[Effects of rituximab on prognosis in myasthenia gravis: A single-center experience from Turkey]. / A rituximab hatása a myasthenia gravis prognózisára: egy központú, törökországi tapasztalat.

Background and purpose: Management of treatment-resistant patients with myasthenia gravis (MG) remains an important issue. This study aimed to evaluate the effects of rituximab (RTX) treatment on the prognosis of patients with acetylcholine receptor autoantibody-positive (AChR-Ab+), muscle-specific kinase autoantibody-positive (MuSK-Ab+), or seronegative or double seropositive MG. Methods: Nineteen patients treated with RTX between 2015 and 2020 were included in this study. Demographic and clinical characteristics, prognosis, and prognostic predictors of MG were evaluated retrospectively. The Myas-thenia Gravis Foundation of America Post-Inter-vention Status (MGFA-PIS) before RTX treatment (pre-RTX) and after RTX treatment (post-RTX) were recorded. Results: A total of 10 patients (52.6%) were AchR Ab+, 6 patients (31.6%) were MuSK Ab+, 1 patient (5.3%) was seronegative, and 2 patients (10.5%) were double seropositive. Steroid dose was pre-RTX 38.9±5.7 (25-45), it was post-RTX 10.5±10.3 (0-30) (p<0.001). Post-RTX steroid treatment was discontinued in 6 of 19 patients (p=0.041). Only three patients received intravenous immunoglobulin at the post-RTX follow-up (p<0.001). In post-RTX 12th month, the MGFA-PIS score was as minimally manifestation or better in 9 patients (47.3%) and improved or was better in 18 patients (94.7%) (p-value 0.004; <0.001, respectively). Conclusion: The improvement in MGFA-PIS scores post-RTX was similar in MuSK-Ab+ and AChR-Ab+ patients. The data are insufficient in seronegative and double seropositive patients and RTX must be considered in the treatment of suitable patients with MuSK-Ab+ and AChR-Ab+ refractory MG.

Assessment of genes involved in behavior, learning, memory, and synaptic plasticity following status epilepticus in rats.

OBJECTIVE: In this study, it was aimed to evaluate cognitive and behavioral changes after status epilepticus (SE) induced by pentylenetetrazole in immature rats via Morris water maze and open-field area tests and to assess alterations in expression of 84 key genes involved in synaptic plasticity after SE. METHOD: The study was conducted on 30 immature rats (12-days old). The rats were assigned into groups as control and experiment (SE) groups. The SE was induced by pentylenetetrazole in 12-days old rats. In addition, experiment group was divided into two groups as mature (n = 8) and immature SE (n = 8) subgroups. Again, the control group was divided into two groups as mature (n = 7) and immature control (n = 7) subgroups. Hippocampal tissue samples were prepared, and expression of 84 key genes involved in synaptic plasticity was assessed in Genome and Stem Cell Center of Erciyes University before behavioral tests in immature rats (22-days old) and after open-filed area and Morris water maze tests in mature rats (72-days old) in both experiment and control groups. RESULTS: No significant difference was detected in behavioral tests assessing spatial memory and learning among groups. Significant differences were detected, ARC (activity-regulated cytoskeleton-associated protein), BDNF (brain-derived neurotrophic factor), MAPK1 (mitogen-activated protein kinase 1), NR4A1 (nuclear receptor subfamily 4 group A member 1), PPP3CA (protein phosphatase 3 catalytic subunit alpha), RGS2 (regulator of G protein signaling 2), and TNF (tumor necrosis factor) gene expressions between control and experiment groups in immature rats whereas in ADCY8 (adenylate cyclase 8), BDNF (brain-derived neurotrophic factor), EGR4 (early growth response 4), and KIF17 (kinesin family member 17) gene expressions between control and experiment groups in mature rats. DISCUSSION: In this study, differences detected in gene expressions of synaptic plasticity after SE indicate in which steps of synaptic plasticity may be problematic in epileptogenesis. The gene expressions in this study may be considered as potential biomarkers; however, epileptogenesis is a dynamic process and cannot be explained through a single mechanism. Future studies on epileptogenesis and studies specifically designed to evaluate genes detected in our study will further elucidate synaptic plasticity in epilepsy and epileptogenesis.

