Kristina Szabo

Treatment and outcomes of acute basilar artery occlusion in the Basilar Artery International Cooperation Study (BASICS): a prospective registry study.

BACKGROUND Treatment strategies for acute basilar artery occlusion (BAO) are based on case series and data that have been extrapolated from stroke intervention trials in other cerebrovascular territories, and information on the efficacy of different treatments in unselected patients with BAO is scarce. We therefore assessed outcomes and differences in treatment response after BAO. METHODS The Basilar Artery International Cooperation Study (BASICS) is a prospective, observational registry of consecutive patients who presented with an acute symptomatic and radiologically confirmed BAO between November 1, 2002, and October 1, 2007. Stroke severity at time of treatment was dichotomised as severe (coma, locked-in state, or tetraplegia) or mild to moderate (any deficit that was less than severe). Outcome was assessed at 1 month. Poor outcome was defined as a modified Rankin scale score of 4 or 5, or death. Patients were divided into three groups according to the treatment they received: antithrombotic treatment only (AT), which comprised antiplatelet drugs or systemic anticoagulation; primary intravenous thrombolysis (IVT), including subsequent intra-arterial thrombolysis; or intra-arterial therapy (IAT), which comprised thrombolysis, mechanical thrombectomy, stenting, or a combination of these approaches. Risk ratios (RR) for treatment effects were adjusted for age, the severity of neurological deficits at the time of treatment, time to treatment, prodromal minor stroke, location of the occlusion, and diabetes. FINDINGS 619 patients were entered in the registry. 27 patients were excluded from the analyses because they did not receive AT, IVT, or IAT, and all had a poor outcome. Of the 592 patients who were analysed, 183 were treated with only AT, 121 with IVT, and 288 with IAT. Overall, 402 (68%) of the analysed patients had a poor outcome. No statistically significant superiority was found for any treatment strategy. Compared with outcome after AT, patients with a mild-to-moderate deficit (n=245) had about the same risk of poor outcome after IVT (adjusted RR 0.94, 95% CI 0.60-1.45) or after IAT (adjusted RR 1.29, 0.97-1.72) but had a worse outcome after IAT compared with IVT (adjusted RR 1.49, 1.00-2.23). Compared with AT, patients with a severe deficit (n=347) had a lower risk of poor outcome after IVT (adjusted RR 0.88, 0.76-1.01) or IAT (adjusted RR 0.94, 0.86-1.02), whereas outcomes were similar after treatment with IAT or IVT (adjusted RR 1.06, 0.91-1.22). INTERPRETATION Most patients in the BASICS registry received IAT. Our results do not support unequivocal superiority of IAT over IVT, and the efficacy of IAT versus IVT in patients with an acute BAO needs to be assessed in a randomised controlled trial. FUNDING Department of Neurology, University Medical Center Utrecht.

Acute Stroke Patterns in Patients With Internal Carotid Artery Disease A Diffusion-Weighted Magnetic Resonance Imaging Study

Background and Purpose— Diffusion-weighted (DW) MRI is a sensitive method that facilitates early stroke pattern identification. There are limited data about the influence of stenosis grade on the development of particular stroke patterns in internal carotid artery (ICA) disease. We therefore investigated the lesion patterns on DW MRI in acute stroke patients with ICA disease. Methods— DW MRI was analyzed in 102 consecutive acute stroke patients with different degrees of ipsilateral ICA disease. Patients were assigned to 1 of 5 observed lesion patterns: (1) territorial ischemia, (2) subcortical ischemia without or (3) with embolus fragmentation, (4) disseminated lesions in distal cortical regions, and (5) multiple lesions in hemodynamic risk zones. In addition, perfusion-weighted (PW) MRI and MR angiography information was included in the assessment. Results— All patterns were observed in the different stages of ICA disease. Half of the patients with high-grade or subtotal stenosis had lesions in hemodynamic risk zones. Territorial stroke occurred in 47.6% of patients with ICA occlusion. Statistical analysis showed a significant relationship between the degree of stenosis and the observed stroke pattern (P =0.001). In 77.8% of patients exhibiting high-grade ICA stenosis, subtotal stenosis, or occlusion, the perfusion lesion was larger than the diffusion lesion (PW/DW mismatch). Conclusions— Although in the individual patient any of the infarct patterns may occur, in statistical terms the incidence of a particular stroke pattern is clearly dependent on the degree of stenosis.

