Current clinical management of CIDP with immunoglobulins in France: An expert opinion.

Treatment strategies in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) must be adapted on a case-to-case basis. Validated and reproducible tools for monitoring treatment response are required at diagnosis, when initiating treatment and throughout follow-up. A task force of French neurologists, experts in neuromuscular disease reference centers, was assembled to provide expert advice on the management of typical CIDP with intravenous immunoglobulins (Ig), and to harmonize treatment practices in public and private hospitals. The task force also referred to the practical experience of treating CIDP with Ig at the diagnostic, induction and follow-up stages, including the assessment and management of Ig dependence, and following the recommendations of the French health agency.

French recommendations for the management of adult & pediatric chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare autoimmune disorder of the peripheral nervous system, primarily affecting the myelin sheath. The pathophysiology of CIDP is complex, involving both humoral and cellular immunity. The diagnosis of CIDP should be suspected in patients with symmetrical proximal and distal motor weakness and distal sensory symptoms of progressive onset, associated with decreased/abolished tendon reflexes. Treatments include intraveinous immunoglobulins, steroids and plasma exchange, with usually an induction phase followed by a maintenance therapy with progressive weaning. Treatment should be rapidly initiated to prevent axonal degeneration, which may compromise recovery. CIDP outcome is variable, ranging from mild distal paresthesiae to complete loss of ambulation. There have been several breakthroughs in the diagnosis and management of CIDP the past ten years, e.g. discovery of antibodies against the node of Ranvier, contribution of nerve ultrasound and magnetic resonance imaging to diagnosis, and demonstration of subcutaneous immunoglobulins efficiency. This led us to elaborate French recommendations for the management of adult & pediatric CIDP patients. These recommendations include diagnosis assessment, treatment, and follow-up.

Changes in neuromuscular function in elders: Novel techniques for assessment of motor unit loss and motor unit remodeling with aging.

Functional muscle fiber denervation is a major contributor to the decline in physical function observed with aging and is now a recognized cause of sarcopenia, a muscle disorder characterized by progressive and generalized degenerative loss of skeletal muscle mass, quality, and strength. There is an interrelationship between muscle strength, motor unit (MU) number, and aging, which suggests that a portion of muscle weakness in seniors may be attributable to the loss of functional MUs. During normal aging, there is a time-related progression of MU loss, an adaptive sprouting followed by a maladaptive sprouting, and continuing recession of terminal Schwann cells leading to a reduced capacity for compensatory reinnervation in elders. In amyotrophic lateral sclerosis, increasing age at onset predicts worse survival ALS and it is possible that age-related depletion of the motor neuron pool may worsen motor neuron disease. MUNE methods are used to estimate the number of functional MU, data from MUNIX arguing for motor neuron loss with aging will be reviewed. Recently, a new MRI technique MU-MRI could be used to assess the MU recruitment or explore the activity of a single MU. This review presents published studies on the changes of neuromuscular function with aging, then focusing on these two novel techniques for assessment of MU loss and MU remodeling.

Immunoglobulin shortage: Practice modifications and clinical outcomes in a reference centre.

BACKGROUND: Growing numbers of indications for intravenous immunoglobulins (IVIg) in recent years has resulted in an increase in the consumption of these products. A lack of raw material has led to IVIg shortage. The objective of this work was to evaluate the impact of this situation on patient care in one French referral centre considering practice modifications and clinical impact. METHODS: All patients treated with IVIg for chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy and myasthenia gravis from October 2017 to October 2018 were included. RESULTS: Out of 142 patients, 111 (78%) had a modification of their IVIg treatment. We noted that 75 (68%) patients had a delay in IVIg treatment, 41 (37%) patients had a decrease in IVIg doses and 31 (28%) experienced IVIg treatment interruption. Thirty percent of patients for whom IVIg treatment was discontinued were switched to other treatments mainly plasma exchange (16%) or corticosteroids (13%). Switches to plasma exchange or corticosteroids were carried out in order to save immunoglobulins for patients who had no other alternatives. Fifty-eight (52%) patients presented a deterioration of their clinical score after IVIg treatment changes including 31 (28%) patients who had a moderate or a clinically significant deterioration. Concerning practice modifications, we noted a substantial though not significant decrease in median IVIg dose for myasthenia gravis and a significant increase in the delay between IVIg courses for chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy (P=0.011 and P=0.018 respectively). CONCLUSION: Our study showed a rather important number of changes in IVIg treatment related to IVIg shortage during the period considered. These changes had a negative impact on the clinical status of some patients.

