Tissue Doppler ultrasound of arm muscles to assess myotonia in myotonic dystrophies: An exploratory study.

INTRODUCTION/AIMS: Myotonia is a key symptom of myotonic dystrophies (DM), and its quantification is challenging. This exploratory study evaluated the utility of tissue Doppler ultrasound (TDU) to assess myotonia in DM. METHODS: Twelve DM patients (seven type-1 DM [DM1] and five type-2 DM [DM2]) and 20 age-matched healthy subjects were included in this cross-sectional study. After measuring cross-sectional areas of the flexor digitorum superficialis (FDS) and extensor digitorum communis (EDC) muscles in a resting state, muscle contraction/relaxation time, time to peak tissue velocity, peak tissue velocity and velocity gradients of these muscles were measured via TDU while performing forced fist unclenching after fist closure. Additionally, grip strength, Medical Research Council Sum score and patient-reported myotonia severity scores were assessed. RESULTS: DM1 and DM2 patients had a lower grip strength than healthy subjects (p = .0001/p = .002). Patient-reported myotonia did not differ between DM1 and DM2 patients. DM1 patients revealed FDS and EDC atrophy compared to DM2 patients and healthy subjects (p = .003/p = .004). TDU revealed prolonged muscle contraction and relaxation times in both DM subtypes, with prolonged time to reach FDS peak relaxation velocity and altered peak FDS relaxation velocity only in DM1 patients (p = .03/p = .003). Peak FDS relaxation velocity correlated inversely with C(C)TG repeat numbers in DM patients. Sensitivity of TDU parameters to detect myotonic dystrophy varied between 50% and 75%, with a specificity of 95%. DISCUSSION: Our exploratory study suggests that TDU could serve as a novel tool to quantify myotonia in DM patients, but larger follow-up studies are warranted to validate its diagnostic accuracy.

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.

Peripheral neuropathy, an independent risk factor for falls in the elderly, impairs stepping as a postural control mechanism: A case-cohort study.

BACKGROUND/AIMS: Peripheral neuropathies perturbate the sensorimotor system, causing difficulties in walking-related motor tasks and, eventually, falls. Falls result in functional dependency and reliance on healthcare, especially in older persons. We investigated if peripheral neuropathy is a genuine risk factor for falls in the elderly and if quantification of postural control via posturography is helpful in identifying subjects at risk of falls. METHODS: Seventeen older persons with a clinical polyneuropathic syndrome of the lower limbs and converging electrophysiology were compared with 14 older persons without polyneuropathy. All participants were characterized via quantitative motor and sensory testing, neuropsychological assessment, and self-questionnaires. Video-nystagmography and caloric test excluded vestibulocochlear dysfunction. For further analysis, all subjects were stratified into fallers and non-fallers. Overall, 28 patients underwent computerized dynamic posturography for individual fall risk assessment. Regression analyses were performed to identify risk factors and predictive posturography parameters. RESULTS: Neuropathy is an independent risk factor for falls in the elderly, while no differences were observed for age, gender, weight, frailty, DemTect test, timed "Up & Go" test, and dizziness-related handicap score. In computerized dynamic posturography, fallers stepped more often to regain postural control in challenging conditions, while the Rhythmic Weight Shift test showed a lack of anterior-posterior bidirectional voluntary control. INTERPRETATION: Our study confirms peripheral neuropathy as a risk factor for older persons' falls. Fallers frequently used stepping to regain postural control. The voluntary control of this coping movement was impaired. Further investigations into these parameters' value in predicting the risk of falls in the elderly are warranted.

[Expert recommendations for magnetic resonance imaging of muscle disorders]. / Expertenempfehlung zur Magnetresonanztomographie bei Muskelerkrankungen.

BACKGROUND: Magnetic resonance (MRI) imaging of the skeletal muscles (muscle MRI for short) is increasingly being used in clinical routine for diagnosis and longitudinal assessment of muscle disorders. However, cross-centre standards for measurement protocol and radiological assessment are still lacking. OBJECTIVES: The aim of this expert recommendation is to present standards for the application and interpretation of muscle MRI in hereditary and inflammatory muscle disorders. METHODS: This work was developed in collaboration between neurologists, neuroradiologists, radiologists, neuropaediatricians, neuroscientists and MR physicists from different university hospitals in Germany. The recommendations are based on expert knowledge and a focused literature search. RESULTS: The indications for muscle MRI are explained, including the detection and monitoring of structural tissue changes and oedema in the muscle, as well as the identification of a suitable biopsy site. Recommendations for the examination procedure and selection of appropriate MRI sequences are given. Finally, steps for a structured radiological assessment are presented. CONCLUSIONS: The present work provides concrete recommendations for the indication, implementation and interpretation of muscle MRI in muscle disorders. Furthermore, it provides a possible basis for the standardisation of the measurement protocols at all clinical centres in Germany.

[Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)]. / Chronische inflammatorische demyelinisierende Polyradikuloneuropathie (CIDP).

Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common chronic autoimmune disease of the peripheral nervous system. It is often difficult to diagnose, but severaly therapeutic options are nowadays available to reduce neurological deficits and to improve the disease course. This article exemplifies the management of CIDP by a typical case study.

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.

Subclinical motor involvement in nonsystemic vasculitic neuropathy determined by the motor unit number estimation method MScanFit.

INTRODUCTION/AIMS: Nonsystemic vasculitic neuropathy (NSVN) is characterized by a predominant lower limb involvement in many patients. Motor unit changes in upper extremity muscles have not been investigated in this subgroup but may be of interest for improving our understanding of the multifocal nature of the disease and counseling of patients about potential future symptoms. In this study we aimed to better understand subclinical motor involvement in the upper extremity muscles of patients with lower limb-predominant NSVN using the new motor unit number estimation (MUNE) method MScanFit. METHODS: In this single-center, cross-sectional study, 14 patients with biopsy-proven NSVN, with no clinical signs of upper extremity motor involvement, were investigated and compared with 14 age-matched healthy controls. All participants were assessed clinically and by the MUNE method MScanFit to the abductor pollicis brevis muscle. RESULTS: The number of motor units and peak CMAP amplitudes were significantly reduced in patients with NSVN (P = .003 and P = .004, respectively). Absolute median motor unit amplitudes and CMAP discontinuities were not significantly different (P = .246 and P = .1, respectively). CMAP discontinuities were not significantly correlated with motor unit loss (P = .15, rho = 0.4). The number of motor units did not correlate with clinical scores (P = .77, rho = 0.082). DISCUSSION: Both MUNE and CMAP amplitudes showed motor involvement in upper extremity muscles in lower limb-predominant NSVN. Overall, there was no evidence of significant reinnervation. Investigations of the abductor pollicis brevis muscle did not show a correlation with overall functional disability of the patients.

The gut microbiome in intravenous immunoglobulin-treated chronic inflammatory demyelinating polyneuropathy.

BACKGROUND AND PURPOSE: The gut microbiome is involved in autoimmunity. Data on its composition in chronic inflammatory demyelinating polyneuropathy (CIDP), the most common chronic autoimmune disorder of peripheral nerves, are currently lacking. METHODS: In this monocentric exploratory pilot study, stool samples were prospectively collected from 16 CIDP patients (mean age 58 ± 10 years, 25% female) before and 1 week after administration of intravenous immunoglobulin (IVIg). Gut microbiota were analyzed via bacterial 16S rRNA gene sequencing and compared to 15 age-matched healthy subjects (mean age 59 ± 15 years, 66% female). RESULTS: The gut microbiota of CIDP patients showed an increased alpha-diversity (p = 0.005) and enrichment of Firmicutes, such as Blautia (p = 0.0004), Eubacterium hallii (p = 0.0004), or Ruminococcus torques (p = 0.03), and of Actinobacteriota (p = 0.03) compared to healthy subjects. IVIg administration did not alter the gut microbiome composition in CIDP in this short-term observation (p = 0.95). CONCLUSIONS: The gut microbiome in IVIg-treated CIDP shows distinct features, with increased bacterial diversity and enrichment of short-chain fatty acid producing Firmicutes. IVIg had no short-term impact on the gut microbiome in CIDP patients. As the main limitation of this exploratory pilot study was small cohort size, future studies also including therapy-naïve patients are warranted to verify our findings and to explore the impact of long-term IVIg treatment on the gut microbiome in CIDP.

