What you feel is not always what you've got. Jean Lhermitte (1877-1959) and the phantom limb phenomenon.

Jean Lhermitte (1877-1959), the French neurologist and psychiatrist, is most often associated with the sign he described in three patients with multiple sclerosis, back in 1927. In 1937, Lhermitte analytically studied a series of 28 amputees experiencing phantom limb sensations further to amputations dating between 1891 and 1934. After having described the main clinical characteristics of this unpublished series, we will detail the ideas advanced by Jean Lhermitte regarding the phenomenon of the phantom limb. Lhermitte will use these observations to develop conceptions of consciousness and the body schema encompassing very modern resonances.

NUTRISEP: Assessment of the nutritional status of patients with multiple sclerosis and link to fatigue.

BACKGROUND: Fatigue is a common complaint in patients with multiple sclerosis (PwMS) and reduces quality of life. Several hypotheses for the pathogenesis of fatigue in MS are proposed ranging from neurological lesions to malnutrition, but none has been conclusively validated through clinical research. OBJECTIVES: The goal of this study was to examine the correlation between fatigue and nutritional status and dietary habits in PwMS. METHODS: This was a cross-sectional, multicenter study conducted at 10 French MS centers and enrolling PwMS with an Expanded Disability Status Scale (EDSS) score between 0 and 7. Plasma level of albumin, magnesium, calcium, iron, vitamin D and B12 evaluated nutritional status. A semi-structured eating behavior questionnaire has been developed to evaluate dietary habits. Evaluation of fatigue used specific questionnaire (EMIF-SEP). Quality of sleep was evaluated by visual analogue scale (VAS), depression with Beck Depression Inventory (BDI-II); dysphagia by DYsphagia in MUltiple Sclerosis questionnaire (DYMUS) and taste disorders by gustometry. Association between nutritional deficiencies and different data such as socio-demographic data, disease characteristics, swallowing and taste disorders, food intake, depression and sleep quality was investigated. RESULTS: A total of 352 patients mean age: 48.1±10.1 years, mean duration of MS: 15.3±9.1 years and median EDSS: 4 were analyzed. Bivariate and multivariate analyses showed a statistically significant correlation between fatigue and depression and use of sleeping pills, while none of the variables related to dietary habits or nutritional status correlated significantly with fatigue. CONCLUSIONS: Dietary habits and nutritional status have little impact on fatigue and general population nutrition recommendations remain the rule for PwMS. In cases of fatigue, specific attention should be paid to depression and use of sleeping pills.

Jean-Alexandre Barré: Babinski's brilliant student.

Guillain-Barré Syndrome, (GBS), is a popular eponym that comes from a paper written in 1916 by Doctors. Guillain, Barré, and Strohl. Its spectrum has been enlarged considerably since the first description of it. Jean Alexandre Barré was a French neurologist, whose name is still widely associated with that of Georges Guillain, (1876-1961). He is also known for the leg manoeuvre. As Joseph Babinski's brilliant student, (1857-1932), we wanted to briefly retrace his biography in order to highlight some of the salient points within it and subjects that are topical for young neurologists today.

CONFISEP: Impact of the Covid-19 pandemic lockdown on patients with multiple sclerosis in the north of France.

We performed an online survey to assess lockdown impact in 176 patients with multiple sclerosis (PwMS) in the north of France. Access to healthcare was reduced for 38% of PwMS, mainly in physiotherapy, general practitioners and neurologists. 49.2% have implemented self-rehabilitation programs. Medical support was maintained for 39.2% through teleconsultations. 76.2% reported a negative impact of lockdown related to worsen disability. 45.5% expressed beneficial effects like strengthening family relationships, and reduced fatigue. Previous studies have found the same results on disability and discontinuation of care. However, even if this period has been challenging for PwMS, most of them have shown excellent adaptability.

[To treat or not to treat asymptomatic bacteriuria before methylprednisolone perfusion]. / Traiter ou ne pas traiter les bactériuries asymptomatiques avant bolus de méthylprednisolone?

The prescription of methylprednisolone for multiple sclerosis acute relapse involves sterilization of urine. An observational study was conducted to clarify the benefit of antibiotic prophylaxis in case of asymptomatic bacteriuria found before methylprednisolone. Ninety-seven patients were included; 32 patients had asymptomatic bacteriuria. Seventeen patients were treated and 15 were not. The number of urinary tract infections in the month following the methylprednisolone was the same in the two groups. The results seem in favor of a therapeutic abstention. A larger study will be performed to confirm these results and determine appropriate recommendations.

Tear analysis as a tool to detect oligoclonal bands in radiologically isolated syndrome.

