, and arterial imaging. It is characterized by a high proportion of minor and unknown-onset strokes, short onset-to-admission time for known-onset patients, rapidly increasing thrombolysis rates, and significant vascular and perfusion imaging abnormalities in the majority of patients.

Intravenous thrombolysis in stroke attributable to cervical artery dissection.

BACKGROUND AND PURPOSE: Intravenous thrombolysis (IVT) for stroke seems to be beneficial independent of the underlying etiology. Whether this is also true for cervical artery dissection (CAD) is addressed in this study. METHODS: We used the Swiss IVT databank to compare outcome and complications of IVT-treated patients with CAD with IVT-treated patients with other etiologies (non-CAD patients). Main outcome and complication measures were favorable 3-month outcome, intracranial cerebral hemorrhage, and recurrent ischemic stroke. Modified Rankin Scale score

Severe post-EBV encephalopathy associated with myelin oligodendrocyte glycoprotein-specific immune response.

The mechanisms leading to CNS disorders after EBV infections are unclear. We report the case of a patient who developed a severe, but reversible, encephalopathy following an infectious mononucleosis. We detected no EBV DNA in the blood or in the cerebrospinal fluid (CSF) and no EBV-specific antibodies in the CSF. However, we found a potent MOG-specific cellular and humoral immune response. Interestingly, MOG-specific cellular immune response rapidly decreased, paralleling the improvement of clinical condition. In conclusion, this detailed study shows that acute EBV infection can trigger a potent auto-inflammatory response in the CNS, without evidence of an overt infection.

Transitory sleep spindles impairment in deep cerebral venous thrombosis.

Sleep spindles may be affected by thalamic or hemispheric ischemic stroke. However, spindles reduction and their relationship with K-complexes following deep cerebral venous thrombosis have not been reported. An 18-year-old woman suffered from a deep cerebral venous thrombosis with vasogenic oedema located predominantly in the thalami. Stage 2 sleep EEG recorded in acute setting showed preservation of K-complexes but absent 12-14 Hz sleep spindles, which were replaced by spindle-like theta oscillations. One month later, the patient having completely recovered, sleep spindles were normally seen on the control EEG. This case illustrates that deep cerebral venous thrombosis, through a vasogenic oedema, may transiently affect thalamic functions such as spindles generation. Furthermore, thalamic impairment may lead to dissociation of spindle and K-complex activity.

Propofol treatment of refractory status epilepticus: a study of 31 episodes.

PURPOSE: Refractory status epilepticus (RSE) is a critical medical condition with high mortality. Although propofol (PRO) is considered an alternative treatment to barbiturates for the management of RSE, only limited data are available. The aim of this study was to assess PRO effectiveness in patients with RSE. METHODS: We retrospectively considered all consecutive patients with RSE admitted to the medical intensive care unit (ICU) between 1997 and 2002 treated with PRO for induction of EEG-monitored burst suppression. Subjects with anoxic encephalopathy showing pathological N20 on somatosensory evoked potentials were excluded. RESULTS: We studied 31 RSE episodes in 27 adults (16 men, 11 women; median age, 41.5 years). All patients received PRO, and six also subsequently thiopental (THP). Clonazepam (CZP) was administered with PRO, and other antiepileptic drugs (AEDs) concomitant with PRO and THP. RSE was successfully treated with PRO in 21 (67%) episodes and with THP after PRO in three (10%). Median PRO injection rate was 4.8 mg/kg/h (range, 2.1-13), median duration of PRO treatment was 3 days (range, 1-9), and median duration of ICU stay was 7 days (range, 2-42). In 24 episodes in which the patient survived, shivering after general anesthesia was seen in 10 episodes, transient dystonia and hyperlipemia in one each, and mild neuropsychological impairment in five. The seven deaths were not directly related to PRO use. CONCLUSIONS: PRO administered with CZP was effective in controlling most of RSE episodes, without major adverse effects. In this setting, PRO may therefore represent a valuable alternative to barbiturates. A randomized trial with these drug classes could definitively assess their respective role in RSE treatment.

Aphasia in hyperacute stroke: language follows brain penumbra dynamics.

During the first few hours after onset, stroke symptoms may evolve rapidly. We studied the correlation between brain perfusion and aphasia changes during the hyperacute phase of stroke using a new technique of perfusion computed tomography (P-CT). Using an aphasia score developed for each language modality, language was evaluated within 6 hours after onset, then sequentially during the first week. Maps of the penumbra and infarct obtained from P-CT images and definite infarct size evaluated using T2 and diffusion-weighted MRI (DWI) on day 3 were rated by a neuroradiologist, blinded to the clinical deficit. Within 6 hours, deficits in all language modalities were present in 13 out of 24 consecutive patients, corresponding to large anterior-posterior perfusion deficits of the left middle cerebral artery (MCA) territory. The aphasia score correlated with a corresponding perfusion deficit in specific areas of the MCA territory, and showed significantly less improvement when the penumbra evolved toward infarction than when at least part of the penumbra was rescued. Our findings suggest a particularly good correlation between the evolution of aphasic symptoms and penumbra dynamics. Further studies on the relevance of penumbra dynamics in function-specific brain areas to decision taking in hyperacute stroke management are required.

