NEMO reshapes the α-Synuclein aggregate interface and acts as an autophagy adapter by co-condensation with p62.

NEMO is a ubiquitin-binding protein which regulates canonical NF-κB pathway activation in innate immune signaling, cell death regulation and host-pathogen interactions. Here we identify an NF-κB-independent function of NEMO in proteostasis regulation by promoting autophagosomal clearance of protein aggregates. NEMO-deficient cells accumulate misfolded proteins upon proteotoxic stress and are vulnerable to proteostasis challenges.

Subarachnoid hemorrhages and aneurysms during the SARS-CoV2-pandemia at a tertiary medical center - Analysis of incidence and outcome.

Introduction: During the COVID-19-pandemic a significant decrease of up to 13% of all kinds of medical emergencies was reported. Similar trends were expected for aneurysmal subarachnoid hemorrhages (aSAH) and/or symptomatic aneurysms.

Research Question: To analyze a correlation of the SARS-CoV2-infection and the incidence of aSAH, and to assess the impact of the pandemic-lockdown on the incidence, the outcome and the course of patients suffering from aSAH and/or aneurysms.

Evidences for Mutant Huntingtin Inducing Musculoskeletal and Brain Growth Impairments via Disturbing Testosterone Biosynthesis in Male Huntington Disease Animals.

Body weight (BW) loss and reduced body mass index (BMI) are the most common peripheral alterations in Huntington disease (HD) and have been found in HD mutation carriers and HD animal models before the manifestation of neurological symptoms. This suggests that, at least in the early disease stage, these changes could be due to abnormal tissue growth rather than tissue atrophy. Moreover, BW and BMI are reported to be more affected in males than females in HD animal models and patients.

Neurotrauma Emergencies during the SARS-CoV2 Pandemic at a Tertiary Medical Center: Analysis of Incidence and Outcome.

Background:  We assess the impact of lockdown in Germany due to the COVID-19 pandemic on the incidence and outcome of neurotrauma emergencies at a tertiary medical center.

Methods:  All neurosurgical emergencies from March 16, 2020 (first lockdown in Germany) to January 31, 2021 were included and compared with a longitudinal case-cohort. Cases were descriptively recorded and retrospectively analyzed with respect to incidence and outcome.

Positive effect of immunomodulatory therapies on disease progression in Huntington's disease? Data from a real-world cohort.

Background: The role of neuroinflammation and autoimmune processes in neurodegenerative diseases is not fully understood. Activation of microglia with expression of proinflammatory cytokines supports the hypothesis that immune processes may play an important role in the pathophysiology of Huntington's disease (HD) and thus, immunomodulating therapies might have potential neuroprotective properties. Until now, no disease-modifying therapy (DMT) is available for HD.

Non-ischemic neurovascular emergencies at a supra-regional medical center during the SARS-CoV2-pandemia.

Objective: To assess the impact of the lockdown in Germany due to the SARS-CoV2-pandemic on the incidence and the outcome of neurovascular emergencies at a tertiary medical center.

Methods: From March 16th, 2020 (first lockdown in Germany) to January 31st, 2021, all neurosurgical emergencies were included and compared to a longitudinal case-cohort. Cases were descriptively recorded and retrospectively analyzed with respect to incidence and outcome.

Germany-wide evaluation of residency in neurological intensive care medicine.

Background: Neurointensive medicine is an important subspecialization of neurology. Its growing importance can be attributed to factors such as demographic change and the establishment of new therapeutic options. Part of the neurological residency in Germany is a six-month rotation on an intensive care unit (ICU), which has not yet been evaluated nationwide.

Mechanical thrombectomy for acute ischemic stroke in COVID-19 patients: multicenter experience in 111 cases.

Background: Data on the frequency and outcome of mechanical thrombectomy (MT) for large vessel occlusion (LVO) in patients with COVID-19 is limited. Addressing this subject, we report our multicenter experience.

Methods: A retrospective cohort study was performed of consecutive acute stroke patients with COVID-19 infection treated with MT at 26 tertiary care centers between January 2020 and November 2021.

Progressive multifocal leukoencephalopathy and immune reconstitution inflammatory syndrome in seven patients with sarcoidosis: a critical discussion of treatment and prognosis.

Progressive multifocal leukoencephalopathy (PML) is a subacute brain infection by the opportunistic John Cunningham (JC) virus. Herein, we describe seven patients with PML, lymphopenia, and sarcoidosis, in three of whom PML was the first manifestation of sarcoidosis. At onset, the clinical picture comprised rapidly progressive spastic hemi- or limb pareses as well as disturbances of vision, speech, and orientation.

Ocrelizumab Treatment in Patients with Primary Progressive Multiple Sclerosis: Short-term Safety Results from a Compassionate Use Programme in Germany.

Objectives: In January 2018, the European Union (EU) approved ocrelizumab in relapsing multiple sclerosis (RMS) and as the first disease-modifying therapy (DMT) for patients with primary progressive multiple sclerosis (PPMS) with efficacy proven in a phase 3 randomised controlled trial. Eleven months prior to the European regulatory approval, a compassionate use programme (CUP) made ocrelizumab available to 489 patients with PPMS in Germany, thereby for the first time providing a therapeutic option to patients with PPMS who could not participate in ocrelizumab studies. Here, we report real-world patient characteristics and short-term safety data of patients with PPMS treated with ocrelizumab in this CUP.

