Publications by authors named "Thierry Maisonobe"

112 Publications

Deep phenotyping of an international series of patients with late-onset dysferlinopathy.

Eur J Neurol 2021 Mar 13. Epub 2021 Mar 13.

Nord/Est/Ile-de-France Neuromuscular Reference Center, Institute of Myology, Pitié-Salpêtrière Hospital, APHP, Sorbonne University, Paris, France.

Background: To describe the clinical, pathological, and molecular characteristics of late-onset (LO) dysferlinopathy patients.

Methods: Retrospective series of patients with LO dysferlinopathy, defined by an age at onset of symptoms ≥30 years, from neuromuscular centers in France and the International Clinical Outcome Study for dysferlinopathy (COS). Patients with early-onset (EO) dysferlinopathy (<30 years) were randomly selected from the COS study as a control group, and the North Star Assessment for Dysferlinopathy (NSAD) and Activity Limitation (ACTIVLIM) scores were used to assess functionality. Muscle biopsies obtained from 11 LO and 11 EO patients were revisited.

Results: Forty-eight patients with LO dysferlinopathy were included (28 females). Median age at onset of symptoms was 37 (range 30-57) years and most patients showed a limb-girdle (n = 26) or distal (n = 10) phenotype. However, compared with EO dysferlinopathy patients (n = 48), LO patients more frequently showed atypical phenotypes (7 vs. 1; p = 0.014), including camptocormia, lower creatine kinase levels (2855 vs. 4394 U/L; p = 0.01), and higher NSAD (p = 0.008) and ACTIVLIM scores (p = 0.016). Loss of ambulation in LO patients tended to occur later (23 ± 4.4 years after disease onset vs. 16.3 ± 6.8 years; p = 0.064). Muscle biopsy of LO patients more frequently showed an atypical pattern (unspecific myopathic changes) as well as significantly less necrosis regeneration and inflammation. Although LO patients more frequently showed missense variants (39.8% vs. 23.9%; p = 0.021), no differences in dysferlin protein expression were found on Western blot.

Conclusions: Late-onset dysferlinopathy patients show a higher frequency of atypical presentations, are less severely affected, and show milder dystrophic changes in muscle biopsy.
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http://dx.doi.org/10.1111/ene.14821DOI Listing
March 2021

Focal chronic inflammatory demyelinating polyradiculoneuropathy: Onset, course, and distinct features.

J Peripher Nerv Syst 2021 Mar 4. Epub 2021 Mar 4.

Département de neurophysiologie clinique, Hôpital de la Pitié-Salpêtrière, APHP Paris VI Université, Paris, France.

Focal chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is defined as involving the brachial or lumbosacral plexus, or one or more peripheral nerves in one upper or one lower limb (monomelic distribution). However, other auto-immune neuropathies such as Lewis-Sumner syndrome (LSS) and multifocal motor neuropathy (MMN) can also have a focal onset. From a retrospective cohort of 30 focal CIDP patients with a monomelic onset dating back at least 2 years, we distinguished patients with plexus involvement (focal demyelinating plexus neuropathy [F-PN], n = 18) from those with sensory or sensorimotor (F-SMN, n = 7), or purely motor (F-MN, n = 5) impairment located in one or several peripheral nerves. Few (39%) F-PN patients had motor nerve conduction abnormalities, but the majority showed proximal conduction abnormalities in somatosensory evoked potentials (80%), and all had focal hypertrophy and/or increased short tau inversion recovery image signal intensity on plexus MRI. Impairment remained monomelic in most (94%) F-PN patients, whereas abnormalities developed in other limbs in 57% of F-SMN, and 40% of F-MN patients (P = .015). The prognosis of F-PN patients was significantly better: none had an ONLS score > 2 at the final follow-up visit, vs 43% of F-SMN patients and 40% of F-MN patients (P = .026). Our findings from a large cohort of focal CIDP patients confirm the existence of different entities that are typically categorized under this one term: on the one hand, patients with a focal plexus neuropathy and on the other, patients with monomelic sensori-motor or motor involvement of peripheral nerves. These two last subgroups appeared to be more likely to evolve to LSS or MMN phenotype, when F-PN patients have a more distinctive long-term, focal, benign course.
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http://dx.doi.org/10.1111/jns.12438DOI Listing
March 2021

Confirmed cases of Neuroborreliosis with involvement of peripheral nervous system: Description of a cohort.

Medicine (Baltimore) 2020 Oct;99(40):e21986

Département de Neurophysiologie Clinique, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.

The manifestations of borreliosis in the peripheral nervous system (PNS) remain poorly described. As the symptoms of neuroborreliosis can be reversed with timely introduction of antibiotics, early identification could avoid unnecessary axonal loss. Our aim was to describe the characteristics of confirmed neuroborreliosis cases involving the PNS diagnosed between 2007 and 2017 in our neuromuscular disease center in a nonendemic area (La Pitié-Salpêtrière Hospital, Paris, France).Neuroborreliosis was defined as follows: compatible neurological symptoms without other cause of neuropathy; cerebrospinal fluid and serum analysis (positive serological tests with ELISA, confirmed by Western Blot); and improvement of symptoms with adapted antibiotherapy. All the patients consulting in our center between 2007 and 2017 underwent electrophysiological study.Sixteen confirmed cases of neuroborreliosis involving the PNS were included: 10 cases of meningoradiculoneuritis, 4 of axonal neuropathy, and 2 of demyelinating neuropathy (one acute and one chronic). Only 4 (25%) patients reported tick bites. Meningoradiculoneuritis was characterized by lymphocytic meningitis, intense pain, cranial nerve palsy, and contrast enhancement of nerve roots on imagery. The patients with axonal neuropathy presented sensory symptoms with intense pain but no motor deficit and meningitis was rare. Nerve biopsy of 1 patient revealed lymphocytic vasculitis. Electrophysiological testing showed sensory or sensorimotor axonal neuropathy (3 subacute and 1 chronic) of the lower limbs, with asymmetrical neuropathy in 1 patients, symmetrical neuropathy in one and monomelic sensory mononeuritis multiplex in another. We also found 1 case of acute demyelinating neuropathy, treated with antibiotherapy and immunoglobulins, and 1 chronic demyelinating neuropathy. Overall, diaphragmatic paralysis was frequent (18.6%). Antibiotherapy (mostly ceftriaxone 3-4 weeks) resulted in symptom resolution.This series gives an updated overview of the peripheral complications of neuroborreliosis to help identify this disease so that timely treatment could avoid axonal loss.
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http://dx.doi.org/10.1097/MD.0000000000021986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7535703PMC
October 2020

CANOMAD: a neurological monoclonal gammopathy of clinical significance that benefits from B-cell-targeted therapies.

