Alexander Mohr

Acute disseminated encephalomyelitis: A follow-up study of 40 adult patients

Objectives: To describe the clinical, CSF, and radiologic findings and long-term follow-up in a cohort of patients with acute disseminated encephalomyelitis (ADEM), and to determine possible prognostic factors for progression to MS. Methods: Forty adults (28 women, mean age 33.5 years) diagnosed with ADEM were analyzed. Clinical symptoms, cranial MRI and CSF findings, and the response to a standardized treatment during the acute phase of the disease were analyzed by chart review. The final diagnosis of ADEM or clinically definite MS was established upon follow-up examination after 8 to 137 months. The patients with ADEM and MS were compared to detect differences between the two groups. Results: Fifteen patients had a preceding infection (n = 14) or immunization (n = 1). The most frequent clinical signs were motor deficit (80%), followed by sensory deficits, brainstem signs, and ataxia. CSF findings were highly variable; normal results were present in 20% of patients. Oligoclonal bands were positive in 65% of patients. Ninety-five percent of all patients improved during the acute phase of the disease. Upon follow-up, 14 patients had developed clinically definite MS. Of the 26 patients with the final diagnosis of ADEM, two patients had died, nine had minor deficits, three had moderate deficits, and 12 patients had no remaining symptoms. Patients with the final diagnosis of ADEM were older, and more often had a preceding infection, clinical signs of brainstem involvement, a higher CSF albumin fraction, and infratentorial lesions. Conclusions: Many patients initially diagnosed with ADEM develop clinically definite MS upon long-term follow-up. The authors found no useful diagnostic criteria for the differentiation of a first episode of MS from monophasic ADEM. The term ADEM may still be employed as a description of a clinical syndrome, but should not be used as a distinct entity until reliable diagnostic criteria have been developed.

Stroke magnetic resonance imaging within 6 hours after onset of hyperacute cerebral ischemia.

We studied the diagnostic and prognostic value of diffusion‐ and perfusion‐weighted magnetic resonancce imaging (DWI and PWI) for the initial evaluation and follow‐up monitoring of patients with stroke that had ensued less than 6 hours previously. Further, we examined the role of vessel patency or occlusion and subsequent recanalization or persistent occlusion for further clinical and morphological stroke progression so as to define categories of patients and facilitate treatment decisions. Fifty‐one patients underwent stroke magnetic resonance imaging (DWI, PWI, magnetic resonance angiography, and T2‐weighted imaging) within 3.3 ± 1.29 hours, and, of those, 41 underwent follow‐up magnetic resonance imaging on day 2 and 28 on day 5. In addition, we assessed clinical scores (on the National Institutes of Health Stroke Scale, Scandinavian Stroke Scale, Barthel Index, and Modified Rankin Scale) on days 1, 2, 5, 30, and 90 and performed volumetric analysis of lesion volumes. In all, 25 patients had a proximal, 18 a distal, and 8 no vessel occlusion. Furthermore, 15 of 43 patients exhibited recanalization on day 2. Vessel occlusion was associated with a PWI‐DWI mismatch on the initial magnetic resonance imaging, vessel patency with a PWI‐DWI match (p < 0.0001). Outcome scores and lesion volumes differed significantly between patients experiencing recanalization and those who did not (all p < 0.0001). Acute DWI and PWI lesion volumes correlated poorly with acute clinical scores and only modestly with outcome scores. We have concluded on the basis of this study that early recanalization saves tissue at risk of ischemic infarction and results in significantly smaller infarcts and a significantly better clinical outcome. Patients with proximal vessel occlusions have a larger amount of tissue at risk, a lower recanalization rate, and a worse outcome. Urgent recanalization seems to be of utmost importance for these patients. Ann Neurol 2001;49:460–469

Magnetic resonance imaging evidence of cytotoxic cerebral edema in acute mountain sickness.

