Repurposing MS Immunotherapies for CIDP and Other Autoimmune Neuropathies: Unfulfilled Promise or Efficient Strategy?

Despite advances in the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and other common autoimmune neuropathies (AN), still-many patients with these diseases do not respond satisfactorily to the available treatments. Repurposing of disease-modifying therapies (DMTs) from other autoimmune conditions, particularly multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), is a promising strategy that may accelerate the establishment of novel treatment choices for AN. This approach appears attractive due to homologies in the pathogenesis of these diseases and the extensive post-marketing experience that has been gathered from treating MS and NMOSD patients. The idea is also strengthened by a number of studies that explored the efficacy of DMTs in animal models of AN but also in some CIDP patients. We here review the available preclinical and clinical data of approved MS therapeutics in terms of their applicability to AN, especially CIDP. Promising therapeutic approaches appear to be B cell-directed and complement-targeting strategies, such as anti-CD20/anti-CD19 agents, Bruton\u27s tyrosine kinase inhibitors and anti-C5 agents, as they exert their effects in the periphery. This is a major advantage because, in contrast to MS, their action in the periphery is sufficient to exert significant immunomodulation

Studienprotokoll: Register zur Prognose akut-symptomatischer Anfälle (PROSA-Register) – eine prospektive multizentrische Beobachtungsstudie

Background: Acute symptomatic epileptic seizures occur in close temporal relation to an acute disturbance of brain function. They are associated with a low risk of subsequent unprovoked seizures; thus, current guidelines recommend not to administer a long-term antiseizure medication; however, in clinical practice long-term secondary seizure prophylaxis is frequently initiated. The seizure prognosis after guideline-conform untreated or only briefly treated acute symptomatic seizures, is so far unknown. Hypothesis: Following an acute symptomatic first epileptic seizure of structural etiology, the 1-year risk of subsequent unprovoked seizures is not higher than 25%, even if antiseizure medication was not applied or for a short period only. Methods: The PROSE register is a single-arm, open, prospective, multicenter observational study. A total of 115 subjects aged 18 years or older with an acute symptomatic first epileptic seizure of structural etiology will be included if the seizure was not a status epilepticus. Intrahospital follow-up will be based on the hospital records. Telephone follow-up interviews will be conducted 3, 6, and 12 months after the acute symptomatic seizure. Discussion: The PROSE register will shed light on current treatment practice of acute symptomatic seizures and the actual seizure outcome within 1 year. The results are assumed to support the current evidence that giving antiseizure medication for a longer period of time exceeding the acute phase of the underlying condition is unnecessary

Antiinflammatorische und immunmodulatorische Effekte intrathekal applizierter humaner Immunglobuline im Rattenmodell der experimentellen autoimmunen Neuritis

Im Tiermodell der experimentellen autoimmunen Neuritis wurden in präventiven und therapeutischen Behandlungen immunmodulatorische Effekte intrathekaler humaner Immunglobulingabe in den Konzentrationen 5-40 mg/kg nachgewiesen. 6-8 Wochen alte Lewis-Ratten wurden mit Myelin-P2-Peptid immunisiert und klinische, elektrophysiologische, histopathologische und immunhistochemische Auswirkungen auf die Entwicklung der Neuritis objektiviert. Demyelinisierung, zelluläre Inflammationsreaktionen, die ICAM-1-abhängige Blut-Nerven-Permeabilität und Komplementaktivierung wird im präventiven sowie therapeutischen Konzept reduziert. Präventiv wirkt die niedrigkonzentrierte Applizierung von 5 mg/kg und 10 mg/kg, während höhere Konzentrationen in den gemessenen Parametern keine Auswirkungen zeigen. Dies ist in den therapeutischen Experimenten anders. Die Gabe höherer Konzentrationen von 20 mg/kg wirkt sich günstiger aus. Ein zentraler Wirkungsvermittler ist der Fc-$\gamma$ Rezeptor II

Chronic inflammatory demyelinating polyneuropathy and pregnancy: systematic review

Pregnancy largely affects disease activity and clinical course in women with immune-mediated neurological disorders. Chronic inflammatory demyelinating polyneuropathy (CIDP) is rare but the most common chronic immune-mediated neuropathy; however, the effects of pregnancy on CIDP have never been investigated except case reports or series. We here provide a systematic review of the literature from 1 January 1969 to 30 June 2020 that revealed 24 women with CIDP, who had onset or relapse during pregnancy. Of these, 17 (71%) developed CIDP during the first pregnancy, and 8 (47%) had a relapse during subsequent pregnancies. Of the 17 patients, in whom the CIDP subtypes were determined, all of them had typical CIDP. First-line treatments for CIDP, such as corticosteroids, immunoglobulin and plasma exchange were efficacious and safe. We suggest that pregnancy can trigger typical CIDP in some women, and women with CIDP have a higher risk of relapse during pregnancy. The onset or relapse of CIDP during pregnancy is a rare but challenging constellation for physicians

Could symptom overlap of COVID-19 and Guillain-Barre syndrome mask an epidemiological association?