Blood 2020 11;136(21):2428-2436

Sorbonne Université, Service d'Hématologie Clinique, Hôpital Pitié-Salpêtrière, Assitance Publique des Hôpitaux de Paris (AP1HP), Paris, France.

CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, immunoglobulin M [IgM] paraprotein, cold agglutinins, and disialosyl antibodies) is a rare syndrome characterized by chronic neuropathy with sensory ataxia, ocular, and/or bulbar motor weakness in the presence of a monoclonal IgM reacting against gangliosides containing disialosyl epitopes. Data regarding associated hematologic malignancies and effective therapies in CANOMAD are scarce. We conducted a French multicenter retrospective study that included 45 patients with serum IgM antibodies reacting against disialosyl epitopes in the context of evocating neurologic symptoms. The main clinical features were sensitive symptoms (ataxia, paresthesia, hypoesthesia; n = 45, 100%), motor weakness (n = 18, 40%), ophthalmoplegia (n = 20, 45%), and bulbar symptoms (n = 6, 13%). Forty-five percent of the cohort had moderate to severe disability (modified Rankin score, 3-5). Cold agglutinins were identified in 15 (34%) patients. Electrophysiologic studies showed a demyelinating or axonal pattern in, respectively, 60% and 27% of cases. All patients had serum monoclonal IgM gammopathy (median, 2.6 g/L; range, 0.1-40 g/L). Overt hematologic malignancies were diagnosed in 16 patients (36%), with the most frequent being Waldenström macroglobulinemia (n = 9, 20%). Forty-one patients (91%) required treatment of CANOMAD. Intravenous immunoglobulins (IVIg) and rituximab-based regimens were the most effective therapies with, respectively, 53% and 52% of partial or better clinical responses. Corticosteroids and immunosuppressive drugs were largely ineffective. Although more studies are warranted to better define the optimal therapeutic sequence, IVIg should be proposed as the standard of care for first-line treatment and rituximab-based regimens for second-line treatment. These compiled data argue for CANOMAD to be included in neurologic monoclonal gammopathy of clinical significance.
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http://dx.doi.org/10.1182/blood.2020007092DOI Listing
November 2020

Homoplasmic deleterious MT-ATP6/8 mutations in adult patients.

Mitochondrion 2020 11 26;55:64-77. Epub 2020 Aug 26.

INSERM U1016 Institut Cochin, CNRS UMR 8104, Université Paris-Decartes-Paris5, Paris, France. Electronic address:

To address the frequency of complex V defects, we systematically sequenced MT-ATP6/8 genes in 512 consecutive patients. We performed functional analysis in muscle or fibroblasts for 12 out of 27 putative homoplasmic mutations and in cybrids for four. Fibroblasts, muscle and cybrids with known deleterious mutations underwent parallel analysis. It included oxidative phosphorylation spectrophotometric assays, western blots, structural analysis, ATP production, glycolysis and cell proliferation evaluation. We demonstrated the deleterious nature of three original mutations. Striking gradation in severity of the mutations consequences and differences between muscle, fibroblasts and cybrids implied a likely under-diagnosis of human complex V defects.
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http://dx.doi.org/10.1016/j.mito.2020.08.004DOI Listing
November 2020

Antibodies against the node of Ranvier: a real-life evaluation of incidence, clinical features and response to treatment based on a prospective analysis of 1500 sera.

J Neurol 2020 Dec 16;267(12):3664-3672. Epub 2020 Jul 16.

Timone Neuroscience Institute, UMR CNRS 7289, Aix-Marseille University, 13005, Marseille, France.

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.
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http://dx.doi.org/10.1007/s00415-020-10041-zDOI Listing
December 2020

Ganglionopathies Associated with MERRF Syndrome: An Original Report.

J Neuromuscul Dis 2020 ;7(4):419-423

Department of Neurology, Neuromuscular Reference Center Nord/Est/Ile de France, Raymond-Poincaré Teaching Hospital, AP-HP, Garches, Paris Saclay University, France.

Neuropathies in Myoclonic Epilepsy with Ragged Red Fibers (MERRF) syndrome are frequent but ganglionopathies have never been reported. We retrospectively identified 24 patients with MERRF mutations in the neuromuscular center Nord/Est/Ile de France (Pitié-Salpêtrière, Paris, France). Seventeen nerve conduction studies (NCS) were available. Five patients had MERRF syndrome and ganglionopathy, a pure sensory neuropathy. All of them displayed ataxia and mild clinical sensory abnormalities. Ganglionopathies have been reported in mitochondrial diseases but never in MERRF syndrome. We suggest that patients presenting with ganglionopathy, especially if associated with myopathy, lipomatosis or epilepsy, should be screened for MERRF mutations.
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http://dx.doi.org/10.3233/JND-200513DOI Listing
January 2020

GGPS1 Mutations Cause Muscular Dystrophy/Hearing Loss/Ovarian Insufficiency Syndrome.

Ann Neurol 2020 08 18;88(2):332-347. Epub 2020 Jun 18.

Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.

