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Abstract Background Late-onset Pompe disease (LOPD) is a rare, hereditary, progressive disorder that is usually characterized by limb-girdle muscle weakness and/or respiratory insufficiency. LOPD is caused by mutations in the acid alpha-glucosidase (GAA) gene and treated with enzyme replacement therapy (ERT). Methods We studied the clinical, brain imaging, and genetic features of the Belgian cohort of late-onset Pompe disease patients (N = 52), and explored the sensitivity of different outcome measures, during a longitudinal period of 7 years (2010–2017), including the activity limitations ActivLim score, 6 min walking distance (6MWD), 10 m walk test (10MWT), MRC sum score, and forced vital capacity (FVC) sitting/supine. Results In Belgium, we calculated an LOPD prevalence of 3.9 per million. Mean age at onset of 52 LOPD patients was 28.9 years (SD: 15.8 y), ranging from 7 months to 68 years. Seventy-five percent (N = 39) of the patients initially presented with limb-girdle weakness, whereas in 13% (N = 7) respiratory symptoms were the only initial symptom. Non-invasive ventilation (NIV) was started in 37% (N = 19), at a mean age of 49.5 years (SD: 11.9 y), with a mean duration of 15 years (SD: 10.2 y) after symptom onset. Brain imaging revealed abnormalities in 25% (N = 8) of the patients, with the presence of small cerebral aneurysm(s) in two patients and a vertebrobasilar dolichoectasia in another two. Mean diagnostic delay was 12.9 years. All patients were compound heterozygotes with the most prevalent mutation being c.-32-13 T > G in 96%. We identified two novel mutations in GAA: c.1610_1611delA and c.186dup11. For the 6MWD, MRC sum score, FVC sitting and FVC supine, we measured a significant decrease over time (p = 0.0002, p = 0.0001, p = 0.0077, p = 0.0151), which was not revealed with the ActivLim score and 10MWT (p > 0.05). Conclusions Awareness on LOPD should even be further increased because of the long diagnostic delay. The 6MWD, but not the ActivLim score, is a sensitive outcome measure to follow up LOPD patients.

Background: Congenital myasthenic syndromes (CMS) are a group of genetic disorders characterized by impaired neuromuscular transmission. CMS typically present at a young age with fatigable muscle weakness, often with an abnormal response after repetitive nerve stimulation (RNS). Pharmacologic treatment can improve symptoms, depending on the underlying defect. Prevalence is likely underestimated. This study reports on patients with CMS followed in Belgium in 2022., Methods: Data were gathered retrospectively from the medical charts. Only likely pathogenic and pathogenic variants were included in the analysis., Results: We identified 37 patients, resulting in an estimated prevalence of 3.19 per 1,000,000. The patients harbored pathogenic variants in CHRNE, RAPSN, DOK7, PREPL, CHRNB1, CHRNG, COLQ, MUSK, CHRND, GFPT1, and GMPPB. CHRNE was the most commonly affected gene. Most patients showed disease onset at birth, during infancy, or during childhood. Symptom onset was at adult age in seven patients, caused by variants in CHRNE, DOK7, MUSK, CHRND, and GMPPB. Severity and distribution of weakness varied, as did the presence of respiratory involvement, feeding problems, and extraneuromuscular manifestations. RNS was performed in 23 patients of whom 18 demonstrated a pathologic decrement. Most treatment responses were predictable based on the genotype., Conclusions: This is the first pooled characterization of patients with CMS in Belgium. We broaden the phenotypical spectrum of pathogenic variants in CHRNE with adult-onset CMS. Systematically documenting larger cohorts of patients with CMS can aid in better clinical characterization and earlier recognition of this rare disease. We emphasize the importance of establishing a molecular genetic diagnosis to tailor treatment choices., Competing Interests: Declaration of competing interest There has been no commercial involvement in the study design or manuscript preparation, and none of the authors report any other conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

International guidelines on the treatment of myasthenia gravis (MG) have been published but are not tailored to the Belgian situation. This publication presents recommendations from a group of Belgian MG experts for the practical management of MG in Belgium. It includes recommendations for treatment of adult patients with generalized myasthenia gravis (gMG) or ocular myasthenia gravis (oMG). Depending on the MG-related antibody a treatment sequence is suggested with therapies that can be added on if the treatment goal is not achieved. Selection of treatments was based on the level of evidence of efficacy, registration and reimbursement status in Belgium, common daily practice and the personal views and experiences of the authors. The paper reflects the situation in February 2024. In addition to the treatment considerations, other relevant aspects in the management of MG are addressed, including comorbidities, drugs aggravating disease symptoms, pregnancy, and vaccination. As many new treatments might potentially come to market, a realistic future perspective on the impact of these treatments on clinical practice is given. In conclusion, these recommendations intend to be a guide for neurologists treating patients with MG in Belgium., (© 2024. The Author(s).)

