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.

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.

[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.

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.

[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.

Modified Blalock-Taussig shunts: results in infants less than 3 months of age.

The optimal procedure for shunting palliation in cyanotic infants remains to be determined. Sixty-two infants less than 3 months of age underwent 63 modified Blalock-Taussig shunts. Their age range at operation was 1 to 84 days (mean, 16 +/- 20 days). Shunts were constructed using 5-mm polytetrafluorethylene tubes in 20 patients and 4-mm polytetrafluoroethylene grafts in 43 patients. There were 13 early deaths (21%; CL, 15% to 27%) of which three deaths (5%; confidence limits, 2% to 9%) were shunt related. The survivors were followed up from 6 to 53 months (mean, 29 +/- 12.5 months). Shunt failure (occlusion, inadequate palliation) occurred in 27 patients. The overall probability rate of adequate shunt function was 58% +/- 8% at 2 years. Univariate and multivariate analyses showed that the size of the graft was a risk factor of shunt failure. Severe distortion of the pulmonary arterial branch was noted in 12 patients. The inferences are: (1) modified Blalock-Taussig shunts provide satisfactory early palliation but late shunt failure is frequent; (2) similar results should be obtained with other shunting procedures; and (3) the optimal procedure should be selected for each cyanotic infant on an individual basis.

[The principal statistical software useful in biomedical research with microcomputers]. / Les principaux logiciels statistiques utilisables en recherche biomédicale sur micro-ordinateur.

The authors describe pragmatic aspects of the use of the main statistical software packages for biomedical research with microcomputers. Data analysis and management facilities and some technical and commercial features are comparatively indicated.

[Erythrocyte aggregation and its repercussions on conjunctival microcirculation in man. Morphometric study and biological correlates]. / L'agrégation érythrocytaire et son retentissement sur la microcirculation conjonctivale chez l'homme. Etude morphométrique et corrélations biologiques.

This study, involving the application of morphometric techniques to the conjunctival capillary bed in man, revealed a rarefaction of functional capillary density in patients with arteriolar sludge. Overall, in the population sample studied, capillary density and the degree of erythrocyte aggregation were correlated to erythrocyte sedimentation rate, despite the existence of discordant cases. These discordances were partially reduced by taking the hematocrit into account. Furthermore, multifactorial analysis of these parameters showed that hematocrit had an inhibitory action on erythrocyte aggregation which was more marked in vitro than in the microcirculation in vivo. By contrast, in vivo aggregation was more influenced by serum albumin levels. In both cases fibrinogen appeared to be the most significant pro-aggregant factor.

[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.

[Non-allergic angioedema: update]. / L'angio-oedème non allergique: mise au point.

PURPOSE: Nonallergic isolated angioedema is an uncommon clinical syndrome raising difficult diagnosis and therapeutic problems. Occurrences linked to a C1Inh are the predominant ones and have to be examined as a priority, taking into account the specificity of the associated follow-up. CURRENT KNOWLEDGE AND KEY POINTS: Diseases with a clinical profile close to hereditary angioneurotic edema, but without C1Inh anomaly, have been described recently. It is in fact family cases, concerning only women, where estrogens seem to play a dominant role. Angioedema's secondary aspects are gathering various pathologies (vasculitis, Gleich's syndrome, angioedema initiated by physical agents). The role played by some drugs must not be forgotten, mainly angiotensin converting enzyme inhibitors, which are at the origin of angiodema in nearly 0.5% of users. FUTURE PROSPECT AND PROJECTS: Uncontrolled activation of the contact system seems to play a major role in the main part of these angiodemas. The efficiency of the tranexaminic acid (which modulates its activation) is to be taken as evident. The key to the future seems to be the development of plasmin and bradykinin inhibitors.

[Renal inflammatory pseudotumor manifesting as a prolonged fever]. / Fièvre prolongée révélatrice d'une pseudotumeur inflammatoire rénale.

INTRODUCTION: Inflammatory pseudo-tumors (IPT) are benign neoplasms associated with local or general manifestations. Renal localization seems exceptional, and no case of fever of unknown origin caused by renal inflammatory pseudo-tumors have been reported. EXEGESIS: The authors report the case of a man presenting fever of unknown origin and inflammatory syndrome. Computerized tomography showed a renal mass. Nephrectomy was performed, and renal inflammatory pseudo-tumor was diagnosed. After surgical exeresis, the clinical and biological abnormalities vanished. CONCLUSION: This rare diagnosis must be considered in these situations. The outcome is excellent.

[Chronic meningitis: aetiologies, diagnosis and treatment]. / Méningites chroniques : étiologies, diagnostic et thérapeutique.

