Immunomodulatory effects of intravenous and subcutaneous immunoglobulin in chronic inflammatory demyelinating polyneuropathy: An observational study.

BACKGROUND AND PURPOSE: It is not known whether the route of administration affects the mechanisms of action of therapeutic immunoglobulin in chronic inflammatory demyelinating polyneuropathy (CIDP). The aim of this study, therefore, was to compare the immunomodulatory effects of intravenous (IVIg) and subcutaneous immunoglobulin (SCIg) in patients with CIDP and in IVIg-treated common variable immunodeficiency (CVID) patients. METHODS: Serum and peripheral blood mononuclear cell samples were obtained from 30 CIDP patients receiving IVIg, 10 CIDP patients receiving SCIg, and 15 patients with CVID receiving IVIg. Samples and clinical data were obtained prior to IVIg/SCIg and at 3 days, 7 days, and, in CIDP patients receiving IVIg, 21 days post-administration. Serum cytokines were assessed by Luminex-based multiplex assay and enzyme-linked immunosorbent assay. Immune cells were characterized by flow cytometry. RESULTS: Immune cell profiles of CIDP and CVID patients differed in frequencies of myeloid dendritic cells and cytotoxic natural killer cells. During treatment with IVIg or SCIg in CIDP patients, cellular immunomarkers were largely similar. CIDP patients receiving IVIg had higher macrophage inflammatory protein (MIP)-1α (p = 0.01), interleukin (IL)-4 (p = 0.04), and IL-33 (p = 0.04) levels than SCIg recipients. IVIg treatment more broadly modulated cytokines in CIDP than SCIg treatment. CONCLUSIONS: Our study demonstrates that the modulation of cellular immunomarkers in CIDP is independent of the application route of therapeutic immunoglobulin. Minor differences were observed between CIDP and CVID patients. In contrast, cytokines were differentially modulated by IVIg and SCIg in CIDP.

Kinesin-5 inhibition improves neural regeneration in experimental autoimmune neuritis.

BACKGROUND: Autoimmune neuropathies can result in long-term disability and incomplete recovery, despite adequate first-line therapy. Kinesin-5 inhibition was shown to accelerate neurite outgrowth in different preclinical studies. Here, we evaluated the potential neuro-regenerative effects of the small molecule kinesin-5 inhibitor monastrol in a rodent model of acute autoimmune neuropathies, experimental autoimmune neuritis. METHODS: Experimental autoimmune neuritis was induced in Lewis rats with the neurogenic P2-peptide. At the beginning of the recovery phase at day 18, the animals were treated with 1 mg/kg monastrol or sham and observed until day 30 post-immunisation. Electrophysiological and histological analysis for markers of inflammation and remyelination of the sciatic nerve were performed. Neuromuscular junctions of the tibialis anterior muscles were analysed for reinnervation. We further treated human induced pluripotent stem cells-derived secondary motor neurons with monastrol in different concentrations and performed a neurite outgrowth assay. RESULTS: Treatment with monastrol enhanced functional and histological recovery in experimental autoimmune neuritis. Motor nerve conduction velocity at day 30 in the treated animals was comparable to pre-neuritis values. Monastrol-treated animals showed partially reinnervated or intact neuromuscular junctions. A significant and dose-dependent accelerated neurite outgrowth was observed after kinesin-5 inhibition as a possible mode of action. CONCLUSION: Pharmacological kinesin-5 inhibition improves the functional outcome in experimental autoimmune neuritis through accelerated motor neurite outgrowth and histological recovery. This approach could be of interest to improve the outcome of autoimmune neuropathy patients.

[Public health situation of CIDP patients in nine German centers-neuritis network Germany]. / Versorgungssituation von CIDP-Patienten in neun deutschen Zentren des Neuritis Netzes.