Background and Purpose: Because Becker muscular dystrophy (BMD) is a heterogeneous disease and only few studies have evaluated adult patients, it is currently still unclear which outcome measures should be used in future clinical trials., Methods: Muscle magnetic resonance imaging, patient-reported outcome measures and a wide range of clinical outcome measures, including motor function, muscle strength and timed-function tests, were evaluated in 21 adults with BMD at baseline and at 9 and 18 months of follow-up., Results: Proton density fat fraction increased significantly in 10/17 thigh muscles after 9 months, and in all thigh and lower leg muscles after 18 months. The 32-item Motor Function Measurement (MFM-32) scale (-1.3%, p = 0.017), North Star Ambulatory Assessment (-1.3 points, p = 0.010) and patient-reported activity limitations scale (-0.3 logits, p = 0.018) deteriorated significantly after 9 months. The 6-min walk distance (-28.7 m, p = 0.042), 10-m walking test (-0.1 m/s, p = 0.032), time to climb four stairs test (-0.03 m/s, p = 0.028) and Biodex peak torque measurements of quadriceps (-4.6 N m, p = 0.014) and hamstrings (-5.0 N m, p = 0.019) additionally deteriorated significantly after 18 months. At this timepoint, domain 1 of the MFM-32 was the only clinical outcome measure with a large sensitivity to change (standardized response mean 1.15)., Discussion: It is concluded that proton density fat fraction imaging of entire thigh muscles is a sensitive outcome measure to track progressive muscle fat replacement in patients with BMD, already after 9 months of follow-up. Finally, significant changes are reported in a wide range of clinical and patient-reported outcome measures, of which the MFM-32 appeared to be the most sensitive to change in adults with BMD., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Introduction: We describe the first case of acute flaccid myelitis (AFM) related to enterovirus D68 (EV-D68) infection in Belgium. The clinical and radiological presentation of AFM associated with EV-D68 although well described currently remains a challenging diagnosis. Through this interesting clinical case, we aimed to review the differential diagnosis of acute flaccid palsy in a child and discuss the specific point of interest related to AFM., Case Presentation: We present the case of a 4-year-old girl with a torticollis associated with an acute palsy of the right upper limb. The magnetic resonance imaging revealed an increased T2 signal intensity of the entire central gray matter of the cervical cord with involvement of the posterior brainstem. A polymerase chain reaction (PCR) conducted on a nasopharyngeal swab was found positive for EV-D68. The definition of AFM proposed by the Center for Disease Control and Prevention (CDC) is an acute-onset flaccid weakness of one or more limbs in the absence of a clear alternative diagnosis and the radiological evidence of gray matter involvement on an MRI picture, and our case fits these two criteria. A prompt and detailed workup is required to distinguish this emergent disease from other forms of acute flaccid palsy. The functional prognosis of AFM is poor, and there are no evidence-based treatment guidelines so far., Conclusion: AFM is an emerging pathology that requires the attention of pediatricians to quickly rule out differential diagnoses and adequately manage the patient. Further research is needed to optimize treatments, improve outcomes, and provide scientifically based guidelines., Competing Interests: The authors declare no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Dominant mutations in CACNA1S gene mainly causes hypokalemic periodic paralysis (PP)(hypoPP). A 68-year-old male proband developed a progressive proximal weakness from the age of 35. Muscle biopsy showed atrophic fibers with vacuoles containing tubular aggregates. Exome sequencing revealed a heterozygous p.R528H (c.1583G>A) mutation in the CACNA1S gene. CACNA1S-related HypoPP evolving to persistent myopathy in late adulthood is a well-known clinical condition. However, isolated progressive myopathy (without PP) was only exceptionally reported and never with an early onset. Reporting a case of early onset CACNA1S-related myopathy in a patient with no HypoPP we intend to alert clinicians to consider it in the differential diagnosis of younger adult-onset myopathies especially when featuring vacuolar changes.

