Investigating the potential link between lunar cycle and multiple sclerosis relapses: a call for further studies.

Multiple sclerosis (MS) is a debilitating disease that causes inflammation of the central nervous system, resulting in myelin damage and axon degeneration. Although the cause of MS remains unknown, various factors such as sex, latitude, sun exposure, serum vitamin D levels, Epstein Barr Virus infection, diet, microbiota and ethnicity are being studied for their potential roles in the development of the disease. While chronobiological factors such as circadian rhythm and seasonality have been explored for their potential influence on the onset, exacerbation, and/or relapses of MS, the potential influence of the lunar cycle on MS has yet to be studied. Therefore, the authors of this letter call for future studies to investigate the possible effects of the lunar cycle on MS activity and course, given evidence suggesting that the lunar cycle may affect sleep, fatigue, melatonin secretion, and mood state in humans. A deeper understanding of the chronobiology of MS could have practical implications for the development of chronotherapeutic strategies and the prevention or mitigation of MS relapses, potentially improving the quality of life of MS patients.

A case-control study of drinking beverages and the risk of multiple sclerosis in Iran.

BACKGROUND: There is no study in the world on the relationship between consuming black and green tea as beverages containing polyphenols and the risk of MS. This study aimed to determine the association between the consumption of green and black tea, coffee, non-alcoholic beer, milk, fruit juices and carbonated beverages with the risk of MS. METHODS AND MATERIALS: This case-control study was performed on 150 patients with MS and 300 healthy individuals as a control group among patients who were referred to the ophthalmology ward of a referral hospital in Ahvaz with the groups matching for age. The data collection tool was a researcher-made questionnaire including demographic information and beverage consumption. Analysis was performed using univariate and multiple logistic regression models. RESULTS: The mean age of patients at the time of diagnosis was 38.55 ± 8.88 years. The results showed that drinking milk (OR = 5.46), natural juice (OR = 2.49), and carbonated beverages (OR = 16.17) were associated with an increased chance of developing MS. However, drinking non-alcoholic beer (OR = 0.48), black tea (OR = 0.20), green tea (OR = 0.29) and coffee (OR = 0.07) were associated with a reduced chance of developing MS. CONCLUSION: The results show that drinking black and green tea, non-alcoholic beer, and coffee are associated with a decrease in the chance of developing MS. The results of this study can be used to design interventional research and to change people's lifestyles to prevent MS.

Effectiveness of acupuncture for fatigue in patients with relapsing-remitting multiple sclerosis: a randomized controlled trial.

BACKGROUND: Fatigue is experienced by more than 65% of individuals with multiple sclerosis (MS). Some studies have supported the effectiveness of acupuncture in improving the symptoms of MS. OBJECTIVE: The present research was intended to investigate the effectiveness of acupuncture plus amantadine compared with amantadine alone on fatigue in patients with relapsing-remitting MS (RRMS) in the remission stage of the disease. METHODS: In this randomized controlled trial, 60 participants with RRMS suffering from fatigue were recruited and randomized equally to acupuncture (n = 30) and control (n = 30) groups. The acupuncture group received treatment 2 to 3 times per week for 10 sessions over 4 weeks. Both the acupuncture and control groups received amantadine 100 mg daily and routine treatment with immuno-modulators. The primary outcome was the fatigue severity scale (FSS) score, which was evaluated at baseline, and after 2 and 4 weeks. The secondary outcome was the Multiple Sclerosis Quality of Life 54 (MSQOL-54) questionnaire score, measured at baseline and the end of the 4-week treatment period. RESULTS: The severity of fatigue was reduced in both groups. However, after 4 weeks of treatment, the reduction of fatigue in the acupuncture group was more significant than in the control group (P < 0.01, mean difference (MD) = -1.14, 95% confidence interval (CI): -1.83 to -0.45). Quality of life, including mental and physical status, was significantly improved in the acupuncture group compared with the control group (P < 0.05, MD = 9.09, 95% CI: 0.46 to 17.73). No adverse events occurred in any of the participants. CONCLUSIONS: Acupuncture combined with amantadine and routine care compared with amantadine and routine care alone appears to be an effective short-term treatment for reducing fatigue and enhancing quality of life, including physical function and mental status, in patients with RRMS.

