Verum versus sham tDCS in the treatment of stroke-induced apraxia: study protocol of the randomized controlled trial RAdiCS -“Rehabilitating (stroke-induced) Apraxia with direct Current Stimulation”

IntroductionStroke is the leading cause of acquired disability in western societies. (Motor) cognitive deficits like apraxia significantly contribute to disability after stroke, harming activities of daily living and rehabilitation outcome. To date, efficient therapeutic options for apraxia remain sparse. Thus, randomized controlled trials (RCTs) are warranted.MethodsBased on promising results of a pilot study, the on-going RAdiCS (Rehabilitating stroke-induced Apraxia with direct Current Stimulation) study is a randomized controlled trial, which follows a double-blinded (investigator and patient), two-arm parallel interventional model. It is designed to include 110 apraxic patients (as diagnosed by the Cologne Apraxia Screening, KAS) in the subacute phase after a left hemisphere (LH) stroke. The University of Cologne initiated the trial, which is conducted in two German Neurorehabilitation Centers.The study aims to evaluate the effect of anodal (versus sham) transcranial direct current stimulation (tDCS) applied over the left posterior parietal cortex (PPC) with an intensity of 2 mA for 10 min on five consecutive days on apraxic deficits. In addition to anodal or sham tDCS, all LH stroke patients undergo a motor (cognitive) training that is performed before and after the stimulation (off-line stimulation).The primary outcome measure is the (differential) change in the overall KAS score after five daily sessions of anodal versus sham tDCS when compared to the baseline assessment before tDCS. Secondary study outcomes include further apraxia scores, aphasia severity, and measures of motor performance and disability after stroke. All outcome measures are obtained in the post-stimulation assessment as well as during follow-up (3–4 months after tDCS)

Neuro-COVID-19 is more than anosmia: clinical presentation, neurodiagnostics, therapies, and prognosis

Purpose of review To provide an overview on current knowledge of neurological symptoms and complications of COVID-19, and to suggest management concepts. Recent findings Headache, dizziness, excessive tiredness, myalgia, anosmia/hyposmia, and ageusia/dysgeusia are common nonspecific neurological manifestations during early COVID-19 disease found in the majority of patients. Less frequent but more severe and specific neurological manifestations include Guillain--Barre syndrome, encephalopathy, encephalitis/meningitis, epileptic seizures, and cerebrovascular events. Beyond standard neurological examination, these require a more extensive work-up, including cerebrospinal fluid assessment, neurophysiological evaluation, neuroimaging, and cognitive testing. Symptomatic treatment is advisable unless the neurological complication's immune pathogenesis is proven. Summary Neurological manifestations of COVID-19 occur during the acute, para-infectious, and 'recovery' phase. Therapeutic management depends on the clinical presentation and neurological work-up

Successful treatment of thromboses of major arteries after ChAdOx1 nCov-19 vaccination

The ChAdOx1 nCoV-19 adenoviral vector vaccine to prevent contracting Covid-19 caused by infection with SARS-CoV-2 has been associated with vaccine-induced immune thrombotic thrombocytopenia (VITT) primarily leading to venous thromboses. Here, we report two cases of major arterial occlusions after ChAdOx1 nCov-19 vaccination, comprising a 42-year-old woman with thrombotic occlusion of the left carotid artery, and a 62-year-old man with occlusion of distal aorta and iliac arteries. Both were successfully treated with intravenous immunoglobulins and non-heparin anticoagulant agents leading to a beneficial short-term outcome of 6 weeks in case 1 and four months in case 2

COVID-19 and neurological training in Europe: from early challenges to future perspectives

The worldwide SARS-CoV-2 pandemic is dramatically affecting health systems with consequences also for neurological residency training. Here we report early experiences and challenges that European neurologists and residents faced. The breadth of the pandemic and the social restrictions induced substantial modifications in both inpatient and outpatient clinical care and academic activities as well, adversely affecting our residency training. On the other hand we see also opportunities, such as gaining more clinical and professional skills. All these drastic and sudden changes lead us to reconsider some educational aspects of our training program that need to be improved in order to better prepare the neurologists of the future to manage unexpected and large emergency situations like the one we are living in these days. A reconsideration of the neurological training program could be beneficial to guarantee high standard level of the residency training in this period and beyond

A systematic review of neurological symptoms and complications of COVID-19

ObjectiveTo study the frequency of neurological symptoms and complications in COVID-19 patients in a systematic review of the literature.MethodsRelevant 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).ResultsA 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.ConclusionThe 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

Gesture meaning modulates the neural correlates of effector-specific imitation deficits in left hemisphere stroke