Objective: A hitherto undescribed phenotype of early onset muscular dystrophy associated with sensorineural hearing loss and primary ovarian insufficiency was initially identified in 2 siblings and in subsequent patients with a similar constellation of findings. The goal of this study was to understand the genetic and molecular etiology of this condition.

Methods: We applied whole exome sequencing (WES) superimposed on shared haplotype regions to identify the initial biallelic variants in GGPS1 followed by GGPS1 Sanger sequencing or WES in 5 additional families with the same phenotype. Molecular modeling, biochemical analysis, laser membrane injury assay, and the generation of a Y259C knock-in mouse were done.

Results: A total of 11 patients in 6 families carrying 5 different biallelic pathogenic variants in specific domains of GGPS1 were identified. GGPS1 encodes geranylgeranyl diphosphate synthase in the mevalonate/isoprenoid pathway, which catalyzes the synthesis of geranylgeranyl pyrophosphate, the lipid precursor of geranylgeranylated proteins including small guanosine triphosphatases. In addition to proximal weakness, all but one patient presented with congenital sensorineural hearing loss, and all postpubertal females had primary ovarian insufficiency. Muscle histology was dystrophic, with ultrastructural evidence of autophagic material and large mitochondria in the most severe cases. There was delayed membrane healing after laser injury in patient-derived myogenic cells, and a knock-in mouse of one of the mutations (Y259C) resulted in prenatal lethality.

Interpretation: The identification of specific GGPS1 mutations defines the cause of a unique form of muscular dystrophy with hearing loss and ovarian insufficiency and points to a novel pathway for this clinical constellation. ANN NEUROL 2020;88:332-347.
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http://dx.doi.org/10.1002/ana.25772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496979PMC
August 2020

Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes.

Nat Genet 2020 05 4;52(5):473-481. Epub 2020 May 4.

Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.

Here we report biallelic mutations in the sorbitol dehydrogenase gene (SORD) as the most frequent recessive form of hereditary neuropathy. We identified 45 individuals from 38 families across multiple ancestries carrying the nonsense c.757delG (p.Ala253GlnfsTer27) variant in SORD, in either a homozygous or compound heterozygous state. SORD is an enzyme that converts sorbitol into fructose in the two-step polyol pathway previously implicated in diabetic neuropathy. In patient-derived fibroblasts, we found a complete loss of SORD protein and increased intracellular sorbitol. Furthermore, the serum fasting sorbitol levels in patients were dramatically increased. In Drosophila, loss of SORD orthologs caused synaptic degeneration and progressive motor impairment. Reducing the polyol influx by treatment with aldose reductase inhibitors normalized intracellular sorbitol levels in patient-derived fibroblasts and in Drosophila, and also dramatically ameliorated motor and eye phenotypes. Together, these findings establish a novel and potentially treatable cause of neuropathy and may contribute to a better understanding of the pathophysiology of diabetes.
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http://dx.doi.org/10.1038/s41588-020-0615-4DOI Listing
May 2020

Motor chronic inflammatory demyelinating polyneuropathy (CIDP) in 17 patients: Clinical characteristics, electrophysiological study, and response to treatment.

J Peripher Nerv Syst 2020 06 26;25(2):162-170. Epub 2020 May 26.

Département de Neurophysiologie Clinique, Hôpital Pitié Salpêtrière, Assistance publique-Hôpitaux de Paris, Paris, France.

Motor chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare and poorly described subtype of CIDP. We aimed to study their clinical and electrophysiological characteristics and response to treatment. From a prospective database of CIDP patients, we included patients with definite or probable CIDP with motor signs and without sensory signs/symptoms at diagnosis. Patients were considered to have pure motor CIDP (PM-CIDP) if sensory conductions were normal or to have motor predominant CIDP (MPred-CIDP) if ≥2 sensory nerve action potential amplitudes were abnormal. Among the 700 patients with CIDP, 17 (2%) were included (PM-CIDP n = 7, MPred-CIDP n = 10); 71% were male, median age at onset was 48 years (range: 13-76 years), 47% had an associated inflammatory or infectious disease or neoplasia. At the more severe disease stage, 94% of patients had upper and lower limb weakness, with distal and proximal weakness in 4 limbs for 56% of them. Three-quarters (75%) responded to intravenous immunoglobulins (IVIg) and four of five patients to corticosteroids including three of three patients with MPred-CIDP. The most frequent conduction abnormalities were conduction blocks (CB, 82%) and F-wave abnormalities (88%). During follow up, 4 of 10 MPred-CIDP patients developed mild sensory symptoms; none with PM-CIDP did so. Patients with PM-CIDP had poorer outcome (median ONLS: 4; range: 22-5) compared to MPred-CIDP (2, range: 0-4; P = .03) at last follow up. This study found a progressive clinical course in the majority of patients with motor CIDP as well as frequent associated diseases, CB, and F-wave abnormalities. Corticosteroids might be considered as a therapeutic option in resistant IVIg patients with MPred-CIDP.
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http://dx.doi.org/10.1111/jns.12380DOI Listing
June 2020

Systemic Lupus Erythematosus Associated With Polyarteritis Nodosa-Like Muscular Vasculitis.

J Clin Rheumatol 2020 Apr 25. Epub 2020 Apr 25.

From the Service de Médicine Interne, Centre de Référence des Maladies Auto-Immunes et Systémiques Rares d'ile de France, Hôpital Cochin, APHP.

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http://dx.doi.org/10.1097/RHU.0000000000001397DOI Listing
April 2020

Brentuximab vedotin treatment associated with acute and chronic inflammatory demyelinating polyradiculoneuropathies.

J Neurol Neurosurg Psychiatry 2020 07 23;91(7):786-788. Epub 2020 Apr 23.

AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie 2-Mazarin et Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière (CRICM), UMRS 975, Paris 75013, France; Inserm U 975, CNRS, UMR 7225, Paris 75013, France, Paris, France.

