Tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK) are clinically overlapping disorders characterized by muscle weakness, thrombocytopenia, spleen anomalies and short stature. They are due to mutations affecting the Ca2+ sensor STIM1 or the Ca2+ channel ORAI1 and leading to aberrant Ca2+ homeostasis. Therapeutic approaches aiming to rebalance intracellular Ca2+ levels largely rescued the multi-systemic phenotype in Stim1R304W/+ mice harboring the most common TAM/STRMK mutation. However, the currently used biomarkers to follow disease progression are costly and inadequate for longitudinal studies. Here, we investigated the suitability of MYOM3 to serve as a robust blood-based biomarker for TAM/STRMK. Using only minimal blood volumes, we detected highly elevated circulating MYOM3 levels in plasma samples from Stim1R304W/+ mice and TAM/STRMK patients with different mutations, and we found that the MYOM3 levels were normalized in Stim1R304W/+ mice undergoing efficient therapies. We also identified skeletal muscle as the primary source of circulating MYOM3, a structural protein of the contractile unit in myofibers, and uncovered that MYOM3 is primarily expressed in regenerating muscle fibers and in fast-twitch type IIa fibers. Overall, this work emphasizes the utility of MYOM3 as a minimally-invasive biomarker for disorders involving myofiber degeneration, and highlights the ability of MYOM3 to detect early muscle dysfunction in TAM/STRMK and evaluate therapeutic efficiency.

BACKGROUND:Spinal muscular atrophy (SMA) types III and IV are the most common late-onset forms, and they progress slowly, making the identification of sensitive biomarkers critical. The Motor Unit Number Index (MUNIX) estimates motor unit loss and may complement traditional electrophysiological measurements such as Compound Muscle Action Potential amplitudes (CMAP). However, their respective performances have never been directly compared in adult SMA. METHODS:In a French multicenter study (NCT04690998), 71 adult patients with SMA and 24 healthy controls underwent clinical and electrophysiological evaluation. MUNIX, CMAP, and Motor Unit Size Index (MUSIX) were recorded in four muscles, and sum scores (SumMUNIX, SumCMAP, SumMUSIX) were calculated. Reliability was assessed using intraclass correlation coefficients (ICCs), and associations with functional outcomes were explored. RESULTS:MUNIX and CMAP effectively distinguished SMA patients from controls, showing strong test - retest reliability. MUNIX showed the highest discriminative performance (AUC = 0.92), while CMAP demonstrated the strongest and most consistent associations with clinical severity. In multivariate analyses, only CMAP remained independently associated with all functional and strength measures, whereas MUNIX and MUSIX lost significance. CONCLUSION:MUNIX demonstrated the highest discriminative performance among biomarkers for differentiating SMA from controls, indicating early motor unit loss even when CMAP values were within normal limits. However, disease burden and functional impairment were better reflected by CMAP, probably due to it integrating both motor unit loss and reinnervation. The complementary nature of these profiles supports their combined use (concurrent application), and longitudinal studies are warranted to assess their responsiveness in adult SMA as well as their appropriateness for clinical trial settings.