European Academy of Neurology/Peripheral Nerve Society Guideline on diagnosis and treatment of Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy. Symptoms may vary greatly in presentation and severity. Besides weakness and sensory disturbances, patients may have cranial nerve involvement, respiratory insufficiency, autonomic dysfunction and pain. To develop an evidence-based guideline for the diagnosis and treatment of GBS, using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology a Task Force (TF) of the European Academy of Neurology (EAN) and the Peripheral Nerve Society (PNS) constructed 14 Population/Intervention/Comparison/Outcome questions (PICOs) covering diagnosis, treatment and prognosis of GBS, which guided the literature search. Data were extracted and summarised in GRADE Summaries of Findings (for treatment PICOs) or Evidence Tables (for diagnostic and prognostic PICOs). Statements were prepared according to GRADE Evidence-to-Decision (EtD) frameworks. For the six intervention PICOs, evidence-based recommendations are made. For other PICOs, good practice points (GPPs) are formulated. For diagnosis, the principal GPPs are: GBS is more likely if there is a history of recent diarrhoea or respiratory infection; CSF examination is valuable, particularly when the diagnosis is less certain; electrodiagnostic testing is advised to support the diagnosis; testing for anti-ganglioside antibodies is of limited clinical value in most patients with typical motor-sensory GBS, but anti-GQ1b antibody testing should be considered when Miller Fisher syndrome (MFS) is suspected; nodal-paranodal antibodies should be tested when autoimmune nodopathy is suspected; MRI or ultrasound imaging should be considered in atypical cases; and changing the diagnosis to acute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP) should be considered if progression continues after 8 weeks from onset, which occurs in around 5% of patients initially diagnosed with GBS. For treatment, the TF recommends intravenous immunoglobulin (IVIg) 0.4 g/kg for 5 days, in patients within 2 weeks (GPP also within 2-4 weeks) after onset of weakness if unable to walk unaided, or a course of plasma exchange (PE) 12-15 L in four to five exchanges over 1-2 weeks, in patients within 4 weeks after onset of weakness if unable to walk unaided. The TF recommends against a second IVIg course in GBS patients with a poor prognosis; recommends against using oral corticosteroids, and weakly recommends against using IV corticosteroids; does not recommend PE followed immediately by IVIg; weakly recommends gabapentinoids, tricyclic antidepressants or carbamazepine for treatment of pain; does not recommend a specific treatment for fatigue. To estimate the prognosis of individual patients, the TF advises using the modified Erasmus GBS outcome score (mEGOS) to assess outcome, and the modified Erasmus GBS Respiratory Insufficiency Score (mEGRIS) to assess the risk of requiring artificial ventilation. Based on the PICOs, available literature and additional discussions, we provide flow charts to assist making clinical decisions on diagnosis, treatment and the need for intensive care unit admission.

European Academy of Neurology/Peripheral Nerve Society Guideline on diagnosis and treatment of Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy. Symptoms may vary greatly in presentation and severity. Besides weakness and sensory disturbances, patients may have cranial nerve involvement, respiratory insufficiency, autonomic dysfunction and pain. To develop an evidence-based guideline for the diagnosis and treatment of GBS, using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, a Task Force (TF) of the European Academy of Neurology (EAN) and the Peripheral Nerve Society (PNS) constructed 14 Population/Intervention/Comparison/Outcome questions (PICOs) covering diagnosis, treatment and prognosis of GBS, which guided the literature search. Data were extracted and summarised in GRADE Summaries of Findings (for treatment PICOs) or Evidence Tables (for diagnostic and prognostic PICOs). Statements were prepared according to GRADE Evidence-to-Decision (EtD) frameworks. For the six intervention PICOs, evidence-based recommendations are made. For other PICOs, good practice points (GPPs) are formulated. For diagnosis, the principal GPPs are: GBS is more likely if there is a history of recent diarrhoea or respiratory infection; CSF examination is valuable, particularly when the diagnosis is less certain; electrodiagnostic testing is advised to support the diagnosis; testing for anti-ganglioside antibodies is of limited clinical value in most patients with typical motor-sensory GBS, but anti-GQ1b antibody testing should be considered when Miller Fisher syndrome (MFS) is suspected; nodal-paranodal antibodies should be tested when autoimmune nodopathy is suspected; MRI or ultrasound imaging should be considered in atypical cases; and changing the diagnosis to acute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP) should be considered if progression continues after 8 weeks from onset, which occurs in around 5% of patients initially diagnosed with GBS. For treatment, the TF recommends intravenous immunoglobulin (IVIg) 0.4 g/kg for 5 days, in patients within 2 weeks (GPP also within 2-4 weeks) after onset of weakness if unable to walk unaided, or a course of plasma exchange (PE) 12-15 L in four to five exchanges over 1-2 weeks, in patients within 4 weeks after onset of weakness if unable to walk unaided. The TF recommends against a second IVIg course in GBS patients with a poor prognosis; recommends against using oral corticosteroids, and weakly recommends against using IV corticosteroids; does not recommend PE followed immediately by IVIg; weakly recommends gabapentinoids, tricyclic antidepressants or carbamazepine for treatment of pain; does not recommend a specific treatment for fatigue. To estimate the prognosis of individual patients, the TF advises using the modified Erasmus GBS outcome score (mEGOS) to assess outcome, and the modified Erasmus GBS Respiratory Insufficiency Score (mEGRIS) to assess the risk of requiring artificial ventilation. Based on the PICOs, available literature and additional discussions, we provide flow charts to assist making clinical decisions on diagnosis, treatment and the need for intensive care unit admission.