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http://dx.doi.org/10.1136/jnnp-2020-323124DOI Listing
July 2020

Electrophysiological features of chronic inflammatory demyelinating polyradiculoneuropathy associated with IgG4 antibodies targeting neurofascin 155 or contactin 1 glycoproteins.

Clin Neurophysiol 2020 04 6;131(4):921-927. Epub 2020 Feb 6.

Referral Centre for Neuromuscular Diseases and ALS, La Timone hospital, Marseille, France; Aix-Marseille University, Timone Neuroscience Institute, UMR CNRS 7289, 13005 Marseille, France. Electronic address:

Objective: Chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) with antibodies against neurofascin 155 (Nfasc155) or contactin-1 (CNTN1) have distinctive clinical features. Knowledge on their electrophysiological characteristics is still scarce. In this study, we are investigating whether these patients have specific electrophysiological characteristics.

Methods: The electrophysiological data from 13 patients with anti-Nfasc155 IgG4 antibodies, 9 with anti-CNTN1 IgG4 antibodies were compared with those of 40 consecutive CIDP patients without antibodies.

Results: All the patients with antibodies against Nfasc155 or CNTN1 fulfilled the EFNS/PNS electrodiagnostic criteria for definite CIDP. There was no electrophysiological difference between patients with anti-CNTN1 and anti-Nfasc155 antibodies. Nerve conduction abnormalities were heterogeneously distributed along nerves trunks and roots. They were more pronounced than in CIDP without antibodies. Motor conduction velocity on median nerve <24 m/s or motor velocity on ulnar nerve <26 m/s or motor distal latency on ulnar nerve >7.4 ms were predictive of positive antibodies against the node of Ranvier with a sensitivity of 59% and a specificity of 93%.

Conclusions: Marked conduction abnormalities may suggest the presence of positive antibodies against the node of Ranvier.

Significance: Anti-Nfasc155 and anti-CNTN1 antibodies target the the paranodal axo-glial domain but are associated with nerve conduction abnormalities mimicking a "demyelinating" neuropathy.
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http://dx.doi.org/10.1016/j.clinph.2020.01.013DOI Listing
April 2020

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome due to RFC1 repeat expansion.

Brain 2020 02;143(2):480-490

Department of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.

Ataxia, causing imbalance, dizziness and falls, is a leading cause of neurological disability. We have recently identified a biallelic intronic AAGGG repeat expansion in replication factor complex subunit 1 (RFC1) as the cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) and a major cause of late onset ataxia. Here we describe the full spectrum of the disease phenotype in our first 100 genetically confirmed carriers of biallelic repeat expansions in RFC1 and identify the sensory neuropathy as a common feature in all cases to date. All patients were Caucasian and half were sporadic. Patients typically reported progressive unsteadiness starting in the sixth decade. A dry spasmodic cough was also frequently associated and often preceded by decades the onset of walking difficulty. Sensory symptoms, oscillopsia, dysautonomia and dysarthria were also variably associated. The disease seems to follow a pattern of spatial progression from the early involvement of sensory neurons, to the later appearance of vestibular and cerebellar dysfunction. Half of the patients needed walking aids after 10 years of disease duration and a quarter were wheelchair dependent after 15 years. Overall, two-thirds of cases had full CANVAS. Sensory neuropathy was the only manifestation in 15 patients. Sixteen patients additionally showed cerebellar involvement, and six showed vestibular involvement. The disease is very likely to be underdiagnosed. Repeat expansion in RFC1 should be considered in all cases of sensory ataxic neuropathy, particularly, but not only, if cerebellar dysfunction, vestibular involvement and cough coexist.
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http://dx.doi.org/10.1093/brain/awz418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009469PMC
February 2020

Randomized, Placebo-Controlled Clinical Trial Combining Pentoxifylline-Tocopherol and Clodronate in the Treatment of Radiation-Induced Plexopathy.

Int J Radiat Oncol Biol Phys 2020 05 24;107(1):154-162. Epub 2020 Jan 24.

Groupe Hospitalier Universitaire, APHP site Pitié-Salpêtrière-Sorbonne Université, Neurologie and CNRS-INSERM, Laboratoire d'Imagerie Biomédicale, Paris, France.

Purpose: Radiation-induced (RI) plexopathy is a rare peripheral nerve injury after radiation therapy for cancer. No treatment has been shown to slow its progression. A pentoxifylline-vitamin E combination significantly reduced RI fibrosis, and its association with clodronate (PENTOCLO) allowed healing of osteoradionecrosis and reduction of neurologic symptoms in phase 2 trials.

Methods And Materials: A placebo-controlled, double-blind trial conducted in adults with RI limb plexopathy without cancer recurrence, randomized in 2 arms to PENTOCLO (pentoxifylline 800 mg, tocopherol 1000 mg, clodronate 1600 mg 5 days per week) or triple placebo. The primary outcome measure after 18 months of treatment was the neurologic Subjective Objective Management Analytic (SOMA) score evaluating pain, paresthesia, and motor disability.

Results: Between 2011 and 2015, 59 patients were included: 1 false inclusion (neoplastic plexopathy), 29 treated with placebo (group P), and 29 treated with the active drugs (group A); 46 patients presented an upper-limb and 12 a lower-limb plexopathy. The mean delay after irradiation was 26 ± 8 years, for patients with neurologic symptoms for 5 ± 5 years. The median global SOMA scores in the P and A groups, respectively, were 9 (range, 6-11) versus 9 (range, 8-11) at M and 9 (range, 5-12) versus 10 (range, 6-11) at M without any significant difference. Analysis of the secondary outcomes showed that SOMA score subdomains for pain and paresthesia were more affected in group A (not significant). The frequency of adverse events was similar in the 2 groups (81% of patients): slight expected vascular-gastrointestinal symptoms in A, but a large excess of RI complications (arterial stenosis).