BACKGROUND AND AIMS:Patients with LMNA gene variants are at high risk for dilated cardiomyopathy and heart failure (HF), but no prediction model for severe HF events exists. This study aimed to describe the incidence of severe HF events and develop a prediction model in a large cohort of patients with adult-onset laminopathies. METHODS:From a population of 660 patients enrolled in the French LMNA nationwide registry, 470 adults were included in the derivation cohort. An independent international validation cohort included 245 additional patients. Baseline characteristics at genetic testing were assessed and the cumulative incidence of the primary endpoint HF-major adverse cardiac events (HF-MACE) was calculated, defined as HF hospitalization, HF-related death, mechanical circulatory support, or heart transplantation. Predictors of HF-MACE were studied after excluding patients with left ventricular ejection fraction (LVEF) <30% at baseline using a Fine-Gray competing risk model, adjusted hazard ratio (aHR) with 95% confidence interval (CI), and Harrell's concordance (C-) index. A secondary composite endpoint, without hospitalization, was also studied. RESULTS:Among 470 patients of the derivation cohort, HF-MACE occurred in 65 over a median follow-up of 7.1 years (interquartile range: 3.4-12.1). Four independent predictors of HF-MACE were identified: male sex (aHR 1.86; 95% CI 1.060-3.290), LVEF <50% (aHR 2.18; 95% CI 1.080-4.400), missense variants in head and rod domains (aHR 2.91; 95% CI 1.110-7.630), and complete left bundle branch block (aHR 2.99; 95% CI 1.400-6.400). The C-index of the model was 0.750 (95% CI 0.720-0.780) in the derivation cohort and 0.758 (95% CI 0.720-0.800) in the validation cohort. The 5-year cumulative incidence of HF-MACE was 1.5% (95% CI 0.6-3.6), 5.0% (95% CI 1.8-8.2), and 22.0% (95% CI 15.6-28.4) among patients with 0, 1, and ≥2 risk factors, respectively. In patients with LVEF <30% at baseline, the 1-year incidence of HF-MACE was 50%, and those patients were excluded from the risk score. CONCLUSIONS:The first prediction model for severe HF events in adult laminopathies was developed, which may facilitate early and optimal preventive management. CLINICAL TRIAL REGISTRATION:URL: https://www.clinicaltrials.gov Unique identifier: NCT03058185.

Introduction: Early diagnosis of amyotrophic lateral sclerosis (ALS) remains challenging due to the absence of a definitive biomarker and the difficulty of demonstrating widespread lower motor neuron (LMN) involvement. Whole-body muscle MRI (WB-MRI) enables comprehensive assessment of muscle involvement and may improve detection of LMN dysfunction. This study aimed to evaluate whether WB-MRI improves diagnostic certainty in ALS when combined with clinical and electromyography (EMG) assessment. Methods: In this prospective single-center study, 47 patients with ALS underwent clinical examination, EMG, and WB-MRI. Diagnostic classification according to the Awaji criteria was assessed using clinical and EMG data alone and after integration of MRI markers of LMN involvement, including fatty infiltration and muscle edema, or muscle edema alone as a surrogate marker. Results: WB-MRI identified additional LMN-involved regions in 27.7% of patients when both fatty infiltration and muscle edema were considered, and in 42.6% when considering muscle edema alone. This resulted in diagnostic upgrading in 14.9% and 25.5% of patients, respectively. The proportion of definite ALS increased from 8.5% to 17.0% when muscle edema alone was considered. MRI had limited impact on diagnostic classification according to the Gold Coast criteria. Among patients without LMN involvement on clinical and EMG assessment (all with bulbar-onset), 50% were reclassified after MRI. Conclusion: WB-MRI improves detection of LMN involvement and increases diagnostic certainty according to the Awaji criteria, with muscle edema appearing to be the most relevant MRI marker for integration into ALS diagnostic assessment.

Background: Despite advancements in spinal muscular atrophy (SMA) management, evaluating outcomes in adults remains difficult. Standard motor scales often show floor/ceiling effects and fail to capture patient-relevant constructs. This creates a disconnect between clinical measurements and the lived experience of adults with SMA, particularly in regulatory contexts requiring demonstrable benefit. This qualitative study explored the evaluation priorities, expectations, and preferences of adults with SMA and the corresponding assessment challenges faced by healthcare practitioners (HCPs).Methods: Semi-structured interviews with 18 adults with SMA (types 1b-3) and 31 multidisciplinary HCPs from 14 specialized French centers were conducted. Data were analyzed using reflexive thematic analysis and triangulation.Results: Adults with SMA found standard assessments burdensome, fatiguing, and lack relevance. Their primary goal was maintaining an acceptable life balance, a dynamic equilibrium between their disease state and an adapted environment. This balance hinged on preserving specific keystone abilities (e.g., joystick control, independent transfers), which are highly individualized and critical for social participation. Patients prioritized the assessment of these specific abilities. HCPs corroborated the limitations of standard tools (insensitivity, confounding factors) and logistical constraints. In response, HCPs have developed numerous "home-made," non-validated assessments and used personalized tools to capture meaningful changes, especially in severely affected patients.Discussion: A discrepancy exists between current standardized SMA assessments and patients priorities. It highlights a need for outcome measures that align with patients' priorities, particularly "keystone abilities." HCPs' innovative approaches offer a promising direction for future assessment development, advocating for a shift towards individualized, holistic evaluation in SMA care.