Prevalence of spasticity and spasticity-related pain among patients with Amyotrophic Lateral Sclerosis.

Although they are common symptoms of ALS, there is little information on the prevalence of spasticity and spasticity-related pain. Consecutive patients were prospectively recruited from an ALS referral center. Clinical assessment, functional scores, features of spasticity-related pains has been recorded. In a cohort of 150 patients, 36% presented with spasticity. Spastic patients were younger, with a longer duration of disease. Spasticity accelerates the functional decline of patients. Spasticity-related pain was reported in 42.5% of spastic patients with mild pain. However, 16.7% of spastic patients presented significant pain with numeric rating scale≥4. More clinical trials are needed to treat spasticity more effectively and to relieve ALS patients.

Should we prevent thrombosis related to intravenous immunoglobulin infusions with systematic anticoagulant prophylaxis?

Intravenous immunoglobulins (IVIg) are commonly used for treatment of dysimmune diseases, but they are known to promote thrombotic events. The medical records of patients who received IVIg infusions to treat neuromuscular disorders were retrospectively studied during two periods: the on-demand period (May 2013-January 2015), when patients received anticoagulant prophylaxis based on personal thrombotic risk factors, and the systematic period (May 2015-January 2017), when patients received systematic anticoagulant prophylaxis. Of the 334 total patients included, 19/153 received anticoagulant prophylaxis in the on-demand period, and 181 were treated in the systematic period. In the on-demand period, thrombosis occurred in three patients (1.96%) as one central retinal artery occlusion, one pulmonary embolism, and one brachiocephalic vein thrombosis. In the systematic period, thrombosis occurred in two patients (1.1%), both as pulmonary embolisms. There was no statistical difference in thrombosis incidence between the periods (P=0.66). The only factor associated with thrombosis was splenectomy (20% versus 0.3% in patients without thrombosis, P=0.03). There were no adverse events due to thromboprophylaxis by low-molecular-weight heparin in either period. Systematic thromboprophylaxis did not significantly reduce the incidence of thrombosis versus thromboprophylaxis based on personal thrombotic risk.

A New Point Mutation in the PMP22 Gene in a Family Suffering From Atypical HNPP.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant inherited disorder commonly presenting with acute-onset, non-painful focal sensory and motor mono neuropathy. In 80% of cases, the genetic defect is a 1.5 Mb deletion on chromosome 17p11.2, including PMP22. Only few cases of partial deletion and point mutations in PMP22 are involved in HNPP. We investigated a 62-years-old man with lower limb plexopathy first considered as Garland's syndrome. A month later, his 29 years old son also consulted for paresthesia on the peroneal nerve.Targeted sequencing of the PMP22 gene identified a c.370delT (p.Trp124Glyfs*31) in both affected patients.We report a new PMP22 point mutation associated with an atypical clinical phenotype of HNPP, a painful plexopathy of the lower limb worsenen by diabetes and a mere paresthesia, but a typical ENMG. This study illustrates the large spectrum of the disease, and emphasizes the importance of a complete ENMG and family history.

Quantitative assessment of sciatic nerve changes in Charcot-Marie-Tooth type 1A patients using magnetic resonance neurography.

