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Objective: To describe the heterogeneity of electrodiagnostic (EDx) studies in Guillain-Barre syndrome (GBS) patients collected as part of the International GBS Outcome Study (IGOS). Methods: Prospectively collected clinical and EDx data were available in 957 IGOS patients from 115 centers. Only the first EDx study was included in the current analysis. Results: Median timing of the EDx study was 7 days (interquartile range 4-11) from symptom onset. Methodology varied between centers, countries and regions. Reference values from the responding 103 centers were derived locally in 49%, from publications in 37% and from a combination of these in the remaining 15%. Amplitude measurement in the EDx studies (baseline-to-peak or peak-to-peak) differed from the way this was done in the reference values, in 22% of motor and 39% of sensory conduction. There was marked variability in both motor and sensory reference values, although only a few outliers accounted for this. Conclusions: Our study showed extensive variation in the clinical practice of EDx in GBS patients among IGOS centers across the regions. Significance: Besides EDx variation in GBS patients participating in IGOS, this diversity is likely to be present in other neuromuscular disorders and centers. This underlines the need for standardization of EDx in future multinational GBS studies.(c) 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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). Graphical Abstract 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.

Introduction: Peripheral neuropathies are a prevalent, heterogeneous group of diseases of the peripheral nervous system. Symptoms are often debilitating, difficult to treat, and usually become chronic. Not only do they diminish patients’ quality of life, but they can also affect medical therapy and lead to complications. To date, for most conditions there are no evidence-based causal treatment options available. Research has increased considerably since the last review in 2014 regarding the therapeutic potential of exercise interventions for patients with polyneuropathy. Objective: Our objective in this systematic review with meta-analysis was to analyze exercise interventions for neuropathic patients in order to update a systematic review from 2014 and to evaluate the potential benefits of exercise on neuropathies of different origin that can then be translated into practice. Methods: Two independent reviewers performed a systematic review with meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Inclusion criteria according to the PICOS approach were: neuropathic patients, exercise interventions only, an inactive or non-exercising control group, and solely randomized controlled trials with the following outcome parameters: neuropathic symptoms, balance parameters, functional mobility, gait, health-related quality of life, and HbA1c (glycated hemoglobin). Results: A total of 41 randomized, controlled trials met all inclusion criteria, 20 of which could be included in the quantitative analysis. Study quality varied from moderate to high. Current data further support the hypothesis that exercise is beneficial for neuropathic patients. This is best documented for patients with diabetic peripheral neuropathy (DPN) (27 studies) as well as for chemotherapy-induced peripheral neuropathy (CIPN) (nine studies), while there are only few studies (five) on all other causes of neuropathy. We found standardized mean differences in favor of the exercise group of 0.27–2.00 for static balance, Berg Balance Scale, Timed-up-and-go-test, nerve conduction velocity of peroneal and sural nerve as well as for HbA1c in patients with DPN, and standardized mean differences of 0.43–0.75 for static balance, quality of life, and neuropathy-induced symptoms in patients with CIPN. Conclusion: For DPN, evidence-based recommendations can now be made, suggesting a combination of endurance and sensorimotor training to be most beneficial. For patients with CIPN, sensorimotor training remains the most crucial component. For all other neuropathies, more high-quality research is needed to derive evidence-based recommendations. Overall, it seems that sensorimotor training has great potential to target most neuropathies and combined with endurance training is therefore currently the best treatment option for neuropathies. Registration Number: (PROSPERO 2019 CRD42019124583)/16.04.2019.

