Rapidly progressive myopathy: unveiling light chain amyloidosis as an initial manifestation of multiple myeloma: a case report and literature review.

We present the case of a 79-year-old man with rapidly progressive myopathy as the initial manifestation of light chain amyloidosis associated with multiple myeloma. The patient experienced progressive lower limb weakness resulting in difficulty climbing stairs. Ancillary tests revealed slightly elevated serum creatine kinase levels. The electromyogram revealed a diffuse myogenic pattern while muscle MRI indicated fatty replacement of the quadriceps muscles. Muscle biopsy revealed the presence of amyloid deposits in the vessel walls. An elevated level of lambda (246 mg/L) light chain was detected. The bone marrow aspiration results were consistent with the diagnosis of multiple myeloma. In conclusion, even if amyloid myopathy is a rare condition, routine screening for amyloid deposits in muscle biopsy is crucial and should be performed systematically. In the present case, it enabled a rapid diagnosis and the beginning of treatment.

8-Iso-prostaglandin F2α as a potential biomarker in patients with unipolar and bipolar depression.

OBJECTIVE: Previous studies have shown that the disturbance of redox homeostasis plays a role in the pathogenesis of mood disorders. It is currently unclear whether oxidative stress parameters can be used as biomarkers (state vs. trait). The aim of the present study was to investigate oxidative stress markers in patients with major depressive disorder (MDD) and bipolar disorder (BP) in acute depressive episodes and remission, and healthy individuals. PATIENTS AND METHODS: Thirty-two patients with a diagnosis of MDD, 32 patients with a diagnosis of BP and 32 matched healthy controls were included in the study. We measured the serum levels of markers of oxidative damage, including 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-Iso-prostaglandin F2α (8-iso-PGF2α; 8-isoprostane), and malondialdehyde (MDA), and also serum activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR) in both acute and remission phase, and in control group. RESULTS: After controlling for the effects of age, sex, body mass index, and smoking status, serum 8-iso-PGF2α levels were significantly higher in both patient groups compared to controls, regardless of disease phase. The activities of GPX and GR were significantly lower in the acute phase in MDD patients compared to controls. Serum GR activity was lower in both acute and remission phase in MDD compared to BP. CONCLUSIONS: Our results suggest that both MDD and BP are associated with a disturbed redox balance with a particularly pronounced increase in serum 8-iso-PGF2α levels in both groups and the presence of glutathione metabolism disorders in MDD patients. Further research is needed to confirm the importance of oxidative stress parameters as potential biomarkers of MDD and BP.

Strategy for genetic analysis in hereditary neuropathy.

Inherited neuropathies are a heterogeneous group of slowly progressive disorders affecting either motor, sensory, and/or autonomic nerves. Peripheral neuropathy may be the major component of a disease such as Charcot-Marie-Tooth disease or a feature of a more complex multisystemic disease involving the central nervous system and other organs. The goal of this review is to provide the clinical clues orientating the genetic diagnosis in a patient with inherited peripheral neuropathy. This review focuses on primary inherited neuropathies, amyloidosis, inherited metabolic diseases, while detailing clinical, neurophysiological and potential treatment of these diseases.

Clinical correlations and long-term follow-up in 100 patients with sarcoglycanopathies.

