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Background Myasthenia gravis (MG) leads to exertion-dependent muscle weakness, but also psychological and social well-being are limited. We aim to describe the burden of disease in MG including sociodemographic, economical, psychosocial as well as clinical aspects, to compare health-related quality of life (HRQoL) of patients with MG to the general population (genP) and to explore risk factors for a lower HRQoL. Methods This case–control study was conducted with MG patients of the German Myasthenia Association. A questionnaire-based survey included sociodemographic and clinical data as well as standardized questionnaires, e.g. the Short Form Health (SF-36). HRQoL was compared to genP in a matched-pairs analysis. Participants of the German Health Interview and Examination Survey for Adults (DEGS1) served as control group. Results In our study, 1660 MG patients participated and were compared to 2556 controls from the genP. Patients with MG showed lower levels of physical functioning (SF-36 mean 56.0, SD 30.3) compared to the genP (mean 81.8, SD 22.1, adjusted difference: 25, 95% CI 22–29) and lower mental health sub-score (SF-36 mean 67.3, SD 19.8, vs. 74.1, SD 16.7, adjusted difference: 5, 95% CI 2–8). Female gender, higher age, low income, partnership status, lower activities of daily life, symptoms of depression, anxiety and fatigue and self-perceived low social support were associated with a lower HRQoL in MG patients. Discussion HRQoL is lower in patients with MG compared to genP. The burden of MG on patients includes economic and social aspects as well as their emotional well-being. New therapies must achieve improvements for patients in these areas. Trial registration information Clinicaltrials.gov, NCT03979521, submitted: June 7, 2019, first patient enrolled: May 1, 2019, https://clinicaltrials.gov/ct2/show/NCT03979521

Dementia due to Alzheimer's Disease (AD) is a neurodegenerative disease for which treatment strategies at an early stage are of great clinical importance. So far, there is still a lack of non-invasive diagnostic tools to sensitively detect AD in early stages and to predict individual disease progression. Magnetic resonance elastography (MRE) of the brain may be a promising novel tool. In this proof-of-concept study, we investigated whether multifrequency-MRE (MMRE) can detect differences in hippocampal stiffness between patients with clinical diagnosis of dementia due to AD and healthy controls (HC). Further, we analyzed if the combination of three MRI-derived parameters, i.e., hippocampal stiffness, hippocampal volume and mean diffusivity (MD), improves diagnostic accuracy.Diagnostic criteria for probable dementia due to AD were in line with the NINCDS-ADRDA criteria and were verified through history-taking (patient and informant), neuropsychological testing, routine blood results and routine MRI to exclude other medical causes of a cognitive decline.21 AD patients and 21 HC (median age 75 years) underwent MMRE and structural MRI, from which hippocampal volume and MD were calculated. From the MMRE-images maps of the magnitude |G*| and phase angle φ of the complex shear modulus were reconstructed using multifrequency inversion. Median values of |G*| and φ were extracted within three regions of interest (hippocampus, thalamus and whole brain white matter). To test the predictive value of the main outcome parameters, we performed receiver operating characteristic (ROC) curve analyses.Hippocampal stiffness (|G*|) and viscosity (φ) were significantly lower in the patient group (both p < 0.001). ROC curve analyses showed an area under the curve (AUC) for | G*| of 0.81 [95%CI 0.68–0.94]; with sensitivity 86%, specificity 67% for cutoff at |G*| = 980 Pa) and for φ an AUC of 0.79 [95%CI 0.66–0.93]. In comparison, the AUC of MD and hippocampal volume were 0.83 [95%CI 0.71–0.95] and 0.86 [95%CI 0.74–0.97], respectively. A combined ROC curve of |G*|, MD and hippocampal volume yielded a significantly improved AUC of 0.90 [95%CI 0.81–0.99].In conclusion, we demonstrated reduced hippocampal stiffness and reduced hippocampal viscosity, as determined by MMRE, in patients with clinical diagnosis of dementia of the AD type. Diagnostic sensitivity was further improved by the combination with two other MRI-based hippocampal parameters. These findings motivate further investigation whether MMRE can detect decreased brain stiffness already in pre-dementia stages, and whether these changes predict cognitive decline.