ObjectivesTo evaluate the effectiveness and safety of zilucoplan in the real-world treatment setting in France.MethodsThis retrospective cohort study evaluated patients with generalized anti-AChR myasthenia gravis (MG) failing current therapy enrolled in the French early access program (EAP) for zilucoplan. Patients were evaluated at enrollment and at Months 1, 3 and 6 with the MG-ADL score, the Myasthenic Muscle Score (MMS-Garches), and the MG-quality of life questionnaire (MG-QoL15r). MG crises and on-treatment adverse events were documented. MG medication use was compared between the six months before and after enrollment.ResultsForty-eight patients were enrolled and treated with zilucoplan (mean age: 56.2 years; 50.9% men). Thirty patients achieved six months follow-up before the EAP ended. Three patients discontinued zilucoplan due to lack of efficacy. Mean MG-ADL score decreased from 7.4 ± 4.4 to M0 to 2.5 ± 2.7 at M6 (p < 0.0001). 9/43 patients achieved minimal symptom expression at M3 and 12/30 at M6. Mean MMS-Garches score was 67.5 ± 20.0 at M0 and 87.5 ± 13.2 at M6 (p < 0.0001). Mean MG-QoL15r score was 18.2 ± 8.6 at M0 and 8.7 ± 8.3 at M6 (p = 0.0156). 15 patients experienced adverse events, leading to discontinuation in four cases. The mean oral corticosteroid dose decreased from 28.8 ± 11.8 mg to 17.9 ± 11.8 (p = 0.001). Six patients experienced MG crises on treatment, compared to 22 in the six months preceding enrollment. treatment.DiscussionFollowing initiation of zilucoplan treatment, we observed an improvement in MG symptoms and a reduction in MG crises and in exposure to oral corticosteroids. Overall, zilucoplan was well-tolerated with no major adverse events reported.Trial registration informationThe study was registered in the clinicaltrials.gov trial registry under the number NCT06815133 (https://clinicaltrials.gov/study/NCT06815133) on February 4th, 2025.

