The nutritional status of relapsing-remitting multiple sclerosis (RRMS) patients compared to that of healthy people: a Turkish hospital-based study.

OBJECTIVE: This study compares the nutritional status and physical activity levels of relapsing-remitting multiple sclerosis (RRMS) patients and healthy people. METHOD: The study included 120 participants: 60 multiple sclerosis (MS) patients and 60 controls. RRMS diagnoses were made based on the 2017 McDonald criteria. The food intake frequency questionnaire was administered to the participants, their threeday food intake records were collected, their activity levels were determined, and anthropometric measurements were made. The differences between the groups were analyzed using the Mann-Whitney U test and Pearson's exact chi-squared test. RESULTS: The participants with MS (46.7%) had a significantly lower rate of shopping for their own food compared to the control group (68.3%) (p = 0.002). The MS group (3.3%) had a lower rate of intake of green leafy vegetables 5 times weekly or more frequently than the control group (20.0%) (p < 0.05); and the control group (35.0%) had a higher consumption rate of pastry more than 1 to 2 times monthly than the MS group (13.3%) (p < 0.05). The participants with MS had a higher intake of fiber, insoluble fiber, and omega 3 fatty acid than the control group (p < 0.05). Expanded Disability Status Scale (EDSS) scores indicates that a positive correlation was found between daily intake of fiber and insoluble fiber (p < 0.05). The patients with MS in the inactive group had a higher EDSS median [2.00(0.00 -5.00)] than the minimal active group [1.25(0.00 -4.00)] (p = 0.034). CONCLUSION: With the increase in disability in MS patients, their physical activity levels decrease and it becomes difficult for them to shop on their own. In addition, the consumption frequency of green leafy vegetables, which take time to prepare and a source of fiber, is also decreasing. It has been shown that fiber intake decreases when the disability increase. Therefore, preventing the progression of disability in MS patients is very important in ensuring diversity in food consumption.

Temporal overexpression of IL-22 and Reg3γ differentially impacts the severity of experimental autoimmune encephalomyelitis.

IL-22 is an alpha-helical cytokine which belongs to the IL-10 family of cytokines. IL-22 is produced by RORγt+ innate and adaptive lymphocytes, including ILC3, γδ T, iNKT, Th17 and Th22 cells and some granulocytes. IL-22 receptor is expressed primarily by non-haematopoietic cells. IL-22 is critical for barrier immunity at the mucosal surfaces in the steady state and during infection. Although IL-22 knockout mice were previously shown to develop experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), how temporal IL-22 manipulation in adult mice would affect EAE course has not been studied previously. In this study, we overexpressed IL-22 via hydrodynamic gene delivery or blocked it via neutralizing antibodies in C57BL/6 mice to explore the therapeutic impact of IL-22 modulation on the EAE course. IL-22 overexpression significantly decreased EAE scores and demyelination, and reduced infiltration of IFN-γ+IL-17A+Th17 cells into the central nervous system (CNS). The neutralization of IL-22 did not alter the EAE pathology significantly. We show that IL-22-mediated protection is independent of Reg3γ, an epithelial cell-derived antimicrobial peptide induced by IL-22. Thus, overexpression of Reg3γ significantly exacerbated EAE scores, demyelination and infiltration of IFN-γ+IL-17A+ and IL-17A+GM-CSF+Th17 cells to CNS. We also show that Reg3γ may inhibit IL-2-mediated STAT5 signalling and impair expansion of Treg cells in vivo and in vitro. Finally, Reg3γ overexpression dramatically impacted intestinal microbiota during EAE. Our results provide novel insight into the role of IL-22 and IL-22-induced antimicrobial peptide Reg3γ in the pathogenesis of CNS inflammation in a murine model of MS.

Transient monocular visual impairment as an initial symptom of COVID-19 infection in an individual with multiple sclerosis receiving teriflunomide.

In December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan and rapidly spread throughout China. Since the outbreak of the pandemic, in addition to the well-known COVID-19 symptoms, various neurological symptoms have been also described in patients with COVID-19. Here, we report an unusual presentation of COVID-19 infection in a teriflunomide-treated individual with multiple sclerosis (MS) who did not interrupt teriflunomide treatment during the infection. The course of the infection was mild in this case as in other reported teriflunomide-treated individuals with COVID-19. COVID-19's presentation may be unusual in people with MS (pwMS). It can also be concluded that teriflunomide may be considered a safe disease-modifying treatment option during the pandemic.