Background Magnetic resonance imaging (MRI) is currently explored as supplemental tool to monitor disease progression and treatment response in various neuromuscular disorders. We here assessed the utility of a multi-parametric magnetic resonance imaging (MRI) protocol including quantitative water T2 mapping, Dixon-based proton density fat fraction (PDFF) estimation and diffusion tensor imaging (DTI) to detect loss of spinal motor neurons and subsequent muscle damage in adult SMA patients. Methods Sixteen SMA patients and 13 age-matched controls were enrolled in this prospective, longitudinal study. All participants underwent MRI imaging including measurements of Dixon-based PDFF and DTI of the sciatic nerve. SMA patients furthermore underwent measurements of muscle water T2 (T2w) of the biceps femoris muscle (BFM) and quadriceps femoris muscle (QFM). Ten participants returned for a second scan six months later. MRI parameter were correlated with clinical data. All patients were on nusinersen treatment. Results There were significantly higher intramuscular fat fractions in the BFM and QFM of SMA patients compared to healthy controls at baseline and after 6 months. Furthermore, T2 values significantly correlated positively with intramuscular fat fractions. The Hammersmith functional motor scale significantly correlated with the QFM’s intramuscular fat fractions. DTI scans of the sciatic nerve were not significantly different between the two groups. Conclusion This study demonstrates that, water T2 mapping and Dixon-based PDFF estimation may distinguish between adult SMA patients and controls, due to massive intramuscular fat accumulation in SMA. More extensive long-term studies are warranted to further evaluate these two modalities as surrogate markers in SMA patients during treatment.

Neben Storungen und Erkrankungen peripherer Nerven sind in den letzten Monaten im Zusammenhang mit COVID-19 („coronavirus disease 2019“) auch Begleitsymptome und Storungen der Muskulatur bzw. der neuromuskularen Transmission beschrieben worden. Im zweiten Teil unserer Zusammenfassung geben wir eine Ubersicht uber haufig berichtete Symptome wie Myalgien und definierte Erkrankungen wie Rhabdomyolysen, Myositiden, Myasthenie und „intensive care unit acquired weakness“ (ICUAW), die im Rahmen eine SARS-CoV-2(„severe acute respiratory syndrome coronavirus 2“)-Infektion bzw. COVID-19 beschrieben wurden. Daruber hinaus werden Kriterien fur eine Kausalitat wie Effektstarke, Plausibilitat, Zeitverlauf und experimentelle Evidenz fur einen kausalen Zusammenhang der in beiden Teilen der Ubersicht beschriebenen COVID-19 assoziierten neuromuskularen Erkrankungen diskutiert. Zum jetzigen Zeitpunkt sind – neben der auch in der Laienpresse bekannten Geruchssinnstorung – vor allem Myalgien als unspezifisches Symptom haufige Folge einer symptomatischen SARS-CoV‑2 Infektion. Andere neuromuskulare Komplikationen erscheinen hinsichtlich ihrer Pathogenese prinzipiell plausibel, aber offenbar selten Folge einer SARS-CoV-2-Infektion zu sein. Prospektive bzw. Kohortenstudien sind notwendig, um eine Kausalitat zu bestatigen und das Risiko abzuschatzen.

In recent months various disorders and diseases of the peripheral nerves (including cranial nerves) and the musculature have been described in association with the pulmonary disease coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the first part of our review the current knowledge about a potential association of a SARS-CoV‑2 infection with dysfunction and diseases of cranial and peripheral nerves is discussed. Anosmia, ageusia, motor cranial nerve involvement and Guillain-Barré syndrome (GBS) were described in a temporal association with a SARS-CoV‑2 infection. Several studies could show that anosmia and ageusia were frequent symptoms of a SARS-CoV‑2 infection. In contrast the failure of other cranial nerves has so far only been sporadically described. A number of case reports and case series indicate a causal association between a SARS-CoV‑2 infection and GBS but epidemiological evidence is still lacking.In den letzten Monaten sind im Zusammenhang mit einer durch das „severe acute respiratory syndrome coronavirus 2“ (SARS-CoV-2) ausgelösten Lungenerkrankung COVID-19 („coronavirus disease 2019“) verschiedene Störungen und Erkrankungen der peripheren Nerven (einschließlich Hirnnerven) und der Muskulatur beschrieben worden. Im ersten Teil unserer Übersicht diskutieren wir den aktuellen Stand einer möglichen Assoziation einer SARS-CoV-2-Infektion mit Affektionen peripherer Nerven (inklusive Hirnnerven). So wurden u. a. eine Anosmie und Ageusie, motorische Hirnnervenbeteiligung und Guillain-Barré-Syndrome (GBS) in zeitlichem Zusammenhang mit einer SARS-CoV-2-Infektion beschrieben. Mehrere Studien konnten zeigen, dass Anosmie und Ageusie häufige Symptome einer SARS-CoV-2-Infektion sind. Im Gegensatz dazu sind andere Hirnnervenausfälle bisher nur vereinzelt beschrieben worden. Eine Reihe von Fallberichten und Fallserien legt einen kausalen Zusammenhang zwischen einer SARS-CoV-2-Infektion und GBS nahe, epidemiologische Evidenz hierfür ist aber ausstehend.