BackgroundPrevious studies on left hemisphere (LH) stroke patients reported effector-specific (hand, fingers, bucco-facial) differences in imitation performance. Furthermore, imitation performance differed between meaningless (ML) and meaningful (MF) gestures. Recent work suggests that a gesture’s meaning impacts the body-part specificity of gesture imitation.MethodsWe tested the hypothesis that the gesture’s meaning (ML vs MF) affects the lesion correlates of effector-specific imitation deficits (here: bucco-facial vs arm/hand gestures) using behavioural data and support vector regression-based lesion-symptom mapping (SVR-LSM) in a large sample of 194 sub-acute LH stroke patients.ResultsBehavioural data revealed a significant interaction between the effector used for imitation and the meaning of the imitated gesture. SVR-LSM analyses revealed shared lesion correlates for impaired imitation independent of effector or gesture meaning in the left supramarginal (SMG) and superior temporal gyri (STG). Besides, within the territory of the left middle cerebral artery, impaired imitation of bucco-facial gestures was associated with more anterior lesions, while arm/hand imitation deficits were associated with more posterior lesions. MF gestures were specifically associated with lesions in the left inferior frontal gyrus and the left insular region. Notably, an interaction of effector-specificity and gesture meaning was also present at the lesion level: A more pronounced difference in imitation performance between the effectors for ML (versus MF) gestures was associated with left-hemispheric lesions in the STG, SMG, putamen, precentral gyrus and white matter tracts.ConclusionThe current behavioural data show that ML gestures are particularly sensitive in assessing effector-specific imitation deficits in LH stroke patients. Moreover, a gesture’s meaning modulated the effector-specific lesion correlates of bucco-facial and arm/hand gesture imitation. Hence, it is crucial to consider gesture meaning in apraxia assessments

A systematic review of neurological symptoms and complications of COVID-19

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

Status of clinical research in neurology in Germany-A national survey

Background and purpose To provide an overview on the status of clinical research in neurology in Germany. Methods German university hospitals, nonuniversity hospitals, and neurological medical practices were surveyed regarding their clinical research activities during the period 2013 to 2017. Results Fifty percent of university hospitals, 10.6% of nonuniversity hospitals, and 5.2% of medical practices in Germany responded to our questionnaire. More than 80% of the clinical studies conducted have been phase III/IV and noninterventional trials (NISs), whereas <1% have been phase I and 3.5% investigator-initiated trials (IITs). University hospitals have conducted most of the phase II-IV trials. NISs have been predominantly performed by medical practices. Fifty-six percent of the university hospitals and less of the nonuniversity institutions confirmed the implementation of standard operating procedures (SOPs). In university hospitals, on average, 11 physicians had acquired a good clinical practice certificate. Overall, 43% of all trials have been performed in neuroimmunology. Conclusions The status of clinical research in neurology in Germany is predominated by NISs and late-phase trials, potentially due to a general lack of easily accessible funding, which leads to a highly competitive environment and fewer opportunities to perform early-phase clinical trials as well as IITs. Our results indicate that there is substantial need for structured support for creating and implementing SOPs to maintain quality standards and guarantee uniformity of performance. This survey assessed many aspects of clinical research and serves as guidance for providing ideas for structured improvement of clinical research in neurology in Germany

Neurological symptoms and complications in predominantly hospitalized COVID‐19 patients: Results of the European multinational Lean European Open Survey on SARS‐Infected Patients (LEOSS)

Background and purposeDuring acute coronavirus disease 2019 (COVID-19) infection, neurological signs, symptoms and complications occur. We aimed to assess their clinical relevance by evaluating real-world data from a multinational registry.MethodsWe analyzed COVID-19 patients from 127 centers, diagnosed between January 2020 and February 2021, and registered in the European multinational LEOSS (Lean European Open Survey on SARS-Infected Patients) registry. The effects of prior neurological diseases and the effect of neurological symptoms on outcome were studied using multivariate logistic regression.ResultsA total of 6537 COVID-19 patients (97.7% PCR-confirmed) were analyzed, of whom 92.1% were hospitalized and 14.7% died. Commonly, excessive tiredness (28.0%), headache (18.5%), nausea/emesis (16.6%), muscular weakness (17.0%), impaired sense of smell (9.0%) and taste (12.8%), and delirium (6.7%) were reported. In patients with a complicated or critical disease course (53%) the most frequent neurological complications were ischemic stroke (1.0%) and intracerebral bleeding (ICB; 2.2%). ICB peaked in the critical disease phase (5%) and was associated with the administration of anticoagulation and extracorporeal membrane oxygenation (ECMO). Excessive tiredness (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.20–1.68) and prior neurodegenerative diseases (OR 1.32, 95% CI 1.07–1.63) were associated with an increased risk of an unfavorable outcome. Prior cerebrovascular and neuroimmunological diseases were not associated with an unfavorable short-term outcome of COVID-19.ConclusionOur data on mostly hospitalized COVID-19 patients show that excessive tiredness or prior neurodegenerative disease at first presentation increase the risk of an unfavorable short-term outcome. ICB in critical COVID-19 was associated with therapeutic interventions, such as anticoagulation and ECMO, and thus may be an indirect complication of a life-threatening systemic viral infection