Impact of vaccination on COVID-19 outcome in multiple sclerosis.

BACKGROUND: COVID-19 continues to challenge neurologists in counselling persons with multiple sclerosis (pwMS) regarding disease-modifying treatment (DMT) and vaccination. The objective here was to characterize predictors of COVID-19 outcome in pwMS. METHODS: We included pwMS with PCR-confirmed COVID-19 diagnosis from a nationwide population-based registry. COVID-19 outcome was classified as either mild or severe. Impact of DMT, specifically anti-CD20 monoclonal antibodies, and vaccination on COVID-19 outcome was determined by multivariable models adjusted for a-priori-risk (determined by a cumulative risk score comprising age, disability and comorbidities). RESULTS: Of 317 pwMS with COVID-19 (mean age 41.8 years [SD 12.4], 72.9% female, median EDSS 1.5 [range 0-8.5], 77% on DMT [16% on antiCD20]), 92.7% had a mild course and 7.3% a severe course with 2.2% dying from COVID-19. Ninety-seven pwMS (30.6%) were fully vaccinated. After a median 5 months from vaccination to SARS-CoV-2 infection (range 1-9), severe COVID-19 occurred in 2.1% of fully vaccinated pwMS compared to 9.5% in unvaccinated pwMS (p=0.018). A-priori-risk robustly predicted COVID-19 severity (R2 0.605; p<0.001). Adjusting for a-priori-risk, anti-CD20 treatment was associated with increased COVID-19 severity (odds ratio [OR] 3.3; R2 0.113; p=0.003), but exposure to any other DMT was not. Fully vaccinated pwMS showed a significantly decreased risk for severe COVID-19 (OR 0.21, R2 0.144, p<0.001). CONCLUSIONS: In a population-based MS cohort, COVID-19 course is primarily predicted by a-priori-risk (depending on age, disability and comorbidities) explaining about 60% of variance. Anti-CD20 treatment is associated with a moderately increased risk, while reassuringly vaccination provides protection from severe COVID-19.

Long-term outcome after COVID-19 infection in multiple sclerosis: a nation-wide multicenter matched-control study.

BACKGROUND: Long-term outcome after COVID-19 in patients with multiple sclerosis (pwMS) is scarcely studied and controlled data are lacking. OBJECTIVE: To compare long-term outcome after COVID-19 in pwMS to a matched control group of pwMS without COVID-19. METHODS: We included pwMS with PCR-confirmed diagnosis of COVID-19 and ≥6 months of follow-up available and, as a control group, pwMS matched 1:1 for age, sex, disability level and disease-modifying treatment type. RESULTS: Of 211 pwMS with COVID-19 (mean age 42.6 years [SD 12.2], 69% female, median EDSS 1.5 [range: 0-7.5], 16% antiCD20), 90.5% initially had a mild COVID-19 course. At follow-up, 70% had recovered completely 3 months (M3) after COVID-19, 83% after 6 months (M6) and 94% after 12 months (M12). Mild initial COVID-19 course was the only significant predictor of complete recovery (odds ratio [OR]: 10.5; p<0.001). Most frequent residual symptoms were fatigue (M3: 18.5%, M6: 13.7%, M12: 7.3%), hyposmia (M3: 13.7%, M6: 5.2%, M12: 1.7%) and dyspnea (M3: 7.1%, M6: 6.6%, M12: 2.8%). Compared to matched controls, fatigue, hyposmia and dyspnea were significantly more frequent at M3 and still slightly at M6, while there was no difference at M12. PwMS with COVID-19 had neither a significantly increased risk for relapses (OR 1.1; p=0.70) nor disability worsening (OR 0.96; p=0.60). DISCUSSION: Long-term outcome of COVID-19 is favourable in a large majority of pwMS with only a small proportion of patients suffering from persistent symptoms usually resolving after 3-6 months. COVID-19 is not associated with increased risk of relapse or disability.

Quantitative trunk sway analysis under challenging gait conditions in early and untreated Parkinson's disease.