Immunomodulatory and anti-oxidative effect of the direct TRPV1 receptor agonist capsaicin on Schwann cells.

Background: Only few studies describe the impact of nutritive factors on chronic inflammatory demyelinating polyneuropathy (CIDP), an inflammatory disease of the peripheral nervous system. The active component of chili pepper, capsaicin, is the direct agonist of the transient receptor potential channel vanilloid subfamily member 1. Its anti-inflammatory effect in the animal model experimental autoimmune neuritis (EAN) has been previously demonstrated.

Novel variants in a patient with late-onset hyperprolinemia type II: diagnostic key for status epilepticus and lactic acidosis.

Background: Hyperprolinemia type 2 (HPII) is a rare autosomal recessive disorder of the proline metabolism, that affects the ALDH4A1 gene. So far only four different pathogenic mutations are known. The manifestation is mostly in neonatal age, in early infancy or early childhood.

Brainstem Encephalitis With Low-Titer Acetylcholine Receptor Antibodies Mimicking Myasthenia Gravis.

To report a rare case of brainstem encephalitis with low-titer acetylcholine receptor antibodies mimicking myasthenia gravis. The patient was investigated with repeated brain MRI, CSF examination, repetitive nerve stimulation, thoracic CT, and serologic screening. Our patient passed away and finally autopsy revealed a definitive diagnosis.

A protein quality control pathway regulated by linear ubiquitination.

Neurodegenerative diseases are characterized by the accumulation of misfolded proteins in the brain. Insights into protein quality control mechanisms to prevent neuronal dysfunction and cell death are crucial in developing causal therapies. Here, we report that various disease-associated protein aggregates are modified by the linear ubiquitin chain assembly complex (LUBAC).

Author Correction: Laquinimod treatment in the R6/2 mouse model.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Peripheral CD19 B-cell counts and infusion intervals as a surrogate for long-term B-cell depleting therapy in multiple sclerosis and neuromyelitis optica/neuromyelitis optica spectrum disorders.

Background: With ocrelizumab another drug is available for the treatment of multiple sclerosis (MS). Little is known on the long-term use of ocrelizumab on immune cell subsets, and no surrogate markers are available. Rituximab (RTX) has been in off-label use for the treatment of MS, neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD) for > 10 years.

Tryptophan immunoadsorption during pregnancy and breastfeeding in patients with acute relapse of multiple sclerosis and neuromyelitis optica.

Background: Up to every fourth woman with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) suffers a clinically relevant relapse during pregnancy. High doses of steroids bear some serious risks, especially within the first trimester of pregnancy. Immunoadsorption (IA) is an effective and more selective treatment option in disabling MS relapse than plasma exchange.

Activation of NPY-Y2 receptors ameliorates disease pathology in the R6/2 mouse and PC12 cell models of Huntington's disease.

Huntington's disease (HD) is a monogenic inherited polyglutamine-mediated neurodegenerative disorder for which effective therapies are currently unavailable. Neuropeptide Y (NPY) has been implicated as a potential therapeutic target in several neurodegenerative diseases, including HD. However, its mechanisms of action in the context of HD pathology remain unknown.

Insight into Metabolic H-MRS Changes in Natalizumab Induced Progressive Multifocal Leukoencephalopathy Brain Lesions.

Background: Progressive multifocal leukoencephalopathy (PML) is a severe complication of immunosuppressive therapies, especially of natalizumab in relapsing-remitting multiple sclerosis (MS). Metabolic changes within PML lesions have not yet been described in natalizumab-associated PML in MS patients.

Objective: To study metabolic profiles in natalizumab-associated PML lesions of MS patients by H magnetic resonance spectroscopy (H-MRS) at different stages during the PML course.

Laquinimod treatment in the R6/2 mouse model.

The transgenic mouse model R6/2 exhibits Huntington's disease (HD)-like deficits and basic pathophysiological similarities. We also used the pheochromocytoma-12 (PC12)-cell-line-model to investigate the effect of laquinimod on metabolic activity. Laquinimod is an orally administered immunomodulatory substance currently under development for the treatment of multiple sclerosis (MS) and HD.

Metabolic profiles by 1H-magnetic resonance spectroscopy in natalizumab-associated post-PML lesions of multiple sclerosis patients who survived progressive multifocal leukoencephalopathy (PML).

Purpose: Early diagnosis and treatment of multiple sclerosis-related progressive multifocal leukoencephalopathy (PML) significantly improve clinical outcomes. However, there is a lack of information regarding the restart of immunomodulatory therapy in the post-PML setting, when multiple sclerosis activity reappears. We aimed at the examination of metabolic differences using 1H-magnetic resonance spectroscopy (1H-MRS) in multiple sclerosis patients at various post-PML stages and at the exploration of differences according to their disease and JC virus (JCV) status.

Inhibition of Huntingtin Exon-1 Aggregation by the Molecular Tweezer CLR01.

Huntington's disease is a neurodegenerative disorder associated with the expansion of the polyglutamine tract in the exon-1 domain of the huntingtin protein (htt). Above a threshold of 37 glutamine residues, htt starts to aggregate in a nucleation-dependent manner. A 17-residue N-terminal fragment of htt (N17) has been suggested to play a crucial role in modulating the aggregation propensity and toxicity of htt.