BACKGROUND AND PURPOSE: Nerve tissue alterations have rarely been quantified in Charcot-Marie-Tooth type 1A (CMT1A) patients. The aim of the present study was to quantitatively assess the magnetic resonance imaging (MRI) anomalies of the sciatic and tibial nerves in CMT1A disease using quantitative neurography MRI. It was also intended to seek for correlations with clinical variables. METHODS: Quantitative neurography MRI was used in order to assess differences in nerve volume, proton density and magnetization transfer ratio in the lower limbs of CMT1A patients and healthy controls. Disease severity was evaluated using the Charcot-Marie-Tooth Neuropathy Score version 2, Charcot-Marie-Tooth examination scores and Overall Neuropathy Limitations Scale scores. Electrophysiological measurements were performed in order to assess the compound motor action potential and the Motor Unit Number Index. Clinical impairment was evaluated using muscle strength measurements and Charcot-Marie-Tooth examination scores. RESULTS: A total of 32 CMT1A patients were enrolled and compared to 13 healthy subjects. The 3D nerve volume, magnetization transfer ratio and proton density were significantly different in CMT1A patients for the whole sciatic and tibial nerve volume. The sciatic nerve volume was significantly correlated with the whole set of clinical scores whereas no correlation was found between the tibial nerve volume and the clinical scores. CONCLUSION: Nerve injury could be quantified in vivo using quantitative neurography MRI and the corresponding biomarkers were correlated with clinical disability in CMT1A patients. The sensitivity of the selected metrics will have to be assessed through repeated measurements over time during longitudinal studies to evaluate structural nerve changes under treatment.

Quantitative sudomotor test helps differentiate transthyretin familial amyloid polyneuropathy from chronic inflammatory demyelinating polyneuropathy.

OBJECTIVE: Transthyretin familial amyloid polyneuropathy (TTR-FAP) is an aggressive hereditary neuropathy characterized by sensory and autonomic dysfunction. There are numerous reports of TTR-FAP misdiagnosed and treated as chronic inflammatory demyelinating polyneuropathy (CIDP), leading to delayed diagnosis, risk of iatrogenic adverse events and increased socio-economic costs. Quantitative sudomotor function measured by electrochemical skin conductance (ESC) appears to be a sensitive test in TTR-FAP. We aimed to evaluate the performance of ESC in differentiating TTR-FAP from CIDP. METHODS: Thirty-eight patients with genetically confirmed hereditary TTR amyloidosis and 26 with definite CIDP according to the EFNS/PNS guidelines and negative TTR-FAP genetic testing were involved in this study. We compared the ESC for feet and hands measured by Sudoscan for each patient. RESULTS: ESC (µS) was significantly lower in TTR-FAP for both hands (72 vs 45, p < 0.0001) and feet (77 vs 35, p < 0.0001). Feet ESC < 64 µS had a 89% sensitivity and a 96% specificity to differentiate between CIDP and TTR-FAP. CONCLUSION: Sudoscan is a fast, non-invasive and easy to perform test, able to distinguish CIDP and TTR-FAP patients with good sensitivity and specificity. SIGNIFICANCE: Sudoscan can be helpful in distinguishing between CIDP and TTR-FAP.

Native versus deglycosylated IgM in anti-MAG neuropathy: Correlation with clinical status - Study of 10 cases.