BACKGROUND: Although radiologically isolated syndrome (RIS) is a newly defined entity, incidental findings of T2 hypersignals on brain MRI can lead to misdiagnosis or useless investigations. The detection of oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) is a major indicator that helps in diagnosis of subclinical inflammatory disease of the central nervous system, but lumbar puncture still remains an invasive option. METHODS: We have prospectively included patients with RIS, have compared the results of CSF and tear OCB detection by isoelectric focusing (IEF) and assessed concordance between OCB detection in tears and in CSF. Tears were collected using a Schirmer strip. RESULTS: In 45 recruited RIS patients, OCBs were detected in CSF for 55% (25/45) and in tears for 50% (21/42) of samples. CONCLUSIONS: We suggest that tear OCB detection may replace CSF OCB detection as a diagnostic tool in patients with RIS and be useful in follow-up.

A prospective observational post-marketing study of natalizumab-treated multiple sclerosis patients: clinical, radiological and biological features and adverse events. The BIONAT cohort.

BACKGROUND AND PURPOSE: BIONAT is a French multicentric phase IV study of natalizumab (NTZ)-treated relapsing-remitting multiple sclerosis (MS) patients. The purpose of this study was to collect clinical, radiological and biological data on 1204 patients starting NTZ, and to evaluate the clinical/radiological response to NTZ after 2 years of treatment. METHODS: Patients starting NTZ at 18 French MS centres since June 2007 were included. Good response to NTZ was defined by the absence of clinical and radiological activity. Data analysed in this first report on the BIONAT study focus on patients who started NTZ at least 2 years ago (n = 793; BIONAT2Y ). RESULTS: NTZ was discontinued in 17.78% of BIONAT2Y. The proportion of patients without combined disease activity was 45.59% during the first two successive years of treatment. Systematic dosage of anti-NTZantibodies (Abs) detected only two supplementary patients with anti-NTZ Abs compared with strict application of recommendations. A significant decrease of IgG,M concentrations at 2 years of treatment was found. CONCLUSIONS: The efficacy of NTZ therapy on relapsing-remitting MS in a real life setting is confirmed in the BIONAT cohort. The next step will be the identification of biomarkers predicting response to NTZ therapy and adverse events.

Herpes encephalitis during natalizumab treatment in multiple sclerosis.

In this case report we describe the first non-fatal herpes simplex virus encephalitis (HSE) case with natalizumab for multiple sclerosis (MS). A 36-year-old woman, previously treated with immunomodulatory and immunosuppressive drugs for MS, developed acute encephalitis after 6 monthly natalizumab perfusions. Brain imaging demonstrated suggestive bi-temporal lesions. Herpes simplex virus type-1 DNA was detected in cerebrospinal fluid. The patient improved gradually after a 21-day course of intravenous acyclovir, but neuropsychiatric changes remained 5 months later. Our non-fatal case of HSE and other reported cases of herpes infections provide evidence of an increased risk with natalizumab and point to the need for clinicians to maintain awareness.

[Urinary, sexual, and bowel disorders in early-stage multiple sclerosis]. / Troubles sphinctériens au stade precoce de la sclérose en plaques.

Most multiple sclerosis (MS) patients experience some bladder, sexual, and/or bowel dysfunction during the course of the disease, which has been closely associated with the quality-of-life scores, including in patients with otherwise low disability. This underlines the need for identifying and treating these problems. Bladder dysfunction produces symptoms of urgency, frequency, and urge incontinence (due to bladder over activity and incomplete emptying), and is found in up to 80% of patients with MS. These symptoms occur in the early stage of the disease and require screening and rigorous monitoring. For many patients, treatment is effective and has been shown to reduce the risks of urologic complications, improve levels of continence, and enhance the patient's quality of life. Sexual disturbances are also present from the beginning and have and greatly influence the quality of life of the MS patient. The findings in the literature show substantial evidence that people with MS experience high levels of sexual dysfunction, most of them with hypoactive sexual behavior often associated with dissatisfaction in the relationship. The most common problems in women are lack of sexual interest and decreased libido, often with problems in orgasmic capacity, while men report erectile dysfunction and also lack of sexual interest. Unlike bladder dysfunction, there have been rather limited advances in the treatment of fecal incontinence and constipation specifically for patients with MS, despite a prevalence of up to 50%. Until now, the management of these problems has been empirical, with a lack of evaluated therapeutic regimes. Biofeedback retraining is an effective treatment in some patients with MS complaining of constipation or fecal incontinence. A response is more likely in patients with limited disability and a nonprogressive disease course. Since treatments and preventive strategies can manage many of these problems, we suggest increasing the focus on these aspects of the disease when consulting patients, including at early stages.

[High prevalence of restless legs syndrome in multiple sclerosis]. / Prévalence élevée du syndrome des jambes sans repos dans la sclérose en plaques.