Introduction!#!Hashimoto thyroiditis (HT) may lead to muscle weakness due to hypothyroid dysfunction. However, clinical experience treating patients with HT suggests that neuromuscular symptoms may develop in these patients despite long-standing euthyroidism.!##!Methods!#!In 24 euthyroid patients with HT and 25 healthy controls, physical fatigability was assessed using the arm movement test (AMT) and 6-min walk test (6MWT). Fatigability was based on calculation of linear trend (LT) reflecting dynamic performance within subsequent constant time intervals. Perception of physical fatigue and muscle pain was analyzed using fatigue (FSMC) and pain questionnaires. Obtained results were correlated with clinical, neurophysiological and lab findings.!##!Results!#!HT patients showed a negative LT in 6MWT significantly differing from stable performance in controls. LT in AMT did not differ between HT and controls. FSMC scores and pain perception revealed significantly higher levels in HT patients than in controls. Physical FSMC score was primarily influenced by pain perception (standardized regression coefficient, beta = 0.633, p = 0.002). Neither pain score nor physical fatigue score showed a correlation with LT in 6MWT nor did mood, or anti-TPO antibody titer.!##!Conclusion!#!A significant physical fatigability could be shown in euthyroid HT patients despite missing obvious neuromuscular deficits in routine testing. Further, elevated pain and fatigue perception in HT patients seem to contribute to nonspecific muscle complaints in these patients. A possible pathogenic role of thyroid autoimmunity in hidden neuromuscular involvement may be suggested

Nerve conductions studies in experimental models of autoimmune neuritis: A meta-analysis and guideline

Nerve conduction studies (NCS) are essential to assess peripheral nerve fiber function in research models of immune-mediated neuritis. However, the current lack of standard protocols and reference values impedes data comparability across models and studies. We performed a systematic review and subsequent meta-analysis of the last 30 years of NCS of immune-mediated neuritis in Lewis-rats. Twenty-six papers met the inclusion criteria for meta-analysis. Extracted data showed considerable heterogeneity of recorded nerve conduction velocity (NCV) and compound muscle action potential (CMAP). Studies also significantly differed in terms of technical, methodical, and data reporting issues. The heterogeneity of the underlying studies emphasizes the need for standardization when conducting and reporting NCS in rats. We provide normative values for NCS of the sciatic nerve of Lewis rats and propose seven items that should be addressed when NCS are performed when studying immune paradigms in Lewis rats

Motor unit number estimation by MScanFit in myotonic dystrophies

MScanFit is a new motor unit number estimation (MUNE) technique applied in motor neuron diseases and polyneuropathies to assess clinical progression and underlying disease pathology. So far, its value in myopathies, especially myotonic dystrophies (MD), has not been investigated

Status epilepticus during the COVID-19 pandemic in Cologne, Germany: data from a retrospective, multicentre registry

BACKGROUND: The “coronavirus disease 2019” (COVID-19) pandemic, caused by the “severe-acute-respiratory-syndrome-coronavirus 2” (SARS-CoV-2), challenges healthcare systems worldwide and impacts not only COVID-19 patients but also other emergencies. To date, data are scarce on the extent to which the COVID-19 pandemic impacted status epilepticus (SE) and its treatment. OBJECTIVE: To assess the influence of the COVID-19 pandemic on the incidence, management and outcome of SE patients. STUDY DESIGN: This is a retrospective, multicentre trial, approved by the University of Cologne (21-1443-retro). METHODS: All SE patients from the urban area of Cologne transmitted to all acute neurological departments in Cologne between 03/2019 and 02/2021 were retrospectively analysed and assessed for patient characteristics, SE characteristics, management, and outcome in the first pandemic year compared to the last pre-pandemic year. RESULTS: 157 pre-pandemic (03/2019–02/2020) and 171 pandemic (from 03/2020 to 02/2021) SE patients were included in the analyses. Acute SARS-CoV-2 infections were rarely detected. Patient characteristics, management, and outcome did not reveal significant groupwise differences. In contrast, regarding prehospital management, a prolonged patient transfer to the hospital and variations in SE aetiologies compared to the last pre-pandemic year were observed with less chronic vascular and more cryptogenic and anoxic SE cases. No infections with SARS-CoV-2 occurred during inpatient stays. CONCLUSIONS: SARS-CoV-2 infections did not directly affect SE patients, but the transfer of SE patients to emergency departments was delayed. Interestingly, SE aetiology rates shifted, which warrants further exploration. Fears of contracting an in-hospital SARS-CoV-2-infection were unfounded due to consequent containment measures. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00415-022-11260-2

Status epilepticus and benzodiazepine treatment: Use, underdosing and outcome - insights from a retrospective, multicentre registry

Objective: To explore the reasons for and outcomes of non- or undertreatment with benzodiazepines (BZDs) in status epilepticus (SE).Methods: We retrospectively analysed all SE patients from the urban area of Cologne over two years.Results: 328 SE patients were eligible, and only 72% were initially treated with BZDs. Of these, only 21.6% were treated sufficiently with BZDs according to current guidelines. SE patients not initially treated with BZDs were significantly older, had less often known epilepsy, had a prolonged arrival time to the emergency room, and presented more often with a non-generalised convulsive semiology. Regarding adequate dosages, patients with a generalised convulsive SE seemed to benefit from a sufficient BZD dosing with significantly shortened mean ventilation duration (37.1 to 208 h), decreased mean intensive care unit (1.7 to 5 days) and in-hospital stay (4.1 to 8.8 days). In contrary, aggressive BZD treatment in non-generalised convulsive SE resulted in a longer inpatient stay (9.2 to 5.8 days) and lower favourable outcome rates at discharge (16% to 63%).Conclusions: The current SE treatment guidelines for first-line BZD therapy in SE were violated in most patients. Sufficient BZD dosing was beneficial in generalised convulsive SE, but not in other forms of SE. SE semiology might be crucial for treatment decisions with BZDs. Further treatment evidence especially in non-generalised convulsive SE is urgently needed.Keywords: Anticonvulsants; Benzodiazepines; Critical care; Guideline adherence; Seizures