Waterpipe Tobacco Smoking and Other Multiple Sclerosis Environmental Risk Factors.

INTRODUCTION: There are a number of well-established risk factors for multiple sclerosis (MS). Other factors, however, showed conflicting or inconsistent results. Here, we examine some factors that are unique to or more practiced in Saudi Arabia (SA) and the Arab region such as waterpipe tobacco smoking (WTS), face veiling, raw milk (RM) and camel milk (CM) consumption, and tuberculosis (TB) infection in addition to other traditional factors. METHODS: This is a sex- and age-matched case-control study in which we used a structured questionnaire to examine the relation between a number of factors and exposures and the risk of MS. Three hundred MS patients and 601 controls were included. Data were analyzed across different statistical models using logistic regression adjusting for age, sex, marital status, duration of breastfeeding, age first joining school, coffee consumption, and face exposure. RESULTS: Cigarette smoking (OR = 1.79, [95% CI: 1.01-3.17], p = 0.047), WTS (OR = 2.25, [95% CI: 1.21-4.15], p = 0.010), and CM consumption (OR = 2.50, [95% CI: 1.20-5.21], p = 0.014) increased the risk of MS, while performing hajj (OR = 0.47, [95% CI: 0.34-0.67], p = 0.001), TB infection (OR = 0.29, [95% CI: 0.11-0.78], p = 0.015), face veiling (OR = 0.32, [95% CI: 0.23-0.47], p = 0.001), and coffee consumption (OR = 0.67, [95% CI: 0.49-0.89], p = 0.008) appeared to be associated with decreased risk. No association was found between fast food, processed meat, soft drinks, animal milk (other than camel), or RM consumption and the risk of MS. CONCLUSION: The results of this case-control study confirm that different means of tobacco smoking are associated with increased risk of MS. It also sheds more light on the complex association between infections and MS.

Vitamin D/CD46 Crosstalk in Human T Cells in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), in which T-cell migration into the CNS is key for pathogenesis. Patients with MS exhibit impaired regulatory T cell populations, and both Foxp3+ Tregs and type I regulatory T cells (Tr1) are dysfunctional. MS is a multifactorial disease and vitamin D deficiency is associated with disease. Herein, we examined the impact of 1,25(OH)2D3 on CD4+ T cells coactivated by either CD28 to induce polyclonal activation or by the complement regulator CD46 to promote Tr1 differentiation. Addition of 1,25(OH)2D3 led to a differential expression of adhesion molecules on CD28- and CD46-costimulated T cells isolated from both healthy donors or from patients with MS. 1,25(OH)2D3 favored Tr1 motility though a Vitamin D-CD46 crosstalk highlighted by increased VDR expression as well as increased CYP24A1 and miR-9 in CD46-costimulated T cells. Furthermore, analysis of CD46 expression on T cells from a cohort of patients with MS supplemented by vitamin D showed a negative correlation with the levels of circulating vitamin D. Moreover, t-Distributed Stochastic Neighbor Embedding (t-SNE) analysis allowed the visualization and identification of clusters increased by vitamin D supplementation, but not by placebo, that exhibited similar adhesion phenotype to what was observed in vitro. Overall, our data show a crosstalk between vitamin D and CD46 that allows a preferential effect of Vitamin D on Tr1 cells, providing novel key insights into the role of an important modifiable environmental factor in MS.

Dietary influence on central nervous system myelin production, injury, and regeneration.

Oligodendrocytes not only produce myelin to facilitate nerve impulse conduction, but are also essential metabolic partners of the axon. Oligodendrocyte loss and myelin destruction, as occurs in multiple sclerosis (MS), leaves axons vulnerable to degeneration and permanent neurological deficits ensue. Many studies now propose that lifestyle factors such as diet may impact demyelinating conditions, including MS. Most prior reviews have focused on the regulatory role of diet in the inflammatory events that drive MS pathogenesis, however the potential for dietary factors to modulate oligodendrocyte biology, myelin injury and myelin regeneration remain poorly understood. Here we review the current evidence from clinical and animal model studies regarding the impact of diet or dietary factors on myelin integrity and other pathogenic features of MS. Some limited evidence exists that certain foods may decrease risk or influence the progression of MS, such as increased intake of fish or polyunsaturated fatty acids, caloric restriction and fasting-mimicking diets. In addition, evidence suggests adolescent obesity or insufficient vitamin D levels increase the risk for developing MS. However, no clear or consistent evidence exists that dietary components exacerbate disease progression. Cumulatively, current evidence highlights the need for more extensive clinical trials to validate dietary effects on MS and to identify diets or supplements that may be beneficial as food-based strategies in the management of MS alone or in combination with conventional disease modifying therapies.