Prevalence of restless legs syndrome (RLS), a clinically defined disorder, varies from 2.5 to 15% among populations. In the French adult population, prevalence is estimated to be 8.5%. RLS is often secondary to a variety of disorders. Neurological conditions usually associated with RLS are neuropathies and Parkinson's disease. There are few studies of its association with multiple sclerosis (MS). The aim of this study was to estimate RLS prevalence in a population of French MS patients. During one month, 17 neurologists from the G-SEP group prospectively recruited 242 patients who fulfilled the Mc Donald criteria for MS. Each patient underwent a standardised questionnaire to verify the international criteria of RLS. We collected date of birth, gender, MS course (relapsing remitting, primary progressive and secondary progressive) and MS duration. Forty-one subjects (18%) met the criteria for RLS. Comparing the RLS group with the group without RLS, no significant differences were found in age, gender and MS duration. RLS was more prevalent in the relapsing remitting MS group. Prevalence of RLS seems to be doubled in MS patients compared to the general population. This finding warrants further study. Identification of this syndrome in MS patients might lead to specific treatments.

Pathologic laughing and intractable hiccups can occur early in multiple sclerosis.

Pathologic laughing occurs in approximately 10% of patients with multiple sclerosis (MS), especially when patients have entered the chronic stage. We describe four patients with MS who, at an early stage, developed pathologic laughing associated, in two cases, with intractable hiccups. In two patients, MRI showed an enhanced lesion in the medulla oblongata and the mesencephalon, two regions suspected of being involved in pathologic laughing and intractable hiccups.

Treatment of progressive forms of multiple sclerosis by cyclophosphamide: a cohort study of 490 patients.

There are no generally effective disease-modifying drugs for progressive forms of multiple sclerosis (MS). Some MS centres use cyclophosphamide (CYC) in secondary progressive (SP) forms of MS, especially after interferon beta-1b (INFbeta-1b) treatment failure. Moreover, there are currently no approved drugs for primary progressive (PP) MS. Using the collected data of patients with progressive MS, we studied clinical patterns that predicted a good response to CYC treatment. Secondly, we compared the therapeutic response of SPMS and PPMS patients to the treatment. Data from 490 MS patients were collected. All patients presented an SP (n = 362) or PP (n = 128) form of the disease and 476 had been treated for at least one year with a monthly pulse of CYC associated with methylprednisolone (MP). CYC treatment was justified because of at least a 1-point worsening on the Expanded Disability Status Scale (EDSS) during the previous year. The EDSS score was assessed at baseline and after 6 months (M6) and 12 months (M12) of treatment. After 12 months of CYC treatment, 78.6% of SPMS and 73.5% of PPMS patients had stabilised or had an improved EDSS score. Response to CYC was not significantly different in the two progressive forms of MS. Twenty-two patients presented noticeable drug side effects, one of whom withdrew from the treatment due to intolerance. Patients with an improved EDSS at M12 had a shorter mean progressive time course (5.1 years) than patients who stabilised or worsened (7.1 years) (p = 0.02). We also observed that poor responders at M6 were also poor responders at M12 (p < 0.001). This large cohort study showed that CYC treatment was well tolerated and suggested that a better response occurred in cases with a short progressive time course. We did not find any difference in treatment response between the two progressive forms of MS. To date, no treatment is approved for PPMS and we therefore propose a trial to test the use of CYC treatment early in the course of the disease in PPMS patients with disability progression.

[General practitioners' approach to relapsing multiple sclerosis]. / Approche des poussées de sclérose en plaques par les médecins généralistes.

Management of multiple sclerosis depends on close multidisciplinary collaboration but general practitioners play a particularly important role, especially in case of relapse, due to their close relationship with the patient. The purpose of this work was to conduct a survey of general practitioners' knowledge of relapsing multiple sclerosis and ascertain their main difficulties in patient management. One hundred seventy-seven practitioners answered a written questionnaire with two headings, diagnostic criteria for relapse and therapeutic approaches. Analysis of the results showed that this common event is under recognized. While 55.9 p.cent of the general practitioners stated they diagnosed relapse by themselves, only 2.8 p.cent knew its exact definition. Differential diagnosis accounted for a large number of mistakes. Our survey also underlined the use of certain therapeutic options (low-dose oral corticosteroid therapy) for which the effectiveness has not been demonstrated. It would be important to propose specific education on relapsing multiple sclerosis for general practitioners and improve cooperation with specialists. An integrated care network might be useful.

Multiple sclerosis, interferon beta and clinical thyroid dysfunction.

