In vivo TSPO imaging in patients with multiple sclerosis: a brain PET study with [18F]FEDAA1106.

BACKGROUND: The activation of microglia, in general, and the upregulation of the translocator protein (18 kDa) (TSPO) system, in particular, are key features of neuroinflammation, of which the in vivo visualization and quantitative assessment are still challenging due to the lack of appropriate molecular imaging biomarkers. Recent positron emission tomography (PET) studies using TSPO radioligands such as [11C]PK11195 and [11C]PBR28 have indicated the usefulness of these PET biomarkers in patients with neuroinflammatory diseases, including multiple sclerosis (MS). [18F]FEDAA1106 is a recently developed PET radioligand for the in vivo quantification of TSPO. In the present study, we aimed at investigating the diagnostic usefulness of [18F]FEDAA1106 in patients with MS. METHODS: Nine patients (three on the interferon beta therapy and six without immunomodulatory therapy; seven females/two males; age 34.2 ± 9.1 years old) with relapsing-remitting MS in acute relapse and with gadolinium (Gd)-enhancing lesion(s) in the magnetic resonance imaging (MRI) scans and five healthy controls (four females/one male, age 38.0 ± 9.7 years old) were investigated in this study. Genetic information about the TSPO binding could not be obtained because knowledge about the importance of genetic background for TSPO binding was not available at the time the study was performed. Dynamic PET measurements were performed using an ECAT EXACT HR system (CTI/Siemens, Knoxville, TN, USA) for a total of 150 min, with a 30-min break after the injection of 153.4 ± 10.2 MBq of [18F]FEDAA1106. Metabolite-corrected arterial plasma samples were used to calculate the input function. PET data were analyzed in the following ways: (1) region-of-interest analysis for cortical and subcortical regions was performed using a two-tissue compartment kinetic model in order to estimate binding potentials (BPND) and distribution volume (VT), (2) the feasibility of the estimation of BPND and VT was investigated for MS lesions, and (3) VT parametric images by a Logan plot and standard uptake value (SUV) images were visually compared with the corresponding MRI, focusing on MRI-identified MS lesions. RESULTS: There were no significant differences in the BPND or VT values between patients with MS and healthy controls. Robust BPND and VT values could not be obtained for most MS lesions due to noisy time-activity curves. Visual inspection of VT and SUV images in all nine patients did not reveal high uptake of the radioligand inside and beyond MRI-identified active MS lesions with the exception of one Gd-enhanced MS lesion in the whole patient population. CONCLUSIONS: In our study, [18F]FEDAA1106 as a PET radioligand could neither differentiate patients with MS from healthy controls nor detect active plaques in the brain of MS patients. Stratification with respect to genetics and binder status might help to uncover the differences between the groups, which could not be detected here. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01031199.

Association of N-acetylaspartate and cerebrospinal fluid Aß42 in dementia.

The interplay of amyloid and mitochondrial function is considered crucial in the pathophysiology of Alzheimer's disease (AD). We tested the association of the putative marker of mitochondrial function N-acetylaspartate (NAA) as measured by proton magnetic resonance spectroscopy within the medial temporal lobe and cerebrospinal fluid amyoid-ß42 (Aß42), total Tau and pTau181. 109 patients were recruited in a multicenter study (40 mild AD patients, 14 non-AD dementia patients, 29 mild cognitive impairment (MCI) AD-type patients, 26 MCI of non-AD type patients). NAA correlated with Aß42 within the AD group. Since the NAA concentration is coupled to neuronal mitochondrial function, the correlation between NAA and Aß42 may reflect the interaction between disrupted mitochondrial pathways and amyloid production.

Macromolecule content influences proton diffusibility in gliomas.