Frequency of carpal tunnel syndrome and hand dysfunction in prediabetes: A cross-sectional, controlled study.

Objectives: This study aims to evaluate the frequency of carpal tunnel syndrome (CTS), to investigate the impairment of hand functions in patients with prediabetes (PD), and to compare laboratory findings of PD patients with and without CTS. Patients and methods: Between June 2018 and January 2019, a total of 115 patients (29 males, 86 females; mean age: 51.4±11.8 years; range, 24 to 78 years) who were recently diagnosed with PD and a total of 54 healthy participants (17 males, 37 females; mean age: 48.4±13.2 years; range, 21 to 78 years) as the control group were included. Demographic and clinical data of the patients including oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) were recorded, and both groups were examined for the presence of CTS. Clinically suspected CTS was confirmed by electrodiagnostic studies. The hand grip strength (HGS) was measured and hand functions were evaluated using the Duruöz Hand Index (DHI). Results: There were no significant differences in the age, sex, occupation, body mass index (BMI), or insulin resistance between the groups. A total of 24 (20.9%) patients with PD and eight (14.8%) healthy controls had CTS (p=0.349). Hand functions were worse in the PD patients than the control group (p=0.044). Age, occupation, BMI, insulin resistance, OGTT at 0 and 2 h, and HbA1c values were similar between the PD patients with or without CTS. Conclusion: Our study, for the first time, reveals that CTS is slightly more common and hand functions are impaired in PD compared to the healthy individuals. Based on these findings, we suggest that hand functions should be evaluated in PD patients.

Clinical findings, etiological factors, and prognosis markers in status epilepticus: a university hospital experience.

OBJECTIVE: To determine the factors affecting mortality and disability in status epilepticus (SE) and to evaluate the prediction ability of the Status Epilepticus Severity Score (STESS) for disability and mortality. MATERIALS AND METHOD: The demographic and clinical characteristics, prognosis and prognosis predictors of 72 patients who were diagnosed with SE between 2013 and 2018 were retrospectively evaluated. The STESS was used to predict prognosis, and the modified Rankin scale (mRS) was used to determine the disability at discharge. RESULTS: The study population had a mean age of 45.4 ± 20.7, and it was found that mortality was 22.2% and acute symptomatic etiology played a 54.1% role in etiology. Advanced age, refractory SE or super-refractory SE, acute symptomatic etiology, and a history of epilepsy were related to mortality, symptomatic etiology (acute, progressive, remote), a history of hospitalization and epilepsy in intensive care or in other departments other than the neurology department were associated with disability. The sensitivity of STESS in predicting mortality was 100%, specificity was 69%, accuracy was 76.4%, positive predictive value (PPV) was 48.5%, and the negative predictive value (NPV) was 100%. The sensitivity of STESS in predicting mobilization during discharge was 55.6% with a 63.9% specificity and 59.7% accuracy, PPV was 60.6%, and NPV was 59%. CONCLUSION: It was observed that STESS strongly predicts a good prognosis; however, it was not found to be useful in predicting motor disability during discharge. Thus, new studies should be conducted to predict and evaluate mobility in SE patients at discharge.

Stratification of the Gut Microbiota Composition Landscape across the Alzheimer's Disease Continuum in a Turkish Cohort.