Nutrition in Multiple Sclerosis: An integrative review of scientific publications from the last 5 years / Nutrición en la Esclerosis Múltiple: Revisión integrativa de las publicaciones científicas en los últimos 5 años

ABSTRACT This study analyzed the profile of scientific production related to the nutritional aspects of the etiology and/or progress of Multiple Sclerosis (MS). We conducted an integrative review that analyzed 64 works published in English, Spanish or Portuguese between 2012 and 2017 on the relationship between nutrition and MS. There was a predominance of studies in humans (54.0%, n= 34) and randomized clinical trials (38.3%, n= 13). The association between vitamin D and etiology progression and/or development of disabilities resulting from MS was the most studied aspect (30.2%, n= 19), followed by studies that evaluated the importance of fat concentration and/or types for MS risk (22.2%, n= 14), and research that analyzed the role of antioxidant vitamins (19.0%; n= 12) in the disease development and/ or evolution. The study showed that most research involves small samples and that a healthy diet contributes to the prevention and mitigation of disease evolution. However, this affirmation cannot be made with regards to dietary supplements. Further research is necessary, from cross-sectional studies to randomized clinical trials considering the wide knowledge gap on this subject.

RESUMEN El presente estudio buscó plantear el perfil de las producciones científicas que relacionan aspectos nutricionales con la etiología y/o progresión de la Esclerosis Múltiple (EM). Fue una revisión integrativa que analizó 63 trabajos publicados en el idioma inglés, español y portugués, entre 2012 a 2017, sobre la relación entre los aspectos nutricionales y la EM. Predominaron estudios con seres humanos (54,0%, n= 34), del tipo ensayo clínico randomizado (38,3%, n= 13). La asociación de la vitamina D con la etiología, progresión y/o desarrollo de incapacidades consecuentes de la EM fue la más estudiada (30,2%, n= 19), seguida de los estudios que evaluaron la importancia de la concentración y/o de los tipos de gordura para el riesgo o progresión de la EM (22,2%, n= 14), y de estudios que analizaron el papel de las vitaminas antioxidantes (19,0%; n= 12) en el desencadenamiento y/o evolución de la enfermedad. La mayoría de los estudios incluyó muestras pequeñas y una dieta saludable que aporta con la prevención y atenuación de la evolución de la enfermedad. No se pueó hacer esta afirmación para los suplementos dietéticos. Son necesarios más estudios, dada la enorme laguna de conocimiento que envuelve el tema.

Short-term changes in frequencies of circulating leukocytes associated with narrowband UVB phototherapy in people with clinically isolated syndrome.

Clinically isolated syndrome (CIS) is the earliest clinical episode in multiple sclerosis (MS). Low environmental exposure to UV radiation is implicated in risk of developing MS, and therefore, narrowband UVB phototherapy might delay progression to MS in people with CIS. Twenty individuals with CIS were recruited, and half were randomised to receive 24 sessions of narrowband UVB phototherapy over a period of 8 weeks. Here, the effects of narrowband UVB phototherapy on the frequencies of circulating immune cells and immunoglobulin levels after phototherapy are reported. Peripheral blood samples for all participants were collected at baseline, and 1, 2, 3, 6 and 12 months after enrolment. An extensive panel of leukocyte populations, including subsets of T cells, B cells, monocytes, dendritic cells, and natural killer cells were examined in phototherapy-treated and control participants, and immunoglobulin levels measured in serum. There were significant short-term increases in the frequency of naïve B cells, intermediate monocytes, and fraction III FoxP3+ T regulatory cells, and decreases in switched memory B cells and classical monocytes in phototherapy-treated individuals. Since B cells are increasingly targeted by MS therapies, the effects of narrowband UVB phototherapy in people with MS should be investigated further.

