Neurological Research and Practice最新文献

Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to COVID-19 (COrona VIrus Disease-2019). SARS-CoV-2 acute infection may be associated with an increased incidence of neurological manifestations such as encephalopathy and encephalomyelitis, ischemic stroke and intracerebral hemorrhage, anosmia and neuromuscular diseases. Neurological manifestations are commonly reported during the post-acute phase and are also present in Long-COVID (LCS) and post-COVID-19 syndrome (PCS). In October 2020, the German Society of Neurology (DGN, Deutsche Gesellschaft für Neurologie) published the first guideline on the neurological manifestations of COVID-19. In December 2021 this S1 guideline was revised and guidance for the care of patients with post-COVID-19 syndrome regarding neurological manifestations was added. This is an abbreviated version of the post-COVID-19 syndrome chapter of the guideline issued by the German Neurological society and published in the Guideline repository of the AWMF (Working Group of Scientific Medical Societies; Arbeitsgemeinschaft wissenschaftlicher Medizinischer Fachgesellschaften).

Background: The individualized clinical and public health management of the COVID-19 pandemic have changed over time, including care of people with PD. The objective was to investigate whether in-hospital COVID-19 outcomes and hospital care utilization of people with PD differed between the first two pandemic waves (W) 2020 in Germany.

Methods: We conducted a nationwide cross-sectional study of inpatients with confirmed COVID-19 and PD between March 1 and May 31 (W1), and October 1 and December 31 (W2), 2020 and 2019, using an administrative database. Outcomes were in-hospital mortality, ICU admission rate, change in hospital care utilization, demographical data, PD clinical characteristics, and selected comorbidities. Differences were assessed between waves, PD/non-PD groups, and years.

Results: We identified 2600 PD COVID-19 inpatients in W2 who in total showed higher in-hospital mortality rates and lower ICU admission rates, compared to both W1 (n = 775) and W1/W2 non-PD COVID-19 inpatients (n = 144,355). Compared to W1, W2 inpatients were more long-term care-dependent, older, more of female sex, and had less advanced disease. During both waves, PD inpatients were older, more frequently male and long-term care-dependent, and showed more risk comorbidities than non-PD COVID-19 inpatients. Decreases in hospital care utilization were stronger than average for PD inpatients but relatively weaker during W2. Non-COVID-19 PD inpatients showed poorer in-hospital outcomes in 2020 than in 2019 with better outcomes during W2.

Conclusions: In-hospital COVID-19 outcomes and hospital care utilization of PD patients in Germany differed between the two pandemic waves in 2020 with increased in-hospital mortality for PD COVID-19. Overall hospital care utilization for PD was increased during W2.

Trial registration: No trial registration or ethical approval was required because data were publicly available, anonymized, and complied with the German data protection regulations.

Background: As part of a larger project commissioned by the German Neurological Society (DGN), this paper focuses on the DGN's German and Austrian honorary members. In particular, the question of whether former membership in the National Socialist German Workers' Party (NSDAP) or other Nazi organizations was an obstacle to becoming an honorary member in the years 1952-1982, and whether victims of the Nazi regime were also considered for honorary membership.

Results: From the early 1950s to the early 1980s, the DGN awarded honorary membership to 55 individuals. Of these, 27 were German or Austrian citizens who were physicians during the Nazi era, and 17 of the 27 (63%) were members of the NSDAP, Storm Troopers (SA), or Schutzstaffel (SS). In the early postwar period, honorary membership was much less frequently awarded to former Nazi Party members than in the years around 1980. Sir Ludwig Guttmann, the only neurologist forced to emigrate, received his honorary membership in 1971. Brief biographies of Hans Jacob, Gustav Bodechtel, Karl Kleist, and Ludwig Guttmann outline exemplary careers and life histories, in addition to highlighting key issues such as concurrent research on "euthanasia" victims, denazification procedures, forced emigration, and the contemporary mindset in the Federal Republic of Germany.

Conclusions: Apparently, a "Nazi past" did not play a decisive role in the selection process for honorary members within the DGN until at least the 1980s. Aside from Guttmann, no other neuroscientist expelled from Germany was honored. With these practices, the Society marginalized its Jewish colleagues for a second time.

Purpose: External ventricular drains (EVD) are commonly used in aneurysmal subarachnoid hemorrhage (aSAH) patients and can be life-saving by diverting cerebrospinal fluid. However, the overall relationship between EVD use and outcome is poorly understood.

Methods: In an exploratory analysis of an aSAH patient cohort, we examined EVD use in relation to modified Rankin Scale (mRS) at hospital discharge and at 6 months (unfavorable outcome = mRS > 2) using univariable and multivariable analyses.