OBJECTIVES: Different compositions of the extra cellular matrix with changing concentrations of more or less hydrophilic components like proteins may have a major influence on the diffusion phenomena found in gliomas. METHODS: 24 patients (14 male / 10 female) with histologically confirmed non necrotic glioma underwent preoperative MRI, including magnetisation transfer (MTR), triple echo T2 weighted (T2W) and diffusion weighted (DWI) sequences. Apparent diffusion coefficient (ADC), quantitative T2 and MTR maps were calculated and regions of interest (ROIs) were placed in the tumour centre (TU) and in the contralateral hemisphere (NWM). Informed consent was obtained. The study was approved by the local ethic comity. RESULTS: Mean values evaluated in the NWM / TU were (± standard deviation); ADC: 0.78 (±0.08) × 10-3 mm2/s / 1.32 (±0.27) × 10-3 mm2/s, T2: 101.66 (±12.00) ms / 252.11 (±104.53) ms, MTR: 0.52 (±0.01) / 0.40 (±0.04). The mean value of each parameter correlated highly significant with the others (p < 0.01). CONCLUSION: Our results suggest that macromolecules binding protons in their vicinity are a major determinant of proton diffusivity in brain tumours in addition to other factors such as mechanical barriers like membranes or the size of the extra-cellular space.

Interrater agreement for final infarct MRI lesion delineation.

BACKGROUND AND PURPOSE: Lesion volume measured on follow-up magnetic resonance imaging (MRI) is commonly used as an outcome parameter in clinical stroke trials. However, few studies have evaluated the optimal sequence choice and the interrater reliability of this outcome measure. The objective of this study was to quantify the geometric interrater agreement for lesion delineation of chronic infarcts on T2-weighted and fluid-attenuated inverse recovery (FLAIR) MRI. METHODS: In a retrospective study of 14 patients, lesions on 90-day follow-up FLAIR and T2 fast spin echo MRI were outlined by 9 independent, blinded, experienced neuroradiologists. Voxel-wise interrater agreement was measured as (1) the volume of the intersection of individual rater's lesion outlines relative to the mean lesion volume (overlap ratio) and (2) the Hausdorff distance between the lesion markings. RESULTS: Mean patient age was 64.4 years (range, 45 to 79). Lesion volumes on FLAIR were, on average, 2.5 mL greater than were T2 volumes (median; P<0.001). We found considerable differences between raters' lesion markings, but interrater agreement was consistently better on FLAIR than on T2 images, as measured by a greater overlap ratio (P<0.0001) and a smaller Hausdorff distance (P<0.0001) on FLAIR than on T2. CONCLUSIONS: FLAIR should be used to quantify follow-up infarct size to minimize interrater variability. Our study suggests that imaging analysis performed by 1 or a few trained readers may be preferred. Future studies should address objective and preferably automated criteria for final lesion delineation.

AGC1 deficiency associated with global cerebral hypomyelination.

The mitochondrial aspartate-glutamate carrier isoform 1 (AGC1), specific to neurons and muscle, supplies aspartate to the cytosol and, as a component of the malate-aspartate shuttle, enables mitochondrial oxidation of cytosolic NADH, thought to be important in providing energy for neurons in the central nervous system. We describe AGC1 deficiency, a novel syndrome characterized by arrested psychomotor development, hypotonia, and seizures in a child with a homozygous missense mutation in the solute carrier family 25, member 12, gene SLC25A12, which encodes the AGC1 protein. Functional analysis of the mutant AGC1 protein showed abolished activity. The child had global hypomyelination in the cerebral hemispheres, suggesting that impaired efflux of aspartate from neuronal mitochondria prevents normal myelin formation.

Imaging in acute stroke--a personal view.

Acute stroke imaging has developed from intraarterial angiography and native, unenhanced CT to highly elaborated tools with the access to a variety of pathophysiological variables ahead of therapy. Despite enduring unresolved problems, we can now obtain a comprehensive view on the individual patient's disease and act fast and specifically under consideration of chances and risks of different therapies. The stroke neuroradiologist is the decisive partner of engaged clinical disciplines and should own a leading role in future acute stroke trials. Weighing the different modalities against each other, there is an established advantage of acute stroke MRI over CT based on diffusion-weighted imaging and the possibility to obtain even more functional information on stroke pathophysiology.

Combination of T2*W and FLAIR abnormalities for the prediction of parenchymal hematoma following thrombolytic therapy in 100 stroke patients.

