Abstract Objectives Retrospective study over the last 30 years of life expectancy in patients suffering from Duchenne muscular dystrophy (DMD). Analysis of the role of ventilatory assistance and ...causes of death. Patients and methods One hundred and nineteen adult DMD patients were hosted during 1981 to 2011 at AFM Yolaine de Kepper centre, Saint-Georges-sur-Loire, France. Patients’ life expectancy was calculated using Kaplan-Meier model. Results Life expectancy without or with ventilatory assistance was 22.16 and 36.23 years, respectively. Similarly, life expectancy of patients born from 1970 (mostly with ventilatory assistance) was 40.95 years old from 1970 and 25.77 years old before 1970. Causes of death changed. Cardiac origins of death have increased from 8% to 44%. Conclusion Ventilator assistance, in this study mostly through tracheotomy prolongs by more than 15 years life expectancy of DMD patients. It allows conservation of a satisfactory quality of life, and should be systematically proposed to patients.
Background and purpose
Fifteen percent of patients with myasthenia gravis (MG) are refractory to conventional treatment. Case reports and a few studies show probable benefit of rituximab in these ...cases. Our objective was to assess the efficacy and the safety of rituximab in patients with MG, in a multicentric real‐life study.
Method
Inclusion criteria were: age > 18 years; MG with anti‐acetylcholine receptor (AChR) antibodies, anti‐muscle‐specific kinase (MuSk) antibodies or significant decrement after repetitive nerve stimulation; Myasthenia Gravis Foundation of America (MGFA) class >II; refractory or steroid‐dependent MG; and treatment with rituximab. Efficacy was assessed at 6 months using the MGFA‐post‐intervention status (PIS) score, the myasthenic muscle score (MMS) and the number of patients receiving steroids <10 mg/day. Data on adverse events were collected.
Results
Twenty‐nine patients were included: 20 with anti‐AChR MG, five with anti‐MuSK MG and four with seronegative MG. MGFA‐PIS score was improved or better (improved, minimal manifestations or remission) in 86.2% of patients after 6 months of treatment (P < 0.0001). The mean MMS increased from 68.8 to 83.1 (P < 0.0001). A decrease in steroid dosage (<10 mg/day) was effective in 57.9% of treated patients. In all, 42.8% of patients experienced adverse events: infections (21.4% of patients); infusion reaction (7%); bradycardia (3.7%); and cytopenia (7%).
Conclusion
The present study demonstrates the efficacy and safety of rituximab in patients with MG. Additional studies remain necessary to determine the role of rituximab in the pharmacopeia of MG treatment and to establish precise recommendations for the infusion protocol.
Background and purpose
To provide a detailed phenotypical description of seronegative patients with generalized myasthenia gravis and antibodies to clustered acetylcholine receptors (AChRs) and to ...assess their frequency amongst a French seronegative generalized myasthenia gravis (SNMG) population.
Methods
A French SNMG database was created and the sera from the 37 patients included in it were analysed by immunofluorescence of cell‐based assays using cotransfection of AChR subunit genes together with rapsyn to densely cluster the AChRs.
Results
Sixteen per cent (n = 6) of the SNMG patients were found to have antibodies to clustered AChR. They presented either with early onset MG and thymic hyperplasia, late onset MG and thymic involution, or thymoma associated MG. They responded well to cholinesterase inhibitors and immunosuppressants.
Conclusions
Patients with antibodies to clustered AChR account for a significant proportion of SNMG patients and resemble patients with AChR antibodies detected by standard radio‐immunoprecipitation.
Background and purpose
Hypertrophy/signal hyperintensity and/or gadolinium enhancement of plexus structures on magnetic resonance imaging (MRI) are observed in two‐thirds of cases of typical chronic ...inflammatory demyelinating polyneuropathy (CIDP). The objective of our study was to determine the additional benefit of plexus MRI in patients referred to tertiary centers with baseline clinical and electrophysiological characteristics suggestive of typical or atypical CIDP.
Methods
A total of 28 consecutive patients with initial suspicion of CIDP were recruited in nine centers and followed for 2 years. Plexus MRI data from the initial assessment were reviewed centrally. Physicians blinded to the plexus MRI findings established the final diagnosis (CIDP or neuropathy of another cause). The proportion of patients with abnormal MRI was analyzed in each group.
Results
Chronic inflammatory demyelinating polyneuropathy was confirmed in 14 patients (50%), as were sensorimotor CIDP (n = 6), chronic immune sensory polyradiculoneuropathy (n = 2), motor CIDP (n = 1) and multifocal acquired demyelinating sensory and motor neuropathy (n = 5). A total of 37 plexus MRIs were performed (17 brachial, 19 lumbosacral and 8 in both localizations). MRI was abnormal in 5/37 patients (14%), all of whom were subsequently diagnosed with CIDP 5/14(36%), after an atypical baseline presentation. With plexus MRI results masked, non‐invasive procedures confirmed the diagnosis of CIDP in all but one patient 1/14 (7%). Knowledge of the abnormal MRI findings in the latter could have prevented nerve biopsy being performed.
Conclusion
Systematic plexus MRI in patients with initially suspected CIDP provides little additional benefit in confirming the diagnosis of CIDP.
Hereditary sensory and autonomic neuropathies (HSAN) type II are characterized by autosomal recessive inheritance, onset at birth and self‐mutilating behavior. Here, we described a new patient with ...congenital insensitivity to pain, sensory neuropathy, acromutilation, and spastic paraplegia. Whole‐exome sequencing showed a homozygous frameshift variant c.577_580del, p.(Lys193Phefs*37) in ARL6IP1. The protein harbors reticulon‐like short hairpin transmembrane domains and has a role in endoplasmic reticulum shaping. The variant causes an additional C‐terminus hydrophobic domain which could disrupt its function. ARL6IP1 interacts with atlastin‐1 responsible for SPG3A and HSAN type ID. This report highlights the role of ARL6IP1 in the pathophysiology of insensitivity to pain and spastic paraplegia.
Abstract The aims of this study were to describe the spectrum of recessively inherited POLG -related disorders, to report new POLG mutations and to discuss genotype-phenotype correlations in order to ...propose a strategy for diagnosis. Twenty eight patients diagnosed with two POLG mutations at 12 tertiary European centers of adult neurology were studied. Exhaustive phenotypic data, brain MRI, muscle analysis, mitochondrial DNA and POLG analysis findings were collected. Five distinct phenotypes were observed: Sensory Ataxic Neuropathy, Dysarthria and Ophthalmoparesis (SANDO), autosomal recessive Progressive External Ophthalmoplegia (arPEO), Spino Cerebellar Ataxia with Epilepsy (SCAE), Mitochondrial Neuro Gastro Intestinal Encephalopathy (MNGIE)-like phenotype and Sensory Ataxic Neuropathy with Ophthalmoparesis but without dysarthria which we propose to name SANO. An increasing gradient of functional severity was appreciated from PEO with the best prognosis, to SANO, SANDO and finally SCAE respectively. Four new missense mutations were found. Regarding genotype/phenotype correlations, P587L mutation was associated with SANO rather than with SANDO (p < 0.005) and W748S mutation was associated with SANDO or SCAE (with more severe disease progression), rather than with SANO or PEO (p < 0.004). Distinguishing between various phenotypes can have important diagnosis and prognosis implications. POLG mutations should be priority searched for in cases of SANDO or SANO. Mitochondrial respiratory chain and mitochondrial DNA studies should be considered in the case of negative POLG analysis or other phenotypes.
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