Conclusions: This first randomized drug trial in RI plexopathy failed to show a beneficial effect. More studies are needed in patients with less advanced disease and fewer confounding comorbidities and with a more sensitive measure to detect a therapeutic effect.
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http://dx.doi.org/10.1016/j.ijrobp.2020.01.002DOI Listing
May 2020

Guillain-Barré Syndrome During Platinum-Based Chemotherapy: A Case Series and Review of the Literature.

Oncologist 2020 01 15;25(1):e194-e197. Epub 2019 Oct 15.

Assistance Publique Hôpitaux de Paris (APHP), Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie 2-Mazarin et Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière (CRICM), Unité Mixte de Recherche (UMR) S975, Paris, France.

Platinum-based chemotherapy is commonly associated with toxic sensory neuropathies, but also, although rarely, with Guillain-Barré syndrome (GBS). We describe five patients who developed GBS while receiving platinum-based chemotherapy for a solid tumor and report the five cases published so far. Most patients had received cumulative platinum doses below known neurotoxic levels, and all of them had an optimal outcome after platinum discontinuation, associated in most cases with administration of intravenous immunoglobulin. Clinical presentation, electroneuromyography, and cerebrospinal fluid analysis help clinicians to differentiate GBS from toxic neuropathy. Platinum compounds are the only chemotherapeutic agents used for solid tumors that have been associated to GBS. Thus, we propose that GBS may constitute a non-dose-dependent side effect of platinum drugs and that awareness needs to be raised among oncologists on this rare but potentially life-threatening complication of platinum chemotherapy. IMPLICATIONS FOR PRACTICE: Many patients on platinum-based chemotherapy for solid tumors develop sensory neuropathy, a common dose-dependent side effect. The authors propose that Guillain-Barré syndrome may constitute an immune-mediated, non-dose-related side effect of platinum-based chemotherapy. Prompt diagnosis of Guillain-Barré syndrome and distinction from classical toxic neuropathy are crucial for optimal treatment. Platinum discontinuation, associated if needed to intravenous immunoglobulin administration, radically changes the course of the disease and minimizes neurological sequelae.
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http://dx.doi.org/10.1634/theoncologist.2019-0255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964130PMC
January 2020

Muscular dystrophy with arrhythmia caused by loss-of-function mutations in .

Neurol Genet 2019 Apr 1;5(2):e321. Epub 2019 Apr 1.

Neurogenetics Group (W.D.R., P.D.J., J.B.), University of Antwerp; the Laboratory of Neuromuscular Pathology (W.D.R., P.D.J., J.B.), Institute Born- Bunge, University of Antwerp; the Neuromuscular Reference Centre (W.D.R., P.D.J., J.B.), Department of Neurology, Antwerp University Hospital, Belgium; Sorbonne Université (I.N., M.B., R.B.Y., G.B.), INSERM U974, Center of Research in Myology, Institute of Myology, G.H. Pitié-Salpêtrière Paris, France; Histology and Cellular Imaging (B.A.), Neuromics Support Facility, VIB-UAntwerp Center for Molecular Neurology, University of Antwerp; Laboratory for Neuropathology (B.D.P., J.D.B.), Division of Neurology, Ghent University Hospital, Belgium; AP-HP, Centre de Référence de Pathologie Neuromusculaire Nord/Est/Ile-deFrance (R.B.Y., B.E.), G.H. Pitié-Salpêtrière, Bioinformatics Unit (C.M.), Necker Hospital, AP-HP, and University Paris Descartes, ; Centre National de Recherche en Génomique Humaine (CNRGH) (A.B., J.F.D.), Institut de Biologie François Jacob, CEA, Université Paris-Saclay, Evry; Laboratoire de Neuropathologie (T.M.), G.H. Pitié-Salpêtrière, Paris, France; Center for Medical Genetics (S.S.), Ghent University Hospital, Belgium; Developmental Dynamics, Imperial Centre for Experimental and Translational Medicine (R.S., T.B.), Imperial College London; John Walton Muscular Dystrophy Research Centre (K.J., A.T., V.S.), MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.

Objective: To study the genetic and phenotypic spectrum of patients harboring recessive mutations in .

Methods: We performed whole-exome sequencing in a multicenter cohort of 1929 patients with a suspected hereditary myopathy, showing unexplained limb-girdle muscular weakness and/or elevated creatine kinase levels. Immunohistochemistry and mRNA experiments on patients' skeletal muscle tissue were performed to study the pathogenicity of identified loss-of-function (LOF) variants in .

Results: We identified 4 individuals from 3 families harboring homozygous LOF variants in , the gene that encodes for Popeye domain containing protein 1 (POPDC1). Patients showed skeletal muscle involvement and cardiac conduction abnormalities of varying nature and severity, but all exhibited at least subclinical signs of both skeletal muscle and cardiac disease. All identified mutations lead to a partial or complete loss of function of through nonsense-mediated decay or through functional changes to the POPDC1 protein.

Conclusions: We report the identification of homozygous LOF mutations in , causal in a young adult-onset myopathy with concomitant cardiac conduction disorders in the absence of structural heart disease. These findings underline the role of POPDC1, and by extension, other members of this protein family, in striated muscle physiology and disease. This disorder appears to have a low prevalence, although it is probably underdiagnosed because of its striking phenotypic variability and often subtle yet clinically relevant manifestations, particularly concerning the cardiac conduction abnormalities.
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http://dx.doi.org/10.1212/NXG.0000000000000321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501641PMC
April 2019

Severe transient myopathy in a patient with progressive multiple sclerosis and high-dose biotin.

Neurology 2019 05 26;92(22):1060-1062. Epub 2019 Apr 26.