BACKGROUND AND PURPOSE: To describe a large series of patients with α, ß, and γ sarcoglycanopathies (LGMD-R3, R4, and R5) and study phenotypic correlations and disease progression. METHODS: A multicentric retrospective study in four centers in the Paris area collecting neuromuscular, respiratory, cardiac, histologic, and genetic data. The primary outcome of progression was age of loss of ambulation (LoA); disease severity was established according to LoA before or after 18 years of age. Time-to-event analysis was performed. RESULTS: One hundred patients (54 γ-SG; 41 α-SG; 5 ß-SG) from 80 families were included. The γ-SG patients had earlier disease onset than α-SG patients (5.5 vs. 8 years; p = 0.022) and ß-SG patients (24.4 years). Axial muscle weakness and joint contractures were frequent and exercise intolerance was observed. At mean follow-up of 22.9 years, 65.3% of patients were wheelchair-bound (66.7% α-SG, 67.3% γ-SG, 40% ß-SG). Dilated cardiomyopathy occurred in all sarcoglycanopathy subtypes, especially in γ-SG patients (p = 0.01). Thirty patients were ventilated and six died. Absent sarcoglycan protein expression on muscle biopsy and younger age at onset were associated with earlier time to LoA (p = 0.021 and p = 0.002). Age at onset was an independent predictor of both severity and time to LoA (p = 0.0004 and p = 0.009). The α-SG patients showed genetic heterogeneity, whereas >90% of γ-SG patients carried the homozygous c.525delT frameshift variant. Five new mutations were identified. CONCLUSIONS: This large multicentric series delineates the clinical spectrum of patients with sarcoglycanopathies. Age at disease onset is an independent predictor of severity of disease and LoA, and should be taken into account in future clinical trials.

Antineoplastic agents exacerbating Charcot Marie Tooth disease: red flags to avoid permanent disability.

BACKGROUND: Charcot Marie Tooth (CMT) disease is the most common form of hereditary neuropathy. Due to the high prevalence of mild and undiagnosed forms, patients with CMT disease may be exposed to severe neurotoxicity following the administration of neurotoxic chemotherapies. The aim of this report is to alert oncologists to the potential to precipitate severe irreversible peripheral neuropathies when administering neurotoxic compounds to undiagnosed CMT patients. MATERIAL AND METHODS: A retrospective research in the OncoNeuroTox database was performed (2010-2016), searching for patients with the diagnosis of chemotherapy-induced peripheral neuropathy (CIPN) and CMT disease. A comprehensive literature review for previously published cases was performed using the Pubmed and Cochrane databases (1972-2017). RESULTS: Among 428 patients with CIPN, we identified eight patients with concomitant CMT disease. Seven patients out of the eight had no previous diagnosis of CMT disease, although accurate familial history disclosed mild signs of peripheral neuropathy in five cases. Patients themselves had minor stigmata of long-standing peripheral damage. Patients received chemotherapy regimens based on vinca alkaloids, taxanes or a combination of vinca alkaloids and platinum compounds. In two cases, cumulative doses were below or equal to the expected neurotoxic threshold. Following chemotherapy administration, patients developed severe length-dependent sensory-motor deficits. Despite early drug discontinuation, most patients remained severely disabled. CONCLUSION: A brief checklist to disclose long-standing signs of peripheral neuropathy could be helpful to detect patients with undiagnosed hereditary neuropathies who could be at risk of developing severe irreversible neurotoxicity following the administration of neurotoxic agents.

Hereditary neuropathies: An update.

Hereditary neuropathies are the most common inherited neuromuscular diseases. Charcot-Marie-Tooth (CMT) disease represents the most common form with an average prevalence ranging from 1/2500 to 1/1200, depending on the studies. To date and with the advances of the latest generation sequencing, more than 80 genes have been identified. Although the common clinical phenotype comprises a progressive distal muscle weakness and sensory loss, foot deformities and decreased or absent tendon reflexes, clinical and electrophysiological phenotypes exhibit great variability. Moreover, atypical phenotypes are arising, overlapping with spastic paraplegia, hereditary sensory neuropathies or amyotrophic lateral sclerosis. The causative genes are involved in various biological processes such as myelin development and maintenance, biosynthesis and degradation of proteins, neuronal structural maintenance, axonal transport, endocytosis, membrane dynamics, ion-channel function and the mitochondrial network. An accurate genetic diagnosis is important for appropriate genetic counselling and treatment options. Therapeutic advances, particularly small interfering RNA therapy, are encouraging in hereditary transthyretin amyloid neuropathy.

