Daniel Golan

Melatonin dysregulation, sleep disturbances and fatigue in multiple sclerosis

BACKGROUND Sleep disruption and fatigue are common in Multiple Sclerosis (MS). Melatonin is one of the major regulators of sleep-wake cycle. The role of melatonin in MS-related sleep disturbances and fatigue as well as the interaction between melatonin and Interferon beta (IFN-β) treatment were the subject of this study. OBJECTIVE To assess the influence of IFN-β treatment on melatonin secretion, fatigue and sleep characteristics in patients with MS. METHODS 13 MS patients and 12 healthy controls participated. Fatigue was evaluated using the Fatigue Impact Scale (FIS), sleep was assessed by actigraphy and day/night levels of 6-sulphatoxy-melatonin (6-SMT) in urine were determined using a highly specific ELISA assay. RESULTS Naïve MS patients demonstrated significantly decreased levels of 6-SMT and disrupted circadian regulation of its secretion, which were increased with IFN-β treatment, in association with improved fatigue. Sleep Efficiency was significantly lower in the MS group compared to controls. CONCLUSION Our findings suggest dysregulation of Melatonin secretion in MS, which may be influenced by IFN-β treatment. The results call for further characterization of the role of neuro-hormones such as melatonin in MS, and their cross-regulation with immune-mediators.

Impact of exposure to war stress on exacerbations of multiple sclerosis.

To assess the relation between stress caused by the perils of rocket attack on civilian centers in northern Israel during the 2006 war between Hezbollah and Israel and multiple sclerosis (MS) exacerbations.

The influence of vitamin D supplementation on melatonin status in patients with multiple sclerosis

BACKGROUND Multiple sclerosis (MS) incidence is higher in geographic regions with less sunlight exposure. Both vitamin D and melatonin are essential mediators of the effect of sunlight in health, and as such are candidates to play a key role in MS. We hypothesized that vitamin D and melatonin may have related influences in patients with MS. METHODS In a randomized, double blind study of 40 IFN-β treated MS patients, 21 patients were assigned to 800 IU of vitamin D3 per day (low dose), while 19 patients received 4,370 IU vitamin D3 per day (high dose) for one year. Serum 25-hydroxy-vitamin-D (25-OH-D) and nighttime urine melatonin metabolite, 6-sulphatoxy-melatonin (6-SMT), were measured at baseline, 3 months and 1 year from enrolment. RESULTS After 3 months supplementation, 25-OH-D levels increased and nighttime melatonin secretion decreased significantly in the high dose group, but not in the low dose group. After 1 year, a decrease in 25-OH-D levels, accompanied by an increase of urine nighttime 6-SMT were observed in the high dose group. Percent change in serum 25-OH-D was significantly and negatively correlated with percent change in urine 6-SMT after 3 months and between 3 months to 1 year. 25-OH-D levels by the end of the study were significantly and negatively correlated to BMI. CONCLUSIONS Melatonin secretion is negatively correlated with alterations in serum 25-OH-D in IFN-β treated patients with MS. The finding suggests that melatonin should be considered as a potential mediator of vitamin D neuro-immunomodulatory effects in patients with MS.

Patients with multiple sclerosis in a war zone: coping strategies associated with reduced risk for relapse