BACKGROUND/PURPOSE: In anti-myelin associated glycoprotein (anti-MAG) neuropathies, there is evidence that anti-MAG antibodies are pathogenic but numerous studies report the absence or a weak correlation between the titers of these antibodies and disease course. In this study we assessed the relationships between MAG and glycosylated moieties located on Fc fragment of IgM anti-MAG. MATERIAL AND METHODS: IgM were extracted from the serum of 8 patients with anti-MAG neuropathy and in 2 patients with anti-MAG antibodies without anti-MAG neuropathy. Anti-MAG activity was performed with pre- and post-deglycosylated IgM extracts using indirect immunofluorescence (IIF) and ELISA. Sera from 49 patients with IgM monoclonal gammopathy without neurological disease were tested as control group (CG). Results were compared to clinical scores. For 4 patients the affinity constant of IgM with MAG was analyzed pre- and post-deglycosylated, using surface plasmon resonance technology (SPR). RESULTS: The relationships between MAG and glycosylated moieties of IgM anti-MAG were confirmed by kinetic and immunological assays. Deglycosylation resulted in a decrease in anti-MAG titers. Post-deglycosylation anti-MAG titers trended with changes in IgM titers and allowed quantifying anti-MAG antibodies without a saturation of the testing method. After deglycosylation, the titers better represented pathogenic activity and help to follow a given patient's clinical status prospectively. Six patients from CG (12.2%) had anti-MAG antibody titers over positive threshold: 1000 Bühlmann-Titer-Units (BTU) supporting the hypothesis of neutral intermolecular interactions between IgM and MAG. Deglycosylation allowed distinguishing infra clinical forms from neutral relationships forms, when the titers are weak but this assay remains essentially a diagnostic tool.

Guillain-Barré syndrome subtypes: A clinical electrophysiological study of 100 patients.

INTRODUCTION: A retrospective analysis was performed to document the clinical and electrophysiological features of Guillain-Barré syndrome (GBS) subtypes using different diagnostic criteria. METHODS: One hundred GBS patients were included. Clinical and laboratory features were analyzed, and patients were classified according to four sets of diagnostic criteria. Electrodiagnostic criteria were also analyzed. RESULTS: A total of 69 patients met Asbury and Cornblath's criteria, 96 met Van der Meché's criteria, 99 met Wakerley's diagnostic classification and 86 met level 1 or 2 of the Brighton criteria. Rates of GBS subtypes were: 69% classic GBS; 8% Miller-Fisher syndrome; 12% paraparetic GBS; 2% pharyngeal-cervical-brachial GBS; and 9% unclassified. Those for electrodiagnostic subtypes were 52% demyelinating and 9% axonal according to Hadden's criteria vs 41% demyelinating and 41% axonal as per Rajabally's criteria. CONCLUSION: In this study of case distribution within the GBS spectrum of a retrospective cohort of French patients, the application of new diagnostic criteria enabled accurate diagnoses and classifications of the different subtypes, and also increased the recognition of axonal GBS.

Prevalence, correlates and impact of pain and cramps in anti-MAG neuropathy: a multicentre European study.

BACKGROUND AND PURPOSE: The frequency of pain and cramps is uncertain in anti-myelin associated glycoprotein antibody (anti-MAG) neuropathy. Whether these symptoms may affect function/quality of life is unknown. METHODS: A cross-sectional study of the prevalence, correlates and impact of pain, pain subtypes and cramps, their severity, frequency and anatomical distribution was performed for 55 clinically stable patients with anti-MAG neuropathy. RESULTS: Pain of any type was reported by 80% of subjects. The most common subtype was paraesthesiae and dysaesthesiae (70%). Cramps were reported by >60% of patients, with lower limb cramps in all and upper limb cramps in about 20%. Cramps affected daily activities in >30% of these subjects, sleep in 60%, ability to exercise in >30%. Total pain score correlated with several Short Form 36 health-related quality of life (SF-36 HR-QoL) measures (P < 0.05), with Inflammatory Rasch-built Overall Disability Scale (I-RODS) (P = 0.006) and 10-m timed walk (P = 0.019). An independent association was ascertained with I-RODS (P = 0.002). Different pain subtypes showed multiple associations with SF-36 HR-QoL measures and/or functional scales. Upper limb cramps had multiple SF-36 HR-QoL functional correlates, with an independent association with the Overall Neuropathy Limitation Score (ONLS) (P = 0.004). Cramp severity correlated with ONLS (P = 0.04) and I-RODS (P = 0.028) and inversely with level of physiotherapy input (P = 0.009). Cramp frequency was associated with tremor score (P = 0.004) and multiple SF-36 HR-QoL subsections. CONCLUSIONS: Neuropathic pain and cramps may affect function and quality of life in anti-MAG neuropathy. Optimizing treatments of these symptoms, including by adequate levels of physiotherapy, may be beneficial in affected patients and requires further research.

