The impact of physical functions on depressive symptoms in people with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease that affects the central nervous system. The impact of MS transcends physical functions and extends to psychological impairment. Approximately 50% of people with MS develop depressive symptoms during their lifetime and depressive symptoms may predict impairment of physical functions. However, prediction of depressive symptoms based on objective measures of physical functions is still necessary. OBJECTIVE: To compare physical functions between people with MS presenting depressive symptoms or not and to identify predictors of depressive symptoms using objective measures of physical functions. METHODS: Cross-sectional study including 26 people with MS. Anxiety and/or depressive symptoms were assessed by the Beck Depression Inventory-II (BDI-II) and by the Hospital Anxiety and Depression Scale (HADS). Outcomes of physical functions included: the Nnnine-hole Ppeg Ttest (NHPT), knee muscle strength, balance control, the Timed Up and Go Test (TUG), and the 6-minute walk test (6MWT). Perceived exertion was measured using the Borg scale. RESULTS: The frequency of depressive symptoms was 42% in people with MS. Balance control during a more challenging task was impaired in people with MS who presented depressive symptoms. Balance could explain 21-24% of the variance in depressive symptoms. 6MWT and TUG presented a trend of significance explaining 16% of the variance in the BDI-II score. CONCLUSIONS: Impairment in physical functions consists in a potential predictor of depressive symptoms in people with MS. Exercise interventions aiming at the improvement of physical functions, together with the treatment of depressive symptoms and conventional medical treatment, are suggested.

Clinical and MRI correlates of CSF neurofilament light chain levels in relapsing and progressive MS.

BACKGOUND: A major aim in MS field has been the search for biomarkers that enable accurate detection of neuronal damage. Besides MRI, recent studies have shown that neuroaxonal damage can also be tracked by neurofilament detection. Nevertheless, before widespread implementation, a better understanding of the principal contributors for this biomarker is of paramount importance. Therefore, we analyzed neurofilament light chain (NfL) in relapsing (RMS) and progressive MS (PMS), addressing which MRI and clinical variables are better related to this biomarker. METHODS: Forty-seven MS patients underwent MRI (3T) and cerebrospinal fluid (CSF) sampling. We measured NfL concentrations using ELISA (UmanDiagnostics) and performed multivariable regression analysis to assess the contribution of clinical and MRI metrics to NfL. RESULTS: NfL correlated with previous clinical activity in RMS (p < 0.001). In RMS, NfL also correlated with Gad+ and cortical lesion volumes. However, after multivariable analysis, only cortical lesions and relapses in previous 12 months remained in the final model (R2 = 0.610; p = 0.009 and p = 0.00008, respectively). In PMS, T1-hypointense lesion volume was the only predictor after multivariate analysis (R2 = 0.564; p = 0.012). CONCLUSIONS: CSF NfL levels are increased in RMS and associated with relapses and cortical lesions. Although NfL levels were correlated with Gad+ lesion volume, this association did not persist in multivariable analysis after controlling for previous clinical activity. We encourage controlling for previous clinical activity when testing the association of NfL with MRI. In PMS, the major contributor to NfL was T1-hypointense lesion volume.

A spring to summer shift of pro-inflammatory cytokine production in multiple sclerosis patients.

Higher MS relapse frequency is observed during warmer months in different regions, but evidence for an underlying immunological variation is lacking. Therefore, we investigated seasonal variations of cytokine production in relapsing-remitting MS patients. Twenty-one patients and eight controls had blood samples drawn in each season, evaluating for IL-10, IL-6, TNF-α and IFN-γ. The lowest levels of cytokine production were observed in spring samples, with a significant increase from spring to summer for most cytokines, and especially IFN-γ and TNF-α. This phenomenon may underlie the higher prevalence of clinical and subclinical MS activity observed in warmer months.

The impact of physical functions on depressive symptoms in people with multiple sclerosis / O impacto das funções físicas nos sintomas depressivos em pessoas com esclerose múltipla

ABSTRACT Background: Multiple sclerosis (MS) is an immune-mediated disease that affects the central nervous system. The impact of MS transcends physical functions and extends to psychological impairment. Approximately 50% of people with MS develop depressive symptoms during their lifetime and depressive symptoms may predict impairment of physical functions. However, prediction of depressive symptoms based on objective measures of physical functions is still necessary. Objective: To compare physical functions between people with MS presenting depressive symptoms or not and to identify predictors of depressive symptoms using objective measures of physical functions. Methods: Cross-sectional study including 26 people with MS. Anxiety and/or depressive symptoms were assessed by the Beck Depression Inventory-II (BDI-II) and by the Hospital Anxiety and Depression Scale (HADS). Outcomes of physical functions included: the Nnnine-hole Ppeg Ttest (NHPT), knee muscle strength, balance control, the Timed Up and Go Test (TUG), and the 6-minute walk test (6MWT). Perceived exertion was measured using the Borg scale. Results: The frequency of depressive symptoms was 42% in people with MS. Balance control during a more challenging task was impaired in people with MS who presented depressive symptoms. Balance could explain 21-24% of the variance in depressive symptoms. 6MWT and TUG presented a trend of significance explaining 16% of the variance in the BDI-II score. Conclusions: Impairment in physical functions consists in a potential predictor of depressive symptoms in people with MS. Exercise interventions aiming at the improvement of physical functions, together with the treatment of depressive symptoms and conventional medical treatment, are suggested.