Background and Objectives:Spinal muscular atrophy (SMA) is a group of genetically heterogeneous motor neuron disorders characterized by progressive, predominantly proximal weakness. Non-5q SMA refers to forms occurring without SMN1 pathogenic variants or deletions. More than half of non-5q SMA cases remain genetically unresolved, and muscle MRI may reveal characteristic patterns supporting diagnosis. Methods:We retrospectively analyzed multicenter data from adults presenting with chronic, progressive, motor-predominant weakness, beginning proximally in the upper or lower limbs, with exclusive or predominant motor involvement on nerve conduction studies and neurogenic changes on EMG. Whole-body MRI was qualitatively graded (Mercuri scale, 42 paired muscles) and quantitatively analyzed in the lower limbs. Results:Among 28 patients (median age 46 [26-50] years), 23 (82.1%) carried pathogenic variants in 13 genes, most commonly VWA1 (n = 5), TRPV4 (n = 4), and VRK1 and DYNC1H1 (n = 3 each). Distinct and reproducible MRI patterns were identified in VRK1-related, DYNC1H1-related, and VWA1-related cases. In VRK1-related SMA, the pattern combined upper limb and iliopsoas sparing with severe gluteal involvement, diffuse thigh involvement, and relative preservation of the posterior tibialis and medial gastrocnemius despite early calf involvement. DYNC1H1-related cases were characterized by sparing of the gluteus maximus, isolated adductor magnus involvement, predominant anterior thigh involvement with marked long head of biceps femoris involvement, and severe triceps surae involvement. In VWA1-related SMA, the pattern included selective gluteus maximus and quadriceps involvement with iliopsoas, gracilis, and sartorius preservation, and predominant peroneal involvement with relative extensor digitorum longus sparing. In TRPV4-related SMA, patterns of muscle involvement were heterogeneous, but the sternocleidomastoid was severely affected in 2 of 4 patients, whereas this muscle remained unaffected in all other cohort members. Discussion:Whole-body muscle MRI appears to be a valuable diagnostic tool for non-5q SMA. Gene-specific imaging signatures, particularly for VRK1, DYNC1H1, and VWA1, can guide targeted genetic testing and support interpretation of variants of uncertain significance. Sternocleidomastoid involvement may represent a specific marker of TRPV4-related SMA. However, confirmation in larger cohorts is needed, although this is constrained by the rarity of these disorders.

MRPS genes, which encode components of the small mitoribosomal subunit, have not been previously linked to adult-onset neurological diseases. These genes play a critical role in mitochondrial translation and the biogenesis of the oxidative phosphorylation system. Whole Genome Sequencing was performed on adult patients presenting with an unexplained neurological picture. In parallel, functional studies were carried out in patient-derived fibroblasts to assess mitochondrial translation and the status of oxidative phosphorylation pathways. Bi-allelic pathogenic variants in MRPS22, MRPS23, and MRPS34 were identified in four patients from unrelated families. All patients presented a similar complex neurological phenotype, including cerebellar ataxia, distal motor neuropathy, pyramidal syndrome, and a distinctive leukoencephalopathy on brain MRI. Additional findings included elevated cerebrospinal fluid (CSF) protein levels and profound cerebral folate deficiency. Functional analyses revealed impaired mitochondrial translation and multiple defects in oxidative phosphorylation. Treatment with oral folinic acid resulted in clinical stabilization, radiological improvement, and normalization of CSF 5-methyltetrahydrofolate levels. Our findings expand the spectrum of mitochondrial diseases caused by defects in mitoribosomal proteins, highlighting their role in adult-onset neurological disorders with distinctive brain imaging features, high CSF protein levels, and cerebral folate deficiency.

Objective To evaluate the effectiveness of Tofersen in patients with superoxide dismutase 1 gene (SOD1-ALS) patients in France in a real-world setting, using disease progression within patient comparisons and with a historical cohort. Patients and Methods Patients with SOD1-ALS were included from across 19 French FILSLAN network centers. Baseline was defined as the treatment initiation date. Main endpoints were the ALSFRS-R progression rate and plasmatic neurofilament light chain (NfL) levels at baseline and 12 months after baseline. Results In the Tofersen Cohort (N=46), within-group comparisons showed that the mean ALS functional rating scale revised (ALSFRS-R) progression rate slowed from 0.53 ± 0.5 at baseline to 0.22 ± 0.3 point/month at 12 months (P=.006). NfL levels significantly decreased from 89.0 ± 9.0 pg/ml at baseline to 29.2 ± 19.5.5 at 12 months (P=.004). Exploratory comparisons with a propensity score (PS) matched historical cohort (39 matched pairs) using a mixed-effects model, ALSFRS-R progression rate at baseline, 6 months, and 12 months after baseline, showed no statistically significant differences between groups P=.30, whereas longitudinal ALSFRS-R scores differed significantly between groups (time-treatment interaction P=.006). The mean survival of the PS matched population was longer in the Tofersen Cohort (42.6 months) than the Historical Cohort (31.8 months) P=.004. Time-dependent adjusted cox analysis showed that Tofersen was associated with a reduction in mortality risk (adjusted HR=0.34; 95% CI, 0.12-0.91; P=.03). Conclusion Tofersen seems to be associated with slower functional decline and reduced NfL levels. While limitations of retrospective design and ALSFRS-R sensitivity must be acknowledged, these findings provide real-world evidence suggesting a clinical benefit of Tofersen.

