Background and purposeFactors such as infarct volume, infarct location and symptom severity can considerably influence long‐term outcome in posterior fossa strokes. The decision about therapy can sometimes be complicated by discrepancies between infarct volume and clinical severity. We aimed to evaluate imaging and clinical parameters possibly influencing long‐term outcome in patients with first‐ever posterior fossa stroke.MethodsImaging was performed on a 3‐T magnetic resonance imaging scanner. Sixty‐one of 1795 patients from the observational 1000Plus and LOBI studies (NCT00715533 and NCT02077582, clinicaltrials.org) were enrolled, meeting the inclusion criteria of first‐ever posterior fossa stroke and magnetic resonance imaging examination within 24 h after symptom onset. Infarcts were classified as belonging to a proximal, middle or distal territory location in the posterior fossa. Good outcome was defined as a modified Rankin scale score of ≤1 at 3 months.ResultsThe largest lesion volumes on diffusion‐weighted imaging on day 0 and fluid attenuation inversion recovery (FLAIR) on day 6 were found in the middle territory location with a median volume of 0.4 mL on diffusion‐weighted imaging and 1.0 mL on FLAIR on day 6 versus 0.1/0.3 mL in the proximal and 0.1/0.1 mL in the distal territory location of the posterior fossa, respectively. Parameters associated with poor outcome were older age (P = 0.005), higher National Institutes of Health Stroke Scale score on admission/discharge (P = 0.016; P = 0.001), larger lesion volumes on FLAIR on day 6 (P = 0.013) and dysphagia (P = 0.02). There was no significant association between infarct location and modified Rankin scale score on day 90.ConclusionInfarct volume and clinical severity, but not infarct location, were the main contributors to poor long‐term outcome in first‐ever posterior fossa strokes.

Background and purpose: Several studies have described an association between insular infarction and mortality. Large infarcts often include the insula and lesion size is associated with mortality. We hypothesized that there is an association between insular infarction and mortality independent of lesion volume.Methods: We included consecutive stroke patients between 1 September 2008 and 11 November 2012 from the 1000Plus database with an acute ischaemic lesion on diffusion-weighted imaging on day 1 and a completed 90-day followup. Insular infarct location was determined using the in-house software Stroke Lesion Atlas. In multiple Cox regression analysis (dependent variable: mortality), we adjusted for insular infarcts, age, lesion volume, history of atrial fibrillation, National Institutes of Health Stroke Scale and previous stroke.Results: We included 736 patients, of whom 168 had an insular infarction. Within a medium follow-up time of 107 days, cumulative survival was 90% in patients with insular infarction and 99% in patients without insular infarction (P < 0.001). Right insular infarction was independently associated with mortality (hazard ratio, 2.60; confidence interval, 1.3-5.4; P = 0.010).Conclusions: In our study, right insular involvement was a prognostic marker for mortality after ischaemic stroke. A selection bias towards patients able to give informed consent warrants further studies.

Background and purpose Central post‐stroke pain ( CPSP ) is a severe chronic neuropathic pain condition defined as a spontaneous pain or allodynia corresponding to a vascular lesion. It usually evolves weeks after stroke, and can distinctively impair the quality of life. Treatment is complex and mostly unsatisfactory. We hypothesized that the anti‐epileptic drug levetiracetam ( LEV ) improves CPSP compared with placebo. The purpose of this study was to examine the efficacy and tolerability of LEV in patients with CPSP . Methods In a double‐blind, placebo‐controlled, crossover study design patients with CPSP lasting at least 3 months and a pain score ≥ 4 on the 11‐point Likert scale were treated over two 8‐week periods with a maximum dose up to 3000 mg LEV or placebo. Primary endpoint was a median pain lowering ≥ 2 in the final treatment week compared with the last baseline week. Secondary outcome measures comprised additional pain ratings, depression, sleep quality, quality of life and patients' global impression of change. Results Of 42 patients, 33 [61.5 years (40–76); 38% women] completed the study. Side effects and withdrawals were more frequent in the LEV ( n = 5) group than in the placebo group ( n = 1). Patients treated with LEV did not show any improvement of pain or changes in secondary outcome parameters compared with placebo. Conclusions LEV is not effective in treatment for CPSP . The mode of action of LEV does not exert an analgesic effect in chronic CPSP .