Background and Purpose-Whether the time of hospital admission is relevant for short-term outcome after stroke is under debate and may depend on care facilities. Methods-We retrospectively analyzed medical records from patients who received thrombolytic therapy within 4.5 hours of stroke onset in a stroke unit of the Charité-University Hospital Berlin (Charité; nϭ291) or within the stroke telemedicine (TEMPiS) network, comprising 12 community hospitals with telestroke units in Bavaria (nϭ616). Results-Thrombolytic therapy was administered during nonworking hours in 59.5% (Charité) and 55.0% (TEMPiS) of patients. A trend toward a lower rate of symptomatic intracranial hemorrhage (3.4% versus 9.2%; Pϭ0.053), clinical worsening (11.9% versus 19.7%; Pϭ0.079), and 7-day mortality (3.4% versus 8.7%; Pϭ0.073) after admission during working hours was seen at Charité. However, multivariable analysis did not show a significant impact of the time of admission on clinical worsening, symptomatic intracranial hemorrhage, or 7-day mortality in both cohorts. Thrombolysis based on brain computed tomography instead of magnetic resonance imaging (odds ratioϭ4.98, 95% CI, 1.09 to 22.7) and more severe National Institutes of Health Stroke Scale score on admission (odds ratioϭ1.15 per point; 95% CI, 1.07 to 1.24) were associated with 7-day mortality at Charité. National Institutes of Health Stroke Scale score on admission (odds ratioϭ1.13 per point; 95% CI, 1.06 to 1.19) and older age (odds ratioϭ1.05 per year; 95% CI, 1.004 to 1.09) were correlated with 7-day mortality in TEMPiS. National Institutes of Health Stroke Scale on admission was the only independent predictor of symptomatic intracranial hemorrhage or clinical worsening in both cohorts. Conclusions-The majority of stroke patients received thrombolysis during nonworking hours. The time of hospital admission did not significantly influence the short-term outcome after thrombolysis. (Stroke. 2011;42:2521-2525.)

Alteration of cerebral perfusion can be considered as a possible therapeutic target in mild cognitive impairment. This randomized, placebo-controlled, double-blind proof-of-concept study assessed effects of omega-3 fatty acids on cerebral perfusion in patients with mild cognitive impairment. In thirteen patients (omega:n=5; placebo:n=8) cerebral perfusion was measured before and after 26-weeks intervention within posterior cortical regions using magnetic resonance imaging. There was a medium effect of intervention on cerebral blood flow (η2=0.122) and blood volume (η2=0.098). The omega group showed an increase in blood flow (mean difference: 0.02 [corresponds to 26.1%], 95% confidence interval:0.00-0.05) and blood volume (mean difference: 0.08 [corresponds to 18.5%], 95% confidence interval:0.01-0.15), which was not observed in the placebo group. These preliminary findings suggest that omega-3 fatty acids supplementation may improve perfusion in cerebral regions typically affected in mild cognitive impairment.Regulation of perfusion may help to maintain brain structure and function and potentially delay conversion to dementia.