BACKGROUND: Diagnosis and treatment of patients with immune-mediated neuropathies is challenging due to the heterogeneity of the diseases. OBJECTIVES: To assess similarities and differences in the current care of patients with immune-mediated polyneuropathies in specialized centers in Germany within the German neuritis network "Neuritis Netz". MATERIAL AND METHODS: We conducted a cross-sectional survey of nine neurological departments in Germany that specialize in the care of patients with immune-mediated neuropathies. We assessed the diagnosis, the approach to diagnostic work-up and follow-up, typical symptoms at manifestation and progression of the disease, and treatment data. RESULTS: This report includes data from 1529 patients per year treated for immune-mediated neuropathies, of whom 1320 suffered from chronic inflammatory demyelinating polyneuropathy (CIDP). Diagnostic work-up almost always included nerve conduction studies, electromyography, and lumbar puncture in accordance with current guidelines. The use of ultrasound, biopsy, and MRI varied. The most important clinical parameter for therapy monitoring in all centers was motor function in the clinical follow-up examinations. A wide range of different immunosuppressants was used for maintenance therapy in about 15% of patients. CONCLUSIONS: These data provide important epidemiological insights into the care of patients with immune-mediated neuropathies in Germany. The further development of specific recommendations for treatment and follow-up examinations is necessary to ensure a uniform standard of patient care. This effort is greatly facilitated by a structured collaboration between expert centers such as Neuritis Netz.

Antibody response after COVID-19 vaccination in intravenous immunoglobulin-treated immune neuropathies.

BACKGROUND AND PURPOSE: This study assessed the prevalence of anti-SARS-CoV-2 antibodies in therapeutic immunoglobulin and their impact on serological response to COVID-19 mRNA vaccine in patients with intravenous immunoglobulin (IVIg)-treated chronic immune neuropathies. METHODS: Forty-six samples of different brands or lots of IVIg or subcutaneous IgG were analyzed for anti-SARS-CoV-2 IgG using enzyme-linked immunosorbent assay and chemiluminescent microparticle immunoassay. Blood sera from 16 patients with immune neuropathies were prospectively analyzed for anti-SARS-CoV-2 IgA, IgG, and IgM before and 1 week after IVIg infusion subsequent to consecutive COVID-19 mRNA vaccine doses and after 12 weeks. These were compared to 42 healthy subjects. RESULTS: Twenty-four (52%) therapeutic immunoglobulin samples contained anti-SARS-CoV-2 IgG. All patients with immune neuropathies (mean age = 65 ± 16 years, 25% female) were positive for anti-SARS-CoV-2 IgG after COVID-19 vaccination. Anti-SARS-CoV-2 IgA titers significantly decreased 12-14 weeks after vaccination (p = 0.02), whereas IgG titers remained stable (p = 0.2). IVIg did not significantly reduce intraindividual anti-SARS-CoV-2 IgA/IgG serum titers in immune neuropathies (p = 0.69). IVIg-derived anti-SARS-CoV-2 IgG did not alter serum anti-SARS-CoV-2 IgG decrease after IVIg administration (p = 0.67). CONCLUSIONS: Our study indicates that IVIg does not impair the antibody response to COVID-19 mRNA vaccine in a short-term observation, when administered a minimum of 2 weeks after each vaccine dose. The infusion of current IVIg preparations that contain anti-SARS-CoV-2 IgG does not significantly alter serum anti-SARS-CoV-2 IgG titers.

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.

Rituximab in non-systemic vasculitic neuropathy: a single-center experience.

OBJECTIVES: This case series reports clinical features and outcome of four patients with non-systemic vasculitic neuropathy (NSVN) treated with the anti-CD20 agent rituximab. METHODS: Clinical, electrophysiological and biopsy data were retrospectively obtained and evaluated. Only patients with pathological definite or probable NSVN were included. Extensive clinical and laboratory work-up excluded systemic vasculitis. Follow-up data for at least 12 months and up to five years is provided. Outcome of the patients was assessed using the MRC-Sum Score, Prineas Score and Neurological Symptom Score. RESULTS: Two of four patients treated with rituximab achieved disease remission and one patient remained stable under anti-CD20 therapy after a required treatment switch due to toxic side effects of cyclophosphamide. One patient deteriorated under rituximab induction. Rituximab was well tolerated in all patients. DISCUSSION: Anti-CD20 therapy might be an alternative in NSVN patients requiring further treatment escalation or treatment switch due to side effects of corticosteroids or cyclophosphamide.

Antibiotics-Induced Intestinal Immunomodulation Attenuates Experimental Autoimmune Neuritis (EAN).