INTRODUCTION: The objective of our study was to determine whether the combination of hypointense spots ("cerebral microbleeds," CMBs) with a leukoaraiosis is associated with the risk of parenchymal hematoma (PH) after thrombolytic therapy. PATIENTS AND METHODS: We analyzed magnetic resonance imaging (MRI) scans acquired within 6 hours after symptom onset from 100 ischemic stroke patients. Multiparametric MRI including a T2*-weighted (T2*w) MRI and fluid attenuated inversion recovery (FLAIR) was performed before thrombolysis in all patients. Initial T2*w imaging was rated by two independent observers for the presence of CMBs smaller than 5 mm. White matter changes were evaluated using an adapted scale of Fazekas and Schmidt. PH was defined in follow-up imaging. FINDINGS: A PH was observed in seven per 100 patients. CMBs were detected by observer 1 in 22 and observer 2 in 20 patients. We found a very low sensitivity (0.14) for prediction of PH by the presence of CMBs. We found a concordant increase in the rate of PH when the periventricular hyperintensity in FLAIR was larger than a thin lining. Sensitivity was good-to-perfect (0.86 and 1.00, observers 1 and 2) and specificity was substantial (0.65 and 0.66). Using the combination of a periventricular matter lesion (PVML)>1 and the presence of CMBs did not improve the prediction of PH. DISCUSSION: A marked periventricular hyperintensity in FLAIR imaging seems to be associated with a substantially increased risk of PH. A combination of CMBs with leukoaraiosis scores did not appear to be beneficial for prognosis.

Comparison of 10 perfusion MRI parameters in 97 sub-6-hour stroke patients using voxel-based receiver operating characteristics analysis.

BACKGROUND AND PURPOSE: Perfusion-weighted imaging can predict infarct growth in acute stroke and potentially be used to select patients with tissue at risk for reperfusion therapies. However, the lack of consensus and evidence on how to best create PWI maps that reflect tissue at risk challenges comparisons of results and acute decision-making in trials. Deconvolution using an arterial input function has been hypothesized to generate maps of a more quantitative nature and with better prognostic value than simpler summary measures such as time-to-peak or the first moment of the concentration time curve. We sought to compare 10 different perfusion parameters by their ability to predict tissue infarction in acute ischemic stroke. METHODS: In a retrospective analysis of 97 patients with acute stroke studied within 6 hours from symptom onset, we used receiver operating characteristics in a voxel-based analysis to compare 10 perfusion parameters: time-to-peak, first moment, cerebral blood volume and flow, and 6 variants of time to peak of the residue function and mean transit time maps. Subanalysis assessed the effect of reperfusion on outcome prediction. RESULTS: The most predictive maps were the summary measures first moment and time-to-peak. First moment was significantly more predictive than time to peak of the residue function and local arterial input function-based methods (P<0.05), but not significantly better than conventional mean transit time maps. CONCLUSIONS: Results indicated that if a single map type was to be used to predict infarction, first moment maps performed at least as well as deconvolved measures. Deconvolution decouples delay from tissue perfusion; we speculate this negatively impacts infarct prediction.

T2' imaging predicts infarct growth beyond the acute diffusion-weighted imaging lesion in acute stroke.

PURPOSE: To show that measurement of the transverse relaxation time that characterizes signal loss caused by local susceptibilities (T2') is sensitive to an increased deoxyhemoglobin concentration in the brain, indicating tissue at risk for infarction. MATERIALS AND METHODS: The study was approved by the local institutional review board; patients or their guardians provided informed consent. Magnetic resonance (MR) imaging was performed within 6 hours of symptom onset and again 1-11 days thereafter in 100 consecutive stroke patients, all of whom received intravenous thrombolytic therapy (mean age, 67 years). The MR imaging protocol included diffusion- and perfusion-weighted imaging for determination of apparent diffusion coefficient (ADC) and time to peak (TTP), along with quantitative T2 and T2* imaging. T2' maps were calculated and visually compared with ADC and TTP lesions by two independent observers. RESULTS: A T2'>ADC mismatch was observed by reader 1 in 73 (73%) of 100 patients, and by reader 2 in 65 (65%) patients. Respective sensitivities of T2'>ADC and of TTP>ADC mismatches for later infarct growth were 0.87 and 0.98 for reader 1 and 0.78 and 0.98 for reader 2, with respective specificities of 0.42 and 0.04 for reader 1 and 0.46 and 0.04 for reader 2. The odds ratios for infarct growth in the presence of a T2'>ADC mismatch were 4.59 (reader 1 P = .002) and 3.10 (reader 2 P = .012), while the odds ratios for TTP>ADC mismatch were 2.22 (reader 1 P = .606) and 1.73 (reader 2 P > .999). CONCLUSION: The presence of a T2'>ADC mismatch is a more specific predictor of infarct growth than is TTP>ADC mismatch and hence may be of clinical value in patient selection for acute stroke therapies in the future.