Guillain-Barré syndrome is the most common cause of acute flaccid paralysis worldwide. Most patients present with an antecedent illness, most commonly upper respiratory tract infection, before the onset of progressive motor weakness. Several microorganisms have been associated with Guillain-Barré syndrome, most notably Campylobacter jejuni, Zika virus, and in 2020, the severe acute respiratory syndrome coronavirus 2. In C jejuni-related Guillain-Barré syndrome, there is good evidence to support an autoantibody-mediated immune process that is triggered by molecular mimicry between structural components of peripheral nerves and the microorganism. Making a diagnosis of so-called classical Guillain-Barré syndrome is straightforward; however, the existing diagnostic criteria have limitations and can result in some variants of the syndrome being missed. Most patients with Guillain-Barré syndrome do well with immunotherapy, but a substantial proportion are left with disability, and death can occur. Results from the International Guillain-Barré Syndrome Outcome Study suggest that geographical variations exist in Guillain-Barré syndrome, including insufficient access to immunotherapy in low-income countries. There is a need to provide improved access to treatment for all patients with Guillain-Barré syndrome, and to develop effective disease-modifying therapies that can limit the extent of nerve injury. Clinical trials are currently underway to investigate some of the potential therapeutic candidates, including complement inhibitors, which, together with emerging data from large international collaborative studies on the syndrome, will contribute substantially to understanding the many facets of this disease.

Diagnosis and treatment of patients with immune-mediated neuropathies is challenging due to the heterogeneity of the diseases.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".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.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.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.HINTERGRUND: Die Diagnose und Behandlung von Patienten mit immunvermittelten Polyneuropathien ist aufgrund der Heterogenität der Erkrankungen herausfordernd.Ein aktueller epidemiologischer Überblick über die Versorgungssituation von Patienten mit immunvermittelten Polyneuropathien innerhalb des deutschen Neuritis-Netzwerks „Neuritis Netz“.Es erfolgte eine Umfrage in neun deutschen neurologischen Zentren, die auf die Betreuung von Patienten mit Immunneuropathie spezialisiert sind. Wir erfassten Diagnose, Vorgehen in der Diagnostik und Nachsorge, typische Symptome bei Manifestation und im Krankheitsverlauf sowie Therapiedaten.Die Erhebung umfasst Daten von 1529 jährlich behandelten Patienten mit Immunneuropathien, 1320 davon mit chronisch inflammatorisch demyelinisierender Polyneuropathie (CIDP). Die Diagnostik umfasste fast immer Lumbalpunktionen sowie Elektroneuro- und -myografien entsprechend den aktuellen Leitlinien. Der Einsatz von Ultraschall, Biopsie und MRT war unterschiedlich. Wichtigster klinischer Parameter zum Therapiemonitoring in allen Zentren war die motorische Funktion in den klinischen Nachuntersuchungen. Zur Erhaltungstherapie wurde bei rund 15 % der Patienten ein breites Spektrum unterschiedlicher Immunsuppressiva eingesetzt.Die Studie liefert wichtige epidemiologische Daten zur aktuellen Versorgungsituation von Patienten mit Immunneuropathien in Deutschland. Die Weiterentwicklung spezifischer Empfehlungen zur Therapie und Nachverfolgung von CIDP-Patienten ist notwendig, um einen einheitlichen Standard der Patientenversorgung zu gewährleisten. Dieses wird durch die strukturierte Zusammenarbeit von Exzellenzzentren wie dem deutschen Neuritis Netz erheblich unterstützt.