RESUMO Introdução: A esclerose múltipla (EM) é uma doença imunomediada que afeta o sistema nervoso central. O impacto da doença transcende as funções físicas e se estende a comprometimento psicológico. Aproximadamente 50% das pessoas com EM desenvolvem sintomas depressivos e estes podem predizer o comprometimento das funções físicas. No entanto, a previsão de sintomas depressivos com base em medidas objetivas das funções físicas ainda é necessária. Objetivos: Comparar funções físicas entre pessoas com EM que apresentam ou não sintomas depressivos e identificar preditores de sintomas depressivos usando medidas objetivas de funções físicas. Métodos: Estudo transversal incluindo 26 pessoas com EM. A ansiedade e/ou sintomas depressivos foram avaliadas pelo Inventário de Depressão de Beck-II (Beck Depression Inventory - BDI-II) e pela Escala Hospitalar de Ansiedade e Depressão. Os resultados das funções físicas incluíram: teste de PEG de nove buracos, força muscular do joelho, controle de equilíbrio, teste Timed Up and Go (TUG) e teste da caminhada de seis minutos (TC6M). A fadiga percebida foi medida usando a escala de Borg. Resultados: A frequência de sintomas depressivos na amostra foi de 42%. O controle do equilíbrio durante tarefa desafiadora foi prejudicado em pessoas com EM e sintomas depressivos. O equilíbrio pode explicar 21-24% da variação nos sintomas depressivos. O TC6M e o TUG apresentaram tendência de significância que explica 16% da variância no escore do BDI-II. Conclusões: O comprometimento das funções físicas é potencial preditor de sintomas depressivos em pessoas com EM. São sugeridas intervenções de exercícios físicos visando melhora das funções físicas, juntamente com o tratamento médico convencional e dos sintomas depressivos.

Disruption of melatonin circadian rhythm production is related to multiple sclerosis severity: A preliminary study.

Sunlight can influence the immune system independently of vitamin D, such as through melatonin production in the pineal gland. Inflammatory disorders can suppress nocturnal melatonin production, but only a few studies have investigated melatonin status in multiple sclerosis (MS). We aimed to study melatonin production in association with clinical and immunological data in MS patients. Eleven treated relapsing-remitting MS (RRMS) patients and eight controls underwent neurological examination and were assessed for fatigue severity and depressive symptoms. Inflammatory cytokines were analyzed in blood samples and concentration of 6-sulfatoxymelatonin (6-SMT) was determined in 24h urine. Patients with an abnormal proportion of overnight 6-SMT (n=8, 72.7%) had higher disability and fatigue severity (p<0.05). Overnight 6-SMT was inversely related with fatigue severity (p=0.016), number of relapses in the previous 12 months (p=0.010) and EDSS scores (p=0.049). In conclusion, disruption of melatonin circadian rhythm production is frequent among RRMS patients and seemingly related to higher disability and fatigue scores. Future studies with larger sample size are necessary to establish melatonin status as a biomarker of disease severity in MS.

Chloroquine treatment enhances regulatory T cells and reduces the severity of experimental autoimmune encephalomyelitis.

BACKGROUND: The modulation of inflammatory processes is a necessary step, mostly orchestrated by regulatory T (Treg) cells and suppressive Dendritic Cells (DCs), to prevent the development of deleterious responses and autoimmune diseases. Therapies that focused on adoptive transfer of Treg cells or their expansion in vivo achieved great success in controlling inflammation in several experimental models. Chloroquine (CQ), an anti-malarial drug, was shown to reduce inflammation, although the mechanisms are still obscure. In this context, we aimed to access whether chloroquine treatment alters the frequency of Treg cells and DCs in normal mice. In addition, the effects of the prophylactic and therapeutic treatment with CQ on Experimental Autoimmune Encephalomyelitis (EAE), an experimental model for human Multiple Sclerosis, was investigated as well. METHODOLOGY/PRINCIPAL FINDINGS: EAE was induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein (MOG35-55) peptide. C57BL/6 mice were intraperitoneally treated with chloroquine. Results show that the CQ treatment provoked an increase in Treg cells frequency as well as a decrease in DCs. We next evaluated whether prophylactic CQ administration is capable of reducing the clinical and histopathological signs of EAE. Our results demonstrated that CQ-treated mice developed mild EAE compared to controls that was associated with lower infiltration of inflammatory cells in the central nervous system CNS) and increased frequency of Treg cells. Also, proliferation of MOG35-55-reactive T cells was significantly inhibited by chloroquine treatment. Similar results were observed when chloroquine was administrated after disease onset. CONCLUSION: We show for the first time that CQ treatment promotes the expansion of Treg cells, corroborating previous reports indicating that chloroquine has immunomodulatory properties. Our results also show that CQ treatment suppress the inflammation in the CNS of EAE-inflicted mice, both in prophylactic and therapeutic approaches. We hypothesized that the increased number of regulatory T cells induced by the CQ treatment is involved in the reduction of the clinical signs of EAE.