Two tales: hemorrhagic transformation but not parenchymal hemorrhage after thrombolysis is related to severity and duration of ischemia: MRI study of acute stroke patients treated with intravenous tissue plasminogen activator within 6 hours.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage represents the most feared complication of treatment with intravenous tissue plasminogen activator. We studied whether perfusion-weighted imaging and diffusion-weighted imaging has the potential to identify patients at risk of severe intracerebral hemorrhage after treatment with intravenous tissue plasminogen activator. METHODS: We analyzed data of prospectively studied MRI selected acute ischemic stroke patients treated with intravenous tissue plasminogen activator within 6 hours. All patients were examined by perfusion- and diffusion-weighted imaging < or =6 hours. Perfusion- and diffusion-weighted imaging lesion volumes were calculated. Hemorrhagic transformation was assessed on follow-up CT or MRI and diagnosed as hemorrhagic transformation, parenchymal hemorrhage, or symptomatic intracerebral hemorrhage according to ECASS II criteria. RESULTS: Of 152 patients, hemorrhagic transformation was seen in 60 (39.5%), parenchymal hemorrhage in 15 (9.9%), and symptomatic intracerebral hemorrhage in 4 (2.6%). Multiple logistic regression analysis identified onset to treatment time after 3 to 6 hours (P<0.001), a larger perfusion-weighted imaging lesion volume (P=0.002), and, as a tendency, a higher score on the National Institutes of Health Stroke Scale on admission (P=0.068) as independent predictors of hemorrhagic transformation. Neither MRI lesion volumes nor severity of symptoms, but rather only an older age tended to be associated with parenchymal hemorrhage (P=0.087). CONCLUSIONS: Our results further support the concept of a different pathogenesis for hemorrhagic transformation and parenchymal hemorrhage. Whereas hemorrhagic transformation should be regarded as a clinically irrelevant epiphenomenon of ischemic damage and reperfusion, parenchymal hemorrhage appears to be related to biologic effects of tissue plasminogen activator and other pre-existing pathologic conditions, which deserve further investigation.

Characterizing physiological heterogeneity of infarction risk in acute human ischaemic stroke using MRI.

Viable tissues at risk of infarction in acute stroke patients have been hypothesized to be detectable as volumetric mismatches between lesions on perfusion-weighted (PWI) and diffusion-weighted magnetic resonance imaging (DWI). Because tissue response to ischaemic injury and to therapeutic intervention is tissue- and patient-dependent, changes in infarct progression due to treatment may be better detected with voxel-based methods than with volumetric mismatches. Acute DWI and PWI were combined using a generalized linear model (GLM) to predict infarction risk on a voxel-wise basis for patients treated either with non-thrombolytic (Group 1; n = 11) or with thrombolytic therapy (Group 2; n = 27). Predicted infarction risk for both groups was evaluated in four ipsilateral regions of interest: tissue acutely abnormal on DWI (Core), tissue acutely abnormal on PWI but normal on DWI that either infarcts (Recruited) or does not (Salvaged), and tissue normal on both DWI and PWI that does not infarct (Normal) by follow-up imaging > or = 5 days. The performance of the models was significantly reduced for the thrombolysed group compared with the group receiving standard treatment, suggesting an alteration in natural progression of the ischaemic cascade. Average GLM-predicted infarction risk values in the four regions were different from one another for both groups. GLM-predicted infarction risk in Salvaged tissue was significantly higher (P = 0.02) for thrombolysed patients than for non-thrombolysed patients, suggesting that thrombolysis rescued tissue with higher infarction risk than typically measured in tissue that spontaneously recovered. The observed spatial heterogeneity of GLM-predicted infarction risk values probably reflects the varying degrees of tissue injury and salvageability that exist after stroke. MRI-based algorithms may therefore provide a more sensitive means for monitoring therapeutic effects on a voxel-wise basis.