Gender Differences in Acute Ischemic Stroke: Etiology, Stroke Patterns and Response to Thrombolysis

Background and Purpose— Differences between women and men in relation to stroke are increasingly being recognized. Methods— From July 2004 until June 2007, 237 acute ischemic stroke (AIS) patients were treated with recombinant tissue plasminogen activator (rtPA) within 3 hours after onset of symptoms in our stroke unit. Baseline characteristics, etiology, CT/MRI stroke patterns, clinical outcome, and complications of women were compared to those of men. Results— Of 237 AIS patients (mean age 70.7 years), 111 (46.8%) were women and 126 (53.2%) were men. Women were older (P=0.001), but history of hyperlipidemia (P=0.03), smoking (P=0.03), and coronary heart disease (P<0.001) was less frequent than in men. Internal carotid artery disease occurred more often in men (P=0.02), whereas atrial fibrillation was observed more often in women (P=0.002). In men borderzone/small embolic and lacunar stroke was found more frequently (39.7 versus 27.2%), whereas women showed a higher percentage of large territorial stroke (72.8 versus 60.3%, P=0.09). Baseline National Institute of Health Stroke Scale scores (12.5 versus 11.3), NIHSS score at discharge (11.0 versus 9.5), 3-month-outcome modified Rankin Scale score, thrombolysis-related (17.1% versus 13.5%) or independent complications (32.4% versus 30.2%), and mortality after 3 months (13.5% versus 9.5%) were similar. Conclusion— Differences of stroke lesion patterns in genders are paralleled by differences in etiology and risk factor profiles (women, cardioembolism; men, large and small vessel disease). Baseline characteristics, rates of rtPA-related and independent complications, as well as clinical outcomes were not different between women and men with AIS.

Characterization of Carotid Artery Plaques Using Real-time Compound B-mode Ultrasound

Background and Purpose— Real-time compound ultrasound imaging is a new technique for improving the image quality of B-mode scanning. We investigated the value of this method for the characterization of atherosclerotic plaques in the internal carotid artery. Methods— Thirty-two patients (22 men, 10 women; mean age, 75 years) with plaques of the internal carotid artery as identified by high-resolution B-mode scanning were investigated with real-time compound ultrasound imaging with the use of a 5- to 12-MHz dynamic range linear transducer on a duplex scanner. Two independent observers rated plaque morphology according to a standardized protocol. Results— The majority of plaques was classified as predominantly echogenic and as plaques of irregular surface, whereas ulcerated plaques were rarely observed. The interobserver agreement for plaque surface characterization was good for both compound ultrasound (&kgr;=0.72) and conventional B-mode (&kgr;=0.65). For the determination of plaque echogenicity, the reproducibility of compound ultrasound (&kgr;w=0.83) was even higher than that of conventional B-mode ultrasound (&kgr;w=0.74). According to a semiquantitative analysis, real-time compound ultrasound was rated superior in the categories plaque texture resolution, plaque surface definition, and vessel wall demarcation. Furthermore, there was a significant reduction of acoustic shadowing and reverberations. Conclusions— Real-time compound ultrasound is a suitable technique for the characterization of atherosclerotic plaques, showing good general agreement with high-resolution B-mode imaging. This advanced technique allows reduction of ultrasound artifacts and improves the assessment of plaque texture and surface for enhanced evaluation of carotid plaque morphology.

Hippocampal Lesion Patterns in Acute Posterior Cerebral Artery Stroke. Clinical and MRI Findings

Background and Purpose— Reports of ischemic stroke affecting the hippocampus are rare. In this study we used diffusion-weighted MRI (DWI) to characterize patients with posterior circulation stroke involving the hippocampus. Methods— Fifty-seven consecutive acute stroke patients with hippocampal infarct (HI) on DWI were analyzed with regard to clinical features and ischemic lesion patterns. The last 20 of these underwent additional neuropsychological testing of short-term, working, and episodic long-term memory. Results— We found unilateral HI in 54 and bilateral HI in 3 patients. Visual analysis identified 4 patterns of DWI lesion affecting (1) the complete hippocampus (15/60), (2) the lateral (19/60) or (3) dorsal (22/60) parts of the hippocampal body and tail, and (4) circumscribed lesions in the lateral hippocampus (4/60), corresponding well to hippocampal vascular anatomy. In all cases DWI showed further ischemic lesions in the posterior circulation. Symptoms from lesions outside the hippocampus were the common leading clinical signs. Whereas mnestic deficits were prominent in only 11/57 patients, neuropsychological examination in 20 patients showed deficits of verbal episodic long-term memory in left and of nonverbal episodic long-term memory in right HI. Conclusion— Several phenotypic lesion patterns can be distinguished in HI that usually occur as part of multifocal PCA ischemia. A careful neuropsychological examination is necessary to detect resulting memory deficits.

