Amandine Sevy

Motor unit number index (MUNIX): Is it relevant in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)?

OBJECTIVE To determine the test-retest reliability of motor unit number index (MUNIX) technique and to explore if the MUNIX sumscore could be related with disability in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS The MUNIX technique was unilaterally assessed in the abductor digiti mini (ADM), the abductor pollicis brevi (APB) and the tibialis anterior (TA) muscles two different times by two blinded examiners. The MUNIX sumscore was calculated by adding the results of the ADM, APB and TA muscles. RESULTS 14 CIDP patients were enrolled. The intraclass correlation coefficient (ICC) was great for inter and intra variability for ADM muscles (0.8 and 0.81), TA muscles (0.86 and 0.89) and MUNIX sumscore (0.76 and 0.83). The MUNIX sumscores from the first and second evaluations were strongly correlated (r=0.83, p<0.001). The MUNIX sumscore was significantly correlated with MRC testing (r=0.71, p<0.01), overall neuropathy limitation scale (ONLS) (r=-0.70, p<0.001), rasch-built overall disability scale (R-ODS) (r=0.71, p<0.001). CONCLUSIONS The MUNIX technique has a good reproducibility and the MUNIX sumscore is related to the disability. SIGNIFICANCE The MUNIX technique estimates the axonal loss and the number of functional motor units. The MUNIX sumscore may be a good instrument to evaluate the CIDP patients during their follow-up.

Improving molecular diagnosis of distal myopathies by targeted next-generation sequencing

Distal myopathies are a heterogeneous group of muscle diseases sharing the clinical pattern of predominant weakness in the feet and/or hands. The classical approach for molecular diagnosis is based on targeted gene-by-gene analysis guided by currently existing combinatorial algorithms.1 Many patients remain undiagnosed. Within the last 5 years, next-generation sequencing (NGS) has emerged as a successful and rapid approach to simultaneously analyse multiple genes in neuromuscular disorders.2 Our objective was to evaluate the efficiency of a targeted NGS approach using a panel of neuromuscular genes on patients with distal myopathies. We first tested its validity in a control group of six index cases (IC) with known molecular diagnosis. Then, we prospectively evaluated this approach by testing a group of 17 IC without molecular diagnosis. ### Patients We prospectively included 54 patients (37 IC and 17 relatives) with a diagnosis of distal myopathy, followed at the Neuromuscular Diseases and ALS Reference Centre of La Timone Hospital, Marseille, France, between 1989 and 2014. Among these 37 IC previously explored by Sanger sequencing, 20 IC had an identified molecular diagnosis: six IC constituted the control group. The remaining 17 undiagnosed IC constituted the test group. A targeted-NGS approach was used to search mutations in 298 neuromuscular genes in both groups. Samples analysed in this study have been prepared and stored by the Center of Biological Resources, Department of Medical Genetics, La Timone Hospital, Marseille, and used following the ethical recommendations of our institution and according to the Declaration of Helsinki. All included patients gave their written consent prior to …

Guillain-Barré syndrome following severe head trauma and spine surgery

Guillain-Barré syndrome (GBS) is an acute-onset inflammatory polyradiculoneuropathy usually triggered by an infectious disease. In some cases, GBS can occur without any preceding infectious episode, like after vaccination, epidural anaesthesia or surgery. A 73 years old woman had head and spine trauma. Body-TDM showed bilateral temporal and right frontal haematomas and fracture of the first lumbar vertebrae. Sextant and kyphoplasty were performed. She presented 14 days after surgery tetraparesis, swallowing difficulties and bilateral facial palsy. Electromyography was consistent with demyelinating neuropathy. Cerebrospinal fluid examination found albumino-cytological dissociation. Viral and bacterial serology and antiganglioside antibodies were negative. She was treated with intravenous immunoglobulins. Four months after discharge she had fully recovered except left peripheral facial palsy. GBS can rarely be triggered by head trauma or spine surgery. Physician must keep in mind this diagnosis whenever their patients present acute-onset neurological worsening in such context.

