Low contrast visual acuity testing is associated with cognitive performance in multiple sclerosis: a cross-sectional pilot study.

BACKGROUND: Cognitive impairment and visual deterioration are two key clinical symptoms in MS and affect 50 to 80% of patients. Little is known about the influence of cognitive impairment on visual tests recommended for MS such as low contrast sensitivity testing. Our objective was to investigate whether low contrast sensitivity testing is influenced by cognitive impairment in multiple sclerosis (MS) patients. METHODS: Cross-sectional study including 89 patients with relapsing-remitting MS. All patients received cognitive evaluation using Rao's Brief Repeatable Battery of Neuropsychological Testing (BRB-N). Visual assessments included low contrast sensitivity (CS) by functional acuity contrast testing and high contrast visual acuity (VA) using ETDRS charts. Retinal morphology as visual impairment correlate was measured using retinal nerve fiber layer (RNFL) thickness by optical coherence tomography. RESULTS: In combined analyses using generalized estimating equation models, Paced Auditory Serial Addition Test (PASAT) and RNFL as well as and the Symbol Digit Modalities Test (SDMT) and RNFL predicted CS. To further control for a potential influence of the anterior visual system we performed partial correlation analyses between visual function and cognitive function test results but controlling for RNFL. Even when controlling for RNFL, CS was associated with PASAT performance and SDMT performance. CONCLUSION: Our data show that: a) cognitive impairment and performance in visual function tests such as low contrast sensitivity testing are associated; b) the main cognitive domains correlating with visual test performance are information processing speed and, to a lesser degree, memory; This preliminary data needs to be substantiated in further studies investigating patients with a higher cognitive burden, healthy controls and in longitudinal settings.

Comparison of three clinical rating scales in Friedreich ataxia (FRDA).

To test the validity and reliability of the scale for the assessment and rating of ataxia (SARA) in Friedreich ataxia (FRDA). SARA is limited to eight items and can be performed rapidly. Ninety-six patients with a molecular genetic diagnosis of FRDA were rated using three different clinical scales, the FRDA Rating Scale (FARS), the International Cooperative Ataxia Rating Scale (ICARS), and SARA. Despite considerable discrepancies in scale size and subscale structure, SARA total scores were significantly correlated with ICARS (r = 0.953, P < 0.0001) and FARS (r = 0.938, P < 0.0001) total scores. SARA total scores also correlated with the activities of daily living (ADL, r = 0.929, P < 0.0001). Although originally developed for the use in dominantly inherited ataxias, which are primarily ataxias of the cerebellar type, SARA can also be used successfully to assess afferent ataxia, which is the predominant form in FRDA. Because SARA is characterized by high interrater reliability and practicability, SARA is applicable and well suited forclinical trials of FRDA.

Vitamin D in the prevention, prediction and treatment of neurodegenerative and neuroinflammatory diseases.

Vitamin D research has gained increased attention in recent times due to its roles beyond bone health and calcium homeostasis, such as immunomodulation. In some parts of the brain and on immune cells, vitamin D hydroxylating enzymes and its receptors are located. Epidemiological evidence demonstrates that deficiency of Vitamin D is relevant for disease risk and course in multiple sclerosis (MS) and presumably also in neuromyelitis optica spectrum disorders (NMOSD), Parkinson's disease (PD), and Alzheimer's disease (AD). Although the exact mechanism underlying vitamin D effects in these diseases remains widely unexplored, human and animal studies continue to provide some hints. While the majority of vitamin D researchers so far speculate that vitamin D may be involved in disease pathogenesis, others could not show any association although none have reported that sufficient vitamin D worsens disease progression. The studies presented in this review suggest that whether vitamin D may have beneficial effects in disease course or not, may be dependent on factors such as ethnicity, gender, diet, vitamin D receptor (VDR) polymorphisms and sunlight exposure. We here review the possible role of vitamin D in the pathogenesis and disease course of MS, NMOSD, PD, and AD and potential therapeutic effects of vitamin D supplementation which may be relevant for predictive, preventive, and personalized medicine. We suggest areas to consider in vitamin D research for future studies and recommend the need to supplement patients with low vitamin D levels below 30 ng/ml to at least reach sufficient levels.

Trichuris suis ova in relapsing-remitting multiple sclerosis and clinically isolated syndrome (TRIOMS): study protocol for a randomized controlled trial.

BACKGROUND: Trichuris suis ova is a probiotic treatment based on the hygiene hypothesis. It has been demonstrated as safe and effective in autoimmune inflammatory bowel diseases and clinical trials indicate that helminth infections also have an immunomodulatory effect in multiple sclerosis.We hypothesize that administering 2,500 Trichuris suis ova eggs orally every two weeks for 12 months is--due to its immunomodulatory and anti-inflammatory effect--significantly more effective than oral placebo in preventing new T2 and Gd+ lesions, as quantified by cerebral MRI and clinical examination, in relapsing-remitting multiple sclerosis and clinically isolated syndrome. METHODS/DESIGN: Fifty patients with relapsing-remitting multiple sclerosis or clinically isolated syndrome with clinical activity, not undergoing any standard therapies, will be randomized 1:1 to Trichuris suis ova 2,500 eggs every two weeks or matching placebo. The safety, tolerability and effect on disease activity and in vivo mechanisms of action of Trichuris suis ova in MS will be assessed by neurological, laboratory and immunological exams and magnetic resonance imaging throughout the 12-month treatment period and over a follow-up period of 6 months. Various immunological analyses will be used to assess the overall patient immune response prior to and at varying time points following treatment with Trichuris suis ova. DISCUSSION: We anticipate that Trichuris suis ova will be well tolerated and more effective than the placebo in preventing new T2 and Gd+ lesions, as quantified by MRI. We also expect the Th1/Th17 proinflammatory response to shift towards the more anti-inflammatory Th2 response. This study has important clinical implications and will involve extensive research on the immunology of helminth therapy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01413243.