Objective
To study the frequency of neurological symptoms and complications in COVID-19 patients in a systematic review of the literature.
Methods
Relevant studies were identified through electronic ...explorations of PubMed, medRxiv, and bioRxiv. Besides, three Chinese databases were searched. A snowballing method searching the bibliographies of the retrieved references was applied to identify potentially relevant articles. Articles published within 1 year prior to April 20th, 2020, were screened with no language restriction imposed. Databases were searched for terms related to SARS-CoV-2/COVID-19 and neurological manifestations, using a pre-established protocol registered on the International Prospective Register of Systematic Reviews database (ID: CRD42020187994).
Results
A total of 2441 articles were screened for relevant content, of which 92 full-text publications were included in the analyses of neurological manifestations of COVID-19. Headache, dizziness, taste and smell dysfunctions, and impaired consciousness were the most frequently described neurological symptoms, the latter more often among patients with a severe or critical disease course. To date, only smaller cohort studies or single cases have reported cerebrovascular events, seizures, meningoencephalitis, and immune-mediated neurological diseases, not suitable for quantitative analysis.
Conclusion
The most frequent neurological symptoms reported in association with COVID-19 are non-specific for the infection with SARS-CoV-2. Although SARS-CoV-2 may have the potential to gain direct access to the nervous system, so far, SARS-CoV-2 was detected in the cerebrospinal fluid in two cases only. Standardized international registries are needed to clarify the clinical relevance of the neuropathogenicity of SARS-CoV-2 and to elucidate a possible impact of SARS-CoV-2 infection on common neurological disease, such as Alzheimer’s, Parkinson’s disease or multiple sclerosis.
Abstract
In 2001, the German Multiple Sclerosis Society, facing lack of data, founded the German MS Registry (GMSR) as a long-term data repository for MS healthcare research. By the establishment of ...a network of participating neurological centres of different healthcare sectors across Germany, GMSR provides observational real-world data on long-term disease progression, sociodemographic factors, treatment and the healthcare status of people with MS. This paper aims to illustrate the framework of the GMSR. Structure, design and data quality processes as well as collaborations of the GMSR are presented. The registry’s dataset, status and results are discussed. As of 08 January 2021, 187 centres from different healthcare sectors participate in the GMSR. Following its infrastructure and dataset specification upgrades in 2014, more than 196,000 visits have been recorded relating to more than 33,000 persons with MS (PwMS). The GMSR enables monitoring of PwMS in Germany, supports scientific research projects, and collaborates with national and international MS data repositories and initiatives. With its recent pharmacovigilance extension, it aligns with EMA recommendations and helps to ensure early detection of therapy-related safety signals.
Background
A moderate to high level of physical activity, including regular exercise, represents an established behavioral and rehabilitative approach for persons with multiple sclerosis (pwMS). ...Although being increasingly proposed to limit disease activity and progression, high-quality evidence is lacking.
Objective
The objective of the study is to provide valuable information for MS clinicians and researchers by systematically evaluating the current state of evidence (i) whether exercise interventions affect established clinical measures of disease activity and progression in pwMS (i.e., EDSS, relapse rate, lesion load, brain volume, MSFC) and (ii) how the physical activity and fitness level interact with these measures.
Methods
Literature search was conducted in MEDLINE, EMBASE, CINAHL, and SPORTDiscus. Evaluation of evidence quality was done based on standards published by The American Academy of Neurology.
Results
It is likely that exercise improves the MSFC score, whereas the EDSS score, lesion load, and brain volume are likely to remain unchanged over the intervention period. It is possible that exercise decreases the relapse rate. Results from cross-sectional studies indicate beneficial effects of a high physical activity or fitness level on clinical measures which, however, is not corroborated by high evidence quality.
Conclusions
A (supportive) disease-modifying effect of exercise in pwMS cannot be concluded. The rather low evidence quality of existing RCTs underlines the need to conduct more well-designed studies assessing different measures of disease activity or progression as primary end points. A major limitation is the short intervention duration of existing studies which limits meaningful exercise-induced effects on most disability measures. Findings from cross-sectional studies are difficult to contextualize regarding clinical importance due to their solely associative character and low evidence quality.
PROSPERO registration number
CRD42020188774.
Multiple sclerosis (MS) is the most common neurological immune-mediated disease leading to disability in young adults. The outcome of the disease is unpredictable, and over time, neurological ...disabilities accumulate. Interferon beta-1b was the first drug to be approved in the 1990s for relapsing-remitting MS to modulate the course of the disease. Over the past two decades, the treatment landscape has changed tremendously. Currently, more than a dozen drugs representing 1 substances with different mechanisms of action have been approved (interferon beta preparations, glatiramer acetate, fingolimod, siponimod, mitoxantrone, teriflunomide, dimethyl fumarate, cladribine, alemtuzumab, ocrelizumab, and natalizumab). Ocrelizumab was the first medication to be approved for primary progressive MS. The objective of this review is to present the modes of action of these drugs and their effects on the immunopathogenesis of MS. Each agent's clinical development and potential side effects are discussed.
