Introduction: Recent research into multiple sclerosis (MS) has focused on the role of microRNAs (miRNAs) in the development of the disease. This study was designed to analyze miR-146a expression in whole blood and fecal samples of patients with MS. The study aimed to analyze clinical data using the miR-146a expression values obtained. Subjects and Methods: This study included patients with relapsing–remitting MS (RRMS) (n = 53), clinically isolated syndrome (CIS) (n = 15), and healthy controls (n = 26). Total RNA was isolated from the participants' whole blood and fecal samples. RNA extraction was performed using QIAamp RNA Blood Mini Kits for blood samples and RNeasy PowerMicrobiome Kits for feces. miR-146a expressions were studied using real-time polymerase chain reaction. Finally, relative expression was correlated with clinicopathologic factors. Results: MiR-146a expression was significantly decreased in the whole blood (P < 0.001) and fecal samples (P = 0.036) of patients with RRMS. There was no significant difference in the miR-146a expression rate between patients with CIS and controls. Moreover, the miR-146a expression level in patients with RRMS was decreased compared with those with CIS (P < 0.001). A significant association was determined between miR-146a expression and sex in blood samples. When sex stratification was applied to expression values obtained from fecal samples, miR-146a expression was downregulated only in females (P = 0.008). Discussion: miRNAs play an essential role in maintaining the stable course of MS, and this process has some sex-specific differences. Expression of fecal miR-146a may be used as a biomarker to diagnose and predict prognosis in patients with RRMS.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarctions and leukoencephalopathy (CADASIL) is the most common hereditary form of cerebral small vessel disease. It is clinically, radiologically, and genetically heterogeneous and is caused by NOTCH3 mutations. Methods: In this study, we analyzed NOTCH3 in 368 patients with suspected CADASIL using next-generation sequencing. The significant variants detected were reported along with the clinical and radiological features of the patients. Results: Heterozygous NOTCH3 changes, mostly missense mutations, were detected in 44 of the 368 patients (~12%). Conclusions: In this single-center study conducted on a large patient group, 30 different variants were detected, 17 of which were novel. CADASIL, which can result in mortality, has a heterogeneous phenotype among individuals in terms of clinical, demographic, and radiological findings regardless of the NOTCH3 variant.

Multiple sclerosis (MS) is an inflammatory, autoimmune demyelinating, and neurodegenerative disorder of the central nervous system. Interactions between environmental factors, predisposition genes, and determining genes appear to be involved in its etiology. Epigenetic mechanisms such as microRNA-mediated gene regulation can determine the susceptibility and severity of autoimmune diseases. Therefore, to determine the role of miR-146a and miR-155 in MS and its developmental stages, the expression levels in the serum of MS and clinically isolated syndrome (CIS) patients were compared with those of healthy controls. In the present study, the expression levels of miR-146a and miR-155 were assessed using quantitative Real-Time PCR in blood samples of 15 CIS patients and 61 relapsing-remitting multiple sclerosis (RRMS) patients alongside 32 healthy patients as controls. Furthermore, any associations with the clinicopathologic variables of the patients were also evaluated. Dysregulations were found only in the miR-146a and miR-155 expressions in the RRMS-Control group. When the RRMS patients were evaluated in terms of the characteristics of sex, annual attack rate, age of diagnosis, duration of follow-up, and immunomodulatory treatments used, no significant differences were observed. However, significant dysregulations were identified in miRNA expression in the vitamin D level, EDSS values, and the number of attacks. ROC curve analysis showed that miR-146a and miR-155 were significant in the RRMS-Control group for the area under the curve (AUC). It is possible that miR-146a may be associated with vitamin D deficiency and disease disability, while miR-155 may be associated with the number of attacks.

Son yıllarda Multipl skleroz (MS) etyolojisinde, internal juguler ven (IJV) ve/veya azigos venlerde venöz drenaj bozukluğu olarak tanımlanan kronik serebrospinal venöz yetmezliğin (KSSVY) etkili olduğu ileri sürülmektedir. Bu teori, MS etyopatogenezinde etkili olduğu düşünülen otoimmün teoriyi toptan yadsıması nedeni ile ciddi tartışmalar başlatmıştır. Bu teori ile, MS etyopatogenezine farklı açılardan bakılması nedeniyle ilgi çekmiş ve bununla ilgili birçok çalışma başlatılmıştır. Çalışmamızda Doppler sonografi (DS), kranial MR venografi (MRV) ve selektif venografi (SV) ile MS hastalarında KSSVY’nin varlığının tespiti, ekstrakraniyal-intrakraniyal venöz yapıların yapısal- fonksiyonel açıdan incelenmesi, sağlıklı kişilerle karşılaştırılması amaçlanmıştır. 25 Relapsing Remitting MS hastasına DS, SV ve kraniyal MRV yapılırken, 20 sağlıklı kişiye kraniyal MR venografi ve Doppler sonografi yapıldı. Hastalarda DS’ de reflü varlığı açısından kontrol grubuna göre istatistiksel olarak anlamlı idi (p