BACKGROUND AND PURPOSE:Absence of FLAIR hyperintensity within an acute infarct is associated with stroke onset <4.5 h. However, some patients rapidly develop FLAIR hyperintensity within this timeframe. We hypothesized that development of early infarct FLAIR hyperintensity would predict hemorrhagic transformation (HT) in patients treated with tissue plasminogen activator (tPA) < 4.5 h after onset. METHODS:Consecutive acute stroke patients treated with intravenous tPA <4.5 h after onset who had MRI before and 1 day after thrombolysis were included. Two raters (blind to HT) independently identified FLAIR hyperintensity with reference to the diffusion-weighted image (DWI) lesion. HT was assessed using T2* MRI at 24 h. Hemorrhagic infarction (HI) was defined as petechial HT without mass effect, and parenchymal hematoma (PH) as HT with mass effect. Multivariable logistic regression analysis for HT included FLAIR status, baseline National Institutes of Health Stroke Scale and DWI lesion volume, leukoaraiosis (Wahlund score), serum glucose and reperfusion. RESULTS:Of 109 patients, 33 (30%) had acute FLAIR hyperintensity. HT occurred in 17 patients (15.6%; 15 HI, 2 PH). HT was more common in FLAIR-positive patients than FLAIR-negative patients (33.3% vs. 9.2%, P = 0.009). Median time-to-scan and median time-to-thrombolysis did not differ significantly between patients with HT and without [97 IQR(68, 155) vs. 90 IQR(73, 119), P = 0.5; 120 IQR(99, 185) vs. 125 IQR(95, 150), P = 0.6, respectively]. In multivariable analysis, only FLAIR hyperintensity was independently associated with HT after thrombolysis (OR 18; 95% CI 2-175, P = 0.013). CONCLUSIONS:Early development of FLAIR hyperintensity within the area of diffusion restriction is associated with increased risk of HT after thrombolysis in acute stroke patients.

Background: Vascular hyperintensities of brain-supplying arteries on stroke FLAIR MRI are common and represent slow flow or stasis. FLAIR vascular hyperintensities (FVH) are discussed as an independent marker for cerebral hypoperfusion, but the impact on infarct size and clinical outcome in acute stroke patients is controversial. This study evaluates the association of FVH with infarct morphology, clinical stroke severity and infarct growth in patients with symptomatic internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion. Methods: MR images of 84 patients [median age 73 years (IQR 65–80), 56.0% male, median NIHSS 7 (IQR 3–13)] with acute stroke due to symptomatic ICA or MCA occlusion or stenosis were reviewed. Vessel occlusions were identified by MRA time of flight and graded with the TIMI score. Diffusion and perfusion deficit volumes on admission and FLAIR lesion volumes on discharge were assessed. The presence and number of FVH were evaluated according to MCA-ASPECT areas, and associations with MR volumes, morphology of infarction, recanalization status, presence of white matter disease and hemorrhagical transformation as well as with stroke severity (NIHSS), stroke etiology and thrombolysis rate were analyzed. Results: FVH were detectable in 75 (89.3%) patients. The median number of FVH was 4 (IQR 2–7). Patients with FVH >4 presented with more severe strokes due to NIHSS (p = 0.021), had larger initial DWI lesions (p = 0.008), perfusion deficits (p = 0.001) and mismatch volumes/ratios (p = 0.005). The final infarct volume was larger (p = 0.005), and hemorrhagic transformation was more frequent (p = 0.029) in these patients. Conclusions: The presence of FVH indicates larger ischemic areas in brain parenchyma predominantly caused by proximal anterior circulation vessel occlusion. A high count of FVH might be a further surrogate marker for initial ischemic mismatch and stroke severity.