BACKGROUND: The composition of gut microbiota plays a pivotal role in priming the immune system and thus impacts autoimmune diseases. Data on the effects of gut bacteria eradication via systemic antibiotics on immune neuropathies are currently lacking. This study therefore assessed the effects of antibiotics-induced gut microbiota alterations on the severity of experimental autoimmune neuritis (EAN), a rat model of Guillain-Barré Syndrome (GBS). Myelin P0 peptide 180-199 (P0 180-199)-induced EAN severity was compared between adult Lewis rats (12 weeks old) that received drinking water with or without antibiotics (colistin, metronidazole, vancomycin) and healthy rats, beginning antibiotics treatment immediately after immunization (day 0), and continuing treatment for 14 consecutive days. Neuropathy severity was assessed via a modified clinical score, and then related to gut microbiota alterations observed after fecal 16S rRNA gene sequencing at baseline and after EAN induction. Effectors of gut mucosal and endoneurial immunity were assessed via immunostaining. EAN rats showed increased gut mucosal permeability alongside increased mucosal CD8+ T cells compared to healthy controls. Antibiotics treatment alleviated clinical EAN severity and reduced endoneurial T cell infiltration, decreased gut mucosal CD8+ T cells and increased gut bacteria that may be associated with anti-inflammatory mechanisms, like Lactobacillus or Parasutterella. Our findings point out a relation between gut mucosal immunity and the pathogenesis of EAN, and indicate that antibiotics-induced intestinal immunomodulation might be a therapeutic approach to alleviate autoimmunity in immune neuropathies. Further studies are warranted to evaluate the clinical transferability of these findings to patients with GBS.

Preventing long-term disability in CIDP: the role of timely diagnosis and treatment monitoring in a multicenter CIDP cohort.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an inflammatory disease affecting the peripheral nerves and the most frequent autoimmune polyneuropathy. Given the lack of established biomarkers or risk factors for the development of CIDP and patients' treatment response, this research effort seeks to identify potential clinical factors that may influence disease progression and overall treatment efficacy. METHODS: In this multicenter, retrospective analysis, we have screened 197 CIDP patients who presented to the University Hospitals in Düsseldorf, Berlin, Cologne, Essen, Magdeburg and Munich between 2018 and 2022. We utilized the respective hospital information system and examined baseline data with clinical examination, medical letters, laboratory results, antibody status, nerve conduction studies, imaging and biopsy findings. Aside from clinical baseline data, we analyzed treatment outcomes using the Standard of Care (SOC) definition, as well as a comparison of an early (within the first 12 months after manifestation) versus late (more than 12 months after manifestation) onset of therapy. RESULTS: In terms of treatment, most patients received intravenous immunoglobulin (56%) or prednisolone (39%) as their first therapy. Patients who started their initial treatment later experienced a worsening disease course, as reflected by a significant deterioration in their Inflammatory Neuropathy Cause and Treatment (INCAT) leg disability score. SOC-refractory patients had worse clinical outcomes than SOC-responders. Associated factors for SOC-refractory status included the presence of fatigue as a symptom and alcohol dependence. CONCLUSION: Timely diagnosis, prompt initiation of treatment and careful monitoring of treatment response are essential for the prevention of long-term disability in CIDP and suggest a "hit hard and early" treatment paradigm.

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's 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.

Motor unit number estimation by MScanFit in myotonic dystrophies.

BACKGROUND: 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. METHODS: Motor unit loss and characteristics of patients with genetically confirmed MD type 1 (n = 7) and type 2 (n = 5) were investigated using MScanFit of the abductor pollicis brevis muscle and compared to age-matched healthy controls. MUNE measures were correlated with muscle impairment determined by the MRC sum score and handgrip strength. RESULTS: MScanFit detected motor unit loss in patients with MD (p = 0.017). There was no significant difference in motor unit loss between MD type 1 and type 2 (p = 0.64). CMAP-discontinuities which, when added up, exceed 50% of the CMAP amplitude were reduced in MD patients (p = 0.0284), but motor unit amplitudes were not significantly different (p = 0.0597). The motor unit loss strongly correlated with the MRC sum score (p = 0.014, Rho = 0.678). CONCLUSIONS: Our study shows the feasibility of MScanFit in MD and its potential to serve as a surrogate marker for overall muscle impairment. Motor unit analysis indicates that neurogenic alterations in both MD subtypes might be present.

Prehospital Levetiracetam Use in Adults With Status Epilepticus: Results of a Multicenter Registry.