INTRODUCTION: Even experienced clinicians may encounter difficulties in making a definitive diagnosis in the early motor stages of Parkinson's disease (PD). We investigated whether quantitative biomechanical trunk sway analysis could support the diagnosis of PD early on. METHODS: We quantified trunk sway performance using body-worn sensors during a test battery of six challenging gait conditions in a cohort of 17 early and untreated PD patients (with evidence of reduced tracer uptake in the basal ganglia on dopamine transporter scans) and 17 age- and sex-matched healthy controls (HCs). RESULTS: Compared to HC, the PD group (Hoehn & Yahr ≤ 2, Unified Parkinson's Disease Rating Scale motor score: mean 13.7 ± 3.5 points) showed significant trunk rigidity in five challenging gait tasks (decreased medio-lateral direction and sway angle area). Post hoc receiver operating characteristic analysis of the significant parameters revealed excellent discrimination with high sensitivity and specificity. CONCLUSION: In the early and untreated motor stages of PD, patients exhibit significant trunk rigidity during challenging gait tasks. Trunk sway motion recorded with body-worn sensors might be a useful tool to disclose a sometimes hard-to-trace cardinal motor sign of PD and support an early clinical diagnosis.

Humoral immune response after COVID-19 in multiple sclerosis: A nation-wide Austrian study.

BACKGROUND: Knowledge on immunity after SARS-CoV-2 infection in patients with multiple sclerosis (pwMS) and the impact of disease-modifying treatment (DMT) is limited. OBJECTIVE: To evaluate degree, duration and potential predictors of specific humoral immune response in pwMS with prior COVID-19. METHODS: Anti-SARS-CoV-2 antibody testing was performed in pwMS with PCR-confirmed diagnosis of symptomatic COVID-19 from a nation-wide registry. Predictors of seropositivity were identified by multivariate regression models. RESULTS: In 125 pwMS (mean age = 42.4 years (SD = 12.3 years), 70% female), anti-SARS-CoV-2 antibodies were detected in 76.0% after a median of 5.2 months from positive PCR. Seropositivity rate was significantly lower in patients on IS-DMT (61.4%, p = 0.001) than without DMT or immunomodulatory DMT (80.6%; 86.0%, respectively). In multivariate analysis, IS-DMT was associated with reduced probability of seropositivity (odds ratio (OR): 0.51; 95% confidence interval (95% CI): 0.17-0.82; p < 0.001). Predefined subgroup analyses showed marked reduction of seropositivity in pwMS on rituximab/ocrelizumab (OR 0.15; 95% CI: 0.05-0.56; p < 0.001). Rate of seropositivity did not change significantly over 6 months. CONCLUSIONS: Humoral immunity is stable after SARS-CoV-2 infection in MS, but is reduced by immunosuppressive DMT, particularly anti-CD20 monoclonal antibodies. This provides important evidence for advising pwMS as well as for planning and prioritizing vaccination.

Assessment of neurological symptoms in adult hydrocephalus occlusus. A pilot study.

BACKGROUND: Comprehensively describe and compare (pre/postoperatively) the clinical symptomatology in adult non-communicated hydrocephalus. Associated hydrocephalus signs were analyzed with the idiopathic Normal Pressure Hydrocephalus Scale (iNPH Scale). A standardized clinical scale for non-communicated hydrocephalus is currently not in use. METHODS: Ten patients with hydrocephalus occlusus (HO) were analyzed. Hydrocephalus signs were examined with the iNPH Scale in gait, neuropsychology, continence, and balance before and three months after treatment with shunt operation or third endoscopic ventriculostomy. RESULTS: Patients significantly improved in iNPH total score (25.8%) and gait score (35.4%) three months after neurosurgical intervention. Domain scores in neuropsychology, continence, and balance reached statistical trends (p ≤ 0.066). Most clinical symptoms and signs at baseline improved after surgery (dizziness, lapse of concentration, gait instability, and headache). CONCLUSION: Patients with non-communicated HO also showed classical hydrocephalus symptoms as communicated in iNPH patients. The iNPH Scale allows a structured neurological assessment over the disease's progress and surgical intervention. Further studies with a larger patient samples are necessary to support our results.

COVID-19 severity and mortality in multiple sclerosis are not associated with immunotherapy: Insights from a nation-wide Austrian registry.