Alzheimer's disease (AD) is a heterogeneous disorder that spans a continuum with multiple phases, including preclinical, mild cognitive impairment, and dementia. Unlike for most other chronic diseases, human studies reporting on AD gut microbiota in the literature are very limited. With the scarcity of approved drugs for AD therapies, the rational and precise modulation of gut microbiota composition using diet and other tools is a promising approach to the management of AD. Such an approach could be personalized if an AD continuum can first be deconstructed into multiple strata based on specific microbiota features by using single or multiomics techniques. However, stratification of AD gut microbiota has not been systematically investigated before, leaving an important research gap for gut microbiota-based therapeutic approaches. Here, we analyze 16S rRNA amplicon sequencing of stool samples from 27 patients with mild cognitive impairment, 47 patients with AD, and 51 nondemented control subjects by using tools compatible with the compositional nature of microbiota. To stratify the AD gut microbiota community, we applied four machine learning techniques, including partitioning around the medoid clustering and fitting a probabilistic Dirichlet mixture model, the latent Dirichlet allocation model, and we performed topological data analysis for population-scale microbiome stratification based on the Mapper algorithm. These four distinct techniques all converge on Prevotella and Bacteroides stratification of the gut microbiota across the AD continuum, while some methods provided fine-scale resolution in stratifying the community landscape. Finally, we demonstrate that the signature taxa and neuropsychometric parameters together robustly classify the groups. Our results provide a framework for precision nutrition approaches aiming to modulate the AD gut microbiota. IMPORTANCE The prevalence of AD worldwide is estimated to reach 131 million by 2050. Most disease-modifying treatments and drug trials have failed, due partly to the heterogeneous and complex nature of the disease. Recent studies demonstrated that gut dybiosis can influence normal brain function through the so-called "gut-brain axis." Modulation of the gut microbiota, therefore, has drawn strong interest in the clinic in the management of the disease. However, there is unmet need for microbiota-informed stratification of AD clinical cohorts for intervention studies aiming to modulate the gut microbiota. Our study fills in this gap and draws attention to the need for microbiota stratification as the first step for microbiota-based therapy. We demonstrate that while Prevotella and Bacteroides clusters are the consensus partitions, the newly developed probabilistic methods can provide fine-scale resolution in partitioning the AD gut microbiome landscape.

Determinants of disability development in patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is one of the most common chronic neurological diseases affecting the central nervous system in young adults. OBJECTIVE: To investigate demographic and clinical factors that are effective in the development of irreversible disability from the onset of MS, and to identify factors that affect the transformation from the relapse-remitting MS (RRMS) phase to the progressive MS (PMS) phase. METHODS: Retrospective study on 741 patients who were diagnosed with RRMS and PMS according to the McDonald criteria, and were enrolled into the Turkish MS database of the Department of Neurology MS Polyclinic, at the Faculty of Medicine, Karadeniz Technical University, in Trabzon, Turkey. Kaplan-Meier analysis was used to evaluate the time taken to reach EDSS 4 and EDSS 6 from the onset of disease, and the time taken between EDSS 4 and EDSS 6. RESULTS: Age of onset >40 years; having polysymptomatic-type onset, pyramidal or bladder-intestinal system-related first episode; ≥7 episodes in the first 5 years; and <2 years between the first two episodes were found to be effective for MS patients to reach EDSS 4 and EDSS 6. The demographic and clinical parameters that were effective for progression from EDSS 4 to EDSS 6 were: pyramidal or bladder-intestinal system-related first episode; 4‒6 episodes in the first 5 years; >2 years until start of first treatment; and smoking. CONCLUSIONS: Our findings reveal important characteristics of MS patients in our region. However, the associations between these parameters and MS pathophysiology remain to be elucidated.

Relation Between the Novel Marker Monocyte to High-Density Lipoprotein Cholesterol Ratio and Severity in Multiple Sclerosis.

INTRODUCTION: This study aimed to establish whether there is a relationship between the Monocyte to High-Density Lipoprotein Cholesterol (HDL-C) ratio (MHR) and severity of disease, and whether it can be used as a new marker for predicting disability in Multiple Sclerosis (MS), a chronic disease, which is usually contracted in early adolescence. METHODS: 184 patient subjects who had been definitively diagnosed with MS, based on the McDonald criteria, and 105 healthy subjects with a similar age and gender profile were included in the study. The patients' Expanded Disability Status Scale (EDSS) scores, MS subtypes, length of time with the disease and demographics were captured. Blood samples were collected for hematologic and biochemical testing. The MHR values were calculated and statistically compared with those of the control group. RESULTS: The average age of the MS patients was 38.3 ± 8.6 years and their average EDSS score was 2.5 [0-7.5]. The patient arm consisted of 118 (64.1%) females and 66 (35.9%) males. In the patients with MS, the MHR was 15.01 ± 0.63 compared to 9.61 ± 0.25 in the controls. This difference was statistically significant (P < 0.001). In the MS patients, the MHR cut-off value was 12.95 compared to controls, which was statistically significant (P < 0.001). Also, a statistically-significant (r: 0.297, P < 0.001) positive correlation was found between the MHR and EDSS score. CONCLUSION: The Monocyte to High-Density Lipoprotein Cholesterol ratio is associated with disease severity and disability in MS patients, and may be used as an independent marker for predicting disability. However, broader-scale studies are needed for more conclusive results.

