Risk of multiple sclerosis in patients with psoriasis receiving anti-IL-17 agents: A case-based review.

Biologics approved for psoriasis exhibit favorable safety profiles, and serious adverse events have rarely been reported. In this report, we present the case of a patient treated with ixekizumab, an anti-interleukin (IL)-17 agent, who 8 months later developed multiple sclerosis (MS). We also review the available literature regarding the use of anti-IL-17 agents in the context of psoriasis and pre-existing or new-onset demyelination. Eight case reports were evaluated as relevant and are presented in our report. In most of the cases secukinumab or ixekizumab administration adequately controlled both skin and pre-existing neurological clinical manifestations. However, there has been a report of MS exacerbation under secukinumab treatment and the occurrence of myelitis in a patient receiving ixekizumab. While the anti-IL-17-biologic-mediated induction of inflammatory events in the central nervous system has not been proven and a causal relationship is lacking, such a probability should be considered in extremely rare cases.

Seasonal adherence to, and effectiveness of, subcutaneous interferon ß-1a administered by RebiSmart® in patients with relapsing multiple sclerosis: results of the 1-year, observational GEPAT-SMART study.

BACKGROUND: Little is known about whether tolerability and adherence to treatment can be influenced by weather and temperature conditions. The objective of this study was to assess monthly and seasonal adherence to and safety of sc IFN-ß1a (Rebif®, Merck) in relapsing-remitting multiple sclerosis (RRMS) patients using the RebiSmart® electronic autoinjector. METHODS: A multicentre, prospective observational study in Greece in adult RRMS patients with EDSS < 6, under Rebif®/RebiSmart® treatment for ≤6 weeks before enrollment. The primary endpoint was monthly, seasonal and annual adherence over 12 months (defined in text). Secondary endpoints included number of relapses, disability, adverse events. RESULTS: Sixty four patients enrolled and 47 completed all study visits (Per Protocol Set - PPS). Mean annual adherence was 97.93% ± 5.704 with no significant monthly or seasonal variations. Mean relapses in the pre- and post- treatment 12-months were 1.1 ± 0.47 and 0.2 ± 0.54 (p < 0.0001, PPS). 10 patients (22%) showed 3-month disability progression, 19 (40%) stabilization and 18 (38%) improvement. EDSS was not correlated to pre- (r = 0.024, p = 0.87) or post-treatment relapses (r = 0.022, p = 0.88). CONCLUSION: High adherence with no significant seasonal or weather variation was observed over 12 months. While the efficacy on relapses was consistent with published studies, we could not identify a relationship between relapses and disability. TRIAL REGISTRATION: Greek registry of non-interventional clinical trials ID: 200136 , date of registration: February 18th, 2013.

Cognitive event-related potentials in multiple sclerosis: Correlation with MRI and neuropsychological findings.

BACKGROUND: Cognitive event-related potentials (ERPs) have been previously correlated with T2 lesion load (Τ2LL) in patients with multiple sclerosis (MS). It is currently unknown, however, whether ERPs also correlate with brain atrophy or the presence of T1 hypointense lesions ("black holes") which reflect tissue destruction and axonal loss. The primary aim of the current study is to explore the effect of neuroradiological parameters such as brain atrophy, T1 and T2 lesion load on auditory ERPs in MS patients. In addition, we correlated cognitive impairment with neurophysiological (ERP) and neuroradiological (MRI) variables and investigated whether a combination of ERP and MRI parameters is capable of distinguishing patients suffering from secondary progressive (SP), primary progressive (PP) and relapsing-remitting (RR) MS. MATERIALS AND METHODS: The study sample consisted of fifty nine MS patients (mean age±SD: 37.82±1.38 years; average disease duration: 6.76±5.3 years) and twenty six age-matched controls (mean age±SD: 41.42±15.39 years). The patients' EDSS and NRS scores were 3.77±2.14 (range: 1-7.5) and 75.88±11.99 (range: 42-94) respectively. ERPs were recorded using the auditory "odd-ball" paradigm. T1 and T2 lesions were automatically segmented using an edge-finding tool and total lesion volumes were calculated. MRI measures of brain atrophy included third ventricle width (THIRDVW) and the ratio of mid-sagittal corpus callosum area to the mid-sagittal intracranial skull surface area (CC/MISS). Statistical analysis was performed using multiple regression, principal component (PCA) and discriminant analysis. RESULTS: T1 lesion load emerged as the most significant predictor of P300 and N200 latency. The rest of the endogenous ERPs parameters (P300 amplitude, N200 amplitude) were not significantly correlated with the MRI variables. PCA of pooled neuroradiological and neurophysiological markers suggested that four components accounted for 64.6% of the total variability. Discriminant analysis based on ERP & MRI markers classified correctly 79.63% of patients in RR, PP and SP subgroups. CONCLUSION: T1 lesion load is the most significant MRI correlate of auditory ERPs in MS patients. Importantly, ERPs in combination with MRI variables can be usefully employed for distinguishing patients with different subtypes of MS.

A quantitative evaluation of damage in normal appearing white matter in patients with multiple sclerosis using diffusion tensor MR imaging at 3 T.

The white matter (WM) of the brain is damaged in multiple sclerosis (MS), even in areas that appear normal on standard MR imaging. The purpose of our study is to evaluate the damage of normal appearing white matter (NAWM) in patients with MS. In our study, 84 MS patients and 42 healthy adults underwent a routine brain MRI, including also diffusion tensor imaging (DTI). All studies were performed on a 3 T MRI scanner. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained. The DTI parameters of NAWM were correlated with expanded disability status scales (EDSS) scores. Our results showed statistically significant differences in FA and ADC values between MS plaques and the symmetrical NAWM, as also between NAWM and the respective white matter in controls. The ADC values of the NAWM correlated with the EDSS scores. The present study demonstrated damage of the NAWM in MS patients, using DTI in 3.0 T. DTI may be used in the detection of subtle damage of the white matter.

Genetic basis of Parkinson disease.

Over the past few years, considerable progress has been made in understanding the molecular mechanisms of Parkinson disease (PD). Mutations in certain genes are found to cause monogenic forms of the disorder, with autosomal dominant or autosomal recessive inheritance. These genes include alpha-synuclein, parkin, PINK1, DJ-1, LRRK2, and ATP13A2. The monogenic variants are important tools in identifying cellular pathways that shed light on the pathogenesis of this disease. Certain common genetic variants are also likely to modulate the risk of PD. International collaborative studies and meta-analyses have identified common variants as genetic susceptibility risk/protective factors for sporadic PD.