Cognition, mood and fatigue in patients in the early stage of multiple sclerosis.

QUESTION UNDER STUDY: Cognitive impairment occurs during multiple sclerosis (MS) and contributes to the burden of the disease, but its effect in the initial phase of MS still needs to be better understood. METHODS: We prospectively studied 127 early MS patients presenting with a clinically isolated syndrome (CIS) or definite MS, a mean disease duration of 2.6 years, and with minor disability (mean Expanded Disability Status Scale score 1.8). Patients were tested for long-term memory, executive functions, attention, fatigue, mood disorders, functional handicap and quality of life (QoL). Twenty-one CIS patients were excluded from study as the diagnosis of MS could not be confirmed. RESULTS: Over the 106 MS patients analysed, 31 (29.3%) were cognitively impaired (23.6% for memory, 10.4% for attention and 5.7% for executive functions). Cognitive deficits were already present in CIS patients in whom the diagnosis was not yet confirmed (20%). Impaired cognition was associated with anxiety (p = 0.05), depression(p = 0.004), fatigue (p = 0.03), handicap (p <0.001) and a lower QoL (p <0.001). After adjustment for QoL, handicap, depression, anxiety and fatigue were no longer associated with the presence of cognitive deficits. CONCLUSIONS: In this well-defined early MS group one third of the patients already exhibited cognitive deficits, which were usually apparent in an effortful learning situation and were generally mild. Mood disorders, fatigue, handicap and decreased QoL were all associated with the occurrence of cognitive deficits. QoL itself appeared to take all the other factors into account. Our results confirm the existence of an interplay between cognitive, affective and functional changes and fatigue in early MS.

Multicontrast connectometry: A new tool to assess cerebellum alterations in early relapsing-remitting multiple sclerosis.

BACKGROUND: Cerebellar pathology occurs in late multiple sclerosis (MS) but little is known about cerebellar changes during early disease stages. In this study, we propose a new multicontrast "connectometry" approach to assess the structural and functional integrity of cerebellar networks and connectivity in early MS. METHODS: We used diffusion spectrum and resting-state functional MRI (rs-fMRI) to establish the structural and functional cerebellar connectomes in 28 early relapsing-remitting MS patients and 16 healthy controls (HC). We performed multicontrast "connectometry" by quantifying multiple MRI parameters along the structural tracts (generalized fractional anisotropy-GFA, T1/T2 relaxation times and magnetization transfer ratio) and functional connectivity measures. Subsequently, we assessed multivariate differences in local connections and network properties between MS and HC subjects; finally, we correlated detected alterations with lesion load, disease duration, and clinical scores. RESULTS: In MS patients, a subset of structural connections showed quantitative MRI changes suggesting loss of axonal microstructure and integrity (increased T1 and decreased GFA, P < 0.05). These alterations highly correlated with motor, memory and attention in patients, but were independent of cerebellar lesion load and disease duration. Neither network organization nor rs-fMRI abnormalities were observed at this early stage. CONCLUSION: Multicontrast cerebellar connectometry revealed subtle cerebellar alterations in MS patients, which were independent of conventional disease markers and highly correlated with patient function. Future work should assess the prognostic value of the observed damage. Hum Brain Mapp 36:1609-1619, 2015. © 2014 Wiley Periodicals, Inc.

Quality of life in multiple sclerosis: translation in French Canadian of the MSQoL-54

Affiliation: Louise Lafortune: Faculté de médecine, Université de Montréal

Interleukin-15 in the pathogenesis of multiple sclerosis and its animal models

L'interleukine-15 (IL-15) contribue au développement et à l’activation des lymphocytes T CD8, des cellules immunes qui ont été impliquées dans plusieurs maladies auto-immunes telle la sclérose en plaques. Des niveaux élevés de l'IL-15 ont été trouvés chez les patients atteints de cette maladie comparativement aux témoins, mais aucune étude n'a examiné les effets de tels niveaux élevés sur les lymphocytes T CD8. Les objectifs de notre étude étaient 1- de caractériser l’expression de l'IL-15 par des lymphocytes B humains et de déterminer ses effets sur les fonctions des lymphocytes T CD8, et 2- d’évaluer l'expression in vivo de l'IL-15 dans des modèles murins de la sclérose en plaques. Nous avons établi que les cellules B humaines augmentaient leur expression de l'IL-15 suite à une stimulation via le CD40. De plus, les fonctions effectrices des lymphocytes T CD8 ont été significativement augmentées lors des co-cultures avec des cellules B alloréactives exprimant l'IL-15. Dans les modèles murins de la sclérose en plaques, nous avons détecté au sein du système nerveux central des cellules immunes exprimant l’IL-15 ainsi que des cellules T CD8 exprimant le récepteur pour cette cytokine à différents stades de la maladie. Nous avons démontré que les cellules B modulent des réponses des lymphocytes T CD8 via l’IL-15, ce qui suggère un rôle pour les cellules B dans la pathogenèse de la sclérose en plaques. Nous avons aussi mis en évidence la présence de cellules exprimant l’IL-15 dans le système nerveux central dans des modèles murins de cette maladie.