Progressive multifocal leukoencephalopathy (PML) is an opportunistic viral disease of the brain—caused by human polyomavirus 2. It affects patients whose immune system is compromised by a ...corresponding underlying disease or by drugs. Patients with an underlying lymphoproliferative disease have the worst prognosis with a mortality rate of up to 90%. Several therapeutic strategies have been proposed but failed to show any benefit so far. Therefore, the primary therapeutic strategy aims to reconstitute the impaired immune system to generate an effective endogenous antiviral response. Recently, anti-PD-1 antibodies and application of allogeneic virus-specific T cells demonstrated promising effects on the outcome in individual PML patients. This article aims to provide a detailed overview of the literature with a focus on these two treatment approaches.
In persons with multiple sclerosis (PwMS), the neutrophil-to-lymphocyte ratio (NLR) is associated with disability status, symptomatology and disease activity. High-intensity interval training (HIIT) ...improves many symptoms in PwMS and may positively influence disease progression. Here, we present results from a randomized controlled trial during inpatient rehabilitation on immediate (single bout) and training (3-week intervention) effects of HIIT versus moderate continuous training on NLR and related cellular inflammation markers. Only HIIT reduced the NLR over the 3-week intervention period. These training effects might be due to repetitive inflammatory states with compensatory anti-inflammatory counterbalancing after each HIIT session.
Objectives
To test if the early kinetics of neurofilament light (NFL) in blood adds to the absolute values of NFL in the prediction of outcome, and to evaluate if NFL can discriminate individuals ...with severe hypoxic–ischemic brain injury (sHIBI) from those with other causes of poor outcome after out-of-hospital cardiac arrest (OHCA).
Design and setting
Monocentric retrospective study involving individuals following non-traumatic OHCA between April 2014 and April 2016. NFL concentrations were determined on a SiMoA HD-1 device using NF-Light Advantage Kits.
Participants
Of 73 patients screened, 53 had serum samples available for NFL measurement at three timepoints (after 3, 24, and 48 h of admission). Of these 53 individuals, 43.4% had poor neurologic outcome at discharge as assessed by Glasgow–Pittsburgh cerebral performance categories, and, according to a current prognostication algorithm, poor outcome due to sHIBI in 20.7%.
Main outcome measure
Blood NFL and its early kinetics for prognostication of outcome and prediction of sHIBI after OHCA.
Results
An absolute NFL > 508.6 pg/ml 48 h after admission, or a change in NFL > 494 pg/ml compared with an early baseline value predicted outcome, and discriminated severe sHIBI from other causes of unfavorable outcome after OHCA with high sensitivity (100%, 95%CI 70.0–100%) and specificity (91.7%, 95%CI 62.5–100%).
Conclusions
Not only absolute values of NFL, but also early changes in NFL predict the outcome following OHCA, and may differentiate sHIBI from other causes of poor outcome after OHCA with high sensitivity and specificity. Our study adds to published data, overall corroborating that NFL measured in blood should be implemented in prognostication algorithms used in clinical routine.
Objective
To compare the available diagnostic criteria for progressive multifocal leukoencephalopathy (PML) diagnosis in a real-world cohort of patients with natalizumab-associated PML and to explore ...opportunities for improvement of such criteria in the context of pharmacovigilance of immunosuppressive therapies.
Methods
We applied the “Mentzers PML case definition” to a dataset of 28 patients with natalizumab-associated PML (many of whom were identified through MRI screening in the context of pharmacovigilance), who were previously rated according to the American Academy of Neurology (AAN) PML diagnostic criteria, and compared the response to both sets of criteria.
Results
The “Mentzers case definition” resulted in a level of certainty 1–3 in patients with a positive JC virus PCR, termed ‘definite’ and ‘probable’ PML according to the AAN diagnostic criteria. Patients that tested negative for JC virus in CSF (29%) were classified level 4 by the “Mentzers case definition”, neglecting the longitudinal clinical and radiological signs of PML available, while the AAN diagnostic criteria separated these patients in ‘possible’ and ‘not PML’.
Conclusions
Both the AAN PML diagnostic criteria and the “Mentzers case definition” require the positive detection of JC virus DNA in CSF to define patients at a higher degree of suspicion of PML. However, as sensitivity of JC virus PCR in CSF is limited and often returns negative in particular in early cases of PML with a mere MRI-based PML suspicion, both criteria have obvious limitations when frequent MRI is used for pharmacovigilance purposes. Thus, revision of PML diagnostic criteria is needed, including the incorporation of lesion evolution, and longitudinal CSF studies that also assess for the presences of intrathecally produced anti-JC virus antibodies.
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