Diffusion-weighted imaging for the differential diagnosis of disorders affecting the hippocampus

Background: The human hippocampus can be affected in a large variety of very different neurological diseases, of which acute ischemic stroke, transient global amnesia, epilepsy, and limbic encephalitis are the most common. Less frequent etiologies include various infections and encephalopathy of different origins. Clinical presentation notably comprises confusional state, altered vigilance, memory deficits of various extent and seizures. While in hypoxic or hypoglycemic encephalopathy, clinical presentation and surrounding circumstances provide some clues to reach the correct diagnosis, in the above-listed more common disorders, signs and symptoms might overlap, making the differential diagnosis difficult. This review presents recent studies using the diffusion-weighted imaging (DWI) technique in diseases involving the hippocampus. Methods: References for the review were identified through searches of PubMed from 1965 to January 2011. Only papers published in English were reviewed. Full articles were obtained and references were checked for additional material where appropriate. Results: All pathologies affecting the hippocampus are associated with distinct lesion patterns on magnetic resonance imaging, and especially DWI has the ability to demonstrate even minute and transient hippocampal lesions. In acute ischemic stroke in the posterior cerebral artery territory, involvement of the hippocampal formation occurs in four distinct patterns on DWI that can be easily differentiated and correspond to the known vascular anatomy of the hippocampus. In the subacute phase after transient global amnesia (TGA), dot-like hyperintense lesions are regularly found in the lateral aspect of the hippocampus on DWI. The DWI lesions described after prolonged seizures or status epilepticus include unilateral or bilateral hippocampal, thalamic, and cortical lesions of various extent, not restricted to vascular territories. In limbic encephalitis, DWI lesions are only infrequently found and usually affect the hippocampus, uncus and amygdala. Furthermore, in some rare cases DWI lesions of different etiology may coexist. Conclusion: In patients with diseases affecting the hippocampus, DWI appears to be useful in differentiating between underlying pathologies and may facilitate a definite diagnosis conducive to an optimal treatment. With a careful clinical examination, experience with the interpretation of DWI findings and knowledge of associated phenomena, it is indeed possible to differentiate between ischemic, ictal, metabolic, and TGA-associated findings.

Features of acute DWI abnormalities related to status epilepticus.

We analyzed the phenomenon of transient regional diffusion-weighted MRI (DWI) hyperintensity in a series of status epilepticus (SE) patients with respect to seizure type, epileptogenic lesions and EEG findings. A prospective series of 54 patients (30 men, 24 women, mean age 61.5 years) admitted with SE was analyzed with regard to clinical semiology, EEG and MRI findings including DWI and EEG recordings in the acute peri-ictal phase. DWI abnormalities occurred most frequently in patients with complex-partial SE (27/50%) and generalized SE (18/33.3%). Forty patients (74.1%) had symptomatic, 13/24.1% cryptogenic and 1/1.9% idiopathic epilepsies. On DWI, the hippocampus was affected in 37/68.5% cases, often in combination with other brain areas (15/40.5%), in particular the pulvinar was affected in 14/25.9% patients. Bilateral DWI changes were found in 8/14.8% patients. No correlation with a specific seizure type was observed. In 21/38.9%, DWI changes were ipsilateral to the epileptogenic brain lesion (p<0.001) and in 5/9.3% contralateral, whereas in the majority of patients, either bilateral changes or no specific epileptogenic lesion were found. EEG abnormalities correlated with lateralization of DWI abnormalities in 44/81.5% (p<0.001). The most common localization of DWI abnormalities associated with ictal activity was the hippocampus and the pulvinar. Combined DWI-MRI and EEG analysis provides clues to seizure localization and propagation, as well as to identify brain structures affected by continuous or frequent ictal activity. This large series of patients with different features (SE type and cause, various epileptogenic lesions) demonstrates the heterogeneity of the phenomenon of peri-ictal DWI changes.

