Identification of protein-protein interaction bridges for multiple sclerosis.

MOTIVATION: Identifying and prioritizing disease-related proteins is an important scientific problem to develop proper treatments. Network science has become an important discipline to prioritize such proteins. Multiple sclerosis, an autoimmune disease for which there is still no cure, is characterized by a damaging process called demyelination. Demyelination is the destruction of myelin, a structure facilitating fast transmission of neuron impulses, and oligodendrocytes, the cells producing myelin, by immune cells. Identifying the proteins that have special features on the network formed by the proteins of oligodendrocyte and immune cells can reveal useful information about the disease. RESULTS: We investigated the most significant protein pairs that we define as bridges among the proteins providing the interaction between the two cells in demyelination, in the networks formed by the oligodendrocyte and each type of two immune cells (i.e. macrophage and T-cell) using network analysis techniques and integer programming. The reason, we investigated these specialized hubs was that a problem related to these proteins might impose a bigger damage in the system. We showed that 61%-100% of the proteins our model detected, depending on parameterization, have already been associated with multiple sclerosis. We further observed the mRNA expression levels of several proteins we prioritized significantly decreased in human peripheral blood mononuclear cells of multiple sclerosis patients. We therefore present a model, BriFin, which can be used for analyzing processes where interactions of two cell types play an important role. AVAILABILITY AND IMPLEMENTATION: BriFin is available at https://github.com/BilkentCompGen/brifin.

Peripheral Vestibular System Involvement in Multiple Sclerosis and Associations with the Disease Severity.

INTRODUCTION: Multiple sclerosis (MS) is an autoimmune disease that can affect balance, gait, and improve fall risk. The aim of this study was to investigate peripheral vestibular system involvement in MS and associations with the disease severity. METHODS: Thirty-five adult patients with MS and 14 age- and gender-matched healthy controls were evaluated using video head impulse test (v-HIT), cervical vestibular evoked myogenic potential (c-VEMP), ocular vestibular evoked myogenic potentials (o-VEMPs), and sensory organization test (SOT) of computerized dynamic posturography (CDP). The results of both groups were compared, and association with EDSS scores was evaluated. RESULTS: There was no significant difference between the groups regarding v-HIT and c-VEMP results (p > 0.05). There was no association of the v-HIT, c-VEMP, and o-VEMP results with EDSS scores (p > 0.05). There was no significant difference between the o-VEMP results of the groups (p > 0.05) except for N1-P1 amplitudes (p = 0.01). The amplitudes of N1-P1 were significantly lower in the patients compared to controls (p = 0.01). There was no significant difference between the SOT results of the groups (p > 0.05). However, significant differences were found within and between groups when the patients were categorized according to their EDSS scores with a cutoff point of 3 (p < 0.05). There were negative correlations between the EDSS scores and composite (r = -396, p = 0.02) and somatosensory (SOM) scores (r = -487, p = 0.04) of CDP in the MS group. CONCLUSION: Although central and peripheral balance-related systems are affected in MS, the impact of disease on the peripheral vestibular end organ is subtle. In particular, the v-HIT, which was mentioned previously as a detector of brainstem dysfunction could not be a reliable tool in the detection of brainstem pathologies in MS patients. The o-VEMP amplitudes may be affected in the early stages of the disease, possibly due to the crossed ventral tegmental tract, oculomotor nuclei, or interstitial nucleus of Cajal involvements. An EDSS score >3 seems a cutoff level indicating abnormalities in balance integration.

Assessment of the optic nerve, optic disc, and perineural area using shear-wave elastography in patients with multiple sclerosis.

PURPOSE: To observe and describe the stiffness changes of the optic nerve in the patients with multiple sclerosis (MS) with or without optic neuritis and healthy adults via shear wave elastography (SWE). METHODS: 70 optic nerves from 35 patients with MS and 60 optic nerves from 30 healthy subjects were included prospectively in the study. The optic nerve (ON), optic disc (OD), and perineural area were evaluated with SWE and optic nerve sheat diameter (ONSD) was measured by ultrasound. RESULTS: The mean age of patients was 39.68 ± 9.99 years. There was no statistically significant difference between the groups in terms of ONSD, SWE ON, SWE OD, and SWE perineural area levels (P > .05). In the MS group; No statistically significant difference was found between patients with and without optic neuritis for the mean age, gender distribution, duration of MS, types of MS, ONSD, SWE ON, SWE OD, SWE perineural area, and Expanded Disability Status Scale (EDSS) scores (P > .05). No statistically significant difference in terms of ONSD, SWE ON, SWE OD, and SWE perineural area between the MS patients with or without optic neuritis and the control group (P > .05). CONCLUSION: Shear wave elastography measurements of the optic nerve, optic disc, and perineural area do not contribute to the evaluation of optic neuritis in a patient with MS.

[A Case of Sporadic Creutzfeldt-Jakob Disease That Developed With Psychiatric Symptoms]. / Psikiyatrik Bulgularla Baslayan Sporadik Creutzfeldt-Jakob Hastaligi Olgusu.

Creutzfeldt-Jakob disease (CJD) is a fairly rare prion sickness characterized by rapidly progressive dementia and neuropsychiatric symptoms. The diversity of clinical characteristics of the disease causes difficulties during diagnosis. The first finding of the disease might be psychiatric symptoms. The male patient who was diagnosed with CJD after dementia, ataxia, and myoclonus developed rapidly following psychiatric symptoms, was presented in order to draw attention to the onset with psychiatric symptoms in CJD.

Genetic Susceptibility to Multiple Sclerosis: The Role of FOXP3 Gene Polymorphism.

INTRODUCTION: It is well recognized that both genetic and environmental factors play an important role in the pathogenesis of multiple sclerosis (MS). Immune pathogenesis of MS focuses on pathogenic CD4+ T lymphocytes. CD4+CD25+ regulatory T cells have suppressive function in this cell group. FOXP3 (forkhead boxP3) transcription factor is a key structure in the development and function of regulatory cells. Functional alterations in FOXP3 gene expression have been observed in various autoimmune diseases. METHODS: We screened a non-synonymous coding single nucleotide polymorphism (exon +2710 C/T) (rs2232369) of human FOXP3 gene in 148 MS patients (118 with Relapsing Remitting MS, 30 with Secondary Progressive MS) and 102 age- and sex-matched healthy controls. The association of polymorphisms with susceptibility, and course of the disease was evaluated. RESULTS: We could not detect any single nucleotide polymorphism in MS patients, however, polymorphic allele was detected in 3% of the control group. Consequently, a genetic association between the FOXP3 gene polymorphism and MS was not revealed. CONCLUSION: The distribution of this polymorphism has not been screened in any other MS populations before. Although we could not succeed to find any association between susceptibility to MS and screened FOXP3 gene polymorphisms, we suggest that this particular polymorphism is not appropriate for these kind of studies in the future.