Gut-oriented interventions in patients with multiple sclerosis: fact or fiction?

OBJECTIVE: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, disimmune disease of the central nervous system whose etiology and pathogenesis remain poorly understood, due to its complex and multifactorial nature. Evidence of a bidirectional connection linking the gut microbiome with the intestinal barrier and the immune system (the gut-brain axis) may have implications for the pathogenesis of inflammatory demyelinating diseases such as MS. This narrative review summarizes the evidence for the gut-brain axis involvement in the pathogenesis of MS and examines the role of gut-oriented interventions in MS. PATIENTS AND METHODS: We reviewed all available studies in PubMed concerning gut-directed interventions and MS. This research was conducted using different combinations of pertinent keywords (multiple sclerosis, immune-mediated inflammatory diseases, autoimmune diseases, first demyelinating event, neurocognition, neurological disorders, neurology practice, risk factors, taxonomic biomarkers, nutrition, diet, dietary additives, complementary treatment, gut bacteria, gut microbiome, microbiome, gut-brain axis, epidemiology, alpha-linolenic acid, fermentative metabolites, fat, saturated fat, monounsaturated fat, polyunsaturated fat, omega-3 fatty acids, calorie restricted diet, fasting, fecal microbiome, fecal microbiota transplantation, animal testing). RESULTS: There is an emerging evidence that alterations in the gut microbiome and increased intestinal permeability may be causative factors in the complex interplay between nutrition, metabolic status and the immune-inflammatory response in patients with MS. This suggests the possibility that modification of lifestyle and the microbiome, for example by specific diets or fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers, may positively influence the pathogenesis of MS. CONCLUSIONS: Although the role of nutritional factors in the pathogenesis of MS remains to be established, there is evidence that appropriate gut-directed interventions such as diet, nutritional supplementation or fecal transplantation may modulate the inflammatory response and improve the course of MS as a complementary treatment in the disease.

Basal vitamin D levels and disease activity in multiple sclerosis patients treated with fingolimod.

BACKGROUND: Several studies have shown an association between 25-hydroxyvitamin D (25[OH]D) levels and multiple sclerosis (MS) susceptibility and/or level of disease activity in patients treated with first line drugs. AIMS: To investigate whether baseline 25[OH]D values could influence disease activity also during treatment with the second-line drug fingolimod (FTY). PATIENTS AND METHODS: We enrolled 176 MS patients who started FTY at the San Raffaele Hospital (OSR) MS center with available 25[OH]D measurement at the time of treatment start. We then prospectively followed them for 2 years with periodic clinical examinations and MRI scans. RESULTS: We found no linear correlation between baseline 25[OH]D levels and annualized relapse rate (ARR) or time to first relapse. However, we observed that patients with serum 25[OH]D ≥ 100 nmol/l showed a lower number of Gd+ and combined unique activity (CUA) lesions at baseline compared to patients with the lowest 25[OH]D levels (less than 50 nmol/l, p value < 0.05). Moreover, they showed fewer CUA lesions at 2-year follow-up also when accounting for baseline level of disease activity (p value < 0.05). CONCLUSIONS: In patients treated with FTY, those with the highest baseline 25(OH)D levels had a significantly lower number of active lesions at baseline; the same effect, even if weaker, was observed also at 2-year follow-up when adjusting for baseline disease activity. Given Vitamin D supplementation safety profile, also if a causal effect has not yet been shown, most of MS patients could probably benefit from 25[OH]D levels above those currently considered to be sufficient.

Use of herbal remedies by multiple sclerosis patients: a nation-wide survey in Italy.

Though recent progress in multiple sclerosis (MS) treatment is remarkable, numerous unmet needs remain to be addressed often inducing patients to look for complementary and alternative medicines (CAM), especially herbal remedies (HR). HR use, scarcely investigated in MS, may cause adverse reactions (AR) and interfere with conventional treatment. We performed a survey aimed at evaluating use and attitudes towards HR and factor associated to HR use. Other CAM use and attitudes have been investigated as well. Multiple-choice questionnaires were distributed to MS out patients attending 14 Italian referral Centers. Multivariable logistic regression was used to identify HR use determinants. Present/past HR use for either MS or other diseases was reported in 35.6 % of 2419 cases (95 % CI 36.0-40.0 %). CAM use was reported in 42.5 % of cases. Independent predictors of HR use were represented by higher education, geographic area, dissatisfaction with conventional treatment of diseases other than MS and benefit perception from CAM use. Both HR and CAM use were not always disclosed to the healthcare professional. In conclusion, HR and other CAM appear to be popular among MS patients. The involvement of the healthcare professionals appears to be scarce with potential risk of AR or interference with conventional treatments.

Risk of fracture prevention in spina bifida patients: correlation between bone mineral density, vitamin D, and electrolyte values.