The objective of this study was to investigate frequency and presentation of clinical thyroid dysfunction in patients treated with interferon beta (IFN-beta). We have collected the cases of clinical thyroid dysfunction in 700 consecutive patients receiving IFN-beta for multiple sclerosis (MS). Five patients (four women, one man) treated with IFN-beta1b developed hyperthyroidism. Three of them have secondary progressive MS, and two have relapsing-remitting MS. It was necessary to stop IFN-beta in three cases; these patients still require carbimazole after several months. In the two other cases, hyperthyroidism disappeared spontaneously. Two patients (one man and one woman) treated with IFN-beta1a developed hypothyroidism. One of them required l-thyroxine. Lastly, an increased thyroid volume without modification of thyroid hormones plasma levels was discovered in a patient receiving IFN-beta1a. Among patients treated with IFN-beta, clinical thyroid dysfunction is much rarer than laboratory thyroid dysfunction. However, this side-effect is sometimes severe.

[Comparison of spectral analysis and non-linear analysis of EEG in patients with cognitive decline]. / Comparaison de l'analyse spectrale et de l'analyse non-linéaire de l'EEG dans les troubles cognitifs.

Twenty-five elder subjects were classified in two groups according to the MMS score and the cognitive evoked potentials. Normal subjects (n = 15) had mean MMS = 27.6 and mean P3 amplitude = 7.1 uV), while patients with cognitive decline (n = 10) had respective values of 18 (MMS) and 3.3 uV (P3). Spectral analysis and non-linear analysis of EEG (recurrence plots of dynamical systems) were performed and both showed statistically significant differences between groups for all the parameters analysed. Subjects' classification with discriminant analysis was slightly better using the non-linear parameters. The recurrence plot method applied to EEGs, gave similar results as the dimension of correlation (D2) calculation, and was in favour of a more constraint and less complex dynamics of brain activity associated with cognitive decline.

Interferon beta1a (Avonex) treatment in multiple sclerosis: similarity of effect on progression of disability in patients with mild and moderate disability.

OBJECTIVE: To compare clinical responses to once-weekly intramuscular interferon-beta-1 a [IFNbeta-1 a, Avonex, Biogen] in multiple sclerosis (MS) patients with baseline Expanded Disability Status Scale (EDSS) < or = 3.5 or > 3.5. METHODS: Patients with relapsing-remitting MS (RRMS), 124 with baseline EDSS < or = 3.5 and 64 RRMS patients with EDSS > 3.5, were consecutively recruited to receive IFNbeta-1 a 30 microg as a once weekly injection for 18 months. The primary endpoint of the study was the number of patients in each group with sustained worsening in disability, defined as 1-point deterioration in EDSS that persisted for at least 6 months during the 18 month follow-up period. Subordinate endpoints included relapse rates and the number of treatment dropouts. RESULTS: Among patients with baseline EDSS < or = 3.5,16.9% experienced a deterioration in EDSS of at least 1 point; 22.5% experienced a deterioration of at least 0.5%. Corresponding rates in patients with baseline EDSS > 3.5 were 23.4% and 29% respectively (no significant differences between patients stratified according to baseline EDSS status). The proportion of patients discontinuing therapy was significantly higher in patients with baseline EDSS > 3.5 than in those with baseline EDSS < or = 3.5 (16/64 versus 12/124; p = 0.005). At the conclusion of follow-up, IFNbeta-1 a therapy was associated with a 31.7% reduction in relapse rate in patients with baseline EDSS < or = 3.5 and a 37% reduction in those with baseline EDSS > 3.5 (difference not significant). CONCLUSIONS: During 18 months of treatment and follow-up, no difference was observed in clinical responses to IFNbeta-1 a between RRMS patients with mild and moderate disability but discontinuation of therapy was more frequent in the more disabled group.

[Treatment of progressive multiple sclerosis with cyclophosphamide]. / Traitement des formes progressives de sclérose en plaques par le cyclophosphamide.

Intravenous (IV) cyclophosphamide is currently used in secondary progressive (SP) and Primary progressive (PP) Multiple Sclerosis (MS) but its efficacy remains uncertain. Furthermore, it is necessary to determine which MS should be successfully treated with IV cyclophosphamide. We retrospectively investigated 111 consecutive patients with progressive MS (21 PPMS and 90 SPMS) treated in an open label fashion with IV cyclophosphamide. We analysed clinical data (gender, age, duration of progression, primary versus secondary MS). The treatment response was assessed by EDSS change after 6 months and 1 year of treatment. The annual relapse average decreased from 1.92 before treatment to 0.39 during the treatment. Age and gender did not influence response to therapy. We did not find any difference of response between PPMS and SPMS. Duration of the progressive phase in SPMS was not a predictive factor of efficacy. A better response was noted in SPMS patients with surimposed relapses than in patients without relapses during the year before treatment (p<0.05). Furthermore, the better response in SPMS patients with relapses before treatment suggests that it is necessary to treat when MS is still in an inflammatory stage.