Leukoaraiosis is a risk factor for symptomatic intracerebral hemorrhage after thrombolysis for acute stroke.

BACKGROUND AND PURPOSE: The aim of the study was to evaluate whether leukoaraiosis (LA) is a risk factor for symptomatic intracerebral hemorrhage (sICH) in patients treated with thrombolysis for acute stroke. METHODS: In this retrospective, multicenter analysis, we evaluated data from acute anterior circulation stroke patients (n=449; <6 hours after symptom onset) treated with thrombolysis. All patients had received standard magnetic resonance imaging evaluation before thrombolysis, including a high-quality T2-weighted sequence. For the analysis, LA in the deep white matter was dichotomized into absent or mild versus moderate or severe (corresponding to Fazekas scores of 0 to 1 versus 2 to 3). RESULTS: The rate of sICH was significantly more frequent in patients with moderate to severe LA of the deep white matter (n=12 of 114; 10.5%) than in patients without relevant LA (n=13 of 335; 3.8%), corresponding to an odds ratio of 2.9 (95% CI, 1.29 to 6.59; P=0.015). In a logistic-regression analysis (including age, National Institutes of Health Stroke Scale score at presentation, and type of thrombolytic treatment), LA remained a significant independent risk factor (odds ratio, 2.9; P=0.03). CONCLUSIONS: LA of the deep white matter is an independent risk factor for sICH after thrombolytic treatment for acute stroke.

Pathophysiology of the Eustachian tube--relevant new aspects for the head and neck surgeon.

OBJECTIVES: The impact of cranio-maxillofacial procedures upon Eustachian tube function is still largely unknown. The aim of this presentation is to depict new aspects of Eustachian tube function and to demonstrate its importance to cranio-maxillofacial surgery. METHODS: Two different groups of patients were examined both clinically and by MRI of the Eustachian tube region. One of these groups comprised 15 adult patients with a history of cleft palate; another consisted of 32 patients with a history of a so-called patulous Eustachian tube. RESULTS: Clinical and MRI-findings revealed that the problem of persistent chronic middle ear disease with cleft palate patients depends crucially on the integrity of the pterygoid hamulus and of the tensor veli palatini muscle after cleft palate repair. The masticatory muscles on the other hand also play an important role in Eustachian tube function in non-cleft patients. CONCLUSION: The maxillofacial surgeon should be aware that he holds a key position for preventing as well as treating Eustachian tube pathophysiology.

Blood-oxygen-level-dependent MRI allows metabolic description of tissue at risk in acute stroke patients.

BACKGROUND AND PURPOSE: The delineation of the "penumbra" is of particular interest in acute stroke imaging. The "mismatch concept" applying perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) appears to be an oversimplification of the underlying electrophysiological tissue status. An additional parameter reflecting the metabolic state of the threatened brain tissue would improve our ability to describe the penumbra. One candidate is deoxyhemoglobin (deoxy-Hb) as an indicator of the oxygen extraction fraction that can be visualized by T2*-based blood oxygen level-dependent (BOLD) imaging. METHODS: We analyzed data from 32 patients with acute stroke in the territory of the middle cerebral artery. MRI included fluid-attenuated inversion recovery, DWI, PWI, time-of-flight angiography, and quantitative T2 and T2* (qT2, qT2*) imaging. Follow-up was performed on day 1 and days 5 to 8. We calculated 1/T2'=1/qT2*-1/qT2. Changes of T2', representing the deoxy-Hb effect, were analyzed by 3D regions of interest (ROIs): apparent diffusion coefficient lesion day 0 (L0), time-to-peak-lesion day 0 (T0), final infarct size days 5 to 8 (F5-8), lesion growth (LG; F5-8-L0), and surviving tissue (ST; T0-F5-8). RESULTS: We observed a clear decrease of T2' in the infarcted hemisphere compared with the unaffected control ROIs. The mean value showed the most pronounced loss of T2' signal intensity in L0 (-15.7%), followed by LG (-10.5%) and ST (-8.0%). CONCLUSIONS: The implementation of BOLD imaging in acute stroke MRI offers a noninvasive estimation of the O2 utilization and is able to add additional information concerning the present metabolic state of the threatened brain tissue. The changes in T2' intensity are visually noticeable in the reconstructed T2' images and provide a better estimation of the real penumbra.