Introduction: Hereditary transthyretin-mediated (hATTR) amyloidosis, a genetic disease caused by mutations in the transthyretin gene, leads to progressive sensory and autonomic neuropathy and/or cardiomyopathy and is associated with renal and ophthalmologic manifestations and a poor prognosis., Methods: This is a retrospective study based on data collected from the medical records of patients with hATTR amyloidosis treated with patisiran between 01 July 2018 and 01 February 2021. Six Belgian neuromuscular reference centers participated, covering all patisiran-treated hATTR amyloidosis patients at the study time. This study was conducted to collect data requested in the context of the reimbursement of patisiran in Belgium., Results: Thirty-one patients were diagnosed with hATTR amyloidosis with polyneuropathy, Coutinho stage 1 or 2, and eligible for active treatment during the data collection period. Of the hATTR amyloidosis patients treated with patisiran (n = 12), seven and five had polyneuropathy stages 1 and 2, respectively. Six patients had cardiac symptoms (New York Heart Association class 2 or above). Follow-up information was available for nine patients. Following patisiran treatment, eight patients showed stable or improved assessments for most neurological or cardiological parameters. Only one patient presented with worsening statuses at the end of the data collection period., Conclusions: The patients with hATTR amyloidosis in Belgium have similar baseline demographics and disease characteristics to those studied in the patisiran APOLLO study and show a similar therapeutic response in the real-world, altering the expected disease progression in most patients., (© 2023. The Author(s).)

HADDTS (Hypotonia, Ataxia, Developmental-Delay and Tooth-enamel defects) is a newly emerging syndrome caused by CTBP1 mutations. Only five reports (13 cases) are available; three contained muscle-biopsy results but none presented illustrated histomyopathology. We report a patient in whom whole-exome sequencing revealed a heterozygous de novo CTBP1 missense mutation (c.1024 C>T; p.(Arg342Trp)). Progressive muscular weakness and myopathic electromyography suggested a myopathological substrate; muscle-biopsy revealed dystrophic features with endomysial-fibrosis, fiber-size variability, necrotic/degenerative vacuolar myopathy, sarcoplasmic/myofibrillar- and striation-alterations, and enzyme histochemical and structural mitochondrial alterations/defects including vacuolar mitochondriopathy. Our report expands the number of cases in this extremely rare condition and provides illustrated myopathology, muscle-MRI, and electron-microscopy. These are crucial for elucidating the nature and extent of the underlying myopathological-correlates and to characterize the myopatholgical phenotype spectrum in this genetic neurodevelopmental condition., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to report., (Copyright © 2023. Published by Elsevier B.V.)

Background: Telemedicine (TM) contributes to bridge the gap between healthcare facilities and patients' homes with neuromuscular disease (NMD) because of mobility issues. However, its deployment is limited due to difficulties evaluating subtle neurological signs such as mild weakness or sensory deficits. The COVID-19 pandemic has disrupted healthcare delivery worldwide, necessitating rapid measures implementation by health care providers (HCPs) to protect patients from acquiring SARS-CoV-2 while maintaining the best care and treatment., Objectives: Given the challenges faced by remote healthcare assistance of NMD patients, we aim to evaluate the use of TM in NMD during the COVID-19 pandemic., Methods: Based on the Model for Assessment-of-Telemedicine-Applications (MAST), we conducted a survey amongst clinicians of the ERN EURO NMD (European-Reference-Network-for-Rare-Neuromuscular-Diseases)., Results: Based on 42 responses over 76 expected ones, our results show that the COVID-19 pandemic significantly increased the number of HCPs using TM (from 60% to 100%). The TM types most used during the COVID-19 period are teleconsultation and consultation by phone, particularly in the context of symptoms worsening in NMD patients with COVID-19 infection. Most European HCPs were satisfied when using TM but as a complementary option to physical consultations. Many responses addressed the issue of technical aspects needing improvement, particularly for elderly patients who need caregivers' assistance for accessing the TM platform., Conclusions: TM has been essential during COVID-19, but its use still presents some limitations for NMD patients with cognitive deficits or for first-time diagnosis. Thus, TM should be used as complement to, rather than substitute, for face-to-face consultations.