Background: In acute ischemic stroke, brain imaging is mandatory in the decision whether to perform intravenous thrombolysis with recombinant tissue plasminogen activator. The most widespread used imaging modality to exclude intracranial hemorrhage is plain computed tomography (CT). However, there is an ongoing debate whether the information provided by magnetic resonance imaging (MRI) could improve the selection of patients for thrombolysis. We investigated whether the choice of imaging modality (MRI vs. CT) affects therapy safety and the patients' outcome. Methods: Analyses are based on data from a prospective, single-center observational study that included all patients with acute ischemic stroke who received intravenous thrombolysis within 4.5 h. Stroke severity was assessed by the National Institutes of Health Stroke Scale. Safety was assessed by rates of symptomatic intracranial hemorrhage (SICH), brain edema with mass effect and 7-day mortality. Outcome was assessed at 3 months as mortality and proportion of independent patients (modified Rankin Scale score between 0 and 2). Results: We analyzed 345 patients of whom 141 received multimodal MRI and 204 received plain CT prior to treatment. Groups did not differ significantly in terms of age, neurological deficit, rate of elevated glucose level or rate of very high blood pressure. However, patients with CT-based thrombolysis had significantly higher rates of cardiac comorbidities (coronary artery disease, heart failure). In the MRI group, we observed a lower rate of 7-day mortality (1 vs. 10%; p = 0.001), a lower rate of SICH (1 vs. 6%; p = 0.010) and a nonsignificantly lower rate of brain edema with mass effect (2 vs. 6%; n.s.). In multivariable analysis, 7-day mortality was independently associated with MRI-based thrombolysis, even if cardiac comorbidities were taken into account. For mortality at 3 months, there was a nonsignificant difference in favor of the MRI group (16 vs. 23%; n.s.). In multivariable analyses, mortality at 3 months was independently associated with older age, higher stroke severity, brain edema with mass effect, SICH, pneumonia and coronary artery disease. Neither mortality nor independent outcome was influenced by initial imaging modality. Conclusions: Thrombolysis based on multimodal MRI is associated with reduced rates of SICH and early death. Our results suggest that these complications affect survival principally in the acute phase after thrombolysis. However, nonneurological and especially cardiac comorbidities also influence survival after stroke and are underrepresented in stroke patients undergoing MRI. Selection bias has to be considered.

Acute hepatic porphyrias (AHP) can cause severe neurological symptoms involving the central, autonomic, and peripheral nervous system. Due to their relative rarity and their chameleon-like presentation, delayed diagnosis and misdiagnosis are common. AHPs are genetically inherited disorders that result from heme biosynthesis enzyme deficiencies and comprise four forms: acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), and ALA-dehydratase porphyria (ALADP). Depending on the clinical presentation, the main differential diagnoses are Guillain-Barré syndrome and autoimmune encephalitis. Red flags that could raise the suspicion of acute porphyria are neurological symptoms starting after severe (abdominal) pain, in association with reddish urine, hyponatremia or photodermatitis, and the presence of encephalopathy and/or axonal neuropathy. We highlight the diagnostic difficulties by presenting three cases from our neurological intensive care unit and give a comprehensive overview about the diagnostic findings in imaging, electrophysiology, and neuropathology.

Background: Anti-glutamic acid decarboxylase antibody (GAD-ab)-associated cerebellar ataxia is a rare neurological disorder characterized by cerebellar symptoms concomitant with high GAD-ab levels in serum and cerebrospinal fluid (CSF). Case Report: We report on 2 female siblings (aged 74 and 76 years) presenting with gradual progression of rotational vertigo, gait ataxia and vertical diplopia, continuously progressing for 6 months and 6 years, respectively. Autoimmune laboratory examinations showed remarkably increased serum and CSF GAD-ab levels. Their medical histories revealed late-onset type 1 diabetes mellitus (T1DM) and other concomitant autoimmune disorders (Grave's disease, Hashimoto's thyroiditis). Cerebral MRI and laboratory examinations were unremarkable. The diagnosis of GAD-ab-associated cerebellar ataxia with particular brainstem involvement was established in both women. After the exclusion of an underlying malignancy, immunosuppressive therapy has been initiated in both patients, which resulted in stabilization in one and in clinical improvement in the other patient. Discussion: The unique association of autoantibody-mediated cerebellar ataxia and late-onset T1DM in 2 siblings with similar clinical and paraclinical phenotypes strengthens the concept that hereditary factors might play a relevant role also in autoimmune diseases so far considered to be sporadic. Moreover, the occurrence of continuous vertical diplopia broadens the clinical spectrum of GAD-ab-associated neurological syndromes.