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect persisting after completion of neurotoxic chemotherapies. This observational study was designed to evaluate the effectiveness of the dietary supplement OnLife® (patented mixture of specific fatty acids and palmitoylethanolamide) in improving symptoms of CIPN in breast and colon cancer patients. Methods: Improvement of CIPN was evaluated in adult patients, previously treated with (neo)adjuvant paclitaxel- (breast cancer) or oxaliplatin-based (colon cancer) therapies, receiving OnLife® for 3 months after completion of chemotherapy. The primary endpoint was to compare the severity of peripheral sensory neuropathy (PSN) and peripheral motor neuropathy (PMN) before and at the end of OnLife® treatment. Secondary endpoints included the assessment of patient-reported quality of life and CIPN symptoms as assessed by questionnaires. Results: 146 patients (n = 75 breast cancer patients and n = 71 colon cancer patients) qualified for analysis; 31.1% and 37.5% of breast cancer patients had an improvement of PSN and PMN, respectively. In colon cancer patients, PSN and PMN improved in 16.9% and 20.0% of patients, respectively. According to patient-reported outcomes, 45.9% and 37.5% of patients with paclitaxel-induced PSN and PMN, and 23.9% and 22.0% of patients with oxaliplatin-induced PSN and PMN experienced a reduction of CIPN symptoms, respectively. Conclusion: OnLife® treatment confirmed to be beneficial in reducing CIPN severity and in limiting the progression of neuropathy, more markedly in paclitaxel-treated patients and also in patients with oxaliplatin-induced CIPN.

Introduction Peripheral neuropathy represents a spectrum of diseases with different etiologies. The most common causes are diabetes, exposure to toxic substances including alcohol and chemotherapeutics, immune-mediated conditions, and gene mutations. A thorough workup including clinical history and examination, nerve conduction studies, and comprehensive laboratory tests is warranted to identify treatable causes. First steps The variability of symptoms allows distinguishing characteristic clinical phenotypes of peripheral neuropathy that should be recognized in order to stratify the diagnostic workup accordingly. Nerve conduction studies are essential to determine the phenotype (axonal versus demyelinating) and severity. Laboratory tests, including genetic testing, CSF examination, nerve imaging, and nerve biopsy, represent additional clinical tests that can be useful in specific clinical scenarios. Comments We propose a flow chart based on five common basic clinical patterns of peripheral neuropathy. Based on these five clinical phenotypes, we suggest differential diagnostic pathways in order to establish the underlying cause. Conclusions The recognition of characteristic clinical phenotypes combined with nerve conduction studies allows pursuing subsequent diagnostic pathways that incorporate nerve conduction studies and additional diagnostic tests. This two-tiered approach promises higher yield and better cost-effectiveness in the diagnostic workup in patients with peripheral neuropathy.

Objective To assess the importance of serum IgG/IgM antibody titers for the differentiation of Lyme neuroborreliosis (LNB) from its mimics. Method This was a retrospective, cross-sectional study conducted at two German neurological centers. Serological parameters (ELISA or CLIA analysis) and clinical presentation of 28 patients with definite LNB were compared to those of 36 patients with neurological symptoms mimicking LNB (mimics). Analysis was performed using receiver operating characteristic (ROC) and binary logistic regression. Results Elevated IgG-titers had a high sensitivity for neuroborreliosis in both centers (0.95 and 1.0). The optimal cutoff-values were set to 26.35 in center A (ELISA), and 64.0 in center B (CLIA). Diagnostic specificity was 0.41 and 0.89 in this constellation. Elevated IgM-titers showed a high diagnostic specificity for a cutoff at 68.10 (A) and 47.95 (B) (0.93 and 0.89). Sensitivity was 0.45 and 0.5. Overall diagnostic accuracy was low in both centers (A: IgG AUC = 0.665, IgM AUC = 0.629; B: IgG AUC = 0.917, IgM AUC = 0.556). In logistic regression of antibody titers and clinical measures, prediction of LNB was significantly better than the “null hypothesis”. Clinical measures showed the highest odds ratio. Conclusion Data show that in addition to the clinical presentation of patients with symptoms suggesting central or peripheral nervous system manifestation, serum IgG- and IgM-titers help to identify LNB-patients. The results should guide physicians counseling patients with suspected LNB about further diagnostic steps and treatment.