BACKGROUND:Parvovirus B19 (B19V) infection has been associated with neurological complications. Rarely, patients present with multiple mononeuropathy (MM). The present study aimed to better characterize the clinical, electrophysiological, and prognostic features of patients with B19V-related MM. METHODS:This retrospective, observational, multicenter study included patients with B19V-related MM diagnosed between January 2015 and January 2025 in seven university hospitals in France and Switzerland. RESULTS:Twenty-one patients were included. Twelve were female (57%). All were immunocompetent. The median age at symptom onset was 40 years [IQR: 31-44]. All patients experienced sensory symptoms, 19 (90%) reported neuropathic pain, nine (43%) developed motor weakness, and seven (33%) had cranial nerve involvement. The most frequently involved nerves were the median (14 patients, 67%), fibular (n = 13; 62%), and ulnar (n = 10; 48%) nerves. B19V IgM antibodies were present in 12/20 patients (60%), and all 21 patients were positive for IgG. B19V DNA was detected in blood by PCR in 20 patients (95%). Nerve biopsy showed necrotizing small-vessel vasculitis in one patient (17%), perivascular lymphocytic and macrophagic infiltrates in five (83%), and B19V DNA was detected by PCR in all four tested nerves. Most patients received immunomodulatory treatment (n = 19; 90%). MM relapse occurred in four patients (19%). A partial recovery was observed in 17/20 patients (85%), two remained stable (10%), and one achieved complete recovery (5%). CONCLUSIONS:B19V infection should be systematically investigated in patients presenting with MM, especially in young individuals (including children) with predominantly sensory symptoms, predominant upper limb nerve involvement, and/or cranial nerve involvement.

Introduction La réalité virtuelle (RV) est une distraction immersive et multisensorielle efficace pour réduire douleur et anxiété dans divers contextes cliniques. Son utilisation lors d’injections intrathécales (IT) reste inexplorée. Objectifs Évaluer l’efficacité de la RV en sus des soins courants (SoC) pour atténuer l’anxiété lors d’injections IT de nusinersen chez des patients atteints de SMA et l’expérience RV des patients/soignants. Méthodes REALITY (NCT05354414) est un essai prospectif, randomisé, croisé, ouvert, mené dans 15 centres français. Des patients≥7 ans recevant des injections IT de nusinersen tous les 4 mois (doses de maintien) étaient randomisés 1:1 pour recevoir lors de leurs prochaines injections IT1/IT2, RV+SoC puis SoC ou inversement. Les critères d’évaluation incluaient : auto-évaluation de l’anxiété et de la douleur, usage d’antalgiques/anxiolytiques, satisfaction et acceptabilité rapportées par les patients et les équipes médicales. Résultats Au total, 59 patients (âge médian 19,7 ans ; SMA II, 40,7 % ; III, 54,2 %) ont eu≥1IT. Aucune réduction significative de douleur, d’anxiété ou de consommation médicamenteuse n’était observée entre RV+SoC vs SoC, bien que les besoins en distractions supplémentaires aient été moindres avec la RV (15,2 % vs 30,9 %). La satisfaction était élevée chez les patients et les soignants. Quatre événements indésirables non graves liés à la RV ont été rapportés. Discussion En France, le SoC assure déjà une prise en charge efficace de l’anxiété, pouvant limiter la détection d’un bénéfice additionnel de la RV. Des études supplémentaires seraient nécessaires pour explorer le moment optimal d’utilisation de la VR (avant vs pendant l’injection IT) et identifier les sous-groupes les plus susceptibles d’en bénéficier. Conclusion La RV associée aux soins courants lors des injections IT semble bien acceptée par patients et soignants, même sans réduction significative de la douleur ou l’anxiété comparée au SoC seul.