Determinants of disability development in patients with multiple sclerosis / Determinantes do desenvolvimento de deficiência em pacientes com esclerose múltipla

Abstract Background: Multiple sclerosis (MS) is one of the most common chronic neurological diseases affecting the central nervous system in young adults. Objective: To investigate demographic and clinical factors that are effective in the development of irreversible disability from the onset of MS, and to identify factors that affect the transformation from the relapse-remitting MS (RRMS) phase to the progressive MS (PMS) phase. Methods: Retrospective study on 741 patients who were diagnosed with RRMS and PMS according to the McDonald criteria, and were enrolled into the Turkish MS database of the Department of Neurology MS Polyclinic, at the Faculty of Medicine, Karadeniz Technical University, in Trabzon, Turkey. Kaplan-Meier analysis was used to evaluate the time taken to reach EDSS 4 and EDSS 6 from the onset of disease, and the time taken between EDSS 4 and EDSS 6. Results: Age of onset >40 years; having polysymptomatic-type onset, pyramidal or bladder-intestinal system-related first episode; ≥7 episodes in the first 5 years; and <2 years between the first two episodes were found to be effective for MS patients to reach EDSS 4 and EDSS 6. The demographic and clinical parameters that were effective for progression from EDSS 4 to EDSS 6 were: pyramidal or bladder-intestinal system-related first episode; 4‒6 episodes in the first 5 years; >2 years until start of first treatment; and smoking. Conclusions: Our findings reveal important characteristics of MS patients in our region. However, the associations between these parameters and MS pathophysiology remain to be elucidated.

RESUMO Introdução: A esclerose múltipla (EM), uma das doenças neurológicas crônicas mais comuns, afeta o sistema nervoso central em jovens adultos. Objetivo: Investigar fatores demográficos e clínicos que são efetivos no desenvolvimento de deficiência irreversível, desde o início da EM, e identificar fatores que afetam a transformação da fase de EM recorrente-remitente (EMRR) para a fase de EM secundária progressiva (EMSP). Métodos: Estudo retrospectivo de 741 pacientes que foram diagnosticados com EMRR e EMSP, de acordo com os critérios de McDonald, e inscritos no banco de dados turco MSBase, do Departamento de Neurologia da MS Polyclinic, da Universidade Técnica de Karadeniz, Turquia. Análise de Kaplan-Meier foi usada para avaliar o tempo para alcançar EDSS 4 e EDSS 6, desde o início da doença e o tempo entre EDSS 4 e EDSS 6. Resultados: Idade de início>40 anos, início do tipo polissintomático, primeiro ataque relacionado ao sistema piramidal ou bexiga-intestinal, ≥7 recaídas nos primeiros 5 anos e <2 anos entre os dois primeiros ataques foram considerados eficazes em pacientes com EM que atingiram EDSS 4 e EDSS 6. Parâmetros demográficos e clínicos que foram efetivos no progresso de EDSS 4 para EDSS 6: primeiro ataque relacionado ao sistema piramidal ou bexiga-intestinal, 4‒6 recaídas nos primeiros 5 anos, >2 anos até o início do primeiro tratamento e tabagismo. Conclusão: Estudo revelou características importantes dos pacientes com EM em nossa região. No entanto, as associações entre esses parâmetros e a fisiopatologia da EM ainda precisam ser elucidadas.