PURPOSE: The aim of our study was to investigate the relationship between bone mineral density (BMD), vitamin D, and electrolyte blood values in patients with spina bifida, to find a possible therapeutic regimen and an intervention to reduce the risk of fractures in this population. METHODS: BMD values were measured in 49 patients (32 females, 17 males; aged 14.1 ± 3.86 years; range 5-20 years) using dual-energy X-ray absorptiometry (DEXA) and were analyzed based on sex, the level of spinal involvement, vitamin D, and electrolyte values, physical activity, body mass index (BMI), and ambulatory status [patients were divided into three subgroups: full-time wheelchair (FTWC), limited ambulator (LA), and full-time ambulator (FTA)]. These data were analyzed considering sex-, age-, and BMD-matched values and compared with those of normal population. RESULTS: BMD was significantly lower in these patients compared with that in the general healthy population (Z-score: -1.2 ± 1.8); in particular, females had Z-score values significantly lower that of the males (Z-score: -2.43 ± 2.02; P < 0.0004). In FTWC subgroup, Z-score was lower than that of the other two subgroups (P < 0.009). Vitamin D values were significantly lower compared with those in the general healthy population (vitamin D spina bifida group: 14.6 ± 8.7 mg/dL; normal subjects: 35 ± 9.8 mg/dL; P < 0.001). Subjects with spina bifida showed hypophosphatemia (<3 mg/dL) because of the lower levels of vitamin D (3.1 ± 0.9 mg/dL; P < 0.001). CONCLUSIONS: Spina bifida patients showed lower BMD, vitamin D, and electrolyte values than the healthy population; hence, they have an increase risk of developing pathological fractures. Vitamin D supplementation for a longer time period could reduce this risk.

Treatment of Wernicke's encephalopathy with high dose of thiamine in a patient with pyloric sub-stenosis: description of a case.

Wernicke's encephalopathy (WE) is an acute or subacute syndrome that results from a deficiency in vitamin B1 (thiamine). The syndrome is characterised by a classical triad of symptoms: nystagmus and ophthalmoplegia,mental-status changes, and unsteadiness of stance and gait. When patients with WE are inappropriately treated with low doses of thiamine, mortality rates average out at 20% and Korsakoff's Psychosis develops in about 85% of survivors(Sechi and Serra in Lancet Neurol 6(5):442­455,2007). We report the case of a patient with a pyloric substenosis that developed a WE, and was treated with high doses of thiamine showing after few days of treatment a great improvement of neurological and neuroradiological assessment, even though cognitive impairment was still severe at discharge and at 6 months follow-up.

Narrowband (TL-01) ultraviolet B phototherapy for pruritus in polycythaemia vera.

BACKGROUND: There are several reports of the efficacy of broadband ultraviolet (UV) phototherapy in the treatment of pruritus associated with polycythaemia vera. OBJECTIVES: To evaluate whether narrowband (TL-01) UVB phototherapy is also effective in treating this condition. METHODS: Ten patients with pruritus associated with polycythaemia vera were treated with narrowband (TL-01) UVB phototherapy. The first irradiation dose was 2/3 of the minimal erythema dose; the treatment schedule consisted of three irradiation sessions per week, with dose increments of 10% each session for skin types I and II, and 15% for skin types III and IV. RESULTS: Patients reported a marked relief of symptoms after an average of six treatments (median cumulative dose 1851.52 mJ cm-2, range 1180.4-2468.4). A complete remission of the pruritus occurred within 2-10 weeks of treatment (median cumulative dose 5371.46 mJ cm-2, range 3271.2-7336.3) in eight of 10 patients. Two patients had only a partial and temporary relief of pruritus after two cycles of treatment and a cumulative dose of 3271.2 mJ cm-2. CONCLUSIONS: Narrowband UVB phototherapy is effective for treatment of pruritus associated with polycythaemia vera, and has the advantage of being less erythemogenic than broadband UVB.

Measuring evoked responses in multiple sclerosis.

Evoked potentials (EPs) have been widely utilised in Multiple Sclerosis (MS) patients to demonstrate the involvement of sensory and motor pathways. Their diagnostic value is based on the ability to reveal clinically silent lesions and to objectivate the central nervous system damage in patients who complain frequently of vague and indefinite disturbances which frequently occurs in the early phases of the disease. The advent of magnetic resonance imaging (MRI) techniques has greatly reduced the clinical utilisation of EPs, which is not fully justifiable, as the information provided by EPs are quite different from those provided by MRI. The abnormalities of evoked responses reflect the global damage of the evoked nervous pathway and are significantly correlated with the clinical findings, while the vast majority of MRI lesions are not associated to symptoms and signs. Transversal and longitudinal studies have demonstrated that EP changes in MS are more strictly related to disability than MRI lesion burden. On the contrary, MRI is more sensitive than EPs in revealing the disease activity. Evoked responses modifications observed in MS are not disease-specific; moreover longitudinal studies showed latency and morphology changes of evoked responses not always related to clinical changes. Such a dissociation can be explained both by technical factors and by subclinical disease activity. To reduce the negative impact of technical aspects, only reproducible parameters of the evoked responses should be used to monitor disease evolution and therapeutic interventions.