Intravenous administration of acetylsalicylic acid during endovascular treatment of cerebral aneurysms reduces the rate of thromboembolic events.

BACKGROUND AND PURPOSE: The purpose of this study is to analyze the effect of a modified intraoperative anticoagulation strategy including acetylsalicylic acid (ASA) on complication rates during endovascular coil embolization. METHODS: Two hundred and sixty-one cerebral aneurysms were treated in 247 patients by endovascular coil embolization from January 2001 to September 2004. Additional intravenous administration of 250 mg ASA was applied since January 2003. Patients treated before (-ASA; n=102 aneurysms) and after that date (+ASA; n=159 aneurysms) were compared. End points were rates of thromboembolism and severity of hemorrhages after intraoperative aneurysm rupture. RESULTS: Thromboembolic events during the procedure were observed more often in the -ASA group (18/102 aneurysms, 17.6%) in comparison with the +ASA group (14/159 aneurysms, 8.8%; P=0.028; Fisher exact test). Aneurysm perforation events occurring during or immediately after the procedure were observed equally often in the -ASA group (7/102 aneurysms, 6.9%) in comparison with the +ASA group (10/159 aneurysms, 6.3%). CONCLUSIONS: Intravenous application of ASA is feasible and safe during interventional aneurysm embolization. ASA seems to be associated with a significant reduction in the rate of thromboembolic events without increase in the rate or severity of intraoperative bleedings.

Low-grade and anaplastic gliomas: differences in architecture evaluated with diffusion-tensor MR imaging.

PURPOSE: To prospectively evaluate whether diffusion-tensor magnetic resonance (MR) imaging depicts differences in World Health Organization (WHO) grade II and III glial brain tumors on the basis of tumor architecture and peritumoral tract invasion. MATERIALS AND METHODS: The study protocol was approved by the local ethics committee, and written informed consent was obtained. Diffusion-tensor MR imaging was performed in 23 patients (15 men, eight women; mean age, 47 years) with histologically confirmed brain gliomas. Eleven of the 23 tumors were low-grade gliomas (WHO grade II) and 12 were anaplastic gliomas (WHO grade III). Regions of interest were placed in the tumor center, tumor border, normal-appearing white matter (NAWM) adjacent to the tumor, and NAWM of the contralateral hemisphere. fractional anisotropy (FA) ratios were calculated for regions of interest in relation to the NAWM of the contralateral hemisphere. Pairwise comparisons were performed by using the Mann-Whitney U test. RESULTS: Median FA ratios for grade II versus grade III gliomas were 0.406 versus 0.405, respectively, for tumor center, 0.733 versus 0.449, respectively, for tumor border, and 0.962 versus 0.943, respectively, for NAWM adjacent to the tumor. Differences in FA ratio between low-grade and high-grade tumors were significant in the tumor border only (P = .01). Differences in FA ratio were not significant between low-grade and high-grade gliomas in the tumor center or in the NAWM adjacent to the tumor. CONCLUSION: The periphery of low-grade gliomas contains a considerable amount of preserved fiber tracts. In high-grade gliomas, however, most of these tracts are disarranged. Low FA ratios in the tumor center are consistent with a high degree of disorganization of myelinated fiber tracts in the center of both low-grade and high-grade gliomas.

A multicenter reproducibility study of single-voxel 1H-MRS of the medial temporal lobe.