Background and Purpose: Ataxia and cough are rare features in hereditary sensory and autonomic neuropathies (HSAN), a group of diseases of mostly unknown genetic cause. Biallelic repeat expansions in RFC1 are associated with cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). This study aimed to investigate the prevalence of RFC1 repeat expansions in a cohort of HSAN patients., Methods: After unremarkable whole-exome sequencing (WES) analysis, we performed repeat-primed PCR to detect intronic RFC1 expansions in 12 HSAN families, who all presented with chronic cough., Results: In these patients, 75% carried biallelic expansions of the pathogenic AAGGG motif. Compared with RFC1-/- cases, RFC1+/+ cases presented more consistently with positive sensory and autonomic symptoms. Afferent ataxia was more severe in the RFC1+/+ cohort and cerebellar ataxia was a common feature (21%)., Conclusions: We demonstrate that RFC1 is a frequent cause of (WES-negative) HSAN with chronic cough and ataxia. The diagnostic yield of RFC1 repeat-primed PCR was surprisingly high, given that HSAN is genetically poorly understood. This combination of HSAN, ataxia, and chronic cough symptoms represents a new nosological entity within the neuropathy-ataxia spectrum., (© 2022 European Academy of Neurology.)

Abstract: Nodal/paranodal IgG4-related chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) rarely involves anticontactin (CNTN1) subtype and exceptionally complicates with nephrotic syndrome. A 65-year-old man developed weakness, facial palsy, and balance impairment; after spontaneous recovery, he severely relapsed 1 month later. Electroneuromyography confirmed CIDP. Proteinorachy (462 mg/dL; N < 45), proteinuria (3.5 g/g creatine), and biopsy-proven membranous nephropathy were identified. Intravenous immunoglobulins, corticosteroids, and plasmaphereses did not allow recovery. Anti-CNTN1 immunoglobulin G4 (IgG4) assay was positive. Rituximab (375 mg/m2/week, 4 weeks) provided obvious improvement. Relapsing-remitting anti-CNTN1-CIDP co-occurring with nephrotic syndrome is exceptional, and its identification is essential because efficient therapies such as rituximab are available for this severe condition., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

C19orf12 gene biallelic mutations lead mainly to neurodegeneration with brain iron accumulation-4. A 15-year-old male and his 17-year-old sister complained of cramps and exercise intolerance. Clinical examination of the boy mainly showed distal amyotrophy and mild weakness, while the sister predominantly had a tetrapyramidal syndrome. Widespread chronic neurogenic signs and hypointense signals on the striatum were present in both patients. Clinical exome sequencing identified, on both patients, the compound heterozygous pathogenic mutations c.204&#95;214del p.(Gly69ArgfsTer10) and c.32C>T p.(Thr11Met). The description of these rare SPG43 and ALS-like phenotypes in the same family contributes to improve genotype-phenotype correlation in C19orf12-related diseases.

Introduction: IgG4 antibodies against neurofascin (Nfasc155 and Nfasc140/186), contactin (CNTN1) and contactin-associated protein (Caspr1) are described in specific subtypes of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Our objective was to assess, in a real-life practice, the incidence, the clinical features and the response to treatment of these forms of CIDP., Methods: 1500 sera of patients suspected of having CIDP from France, Belgium and Switzerland were prospectively tested using a flow cytometry technique. The characteristics of patients with antibodies against the node of Ranvier were compared to 100 seronegative CIDP from our department., Results: IgG4 antibodies against Nfasc155, CNTN1, and Caspr1 were, respectively, detected in 15 (prevalence 1%), 10 (0.7%) and 2 (0.2%) sera. Antibodies specific of the Nfasc140/186 were not detected. All subjects with antibodies against the node of Ranvier fulfilled diagnostic criteria for CIDP. CIDP with anti-Nfasc155 were younger, had more sensory ataxia and postural tremor than seronegative CIDP. CIDP with anti-CNTN1 had more frequent subacute onset and facial paralysis, commoner renal involvement with membranous glomerulonephritis and greater disability, than seronegative CIDP. CIDP with anti-Caspr1 had more frequent respiratory failure and cranial nerve involvement but not more neuropathic pain than seronegative CIDP. Intravenous immunoglobulins were ineffective in most seropositive patients. Rituximab produced dramatic improvement in disability and decreased antibodies titres in 13 seropositive patients (8 with anti-Nfasc155 and 5 with anti-CNTN1 antibodies)., Conclusions: Although rare, anti-paranodal antibodies are clinically valuable, because they are associated with specific phenotypes and therapeutic response.