Myofibrillar myopathies: State of the art, present and future challenges.

Myofibrillar myopathies (MFM) have been described in the mid-1990s as a group of diseases sharing common histological features, including an abnormal accumulation of intrasarcoplasmic proteins, the presence of vacuoles and a disorganization of the intermyofibrillar network beginning at the Z-disk. The boundaries of this concept are still uncertain, and whereas six genes (DES, CRYAB, LDB3/ZASP, MYOT, FLNC and BAG3) are now classically considered as responsible for MFM, other entities such as FHL1 myopathy or Hereditary Myopathy with Early Respiratory Failure linked to mutations of titin can now as well be included in this group. The diagnosis of MFM is not always easy; as histological lesions can be focal, and muscle biopsy may be disappointing; this has led to a growing importance of muscle imaging, and the selectivity of muscle involvement has now been described in several disorders. Due to the rarity of these myopathies, if some clinical patterns (such as distal myopathy associated with cardiomyopathy due to desmin mutations) are now well known, surprises remain possible and should lead to systematic testing of the known genes in case of a typical histological presentation. In this paper, we aim at reviewing the data acquired on the six main genes listed above as well as presenting the experience from two French reference centres, Paris and Marseilles.

Diagnostic power of the non-ischaemic forearm exercise test in detecting glycogenosis type V.

BACKGROUND AND PURPOSE: This was a retrospective study to assess the diagnostic value of the non-ischaemic forearm exercise test in detecting McArdle's disease. METHODS: The study is a retrospective diagnostic study over 15 years (1999-2013) on a referred sample of patients suffering from exercise intolerance and various muscle complaints, generally with elevated creatine kinase (CK). In all, 1226 patients underwent the non-ischaemic forearm exercise test. Blood lactate, ammonia and CK levels were analyzed. DNA analyses and/or muscle biopsies were assessed to confirm the diagnosis of McArdle's disease. The results of 60 volunteers were used to compare with the results of study subjects. RESULTS: In this cohort, 40 patients were finally diagnosed with McArdle's disease. Absolute values of lactate and ammonia rise were used to discriminate all McArdle patients from healthy patients. A sensitivity and specificity of respectively 100% and 99.7% were calculated. The 24-h CK level showed no significant difference from the CK level at the day of the test and confirms the safety of the test. CONCLUSIONS: This study has formally assessed the diagnostic value of the non-ischaemic forearm exercise test in the detection of McArdle's disease. Very high sensitivity and specificity were observed. Furthermore, the test is easy to set up and to perform, it is non-traumatic and cost effective. It may circumvent a muscle biopsy in McArdle patients presenting the most common mutations. Hence, it is a perfect and safe screening instrument to detect patients with McArdle's disease. Glycogen storage disease type III patients, however, may show similar patterns to McArdle patients.

Bethlem myopathy: long-term follow-up identifies COL6 mutations predicting severe clinical evolution.

OBJECTIVE: Mutations in one of the 3 genes encoding collagen VI (COLVI) are responsible for a group of heterogeneous phenotypes of which Bethlem myopathy (BM) represents the milder end of the spectrum. Genotype-phenotype correlations and long-term follow-up description in BM remain scarce. METHODS: We retrospectively evaluated the long-term clinical evolution, and genotype-phenotype correlations in 35 genetically identified BM patients (23 index cases). RESULTS: Nineteen patients showed a typical clinical picture with contractures, proximal weakness and slow disease progression while 11 presented a more severe evolution. Five patients showed an atypical presentation, namely a limb girdle muscle weakness in 2 and a congenital myopathy pattern with either no contractures, or only limited to ankles, in 3 of them. Pathogenic COL6A1-3 mutations were mostly missense or in frame exon-skipping resulting in substitutions or deletions. Twenty one different mutations were identified including 12 novel ones. The mode of inheritance was, autosomal dominant in 83% of the index patients (including 17% (N=4) with a de novo mutation), recessive in 13%, and undetermined in one patient. Skipping of exon 14 of COL6A1 was found in 35% of index cases and was mostly associated with a severe clinical evolution. Missense mutations were detected in 39% of index cases and associated with milder forms of the disease. CONCLUSIONS: Long-term follow-up identified important phenotypic variability in this cohort of 35 BM patients. However, worsening of the functional disability appeared typically after the age of 40 in 47% of our patients, and was frequently associated with COL6A1 exon 14 skipping.