From the Department of Neurology (E.M.), Department of Genetics and Reference Centre for Adult Neurometabolic Diseases (F.M.), and Department of Neurophysiology and Neuropathology (T.M.), AP-HP, Hôpital Pitié-Salpêtrière; Institut du Cerveau et de la Moelle Épinière, UPMC-Paris 6, UMR S 1127 and Inserm U 1127, and CNRS UMR 7225 (F.M., B.S.), Sorbonne Université, Paris, France; Laboratory of Inborn Errors of Metabolism (C.A.), Centre Hospitalier Universitaire de Lyon, France; and Department of Neurology (B.S.), AP-HP, Hôpital Saint-Antoine, Paris, France.

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http://dx.doi.org/10.1212/WNL.0000000000007576DOI Listing
May 2019

Rituximab in chronic inflammatory demyelinating polyradiculoneuropathy with associated diseases.

J Peripher Nerv Syst 2018 12 7;23(4):235-240. Epub 2018 Oct 7.

Department of Clinical Neurophysiology, APHP, Pitié-Salpêtrière Hospital, Paris, France.

We aimed to analyse the response to rituximab in a cohort of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients with associated disorders. We conducted a clinical and electrophysiological retrospective monocentric study in 28 CIDP patients. Response to rituximab was defined as (a) a five-point increase in the Medical Research Council sum score or a one-point decrease in the Overall Neuropathy Limitations Scale score, compared to the score at the first rituximab infusion, or (b) the discontinuation of, or reduced need for, the last treatments before rituximab initiation. Twenty-one patients (75%) were responders to rituximab. The median time before response was 6 months (1-10 months). Only two patients needed to be treated again during a median follow-up of 2.0 years (0.75-9 years). Interestingly, the response rate was good in patients with associated autoimmune disease (5/8) and similar to the response rate observed in patients with a haematological disease (16/20) (P = 0.63). A shorter disease duration was associated with a better clinical response to rituximab (odds ratio 0.81, P = 0.025) and the response rate was better (P = 0.05) in common forms (83.3%) than in sensory forms (42.9%). No major adverse events were recorded. Rituximab is efficacious in CIDP patients with haematological or autoimmune disease. It improves clinical response and decreases dependence on first-line treatments.
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http://dx.doi.org/10.1111/jns.12287DOI Listing
December 2018

Immune checkpoint inhibitor-related myositis and myocarditis in patients with cancer.

Neurology 2018 09 8;91(10):e985-e994. Epub 2018 Aug 8.

From Sorbonne Université (M.T., D.P.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, APHP, Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix, Service de Neurologie 2-Mazarin; OncoNeuroTox Group (M.T., T.M., N.W., T.L., D.P.), Center for Patients With Neurological Complications of Oncologic Treatments, Hôpitaux Universitaires Pitié-Salpetrière-Charles Foix et Hôpital Percy, Paris, France; Department of Oncologic Pathology (M.T.), Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, MA; Service de Neuropathologie Raymond Escourolle (T.M., S.L.-L.), Départment de Neurophysiologie Clinique (T.M., T.L., S.L.-L.), Département de Médecine Interne et Immunologie Clinique (B.H., Y.A., O.B.), and Centre de Référence de Pathologie Neuromusculaire Paris-Est (B.H., A.B., Y.A., O.B., S.L.-L.), APHP, Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix, Paris, France; Charité-Universitatsmedizin Berlin Klinik fur Neurologie mit Experimenteller Neurologie (S.K.), Experimentelle Neurologie; Centrum fur Schlaganfallforschung Berlin (S.K.), Germany; Service de Réanimation Médicale (O.B.H.S.), Service de Médecine Interne (T.-A.S.), and Département de Dermatologie (N.K.), Hôpital Cochin, APHP, Hôpitaux Universitaires Paris Centre; Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris) (B.H.), Sorbonne Universités; Service d'Explorations Fonctionnelles (K.A.), APHP, Hôpital Ambroise Paré, Boulogne-Billancourt; Service de Pneumologie (C.L.) and Service d'Anatomie Pathologique (J.-F.B.), Centre Hospitalier Chartres-Louis-Pasteur, Le-Coudray; Service de Dermatologie (P.L.), APHP, Hôpital Saint Louis; Service de Pneumologie et Oncologie Thoracique (J.C.), Centre de Compétences pour les Maladies Pulmonaires Rares, APHP, Hôpital Tenon, Sorbonne Universités; Sorbonne Université (N.W.), Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM, Centre de Recherche Saint-Antoine, APHP, Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix, Département de Neurologie, Unité de réanimation neurologique; Inserm UMR974 (Y.A., O.B.), Centre de recherche en myologie, Université Pierre-et-Marie-Curie, Sorbonnes Universités, Paris, France; and Department of Neuropathology (W.S.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Germany.

Objective: To report the clinicopathologic features and outcome of myositis in patients treated with immune checkpoint inhibitors (ICIs) (irMyositis).

Methods: We retrospectively analyzed patients diagnosed with irMyositis in tertiary centers in Paris, France, and Berlin, Germany, from January 2015 to July 2017. The main outcomes were clinical manifestations and muscle histology, which included major histocompatibility complex class I (MHC-I), C5b-9, CD3, CD4, CD8, CD20, CD68, programmed cell death protein 1 (PD-1), programmed cell death 1 ligand 1 (PD-L) 1, and programmed cell death 1 ligand 2 (PD-L2).

Results: Ten patients with metastatic cancer were included; median age was 73 (range 56-87) years. Median follow-up duration was 48 (range 16-88) weeks. Six patients developed myositis during nivolumab therapy, 1 patient during pembrolizumab, 1 patient during durvalumab, and 2 patients during combined nivolumab and ipilimumab. Median delay between ICI initiation and myositis onset was 25 (range 5-87) days. Clinical manifestations were dominated by acute or subacute myalgia (8 patients) and limb-girdle (7), axial (7), and oculomotor (7) weakness. Four patients had evidence of myocarditis. In all patients, creatine kinase levels were elevated (median 2,668, range 1,059-16,620 U/L), while anti-acetylcholine receptor and myositis-associated antibodies were negative. Electrodiagnostic studies showed myopathic process without decrement in all patients. Muscle biopsy constantly showed multifocal necrotic myofibers, sarcolemmal MHC-I, and endomysial inflammation, consisting mainly of CD68+ cells expressing PD-L1 and CD8+ cells expressing PD-1. ICI treatment was withdrawn in all patients; 9 patients received immunosuppressive therapy, which consistently led to marked clinical improvement.