Ketogenic diets attenuate cyclooxygenase and lipoxygenase gene expression in multiple sclerosis.

BACKGROUND: Adapted ketogenic diet (AKD) and caloric restriction (CR) have been suggested as alternative therapeutic strategies for inflammatory, hyperproliferative and neurodegenerative diseases. Pro-inflammatory eicosanoids have been implicated in the pathogenesis of multiple sclerosis since they augment vascular permeability and induce leukocyte migration into the brain. We explored the impact of ketogenic diets on gene expression of biosynthetic enzymes for pro- (ALOX5, COX1, COX2) and anti-inflammatory (ALOX15) eicosanoids in patients with relapsing-remitting multiple sclerosis. METHODS: 60 adults were prospectively recruited for this six months randomized controlled trial and the impact of dietary treatment on the Multiple Sclerosis Quality of Life-54 index (ClinicalTrials.gov (NCT01538355) has previously been published. Here we explored 24 patients (8 controls, 5 on CR and 11 on AKD). For statistical analysis we combined the two diet groups to a single pooled treatment group. FINDINGS: Inter-group comparison indicated that expression of the pro-inflammatory ALOX5 in the pooled treatment group was significantly (p < 0.05) reduced when compared with the control group. Moreover, intra-group comparison (same individuals before and after dietary treatment) suggested significantly impaired expression of other pro-inflammatory enzymes, such as COX1 (p < 0.001) and COX2 (p < 0.05). Finally, pretreatment cross-group analysis revealed a significant positive correlation between expression of pro-inflammatory ALOX5 and COX2 and an inverse correlation of ALOX5 and COX1 expression with the MSQoL-54 index. INTERPRETATION: Ketogenic diets can reduce the expression of enzymes involved in the biosynthesis of pro-inflammatory eicosanoids. Pharmacological interference with eicosanoid biosynthesis might constitute a strategy supplementing current therapeutic approaches for MS.

Perspectives of Medieval Persian Medicine on Multiple Sclerosis.

INTRODUCTION: Traditional Persian Medicine (TPM) was the prevailing practice of medicine in the Eurasia region up through the 18th century, a practice of medicine stemming back to Hippocrates and to the 5000 year old civilization of the region. It is a school of medicine which touches on many a delicate points which may seem unimaginable within the realm of modern allopathic medicine. This practice of ancient medicine besides shedding light on various possible theoretical modern day disorders serves as a vast resource for therapeutics. In this paper, we present study of the manuscripts of this ancient medical practice in search of symptom presentations coinciding with presentation of multiple sclerosis (MS). MATERIAL & METHOD: This paper represents a comprehensive search through TPM texts and manuscripts with the intention to seek possible clues on MS from potentially valuable age-old resources. We predominantly focused our search on the works of five eminent physicians of Medieval Persia: Avicenna (980-1037 AD), Haly Abbas (949-982 AD), Rhazes (865-925 AD), Averroes (1126-1198 AD) and Jorjani (1042-1137 AD). RESULTS: In this paper, the authors attempt a theory and conclude with high probability that a conjunction of a series of signs, symptoms found in TPM texts under the terms khadar, isterkha and falej form the symptoms and the disease pattern of modern day MS. This theory draws upon existent similarities in terms of disease pathology, disease patterns and predisposing factors seen between MS and the related morbidities within Persian Medicine. CONCLUSION: We recommend further examinations of such potentially valuable long-standing resources, examining the diagnoses and treatments as set forth by Persian Medicine through international collaboration within the global scientific community.

Review of the novelties from the 32nd ECTRIMS Congress, 2016, presented at the 9th Post-ECTRIMS Meeting (II). / Revision de las novedades del XXXII Congreso ECTRIMS 2016, presentadas en la IX Reunion Post-ECTRIMS (II).