Rare cases of Guillain-Barré syndrome after COVID-19 vaccination, Germany, December 2020 to August 2021.

BackgroundGuillain-Barré syndrome (GBS) has been associated with vaccination against COVID-19.AimWe aimed to compare clinical characteristics and analyse excess GBS cases following administration of different COVID-19 and influenza vaccines in Germany versus the expected numbers estimated from pre-pandemic background incidence rates.MethodsWe analysed safety surveillance data reported to the German national competent authority between 27 December 2020 and 31 August 2021. GBS cases were validated according to Brighton Collaboration (BC) criteria. We conducted observed vs expected (OvE) analyses on cases fulfilling BC criteria levels 1 to 4 for all four European Medicines Agency-approved COVID-19 vaccines and for influenza vaccines.ResultsA total of 214 GBS cases after COVID-19 vaccination had been reported, of whom 156 were eligible for further analysis. Standardised morbidity ratio estimates 3-42 days after vaccination were 0.34 (95% confidence interval (CI): 0.25-0.44) for Comirnaty, 0.38 (95% CI: 0.15-0.79) for Spikevax, 3.10 (95% CI: 2.44-3.88) for Vaxzevria, 4.16 (95% CI: 2.64-6.24) for COVID-19 Vaccine Janssen and 0.60 (95% CI: 0.35-0.94) for influenza vaccines. Bilateral facial paresis was reported in 19.7% and 26.1% of the 156 GBS cases following vaccination with Vaxzevria and COVID-19 Vaccine Janssen, respectively, and only in 6% of cases exposed to Comirnaty.ConclusionThree and four times more GBS cases than expected were reported after vaccination with Vaxzevria and COVID-19 Vaccine Janssen, respectively, therefore GBS might be an adverse event of vector-based vaccines. Bifacial paresis was more common in cases with GBS following vaccination with vector-based than mRNA COVID-19 vaccines.

[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.

Guillain-Barré syndrome.

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.

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.

Electrodiagnostic subtyping in Guillain-Barré syndrome: Use of criteria in practice based on a survey study in IGOS.

Electrodiagnostic (EDx) studies are helpful in diagnosing and subtyping of Guillain-Barré syndrome (GBS). Published criteria for differentiation into GBS subtypes focus on cutoff values, but other items receive less attention, although they may influence EDx subtyping: (a) extensiveness of EDx testing, (b) nerve-specific considerations, (c) distal compound muscle action potential (CMAP)-amplitude requirements, (d) criteria for conduction block and temporal dispersion. The aims of this study were to investigate how these aspects were approached by neuromuscular EDx experts in practice and how this was done in previously published EDx criteria for GBS. A completed questionnaire was returned by 24 (of 49) members of the electrophysiology expertise group from the International GBS Outcome Study. Six published EDx criteria for GBS subtyping were compared regarding these aspects. The indicated minimal number of motor nerves to study varied among respondents and tended to be more extensive in equivocal than normal studies. Respondents varied considerably regarding usage of compression sites for subtyping (median/wrist, ulnar/elbow, peroneal/fibular head): 29% used all variables from all sites, 13% excluded all sites, and 58% used only some sites and/or variables. Thirty-eight percent of respondents required a minimal distal CMAP amplitude to classify distal motor latency as demyelinating, and 58% did for motor conduction velocity. For proximal/distal CMAP-amplitude ratio and F-wave latency, a requisite minimal CMAP amplitude was more often required (79%). Also, the various published criteria sets showed differences on all items. Practical use of EDx criteria for subtyping GBS vary extensively across respondents, potentially lowering the reproducibility of GBS subtyping.