The present study applied T2- and diffusion-weighted magnetic resonance imaging to examine if mild cerebral edema and subsequent brain swelling are implicated in the pathophysiology of acute mountain sickness (AMS). Twenty-two subjects were examined in normoxia (21% O2), after 16 hours passive exposure to normobaric hypoxia (12% O2) corresponding to a simulated altitude of 4,500 m and after 6 hours recovery in normoxia. Clinical AMS was diagnosed in 50% of subjects during hypoxia and corresponding headache scores were markedly elevated (P < 0.05 versus non-AMS). Hypoxia was associated with a mild increase in brain volume (+ 7.0 ± 4.8 ml, P < 0.05 versus preexposure baseline) that resolved during normoxic recovery. Hypoxia was also associated with an increased T2 relaxation time (T2rt) and a general trend toward an increased apparent diffusion coefficient (ADC). During the normoxic recovery, brain volume and T2rt recovered to pre-exposure baseline values, whereas a more marked reduction in ADC in the splenium of the corpus callosum (SCC) was observed (P < 0.05). While changes in brain volume and T2rt were not selectively different in AMS, ADC values were consistently lower (P < 0.05 versus non-AMS) and associated with the severity of neurologic symptoms. Acute mountain sickness was also characterized by an increased brain to intracranial volume ratio (P < 0.05 versus non-AMS). These findings indicate that mild extracellular vasogenic edema contributes to the generalized brain swelling observed at high altitude, independent of AMS. In contrast, intracellular cytotoxic edema combined with an anatomic predisposition to a ‘tight-fit’ brain may prove of pathophysiologic significance, although the increase in brain volume in hypoxia was only about 0.5% of total brain volume.

Free Radical-Mediated Damage to Barrier Function is not Associated with Altered Brain Morphology in High-Altitude Headache:

The present study combined molecular and neuroimaging techniques to examine if free radical-mediated damage to barrier function in hypoxia would result in extracellular edema, raise intracranial pressure (ICP) and account for the neurological symptoms typical of high-altitude headache (HAH) also known as acute mountain sickness (AMS). Twenty-two subjects were randomly exposed for 18 h to 12% (hypoxia) and 21% oxygen (O2 (normoxia)) for collection of venous blood (0 h, 8 h, 15 h, 18 h) and CSF (18 h) after lumbar puncture (LP). Electron paramagnetic resonance (EPR) spectroscopy identified a clear increase in the blood and CSF concentration of O2 and carbon-centered free radicals (P > 0.05 versus normoxia) subsequently identified as lipid-derived alkoxyl (LO•) and alkyl (LC•) species. Magnetic resonance imaging (MRI) demonstrated a mild increase in brain volume (7.0 ± 4.8mL or 0.6% ± 0.4%, P > 0.05 versus normoxia) that resolved within 6 h of normoxic recovery. However, there was no detectable evidence for gross barrier dysfunction, elevated lumbar pressures, T2 prolongation or associated neuronal and astroglial damage. Clinical AMS was diagnosed in 50% of subjects during the hypoxic trial and corresponding headache scores were markedly elevated (P > 0.05 versus non-AMS). A greater increase in brain volume was observed, though this was slight, independent of oxidative stress, barrier dysfunction, raised lumbar pressure, vascular damage and measurable evidence of cerebral edema and only apparent in the most severe of cases. These findings suggest that free-radical-mediated vasogenic edema is not an important pathophysiological event that contributes to the mild brain swelling observed in HAH.

Thrombolytic therapy for ischemic stroke--a review. Part II--Intra-arterial thrombolysis, vertebrobasilar stroke, phase IV trials, and stroke imaging.