Executive function and memory in patients with relapsing-remitting multiple sclerosis. 'Funci??n ejecutiva y memoria en pacientes con esclerosis m??ltiple recurrente-remitente'

Resumen tomado de la publicaci??n

Mnesic performance and executive functions in patients with multiple sclerosis (MS)

The Episodic Memory (EM) and the Executive Functions (EF) are cognitive areas that are affected in patients with diagnosis of Multiple Sclerosis (MS). Nowadays there exists scarce works destined to explore the infl uence of the EF on measures of mnesic performance in MS. For this reason, we analyze the effect of the EF on the performance in a set of memory measures. We worked with a clinical group (n=36) and with a control group (n=36) compared by age and educational level. The results show that the clinical group obtained significantly low average values in all the mnesic indexes (with exception of recognition) and in all the executive measures. All the executive indexes showed significant associations with some of the indexes of mnesic performance. These findings suggest that the problems in the episodic memory in EM patients could be analyzed as the manifestation of a global disorder that could be similar to the one that involves the EF. 

Multiple sclerosis: evidence and controversies

Introduction: Multiple sclerosis is a chronic recurrent inflammatory disorder of the central nervous system. The pharmacological treatment of multiple sclerosis has been evaluated with multiple controlled clinical trials that allow the clinician to count with evidence based information to decide the more indicated treatment for each patient. Methodology: A review of the scientific literature was conducted to clarify controversial issues in a clinical relevant topic. Development: The diagnostic criteria and different treatments available are reviewed, in order to consider the clinical utility of the disease modifying agents such as the immunomodulatory treatments. The three used types of interferon are well tolerated and reduce in approximately a third the number of bouts in the remitent recurrent form; there is no significant difference between the three of them.

Emotion recognition in multiple sclerosis

The effect of multiple sclerosis (MS) on the ability to identify emotional expressions in faces was investigated, and possible associations with patients’ characteristics were explored. 56 non-demented MS patients and 56 healthy subjects (HS) with similar demographic characteristics performed an emotion recognition task (ERT), the Benton Facial Recognition Test (BFRT), and answered the Hospital Anxiety and Depression Scale (HADS). Additionally, MS patients underwent a neurological examination and a comprehensive neuropsychological evaluation. The ERT consisted of 42 pictures of faces (depicting anger, disgust, fear, happiness, sadness, surprise and neutral expressions) from the NimStim set. An iViewX high-speed eye tracker was used to record eye movements during ERT. The fixation times were calculated for two regions of interest (i.e., eyes and rest of the face). No significant differences were found between MS and HC on ERT’s behavioral and oculomotor measures. Bivariate and multiple regression analyses revealed significant associations between ERT’s behavioral performance and demographic, clinical, psychopathological, and cognitive measures.

Refinement of the Clinical Scenario Evaluation Framework for Assessment of Competing Development Strategies with an Application to Multiple Sclerosis

When competing strategies for development programs, clinical trial designs, or data analysis methods exist, the alternatives need to be evaluated in a systematic way to facilitate informed decision making. Here we describe a refinement of the recently proposed clinical scenario evaluation framework for the assessment of competing strategies. The refinement is achieved by subdividing key elements previously proposed into new categories, distinguishing between quantities that can be estimated from preexisting data and those that cannot and between aspects under the control of the decision maker from those that are determined by external constraints. The refined framework is illustrated by an application to a design project for an adaptive seamless design for a clinical trial in progressive multiple sclerosis.

Iron and zinc status in multiple sclerosis patients with pressure sores

Measurements of weighted dietary intakes and plasma determinations of albumin, iron, zinc, ascorbic acid and TIBC were carried out on twenty female multiple sclerosis patients in a long-stay hospital for disabled people. The group included ten patients with a recent history of pressure sores, closely matched with ten patients without pressure sores. Mean daily intake of carbohydrate was found to be higher in the non-pressure sore group whilst intake of zinc was lower in this group. Intakes of all other nutrients were comparable between the two groups. For both groups, intakes of energy, folate, vitamin D, iron and zinc were less than recommended values. Mean plasma levels of albumin and iron were towards the lower limit of the normal range, whilst that for zinc was considerably less than the normal range. Plasma TIBC was slightly above the normal range. Levels of plasma iron and zinc were significantly lower in the pressure sore group. The data indicate that severely disabled hospitalized patients with multiple sclerosis may be at risk of poor nutritional status. The results suggest that in the presence of pressure sores, there are increased requirements for specific nutrients, notably zinc and iron. Consideration is given to the possible value of supplementation of these individuals.

Quality of life and multiple sclerosis: comparison between people with multiple sclerosis and people from the general population

This paper evaluated the quality of life (QOL) of people with multiple sclerosis (MS) and people from the general population. Gender differences between the 2 groups of respondents and the influence of coping style on adjustment were also evaluated. The participants were 381 (144 males, 237 females) people with MS, and 291 (101 males, 190 females) people from the general population. The results demonstrated that people with MS experienced lower levels of QOL than people from the general population for both the objective and subjective dimensions of all domains (physical health, psychological adjustment, social relationships, environmental adjustment). All coping strategies (problem-focused, focusing on the positive, detachment, wishful thinking, seeking social support) were important predictors of QOL for both males and females with MS, with wishful thinking being the strongest predictor of poor QOL. These results are discussed in terms of the various factors that impact on QOL among people with MS, and the types of coping strategies that are most adaptive in improving the QOL of people with this illness.