Joachim Röther

Magnetic Resonance Imaging Criteria for Thrombolysis in Acute Cerebral Infarct

Background and Purpose— Magnetic resonance imaging (MRI) selection of stroke patients eligible for thrombolytic therapy is an emerging application. Although the efficacy of therapy within 3 hours after onset of symptoms with intravenous (IV) tissue plasminogen activator (tPA) has been proven for patients selected with computed tomography (CT), no randomized, double-blinded MRI trial has been published yet. Summary of Review— MRI screening of acute stroke patients before thrombolytic therapy is performed in some cerebrovascular centers. In contrast to the CT trials, MRI pilot studies demonstrate benefit of therapy up to 6 hours after onset of symptoms. This article reviews the literature that has lead to current controlled MRI-based thrombolysis trials. We examined the MRI criteria applied in 5 stroke centers. Along with the personal views of clinicians at these centers, the survey reveals a variety of clinical and MRI technical aspects that must be further investigated: the therapeutic consequence of microbleeds, the use of magnetic resonance angiography, dynamic time windows, and others. Conclusion— MRI is an established application in acute evaluation of stroke patients and may suit as a brain clock, replacing the currently used epidemiological time clock when deciding whether to initiate thrombolytic therapy. MRI criteria for thrombolytic therapy are applied in some cerebrovascular centers, but the results of ongoing clinical trials must be awaited before it is possible to reach consensus.

Predictors of Apparent Diffusion Coefficient Normalization in Stroke Patients

Background and Purpose— We sought to describe the frequency of normalization of apparent diffusion coefficient (ADC) values that are decreased in hyperacute stroke and to identify characteristics of tissue demonstrating normalization. Methods— Sixty-eight acute ischemic stroke patients underwent MRI examination (including diffusion/perfusion imaging and MR angiography) within 6 hours (mean, 2.8 hours) after symptom onset, after 24 hours, and again 4 to 7 days later. Lesion volumes with decreased ADC and delayed time to peak in perfusion imaging were determined. In patients showing ADC normalization, volumes with ADC decrease graded as <50%, 50% to 60%, 60% to 70%, and 70% to 80% of the contralateral value were determined by thresholding. Patients were categorized as normalizers (demonstrating ADC normalization in >5 mL tissue with initially decreased ADC) or nonnormalizers (demonstrating ADC normalization in <5 mL tissue). Results— Fourteen patients (19.7%) were classified as normalizers. Eleven of 31 patients (35.5%) initially imaged <3 hours after stroke onset and 3 of 37 (7.5%) of those imaged 3 to 6 hours after onset were normalizers. ADC normalization occurred predominantly in the basal ganglia and white matter after thrombolytic therapy in patients with more distal vessel occlusions. All normalizers demonstrated at least partial tissue reperfusion. Tissue with more severe initial decrease in ADC was less likely to demonstrate normalization. Conclusions— ADC normalization is not a rare event in acute stroke after tissue reperfusion. Brain tissue with initially decreased ADC, especially within 3 hours after stroke onset, may include “tissue at risk.”

Negative dip in BOLD fMRI is caused by blood flow--oxygen consumption uncoupling in humans.

The sensitivity of MRI for local changes in the deoxyhemoglobin concentration is the basis of the blood oxygen level dependent (BOLD) effect. Time-resolved fMRI studies during visual activation show an early signal intensity (SI) decrease indicating a short lasting uncoupling of oxygen consumption and cerebral blood flow (CBF) before a SI increase due to the overcompensating hemodynamic response occurs. Normal neuronal activity may be preserved despite absent vascular responsiveness. Here we show that a negative BOLD effect occurs during motor activation in an asymptomatic patient with severely disturbed cerebral autoregulation due to extracranial artery disease. This is thought to be due to oxygen consumption in the absence of a hemodynamic response. This rare case of a persisting uncoupling of oxygen metabolism and CBF serves as a model that supports changes of the cerebral blood oxygen saturation as the major contributor of the BOLD effect.