For the ninth year in a row the Post-ECTRIMS Meeting has been held in Madrid (Spain) with the aim of presenting and discussing the hottest issues debated at the ECTRIMS Congress by renowned specialists in multiple sclerosis in our country. One outcome of this scientific activity, endorsed by the Spanish Neurology Society, is this review article, which is published in two parts. This second part reflects the current controversy over the management of multiple sclerosis, especially as regards the progressive forms and their differential diagnosis. The work presents the latest advances in remyelination, where the use of the micropillar technique in laboratory stands out, and in neuroprotection, which is reviewed through a study of the optic nerve. Anti-CD20 antibodies are a very promising development and we find ourselves before a new mechanism of action and therapeutic target in cells to which little attention has been paid to date. Another notable fact is the high correlation between the levels of neurofilaments in cerebrospinal fluid and in serum, which could make it possible to avoid the use of cerebrospinal fluid as a biological sample in future studies of biomarkers. The review also provides a preview of the advances in clinical research, which will converge in clinical practice in the future, thereby conditioning the steps that should be taken in the therapeutic management of multiple sclerosis.

TITLE: Revision de las novedades del XXXII Congreso ECTRIMS 2016, presentadas en la IX Reunion Post-ECTRIMS (II).Por noveno año consecutivo se ha celebrado en Madrid (España) la Reunion Post-ECTRIMS con el objetivo de presentar y discutir los temas mas debatidos en el congreso ECTRIMS de la mano de reconocidos especialistas en esclerosis multiple de nuestro pais. Fruto de esta reunion cientifica, avalada por la Sociedad Española de Neurologia, se genera este articulo de revision que sale publicado en dos partes. En esta segunda parte se pone de manifiesto la controversia actual en el manejo de la esclerosis multiple, especialmente en cuanto a formas progresivas y diagnostico diferencial se refiere. Se presentan los ultimos avances en remielinizacion, donde destaca el uso de la tecnica con micropilares en el laboratorio, y en neuroproteccion, la cual se revisa a traves del estudio del nervio optico. Los anticuerpos anti-CD20 ofrecen grandes expectativas, y estamos ante un nuevo mecanismo de accion y diana terapeutica en unas celulas a las que les habiamos prestado poca atencion hasta la fecha. Otro hecho destacable es la elevada correlacion entre los niveles de neurofilamentos en el liquido cefalorraquideo y el suero, que podria evitar el uso del liquido cefalorraquideo como muestra biologica en futuros estudios de biomarcadores. Tambien se anticipan los avances en investigacion clinica que en el futuro acabaran convergiendo en la practica clinica, condicionando los pasos que se deberan seguir en el abordaje terapeutico de la esclerosis multiple.

A systematic review of the effects of modifiable risk factor interventions on the progression of multiple sclerosis.

BACKGROUND: Several risk factors are associated with multiple sclerosis (MS) progression and may be amenable to intervention. OBJECTIVE: To systematically review the evidence for interventions targeting risk factors for MS progression. METHODS: We searched six databases and existing reviews till March 2015 and consulted with experts to identify randomized controlled trials (RCTs) of interventions targeting MS risk factors (PROSPERO 2015:CRD42015016461). RESULTS: In total, 37 RCTs met inclusion criteria. Expanded Disability Status Scale (EDSS) scores after exercise interventions did not differ compared with untreated controls (standardized mean differences (SMDs): 0.02; confidence interval (CI): -0.40, 0.44; I2: 0%; seven RCTs; very low quality of evidence (QoE)). Dietary interventions did not show a statistically significant effect on the relative risk (RR) of progression (RR: 0.86; CI: 0.67, 1.05; I2: 0%; four RCTs; moderate QoE) compared to placebo. EDSS scores after vitamin D supplementation were not significantly different from placebo (SMD: -0.15; CI: -0.33, 0.02; I2: 0%; five RCTs; very low QoE). CONCLUSION: We did not identify any risk factor interventions with significant effects on MS progression, but the overall QoE was limited. More adequately powered trials are needed on vitamin D supplementation, long-term exercise, and smoking cessation.

Vitamin D deficiency and its role in neurological conditions: A review.