The objective of this article is to examine the role of coping strategies in multiple sclerosis outcomes among civilians under a military attack during the 2006 war between Hezbollah and Israel. Participants were 156 patients with relapsing—remitting multiple sclerosis. We analysed the relationships between coping and emotional distress and between coping and multiple sclerosis exacerbation. We also assessed a model of the relationship between perceived stress, event-related stress, and coping with increased risk of multiple sclerosis exacerbations using multivariate logistic regression. Ways of coping and subjective stress were evaluated by means of structured interviews using questionnaires previously validated. The more distressed our respondents were during the war, the more likely they were to employ a variety of ways of coping. Correlation coefficients between coping scores and perceived war stress ranged from 0.2 to 0.44 (p < 0.001—0.01). Correlation coefficients between the various coping scores and broader indices of distress ranged from 0.28 to 0.5 (p < 0.001). Of the remitting patients during and following the war, 47.1% reported the use of ‘direct coping and planning’, compared to 16.7% of patients who relapsed during the same period (p = 0.014). ‘Direct coping and planning’ was negatively related to exacerbation of multiple sclerosis symptoms (OR = 0.1, 95% CI = 0.02—0.5). The Nagelkerke R 2 was 0.26. Our findings point to an association between ‘direct coping and planning’ and reduced multiple sclerosis relapse rate during wartime. Further research should explore whether the employment of specific ways of coping can reduce the risk for relapse among patients with multiple sclerosis during periods of distress.

The impact of subjective cognitive fatigue and depression on cognitive function in patients with multiple sclerosis

Background: The association between subjective cognitive fatigue and objective cognitive dysfunction in patients with multiple sclerosis (PwMS) has been studied, with conflicting results. Objective: To explore the impact of fatigue on cognitive function, while controlling for the influence of depression, disability, comorbidities, and psychotropic medications. Methods: PwMS completed a computerized cognitive testing battery with age- and education-adjusted cognitive domain scores. Disability (Expanded Disability Status Scale (EDSS)), cognitive fatigue, and depression were concurrently evaluated. Results: In all, 699 PwMS were included. Both cognitive fatigue and depression were significantly and negatively correlated with the same cognitive domains: information processing speed, executive function, attention, motor function, and memory (−0.15 ⩽ r ⩽ −0.14 for cognitive fatigue; −0.24 ⩽ r ⩽ −0.19 for depression). Multivariate analysis revealed significant but small independent correlations only between depression and neuropsychological test results, while cognitive fatigue had no independent correlation with objective cognitive function except for a trend toward impaired motor function in highly fatigued PwMS. Depression and cognitive fatigue accounted for no more than 6% of the variance in objective cognitive domain scores. Conclusion: Cognitive fatigue is not independently related to objective cognitive impairment. Depression may influence cognitive function of PwMS primarily when it is severe. Cognitive impairment in PwMS should not be ascribed to fatigue or mild depression.

Cognitive Function of Patients with Crohn's Disease is Associated with Intestinal Disease Activity.

Background:Systemic inflammation and nutritional deficiencies are characteristics of Crohns disease (CD) and have been suggested to influence cognitive performance. This study assessed cognitive function in patients with CD. Methods:Participants were adult patients with CD arriving at routine follow-up. Subjective cognitive complaints, depression, anxiety, fatigue, and sleep were evaluated by validated questionnaires. CD characteristics, blood tests, and Crohns disease activity index were obtained. Nutritional risk index was derived from serum albumin and change in body weight. Montreal cognitive assessment was used for screening. Patients with either subjective cognitive complaints or Montreal cognitive assessment score ⩽26 were tested by a computerized cognitive testing battery, with analysis of scores in 7 cognitive domains (CogDs) and an average of the CogD scores-global cognitive score (GCS). Impaired CogD was defined as scoring more than 1 SD below age and education adjusted average. Results:A total of 105 patients were recruited and 61 were tested with computerized cognitive testing battery. Mean age was 39 ± 13 and mean education years were 14 ± 2. The most commonly impaired CogDs were information processing speed (33%) and verbal function (28%). Crohns disease activity index, nutritional risk index, and hemoglobin were significantly correlated with GCS (r = −0.34, 0.39, 0.33; P = 0.007, 0.003, 0.01). Linear regression revealed significant correlations between Crohns disease activity index, nutritional risk index, and GCS (&bgr; = −0.3, 0.29; P = 0.03, 0.04), independent of depression. This model explained 24% of the variance in GCS. Conclusions:Cognitive performance is related to CD activity and nutritional status. The results provide insight into potential influence of nutrition and inflammation on cognitive function. Further studies on cognitive function of patients with CD are warranted.