Multicenter study of levodopa carbidopa intestinal gel in Parkinson's disease: the Turkish experience

Background/aim: Our purpose was to determine the efficacy of levodopa carbidopa intestinal gel (LCIG) in a series of Turkish patients with Parkinson's disease (PD). Materials and methods: We had telephone calls with 54 patients from 11 neurology centers who were on LCIG treatment, and 44 patients or their caregivers were included in an eight-item survey between September 2015 and June 2016. The reliability and validity of the survey were evaluated with intraclass correlation coefficients for every question separately. Results: Average age of the patients were 63.48 and the duration of PD was 12.79 years. Average LCIG treatment period was 15.63 months. Percentages of the patients who reported they were 'better' after LCIG treatment were as follows: 80% for time spent off, 55% for dyskinesia, 65% for tremor, 85% for gait disorder, 50% for pain, 50% for sleep disorders, 42.5% for depression, 32.5% for incontinence, and 70% for activities of daily living. Cronbach's alpha was 0.795 and the intraclass correlation coefficient was reliable for the items. Conclusion: As detected by a survey performed by telephone calls with good interrater reliability, patients with PD improve with LCIG treatment in many aspects of the disease.

Evaluation of Retinal Changes in Progressive Supranuclear Palsy and Parkinson Disease.

BACKGROUND: Differentiating Parkinson disease (PD) from progressive supranuclear palsy (PSP) can be challenging early in the clinical course. The aim of our study was to see if specific retinal changes could serve as a distinguishing feature. METHODS: We used spectral domain optical coherence tomography (SD-OCT) with automatic segmentation to measure peripapillary nerve fiber layer thickness and the thickness and volume of retinal layers at the macula. RESULTS: Thicknesses of superior peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer, inner plexiform layer, inner nuclear layer, and macular volume were more affected in PSP compared with PD (P < 0.05). Thicker inferotemporal pRNFL and lower macular volume were detected in levodopa users compared with nonusers in patients with PD. CONCLUSIONS: PD and PSP are associated with distinct changes in retinal morphology, which can be assessed with SD-OCT.

Evaluation of Utilizing the Distinct Genes as Predictive Biomarkers in Late-Onset Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by a devastating decline in cognitive activities among all types of dementia, and it severely affects the quality of life. Late-onset AD (LOAD) occurs after the age of 65 years and develops sporadically. Although aging comes first along the main risk factors underlying LOAD, disease-causing susceptibility genes have been associated with disease pathogenesis. In our study, we included the genes PARP1 , POLB , HTRA2 , SLC1A2 , HS1BP3 , and DRD3 to be investigated in LOAD patients based on their expression levels. Within this framework, we aimed to determine the possible functions of these genes in the pathophysiology of the disease. We investigated whether the utilization of these genes as biomarkers in the early diagnosis of LOAD may help the treatment scheme to be applied in the clinic. We involved 50 individuals in the study and collected peripheral blood samples from the patients and control groups for molecular genetic analysis. Subsequently, RNA was extracted from the peripheral blood samples, and expression analyzes were performed using qualitative reverse transcription polymerase chain reaction. The results obtained were evaluated by using proper statistical methods. Our results demonstrated that there was no difference between patient and control groups in terms of HTRA2 , DRD3 , HS1BP3 , and POLB genes. The expression levels of the SLC1A2 and PARP1 genes were significantly lower in the patient group compared with the control group. In conclusion, we presume that the PARP1 and SLC1A2 genes can be utilized as molecular biomarkers for LOAD.

A Novel SGCE Nonsense Variant Associated With Marked Intrafamilial Variability in a Turkish Family With Myoclonus-Dystonia.

BACKGROUND: Myoclonus-Dystonia syndrome (M-D) is an autosomal-dominant movement disorder related to SGCE gene pathogenic variants. Although there can be observed variability in clinical findings, here we describe intrafamilial variability in a Turkish family with a novel nonsense SGCE pathogenic variant. METHODS: A family with variable clinical symptoms resembling M-D were referred to our clinic. After preliminary diagnosis, patients were tested for mutations in the SGCE gene by Sanger sequencing. RESULTS: Novel pathogenic heterozygous nonsense mutation in exon 3, c.272T>G; p.Leu91* (NM_003919.2) were observed in affected family members. CONCLUSION: Intrafamilial clinical variability, despite the same pathogenic variant described in this work, suggests that there are regulatory factors, epigenetic or environmental modifiers, which are the subject of a matter for future studies.