A comprehensive analysis of the epidemiology and clinical characteristics of anti-LRP4 in myasthenia gravis.

Double-seronegative myasthenia gravis (dSN-MG, without detectable AChR and MuSK antibodies) presents a serious gap in MG diagnosis and understanding. Recently, autoantibodies against the low-density lipoprotein receptor-related protein 4 (LRP4) have been identified in several dSN-MG sera, but with dramatic frequency variation (∼2-50%). We have developed a cell based assay (CBA) based on human LRP4 expressing HEK293 cells, for the reliable and efficient detection of LRP4 antibodies. We have screened about 800 MG patient sera from 10 countries for LRP4 antibodies. The overall frequency of LRP4-MG in the dSN-MG group (635 patients) was 18.7% but with variations among different populations (range 7-32.7%). Interestingly, we also identified double positive sera: 8/107 anti-AChR positive and 10/67 anti-MuSK positive sera also had detectable LRP4 antibodies, predominantly originating from only two of the participating groups. No LRP4 antibodies were identified in sera from 56 healthy controls tested, while 4/110 from patients with other neuroimmune diseases were positive. The clinical data, when available, for the LRP4-MG patients were then studied. At disease onset symptoms were mild (81% had MGFA grade I or II), with some identified thymic changes (32% hyperplasia, none with thymoma). On the other hand, double positive patients (AChR/LRP4-MG and MuSK/LRP4-MG) had more severe symptoms at onset compared with any single positive MG subgroup. Contrary to MuSK-MG, 27% of ocular dSN-MG patients were LRP4 antibody positive. Similarly, contrary to MuSK antibodies, which are predominantly of the IgG4 subtype, LRP4 antibodies were predominantly of the IgG1 and IgG2 subtypes. The prevalence was higher in women than in men (female/male ratio 2.5/1), with an average disease onset at ages 33.4 for females and 41.9 for males. Overall, the response of LRP4-MG patients to treatment was similar to published responses of AChR-MG rather than to MuSK-MG patients.

Antibodies to clustered acetylcholine receptor: expanding the phenotype.

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.

[Congenital myasthenic syndromes: difficulties in the diagnosis, course and prognosis, and therapy--The French National Congenital Myasthenic Syndrome Network experience]. / Syndromes myasthéniques congénitaux: difficultés diagnostiques, évolution et pronostic, thérapeutique--l'expérience du réseau national "Syndromes Myasthéniques Congénitaux".

Congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders caused by genetic defects affecting neuromuscular transmission and leading to muscle weakness accentuated by exertion. Three different aspects have been investigated by members of the national French CMS Network: the difficulties in making a proper diagnosis; the course and long-term prognosis; and the response to therapy, especially for CMS that do not respond to cholinesterase inhibitors. CMS diagnosis is late in most cases because of confusion with other entities such as: congenital myopathies, due to the frequent presentation in patients of myopathies such as permanent muscle weakness, atrophy and scoliosis, and the abnormalities of internal structure, diameter and distribution of fibers (type I predominance, type II atrophy) seen on biopsy; seronegative autoimmune myasthenia gravis, when CMS is of late onset; and metabolic myopathy, with the presence of lipidosis in muscle. The long-term prognosis of CMS was studied in a series of 79 patients recruited with the following gene mutations: CHRNA; CHRNE; DOK7; COLQ; RAPSN; AGRN; and MUSK. Disease-course patterns (progressive worsening, exacerbation, stability, improvement) could be variable throughout life in a given patient. DOK7 patients had the most severe disease course with progressive worsening: of the eight wheelchair-bound and ventilated patients, six had mutations of this gene. Pregnancy was a frequent cause of exacerbation. Anticholinesterase agents are the first-line therapy for CMS patients, except for cases of slow-channel CMS, COLQ and DOK7. In our experience, 3,4-DAP was a useful complement for several patients harboring CMS with AChR loss or RAPSN gene mutations. Ephedrine was given to 18 patients (eight DOK7, five COLQ, four AGRN and one RAPSN). Tolerability was good. Therapeutic responses were encouraging even in the most severely affected patients, particularly with DOK7 and COLQ. Salbutamol was a good alternative in one patient who was allergic to ephedrine.

