Jean-Philippe Camdessanché

Comparative efficacy of fingolimod vs natalizumab: A French multicenter observational study

Objective: To compare natalizumab and fingolimod on both clinical and MRI outcomes in patients with relapsing-remitting multiple sclerosis (RRMS) from 27 multiple sclerosis centers participating in the French follow-up cohort Observatoire of Multiple Sclerosis. Methods: Patients with RRMS included in the study were aged from 18 to 65 years with an Expanded Disability Status Scale score of 0–5.5 and an available brain MRI performed within the year before treatment initiation. The data were collected for 326 patients treated with natalizumab and 303 with fingolimod. The statistical analysis was performed using 2 different methods: logistic regression and propensity scores (inverse probability treatment weighting). Results: The confounder-adjusted proportion of patients with at least one relapse within the first and second year of treatment was lower in natalizumab-treated patients compared to the fingolimod group (21.1% vs 30.4% at first year, p = 0.0092; and 30.9% vs 41.7% at second year, p = 0.0059) and supported the trend observed in nonadjusted analysis (21.2% vs 27.1% at 1 year, p = 0.0775). Such statistically significant associations were also observed for gadolinium (Gd)-enhancing lesions and new T2 lesions at both 1 year (Gd-enhancing lesions: 9.3% vs 29.8%, p < 0.0001; new T2 lesions: 10.6% vs 29.6%, p < 0.0001) and 2 years (Gd-enhancing lesions: 9.1% vs 22.1%, p = 0.0025; new T2 lesions: 16.9% vs 34.1%, p = 0.0010) post treatment initiation. Conclusion: Taken together, these results suggest the superiority of natalizumab over fingolimod to prevent relapses and new T2 and Gd-enhancing lesions at 1 and 2 years. Classification of evidence: This study provides Class IV evidence that for patients with RRMS, natalizumab decreases the proportion of patients with at least one relapse within the first year of treatment compared to fingolimod.

Devic disease and thymoma with anti-central nervous system and antithymus antibodies.

A patient with myasthenia gravis and thymoma developed neuromyelitis optica (NMO) and necrotizing myositis 4 months after treatment of the tumor. Antibodies reacting with the CNS and thymic epithelial cells were detected in the serum during the acute phase of NMO, suggesting that the NMO was linked to the thymoma.

A clinical pattern-based etiological diagnostic strategy for sensory neuronopathies: a French collaborative study.

Sensory neuronopathies (SNNs) encompass paraneoplastic, infectious, dysimmune, toxic, inherited, and idiopathic disorders. Recently described diagnostic criteria allow SNN to be differentiated from other forms of sensory neuropathy, but there is no validated strategy based on routine clinical investigations for the etiological diagnosis of SNN. In a multicenter study, the clinical, biological, and electrophysiological characteristics of 148 patients with SNN were analyzed. Multiple correspondence analysis and logistic regression were used to identify patterns differentiating between forms of SNNs with different etiologies. Models were constructed using a study population of 88 patients and checked using a test population of 60 cases. Four patterns were identified. Pattern A, with an acute or subacute onset in the four limbs or arms, early pain, and frequently affecting males over 60 years of age, identified mainly paraneoplastic, toxic, and infectious SNN. Pattern B identified patients with progressive SNN and was divided into patterns C and D, the former corresponding to patients with inherited or slowly progressive idiopathic SNN with severe ataxia and electrophysiological abnormalities and the latter to patients with idiopathic, dysimmune, and sometimes paraneoplastic SNN with a more rapid course than in pattern C. The diagnostic strategy based on these patterns correctly identified 84/88 and 58/60 patients in the study and test populations, respectively.

Identifying a therapeutic window in acute and subacute inflammatory sensory neuronopathies

BACKGROUND Patients with inflammatory sensory neuronopathy (SNN) may benefit from immunomodulatory or immunosuppressant treatments if administered timely. Knowing the temporal profile of neuronal loss in dorsal root ganglia will help to ascertain whether a final diagnosis may be reached before the occurrence of irreversible neuronal injuries. Thus, we addressed the evolution of neuronal loss in SNN by using sensory nerve action potentials (SNAPs) as a surrogate marker of neuron degeneration. METHODS Eighty-six patients with acute/subacute inflammatory SNN (paraneoplastic, associated with dysimmune diseases, or idiopathic) were retrospectively studied. The monthly SNAP reduction was determined and normalized with the lower limit of normal. Disability progression was expressed by the modified Rankin score and correlated with SNAP reduction. RESULTS The monthly SNAP reduction was similar in the four limbs although the median nerve was less severely affected. The monthly SNAP reduction was very severe within the first two months of evolution, began to slow down after seven months, and stabilized after ten months. It was tightly correlated with disability progression. Kaplan-Meier analysis showed that the median time until matching the diagnostic criteria of SNN was 8.5 months. Within this period, 42% of nerves remained excitable. CONCLUSIONS Developing treatment aiming at the stabilization of SNN is possible within the first 8 months of evolution. An improvement of the disease is possible if patients are treated within two months, which needs an early referral to an expert center and ENMG testing of the radial and ulnar nerves, which are most sensitive to changes.

N-hexane exposure: a cause of small fiber neuropathy: Guimarães-Costa et al

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.

Étude comparative de l’apport de la biopsie cutanée et des potentiels évoqués laser pour l’étude des petites fibres dans les neuropathies sensitives cliniquement pures

Introduction La biopsie cutanee (BC) et les potentiels evoques laser (PEL) sont les deux examens de reference pour le diagnostic de neuropathie des petites fibres (NPF). Pourtant, ils n’ont jamais ete compares. Objectif Comparer les resultats de la BC et des PEL chez des patients presentant une neuropathie sensitive cliniquement pure avec une atteinte des petites fibres pure ou non. Materiel et methodes Nous avons realise une etude prospective monocentrique chez 50 patients. Douze avaient une NPF pure longueur-dependante (LD), 15 une neuronopathie (NNS) petites fibres pure, 12 une neuropathie sensitive distale mixte et 11 une NNS mixte. Les patients ont tous beneficie d’une BC proximale et distale sur un membre inferieur avec determination de la densite en fibres nerveuses intra-epidermiques, et d’un enregistrement du potentiel N2P2 en PEL (YAP ou CO2) sur 8 territoires. Resultats La BC et les PEL ont detecte une atteinte des petites fibres avec une sensibilite de 82 et 84 % respectivement. Cette difference n’est pas statistiquement significative. La concordance entre les deux techniques etait de 74%. Elle etait de 67 % et 82,6 % pour les NPF pures et les neuropathies mixtes respectivement. Les deux techniques ne sont pas performantes pour determiner le caractere LD ou non de la neuropathie avec une sensibilite respective de 46,7 % et 51 %. Discussion Notre etude confirme la bonne sensibilite de la BC et des PEL pour faire le diagnostic de NPF sans superiorite globale d’une technique. Elle montre une concordance correcte des deux explorations et leur faible performance pour determiner le caractere LD ou non de la neuropathie principalement en lien avec la frequence des atteintes proximales infracliniques. Conclusion La BC et les PEL sont deux techniques sensibles et concordantes pour l’etude des petites fibres nerveuses dans le cadre des neuropathies sensitives pures.