Review of the literature: Articles published in the last five years that have changed my daily practice.

Over the last five years, the management of peripheral neuropathies has become structured by the publication of recognized diagnostic criteria for inflammatory neuropathies and the elaboration of a function score, the R-ODS, used to evaluate the progression of these neuropathies. The concept of nodo-paranodopathy has enriched the concept of peripheral neuropathies, over-riding the classical mechanisms of axonal and demyelinating mechanisms. The structures of the nodes of Ranvier, gangliosides, contractin and neurofascin are preferential targets for auto-antibodies responsible for dysimmune neuropathies. Concerning treatments, immunosuppressors have demonstrated their efficacy for the treatment of anti-MAG neuropathies. Corticosteroid treatments are also in the limelight, demonstrating a different response profile than intravenous immunoglobulins for CIDP. But the most remarkable therapeutic progress has been made in the domain of hereditary neuropathies. The first trial versus placebo produced positive results in CMT1a. Finally, the era of genetic therapy appears to have come to fruition with the interfering RNA trial for familial amyloid neuropathies.

Revisiting the spectrum of lower motor neuron diseases with snake eyes appearance on magnetic resonance imaging.

BACKGROUND AND PURPOSE: The 'snake eyes' sign refers to bilateral hyperintensities of the anterior horns on axial spinal cord imaging. Based on sporadic reports, it has been associated with a range of lower motor neuron (LMN) syndromes, such as spondylotic amyotrophy and Hirayama disease, as well as spinal cord infarction. The objective of our study was to comprehensively characterize the full diagnostic spectrum of LMN syndromes with this radiological clue and discuss potential aetiological factors. METHODS: A large patient cohort with snake eyes sign and upper limb LMN degeneration was recruited from three French neuromuscular units. Patients underwent detailed electrophysiological, radiological, clinical and anamnestic profiling. RESULTS: Twenty-nine patients were ascertained and followed up for 9.5 ± 8.6 years. The majority of the patients were male (86.2%) with a mean age of 37.3 ± 14.4 years. Symptoms were bilateral in most cases (86.2%). Patients with predominantly proximal and distal deficits were equally represented (44.8% and 55.2%, respectively). A history of preceding trauma or intense physical activity was confirmed in 58.6% of the cases; 27.6% of the patients were given an initial clinical diagnosis of amyotrophic lateral sclerosis (ALS), and 51.7% were originally suspected to have multifocal motor neuropathy. None of the patients developed ALS on longitudinal follow-up. CONCLUSION: The snake eyes sign on magnetic resonance imaging is associated with a wide spectrum of neurological conditions and is more common in young men with a history of strenuous activity or antecedent trauma. The recognition of this syndrome is crucial as many of these patients are initially misdiagnosed with ALS.

[Efficacy of autologous peripheral blood stem cell transplantation (auto-PBSCT) on the neuropathic manifestations in POEMS syndrome]. / Efficacité à moyen terme de l'autogreffe de cellules souches hématopoïétiques périphériques sur la polyneuropathie du syndrome POEMS: expérience chez 5 cas.