Spinal dural arteriovenous fistulas (SDAVFs) are often misdiagnosed as their symptoms are non-specific, leading to treatment delay and a poor outcome. We describe the case of a 53-year-old man with a history of progressive paraparesis that worsened abruptly after an epidural corticosteroid injection. We highlight here the need for high diagnostic suspicion for an SDAVF in patients deteriorating after an epidural injection and an indication of repeated spine imaging in such cases. Finally, this is the first reported case of an SDAVF in a HIV-positive patient and it emphasizes the need for a broad differential diagnosis., Learning Points: Consider an SDAVF in cases of slowly progressive paraparesis and hypoaesthesia, especially if symptoms worsen after an epidural injection.The need for an in-depth work-up including repeated angiographic explorations in cases where no malformation is found in a straightforward manner.In a patient infected with HIV, even though a broad range of neuromuscular diseases can be suspected, non-related aetiologies should not be forgotten., Competing Interests: Conflicts of Interests: From 2008 to 2017, Dr Remiche received several financial awards from Sanofi Genzyme, Santhera Pharmaceuticals, CSL Behring and C.A.F.-D.C.F. cvba-scrl such as: travel grants and financial support in order to attend scientific meetings, a consultancy honorarium, a speaker honorarium, a grant to conduct academic study and a grant to organize a scientific meeting. No potential conflict of interest is reported by the other authors., (© EFIM 2020.)

Objective: To describe the clinical and molecular genetic findings in a family segregating a novel mutation in the AIFM1 gene on the X chromosome., Methods: We studied the clinical features and performed brain MRI scans, nerve conduction studies, audiometry, cognitive testing, and clinical exome sequencing (CES) in the proband, his mother, and maternal uncle. We used in silico tools, X chromosome inactivation assessment, and Western blot analysis to predict the consequences of an AIFM1 variant identified by CES and demonstrate its pathogenicity., Results: The proband and his maternal uncle presented with childhood-onset nonprogressive cerebellar ataxia, hearing loss, intellectual disability (ID), peripheral neuropathy, and mood and behavioral disorder. The proband's mother had mild cerebellar ataxia, ID, and mood and behavior disorder, but no neuropathy or hearing loss. The 3 subjects shared a variant (c.1195G>A; p.Gly399Ser) in exon 12 of the AIFM1 gene, which is not reported in the exome/genome sequence databases, affecting a critical amino acid for protein function involved in NAD(H) binding and predicted to be pathogenic with very high probability by variant analysis programs. X chromosome inactivation was highly skewed in the proband's mother. The mutation did not cause quantitative changes in protein abundance., Conclusions: Our report extends the molecular and phenotypic spectrum of AIFM1 mutations. Specific findings include limited progression of neurologic abnormalities after the first decade and the coexistence of mood and behavior disorder. This family also shows the confounding effect on the phenotype of nongenetic factors, such as alcohol and drug use and side effects of medication., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Late-onset glycogen storage disease type II is associated with variable muscle phenotypes. Epidemiological data suggest that its prevalence is lower in Belgium than in bordering countries like The Netherlands., Objective: We investigated whether such low estimated prevalence is due to missed diagnoses., Methods: We screened 100 patients with muscle phenotypes of undetermined origin using a dried blood spot test for alpha-acid glucosidase (GAA) activity. Patients with low activity at screening were re-tested by the same method and, if low activity was confirmed, GAA gene analysis was performed., Results: The screening test revealed lower than normal GAA activity in 15 patients, but in only two of them it was low enough to be considered in the disease range. Retesting confirmed lower than normal GAA activity in five patients, but in all of them it was above the disease range. A single patient carried a heterozygous known pathogenic GAA mutation, whose significance in this case remains undetermined., Conclusions: We conclude that reported low prevalence estimates in Belgium are not likely to be due to an underdiagnosis bias. Lower prevalence compared to neighbouring The Netherlands may be due to different ethnic stratification of our patients. Diagnostic strategies should keep into account the expected prevalence of a disease in specific populations.