[Ocular myasthenia: diagnosis and treatment]. / Myasthénies oculaires : diagnostic et traitement.

Myasthenia gravis is a rare, auto-immune disorder of the neuromuscular junction. Onset signs frequently involve ocular muscles, accounting for ptosis and/or diplopia in more than 75% of cases. Among the cases with purely ocular muscle involvement, less than one half will never progress towards a more general form of myasthenia. However, even if they do not share the potentially life-threatening course of generalized myasthenia, purely ocular forms are often responsible for severe impairment in everyday life. The diagnosis is essentially based on fluctuations in the time and topography of the ocular muscle weakness. It still remains uneasy, as investigations such as electromyography, search for antiacetycholine receptor antibodies (positive in 50% of cases of purely ocular myasthenia), and edrophonium chloride test sometimes yield false negative results. Whereas some patients get better while on anticholinesterasic drugs alone, most of them will experience insufficient improvement and need steroids and/or immunosuppressant drugs. There is no indication for plasma exchanges, intravenous immunoglobulin or thymectomy (except in the presence of thymoma). This treatment could well decrease the risk of an evolution towards generalized myasthenia. The reasons underlying the vulnerability of ocular motor muscles in myasthenia are complex and several factors (linked to immunology, anatomy and function) may combine to bring about their specific involvement. In the future, randomized, controlled trials will be necessary, in order to determine a more rational approach of the treatment of ocular myasthenia, which currently lies mostly on retrospective data and the expertise of reference centers implicated in the management of the disease.

Cardiac involvement is frequent in patients with the m.8344A>G mutation of mitochondrial DNA.

BACKGROUND: Cardiac complications, such as myocardial disease and arrhythmias, are frequent and may be severe in patients with mitochondrial disease. We sought to determine the prevalence and the prognostic value of cardiac abnormalities in a series of patients carrying the m.8344 A>G mutation. METHODS: We retrospectively collected data concerning a cohort of patients carrying the m.8344A>G mutation. Patients systematically underwent neurologic examination, muscular biopsy, measurement of forced vital capacity, and cardiac evaluation including electrocardiogram, echocardiography, and 24-hour ambulatory electrocardiogram at diagnosis. Neurologic and cardiac evaluations were repeated during follow-up at least every 2 years. RESULTS: Eighteen patients (mean age 39.3 +/- 17.3 years, 10 women) from 8 families were investigated. Mean follow-up duration was 5.0 +/- 2.7 years. Cardiac abnormalities were identified at diagnosis in 8 patients (44.4%, age 39.1 +/- 17.7 years), including dilated cardiomyopathy in 4, Wolff-Parkinson-White syndrome in 3, incomplete left bundle branch block in 1, and ventricular premature beats in 1. Two additional patients developed left ventricular dysfunction during follow-up and 2 patients died due to heart failure. Subgroup analyses identified early age at disease onset as the only factor significantly associated with myocardial dysfunction. CONCLUSIONS: We identified a high prevalence of ventricular dysfunction and Wolff-Parkinson-White syndrome. Myocardial involvement was associated with an increased risk of cardiac death due to heart failure, suggesting that cardiac investigations should be systematically considered in patients carrying the m.8344A>G mutation.