PURPOSE: Chronic meningitis are very uncommon and account for less than 10% of all meningitis cases. Their symptoms are uncunth and there outcome is insidious. Therefore, they remain often unknown. There are only a few published reports on this disease, so diagnosis and therapeutic approachs are difficult. CURRENT KNOWLEDGE AND KEY POINTS: Positive chronic meningitis diagnosis is easy. However, determining the cause of chronic meningitis remains dilemma, as many infectious and noninfectious processes (including inflammatory, neoplastic or autoimmune aetiologies or as a result of a chemical exposure) can result in the chronic meningitis syndrome. In order to institute a pertinent treatment, sometimes urgently needed, diagnostic approach must be extremely rigourous and accutely orientated. Nevertheless, although extensive investigations, 30% of the aetiologies remain undetermined. Only two choices are left for the medical physician: an aggressive attitude based on complementary investigations or a contemplated therapy with a close clinical and biological control. On the other hand, when the patient's condition is quickly deterioring without a clear and proved aetiology, it is sometimes necessary to institute an empirical treatment, not always properly determined and sometimes contreversial. Besides, few reports on prognosis and outcome od idiopathic chronic meningitis have been published. FUTURE PROSPECTS AND PROJECTS: After a review of aetiologies and diagnostic investigations chronic meningitis, we propose a practical experience attitude about management and treatment of chronic meningitis. Thus, large-scale studies about the follow up chronic meningitis in long term, in particular those without aetiology, treated or no, should improve the outcome of this chronic syndrome.

[Diagnostic delay in Horton's disease. Analysis of the diagnostic delay based on a retrospective study of 130 cases]. / Le retard diagnostique dans la maladie de Horton. Analyse du délai diagnostique à partir d'une étude rétrospective de 130 cas.

Temporal arteritis (Horton's disease) is a multifocal granulomatous arteritis which affects elderly people. Its prognosis depends upon the risk of blindness. In a retrospective study of 130 patients we paid special attention to the delay in diagnosis and its relation to the occurrence of ophthalmic complications. In 73 patients (56.2%), this delay exceeded 3 months and reached more than one year in 22 of them. It was not influenced by age or sex. In requests for admission, the diagnosis of temporal arteritis was suggested in only 28 of the 130 cases; 17.7% of the patients were blind. There was a significant increase in the occurrence of ophthalmic lesions when the diagnosis was delayed by 2 to 6 months. In 6 cases, blindness had been preceded by transient amaurosis. These findings confirm that temporal arteritis is belatedly diagnosed by practitioners and that blindness could be avoided by an earlier diagnosis.

[Clinical study of 105 cases of isolated weight loss in internal medicine]. / Etude clinique de 105 cas d'amaigrissements isolés en médecine interne.

We arbitrarily define "isolated weight loss" as the loss of at least 10 p. 100 of body weight over less than one year, without any single cause being disclosed by questioning, physical examination and such paraclinical examinations as blood electrolytes, blood count and differential, routine dipstick urinalysis and X-ray of the chest. Among the 105 patients we studied, the causes of isolated weight loss were: (1) psychic disorders (chiefly depression) in 60 p. 100 of the cases; (2) a variety of organic diseases in 29 p. 100, including gastrointestinal diseases (8 p. 100), cardiovascular and respiratory diseases (6 p. 100), Horton's disease (4 p. 100), Portuguese amyloidosis (1 p. 100), unexplained inflammatory syndrome (1 p. 100), endocrine disease (hyperthyroidism, 4 p. 100) and intoxication with medicines, alcohol or heroin (5 p. 100); (3) no definite cause could be found in 11 p. 100 of the cases. We suggest a diagnostic approach involving a limited number of examinations, viz.: erythrocyte sedimentation rate, measurement of transaminases, gamma GT and alkaline phosphatase enzymes, abdominal ultrasonography and ultra-sensitive TSH assay. We consider it important to switch from useless paraclinical tests to the detection and management of psychic disorders. Weight loss is a frequent motive of consultation, but its diagnostic value is often misunderstood. The purpose of this study was to provide data for the artiological diagnosis of isolated weight loss--a relatively frequent problem in internal medicine.

[Systemic mastocytosis: incidence and risks of vasomotor seizures]. / Mastocytose systémique: fréquence et risques des crises vasomotrices.

We report on 9 cases of systemic mastocytosis which underline the frequency and the potential severity of this disease. All patients had intercritical signs (usually urticaria). Seven patients had also typical crises with flush and vascular collapses are observed together, doctors should measure histamine blood level and perform correct biopsy.