Abstract: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated polyradiculoneuropathy leading to disability via inflammatory demyelination of peripheral nerves. Various therapeutic approaches with different mechanisms of action are established for the treatment of CIDP. Of those, corticosteroids, intravenous or subcutaneous immunoglobulin, or plasma exchange are established first-line therapies as suggested by the recently revised EAN/PNS guidelines for the management of CIDP. In special cases, immunosuppressants or rituximab may be used. Novel therapeutic approaches currently undergoing clinical studies include molecules or monoclonal antibodies interacting with Fc receptors on immune cells to alleviate immune-mediated neuronal damage. Despite various established therapies and the current development of novel therapeutics, treatment of CIDP remains challenging due to an heterogeneous disease course and the lack of surrogate parameters to predict the risk of clinical deterioration. This review summarizes established therapies for CIDP and provides an outlook on future therapeutic approaches.

Peripheral neuropathy is one of the most common side effects of chemotherapy, affecting up to 60% of all cancer patients receiving chemotherapy. Moreover, paclitaxel induces neuropathy in up to 97% of all gynecological and urological cancer patients. In cancer cells, paclitaxel induces cell death via microtubule stabilization interrupting cell mitosis. However, paclitaxel also affects cells of the central and peripheral nervous system. The main symptoms are pain and numbness in hands and feet due to paclitaxel accumulation in the dorsal root ganglia. This review describes in detail the pathomechanisms of paclitaxel in the peripheral nervous system. Symptoms occur due to a length-dependent axonal sensory neuropathy, where axons are symmetrically damaged and die back. Due to microtubule stabilization, axonal transport is disrupted, leading to ATP undersupply and oxidative stress. Moreover, mitochondria morphology is altered during paclitaxel treatment. A key player in pain sensation and axonal damage is the paclitaxel-induced inflammation in the spinal cord as well as the dorsal root ganglia. An increased expression of chemokines and cytokines such as IL-1β, IL-8, and TNF-α, but also CXCR4, RAGE, CXCL1, CXCL12, CX3CL1, and C3 promote glial activation and accumulation, and pain sensation. These findings are further elucidated in this review.

ObjectiveTo evaluate the utility of nerve magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and muscle MRI multi-echo Dixon for assessing lower motor neuron (LMN) degeneration in amyotrophic lateral sclerosis (ALS).MethodsIn this prospective observational cohort study, 14 patients with ALS and 13 healthy controls underwent a multiparametric MRI protocol, including DTI of the sciatic nerve and assessment of muscle proton density fat fraction of the biceps femoris and the quadriceps femoris muscles by a multi-echo Dixon sequence.ResultsIn ALS patients, mean fractional anisotropy values of the sciatic nerve were significantly lower than those of healthy controls. The quadriceps femoris, but not the biceps femoris muscle, showed significantly higher intramuscular fat fractions in ALS.InterpretationOur study provides evidence that multiparametric MRI protocols might help estimate structural nerve damage and neurogenic muscle changes in ALS.