Local Intra-Arterial Fibrinolysis in Acute Hemispheric Stroke: Effect of Occlusion Type and Fibrinolytic Agent on Recanalization Success and Neurological Outcome

Background: To evaluate the effect of occlusion type and fibrinolytic agent on recanalization success and clinical outcome in patients undergoing local intra-arterial fibrinolysis (LIF) in acute hemispheric stroke. Methods: LIF was performed in 137 patients with angiographically established occlusion in the carotid circulation within 6 h of stroke onset. Retrospective analysis included recanalization success, recanalization time, type of occlusion and fibrinolytic treatment mode. Five types of occlusion were categorized: intracranial bifurcation (carotid ‘T’) of the internal carotid artery (ICA; n = 35); proximal segment of the middle cerebral artery (MCA; n = 66); distal segment of the MCA (n = 20); extracranial ICA with MCA embolism (n = 8); multiple peripheral branches of the anterior cerebral artery and the MCA (n = 8). Neurologic outcome was evaluated after 3 months by Barthel Index (BI) as good (BI >90), moderate (BI 50–90), poor (BI <50) or death. Results: Recanalization was achieved in 74 patients (54%). Mean recanalization time in recanalized patients was 91 min. Neurologic outcome was good in 48 patients (35%), moderate in 34 (25%), poor in 30 (22%) and 25 died (18%). Outcome was significantly better in recanalized than in nonrecanalized patients (p < 0.001). Treatment results were significantly better in proximal and distal MCA occlusion than in carotid ‘T’ occlusions (p < 0.001). Recanalization success hardly differed between urokinase and rt-PA. Combined treatment with rt-PA and lys-plasminogen tended toward a faster recanalization. Parenchymal hemorrhage occurred in 13 patients (9%). Conclusion: The type of occlusion is of high prognostic value for successful fibrinolysis in the anterior circulation. However, recanalization is a time-consuming process even with an intra-arterial approach. Recanalization did not differ between type or dosage of plasminogen activators. Further innovative attempts are warranted towards hastening recanalization time in endovascular acute stroke treatment.

Cerebral Blood Flow Predicts Lesion Growth in Acute Stroke Patients

Background and Purpose— We sought to study the role of MRI-derived cerebral blood flow (CBF) measurements for the prediction of lesion development in acute stroke patients. Methods— Thirty-two patients were treated with tissue plasminogen activator. Diffusion-weighted (DWI) and perfusion-weighted MRI, T2-weighted imaging, and MR angiography were performed before treatment (2.8±0.9 hours after symptom onset) and on follow-up (days 1 and 7). CBF thresholds (12 and 22 mL/100 g per minute) were applied to bolus tracking MRI maps to determine predictive cutoff levels. Results— In 21 patients (group A), the terminal lesion volume (T2-weighted imaging) was larger than the initial DWI lesion volume (89±93 versus 21±38 mL). In 11 patients (group B), the terminal lesion volume was smaller than the initial DWI lesion volume (7±27 versus 15±29 mL). The initial DWI lesion volume did not differ between both groups. The presence of a tissue volume ≥50 mL with a CBF value ≤12 mL/100 g per minute was predictive for lesion enlargement to day 7 in T2-weighted imaging (positive predictive value, 0.80). Conclusions— The presence of a tissue volume ≥50 mL with a CBF value ≤12 mL/100 g per minute predicts further lesion growth in hyperacute stroke patients. MRI-derived CBF values, with all their present limitations, are valuable in early estimation of prognosis of stroke patients.

Apparent Diffusion Coefficient Decreases and Magnetic Resonance Imaging Perfusion Parameters are Associated in Ischemic Tissue of Acute Stroke Patients

Perfusion-and diffusion-weighted magnetic resonance imaging scans are thought to allow the characterization of tissue at risk of infarction. The authors tested the hypothesis that the apparent diffusion coefficient (ADC) decrease should be associated with the severity of the perfusion deficit in ischemic tissue of acute stroke patients. Perfusion-and diffusion-weighted scans were performed in 11 patients with sudden onset of neurologic deficits within the last 6 hours and T2-weighted magnetic resonance imaging scans were obtained after 6 days. Parameter images of the maximum of the contrast agent concentration, time to peak, relative cerebral blood volume, relative cerebral blood flow, and relative mean transit time were computed from the perfusion-weighted data. A threshold function was used to identify tissue volumes with stepwise ADC decreases. An onionlike distribution of successively decreasing ADC values was found, with the lowest ADC in the center of the ischemic region. Correspondingly, tissue perfusion decreased progressively from the periphery toward the ischemic core. This effect was most pronounced in the time-to-peak maps, with a linear association between ADC decrease and time-to-peak increase. Apparent diffusion coefficient values decreased from the periphery toward the ischemic core, and this distribution of ADC values was strongly associated with the severity of the perfusion deficit.