BACKGROUND AND PURPOSE: Status epilepticus (SE) is a neurological emergency due to prolonged seizure activity or multiple seizures without full recovery in between them. Prehospital SE management is crucial since its duration is correlated with higher morbidity and mortality rates. We examined the impact of different therapeutic strategies in the prehospital setting with a focus on levetiracetam. METHODS: We initiated the Project for SE in Cologne, a scientific association of all neurological departments of Cologne, the fourth-largest city in Germany with around 1,000,000 inhabitants. All patients with an SE diagnosis were evaluated over 2 years (from March 2019 to February 2021) to determine whether prehospital levetiracetam use had a significant effect on SE parameters. RESULTS: We identified 145 patients who received initial drug therapy in the prehospital setting by professional medical staff. Various benzodiazepine (BZD) derivatives were used as first-line treatments, which were mostly used in line with the recommended guidelines. Levetiracetam was regularly used (n=42) and mostly in combination with BZDs, but no significant additional effect was observed for intravenous levetiracetam. However, it appeared that the administered doses tended to be low. CONCLUSIONS: Levetiracetam can be applied to adults with SE in prehospital settings with little effort. Nevertheless, the prehospital treatment regimen described here for the first time did not significantly improve the preclinical cessation rate of SE. Future therapy concepts should be based on this, and the effects of higher doses should in particular be reexamined.

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.

2,4-Dinitrophenol does not exert neuro-regenerative potential in experimental autoimmune neuritis.

OBJECTIVE: We evaluated the potential neuro-regenerative effects of the mitochondrial uncoupler 2,4-Dinitrophenol in experimental autoimmune neuritis, an animal model for an acute autoimmune neuropathy. METHODS: Experimental autoimmune neuritis was induced in Lewis rats. Different concentrations of 2,4-Dinitrophenol (1 mg/kg, 0.1 mg/kg and 0.01 mg/kg) were applied during the recovery phase of the neuritis (at days 18, 22 and 26) and compared to the vehicle. Any effects were assessed through functional, electrophysiological, and morphological analysis via electron microscopy of all groups at day 30. Additional immune-histochemical analysis of inflammation markers and remyelination of the sciatic nerves were performed for the dosage of 1 mg/kg and control. RESULTS: No enhancement of functional or electrophysiological recovery was observed in all 2,4-Dinitrophenol-treated groups. Cellular inflammation markers of T cells (CD3+) were comparable to control, and an increase of macrophages (IbA1+) invasion in the sciatic nerves was observed. Treatment with 2,4-Dinitrophenol reduced axonal swelling in myelinated and unmyelinated fibers with an increased production of brain-derived neurotrophic factor. CONCLUSION: Our findings do not support the hypothesis that repurposing of the mitochondrial uncoupler 2,4-Dinitrophenol exerts functionally relevant neuro-regenerative effects in autoimmune neuritis.

CIDP: Analysis of Immunomarkers During COVID-19 mRNA-Vaccination and IVIg-Immunomodulation: An Exploratory Study.

Availability of COVID-19 mRNA vaccine for patients with chronic inflammatory demyelinating polyneuropathy (CIDP) treated with intravenous immunoglobulin (IVIg) raises the question of whether COVID-19 mRNA vaccine influences disease activity or IVIg-mediated immunomodulation in CIDP. In this exploratory study, blood samples of CIDP patients on IVIg treatment were longitudinally analyzed before and after vaccination with a COVID-19 mRNA vaccine. A total of 44 samples of eleven patients were characterized at four timepoints by ELISA and flow cytometry in terms of immunomarkers for disease activity and IVIg-immunomodulation. Apart from a significantly lower expression of CD32b on naïve B cells after vaccination, no significant alteration of immunomarkers for CIDP or IVIg-mediated immunomodulation was observed. Our exploratory study suggests that COVID-19 mRNA vaccine does not have a relevant impact on immune activity in CIDP. In addition, immunomodulatory effects of IVIg in CIDP are not altered by COVID-19 mRNA vaccine. This study was registered in the German clinical trial register (DRKS00025759). Overview over the study design. Blood samples of CIDP patients on recurrent IVIg treatment and vaccination with a COVID-19 mRNA vaccine were obtained at four timepoints for cytokine ELISA and flow cytometry, to assess key cytokines and cellular immunomarkers for disease activity and IVIg-immunomodulation in CIDP.

Comparative analysis of albumin quotient and total CSF protein in immune-mediated neuropathies: a multicenter study on diagnostic implications.