Stroke in a young patient treated by alteplase heralding an acquired thrombotic thrombocytopenic purpura

Background and purpose: Thrombotic thrombocytopenic purpura (TTP) is a life‐threatening multisystem disorder characterized by thrombocytopenia and fluctuating neurological symptoms due to microinfarcts. In rare cases, large cerebral arteries can be occluded. Summary of the case: We report on a 30‐year‐old woman with a first‐ever acute stroke related to a right proximal MCA M1 occlusion. Platelet count was normal at admission and progressively decreased 6 days after intravenous thrombolysis with the occurrence of a hemolytic anemia with schistocytes. Most biological anomalies reversed after plasma exchange. No hemorrhagic complication occurred. Diagnosis of initial TTP was confirmed by low ADAMTS13 activity and positivity of anti‐ADAMTS13 antibody. Conclusion: This observation highlights the fact that even if platelet count and hemoglobin rate are normal in the beginning, an acute ischemic stroke in a young patient can be related to TTP. Faced with subsequent thrombopenia, practitioners should be aware of acquired TTP, and, thus, schistocytes, haptoglobin, and LDH assays should be performed. Early diagnosis is paramount to start the life‐saving plasma exchanges. J. Clin. Apheresis, 2011.

New strategy for improving the diagnostic sensitivity of repetitive nerve stimulation in myasthenia gravis

Introduction: The diagnostic sensitivity of repetitive nerve stimulation (RNS) in patients with myasthenia gravis (MG) varies as a function of the number of muscles or the choice of muscles studied. Methods: By exploring 12 muscles bilaterally, we evaluated the global sensitivity of RNS at rest, the sensitivity in different clinical forms, and the sensitivity of different combinations of muscles studied. Results: The global sensitivity of RNS was 82%, and specificity was 100%. The sensitivity in the MG subgroups was as follows: ocular (O) = 67%; oculobulbar (OB) = 86%; and generalized (G) = 89%. The most sensitive muscles were the anconeus in group O, orbicularis oculi (OO) or nasalis in group OB, and the trapezius in group G. Maximum sensitivity was obtained by exploring OO, trapezius, and anconeus bilaterally. Conclusions: We recommend bilateral exploration of at least 3 muscles, a facial muscle, trapezius, and anconeus. Muscle Nerve 55: 532–538, 2017

Detection of proximal conduction blocks using a triple stimulation technique improves the early diagnosis of Guillain–Barré syndrome

OBJECTIVE Current diagnostic electrophysiological criteria can miss the early stages of Guillain-Barré syndrome (GBS). We evaluated the diagnostic efficiency of the triple stimulation technique (TST) in highlighting proximal conduction blocks (CBs) in patients who do not meet the electrophysiological criteria for GBS. METHODS All patients with a diagnosis of clinical GBS referred to our center between September 2014 and January 2016 were included in the study. For patients who did not fulfill the electrophysiological criteria of GBS, we performed the TST examination. RESULTS Among the 44 included patients, 86% fulfilled the electrophysiological criteria of GBS during the initial nerve conduction study (NCS). The six remaining patients had proximal CBs revealed by TST examination. Therefore, a combination of a conventional NCS and the TST allowed 100% of the patients to be electrophysiologically diagnosed. CONCLUSIONS TST is useful for the diagnosis of GBS in association with NCS, particularly in the early stages of the disease. SIGNIFICANCE TST is a useful tool for GBS diagnosis at the early stages of the disease.

Motor unit number index (MUNIX) in patients with anti-MAG neuropathy

OBJECTIVE To investigate the relationship between Motor Unit Number Index (MUNIX) and functional scales in patients with anti-Myelin Associated Glycoprotein (MAG) neuropathy and to know if MUNIX is modify after rituximab (RTX) therapy. METHODS 17 patients were enrolled, of whom 6 were prospectively evaluated during one year after RTX treatment. MUNIX technique was assessed in abductor digiti mini (ADM), abductor pollicis brevi (APB) and tibialis anterior (TA) muscles. MUNIX sum score was calculated by adding the results of ADM, APB and TA muscles. RESULTS MUNIX sum score was correlated with overall neuropathy limitation scale (ONLS) (r=-0.55, p=0.02), grip strength in dominant hand (r=0.63, p=0.01) MRC testing (r=0.71, p<0.001) and CMAP sum score (r=0.71, p=0.001). Twelve months after RTX, four patients improved their disability measured on the ONLS score, five patients had improved MUNIX sum score with a median increase of 37% compared to initial evaluation. CONCLUSIONS MUNIX is related to motor impairment and disability in anti-MAG neuropathy and MUNIX is modified after immunosuppressive treatment. SIGNIFICANCE Considering its advantages, MUNIX may be a suitable test to evaluate anti-MAG neuropathy in clinical trials.

