Impact of physical activity, physical fitness and exercises on cognitive impairment in patients with multiple sclerosis: A review of evidence and underlying mechanisms.

Cognitive impairment in persons with MS (pwMS) occurs commonly, early and independently of other clinical features of the disease. MS-related cognitive impairment is mainly characterized by weakening of information processing speed, working memory and episodic memory. Much evidence, based on both neuropsychological and neuroimaging outcomes, highlights successful cognitive rehabilitation interventions. In this context, promotion of physical activity and exercise training could be a dual, motor and cognitive, rehabilitation method. The aim of this article is, firstly, to review existing evidence regarding the effects of exercise on cognition among pwMS, and secondly, to explore the possible mechanisms of action of the cognitive-motor coupling.

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.

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.

Low back pain in patients with multiple sclerosis: A systematic review and the prevalence in a French multiple sclerosis population.

PURPOSE: The prevalence and management of back pain in MS patients was assessed by a systematic review, and the results of a survey on the characteristics of low back pain in a sample of French MS patients are reported. METHODS: A systematic search was conducted according to the PRISMA guidelines. The outcomes of interest included the prevalence of back pain, severity of pain and impact on daily activities. Moreover, the prevalence of low back pain and its consequences on daily living in a large French MS population were assessed. RESULTS: Fourteen studies were included in the systematic review. The prevalence of back pain in MS patients ranged from 8.6 to 50%, but that of low back pain in particular ranged from 41.6 to 52.4%. Concerning the survey, 237 patients participated in the online questionnaire. The prevalence of low back pain in the French MS patients was 76.4%. The patients with chronic low back pain had more limitations in their daily life activities than those without chronic low back pain. CONCLUSION: Patients with MS commonly suffer from low back pain, but it is still an underdiagnosed cause of pain that reduces one's ability to perform activities in daily life.

Anticipatory postural adjustment during gait initiation in multiple sclerosis patients: A systematic review.

BACKGROUND: Multiple sclerosis (MS) causes balance and walking disorders. Gait initiation is the complex transition between standing and walking and is characterized by two distinct phases: the anticipatory postural adjustment (APA) phase followed by the execution of the first step phase. RESEARCH AIM: To determine alterations in the APA during gait initiation in patients with MS. METHODS: A systematic search was conducted in May 2018. The search was carried out by the use of the following databases: PubMed, Web of Science and the Cochrane Library. The following keywords were used: MS, gait initiation, step initiation, and postural adjustment(s). Outcomes of interest were the variables generally used to assess APA, including electromyography, force-plate data, or video-based data, duration of APA, and length of first step. The Ottawa scale was used to assess the quality of the studies. RESULTS: Eight case-control studies were included; one was a transverse study. A total of 215 MS patients and 116 healthy subjects were included with ages ranging from 22 to 76 years old. In MS patients, Expanded Disability Status Scale (EDSS) scores ranged from 0 to 7. APA CoP displacements were smaller in the anteroposterior axis. Four studies evaluated muscle activation during APA. The latencies of all muscles were delayed, and smaller magnitudes of muscle activity during APA were found, even in the early stage of disease. The first step was shorter in MS patients than in healthy patients. No previous study has reported joint movement or trunk inclination during gait initiation. SIGNIFICANCE: This review illustrates the gap in knowledge of APA alterations in MS patients. APA assessment in the early stage of MS could be an interesting measure to characterize balance, dynamic control and risk of fall for such patients.

[100 essential drugs. An internal medicine approach]. / Les 100 médicaments essentiels. Une approche de médecine interne.

PURPOSE: Up to 4600 drugs in about 15,000 pharmaceutical forms are available in France which may be a source of misuse with increased occurrence of side effects and costs. While the World Health Organization is encouraging each developed country to work out its own list of essential drugs. The list provided in 2008 by the French Office for the safety of health products has had so far limited impact on practice, so it became obvious to a group of internists to work out a "wise list" of 100 essential medicines covering 95% of the disorders observed in France. METHODS: In June 2011, 10 internists agreed to each provide a list of 100 essential medicines, according to individual experience. In December 2011, a meeting of the participants provided a list as initial consensus and mandated five among them to make proposals for those areas neglected by too many participants or in which needless dispersion of medicines was stated. After internet-facilitated exchanges, an additional list was validated in mild-January 2012. RESULTS: Fifty-four drugs were included in the list of initial consensus (including nine selected by all 10 participants), and 46 in the additional list. So the final "wise list" included 100 drugs. In June 2012, 56 of these drugs were available as generics. This list was compared to those lists set out by five countries in the European Union. CONCLUSION: Generating such a list is feasible. Undoubtedly still non-comprehensive, this list will benefit from the expertise of 14 general practitioners who are currently working out a similar list across France. The final list will be submitted for validation by the French associations of generalist teachers and Internists.