Introduction: Multiple Sclerosis (MS) is a multifactorial, immune-mediated disorder that occurs in genetically predisposed people. Vitamin D might be an important environmental factor in the development and prevention of MS disease. We aimed to investigate the role of vitamin D in MS disease activity. Material and Methods: The study was designed as a prospective study. Thirty-two patients and 15 healthy subjects were included. Variables were MS disease duration, number of relapses, Expanded Disability Status Scale (EDSS) scores, serum vitamin D levels, assessments through neuropsychological tests relevant to depression, cognition, anxiety and fatigue. Results: The mean age of the subjects was 32.6±6.9 years. A significant positive correlation was found between the vitamin D level during relapse and remission. A statistically significant difference was found between the patients in relapse and controls in serum vitamin D levels (p=0.002). A statistically significant difference was found between the patients in relapse and patients in remission, in serum vitamin D concentrations (p<0.001). Statistically significant differences were found between the patients in relapse and controls in MMSE, Beck Depression Inventory, Benedict's Cognition Test, Fatigue Severity Scale, PASAT, State-Trait Anxiety Inventory scores (p=0.01, p<0.001, p=0.01, p<0.001, p=0.007, p<0.001 and p<0.001, respectively). Conclusion: Vitamin D in association with other therapies may prevent the progression of MS-related disabilities and the relapses in RRMS. Vitamin D levels may have effects on the symptoms (depression, anxiety, cognitive deterioration, and fatigue) which are frequently seen in the course of MS.

Objectives: In our study, we investigated the effects of modafinil therapy on clinical and neurophysiological tests of multiple sclerosis (MS) patients with fatigue.Methods: The study was performed on 18 MS patients (16 females, 2 males) at Uludağ University School of Medicine, Department of Neurology, who are followed up according to Mc Donald’s criteria, who had 36 points or above based on the fatigue assesment scala (FAS), whose Beck depression inventory points were 16 and below, whose thyroid, liver and renal functions were evaluated as normal, and who had no systemic disorder. All patients had neurological examination and their expanded disability status scale (EDSS), fatigue impact scala (FIS) and multiple sclerosis quality of life (MSQoL-54) were evaluated. Somatosensory evoked potential (SEP), visual evoked potential (VEP), brainstem auditory evoked potential (BAEP), visual event related evoked potential (visual P300) were performed in our neurophysiology laboratory. After that the patients were given modafinil 100 mgr 1×1 (morning) for 1 week, the following weeks 2×1 (morning and noon). At the end of the 6 weeks of therapy the patients were called to the neurology polyclinic, and their neurological examinations, EDSS, FIS, MSQoL-54, SEP, VEP, BAEP and visual P300 were repeated.Results: When the patients’ previous and subsequent FIS and MSQoL-54 total scores were compared, a significant statistical difference was found. When all 3 subgroups of FIS (consciousness, physical and social) were evaluated after the modafinil therapy, a significant statistical decrease in previous and successive scores were found. It is found out that modafinil therapy improves life quality which is evaluated due to MSQoL-54 (p < 0.05). A significant statistical relation between the number of MS disease attacks and the three subgroups of MFIS was not figured out (p > 0.05). There were no statistically significant relation between the FAS, EDSS and Beck depression inventory scores before the modafinil therapy had been applied (p > 0.05). There was a statistically correlation between Beck depression inventory score and FIS’s social subgroup (p = 0.017). When the patient’s SEP, VEP, BAEP, visual P300 average test values before and after the modafinil therapy were compared, a statistically significant difference was not observed.Conclusions: In our study, it is found that modafinil therapy, which is used against fatigue, one of the MS disase’s most common symptom, has a positive impact on MS life quality and patients’ clinical symptoms of fatigue, although it has no effect on patients’ evoked potential methods (BAEP, SEP, VEP, visual P300) performed in neurophysiology laboratory.