Evolution of hepatitis E virus-associated meningo-polyradiculoneuropathy on ribavirin

Autochthonous hepatitis E virus (HEV) infection has emerged during the past decade in Europe and is linked to a porcine reservoir [1,2]. In addition, chronic HEV infections were reported in severely immunocompromised patients, and ribavirin was shown to be efficient against HEV replication in such a setting, being more rarely used in severe acute hepatitis E [1,3]. Unexpectedly, HEV infections are increasingly associated with neurological disorders, mostly Guillain–Barré syndrome and neuralgic amyotrophy [1,3,4]. Ribavirin use was only reported in nine cases of HEV-associated neurological disorders [1]. Here we report the evolution of a patient presenting HEV-associated meningo-polyradiculoneuropathy and treated with ribavirin. A 56-year-old male presented with a 6-day history of rightsided shoulder pain and proximal weakness of the four limbs of sudden onset. One day later, he walked with difficulty. The patient had taken antibiotics for a dental abscess and had presented with rhinopharyngitis 4 weeks and 3 weeks previously, respectively, but reported no prior trauma, strenuous exercise, autoimmune disease, immunomodulatory treatment, excessive alcohol intake, drug abuse or particular family history. Neurological examination showedweakness of the deltoid and infraspinatus muscles (Fig. 1a). The distal upper muscles and proximal lower limb muscles were also affected bilaterally. Bilateral hypopallesthesia over the right axillary nerve territory and fingertips was observed. Electroneuromyography supported a diagnosis of polyradiculopathy. Cerebrospinal fluid (CSF) analysis showed a raised protein level (0.87 g/L) and leukocyte count (100 cells/mm3; 90% mononuclear cells). Blood tests revealed liver cytolysis [alanine aminotransferase level (ALT) of 640 IU/L] and elevated γ-glutamyl transferase (106 IU/L) (Fig. 1a). Bilirubinaemia was 10 μmol/L. Molecular and/or serological markers of infection with hepatitis A–C viruses, Epstein–Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus (HSV), varicella zoster virus (VZV), human immunodeficiency virus (HIV), Borrelia burgdorferi, Treponema pallidum, Brucella, Coxiella, Bartonella and Rickettsia were negative or indicated past infections. HEV infection was diagnosed based on anti-HEV IgM/IgG positivity (test/cut-off optical density ratios of 11 and 14, respectively; Wantai Assays, China) and detection of HEV genotype 3f (GenBank no. KX012625) in serum (2.7 log10 copies/mL) (Fig. 1) [2]. The CSF tested negative by PCR for HEV, West Nile virus, Toscana virus, enterovirus, CMV, EBV, HSV and VZV, and bacterial culture was negative. No intrathecal immunoglobulin synthesis and no anti-ganglioside antibodies were detected. The patient reported recent consumption of pig liver sausage, a wellestablished source of HEV [1–3]. The patient received a 5-day course of intravenous immunoglobulins (IVIG; 2 g/kg/day) followed by ribavirin (800mg/day) for 3months. HEV RNAwas undetectable and the ALT had returned to normal values when tested 7 weeks later. Pain disappeared within 25 days and the patient’s mobility steadily improved. Three months post-onset, neurological examination was normal apart from distal left upper muscles that remained slightly affected. Five HEV infections associated with signs indicative of meningopolyradiculoneuropathy, including increased protein level and pleocytosis in the CSF, have been reported previously [1]. All were European cases of autochthonous infection with HEV genotype 3, which predominates in autochthonous cases on this continent [1–3]. HEV RNA was detected in the CSF from three patients [1]. Ribavirin treatment has been reported to date in nine HEV-infected patients with neurological disorders; none presented meningopolyradiculoneuropathy [1]. Two of these nine patients were HIVinfected, two were kidney or liver transplant recipients, and three had chronic hepatitis E. Five (56%) of the nine patients who received ribavirin compared with 33 (49%) of 68 patients who did not experienced complete recovery of neurological disorders. However, ribavirin was co-administered with IVIG in four cases and with pegylated-interferon in two cases, whilst the immunosuppressant dose was reduced in another patient (a renal transplant recipient). Overall, the scarcity of cases, the diversity of clinical presentations and settings, the differences in duration of ribavirin treatment and follow-up, and the absence of a control group preclude drawing any conclusions on the effect of ribavirin both on the intensity and persistence of neurological symptoms. Besides, the mechanisms by which HEV might cause neurological disorders are not elucidated. This virus may trigger an immune response that damages the peripheral nervous system or it may infect the nervous system [1,3,4]; it was recently shown to replicate in oligodendrocytes [5]. In the present case, viral clearance and normalisation of liver parameters were observed when assessed 6 weeks postribavirin introduction, and clinical recovery was almost complete 3 months post-onset. Noteworthy, at the time of HEV diagnosis, the HEV RNA load was low in serum and was undetected in the CSF. Thus, it is unclear whether ribavirin was useful in this patient. The frequency of HEV infection in patients with neurological disorders may be underestimated as it is probably still not sought systematically. Recent studies revealed retrospectively that it accompanied ca. 5% and 10% of cases of Guillain–Barré syndrome and neuralgic amyotrophy, respectively [4]. Here, HEV infection was clinically asymptomatic and was only diagnosed secondarily to investigation of neurological disorder. In summary, current knowledge does not allow resolving the effect of ribavirin in meningo-polyradiculoneuropathy or other neurological disorders, and additional reports are needed on HEV pathogenesis and ribavirin treatment. HEV should be sought in any case of meningo-polyradiculoneuropathy, particularly when associated with liver perturbations. Funding: None. Competing interests: None declared. Ethical approval: Not required.