Central Horner's syndrome with contralateral ataxic hemiparesis: a diencephalic alternate syndrome.

OBJECTIVE: To assess whether thalamic strokes presenting with a central Horner's syndrome (HS) show specific clinicoanatomic patterns. METHODS: From the Lausanne Stroke Registry (period 1993 to spring 2002), the authors selected all patients with thalamic stroke presenting with ipsilateral HS. Patients with complete infarction of the posterior cerebral artery territory, with involvement of middle cerebral artery territory or bilateral lesions, were excluded. Lesions on brain MRI were correlated with standard neuroanatomic templates. RESULTS: Nine patients with thalamic infarction presenting with central HS were found; all showed contralateral ataxic hemiparesis (AH). Lesions involved the anterior or paramedian thalamus and extended to the hypothalamic or rostral paramedian mesencephalic area in all but one subject. Associated clinical signs included dysphasia (two patients), somnolence (six), vertical gaze paresis (two), asterixis (two), and hemihypesthesia (three). CONCLUSION: The alternate clinical pattern of central HS with contralateral AH is a stroke syndrome of the diencephalic-mesencephalic junction, resulting from the involvement of the common arterial supply to the paramedian/anterior thalamus, the posterior hypothalamus and the rostral paramedian midbrain.

[Thrombolysis of acute ischemic cerebral vascular accident: roles of the physician and the peripheral hospital]. / Thrombolyse de l'accident vasculaire cérébral ischémique aigu: rôles du praticien et de l'hôpital périphérique.

Thrombolysis administered intravenously within 3 hours (or within 6 hours intra-arterially) after symptoms onset improves the functional outcome of acute ischemic stroke patients. In Switzerland this treatment is only performed by specialized centers. At the level of a community hospital or a general practitioner, the management is based on the appropriate selection of patients in whom thrombolysis could be indicated, followed by their immediate transfer to a reference medical center. Because of the very short therapeutic window, specific criteria have to be used. We present the guidelines of Les Cadolles Hospital in Neuchâtel established in collaboration with the Department of Neurology of the University Hospital of Lausanne and a retrospective analysis of emergency admissions for suspected stroke at Les Cadolles between January 1st 2001 and December 31st 2002.

MR pattern of hyperacute cerebral hemorrhage.

Magnetic resonance (MR) pattern of cerebral hemorrhage relates mainly to the relaxation and susceptibility effects of iron-containing hemoglobin degradation products, as well as to their intra- or extracellular location. The purpose of this article is to report two acute stroke patients who underwent thrombolytic therapy and developed hyperacute cerebral hemorrhage during their admission cerebral MR survey. They constitute the earliest MR appearance of hyperacute intracerebral bleeding reported in the literature, featuring increased diffusion properties and persistent susceptibility effect on perfusion-weighted imaging (PWI)-series.

Prognostic accuracy of cerebral blood flow measurement by perfusion computed tomography, at the time of emergency room admission, in acute stroke patients.

The purpose of this study was to determine the prognostic accuracy of perfusion computed tomography (CT), performed at the time of emergency room admission, in acute stroke patients. Accuracy was determined by comparison of perfusion CT with delayed magnetic resonance (MR) and by monitoring the evolution of each patient's clinical condition. Twenty-two acute stroke patients underwent perfusion CT covering four contiguous 10mm slices on admission, as well as delayed MR, performed after a median interval of 3 days after emergency room admission. Eight were treated with thrombolytic agents. Infarct size on the admission perfusion CT was compared with that on the delayed diffusion-weighted (DWI)-MR, chosen as the gold standard. Delayed magnetic resonance angiography and perfusion-weighted MR were used to detect recanalization. A potential recuperation ratio, defined as PRR = penumbra size/(penumbra size + infarct size) on the admission perfusion CT, was compared with the evolution in each patient's clinical condition, defined by the National Institutes of Health Stroke Scale (NIHSS). In the 8 cases with arterial recanalization, the size of the cerebral infarct on the delayed DWI-MR was larger than or equal to that of the infarct on the admission perfusion CT, but smaller than or equal to that of the ischemic lesion on the admission perfusion CT; and the observed improvement in the NIHSS correlated with the PRR (correlation coefficient = 0.833). In the 14 cases with persistent arterial occlusion, infarct size on the delayed DWI-MR correlated with ischemic lesion size on the admission perfusion CT (r = 0.958). In all 22 patients, the admission NIHSS correlated with the size of the ischemic area on the admission perfusion CT (r = 0.627). Based on these findings, we conclude that perfusion CT allows the accurate prediction of the final infarct size and the evaluation of clinical prognosis for acute stroke patients at the time of emergency evaluation. It may also provide information about the extent of the penumbra. Perfusion CT could therefore be a valuable tool in the early management of acute stroke patients.