Background: Hyponatremia is associated with unstable gait and propensity to falls. The potential contribution of peripheral nervous system dysfunction induced by hyponatremia has not yet been addressed by prospective studies., Design: In the first part of this prospective study, we performed two tests evaluating muscle strength (grip test and quadriceps isometric contraction test) together with a timed up and go (TUG) test in 11 patients with chronic mild-to-moderate hyponatremia before and after the normalization of natremia. In the second part, we measured nerve conduction velocities and F-wave latencies in nine patients with profound hyponatremia (< 125 mmol/L) before and after the normalization of natremia., Results: No significant change in muscle strength was observed when natremia was corrected from 127·7 ± 2·5 to 136·1 ± 1·8 mmol/L, contrary to a significant improvement in TUG from 14·9 ± 5·1 to 12·5 ± 4·7 s (P = 0·006). Nerve conduction velocities and F-wave latencies showed significant improvement in most of the studied nerves when natremia was corrected from 121·9 ± 2·4 to 135·5 ± 3·4 mmol/L (e.g. mean increase of 14·3% for motor nerve conduction and mean decrease of 21·6% for F-wave latency of left peroneal nerve)., Conclusion: Whereas chronic mild-to-moderate hyponatremia has no impact on muscle strength, we demonstrate for the first time an impact of profound hyponatremia on nerve conduction studies. Further studies are needed to ascertain the contribution of these latter results on gait disturbances, propensity to falls and attention deficits associated with hyponatremia., (© 2016 Stichting European Society for Clinical Investigation Journal Foundation.)

We report a novel and particularly unusual type of mutation, namely, large deletion in the RYR1 gene, in a Belgian family with myopathy: Patients were found to be compound heterozygous and presented a clinico-pathological phenotype characterized by late-onset and recessive myopathy with cores. We depict the clinical, electrophysiological, pathological and molecular genetic characteristics of family members. To date, large deletions in the RYR1 gene have been reported in only two cases. Both involved different mutations and, in sharp contrast to our cases, presented with a very early-onset, neonatal, and a very severe or lethal phenotype. Overview of reported clinico-pathologic phenotypes, also highlights the rarity of combined late-onset/recessive co-occurrence in this group of myopathies with cores. Finally, this report underlines the broadening spectrum in this group of myopathologic disorders and highlights the concept of 'RYR1-associated/related core myopathies'., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Glycogen storage disease type II (GSDII) is a lysosomal storage disorder caused by acid alpha-1,4-glucosidase deficiency and associated with recessive mutations in its coding gene GAA. Few studies have provided so far a detailed phenotypical characterization in late onset GSDII (LO-GSDII) patients. Genotype-phenotype correlation has been previously attempted with controversial results. We aim to provide an in-depth description of a cohort (n = 36) of LO-GSDII patients coming from the north of Italy and compare our population's findings to the literature. We performed a clinical record-based retrospective and prospective study of our patients. LO-GSDII in our cohort covers a large variability of phenotype including subtle clinical presentation and did not differ significantly from previous data. In all patients, molecular analysis disclosed GAA mutations, five of them being novel. To assess potential genotype-phenotype correlations we divided IVS1-32-13T>G heterozygous patients into two groups following the severity of the mutations on the second allele. Our patients harbouring "severe" mutations (n = 21) presented a strong tendency to have more severe phenotypes and more disability, more severe phenotypes and more disability, higher prevalence of assisted ventilation and a shorter time of evolution to show it. The determination of prognostic factors is mandatory in order to refine the accuracy of prognostic information, to develop follow-up strategy and, more importantly, to improve the decision algorithm for enzyme replacement therapy administration. The demonstration of genotype-phenotype correlations could help to reach this objective. Clinical assessment homogeneity is required to overcome limitations due to the lack of power of most studies.

Neurological complications of AH1N1 vaccination such as Guillain-Barré syndrome were described in the previous years. Several reports suggest that hereditary neuropathies may be a predisposing factor for immune-mediated neuropathies. We report the case of a 54-year-old female who developed chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) 5 weeks after AH1N1 vaccination. She had no previous neurological history, but neurophysiological features led us to suspect an underlying hereditary neuropathy. PMP22 gene analysis showed a typical deletion, confirming the diagnosis of hereditary neuropathy with liability to pressure palsies (HNPP). We observed a significant clinical and neurophysiological improvement of the neuropathy after intravenous immunoglobulin treatment. This is, to our knowledge, the first reported case of CIDP potentially triggered by AH1N1 vaccination. This and previous observations suggest that genetic-determined neuropathies could predispose to the occurrence of immune-mediated neuropathies. One must recall the possibility of a superimposed hereditary neuropathy like HNPP in patients with a clinical presentation of CIDP, especially when positive family history or unexpected neurophysiological features are present.

