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ABSTRACT Objective We aim to describe and characterize two unrelated Spanish families suffering from an autosomal dominant autophagic vacuolar myopathy caused by repeat expansions in PLIN4. Methods We evaluated the clinical phenotype and muscle imaging, and performed a genetic workup that included exome sequencing, muscle RNAseq, and long‐read genome sequencing. Muscle pathology was assessed by means of histochemistry, electron microscopy, PLIN4, p62, LC3, and NBR1 immunofluorescence and/or western blotting. Detailed characterization of autophagic vacuoles was performed. Results Patients presented around the age of 30 with mild proximal weakness followed by prominent distal weakness in lower legs, eventually spreading to other muscle groups. Muscle biopsies showed unique pathological features characterized by numerous rimmed vacuoles that displayed sarcolemmal features and were located beneath the sarcolemma and within the cytoplasm. Ultrastructural studies showed autophagic vacuoles, replications, and loops of the basal lamina and tubulofilamentous sarcoplasmic inclusions. p62 and NBR1 co‐localized with PLIN4 at the sarcolemma and vacuoles. LC3 immunoreactivity and other lysosomal markers were increased at the vacuoles. Targeted long‐read sequencing of PLIN4 in affected individuals revealed a single expanded allele of 39 × 99 bp repeats in family 1 and of 37 × 99 bp repeats in family 2. Interpretation We characterize two new families suffering from an autosomal dominant myopathy carrying repeat expansions in PLIN4. Subsarcolemmal p62 expression is a powerful although nonspecific marker of this disease. No correlation between the size of the expansion and clinical severity can be clearly established. PLIN4 expansions should be considered in the diagnosis of autosomal dominant vacuolar myopathies, especially when sarcolemmal features are present.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated disease of the peripheral nerves characterized by proximal and distal muscle weakness and sensory abnormalities. CIDP has been associated with various pathophysiological mechanisms that are not fully understood and that likely differ across groups of patients. It has been proposed that an interplay of different immunopathological mechanisms including the cellular, humoral and complement pathways play a key role in peripheral nerve damage in CIDP. Currently approved treatments and therapies in research often target different potential pathophysiological mechanisms. The efficacy of these different treatments can shed light on the prominence of particular pathophysiological pathways in subsets of patients with CIDP. For example, the complement pathway plays a key role in promoting macrophage-mediated demyelination, and complement inhibitors are under development as new targets in CIDP treatment, with mixed results. The neonatal Fc receptor (FcRn) has also been targeted as a promising treatment avenue due to its role in immunoglobulin G degradation. Efgartigimod is the first FcRn blocker approved for the treatment of CIDP. This review provides an overview of key proposed mechanisms of action in CIDP pathophysiology in the context of both basic scientific findings and treatment targets in recent clinical studies.

Background and purpose The purpose was to perform a nationwide epidemiological study of Guillain–Barré syndrome (GBS) in Spain, analysing background incidences and seasonal variation and trying to identify incidence changes during the coronavirus disease 2019 (COVID‐19) years. Methods This was an observational study collecting all GBS diagnoses from the National Epidemiological Surveillance Network collected by the Ministry of Health. Patients discharged with GBS as the main diagnosis and admitted during 2018–2021 were included. Data on the incidence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infections were obtained from the National Epidemiology Centre. Results In total, 3147 cases were included, 832 in 2018, 861 in 2019, 670 in 2020 and 784 in 2021. Nationwide hospital incidence was 1.78 in 2018, 1.71 in 2019, 1.41 in 2020 and 1.66 in 2021, with an increased frequency in males, the elderly population and in the winter season. Eleven per cent of GBS patients needed ventilatory support. GBS and SARS‐CoV‐2 incidences did not correlate with one another (r = −0.29, p = 0.36). GBS incidence decreased during 2020 and during the COVID‐19 lockdown period in comparison to the same months of 2018–2019. Conclusions The incidence of GBS in Spain is similar to that of other countries. Despite prior reports describing a significant increase in COVID‐19‐associated GBS in Spain, a significant drop of GBS incidence during the SARS‐CoV‐2 pandemic was detected, probably due to prevention measures.

Background The clinical status and treatment response of patients with peripheral neuropathies (PNs) rely on subjective and inaccurate clinical scales. Wearable sensors have been evaluated successfully in other neurological conditions to study gait and balance. Our aim was to explore the ability of biomechanical analysis using wearable technology to monitor disease activity in PN. Methods We conducted a single-center, longitudinal study to analyze gait parameters in PN patients and healthy controls using wearable biomechanical sensors. We used a novel technology that registers and integrates data from multiple wearable inertial sensors placed at different locations and plantar insoles. This system allows measuring kinematics, spatio-temporal parameters and plantar pressure. Patients wore the wearable system while performing the 2-min walking test (2MWT). Results We included 37 chronic inflammatory demyelinating polyneuropathy (CIDP) patients, 3 chronic ataxic neuropathy, ophthalmoplegia, immunoglobulin M [IgM] paraprotein (CANOMAD) patients, 21 monoclonal gammopathy patients of undetermined significance associated with IgM (IgM-MGUS) patients, 7 patients with autoimmune nodopathies, 11 patients with hereditary neuropathies, and 50 healthy controls. First, we analyzed the sensor's ability to detect changes in ataxia and steppage gait severity and found significant differences in spatiotemporal and angular variables of the gait cycle. Second, we found correlations between biomechanical features and clinical scales and with the specific gait phenotype they associated with. Finally, we demonstrated that this technology is able to capture clinically significant changes in gait features over time. Conclusions Our study provides proof-of-concept that wearable technology effectively detects and grades gait impairment, captures clinically relevant changes, and could enhance gait assessment in routine care and clinical research for patients with PN.