BACKGROUND: The COVID-19 pandemic challenges neurologists in counselling patients with multiple sclerosis (pwMS) regarding their risk by SARS-CoV-2 and in guiding disease-modifying treatment (DMT). OBJECTIVE: To characterize the prevalence and outcome of COVID-19 in pwMS specifically associated with different DMT in a nationwide population-based study. METHODS: We included patients aged ≥18 years with a confirmed diagnosis of MS and a diagnosis of COVID-19 established between January 1, 2020 and December 31, 2020. We classified COVID-19 course as either mild, severe or fatal. Impact of DMT and specifically immunosuppressants (alemtuzumab, cladribine, fingolimod, ocrelizumab or rituximab) on COVID-19 outcome was determined by multivariable models, adjusted for a-priori-risk. RESULTS: Of 126 MS patients with COVID-19 (mean age 43.2 years [SD 13.4], 71% female), 86.5% had a mild course, 9.5% a severe course and 3.2% died from COVID-19. A-priori-risk significantly predicted COVID-19 severity (R2 0.814; p<0.001) and mortality (R2 0.664; p<0.001). Adjusting for this a-priori-risk, neither exposure to any DMT nor exposure to specific immunosuppressive DMT were significantly associated with COVID-19 severity (odds ratio [OR] 1.6; p = 0.667 and OR 1.9; p = 0.426) or mortality (OR 0.5; p = 0.711 and 2.1; 0.233) when compared to no DMT. CONCLUSIONS: In a population-based MS cohort, COVID-19 outcome was not associated with exposure to DMT and immunosuppressive DMT when accounting for other already known risk factors. This provides reassuring evidence that COVID-19 risk can be individually anticipated in MS and-except for a very small proportion of high-risk patients-treatment decisions should be primarily focused on treating MS rather than the pandemic.

N,N-Dimethylglycine in patients with progressive multiple sclerosis: result of a pilot double-blind, placebo, controlled randomized clinical trial.

Oral administration of N,N-Dimethylglycine (DMG), a tertiary amino acid, presumably enhances oxygen utilization by tissue and complex with free radicals. Beneficial effects are improved endurance performance and reduction fatigue in humans and animals. This pilot study reports the results over a one-year double-blind, placebo-controlled trial of DMG in 30 randomized patients with progressive multiple sclerosis. No treatment effects were found between the placebo group and the DMG group for disability, fatigue, cognitive, or gait parameters.

A comprehensive clinico-radiological, neuropsychological and biomechanical analysis approach to patients with idiopathic normal pressure hydrocephalus.

BACKGROUND: A systematic approach to patients with suspected idiopathic normal pressure hydrocephalus (iNPH) is essential to recognize the subset of patients who may benefit from ventriculoperitoneal shunt surgery (VPS). Quantitative biomechanical analysis of gait and balance (QBAGB) may help objectify the response to the cerebrospinal fluid tap test (CSF-TT) and VPS outcome after 3 months and support identification of candidates for VPS. METHODS: We retrospectively reviewed data from all patients with probable iNPH who 1) underwent clinico-radiological and neuropsychological assessments using validated scales (iNPH Scale and iNPH Radscale) at our centre in the period from January to December 2018; and 2) had completed QBAGB before CSF-TT ('baseline'), shortly after CSF-TT, and at three months after either VPS or conservative treatment. RESULTS: At the time-points 'after CSF-TT' and '3 months', patients with iNPH and VPS (n = 11) significantly improved on the Kiefer Scale score, iNPH Scale total score and gait domain score, as well as in gait velocity and step length measured by QBAGB. In contrast, patients without surgery (n = 10) had unchanged iNPH Scale scores and motor performance throughout. Using data from all patients, we calculated cut-off levels for substantial improvements in gait velocity, step length, and the iNPH Scale domain gait score at the time-point 'after CSF-TT'. CONCLUSION: QBAGB helps to objectify the response to CSF-TT to select candidates for VPS and corroborates clinico-radiological and neuropsychological data derived from validated scales. The QBAGB cut-off values for substantial improvement after CSF-TT need further elucidation in larger, preferably prospective studies.

Month-of-birth-effect in multiple sclerosis in Austria.

BACKGROUND: The month-of-birth-effect (MoBE) describes the finding that multiple sclerosis (MS) patients seem to have been born significantly more frequently in spring, with a rise in May, and significantly less often in autumn and winter with the fewest births in November. OBJECTIVES: To analyse if the MoBE can also be found in the Austrian MS population, and if so, whether the pattern is similar to the reported pattern in Canada, United Kingdom, and some Scandinavian countries. METHODS: The data of 7886 MS patients in Austria were compared to all live births in Austria from 1940 to 2010, that is, 7.256545 data entries of the Austrian birth registry and analysed in detail. RESULTS: Patterns observed in our MS cohort were not different from patterns in the general population, even when stratifying for gender. However, the noticeable and partly significant ups and downs over the examined years did not follow the distinct specific pattern with highest birth rates in spring and lowest birth rates in autumn that has been described previously for countries above the 49th latitude. CONCLUSION: After correcting for month-of-birth patterns in the general Austrian population, there is no evidence for the previously described MoBE in Austrian MS patients.