[Thrombotic microangiopathy with anti-ADAMTS 13 antibodies revealing an acute Q fever]. / Micro-angiopathie thrombotique avec anticorps anti-ADAMTS 13 révélant une fièvre Q aiguë

INTRODUCTION: Q fever can commonly mimic systemic diseases, leading to several immunological manifestations. Thrombotic micro-angiopathies manifest as a spectrum of related disorders in the form of thrombocytopenic purpura and hemolytic uremic syndrome. CASE REPORT: We report a 77-year-old woman, who presented an acquired thrombotic microangiopathy with renal expression associated with the presence of anti-ADAMTS 13 antibodies, which occurred during an acute infection by Coxiella burnetii (acute Q fever). CONCLUSION: Auto-immune disorders are well-known in chronic or acute Q fever but to our knowledge, this is the first reported observation of thrombotic microangiopathy with anti-ADAMTS 13 antibodies.

[Whipple's disease: a curable encephalitis]. / La maladie de Whipple : une cause curable d'encéphalite.

INTRODUCTION: Whipple's disease is a rare systemic infectious disorder. It may present with a wide range of clinical manifestations and therefore its diagnosis may be challenging. CASE REPORT: We report a 45-year-old man who presented with acute encephalitis related to Whipple's disease. Despite the negativity of the polymerase chain reaction (PCR) test in cerebrospinal fluid, diagnosis was obtained by histopathology, PCR tests and immunohistochemistry in multiple samples. The outcome with antibiotherapy was considered as "spectacular". CONCLUSION: Whipple's disease is a rare cause of encephalitis. Its diagnosis needs the confrontation of histology and PCR tests in multiple samples. The outcome with an adapted antibiotherapy may be very successful.

[Bradykinin mediated angioedema]. / Les angiœdèmes bradykiniques héréditaires ou acquis.

Bradykinin angioedema (AE) are characterized by acute recurrent episodes of localized swelling. They are not associated with pruritus or erythema, and are short-lived (24 to 72 hours), disappearing without any sequelae. Corticosteroids are useless. Skin or mucous membranes (upper respiratory and intestinal) could be affected. Bradykinin AE can be secondary to: (1) AE associated with C1 inhibitor deficiency (hereditary or acquired); (2) drug-induced AE (converting enzyme inhibitors…); (3) type III AE type (oestrogen dependant) without C1 inhibitor deficiency. These type III AE can be associated with a gain of function mutation that markedly increases factor XII activity. Prognosis depends on the laryngeal attacks (resulting in 25 % of death in the absence of specific treatment). In case of severe attacks, icatibant (bradykinin receptor antagonist) or C1 inhibitor concentrate can be used. In case of frequent attacks, long-term therapy with danazol or tranexamic acid is effective.

[Idiopathic systemic capillary leak syndrome: a case report with cardiac involvement]. / Syndrome d'hyperperméabilité capillaire idiopathique : à propos d'un cas avec atteinte cardiaque.

Systemic capillary leak syndrome (SCLS) is characterized by recurrent hypovolemic shock associated with edema, hemoconcentration and paradoxal hypoprotidemia due to leakage into the interstitial space. We report a new case with cardiac involvement. A 62-year-old man had two recurrent hypovolemic shocks with SCLS's criteria, associated twice with cardiac systolic dysfunction and atrial fibrillation. This report should enhance physician awareness of SCLS, which is a rare and severe disease, and its cardiac involvement.

Type III hereditary angio-oedema: clinical and biological features in a French cohort.

BACKGROUND: Hereditary angio-oedema (HAE) has been associated with C1inhibitor deficiency. The first cases of type III HAE were described in patients with normal C1Inh antigenic protein level and function and normal C4 levels in 2000. This finding has been reported mostly in women with a family history and may be influenced by exogenous oestrogen exposure. OBJECTIVES: The purpose of this article is to describe the clinical, biological and genetic characteristics of a French population suffering from type III HAE. PATIENTS AND METHODS: We conducted a retrospective analysis of angio-oedema (AE) cases seen in the National Reference Centre of AE between 2000 and 2009. RESULTS: We found 26 patients (from 15 unrelated families) with type III HAE. All but four were women and presented with typical AE attacks, exacerbated by pregnancy or oral contraceptives containing oestrogens (OC). We also found that 54.5% of women were worsened with oestrogen and 23% were oestrogen dependent. All patients improved on long-term prophylactic tranexamic acid treatment; some acute attacks improved with C1Inh concentrate infusion. All of the patients had normal C1Inh and C4 levels. C1Inh function was also normal, except in women receiving OC or during a pregnancy: transient, moderately low levels (32-74% of the normal range) were found in 18 patients tested (67%). No SERPING1 gene mutation was found. Six patients from three unrelated families were heterozygous for an F12 gene variant. CONCLUSION: Diagnosis of type III HAE should be based on clinical (typical attacks, often hormonally influenced), laboratory (normal C1Inh antigenic protein) and genetic (F12 gene mutation) evidence.