INTRODUCTION: POEMS syndrome (polyneuropathy, organomegaly, endocrynopathy, M-protein, and skin changes) is a rare multisystem disease associated with plasma cell dyscrasia. The efficacy of autologous peripheral blood stem cell transplantation (auto-PBSCT) reported in case series has been mainly based on hematologic criteria and clinical recovery of peripheral neuropathy dysfunctions but has not been specifically evaluated. This retrospective study aimed to analyze the efficacy of auto-PBSCT on disability and electrophysiological patterns in patients with POEMS syndrome. METHODS: Five patients presenting with POEMS syndrome received auto-PBSCT. Disability was evaluated before treatment and at 6 and 12 months using the Overall Neuropathy Limitation Scale (ONLS) and MRC sumscore of 28 muscles. Nerve conduction studies were performed before and one year after treatment, on median, ulnar, fibular and tibial nerves. RESULTS: Mean age was 60.6 years (49-70). Disease duration between first symptoms and auto-PBSCT was 15.4 months (2-33). Before auto-PBSCT, mean ONLS score was 4.2 (1-10) and mean MRC sumscore 115.8/140 (74-140). At M6, mean ONLS score decreased and mean MRC sumscore increased; both were improved in all patients at M12: mean ONLS score 3 (range 0-8) at M6 and 2.2 (range 0-7) at M12; mean MRC sumscore 118/140 (77-140) at M6 and 122.4/140 (80-140) at M12. Significant recovery in electrophysiological patterns was observed in all patients on ulnar and median nerves: before-after treatment differences were observed for motor conduction velocities (34.41 vs. 45.47 m/s; P<0.001), distal CMAP amplitudes (5.04 vs. 5.96 mV; P=0.004), and sensory conduction velocities (43.20 vs. 49.20 m/s; P=0.001). Distal CMAP amplitude remained low in fibular and tibial nerves (0.41 vs. 0.17 mV). CONCLUSIONS: Clinical and electrophysiological improvement is obvious in POEMS syndrome peripheral neuropathy within one year after treatment with auto-PBSCT, undoubtedly resulting from extensive remyelinisation and axonal regeneration. Further studies are required to examine long-term outcome in patients with POEMS syndrome given auto-PBSCT.

[Electrodiagnostic criteria for early diagnosis of bulbar-onset ALS: a comparison of El Escorial, revised El Escorial and Awaji algorithm]. / Apport de l'électromyogramme dans le diagnostic précoce des SLA à début bulbaire: comparaison des critères d'El Escorial, d'El Escorial modifiés et d'Awaji.

INTRODUCTION: Diagnosis of bulbar ALS is difficult at the early stage of the disease. According to guidelines, early diagnosis is better in view to optimize the management of affected patients. To improve the sensitivity without losing specificity of the prior criteria, the Board of Awaji has proposed modified electrodiagnostic criteria for ALS. The aim of this study was to evaluate the contribution of needle electromyography in early diagnosis of bulbar ALS by comparing the El Escorial criteria (EEC), Revised El Escorial Criteria (R-EEC) and Awaji algorithm (AA). METHODS: In a retrospective study, we analysed clinical and electrophysiological data of 46 patients followed in our center for a bulbar-onset ALS seen for the first time between January 2007 and February 2011. All these patients had bulbar-onset ALS probable or certain at the last follow-up. All data were collected during the first clinical examination and the first electrophysiological study. RESULTS: Mean age of the population was 69 (37-90years, sex ratio: 0.91). Using the EEC, 9 patients were diagnosed as definite or probable ALS at the first consultation. Applying the R-EEC, 13 patients were diagnosed as definite or probable ALS and using the AA, 23 patients were diagnosed as definite or probable ALS. The sensitivity of the EEC was 19.5%, the R-EEC was 28.2% and for AA was 49.98%. CONCLUSION: AA are more sensitive in early diagnosis of bulbar ALS compared to R-EEC with the contribution of ENMG and when fasciculations are considered as evidence of spontaneous activity. Such an approach can contribute to accelerate an optimal management of the disease. AA are a breakthrough in the diagnosis of ALS especially in the bulbar-onset forms.

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.

Pain assessment in Charcot-Marie-Tooth (CMT) disease.