Intravenous immunoglobulins (IVIg) are standard treatment for Guillain-Barré syndrome (GBS). Their exact mechanisms of action are versatile and not fully understood. One possible mechanism is neutralization of circulating autoantibodies via binding to anti- idiotypic antibodies forming idiotype-anti-idiotype dimeric IgG immune complexes. To examine the role of immune complex formation as mechanism of action for IVIg in GBS, 34 C57Bl/6 mice were either treated with anti-ganglioside antibodies and IVIg or IVIg and PBS alone, whereas eight additional mice were treated either with anti-ganglioside autoantibodies and IVIg or anti-ganglioside autoantibodies alone. Subsequently IgG dimer formation was assessed by high performance liquid chromatography (HPLC) and enzyme- linked immunosorbent assay (ELISA). In addition, IgG dimer formation was measured in sera of eight GBS patients who were treated with IVIg. In mice, a significant increase of dimeric IgG after administration of anti-ganglioside antibodies and IVIg could be observed. Re-monomerized IgG dimers showed immunoreactivity against gangliosides and serum immunoreactivity was significantly reduced after IVIg infusion. Likewise also in GBS patients, IgG dimer formation could be detected after IVIg treatment. Our data indicate that dimeric IgG immune complexes contain anti-idiotypic antibodies and provide proof of concept that IVIg treatment in GBS results in measurable amounts of IgG dimers. Larger patient cohorts are needed to evaluate serum IgG dimer increase as a possible marker for treatment response in GBS. Graphical Abstract Mechanism of action: Intravenous immunoglobulins (IVIg) and anti-ganglioside antibodies form dimeric IgG immune complexes, preventing axonal damage in Guillain-Barré Syndrome.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disorder causing inflammatory demyelination of peripheral nerves and consecutive disability. Diagnostic criteria and treatments are well established, but it is unknown how clinical practice may differ in different geographical regions. In this multicentre study, clinical management of CIDP was compared in 44 patients from Germany, India and Norway regarding diagnostic and therapeutic procedures. All centres used EFNS/PNS diagnostic criteria for CIDP but diagnostic workup varied regarding screening for infectious diseases, genetic testing and nerve biopsy. Intravenous immunoglobulin and prednisolone were the most common therapies in all centres with differences in indication and dosage. Patients from the Indian cohort were the most severely affected with less diverse therapeutic approaches, whereas psychological strain did not differ significantly from the two other cohorts. Our exploratory study discloses an unaddressed issue in management of CIDP that should be further investigated to optimise standard of care for CIDP worldwide.

Background and aims Peripheral neuropathy is a common side effect of paclitaxel. Clinical studies suggest that different paclitaxel formulations influence the severity and time course of paclitaxel-induced peripheral neuropathy. We compared two paclitaxel formulations, nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and Cremophor EL paclitaxel (CreEL-paclitaxel), for their toxicity, distribution, and clearance in the peripheral nervous system. Methods Neuronal F11 cells were used to detect changes in morphology, cell nuclei size, and cell viability after nab- or CreEL-paclitaxel treatment via MTT Assay and immunohistochemistry. C57BL/6 mice were treated with 50 mg/kg of nab-paclitaxel or CreEL-paclitaxel. Paclitaxel levels in serum, liver, dorsal root ganglia (DRG), and sciatic nerve (SCN) were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Accumulation of paclitaxel in DRG neurons and SCN was visualized by immunostainings. Neurotoxicity was evaluated after a 4-week treatment regime with nab- or CreEL-paclitaxel by nerve morphology, behavioral and functional assays. Results In vitro cell nuclei size and morphology were similar between the two treatment groups. Viability was increased in neurons exposed to nab-paclitaxel compared to CreEL-paclitaxel. In vivo paclitaxel mostly accumulated in DRG. SCN displayed lower paclitaxel uptake. The two paclitaxel formulations mainly accumulated in neurofilament 200-positive large-caliber neurons and less in Isolectin B4-, or Calcitonin Gene-Related Peptide-positive small-caliber neurons. Sensory nerve conduction studies demonstrated increased sensory latencies after 11 days in nab-paclitaxel treated animals, while an increase occurred after 22 days in CreEL-paclitaxel treated animals. Behavioral testing did not reveal significant differences between the different groups. Skin denervation, axon count, myelin thickness, and F4/80-positive cell accumulation were comparable between the two treatment groups. Interpretation Our findings indicate that different drug formulations impact the severity of neuropathy induced by paclitaxel via different tissue uptake. Neurotoxicity was comparable between the two paclitaxel formulations. This article is protected by copyright. All rights reserved.