BACKGROUND AND PURPOSE:External counterpulsation (ECP) noninvasively improves myocardial and organ perfusion via diastolic augmentation. The effects on cerebral blood flow velocities (CBFV) and hemodynamics are controversial. In this study, the effect of active ECP treatment on CBF in healthy subjects was continuously measured.METHODS:In 9 healthy volunteers (mean age 34.1 ± 11.1 years, 4 females), 20-min active ECP treatment was performed. CBFV in the middle cerebral artery were detected via transcranial Doppler. CBFV were registered continuously before, during and after ECP. The protocol was repeated twice.RESULTS:At onset of ECP, immediate changes in CBFV were observed: peak diastolic blood flow velocities increased from baseline to treatment (63 vs. 76 cm/s; p < 0.001) and diastolic blood flow augmentation was maintained throughout ECP. Peak systolic (87 vs. 78 cm/s; p < 0.001) and end-diastolic velocities (40 vs. 28 cm/s; p < 0.001) decreased significantly, while mean CBFV maintained constant (59 vs. 58 cm/s; not significant). The pulsatility index and resistance index as indirect parameters for peripheral vascular resistance increased during ECP (pulsatility index 0.79 vs. 0.89, p < 0.001; resistance index 0.54 vs. 0.64; p < 0.001).CONCLUSIONS:ECP did not increase mean CBFV in healthy subjects even though peak diastolic CBFV were significantly augmented. Changes in CBFV and transcranial Doppler waveform characteristics suggest that the mean flow of the middle cerebral artery is maintained stable via cerebrovascular autoregulatory mechanisms.

Vorraussetzung der Perfusionsmessung ist die geeignete Wahl eines Gefäßes zur Bestimmung der arteriellen 'input' Funktion (AIF).

Purpose: Ultrasound (US) perfusion imaging of ischemic stroke has mainly been applied to large middle cerebral artery infarction. We investigated whether small stroke involving the thalamus can also be detected.Materials and Methods: Phase inversion harmonic imaging (PIHI) was applied to patients with small infarctions involving the thalamus (maximal longitudinal infarct diameter less than 3 cm). PIHI was performed from both the left and right side in axial diencephalic planes. Infarct size and location as well as perfusion properties (MTT maps) were known from MRI. US perfusion parameters were derived from the signal enhancement time course (bolus kinetics, Sono-Vue (R)) for peak-signal increase and time-to-peak.Results: Seventeen patients (52 +/- 11 years, 24% female) with 18 strokes (16 unilateral, 1 bilateral) were included. Six US examinations (18%) were inadequate for analysis due to an insufficient transtemporal bone window. US perfusion depicted 90% of infarcts with a longitudinal diameter of more than 2cm. Infarcts with a longitudinal diameter of less than 2 cm were hardly identified.Conclusion: PIHI allows identification of a small infarction involving the thalamus subject to infarct size.

Background: Stroke MRI and the mismatch of DWI lesion and perfusion imaging (PI) deficit volumes may help to replace CT guided selection for thrombolysis based on a rigid time frame and hemorrhage exclusion. Two studies, DEFUSE and EPITHET, investigated the mismatch concept with relatively low recruiting rates. Therefore, confirmation of the positive results in a larger cohort is desirable. Provided with a purely research dedicated 3T MR scanner installed on the neurologic ward we are able to screen all patients with a suspected cerebrovascular event. We hypothesize that the prognostic value of the mismatch concept strongly depends on vessel status and stroke-to-MRI time.

Hintergrund: Die Möglichkeit, mit Ultraschall (US) Veränderungen der Blut-Hirn-Schranke (BHS) zu induzieren, ist bekannt. In letzter Zeit wurden im Rahmen von Studien zur Sonothrombolyse und zu US-induzierten Veränderungen der zerebralen Hämodynamik Blutungskomplikationen und Störungen der BHS berichtet.

Studies from the ImagingNet within the Competence Not Stroke were important steps towards acceptance of stroke MRI and understanding of pothophysiology of ischemic stroke. It could be shown that MRI is at least as good as CT in the detection of early acute cerebral hemorrhage, but it may be even better in the detection of "chronic micro-bleeds". Secondly, diffusion-weighted MRI (DWI) is now proven highly sensitive in the detection of early ischemic infarction. Finally, the combination of DWI and perfusion-weighted Imaging (PWI) gives a useful operational mismatch"-definition and new insights into the pathophysiology of ischemic stroke which is relevant for therapeutic decisions outside the 3-hour-time-window for systemic thrombolysis.