Peripheral neuropathy implies damages to neurons belonging to the peripheral nervous system which includes cranial nerves, spinal nerves' roots, spinal ganglia, nerve trunks and their divisions, and, the autonomic nervous system. Peripheral neuropathies are frequent in the general population (prevalence: 2,4%). We present a review of the recent literature and highlight diagnostic approaches for certain types of neuropathies particularly the most frequent ones or those requiring peculiar attention in first-line medicine. We also present epidemiologic data and data related to sural nerve biopsies from our centre. The determination of the location and the topography of the affected sites, integrated into the global context of the patient, is essential to provide an etiologic diagnosis. The median nerve compression within the carpal tunnel and polyneuropathies are the most frequent forms of peripheral neuropathies. More than one hundred causes of polyneuropathies are described and they are divided into acquired, genetically determined and idiopathic. We highlight a largely adopted diagnostic strategy concerning polyneuropathies and describe the Guillain-Barre syndrome, the alcohol-related polyneuropathy and the controversies about the benefit of the B vitamin therapy and its dangers. At the Hôpital Erasme, since 2008, more than 1372 patients with peripheral neuropathy were identified. Results of sural nerve biopsies performed in seventeen of them do not largely differ from those of other centres of expertise. We conclude that the diagnosis of peripheral neuropathy usually requires the expertise of a neurologist, but, first line caregivers must be able to recognize and refer patient when needed.

Background: Pompe's disease is an inherited metabolic myopathy caused by acid α-glucosidase deficiency. Early diagnosis optimizes the treatment effectiveness., Methods: One-hundred-thirty-seven consecutive patients with unexplained hyperCKemia underwent the assessment of acid α-glucosidase activity on dried blood spot. Second tier confirmatory testing in positive patients included the assessment of α-glucosidase activity on lymphocytes or muscle tissue and molecular analysis., Results: Three patients were diagnosed with later-onset Pompe's disease, revealing 2.2% prevalence in asymptomatic hyperCKemia. Moreover, three patients positive to the screening revealed abnormal biochemical second tier testing, but were heterozygous for the common c.-32-13T>G mutation at molecular level., Conclusions: The selective screening for later-onset Pompe's disease in asymptomatic hyperCKemia allowed the identification of affected patients in a pre-clinical stage. Additionally, the identification of carriers with biochemical alterations related to Pompe's disease extends the spectrum of its manifestations to heterozygous subjects., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Respiratory failure associated with diaphragmatic weakness is the first cause of death in late-onset type II glycogenosis (LO-GSDII). We aim to identify predictive factors of diaphragmatic weakness and investigate the pathophysiology of respiratory muscles impairment. Pulmonary function and chest wall volumes were measured in ten patients and eight controls (supine and seated). According to the change in forced vital capacity in supine (ΔFVC) we considered patients with (DW, ΔFVC>25%) and without (noDW, ΔFVC<25%) diaphragmatic weakness. Postural change made the supine abdominal contribution to tidal volume (%VAB) of DW to fall and the ribcage to increase and good correlation was found between %VAB and ΔFVC (R=0.776). Patients showed reduced chest wall and abdominal inspiratory capacity (ICCW and ICAB) (p<0.001) and low abdominal expiratory reserve volume (p<0.01). Passing to supine DW did not increase ICCW and ICAB. ΔFVC occurs in LO-GSDII due to weakened diaphragm and abdominal muscles while intercostals are preserved. %VAB represents a new reliable index to detect diaphragmatic weakness., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Distal acquired demyelinating symmetric (DADS) neuropathy is clinically characterised by distal motor and sensory disturbances. Typically DADS does not respond or responds poorly to intravenous immunoglobulins (IVIg). We report the case of a 58-year-old patient who developed distal paraparesis. Serum electrophoresis demonstrated monoclonal IgM paraproteinemia having an anti-GM1 but no anti-MAG activity. Conduction velocities showed demyelinating pattern. Work-up excluded a lymphoproliferative disorder After IVIg treatment we observed a clinical and neurophysiological improvement. Regarding these peculiar findings, we suggest that DADS needs to be splitted in several forms determined among others by clinical, neurophysiological and antiganglioside profile and therapeutic response. We advocate to perform systematic antiganglioside antibodies assay additionnaly to anti-MAG when DADS is suspected in order to improve dysimmune neuropathies classification.