Apart from disorders and diseases of the peripheral nerves, symptoms and disorders of the musculature and the neuromuscular transmission have also been described in association with coronavirus disease 2019 (COVID-19). In the second part of our review we provide an overview about frequently reported symptoms, such as myalgia as well as defined disorders, such as rhabdomyolysis, myositis, myasthenia and intensive care unit (ICU)-acquired weakness, which have been described during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections or COVID-19.Furthermore, the criteria for a causality, such as association strength, plausibility, time course, and experimental evidence for a causal association that should be applied for the COVID-19-asssociated neuromuscular conditions described in the two parts of the review are discussed. At present, in addition to anosmia, which is also known in the lay press, myalgia in particular as a nonspecific symptom are frequent sequelae of a symptomatic SARS-CoV‑2 infection. Other neuromuscular complications seem to be principally plausible (considering the pathogenesis) but apparently rare consequences of a SARS-CoV‑2 infection. Prospective or cohort studies are necessary to confirm a causality and assess the risk.Neben Störungen und Erkrankungen peripherer Nerven sind in den letzten Monaten im Zusammenhang mit COVID-19 („coronavirus disease 2019“) auch Begleitsymptome und Störungen der Muskulatur bzw. der neuromuskulären Transmission beschrieben worden. Im zweiten Teil unserer Zusammenfassung geben wir eine Übersicht über häufig berichtete Symptome wie Myalgien und definierte Erkrankungen wie Rhabdomyolysen, Myositiden, Myasthenie und „intensive care unit acquired weakness“ (ICUAW), die im Rahmen eine SARS-CoV-2(„severe acute respiratory syndrome coronavirus 2“)-Infektion bzw. COVID-19 beschrieben wurden. Darüber hinaus werden Kriterien für eine Kausalität wie Effektstärke, Plausibilität, Zeitverlauf und experimentelle Evidenz für einen kausalen Zusammenhang der in beiden Teilen der Übersicht beschriebenen COVID-19 assoziierten neuromuskulären Erkrankungen diskutiert. Zum jetzigen Zeitpunkt sind – neben der auch in der Laienpresse bekannten Geruchssinnstörung – vor allem Myalgien als unspezifisches Symptom häufige Folge einer symptomatischen SARS-CoV‑2 Infektion. Andere neuromuskuläre Komplikationen erscheinen hinsichtlich ihrer Pathogenese prinzipiell plausibel, aber offenbar selten Folge einer SARS-CoV-2-Infektion zu sein. Prospektive bzw. Kohortenstudien sind notwendig, um eine Kausalität zu bestätigen und das Risiko abzuschätzen.

Das periphere Nervensystem kann auf ganz unterschiedliche Art und Weise durch Infektionen geschadigt werden. Eine direkte Invasion der peripheren Nerven kann auftreten. Einige Erreger bilden Toxine, die die nervale Funktion und die neuromuskulare Ubertragung blockieren. Hierzu gehort auch Clostridium tetani, welches das Toxin Tetanospasmin bildet. Auch wenn dieses primar zentrale inhibitorische Interneurone beeintrachtigt, und somit eine zentrale klinische Symptomatik hervorruft, wird es in diesem Kapitel behandelt, da es zu den Toxin bildenden Erregern gehort.

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.

BACKGROUND AND PURPOSE The aim was to assess the organization and short-term changes of motor units in adult patients with spinal muscular atrophy (SMA) treated with nusinersen. METHODS In this single-centre cross-sectional and longitudinal study 15 adult patients with SMA type 3 were assessed and compared to 15 age-matched healthy controls and nine patients with amyotrophic lateral sclerosis. Moreover, 10 patients with SMA were followed up after 4-8 months. All patients were investigated clinically and by the motor unit number estimation method MScanFit of the abductor pollicis brevis muscle. RESULTS The number of motor units (p

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.