OBJECTIVE: The objective of our study was to describe and evaluate the prevalence of chronic pain in persons with Charcot-Marie-Tooth (CMT) disease during a multidisciplinary consultation at the Center of Reference for Neuromuscular Diseases. METHODOLOGY: This prospective study was conducted between 2008 and 2010, it was a partnership between a Center of Reference for Neuromuscular Diseases (Centre de référence des maladies neuromusculaires [CRMD]) and a Department for the Assessment and Treatment of Pain (Département d'évaluation et de traitement de la douleur [DETD]). The evaluation consisted in a complete assessment of each patient during the first multidisciplinary consultation, with a previously established diagnosis validated by genetic testing, by various specialists: neurologist, PM&R physician, pain management specialist and physiotherapist. The evaluation tools used were Visual Analogical Scale (VAS), Hospital Anxiety and Depression Scale (HAD), DN4 scale, Neuropathic Pain Symptom Inventory (NPSI) (if DN4≥4), Pain Questionnaire of Saint Antoine (QDSA) (if DN4<4), body representation to define the painful areas, Overall Neuropathy Limitations Scale (ONLS), Medical Research Council scale (MRC), Short Questionnaire on Pain (QCD), VAS during transfers, self-care, getting dressed and physiotherapy sessions and quantified use of analgesics. RESULTS: A total of 50 patients were included (28 women, 22 men); two patients (one man and one woman) were discarded from the study because of missing pain assessment data. Mean age was 47years (R: 14-85), in average the symptoms had been present for the past 20years (R: 0.3-68), most patients had little impairment, the mean MRC was 53 (R: 36-60), with CMT1A being predominant (CMT1A: 76.9%, CMTX: 13.5%, CMT2: 5.8%, CMT4: 3.8%). It is noted that 65.4% of patients reported some pain with a mean duration of pain at 140months (R: 5-660). The mean VAS was 5.5 (R: 1-10), greater than 4 in 79.4% of cases, requiring the use of analgesics in 38.4% of cases (step 1: 60%, step 2: 40% on the WHO pain relief ladder). The predominant location of the pain was distal, peripheral and symmetric (64.7%); furthermore the feet were affected in 80% of cases. DN4 was positive in 40.6% of painful patients. In 62.5% of the cases, the pain did not have an underlying mechanical origin. The emotional impact remained quite modest (HAD: A=8; D=5). Patients with CMT1A seemed less affected by pain (P=0.03). CONCLUSION: This original study describes the pain in patients with CMT disease during a primary multidisciplinary consultation. We see that in 66% of cases, patients do report some pain, this pain is usually moderate, preferentially located in the extremities and is symmetric. In 62.5% of cases, the pain has a neuromuscular origin with a positive DN4 in 50% of cases in this etiology. In our study, patients with CMT1A report less pain than patients with other CMT types. This disease being quite rare (rare disease), the number of patients did not allow us to bring up statistically significant results. The pain must be thoroughly screened for because of its frequency in persons with CMT.

[Improvement of severe and intravenous immunoglobulin-dependent multifocal motor neuropathy with conduction block after long-term rituximab]. / Amélioration d'un cas de neuropathie motrice multifocale avec blocs de conduction sévère, dépendant des immunoglobulines intraveineuses, après adjonction de rituximab au long cours.

INTRODUCTION: Some patients suffering from multifocal motor neuropathy with conduction blocks (MMNCB) are still disabled after treatment with intravenous immunoglobulin (IVIg). CASE REPORT: We report the benefits of a combination of rituximab (RTX) and IVIg in the case of a 72-year-old man with MMNCB. DISCUSSION: Despite an IVIg treatment, the patient had severe motor weakness of the four limbs which limited daily living activity. Azathioprine, mycophenolate mofetyl and cyclophosphamid did not improve the patient's status. Adjunction of rituximab to IVIg therapy increased muscle strength measured on MRC sum score and reduced disability evaluated on ONLS (Overall Neuropathy Limitation Scale) score in the long term (37 months). In spite of the improvement of his neurological status, the patient remained dependent on IVIg. CONCLUSION: RTX could be proposed as a long-term complementary treatment for some severe cases of IVIg-dependent NMMBC. These results must be confirmed in a randomized controlled study.