Objectives: Multiple Sclerosis (MS) is a chronic disease which affects physical,psychological and social functioning of patients. In this study we aim to indicate psychiatric comorbidity, some psychosocial factors and their associations with quality of life in patients with MS. Methods: A total of 227 patients underwent psychiatric examination and the following scales were applied: Socio-demographic data form, Hospital Anxiety and Depression Scale (HADS), Multiple Sclerosis Quality of Life-54 (MSQOL-54), Psychosocial Adjustment to Illness Scale-Self report (PAIS-SR) and Multidimensional Scale of Perceived Social Support (MSPSS). Results: Among 227 patients with MS, 67.8% (n = 154) had psychiatric diagnosis; 24.2% (n = 55) had depression,19.8% (n = 45) had adjustment disorder, 14.9% (n = 34) had anxiety disorder, 7.1% (n=16) had dysthymic disorder and 1.8% (n = 4) had bipolar disorder. Patients with a psychiatric diagnosis had lower scores in role limitations due to emotional problems, emotional well-being, health perceptions, social function, cognitive function, health distress and mental health composite of MSQOL-54. PAIS-SR and MSPSS scores were significantly lower in MS patients with a psychiatric diagnosis. PAIS-SR scores were negatively correlated with role limitations-emotional, emotional well-being, social function, sexual function, satisfaction with sexual function, physical health composite and mental health composite scores of MSQOL-54. MSPSS total score was positively correlated with emotional well-being score of MSQOL-54. Conclusions: In MS patients, there is a high prevalence of psychopathology and it is associated with quality of life, perceived social support and psychosocial adjustment of the patients. Quality of life is reduced especially in emotional and mental aspects in patients with a psychiatric diagnosis. Diagnosis and treatment of psychopathology in MS patients seems crucial to decrease disease burden.

Walking limitations play a key role in the development of disability in multiple sclerosis (MS) patients. Vast majority of patients, even in the very early stages of the disease, experience walking disturbances. Measuring capacity and performance in lower extremities enables us to 1) monitor disease pregression; 2) evaluate treatment responses; 3) determine the necessity of new treatment strategies on time. The purpose of this review is to highlight the importance of regular walking assessments in MS patients, give idea about which measurement tools to choose, and provide insight for future investigations in the light of new technological developments.

Since the first approved parenteral drug for the treatment of multiple sclerosis (MS) in 1993 (interferon [IFN] beta, and later glatiramer acetate [GA]), today there are both parenteral and oral treatment options for MS. After IFN beta preparations, glatiramer acetate was developed; and, until the approval of natalizumab in 2006, those dominated the treatment of MS. Later on, among oral drug options, cladribine made a promising entry; however, due to safety concerns, it was withdrawn soon. Afterwards, with the understanding of the role of sphingosine-1 phosphate (S1P) receptors in the pathogenesis of MS, fingolimod was approved in 2010, which was followed by other oral agents such as teriflunomide and dimethyl fumarate. Recently newer IV treatment options such as alemtuzumab, rituximab and ocrelizumab have widened the treatment arena. Recently, after submitting new efficacy and safety data, cladribine was approved for MS by EMA, in 2017. Moreover, seven years after its rejection due to safety reasons, in August 2018 FDA accepted to re-evaluate the data of cladribine as a treatment option for relapsing remitting MS (RRMS). Another oral treatment option, Laquinimod, was not approved because it could not be shown to slow disability progression despite favourable effect in relapsing MS. Newer generation S1P receptor modulators are being investigated currently, and they are expected to come into the treatment arena soon. In this article, mechanisms of actions, clinical trial results, and side effects of the newer drugs used for MS, are reviewed. IFN beta and glatiramer acetate were not included since they have clinical experience nearing 30 years.

BACKGROUND:Cognitive impairment (CI) is a common problem in multiple sclerosis (MS), may occur either in early or late phase of the disease, and impairs quality of life.OBJECTIVES:This study aimed to determine the prevalence of CI and related risk factors in relapsing-remitting MS (RRMS) patients in Turkey.METHODS:The present cross-sectional, multi-center, and nationally representative study included RRMS patients. Sociodemographic characteristics, cognitive functions and additional outcomes were compared between patients with and without CI.RESULTS:The analyses included 487 RRMS patients. According to the BRB-N battery results, CI prevalence was 53.7%. There was a negative significant correlation of BRB-N subtests with age, disease duration, and EDSS and MSNQ-patient rated scores. On the logistic regression analysis, increased age, living in village/rural area, high income level, and high EDSS score were significant increasing risk factors in the development of CI.CONCLUSIONS:This is the first national cognitive data obtained from MS in Turkey, which is a country between Europe and Asia and thus has characteristics of both continents. The similarity of the results of the present study obtained from Turkey to the Western-based data indicates that CI is universal in MS and the main factors affecting CI have not changed.