Introduction: Blood-cerebrospinal fluid (CSF) barrier dysfunction is pivotal for diagnosing immune-mediated neuropathies, especially in spinal nerve root inflammation. Typically, either total CSF protein or the CSF to serum albumin ratio (QAlb) is measured. Total CSF protein measurements have limitations, notably its fixed reference value regardless of age, in contrast to the age-dependent reference for QAlb. Our goal was to evaluate both markers in patients with immune-mediated neuropathies. Methods: In our multicenter research, we collected retrospective CSF data from patients suffering from immune-mediated neuropathies across four German research centers. These parameters were analyzed in relation to their clinical characteristics. Results: Out of 419 samples, 36 (8.6%) displayed a notable variation between total CSF protein and QAlb values. A detailed analysis revealed that patients displaying elevated QAlb but normal total CSF protein levels were significantly younger at disease onset (p = 0.01), at the time of diagnosis (p = 0.005), and when undergoing lumbar puncture (p = 0.001) compared to patients with elevated CSF protein and normal QAlb levels. These effects were especially evident for the subgroup of samples derived by female patients. Discussion: Our work confirms the crucial role of QAlb in diagnosing immune-mediated neuropathies and particularly its efficacy as a marker for evaluating the blood-CSF barrier in patients with an earlier disease onset. Considering the significance of the albumin quotient, its assessment is especially advisable in younger patients of female sex to avoid missing a potential barrier dysfunction that might be falsely negative when using total protein.

Prognosis and management of acute symptomatic seizures: a prospective, multicenter, observational study.

BACKGROUND: Acute symptomatic epileptic seizures are frequently seen in neurocritical care. To prevent subsequent unprovoked seizures, long-term treatments with antiseizure medications are often initiated although supporting evidence is lacking. This study aimed at prospectively assessing the risk of unprovoked seizure relapse with respect to the use of antiseizure medications. It was hypothesized that after a first acute symptomatic seizure of structural etiology, the cumulative 12-month risk of unprovoked seizure relapse is ≤ 25%. METHODS: Inclusion criteria were age ≥ 18 and acute symptomatic first-ever epileptic seizure; patients with status epilepticus were excluded. Using telephone and mail interviews, participants were followed for 12 months after the acute symptomatic first seizure. Primary endpoint was the occurrence and timing of a first unprovoked seizure relapse. In addition, neuro-intensivists in Germany were interviewed about their antiseizure treatment strategies through an anonymous online survey. RESULTS: Eleven of 122 participants with structural etiology had an unprovoked seizure relapse, resulting in a cumulative 12-month risk of 10.7% (95%CI, 4.7%-16.7%). None of 19 participants with a non-structural etiology had a subsequent unprovoked seizure. Compared to structural etiology alone, combined infectious and structural etiology was independently associated with unprovoked seizure relapse (OR 11.1; 95%CI, 1.8-69.7). Median duration of antiseizure treatment was 3.4 months (IQR 0-9.3). Seven out of 11 participants had their unprovoked seizure relapse while taking antiseizure medication; longer treatment durations were not associated with decreased risk of unprovoked seizure relapse. Following the non-representative online survey, most neuro-intensivists consider 3 months or less of antiseizure medication to be adequate. CONCLUSIONS: Even in case of structural etiology, acute symptomatic seizures bear a low risk of subsequent unprovoked seizures. There is still no evidence favoring long-term treatments with antiseizure medications. Hence, individual constellations with an increased risk of unprovoked seizure relapse should be identified, such as central nervous system infections causing structural brain damage. However, in the absence of high-risk features, antiseizure medications should be discontinued early to avoid overtreatment.

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.

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.

Anti-inflammatory and immunomodulatory potential of human immunoglobulin applied intrathecally in Lewis rat experimental autoimmune neuritis.

Intravenous human immunoglobulins dominate in the treatment of autoimmune neuropathies. We introduce intrathecal application as a new option for experimental autoimmune neuritis in Lewis rats. After immunisation with neuritogenic P2 peptide, we show a therapeutic and preventive effect of intrathecal human immunoglobulins (5-40mg/kg) on clinical and electrophysiological neuritis signs. Histology corroborated a lower degree of inflammation, demyelination, ICAM-1-dependent blood-nerve-barrier permeability and complement activation in the sciatic nerve. After preventive application, immunoglobulins induced a Th2 cytokine shift in the peripheral nerves already before clinical neuritis signs. Intrathecal immunoglobulin application could be a novel immunomodulatory option for autoimmune neuropathies.