Fingolimod Alters Tissue Distribution and Cytokine Production of Human and Murine Innate Lymphoid Cells.

Sphingosine-1 phosphate receptor 1 (S1PR1) is expressed by lymphocytes and regulates their egress from secondary lymphoid organs. Innate lymphoid cell (ILC) family has been expanded with the discovery of group 1, 2 and 3 ILCs, namely ILC1, ILC2 and ILC3. ILC3 and ILC1 have remarkable similarity to CD4+ helper T cell lineage members Th17 and Th1, respectively, which are important in the pathology of multiple sclerosis (MS). Whether human ILC subsets express S1PR1 or respond to its ligands have not been studied. In this study, we used peripheral blood/cord blood and tonsil lymphocytes as a source of human ILCs. We show that human ILCs express S1PR1 mRNA and protein and migrate toward S1P receptor ligands. Comparison of peripheral blood ILC numbers between fingolimod-receiving and treatment-free MS patients revealed that, in vivo, ILCs respond to fingolimod, an S1PR1 agonist, resulting in ILC-penia in circulation. Similarly, murine ILCs responded to fingolimod by exiting blood and accumulating in the secondary lymph nodes. Importantly, ex vivo exposure of ILC3 and ILC1 to fingolimod or SEW2871, another S1PR1 antagonist, reduced production of ILC3- and ILC1- associated cytokines GM-CSF, IL-22, IL-17, and IFN-γ, respectively. Surprisingly, despite reduced number of lamina propria-resident ILC3s in the long-term fingolimod-treated mice, ILC3-associated IL-22, IL-17A, GM-CSF and antimicrobial peptides were high in the gut compared to controls, suggesting that its long term use may not compromise mucosal barrier function. To our knowledge, this is the first study to investigate the impact of fingolimod on human ILC subsets in vivo and ex vivo, and provides insight into the impact of long term fingolimod use on ILC populations.

Awareness of Migraine Among Primary Care Physicians in Turkey: A Regional Study.

INTRODUCTION: Migraine is a primary headache that involves genetic and environmental factors. In studies conducted in different countries, migraine was shown to be underdiagnosed, treated insufficiently, and highly related to disability. The primary aim of this study was to identify the competence in making a diagnosis of migraine by primary care physicians who provide basic health care to patients. METHODS: Primary care physicians (266 individuals) working in the primary health service centers located within the borders of Kayseri province were included in our study. The research was conducted by using techniques such as face-to-face meetings with the primary care physicians and by participants filling in questionnaires. A neurologist evaluated the questionnaire form. The information provided by the participants was evaluated according to the migraine without aura diagnostic criteria prepared by the International Headache Society (ICHD-3 Beta). RESULTS: Only 10.5% participants were able to give the complete diagnostic criteria of migraine without aura. The most well-known properties were unilateral (53.4%) and pulsating headaches (47%). CONCLUSION: This study showed that educational programs are required regarding migraines for primary care physicians, supported by complete educational material.

Female Parkinson's disease caregivers have much anxiety and depressive symptom.

OBJECTIVE: Parkinson's Disease Caregivers (PDC) play an important role, especially in the medium and advanced phase of the disease for patients' daily life activities, treatment, and follow-up. The aim of this study is to attract attention to the factors which place PDC at risk of psychological problems and to give consideration to these factors. MATERIALS AND METHODS: First of all, the 80 participants, who were PDC, filled in the demographic information form. The Hospital Anxiety and Depression Scale (HADS) was applied in order to determine the psychological status of the PDC. RESULTS: The average age of PDC in the study was found as 47.94. While 11 (13.8%) of the PDC had undergone psychiatric treatment in the past, four of them (5%) were currently receiving treatment. Twenty-eight (35%) of those who provide care have experience in patient care, whereas 52 (65%) of them have no prior experience in caring for patients. Thirty-six (45%) of the PDC reported that they had difficulties, which were mostly psychological. According to the HADS which was applied, anxiety was seen in 26 of those who provide care (32.5%), while depression was seen in 41 (51.3%). CONCLUSION: This study is the first to provide data on the psychological status of PDC in our country. It is important that PDC's psychological problems are reduced by psychotherapy or, if necessary, by treatment. This situation has a direct negative effect on the patient's daily life activities.

The Level of Knowledge of Parkinson's Disease among Nonprofessional Caregivers in a Movement Disorders Center in Turkey.