Objective: To investigate fatigue and sleep disorders based on demographic, clinical and polysomnographic data and show their effects on the quality of life in multiple sclerosis (MS) patients. Materials and Methods: Thirty MS patients were enrolled in the study depending on the results of the polysomnography (PSG), Fatigue Severity scale, Epworth Sleepiness scale (ESS), Pittsburgh Sleep Quality lindex, Beck Depression and Anxiety inventories. Patients, using (n=16) and non-using (n=14) interferon, were compared with each other in all parameters; ESS and PSG data were compared with a control group consisting of 19 healthy people. Short form-36 (SF-36) data were also compared with the society norms. Results: Central fatigue was observed in 86.7% of the patients. PSG data revealed that stage N2 sleep duration of those who did not use interferon was significantly longer than those who used it (p<0.001). According to the PSG, total sleep time, sleep efficiency, stage N3 and rapid eye movement time, mean respiratory disturbance index, sleep latency and the mean value of total leg movements were significantly higher in the patient group than in the control group (p<0.001). All parameters of SF-36 were significantly lower in patient group (p<0.001). The stage N3 sleep time length was found related with physical component summary of SF-36 (p<0.001). Conclusion: MS patients have high level of fatigue and additionally there are weighty disturbances in objective and subjective sleep parameters. Our findings were revealed that all the components of quality of life decreased significantly in these patients. Furthermore, our study showed that deep sleep duration was related with physical activity and emphasized the importance of sleep evaluation in MS patients.

In recent years, an increasing number of research papers revealed that the compositional and volumetric alterations in the extracellular matrix are the consequences of aging and may be related to Alzheimer's disease (AD). In this study, we aimed to demonstrate the alterations in hippocampal extracellular fluid proteins in vivo using the 5XFAD mouse model. Samples were obtained from hippocampi of 5XFAD mice (n = 6) and their non-transgenic littermates by intracerebral push-pull perfusion technique at 3 months of age, representing the pre-pathological stage of the AD. Proteins in the hippocampal perfusates were analyzed by Ultra Performance Liquid Chromatography-Electrospray Ionization Quadrupole Time-of-Flight Mass Spectrometry (UPLC-ESI-qTOF-MS/MS). 178 proteins were identified and 19 proteins of them were found to be statistically significantly altered (p≤0.05, fold change ≥40%, unique peptide count ≥3) in the hippocampal CA1 extracellular fluid of the 5XFAD mouse model. Ingenuity pathway analysis of the protein expression results identified IL6 as an upstream regulator. The upregulation of IL6 was validated by immunohistochemical staining of the hippocampus and cortex of the 5XFAD mice prior to Aβ plaque formation. Furthermore, the iron level in the hippocampus was measured by inductively coupled plasma-mass spectrometry as IL6 is mentioned in several studies to take part in iron homeostasis and inflammation and found to be increased in 5XFAD mice hippocampus. Alterations in extracellular matrix proteins in addition to increasing amount of hippocampal IL6 and iron in the early stages of AD may reveal inflammation-mediated iron dyshomeostasis in the early stages of neurodegeneration.

Introduction: Cognitive impairment is also an important cause of disability in MS in addition to motor, sensory, visual, and cerebellar affections. The aim of this study is to show the relation between the cognitive disability in MS with brain atrophy and retinal nerve fiber layer (RNFL). Methods: Forty-three multiple sclerosis (MS) patients, and 15 healthy individuals as controls were included in the study. MS patients were divided into three groups as relapsing-remitting MS (RRMS), relapsingremitting with optic neuritis (RRMS+ON), and secondary-progressive MS (SPMS). An experienced psychologist performed modified Wechsler Memory Scale Revised form (WMS-R), Lines Orientation test, Stroop Color Word Interference test (STROOP), Standard Raven Progressive Matrices (SRPM), Benton Facial Recognition Test, verbal fluency test, and Paced Auditory Serial Addition tests in all cases. Optic coherence tomographies (OCT) were done. Cranial subcortical volumes of all subjects were measured using 3-dimensonal T1 A imagines obtained by the cranial subcortical 1.5 tesla MR device (fully automatic Freesurfer program). Brain parenchymal fractions were calculated by proportioning the obtained volume measurements to the total intracranial volume. Results: Fifty-eight subjects (65.5% female, 34.5% male) were enrolled in the study. There were significant differences among the groups in terms of parenchymal thickness, volumes of third ventricle, and white matter. There was a significant correlation between the volumes of the deep gray matter, mesial temporal structures and lateral ventricular volumes, and the test results of the WMS-R. OCT scores of all MS patients, whether or not they experienced optic neuritis, had increased, being worse especially in the SPMS group. Correlation between RNFL and the brain parenchymal fractions of the patients were statistically significant. Conclusion: Manual methods instead of automatic segmentation method are being more commonly used in the studies with brain atrophy and MS in our country. A significant correlation between OCT scores and brain atrophy is shown with our present study, and this is followed as a reflection of decrease in cognitive tests that provides valuable and reliable knowledge for the literature.