Conclusions: irMyositis presents with remarkably homogeneous and unique clinicopathologic features, expanding the nosologic spectrum of inflammatory myopathies in patients with cancer. ICI withdrawal and treatment with corticosteroids improve outcome.
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http://dx.doi.org/10.1212/WNL.0000000000006124DOI Listing
September 2018

Pathology of Nerve Biopsy and Diagnostic Yield of PCR-Based Clonality Testing in Neurolymphomatosis.

J Neuropathol Exp Neurol 2018 09;77(9):769-781

Service et Laboratoire de Neurologie, Centre National de Référence "Neuropathies Périphériques rares", CHRU Limoges, Limoges, France.

Infiltration of the peripheral nervous system (PNS) by lymphoma, called neurolymphomatosis, is a rare condition among the spectrum of lymphoma-associated neuropathies; its diagnosis is challenging. Cerebrospinal fluid (CSF) analysis is of great value, but nerve biopsy (NB) may be necessary to prove invasion by malignant cells. Clonality polymerase chain reaction (PCR)-based analysis is a validated method in the diagnosis of hematological malignancies, but there are very little data on its diagnostic yield on NB samples. We explored the contribution of NB with clonality analysis to the diagnosis of neurolymphomatosis in 15 patients with negative CSF analysis. Moreover, we assessed the performance of clonality testing in a case-control manner, using patients with inflammatory infiltrates on NB as controls. Neurolymphomatosis was the first manifestation of lymphoma in 60% and could be diagnosed on routine histology alone in 40%. Clonality testing showed monoclonal rearrangement in 86.7% and was unsuccessful in 8.1%. Performance of clonality testing was as follows: 92.9% positive predictive value, 90% negative predictive value, 86.7% sensitivity, 94.7% specificity. This study confirms the diagnostic challenge of neurolymphomatosis, the usefulness of NB in patients with negative CSF analysis, and highlights the high yield of PCR-based clonality testing to assess the malignant nature of PNS lymphoid infiltrates.
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http://dx.doi.org/10.1093/jnen/nly055DOI Listing
September 2018

Symptomatic muscular sarcoidosis: Lessons from a nationwide multicenter study.

Neurol Neuroimmunol Neuroinflamm 2018 May 16;5(3):e452. Epub 2018 Mar 16.

AP-HP (F.C.A., S.A, J.H., A.M., M.P., Z.A), Service de Médecine Interne 2, Institut e3m, Hôpital de la Pitié-Salpêtrière, Centre National de Référence Maladies Systémiques Rares, Lupus, Syndrome des anticorps antiphospholipides; Université Paris VI (F.C.A., J.H., O.B.), UPMC, Sorbonnes Universités; AP-HP (T.M.), Département de neurophysiologie et de neuropathologie, Hôpital de la Pitié-Salpêtrière, Paris; Service de Pneumologie (V.C.), Centre des maladies pulmonaires rares, Lyon; AP-HP (T.P.), Service de Médecine Interne, Hôpital Bichat; AP-HP (L.G., B.H., O.B., Z.A.), Service de Médecine Interne et immunologie clinique, Hôpital de la Pitié-Salpêtrière, Paris; AP-HP (M.S.), Service de Médecine Nucléaire, Hôpital Avicenne, Bobigny; Service de Médecine Interne (P.M.), CHU Bordeaux, Bordeaux; AP-HP (H.N., D.V.), Service de Pneumologie, Hôpital Avicenne, Bobigny, France.

Objectives: To describe clinicopathologic features of muscular sarcoidosis and the associated sarcoidosis phenotype through a nationwide multicenter study.

Methods: Patients were included if they had histologically proven sarcoidosis and symptomatic muscular involvement confirmed by biological, imaging, or histologic examinations.

Results: Forty-eight patients (20 males) were studied, with a median age at muscular symptoms onset of 45 years (range 18-71). Four patterns were identified: a nodular pattern (27%); smoldering phenotype (29%); acute, subacute, or progressive myopathic type (35%); and combined myopathic and neurogenic pattern (10%). In all patterns, sarcoidosis was multivisceral with a median of 3 extramuscular organs involved (mostly lungs, lymph nodes, eyes, and skin) and a prolonged course with long-term use of corticosteroids and immunosuppressive drugs. Muscular patterns differed according to clinical presentation (myalgia, nodules, or weakness), electromyographic findings, muscular MRI, and response to sarcoidosis treatment. The myopathic and neuromuscular patterns were more severe.

Conclusion: This nationwide study of muscular sarcoidosis allowed the identification of 4 patterns of granulomatous myositis, which differed by phenotypes and the clinical course.
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http://dx.doi.org/10.1212/NXI.0000000000000452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962889PMC
May 2018

Livedoid Vasculopathy: A French Observational Study Including Therapeutic Options.

Acta Derm Venereol 2018 Oct;98(9):842-847

Department of Dermatology, Hôpital Tenon, APHP, Paris, France.

Livedoid vasculopathy is a rare thrombotic cutaneous disease. This observational study aimed to assess the clinical and biological features of livedoid vasculopathy and the efficacy of treatments. Patients enrolled had typical livedoid vasculopathy both clinically and histologically. Investigation of thrombophilia was performed. Electromyography was undertaken in the presence of symptoms suggesting peripheral neuropathy. Eighteen women and 8 men were included, with a mean age of 35.5 years at onset. Twenty patients had at least one thrombophilia factor. Ten patients had a peripheral neuropathy with 2 of these patients demonstrating a specific thrombo-occlusive vasculopathy on muscle biopsy. Anticoagulation with low molecular weight heparin was the most prescribed therapy and was associated with the best outcome (effective in 14 patients). Eight patients had severe disease refractory to anticoagulation and required intravenous immunoglobulins, producing a good response in 6 patients.
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http://dx.doi.org/10.2340/00015555-2965DOI Listing
October 2018

Motor neuron disease of paraneoplastic origin: a rare but treatable condition.