Cas clinique des Printemps de la Médecine interneJournée Bernard DevulderTout est dans la chronologie…Bilateral xerophthalmia in a 60-year-old man

Un homme, âgé de 60 ans, ancien plombier chauffagiste, était dressé pour le bilan étiologique d’une xérophtalmie bilatérale nvalidante et douloureuse. Il avait très peu fumé, avait reçu un oup d’arc de soudure dans l’œil gauche sans complication. Il se laignait toujours de son dos depuis l’opération d’une hernie disale L5-S1 qui s’était compliquée d’une fibrose cinq ans après, ayant écessité alors le recours à des perfusions d’Anafranil®. L’histoire e la maladie avait commencé trois ans auparavant, 15 jours près une chirurgie pour une polypose naso-sinusienne, par des ouleurs et des démangeaisons de l’œil droit qui conduisaient apidement à une kératite. Le même phénomène se produisait econdairement à l’œil adelphe. Le patient se plaignait égaleent de paresthésies douloureuses de la face, le matin au réveil. ’examen retrouvait alors une anesthésie cornéenne bilatérale solée. L’électromyogramme (EMG) confirmait l’atteinte sensitive rigéminale périphérique bilatérale. L’IRM encéphalique montrait n épaississement temporal méningé bilatéral qui n’était plus etrouvé sur un examen de contrôle effectué six mois plus tard. l n’y avait pas de syndrome inflammatoire. La biopsie d’une adé-

Tout est dans la chronologie

Un homme, âgé de 60 ans, ancien plombier chauffagiste, était dressé pour le bilan étiologique d’une xérophtalmie bilatérale nvalidante et douloureuse. Il avait très peu fumé, avait reçu un oup d’arc de soudure dans l’œil gauche sans complication. Il se laignait toujours de son dos depuis l’opération d’une hernie disale L5-S1 qui s’était compliquée d’une fibrose cinq ans après, ayant écessité alors le recours à des perfusions d’Anafranil®. L’histoire e la maladie avait commencé trois ans auparavant, 15 jours près une chirurgie pour une polypose naso-sinusienne, par des ouleurs et des démangeaisons de l’œil droit qui conduisaient apidement à une kératite. Le même phénomène se produisait econdairement à l’œil adelphe. Le patient se plaignait égaleent de paresthésies douloureuses de la face, le matin au réveil. ’examen retrouvait alors une anesthésie cornéenne bilatérale solée. L’électromyogramme (EMG) confirmait l’atteinte sensitive rigéminale périphérique bilatérale. L’IRM encéphalique montrait n épaississement temporal méningé bilatéral qui n’était plus etrouvé sur un examen de contrôle effectué six mois plus tard. l n’y avait pas de syndrome inflammatoire. La biopsie d’une adé-