INTRODUCTION:The aim of our study is to compare mortality rates, causes of death and associated risk factors for idiopathic inflammatory myopathies (IIM) and their various subtypes in a hospital-based cohort, specially IMNM (immune-mediated necrotizing myopathy). MATERIALS AND METHODS:This retrospective study was conducted using the MIIRTALITY cohort, including patients followed for IIM from 2010 to 2022. They were then categorized into five subtypes: dermatomyositis (DM), polymyositis (PM), antisynthetase syndrome (ASS), immune-mediated necrotizing myopathy (IMNM) and overlap myositis (OM). Survival analysis based on IIM subtypes was performed using the Kaplan-Meier method. Cox proportional hazards models were used to determine baseline variables associated with mortality. RESULTS:During the study period, 33 of the 225 patients enrolled in this study died. IMNM have a mortality rate of 1.7 per 100 person-year. The poorest rate of survival was found in patients with DM (HR 3.32; 95% CI 1.61-6.86; p = 0.001), and the lowest mortality rate, when compared to the rest of IIM, was found in patients with ASS (HR 0.41; 95% CI 0.19-0.88). The presence of malignancy was associated with a markedly increased risk of death (HR 12.2; 95% CI 3.09-48.13; p < 0.001). Joint involvement and classification as a non-DM IIM subtype were associated with a reduced risk of death (HR 0.37; 95% CI 0.18-0.76; p = 0.006 and HR 0.06; 95% CI 0.01-0.36; p = 0.002), respectively. CONCLUSION:Dermatomyositis had the highest mortality among IIM subtypes in our hospital-based cohort, ASS was associated with better survival, highlighting the importance of differentiating IIM subtypes so as to personalize treatment and follow-up strategies. In our hospital-based cohort, IMNM mortality was not higher than that of others subtypes. These findings underscore the importance of distinguishing IIM subtypes to personalize treatment and follow-up strategies.

Late-onset Pompe disease (LOPD) is a progressive myopathy. Enzyme replacement therapy is effective, but long-term outcomes vary. Avalglucosidase alfa, shown to be non-inferior to alglucosidase alfa in a phase 3 trial, became available in France through compassionate use for patients with insufficient response to alglucosidase alfa. METHODS:Data from the French Pompe registry were analyzed for patients who switched to avalglucosidase alfa with at least 1 year of follow-up. Respiratory function (forced vital capacity, FVC) and motor function evaluated with gait performance (Six-Minute Walk Test, 6MWT) were assessed before the switch, and one and 2 years after. Individual changes were compared using paired-sample tests. RESULTS:Forty-seven adult patients were included. A stabilization of motor decline was observed: prior to switching, the 6MWT decreased by -27 m/year, whereas an improvement of +17 m/year was seen during the first year after the switch (p = 0.001), followed by overall stability in the second year (-10 m/year, p = 0.280). Respiratory changes were not statistically significant: a decline of 60 mL/year before the switch versus 10 mL/year after 1 year (p = 0.161), and 20 mL/year during the second year (p = 0.346). Three patients died during follow-up, with causes unrelated to the disease or treatment. DISCUSSION:Gait deterioration halted during the first year after transitioning to avalglucosidase, with sustained stabilization thereafter, while respiratory parameters showed minimal change. For patients experiencing significant walking decline under alglucosidase alfa therapy, switching to avalglucosidase alfa resulted in disease stabilization, beginning with mild improvement in the first year and a return to pre-switch baseline thereafter.