With an increasing number of patients being diagnosed with Alzheimer's disease (AD) daily, it has become one of the major problems in public health. The increase in the number of dementia patients in low- and middle-income countries is expected to be much more than that in developed countries. As a result, the economic burden of dementia, both worldwide and in Turkey, is growing. Moreover, AD leads to emotional burdens and psychological distress in family member(s) and caregiver(s) alongside the patient. Each stage of AD imposes different responsibilities on caregivers, increasing their burden. The suffering and emotional burdens of caregivers from these responsibilities lead to a decreased quality of life and disturbed body physiology. Incapacity, despair, weariness, and loneliness are the hidden emotions of this iceberg. This review aims to gather the results of studies on caregiver burden in different stages of AD, attract attention to those results that may have been ignored in Turkey, and shed light on the solutions required to overcome the problems in caregiving of AD patients.

Some incidental findings on cranial imaging may render every one speechless. Brain plasticity in childhood and slow expansion of arachnoid cyst may be possible explanations of the discordance between the clinical and radiological findings. Here, we presented an asymptomatic, incidentally detected arachnoid cyst accompanied by compression of most parts of brain, displacing the motor cortex to the occipital parts of the existing brain tissue. The case was discussed in the light of the rare patients in the literature.

Introduction: Myasthenia Gravis (MG) is a chronic disease which affects physical, psychological and social functioning of patients. In this study we aim to determine psychiatric comorbidity, some psychosocial factors and their relations with quality of life in patients with MG.Methods: A total of 52 patients underwent psychiatric examination and the following scales were applied: Socio-demographic data form, Hospital Anxiety and Depression Scale (HADS), Quality of Life (QOL) Scale Short Form 36 (SF-36), Psychosocial Adjustment to Illness Scale-Self report (PAIS-SR), Multidimensional Scale of Perceived Social Support (MSPSS) and Posttraumatic Growth Inventory (PTGI).Results: Among 52 patients with MG, 36.5% (n=19) had no psychiatric diagnosis; 21.2% (n=11) had adjustment disorder; 19.2% (n=10) had depression and 23.1% (n=12) had anxiety disorder. Patients with a psychiatric diagnosis had lower scores in general health, vitality, social functioning, emotional role and mental health domains of SF-36. PAIS-SR scores, total MSPSS and friends scores were signifitcantly higher in patients without a psychiatric diagnosis. Significant correlaions of psychosocial factors with quality of life were determined.Conclusion: In MG patients, there is a high prevalence of psychopathology and it is associated with quality of life, perceived social support and psychosocial adjustment of the patients. Quality of life is reduced in both physical and mental aspects. Diagnosis and treatment of psychopathology in MG patients is crucial to decrease disease burden.

The cardinal symptoms of limbic encephalitis are amnesia, epileptic seizure and behavioural change. In addition to them, confusion, irritability, depression, sleep problems, hallucination and psychosis can be seen as symptoms. Limbic encephalitis can be confused with metabolic diseases, infections, vasculitis and tumor. The study of autoantibody is helpful on differential diagnosis. The 20 year old patient applied us with the symptoms of behavioural change, amnesia and seizures. As a result of the examination of the available symptoms, EEG, MR, serum and CSF of the patient VGKV positive limbic encephalitis has been confirmed on the patient. The patient who has died on the process of treatment has been discussed in company with literature. For the patients whose pshyciatric symptoms are in the foreground, limbic encephalitis should take place among the differential diagnosis. The autoimmune encephalitis that are being more and more detectable are a part of this group. So, getting help from certain centers as neuroimmunology laboratory is becoming crucial in terms of diagnosis of cases.