Proton magnetic resonance spectroscopy ((1)H-MRS) has provided evidence for a reduction of N-acetyl-aspartate (NAA) in the medial temporal lobe (MTL) in cerebral disorders such as Alzheimer's Disease. Within the (1)H-MRS study of the German Research Network on Dementia, we determined the multicenter reproducibility of single-voxel (1)H-MRS of the MTL. At five sites with 1.5T MR systems, single-voxel (1)H spectra from the MTL of an identical healthy subject were measured. The same subject was also examined at one of the sites five times to assess intracenter stability. The protocol included water-suppressed spectra with TE 272 ms and TE 30 ms and unsuppressed spectra for absolute quantification of metabolite concentrations. The intracenter reproducibility of absolute NAA concentration, expressed as coefficient of variation (CV), was 1.8%. CV for the concentrations of creatine (Cr), choline (Cho), and myoinositol (MI) and for the ratios NAA/Cr, NAA/Cho, and MI/NAA varied by 11-16%. Intercenter CV was 3.9% for NAA and were below 10% for all other metabolites and metabolic ratios. Our study demonstrates that quantitative assessment of NAA with single-voxel MRS can be performed with high intercenter reproducibility. This is the basis for applying (1)H-MRS in large-scale early recognition and treatment studies in MTL affecting disorders.

Outcome and symptomatic bleeding complications of intravenous thrombolysis within 6 hours in MRI-selected stroke patients: comparison of a German multicenter study with the pooled data of ATLANTIS, ECASS, and NINDS tPA trials.

BACKGROUND AND PURPOSE: We compared outcome and symptomatic bleeding complications of intravenous tissue plasminogen activator (IV-tPA) within 6 hours of symptom onset in MRI-selected patients with acute middle cerebral artery infarction with the pooled data of the large stroke tPA trials. METHODS: Patients were examined by perfusion-weighted and diffusion-weighted imaging < or =6 hours. Within 3 hours, patients were treated according to Second European-Australasian Acute Stroke Study (ECASS II) criteria. After 3 to 6 hours, treatment with IV-tPA was performed based on MRI findings. Favorable outcome was assessed after 90 days using a dichotomized modified Rankin scale score of 0 to 1. Intracerebral bleeding complications were assessed on follow-up MRI or computed tomography. Data were compared with the pooled placebo and pooled tPA patients of the ATLANTIS, ECASS, and National Institute of Neurological Disorders and Stroke (NINDS) tPA trials. RESULTS: From 174 MRI-selected tPA patients, 62% (n=108) were treated in < or =3 hours and 38% (n=66) after 3 to 6 hours. Favorable outcome was more frequent in MRI-selected tPA patients (48% [95% CI, 39 to 54]) compared with pooled placebo (33% [95% CI, 31 to 36]; P<0.001) and pooled tPA patients (40% [95% CI, 37 to 42]; P=0.046). Odds ratios for favorable outcome in the MRI-selected tPA group were 1.82 (1.32 to 2.51) compared with the pooled placebo and 1.39 (1.01 to 1.92) compared with the pooled tPA group. The rate of symptomatic intracerebral hemorrhage in MRI-selected tPA patients (3% [95% CI, 0 to 5]) was lower than in the pooled tPA group (8% [95% CI, 7 to 10]; P=0.012) and comparable to the pooled placebo group (2% [95% CI, 1 to 3]; P=0.392). CONCLUSIONS: This study supports that it is safe and effective to expand the time window for IV-tPA up to 6 hours in patients with tissue at risk as defined by MRI.

Cerebral vasculitis following oral methylphenidate intake in an adult: a case report.

Methylphenidate is structurally and functionally similar to amphetamine. Cerebral vasculitis associated with amphetamine abuse is well documented, and in rare cases ischaemic stroke has been reported after methylphenidate intake in children. We report the case of a 63-year-old female who was treated with methylphenidate due to hyperactivity and suffered from multiple ischaemic strokes. We consider drug-induced cerebral vasculitis as the most likely cause of recurrent ischaemic strokes in the absence of any pathological findings during the diagnostic work-up. We conclude that methylphenidate mediated vasculitis should be considered in patients with neurological symptoms and a history of methylphenidate therapy. This potential side-effect, though very rare, represents one more reason to be very restrictive in the use of methylphenidate.