3-week whole body vibration does not improve gait function in mildly affected multiple sclerosis patients--a randomized controlled trial.

OBJECTIVE: To investigate the effects of whole body vibration (WBV) training on gait function in persons with mild multiple sclerosis (MS). DESIGN: A randomized controlled trial. SUBJECTS: 18 patients with MS were assigned randomly to WBV (intervention group) or to placebo WBV. METHODS: Both groups performed a 3-week training period under static conditions on a vibration platform. In the placebo group, the vibration platform was covered and therefore vibrations could not operate. Gait function (gait velocity, stride length, double support phase, single-step variability left and right) was assessed at baseline, after 3-weeks of WBV intervention or sham WBV, 4-weeks after baseline, and 5-weeks after baseline using a mobile plantar food pressure system and the "Timed Up and Go" test under four different gait conditions (comfortable overground gait, comfortable gait on treadmill, -20% comfortable gait velocity on treadmill and +20% comfortable gait velocity on treadmill). RESULTS: None of the outcome measures of gait function showed statistically significant alterations following 3-weeks of intervention/placebo WBV. CONCLUSION: The applied protocol of WBV does not show a meaningful improvement of gait function in mildly affected MS patients.

Neuromyelitis optica in Austria in 2011: to bridge the gap between neuroepidemiological research and practice in a study population of 8.4 million people.

BACKGROUND: In 2008 the Austrian Task Force for Neuromyelitis Optica (NMO) started a nation-wide network for information exchange and multi-centre collaboration. Their aim was to detect all patients with NMO or NMO spectrum disorders (NMO-SD) in Austria and to analyse their disease courses and response to treatment. METHODS: (1) As of March 2008, 1957 serum samples (of 1557 patients) have been tested with an established cell based immunofluorescence aquaporin-4 antibody (AQP4-ab) assay with a high sensitivity and specificity (both >95%). All tests were performed in a single reference laboratory (Clinical Dept. of Neurology of the Innsbruck Medical University). (2) A nation-wide survey with several calls for participation (via email newsletters, articles in the official journal of the Austrian Society of Neurology, and workshops) was initiated in 2008. All collected data will be presented in a way that allows that every individual patient can be traced back in order to ensure transparency and to avoid any data distortion in future meta-analyses. The careful and detailed presentation allows the visualization and comparison of the different disease courses in real time span. Failure and response to treatment are made visible at one glance. Database closure was 31 December 2011. All co-operators were offered co-authorship. RESULTS: All 71 NMO- or NMO-SD patients with AQP4-ab positivity (age range 12.3 to 79.6 years) were analysed in detail. Sex ratio (m:f = 1:7) and the proportion of patients without oligoclonal bands in cerebrospinal fluid (86.6%) were in line with previously published results. All identified patients were Caucasians. CONCLUSIONS: A nationwide collaboration amongst Austrian neurologists with good network communications made it possible to establish a database of 71 AQP4-ab positive patients with NMO/NMO-SD. This database is presented in detail and provides the basis for further studies and international cooperation in order to investigate this rare disease.

Rapidly progressive dementia with thalamic degeneration and peculiar cortical prion protein immunoreactivity, but absence of proteinase K resistant PrP: a new disease entity?

BACKGROUND: Human prion diseases are a group of rare fatal neurodegenerative conditions with well-developed clinical and neuropathological diagnostic criteria. Recent observations have expanded the spectrum of prion diseases beyond the classically recognized forms. RESULTS: In the present study we report six patients with a novel, apparently sporadic disease characterised by thalamic degeneration and rapidly progressive dementia (duration of illness 2-12 months; age at death: 55-81 years). Light and electron microscopic immunostaining for the prion protein (PrP) revealed a peculiar intraneuritic distribution in neocortical regions. Proteinase K resistant PrP (PrPres) was undetectable by Western blotting in frontal cortex from the three cases with frozen tissue, even after enrichment for PrPres by centrifugation or by phosphotungstic acid precipitation. Conformation-dependent immunoassay analysis using a range of PK digestion conditions (and no PK digestion) produced only very limited evidence of meaningful D-N (denatured/native) values, indicative of the presence of disease-associated PrP (PrPSc) in these cases, when the results were compared with appropriate negative control groups. CONCLUSIONS: Our observation expands the spectrum of conditions associated with rapidly progressive dementia and may have implications for the understanding of the pathogenesis of prion diseases.