Clinical and MRI characteristics of acute migrainous infarction

Objective: Migrainous infarction is considered a rare complication of migraine. Although several studies reported silent brain lesions on neuroimaging in patients with migraine with aura, knowledge about lesion patterns in acute migrainous infarction is scarce. We investigated clinical and MRI characteristics in a series of patients with migraine-associated acute cerebral ischemia. Methods: Seventeen patients among 8,137 stroke patients over an 11-year period were included. All had undergone a dedicated stroke workup including diffusion-weighted imaging (DWI) and a detailed assessment of clinical features and of vascular risk factors. Results: The majority of patients presented with prolonged aura symptoms (visual aura 82.3%, sensory dysfunction 41.2%, and aphasia 5.9%; median NIH Stroke Scale score 2). Presentation at hospital was significantly delayed after symptom onset (mean 33 hours). A total of 70.6% had acute ischemic lesions in the posterior circulation; the middle cerebral artery territory was affected in 29.4%. Small lesions were present in 64.7%; multiple lesions were found in 41.2%. No overlapping ischemic lesions of different vascular territories were found. The prevalence of a patent foramen ovale was high (64.7%). Conclusions: This study supports previous observations that migrainous infarction mostly occurs in the posterior circulation, and in younger women with a history of migraine with aura. Acute ischemic lesions were often multiple and located in distinct arterial territories. As there were no overlapping ischemic lesions, hemodynamic compromise during the development of migraine is unlikely the cause of infarction. Differentiation between migrainous infarction and prolonged migraine aura is difficult and associated with delayed admission of patients.

Assessment of Intracranial Collateral Flow by Using Dynamic Arterial Spin Labeling MRA and Transcranial Color-Coded Duplex Ultrasound

Background and Purpose— To evaluate the potential of a new dynamic MRA sequence (DynAngio) based on arterial spin labeling for the assessment of intracranial collateral flow. Methods— Twelve patients with unilateral internal carotid artery obstruction were investigated. Different patterns of collateral flow were compared between DynAngio, transcranial color-coded duplex ultrasound, and time-of-flight MRA. Results— There was a good agreement between the methods, with sensitivities between 80% and 90%. Small collateral vessels were detected more frequently with DynAngio compared to time-of-flight MRA. Conclusion— DynAngio provides anatomic and similar to transcranial color-coded duplex ultrasound functional information on collateral flow for the assessment of intracranial hemodynamics.

Predictors and early outcome of hemorrhagic transformation after acute ischemic stroke.

Background: Hemorrhagic transformation (HT) after acute ischemic stroke is frequently detected using magnetic resonance imaging (MRI), in particular in patients treated with tissue plasminogen activator (tPA). Knowledge about causes and early clinical consequences of HT mostly arises from computed tomography-based studies. We analyzed potential predictors and early outcome of HT after stroke detected by MRI with T2*-weighted gradient echo sequences (T2*-MRI). Methods: 122 consecutive stroke patients (mean age 65.5 years, 41% women) who underwent T2*-MRI within 6–60 h after stroke onset were included. 25.4% of patients were treated with tPA; the overall detection rate of HT on T2*-MRI was 20.5%. Potential predictors of HT, such as age, sex, blood pressure, stroke etiology, prior antithrombotic medication, neurological deficit on admission, tPA treatment, and specific MRI findings, were analyzed. In addition, we evaluated the effect of HT on early outcome: a decrease of >4 points on the National Institute of Health Stroke Scale (NIHSS) on day 5 was considered early improvement, and an increase of >4 points was considered early deterioration. Results: The main predictor for occurrence of HT was tPA treatment (48.4 vs. 11.1%; odds ratio 7.50; 95% confidence interval 2.9–19.7; p < 0.001). Furthermore, the development of HT was associated with a severer neurological deficit on admission (mean NIHSS score 9.9 vs. 5.9; p = 0.003), and territorial infarction (88 vs. 58.8%; p = 0.007). 19 patients (15.6%) showed early improvement which was associated with the occurrence of HT (p = 0.011) and tPA treatment (p < 0.001). Conclusions: HT is a frequent finding on T2*-MRI in patients with acute ischemic stroke associated with tPA treatment, territorial infarction and severer neurological deficits on admission. However, HT does not cause clinical deterioration; it is rather related to a favorable early outcome likely reflecting early recanalization and better reperfusion in these patients.