Results: EVDs were placed in 31 of 56 (55.4%) patients and more often in women than men (66.7% vs 35.0%, p = 0.022) despite similar rates of hydrocephalus. Women had greater ICU [18 (13.5-25) vs 11.5 (6.5-18.5) days, p = 0.014] and hospital lengths of stay (LOS) [20.5 (16.5-34) vs 13.5 (10.5-27) days, p = 0.015] than men and greater mRS at discharge [4 (3-5) vs 3 (2-3.5), p = 0.011] although mRS at 6 months was similar. Patients with EVDs had longer ICU and hospital LOS and greater mRS at discharge [5 (3-6) vs 2 (2-3), p < 0.001] and at 6 months [4 (2-6) vs 1 (0-2), p = 0.001] than those without an EVD. In multivariable models, EVD use was associated with unfavorable 6-month outcome accounting for age, sex, and admission modified Fisher scale, but not in models adjusting for Hunt and Hess scale and World Federation of Neurological Surgeons scale.

Conclusion: In an aSAH cohort, the use of EVDs was associated with female sex and longer LOS, and may be linked to functional outcomes at discharge and at 6 months, although these associations warrant further investigation.

A 71-year-old male patient was diagnosed with LGI1 encephalopathy 4 weeks following a first ChAdOx1 nCov-19 vaccination. Extensive work-up including analysis of CSF and PET examination did not reveal a tangible cause so that a vaccine-associated encephalopathy was considered as differential diagnosis. Under steroid treatment, the faciobrachial dystonic seizures subsided.

Background: In Dravet syndrome (DS), a rare epileptic and developmental encephalopathy, the effectiveness of a new treatment is predominantly measured in terms of seizure frequency. However, this may not fully capture the impact of a treatment on the broader aspects of the syndrome and patients' health-related quality of life (HRQoL). Using a previously published survey which collected data from DS patients and their carers on the broader manifestations of their syndrome, their HRQoL, and their experience of seizures, this study created composite measures of symptom severity to offer new perspectives on the multifaceted aspects of this rare condition.

Methods: Survey responses on the severity of physical and psychosocial symptoms were combined with independent assessments of disability and care need, to generate three composite symptom scores assessing the manifestations of DS (physical, psychosocial and care requirements). Variation in HRQoL was investigated in multiple regression analyses to assess the strength of association between each of these composite measures and three forms of seizure measures (seizure frequency, days with no seizures and longest interval without seizures), as experienced over a 4- and 12-week period.

Results: Composite scores were calculated for a cohort of 75 primarily paediatric patients who were enrolled in the study. Strong associations were found between each of the three composite symptom scores and each of the three seizure measures, with the regression coefficient on symptom score highly significant (p ≤ 0.001) in all nine comparisons. Separate regressions using predictors of HRQoL (Kiddy KINDL and Kid KINDL) as the dependent variable were inconclusive, identifying only behavioural/attention problems and status epilepticus as significant predictors of HRQoL.

Conclusions: These results allow the development of a composite score that may be useful in developing a clinical understanding of the severity of DS for an individual patient and establishing their treatment goals. Where measurement of long-term sequalae of disease is not feasible, such as clinical trials, correlation of the composite score with experience of seizures and seizure-free periods may allow a better contextualisation of the results of short-term assessments.

Trial registration: German Clinical Trials Register (DRKS), DRKS00011894. Registered 16 March 2017, http://www.drks.de/ DRKS00011894.

Introduction: Isocitrate dehydrogenase (IDH) mutations are disease-defining mutations in IDH-mutant astrocytomas and IDH-mutant and 1p/19q-codeleted oligodendrogliomas. In more than 80% of these tumors, point mutations in IDH type 1 (IDH1) lead to expression of the tumor-specific protein IDH1R132H. IDH1R132H harbors a major histocompatibility complex class II (MHCII)-restricted neoantigen that was safely and successfully targeted in a first-in human clinical phase 1 trial evaluating an IDH1R132H 20-mer peptide vaccine (IDH1-vac) in newly diagnosed astrocytomas concomitant to standard of care (SOC).

Methods: AMPLIFY-NEOVAC is a randomized, 3-arm, window-of-opportunity, multicenter national phase 1 trial to assess safety, tolerability and immunogenicity of IDH1-vac combined with avelumab (AVE), an immune checkpoint inhibitor (ICI) targeting programmed death-ligand 1 (PD-L1). The target population includes patients with resectable IDH1R132H-mutant recurrent astrocytoma or oligodendroglioma after SOC. Neoadjuvant and adjuvant immunotherapy will be administered to 48 evaluable patients. In arm 1, 12 patients will receive IDH1-vac; in arm 2, 12 patients will receive the combination of IDH1-vac and AVE, and in arm 3, 24 patients will receive AVE only. Until disease progression according to immunotherapy response assessment for neuro-oncology (iRANO) criteria, treatment will be administered over a period of maximum 43 weeks (primary treatment phase) followed by facultative maintenance treatment.

Perspective: IDH1R132H 20-mer peptide is a shared clonal driver mutation-derived neoepitope in diffuse gliomas. IDH1-vac safely targets IDH1R132H in newly diagnosed astrocytomas. AMPLIFY-NEOVAC aims at (1) demonstrating safety of enhanced peripheral IDH1-vac-induced T cell responses by combined therapy with AVE compared to IDH1-vac only and (2) investigating intra-glioma abundance and phenotypes of IDH1-vac induced T cells in exploratory post-treatment tissue analyses. In an exploratory analysis, both will be correlated with clinical outcome.

Trial registration: NCT03893903.