J Neurol 2018 Jul 3;265(7):1590-1599. Epub 2018 May 3.

Département de Neurophysiologie clinique, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.

Paraneoplastic motor neuron disorders (MND) are rare conditions; their exact clinical and electrophysiological phenotype have not been exhaustively described yet. The purpose of this study is to depict the main characteristics of paraneoplastic MND to highlight the features that may allow its diagnosis. Based on the description of eight original cases, and on the revision of 21 patients identified from a systematic review of the literature, the main features of paraneoplastic MND can be summarized as follows: (1) subacute; (2) lower motor neuron syndrome, associated or not with upper motor neuron involvement; (3) predominant asymmetric upper limb involvement; (4) presence of other non-motor neurological manifestations, including sensory neuronopathy; (5) signs of inflammation in the cerebrospinal fluid (CSF); (6) neurological improvement or stabilization after immunotherapy and tumor treatment. The diagnosis of paraneoplastic MND may be difficult because of its rarity, the absence of pathognomonic clinical features, and the frequent absence of prior tumor history. However, it is of capital importance to correctly identify patients with paraneoplastic MND, as this represents a potentially treatable condition. In the presence of subacute lower motor neuron impairment, especially when atypical clinical features for degenerative MND or other non-motor neurological manifestations are present, we recommend testing for onconeural antibodies. In the case, the search for onconeural antibodies is negative, but it exists a strong clinical suspicion for a paraneoplastic etiology; CSF analysis and total-body 18FDG-PET/CT imaging should be performed to circumstantiate diagnosis.
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http://dx.doi.org/10.1007/s00415-018-8881-0DOI Listing
July 2018

N-hexane exposure: a cause of small fiber neuropathy.

J Peripher Nerv Syst 2018 Jun 26;23(2):143-146. Epub 2018 Mar 26.

National Referral Center for Neuromuscular Diseases, Institut Hospitalo-Universitaire (IHU) de Neurosciences, University Hospital Pitié Salpêtrière, Paris, France.

A 59-year-old woman presented with progressive paresthesias of all of her limbs for 4 years, associated with neuropathic pain, tingling in the tongue and allodynia, consistent with small fiber neuropathy (SFN). Several systemic symptoms and signs were found on clinical examination and laboratory work-up. Neurological investigations including neurophysiologic test and skin biopsy supported the diagnosis of SFN. Chronic exposure to N-hexane was then disclosed and suspected to be the cause of the disease. Following the discontinuation of chronic N-hexane exposure, the patient had a progressive improvement of all signs and symptoms, reinforcing the correlation between exposure to N-hexane, and development of SFN. Exposure to N-hexane may be considered as a novel reversible cause of SFN, which underlines the need to look for toxic etiologies in the diagnosis of SFN.
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http://dx.doi.org/10.1111/jns.12261DOI Listing
June 2018

Architectural B-cell organization in skeletal muscle identifies subtypes of dermatomyositis.

Neurol Neuroimmunol Neuroinflamm 2018 May 6;5(3):e451. Epub 2018 Mar 6.

Author affiliations are provided at the end of the article.

Objective: To study the B-cell content, organization, and existence of distinct B-cell subpopulations in relation to the expression of type 1 interferon signature related genes in dermatomyositis (DM).

Methods: Evaluation of skeletal muscle biopsies from patients with adult DM (aDM) and juvenile DM (jDM) by histology, immunohistochemistry, electron microscopy, and quantitative reverse-transcription PCR.

Results: We defined 3 aDM subgroups-classic (containing occasional B cells without clusters), B-cell-rich, and follicle-like aDM-further elucidating IM B-lymphocyte maturation and immunity. The quantity of B cells and formation of ectopic lymphoid structures in a subset of patients with aDM were associated with a specific profile of cytokines and chemokines involved in lymphoid neogenesis. Levels of type 1 interferon signature related gene expression paralleled B-cell content and architectural organization and link B-cell immunity to the interferon type I signature.

Conclusion: These data corroborate the important role of B cells in DM, highlighting the direct link between humoral mechanisms as key players in B-cell immunity and the role of type I interferon-related immunity.
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http://dx.doi.org/10.1212/NXI.0000000000000451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840889PMC
May 2018

Quantitative neuroimaging biomarkers in a series of 20 adult patients with POLG mutations.

Mitochondrion 2019 03 21;45:22-28. Epub 2018 Feb 21.

Sorbonne Université, UPMC-Paris 6, UMR S 1127 and Inserm U 1127, and CNRS UMR 7225, and Institut du Cerveau et de la Moelle épinière, F-75013, Paris, France; AP-HP, Pitié-Salpêtrière University Hospital, Department of Genetics, Paris, France; University Pierre and Marie Curie, Neurometabolic Research Group, Paris, France. Electronic address:

Mutations in the gene encoding polymerase gamma (POLG) are a common cause of mitochondrial diseases in adults. We retrospectively analyzed volumetric and diffusion tensor imaging data from 20 adult POLG-mutated patients compared to healthy controls. We used an original clinical binary load score and electroneuromyography to evaluate disease severity. Patients showed atrophy in the basal ganglia, amygdala, and brainstem (p < 0.05) compared to controls, as well as decreased fractional anisotropy (FA) in the cingulate gyrus, the internal capsule and the corona radiata (p < 0.05). Clinical scores correlated with decreased FA and increased radial diffusivity in several brain regions (p < 0.05).
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http://dx.doi.org/10.1016/j.mito.2018.02.001DOI Listing
March 2019