Phenotype genotype analysis in 15 patients presenting a congenital myasthenic syndrome due to mutations in DOK7.

Congenital myasthenic syndromes (CMSs) are a heterogeneous group of diseases caused by genetic defects affecting neuromuscular transmission. Mutations of DOK7 have recently been described in recessive forms of CMS. Dok-7 is a cytoplasmic post-synaptic protein co-activator of the muscle-specific receptor-tyrosine kinase (MuSK) involved in neuromuscular synaptogenesis and maintenance. We report clinical, morphological and molecular data on 15 patients with mutations in DOK7. Eleven different mutations (5 novel) were identified and all patients but one were found to carry at least the common c.1124_1127dupTGCC mutation. Patients with DOK7 mutations have a particular limb-girdle pattern, without tubular aggregates but a frequent lipidosis on the muscle biopsy. Changes in pre- and post-synaptic compartments of the neuromuscular junction were also observed in muscle biopsies: terminal axons showed defective branching which resulted in a unique terminal axon contacting en passant postsynaptic cups. Clinical features, muscle biopsy findings or response to therapy were confusing in several patients. Characterization of this distinct phenotype is essential to provide clues for targeted genetic screening and to predict the therapeutic response to anticholinesterase treatments or ephedrine as has been suggested.

Relapsing demyelinating disease affecting both the central and peripheral nervous systems.

BACKGROUND: Clinical and electromyographic findings of chronic inflammatory demyelinating polyradiculopathy (CIDP) are occasionally observed in patients with multiple sclerosis (MS). OBJECTIVE: To define a new inflammatory demyelinating disease unlike MS or CIDP. RESULTS: This study reports on five patients with a demyelinating disease affecting the central nervous system (CNS) and peripheral nervous system (PNS). Each case presented a relapsing-remitting course in which CNS involvement preceded PNS involvement. All patients fulfilled Barkhof's criteria on MRI and the McDonald criteria for MS. Two patients had grey matter lesions with typical white matter changes. No systemic inflammatory disease and no metabolic or inflammatory factor for peripheral neuropathy were found. In all cases electromyography showed a demyelinating peripheral neuropathy without conduction block. Four patients fulfilled the European Federation of Neurological Societies/PNS guideline for CIDP and Nicolas et al's criteria for CIDP, one of whom also fulfilled the Ad Hoc Subcommittee criteria for CIDP. Nerve biopsy, performed in two patients, showed histological evidence of CIDP. An improvement in clinical status and neurophysiological parameters was observed in three patients after treatment with either intravenous immunoglobulin (n = 1) or cyclophosphamide (n = 2). CONCLUSION: The CNS and PNS demyelination, the absence of oligoclonal bands and the peripheral demyelination without conduction block indicate pathogenic mechanisms different from MS and CIDP. The chronology of events suggests an entity unlike that involved in acute demyelinating encephalomyelitis. Immunological reactivity against antigens common to peripheral and central myelin may explain why the demyelinating disease affected both the CNS and PNS.

Neuropathy in lymphoma: a relationship between the pattern of neuropathy, type of lymphoma and prognosis?