[Neuromuscular manifestations in long-COVID syndrome]. / Neuromuskuläre Manifestationen beim Long-COVID-Syndrom.

The term long-COVID syndrome encompasses symptoms that occur after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, persisting over a period of several weeks, and which cannot be explained by another diagnosis. Long-COVID is considered to be a multiorgan condition. In this review article, the data regarding neuromuscular manifestations of long-COVID syndrome are summarized and evaluated based on criteria, such as effect size, plausibility, coherence, and experimental evidence. So far, myalgia and autonomic dysfunction (especially postural tachycardia syndrome) have been postulated as neuromuscular symptoms of long-COVID; however, the evidence to date is limited. In addition to very heterogeneous methodologies and different definitions of long-COVID in the clinical studies, conclusive experimental data supporting the described symptoms as a specific long-term consequence of COVID-19 are lacking.

Persistent hypokalaemia and intermittent muscle weakness.

A man in his 20s gave a 9-year history of recurrent muscle pain and weakness, occurring mostly after exercise, and lasting for up to 2 days. There had been one episode of severe rhabdomyolysis after cold exposure. He also had longstanding hypokalaemia, which was key to his correct diagnosis but was not followed. This case highlights the importance of an appropriately methodical investigation of weak hypokalaemic patients, and the relevance of hypokalaemia as a cause of neuromuscular symptoms not related to muscular channelopathies.

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.

Intravenous immunoglobulin treatment for mild Guillain-Barré syndrome: an international observational study.

OBJECTIVE: To compare the disease course in patients with mild Guillain-Barré syndrome (GBS) who were treated with intravenous immunoglobulin (IVIg) or supportive care only. METHODS: We selected patients from the prospective observational International GBS Outcome Study (IGOS) who were able to walk independently at study entry (mild GBS), treated with one IVIg course or supportive care. The primary endpoint was the GBS disability score four weeks after study entry, assessed by multivariable ordinal regression analysis. RESULTS: Of 188 eligible patients, 148 (79%) were treated with IVIg and 40 (21%) with supportive care. The IVIg group was more disabled at baseline. IVIg treatment was not associated with lower GBS disability scores at 4 weeks (adjusted OR (aOR) 1.62, 95% CI 0.63 to 4.13). Nearly all secondary endpoints showed no benefit from IVIg, although the time to regain full muscle strength was shorter (28 vs 56 days, p=0.03) and reported pain at 26 weeks was lower (n=26/121, 22% vs n=12/30, 40%, p=0.04) in the IVIg treated patients. In the subanalysis with persistent mild GBS in the first 2 weeks, the aOR for a lower GBS disability score at 4 weeks was 2.32 (95% CI 0.76 to 7.13). At 1 year, 40% of all patients had residual symptoms. CONCLUSION: In patients with mild GBS, one course of IVIg did not improve the overall disease course. The certainty of this conclusion is limited by confounding factors, selection bias and wide confidence limits. Residual symptoms were often present after one year, indicating the need for better treatments in mild GBS.

Motor unit number estimation in adult patients with spinal muscular atrophy treated with nusinersen.

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 < 0.001) was significantly lower in patients with SMA compared to healthy controls at study entry. Mean unit amplitude, median amplitude and largest unit (p < 0.001) were significantly increased in patients with SMA. Patients with amyotrophic lateral sclerosis showed a significant reduction of compound muscle action potential (p = 0.005) and number of motor units (p = 0.03) compared to patients with SMA, accompanied by a larger median amplitude (p = 0.03). A prospective analysis identified patients with the ability to walk to improve the number of motor units (p = 0.046) accompanied by a decreased median amplitude (p = 0.03). Electrophysiological measures showed a moderate to strong correlation with clinical scores. CONCLUSION: Patients with SMA show loss of motor units in distal muscles. MScanFit variables indicate that compound muscle action potential amplitudes are maintained by collateral sprouting. Prospective analyses suggest that milder affected adult patients with SMA preferentially benefit from nusinersen treatment through recovery of smaller motor units. Correlations with clinical scores underline the potential of MScanFit as a surrogate marker.