IntroductionMyasthenia gravis (MG) is an autoimmune disorder characterised by autoantibodies against the acetylcholine receptor (AChR-Ab). Morvan syndrome (MoS) is a rarer autoimmune disease with neuromyotonia, dysautonomia and encephalopathy, associated with antibodies targeting contactin-associated protein-like 2 (CASPR2) and may coexist with MG, particularly in patients with thymoma.Case ReportA 57-year-old man with AChR-Ab MG was treated with pyridostigmine and prednisone for one year and then presented with a severe exacerbation. The symptoms were not controlled despite intravenous immunoglobulins and plasmapheresis. Chest CT revealed a thymoma. Zilucoplan (a C5 complement inhibitor) was started, with rapid improvement. Efgartigimod (a neonatal Fc receptor (FcRn) antagonist) was added to stabilise residual symptoms prior to thymectomy. Three weeks after the third and final efgartigimod cycle, the patient had no symptoms of MG but began to develop profuse sweating, then generalised hypertonia, fasciculations, myoclonus and dysautonomia, consistent with MoS, which were confirmed by the presence of anti-CASPR2 antibodies. Symptoms improved markedly after resumption of efgartigimod.ConclusionThis case provides the first evidence of the efficacy of efgartigimod in the treatment of MoS and suggests that FcRn inhibition may be beneficial in IgG4-mediated disorders beyond MG. It also highlights the importance of considering coexisting autoimmune conditions in thymoma, particularly when new symptoms occur under selective immune modulation. Finally, it emphasises the need to understand immunopathological mechanisms when choosing immunomodulatory treatment.

BACKGROUND AND OBJECTIVES:Mortality in Late-Onset Pompe Disease (LOPD) has been associated with the rapid progression of respiratory and motor impairment. However, an in-depth approach to the exact causes of death in these patients is still lacking. METHODS:In this retrospective cohort study, we analyzed the cause of death and the comorbidities of all deceased patients from the French Late-Onset Pompe Disease registry. RESULTS:By the time of the last extraction, 60 patients diagnosed with LOPD and monitored were registered as deceased in the French national registry, out of a total of 260 patients included. The median age of death was 70.5 years, while the median age of diagnosis was 58 years. The causes of death were divided into disease-related, accounting for 46.6% of deaths, and non-disease-related, comprising 28.3% of total deaths. Fifteen patients (25%) died of an unknown cause. The most frequent etiology of disease-related death was respiratory failure (n = 14), while for the non-disease-related group, malignant neoplasm was the most common (n = 8). Patients in the non-disease-related death group had significantly higher forced vital capacity (FVC) values compared to those in the disease-related death group (54.7% vs. 38%). Treatment-wise, the median period elapsed from diagnosis to ERT introduction was higher in the disease-related group. DISCUSSION:This is the first study to focus on the specific causes of death of LOPD patients. The majority of the LOPD deaths in the French registry were attributed to respiratory failure and malignant neoplasms.

BackgroundSpinal muscular atrophy (SMA) is a severe neurodegenerative disease affecting children. Three innovative disease-modifying therapies (DMTs)-nusinersen, risdiplam, and onasemnogene abeparvovec-are available for treatment.ObjectiveTo provide a descriptive overview of patients enrolled in the Registre SMA France until July 22, 2024.MethodsRegistre SMA France is a multicenter, national observational registry that includes patients with SMA-children and adults, treated or untreated. Data collection began retrospectively in 2016 and prospectively in 2020, with a 10-year follow-up plan. The coordinating center is the neuropediatric department of Garches Hospital (AP-HP), while methodological and, regulatory and operational management, are provided by the Clinical Research Unit of AP-HP Paris-Saclay. Financial support is provided through unrestricted grants from Biogen, Novartis, and Roche. Data on patient characteristics, medical and surgical follow-up, treatments, adverse events, and quality of life are recorded via structured forms, with additional modules developed as required (e.g., hematological monitoring post-gene therapy in 2021). Data quality is ensured through routine checks and periodic monitoring.ResultsBy July 22, 2024, 1299 patients from 59 centers were enrolled (299 SMA1, 502 SMA2, 469 SMA3, 19 SMA4, 10 presymptomatic). Of these, 76.2% received DMT (nusinersen: 46.1%, risdiplam: 23.2%, onasemnogene abeparvovec: 9.2%), with 21.5% undergoing sequential or combination therapy. Major complications included ventilatory support (SMA1: 69.9%, SMA2: 64.5%, SMA3: 18.1%), enteral feeding (SMA1: 56.2%SMA1), and spine surgery (SMA2: 24.5%). Survival was significantly higher in treated SMA1 and SMA2 cases.ConclusionThis registry serves as a key resource for understanding the clinical course and treatment outcomes of SMA in the real world, supporting future research and informing clinical and policy decisions in the era of DMTs.Trial registrationNCT04177134.