Introduction. Only a few studies have been conducted to determine the level of knowledge among caregivers about Parkinson's disease (PD). The aim of the current study was to determine the knowledge of PD among caregivers at a movement disorder clinic in Turkey. Methods. We conducted a questionnaire based interview with the subjects in a tertiary care neurology facility in Turkey. The questions were divided into two parts covering the symptomatology and treatment of PD. A questionnaire consisting of 10 questions was applied to the subjects who had to mark the correct option in a stipulated time. Results. Eighty caregivers were included in the study. The caregivers' mean age was 47.94 years (SD = 12.40). There were 47 female caregivers (58.8%). The most well-known question was that the number of drugs given to the patient may vary with time (76.3%), whereas "the benefit noted in the patient's treatment decreases over time" was the least known question (11.3%). Discussion. This study is the first in our country and shows the necessity to increase the knowledge of PD among caregivers and the public. Education programs may have a positive role in imparting knowledge to the caregivers of PD patients.

Balance performance in three forms of multiple sclerosis.

OBJECTIVES: To compare and document balance performance between patients with multiple sclerosis (MS) and healthy control subjects and balance performance among patients with different MS forms using a set of clinical balance tests. MATERIAL AND METHODS: Twenty eight primary progressive (PPMS), 34 secondary progressive (SPMS), and 62 relapsing remitting (RRMS), totalling 124 MS patients were included in the present study. Results from patients were compared with those of 31 healthy control subjects matching in age, gender, weight and height. Ashworth scale, mini-mental state examination and motricity index were used consecutively to evaluate spasticity, cognitive impairment and lower extremity muscle strength. Vision, sensation, proprioception, cerebellar and vestibular tests were also performed on the patients. The balance performance was evaluated using a set of clinical tests including steady stance tests (eyes in opened and closed positions, feet apart, feet together, stride stance, tandem stance and single stance), self-generated perturbations (functional reach, arm raise and step test), external perturbations, Tinetti-gait and 10 m gait time tests. RESULTS: There were no differences in age, sex, weight, height, sense impairment and lower extremity strength in patients with the three MS forms (p>0.05). No difference was found among patients with the three MS forms and the control subjects in the test of eyes closed with feet apart (p>0.05). The PPMS patients in all the balance tests except tests of eyes closed with feet apart and eyes opened with feet together, SPMS patients in all the balance tests except that of eyes closed with feet apart and RRMS patients in tandem stance, single leg stance, self-generated perturbations, external perturbations, Tinetti-gait and 10 m gait time tests had weaker balance than the control subjects (p<0.001). There were some differences between patients in the PPMS and SPMS groups in the eyes closed and feet apart test, between patients in the PPMS and RRMS groups in all the balance tests except eyes closed and feet apart and eyes opened and feet together tests and between patients in SPMS and RRMS group in all the balance tests except right and left arm raised tests (p<0.001). CONCLUSION: Balance in MS patients is impaired. The results of the present study show that there is more impairment in progressive MS forms than in RRMS. Meanwhile, patients with progressive MS are more likely to fall.

Monitoring interferon ß treatment response with magnetic resonance spectroscopy in relapsing remitting multiple sclerosis.

The aim of this study is to compare the white matter of multiple sclerosis (MS) patients with healthy controls and to monitor the response to the treatment with magnetic resonance spectroscopy (MRS).Fifteen healthy controls and 36 recently diagnosed MS patients never treated with interferon ß were included in this study. In the patient group, MRS was performed before treatment, at 6th and 12th month after the initiation of treatment and once in control group. Patient group was divided into 3 interferon groups randomly. Physical examination findings were recorded as Expanded Disability Status Scale scores before treatment, at 6th and 12th month of interferon treatment.At the end of 1 year follow up, 26 of 36 patients completed the study. In patients' white matter lesions, N-acetylaspartate/creatine (NAA/Cr) ratios were lower than control group's white matters. NAA/Cr ratios were higher in control group's white matter than patient's normal appearing white matter but this difference was not statistically significant. There was no difference in choline/creatine (Cho/Cr) ratios between 2 groups. In follow-up period, NAA/Cr and Cho/Cr ratios obtained from patients' white matter lesions and normal appearing white matter did not change statistically.This study showed that in MS patients' white matters, especially in white matter lesions, neuron viability is reduced compared with healthy controls' normal white matter; and in the patients treated with interferon ß NAA/Cr ratios remained stable. These stable levels of metabolite ratios in the patients who received interferon ß therapy can be explained with either the shortness of the follow-up period post-treatment or may reflect a positive effect of the beta interferon therapy on the progress of MS.