This review exposes recent advances on the role of vitamin D, cholecalciferol, a secosteroid, in the central nervous system. In humans, vitamin D arises from cutaneous transformation of 7-dehydrocholesterol under the effect of UVB exposure or from food intake. Vitamin D has an immunomodulatory role through its anti-inflammatory and anti-autoimmune actions. In the nervous system, vitamin D is involved in the regulation of calcium-mediated neuronal excitotoxicity, in the reduction of oxidative stress, and in the induction of synaptic structural proteins, neurotrophic factors and deficient neurotransmitters. Reduced exposure to sunlight and low food intake can lead to vitamin D deficiency. Increasing evidence highlights the impact of vitamin D deficiency as a favoring factor in various central or peripheral neurological diseases, especially multiple sclerosis and several neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease. Recently, several clinical trials on vitamin D supplementation stressed the role of vitamin D as a protective and/or prognostic factor in the onset and progress of such neurological conditions.

Increased incidence of multiple sclerosis in systemic sclerosis: A nationwide cohort study.

OBJECTIVE: Previous studies showed inconsistent results on the association of systemic sclerosis (SSc) with multiple sclerosis (MS), and are limited by a lack of adjustment for sex and age. The goals of this retrospective cohort study were to evaluate whether SSc is associated with increased incident MS independent of sex and age. METHODS: We enrolled patients with SSc from Taiwan's Registry of Catastrophic Illness Database and referent subjects from the National Health Insurance Research Database. Each SSc patient was matched to at most three referent subjects by sex, age, month and year of initial diagnosis of SSc. Incidence of MS in SSc patients and corresponding 95% confidence interval (95% CI) were calculated. Cox hazard regression was used to calculate the hazard ratio (HR) of MS. RESULTS: The study enrolled 1171 patients with SSc and 3409 referent subjects. Patients with SSc had higher incidence of MS than referent subjects (9.35 per 1000 person-years, 95% CI=6.86-11.85; 0.13 per 1000 person-years, 95% CI=0.03-0.37, respectively). Similar results also occurred in both men and women. SSc was associated with increased incidence of MS after adjusting for sex and age (HR: 69.48, 95% CI=21.69-222.54). CONCLUSION: SSc is associated with increased incidence of MS, independent of sex and age of the patients. Multidisciplinary teams should guide the assessment, treatment, and holistic care of SSc patients to reduce its morbidity.

Paresthesia: A Review of Its Definition, Etiology and Treatments in View of the Traditional Medicine.

OBJECTIVE: To search major Islamic Traditional Medicine (ITM) textbooks for definition, etiology and medicinal plants used to manage 'khadar' or 'paresthesia', a common sensory symptom of multiple sclerosis (MS) and peripheral neuropathies. In addition, the conformity of the efficacy of ITM-suggested plants with the findings from modern pharmacological research on MS will be discussed. METHODS: Data on the medicinal plants used to treat 'khadar' were obtained from major ITM texts. A detailed search in PubMed, ScienceDirect, Scopus and Google Scholar databases was performed to confirm the effects of ITM-mentioned medicinal plants on MS in view of identified pharmacological actions. RESULTS: Moringa oleifera Lam., Aloe vera (L.) Burm.f., Euphorbia species, Citrullus colocynthis (L.) Schrad., and Costus speciosus (Koen ex. Retz) Sm. are among the most effective ITM plants for the management of 'khadar'. Recent experimental evidence confirms the effectiveness of the mentioned plants in ameliorating MS symptoms. Moreover, according to ITM, prolonged exposure to cold and consuming foodstuff with cold temperament might be involved in the etiopathogenesis of MS. CONCLUSIONS: The use of traditional knowledge can help finding neglected risk factors as well as effective and safe therapeutic approaches, phytomedicines and dietary habits for the management of paresthesia and related disorders such as MS.

Role of socioeconomic position in multiple sclerosis etiology.

Multiple sclerosis (MS) is a debilitating autoimmune disease with a prominent inflammatory component. There have been strides identifying genetic and environmental MS risk factors, though much of the disease risk remains unknown. Recent large observational studies suggest adverse socioeconomic position increases the risk for MS, however the mediating biological processes are not understood. We hypothesize a prominent role for stress response, both the autonomic nervous system and the hypothalamic-pituitary-adrenal axis, which become maladaptive under frequent or chronic stimulation resulting in a proinflammatory phenotype. Thus, adverse SEP and chronic stress may predispose individuals for MS.