BACKGROUND AND AIMS:Hereditary transthyretin amyloidosis (ATTRv) should be considered in patients diagnosed with intravenous immunoglobulin (IVIg)-resistant chronic inflammatory demyelinating polyradiculoneuropathy (IVIg-NR CIDP). In this 1-year long, retrospective, multicentric study, an online questionnaire was sent to 1100 French healthcare professionals (HCPs) investigating: (i) how many IVIg-NR CIDP patients they followed; (ii) how many IVIg-NR CIDP patients had undergone TTR gene analysis; and (iii) how many IVIg-NR CIDP patients were eventually diagnosed with ATTRv. The questionnaire was sent every 3 months for 1 year and contained information on ATTRv clinical manifestations and diagnosis. RESULTS:One-hundred and ten (10%) HCPs responded. A total of 2131 patients with CIDP were identified, including 315 (22.1%) with IVIg-NR CIDP. TTR gene analysis was performed in 144 patients and was positive in 43 cases (29.9%). CONCLUSIONS:This study demonstrates that ATTRv should be investigated systematically in patients diagnosed with IVIg-NR CIDP. HCP-directed information campaigns are useful for modifying diagnostic practices.

BACKGROUND:Diagnostic wandering and impasse are major challenges for rare disease management. This study describes the characteristics of patients with rare neuromuscular diseases (RNMDs) without a diagnosis being managed by the French national network for RNMDs (FILNEMUS). METHODS:Data for RNMD patients managed by FILNEMUS centers between January 2017 and November 2022 were extracted from the French National Rare Disease Database (BNDMR). A network-wide, standardized, and quality-controlled process was established to collect additional data for patients without a diagnosis. The demographic and socioeconomic characteristics of these patients were then compared with patients with a confirmed diagnosis. RESULTS:13.5% of patients evaluated (n = 5696/42,256) had no confirmed diagnosis. Comparison with 25,682 managed in the same centers and during the same periods with a confirmed diagnosis revealed that socioeconomic characteristics and region of residence did not influence diagnostic status. However, lack of a confirmed diagnosis was more common in patients aged > 50 years, and older patients had longer periods between first symptom onset and first interaction with an expert center. Evaluation of medical records identified eight RNMDs associated with increased risk of diagnostic wandering and impasse. CONCLUSIONS:The FILNEMUS national network of expert centers has enabled equality of care for RNMD patients across France, but further measures are needed to promote more rapid referral to these centers, reduce times to first consultation, and maintain patient engagement in the diagnostic process, particularly for later-onset RNMDs.

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by a typical pattern of muscle involvement, yet it encompasses a wide spectrum of phenotypes, including less common features that remain incompletely defined in the literature. While previous studies have highlighted this clinical variability, no consensus has been reached on how to classify uncommon manifestations, nor have specific predictors been identified. This study aims to describe these uncommon features and explore potential predictors, utilizing data from the French FSHD registry. To this end, we analysed data from 306 FSHD1 patients across nine French neuromuscular referral centres. Descriptive statistics, univariate analyses, and multiple logistic regression models were employed to examine uncommon characteristics and their predictors. Uncommon features were observed in 19.6