ZusammenfassungIm Rahmen multizentrischer Studien im Subnetz „Bildgebende Verfahren beim akuten Schlaganfall“ (ImagingNet) im Kompetenznetz Schlaganfall wurden wichtige Fragen zur Pathophysiologie der akuten zerebralen Ischämie und zum Stellenwert der MR-Bildgebung für Therapieentscheidungen beantwortet. Erstens kann man heute davon ausgehen, dass die Kernspintomographie (MRT) der Computertomographie im Nachweis akuter zerebraler Blutungen mindestens gleichwertig, bei der Darstellung chronischer „Mikrobleeds” aber überlegen ist. Zweitens hat sich die diffusionsgewichtete MRT (DW-MRT) als hoch sensitives Instrument in der sehr frühen Darstellung akuter zerebraler Ischämien erwiesen. Drittens bildet die Kombination aus DW-MRT und perfusionsgewichteter MRT (PW-MRT) ein zuverlässiges operationales Mismatch-Konzept zum Verständnis der Pathophysiologie der zerebralen Ischämie. Die Anwendung des Schlaganfall-MRT ist relevant für Therapieentscheidungen auch außerhalb des 3-Stundenfensters.

Background and Purpose - We investigated whether transient ischemic attacks ( TIAs) before stroke can induce tolerance by raising the threshold of tissue vulnerability in the human brain.Methods - Sixty-five patients with first-ever ischemic territorial stroke received diffusion- and perfusion-weighted MRI within 12 hours of symptom onset. Epidemiological and clinical data, lesion volumes in T2, apparent diffusion coefficient ( ADC) maps and perfusion maps, and cerebral blood flow and cerebral blood volume values were compared between patients with and without a prodromal TIA.Results - Despite similar size and severity of the perfusion deficit, initial diffusion lesions tended to be smaller and final infarct volumes were significantly reduced ( final T2: 9.1 [interquartile range, 19.7] versus 36.5 [91.2] mL; P = 0.014) in patients with a history of TIA ( n = 16). This was associated with milder clinical deficits.Conclusions - The beneficial effect of TIAs on lesion size in ADC and T2 suggests the existence of endogenous neuroprotection in the human brain.

BACKGROUND AND PURPOSE Using perfusion- and diffusion-weighted MR imaging in acute ischemic stroke of the middle cerebral artery (MCA), previous studies have shown a typical pathophysiologic pattern that is characterized by a perfusion deficit larger than the diffusion lesion (mismatch), with the final lesion usually comprising the initial diffusion lesion (core) plus parts of the initial mismatch area. Little is known about underlying pathophysiology in small ischemic stroke. In this study, we used perfusion- and diffusion-weighted MR imaging to investigate the underlying pathophysiology of small subcortical ischemia. METHODS Six consecutive patients (age range, 42-76 years) with small subcortical ischemia were examined by using a 1.5-T MR system 2-5, 22-55, and 144-392 hours after the onset of symptoms. T2-weighted, diffusion-weighted imaging at b=0 s/mm2 and b=1000 s/mm2, and bolus-track perfusion-weighted imaging were performed. Lesion sizes were determined on the basis of T2-weighted findings as well as those of apparent diffusion coefficient (ADC) maps and CBF. RESULTS In every patient, the initial CBF lesion was smaller than the initial ADC lesion. Both the CBF lesion and the ADC lesion increased in size from first to second examination. In all instances, however, the CBF lesion remained smaller than the ADC lesion. The CBF lesion observed during the acute phase and the one seen on the following days were both smaller than the final T2 lesion. CONCLUSION Our data suggest that in contrast to previous findings in MCA ischemia in small subcortical infarcts tissue damage may spread beyond the area of the initial perfusion disturbance. In light of the small number of patients, further studies will have to address the relevance of this observation.