ObjectiveIntra-arterial thrombolytic therapy for carotid and vertebrobasilar stroke may result in a more rapid clot lysis and higher recanalization rates than can be achieved with intravenous thrombolysis and thus may warrant the more invasive and time-consuming therapeutic approach. We present an overview of all hitherto completed trials of intra-arterial thrombolytic therapy for carotid and vertebrobasilar artery stroke including recommendations for therapy and a meta-analysis. Furthermore, new imaging techniques such as diffusion- and perfusion-weighted magnetic resonance imaging and their impact on patient selection are discussed. Finally, phase IV trials of thrombolysis in general and cost efficacy analyses are presented. Data SourcesWe performed an extensive literature search not only to identify the larger and well-known randomized trials but also to identify smaller pilot studies and case series. Trials included in this review, among others, are the PROACT I and PROACT II studies and the Cochrane Library report. ConclusionIntra-arterial thrombolytic therapy of acute M1 and M2 occlusions with 9 mg/2 hrs pro-urokinase significantly improves outcome if administered within 6 hrs after stroke onset. Seven patients need to be treated to prevent one patient from death or dependence. Vertebrobasilar occlusion has a grim prognosis and intra-arterial thrombolytic therapy to date is the only life-saving therapy that has demonstrated benefit with regard to mortality and outcome, albeit not in a randomized trial. New magnetic resonance imaging techniques may facilitate and improve the selection of patients for thrombolytic therapy. Presently, thrombolytic therapy is still underutilized because of problems with clinical and time criteria, and lack of public and professional education to regard stroke as a treatable emergency. If applied more widely, thrombolytic therapy may result in profound cost savings in health care and reduction of long-term disability of stroke patients.

Individual voxel-based subtype prediction can differentiate progressive supranuclear palsy from idiopathic parkinson syndrome and healthy controls

Voxel‐based morphometry (VBM) shows a differentiated pattern in patients with atypical Parkinson syndrome but so far has had little impact in individual cases. It is desirable to translate VBM findings into clinical practice and individual classification. To this end, we examined whether a support vector machine (SVM) can provide useful accuracies for the differential diagnosis. We acquired a volumetric 3D T1‐weighted MRI of 21 patients with idiopathic Parkinson syndrome (IPS), 11 multiple systems atrophy (MSA‐P) and 10 progressive supranuclear palsy (PSP), and 22 healthy controls. Images were segmented, normalized, and compared at group level with SPM8 in a classical VBM design. Next, a SVM analysis was performed on an individual basis with leave‐one‐out cross‐validation. VBM showed a strong white matter loss in the mesencephalon of patients with PSP, a putaminal grey matter loss in MSA, and a cerebellar grey matter loss in patients with PSP compared with IPS. The SVM allowed for an individual classification in PSP versus IPS with up to 96.8% accuracy with 90% sensitivity and 100% specificity. In MSA versus IPS, an accuracy of 71.9% was achieved; sensitivity, however, was low with 36.4%. Patients with IPS could not be differentiated from controls. In summary, a voxel‐based SVM analysis allows for a reliable classification of individual cases in PSP that can be directly clinically useful. For patients with MSA and IPS, further developments like quantitative MRI are needed. Hum Brain Mapp, 2011.

Thrombolytic therapy for ischemic stroke—A review. Part I—Intravenous thrombolysis

ObjectiveThrombolytic therapy for acute ischemic stroke was implemented into clinical routine 4 yrs ago. Unfortunately, at present <2% of eligible patients receive thrombolytic therapy. We present an overview of all hitherto completed trials of intravenous thrombolytic therapy for carotid artery stroke including recommendations for therapy and diagnostic procedures and their impact on patient selection and meta-analyses. Data Sources We performed an extensive literature search not only to identify the larger and well-known randomized trials but also to identify smaller pilot studies and case series. Trials included in this review, among others, are the National Institute of Neurologic Disorders and Stroke (NINDS) study, European Cooperative Acute Stroke Study I and II, and Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) A and B and two large meta-analyses, including the Cochrane Library report. ConclusionIntravenous thrombolytic therapy with recombinant tissue plasminogen activator has demonstrated a significant benefit and has proven to be safe for patients who can be treated within 3–6 hrs after symptom onset. This benefit is at the cost of an increased rate of symptomatic intracranial hemorrhage without a significant effect on overall mortality. In general, the benefit of thrombolysis decreases and the risks increase with progressing time after symptom onset. Presently, thrombolytic therapy is still underutilized because of problems with clinical and time criteria, and lack of public and professional education to regard stroke as a treatable emergency. If applied more widely, thrombolytic therapy may result in profound cost savings in health care and reduction of long-term disability of stroke patients.

Multi-site voxel-based morphometry--not quite there yet.