BACKGROUND: Neuropathies associated with lymphoma (NAL) are rare and present a great clinical heterogeneity, making them difficult to diagnose and worsening their prognosis. OBJECTIVES: (1) To report the different patterns of NAL and discuss the mechanisms encountered; (2) to determine the relationship between a given type of lymphoma and a specific type of neuropathy; and (3) to assess the prognosis of NAL. METHODS: Among 150 patients with lymphoma and neuropathy, we selected 26 in whom the neuropathy was not related to drug induced or IgM-antimyelin associated glycoprotein neuropathies. The pattern of neuropathy was defined in terms of its clinical and electrophysiological features. Neurological improvement, haematological remission and occurrence of death were taken into account to determine the prognosis. RESULTS: 13 patients (50%) had a demyelinating polyneuropathy (PNP), seven (27%) had a radiculopathy linked to proximal root tumoral infiltration and six (23%) had an axonal multiple mononeuropathy (MM) related to distal lymphomatous infiltration or to paraneoplastic microvasculitis. Hodgkin's lymphoma was only associated with demyelinating PNP. High grade B cell lymphoma was strongly associated with radiculopathy. Neurological improvement was observed in 69% of patients with demyelinating PNP, 29% with radiculopathy and 50% with MM. Haematological remission was observed in 46% of patients with demyelinating PNP, 29% with radiculopathy and 83% with MM. CONCLUSIONS: Demyelinating PNP, the most frequently observed neuropathy in this study, had the best neurological prognosis. Chemotherapy combined with immune mediated treatment was the most effective treatment in this group. Identifying the type and mechanism of NAL is crucial in order to define the therapeutic strategy and improve the prognosis.

[Polymyositis and cranial neuropathy]. / Polymyosite et atteinte de nerfs crâniens.

BACKGROUND: Polymyositis with cranial neuropathy has been rarely reported. CASE REPORTS: We describe here three cases of polymyositis with trigeminal or facial neuropathy. Patients had muscular weakness, myalgia, rhabdomyolysis, endomysial infiltration with necrosis and regeneration at biopsy of muscle and, for two of them, a myopathic pattern at electromyogram. Two patients had also a Sjögren's syndrome and anti-nuclear antibodies. Anti-JO1 antibodies were presents in only one case. The outcome for one patient was good with corticosteroids alone. One other improved with the adjunction of immunoglobulin. The third one had a macrocheilia, a facial diplegia, antibodies against voltage-gated potassium channels and a neuromyotonia secondary to a paraneoplastic syndrome. He died after one year despite a treatment by corticosteroids and immunoglobulin. Patients fulfilled the diagnosis of polymyositis according to clinical, electromyographic, biological and histopathologic criteria. For the two patients with Sjögren's syndrome, the question of a primitive or a secondary Sjögren's syndrome remains unknown. CONCLUSION: The occurrence of a cranial neuropathy in polymyositis should make us looking for an association with paraneoplastic syndrome or connective tissue disease.

[Myasthenia gravis and pregnancy: clinical course and management of delivery and the postpartum phase]. / Myasthénie auto-immune et grossesse: évolution clinique, accouchement et post-partum.

OBJECTIVES: To study influences of pregnancy on the time-course of myasthenia gravis (MG) and of MG on pregnancy, delivery, postpartum and newborn. METHODS: We retrospectively collected data from 100 women affected with MG, hospitalized between 1994 and 2003 in departments of Neurology of Lille University Hospital. RESULTS: Eighteen patients had a total of 36 pregnancies, occurring 7.2 years on average after MG onset. MG exacerbation occurred in 7 patients (26 percent) during pregnancy and in 4 (14.8 percent) during postpartum. One patient died of acute respiratory failure during postpartum. Delay between the onset of MG and pregnancy was the only variable significantly associated with MG exacerbation: 5.8 years when exacerbation and 9.5 years when no exacerbation (p=0.03). Seven miscarriages, two therapeutic abortions and no death at birth were reported. Levels of anti-acetylcholine receptor antibodies were abnormal in 3 of 27 newborns (11 percent), but only one (3.7 percent) developed seronegative transient neonatal myasthenia gravis. DISCUSSION: During pregnancy, the clinical course of MG is variable but exacerbations were associated with a shorter delay between MG diagnosis and pregnancy. The risk of transient neonatal myasthenia gravis is relatively small but exists even when the parturient has stable MG without elevated levels of anti-acetylcholine receptor antibodies. CONCLUSION: Our study confirms pregnancy is more difficult to manage at the beginning of MG. Given the unpredictable course of MG during pregnancy, we recommend women affected with MG to begin a pregnancy when the disease is stable.