Assessing allergic rhinitis in developing countries.

BACKGROUND: Allergic rhinitis (AR) affects 5% to 40% of the general population. In developing countries, AR is poorly documented and tracked due to a lack of appropriate diagnostic tools. OBJECTIVE: 1) To validate a questionnaire standardised in industrialised countries to ascertain AR, the Score For Allergic Rhinitis (SFAR), in developing countries; 2) to better understand AR prevalence previously reported from developing countries by comparing results from the SFAR and the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires. METHODS: Six African countries were selected for their climates. In each country, 70 individuals with and 30 without nasal symptoms filled out the SFAR and the ISAAC questionnaires. Skin prick tests (SPTs) for allergens were performed by the physician if necessary. RESULTS: The SFAR presented a close match with the gold standard (the physician's diagnosis of AR backed up by SPT where necessary) in terms of various performance parameters. In particular, it showed high sensitivity (0.84) and specificity (0.81). Compared to the ISAAC questionnaire, the SFAR had greater sensitivity and equal specificity. CONCLUSIONS: In the absence of a medical visit, the SFAR is a useful standardised screening instrument for the collection of information needed for the identification of AR in developing countries.

[Acute respiratory distress syndrome as the presenting manifestation of an antisynthetase syndrome]. / Pneumopathie aiguë sévère révélatrice d'un syndrome des anticorps antisynthétases.

The antisynthetase syndrome is a subgroup of idiopathic inflammatory muscle diseases. Its characteristics are interstitial lung disease, myositis, polyarthritis, mechanic's hand like cutaneous involvement, and the presence of antisynthetase antibodies (anti-Jo1). The lung disease is the presenting feature in 50% of cases. We report a patient with an antisynthetase syndrome, revealed by an acute respiratory distress syndrome. This patient was already followed-up for a scleroderma and presented a probable overlap syndrome. The disease course was favourable with anti-CD20 therapy.

[Tuberous sclerosis without mental impairment, diagnosed in adulthood]. / Sclérose tubéreuse de Bourneville sans altération intellectuelle, diagnostiquée à l'âge adulte.

INTRODUCTION: Tuberous sclerosis complex (TSC) is an autosomal dominant inherited phakomatosis, usually diagnosed in childhood and characterized by cutaneous and neurological tumors, the latter often leading to epilepsy and mental retardation. EXEGESIS: We report a case of TSC diagnosed in a 33-year-old man, without any known family history of phakomatosis, presenting with facial angiofibromas, hypomelanotic macules, a giant-cell astrocytoma and retinal phakomas without any mental impairment or epilepsy. CONCLUSION: TSC may occur in patients who do not have any family history of phakomatosis because de novo mutations are frequent. TSC may be diagnosed in adulthood since a high phenotypic variability is observed. Facial angiofibromas are highly suggestive of tuberous sclerosis complex. They should lead to brain imaging in search for astrocytoma, subependymal nodules and cortical tubers which number is directly correlated with the risk of seizures and the degree of mental impairment.

[Non-histaminic angiodema management: diagnostic and therapeutic interest of tranexamic acid]. / Intérêt diagnostic et thérapeutique de l'acide tranexamique dans les angio-oedèmes non-histaminiques.

INTRODUCTION: The diagnosis of chronic angioedema (localised and reversible oedema) is sometimes very difficult when there is no efficiency of anti-histaminics and corticosteroids. In these cases, bradykinin angioedema must be mentioned. Tranexamic acid is efficient and must be proposed. STUDY: We reported seven patients who have a non-histaminergic angioedema since an average of 8 years. Corticosteroids and histamine-1 blockers were not efficient. Daily tranexamic acid treatment (1 g x 3 per day) controlled the disease. Three patients had no more attack. The C1Inh antigen and function levels were normal. No secondary effect was described and all patients are still being treated (average of 20 months). CONCLUSION: When a non-histaminergic angioedema is suspected, tranexamic acid must be proposed as attack's treatment and as prophylactic treatment.