Reperfusion after Severe Local Perfusion Deficit Precedes Hemorrhagic Transformation: An MRI Study in Acute Stroke Patients

Background: We applied magnetic resonance imaging to analyze the degree of local diffusion and perfusion abnormalities and the status of reperfusion in regions with subsequent hemorrhagic transformation (HT). Methods: 51 patients with acute ischemic stroke were studied by diffusion- and perfusion-weighted imaging within 3.0 ± 0.8 h, on day 1 and days 5–8. After realignment of the image data sets, the parameter maps of the apparent diffusion coefficient (ADC), cerebral blood flow (CBF) and cerebral blood volume (CBV), and mean transit time were analyzed in the area of subsequent HT. The degree of local diffusion and perfusion impairment in the HT area was compared with the entire diffusion and perfusion abnormality. Reperfusion status was separately assessed for the entire perfusion abnormality and the HT area. Results: HT was observed in 19/51 patients (37.2%) within 8 days after symptom onset. Areas destined for HT revealed a more severe decrease in ADC (to 70 ± 13%; p < 0.01), CBV (to 31 ± 26%; p < 0.001) and CBF (to 28 ± 19%; p < 0.001) compared to the entire perfusion abnormality. Local reperfusion in the HT area was seen in 18/19 patients. The presence of HT did not coincide with a worse clinical outcome. Discussion: HT is the result of reperfusion in the region with the most severe local perfusion impairment and does not influence the neurological outcome.

Are There Time-Dependent Differences in Diffusion and Perfusion Within the First 6 Hours After Stroke Onset?

Background and Purpose— Stroke heterogeneity in computed tomography-based studies has been attributed as main cause for missing efficacy of intravenous tissue plasminogen activator (tPA) therapy within 3 to 6 hours. We investigated early time-dependent differences in acute stroke pathophysiology by multiparametric magnetic resonance imaging (MRI). Methods— Stroke MRI of 112 acute ischemic stroke patients within <6 hours were dichotomized into a <3-hour group (n=52) and a 3- to 6-hour group (n=60). Infarct volume was determined on days 5 to 8. Lesion volumes were determined for apparent diffusion coefficient (ADC_man) and the subregion with ADC values <550×10−9 mm/s 2 (ADC <550), and for the time-to-peak (TTP) delay of 2 to 4 seconds, 4 to 6 seconds, 6 to 8 seconds, and >8 seconds. A subsample analysis was performed for occlusions of the middle carotid artery (MCA) trunk (n=36) and MCA branches (n=30), and for all patients treated by intravenous tPA (n=70). Results— ADC and TTP lesion volumes were not different within <3 hours compared with volumes at 3 to 6 hours. In patients receiving intravenous tPA (n=70), there were no significant differences in ADC_man, TTP >2 seconds, and infarct volume (days 5 to 8) between the 2 groups. There was a greater proportion of ADC <550/ADC_man, which was most pronounced in patients with MCA trunk occlusions after 3 to 6 hours and a larger mismatch in the <3-hour group compared with that of the 3- to 6-hour group. In MCA branch occlusions, there was a less severe TTP delay after 3 to 6 hours. However, all differences missed the significance level (P =0.05) after correction for multiple testing. Conclusions— We observed no significant time-dependent differences within 6 hours after stroke onset in degree and volume of diffusion and perfusion impairment. An exclusion from intravenous tPA solely based on a rigid 3-hour time window seems unjustified in MRI-confirmed ischemic stroke.

Folgen aus neurologischer Sicht — was bleibt?

Von dem letzten Ausbruch des Escherichia coli (STEC) Serotyp O104 in Norddeutschland im Jahr 2011 waren mehr als 3.800 registrierte Patienten betroffen. Ein Viertel von ihnen entwickelte ein hämolytisch urämisches Syndrom (HUS). In diesem Beitrag werfen wir einen Blick auf die kurz- und mittelfristigen Folgen mit Darstellung der neurologischen, neuroradiologischen and neuropathologischen Ergebnisse dieser bisher weltweit größten Kohorte von Erwachsenen mit „Neuro-EHEC“.