Voxel-based morphometry (VBM) is a widely applied method in computational neurosciences but it is currently recommended to compare only data collected at a single MRI scanner. Multi-site VBM would be a desirable approach to increase group size and, thus, statistical power. We aimed to assess if multi-site VBM is feasible on similar hardware and compare the magnitude of inter- and intra-scanner differences. 18 healthy subjects were scanned in two identical 3T MRI scanners using different head coil designs, twice in scanner A and once in scanner B. 3D T1-weighted images were processed with SPM8 and FSL4.1 and compared as paired t-test (scan versus re-scan) on a voxel basis by means of a general linear model (GLM). Additionally, coefficient-of-difference (coeffD) maps were calculated for respective pairs of gray matter segmentations. We found considerable inter-scanner differences clearly exceeding a commonly used GLM significance threshold of p<0.05 (FWE corrected). The spatial pattern of detected differences was dependent on whether SPM8 or FSL4.1 was used. The inclusion of global correcting factors either aggravated (SPM8) or reduced the GLM detected differences (FSL4.1). The coeffD analysis revealed markedly higher variability within the FSL4.1 stream both for the inter- and the intra-scanner comparison. A lowered bias cutoff (30 mm FWHM) in SPM8 improved the comparability for cortical areas. Intra-scanner scan/re-scan differences were generally weaker and did not exceed a p<0.05 (FWE corrected) threshold in the GLM analysis. At 3T profound inter-scanner differences are to be expected that could severely confound an unbalanced VBM analysis. These are like related to the receive bias of the radio-frequency hardware.

T2*-weighted MRI in diagnosis of multiple system atrophy : A practical approach for clinicians

BackgroundPutaminal iron deposition is a histopathological feature of multiple system atrophy (MSA), which is not observed in patients with idiopathic Parkinson’s disease (PD). T2*-weighted magnetic resonance imaging (MRI) gradient echo (GE) sequences are sensitive for paramagnetic susceptibility changes and therefore may support the clinical differential diagnosis between MSA and PD.MethodsWe evaluated putaminal signal intensities on 1.0 Tesla scans of 52 MSA patients, 88 patients with PD and 29 healthy control subjects.ResultsThe typical finding in T2* GE sequences of MSA patients was a signal loss of the dorsolateral putamen, which showed a high specificity (>0.91), but was present in only a subpopulation of patients (sensitivity 0.64–0.69). The combination of the latter with additional presence of a hyperintense lateral rim in fluid attenuated inversion recovery (FLAIR) sequences increased the specificity to 0.97. Using a quantitative evaluation of putaminal signal intensities in defined regions of interest MSA and PD could be discriminated with a diagnostic accuracy (r) of up to 0.82.ConclusionAlthough the separation of groups remains incomplete, the use of T2*-weighted GE sequences combined with FLAIR may be helpful for the differential diagnosis of MSA versus PD considering its fast application, easy evaluation, broad availability, the specificity of findings and the presence of putaminal signal loss already at early disease stages.

Evaluation of angiographic computed tomography in the follow-up after endovascular treatment of cerebral aneurysms—a comparative study with DSA and TOF-MRA

Following coil embolization of intracranial aneurysms, many centers perform at least one digital subtraction angiography (DSA) continuing with time-of-flight magnetic resonance angiography (TOF-MRA). Angiographic computed tomography (ACT) provides high-resolution data from a rotational acquisition of a c-arm-mounted flat panel detector. This study evaluates possible advantages of applying ACT in aneurysm follow-up. In 22 patients DSA examinations with a rotational acquisition were performed. Rotational data were processed into an isotropic high-resolution volume. TOF-MRA was performed the day before DSA. Three experienced neuroradiologists performed a rating of the occlusion rate and a subjective method comparison. Weighted κ statistics were calculated to assess the level of interobserver agreement. Compared to DSA, the diagnostic value of ACT as well as of TOF-MRA was rated to be inferior, although the sensitivity of detecting residual necks was higher with both techniques. Compared to TOF-MRA, ACT achieves favorable ratings only in aneurysms after stent-remodeling. Interobserver agreement was high for all techniques. Ratings of the occlusion rate correlated highly between all observers (r > 0.85, p < 0.001, respectively). In selected patients ACT can add valuable diagnostic information to DSA. TOF-MRA remains a highly sensitive method for aneurysm follow-up.