The role of oligoclonal band count and IgG index in treatment response and disease activity in multiple sclerosis.

BACKGROUND/AIM: Multiple sclerosis (MS) is an inflammatory demyelinating central nervous system (CNS) disease. Among the paraclinical tests, brain and spinal Magnetic Resonance Imaging (MRI) is primarily involved in the diagnosis process, and cerebrospinal fluid (CSF) analysis is fundamental in diagnosing MS and the differential diagnosis. A positive relationship was demonstrated between oligoclonal band (OCB) positivity, CSF band number and immunoglobulin G(IgG) index. The study aimed to evaluate whether the number of OCB can predict disease activity and determine a correlation with the IgG index. METHODS: Our study included 401 MS patients who had relapsing-remitting multiple sclerosis (RRMS), primary progressive multiple sclerosis (PPMS), secondary progressive multiple sclerosis (SPMS), clinic isolated syndrome (CIS), radiologic isolated syndrome (RIS), Neuromyelitis optica spectrum disorder (NMOSD) and Acute disseminated encephalomyelitis (ADEM) with OCB number groups of 2-4, 4-8, 8-12, and 12 and above. RESULTS: No significant correlation was observed between IgG index, pre-and post-treatment EDSS (Expanded Disability Status Scale Scores) and disease-modifying therapies (DMT). Drug response was better in the patient group with band number between 2 and 8 and post-treatment EDSS scores were lower (1.62±0.44). CONCLUSION: The study results suggested that band number may be as valuable as the IgG index and a predictive biomarker for disease activity.

Erratum: Clinical and Demographic Characteristics and Two-Year Efficacy and Safety Data of 508 Multiple Sclerosis Patients with Fingolimod Treatment.

[This corrects the article on p. 23 in vol. 60, PMID: 36911568.].

Clinical and Demographic Characteristics and Two-Year Efficacy and Safety Data of 508 Multiple Sclerosis Patients with Fingolimod Treatment.

Introduction: Fingolimod is the first oral immunomodulatory treatment used as secondary care therapy in the treatment of multiple sclerosis for the last 10 years. The objective of our study is to reveal the experiences of the first generic fingolimod active ingredient treatment in different centers across Turkey. Method: The first generic fingolimod efficacy and safety data of patients followed-up in 29 different clinical multiple sclerosis units in Turkey were analyzed retrospectively. Data regarding efficacy and safety of the patients were transferred to the data system both before the treatment and on the 6th, 12th and 24th month following the treatment. The data were analyzed using the IBM SPSS 20.00. P value of <0.05 was considered to be statistically significant. Results: A total of 508 multiple sclerosis patients, 331 of whom were women, were included in the study. Upon comparing the Expanded Disability Status values before and after the treatment, a significant decrease was observed, especially at month 6 and thereafter. Since bradycardia occurred in 11 of the patients (2.3%), the first dose had to be longer than 6 hours. During the observation of the first dose, no issues that could prevent the use of the drug occured. Side effects were seen in 49 (10.3%) patients during the course of fingolimod treatment. Respectively, the most frequent side effects were bradycardia, hypotension, headache, dizziness and tachycardia. Conclusion: The observed results regarding efficacy and safety were similar to clinical trial data in the literature and real life data in terms of the first equivalent with fingolimod active ingredient.

The comparative effectiveness of fingolimod, natalizumab, and ocrelizumab in relapsing-remitting multiple sclerosis.

BACKGROUND: Fingolimod, natalizumab, and ocrelizumab are commonly used in the second-line treatment of relapsing-remitting multiple sclerosis (RRMS). However, these have only been compared in observational studies, not in controlled trials, with limited and inconclusive results being reported. A comparison of their effect on relapse and disability in a real-world setting is therefore needed. OBJECTIVES: The objective of this study was to compare the efficacy of fingolimod, natalizumab, and ocrelizumab in reducing disease activity in RRMS. METHODS: This multicenter, retrospective observational study was carried out with prospectively collected data from 16 centers. All consecutive RRMS patients treated with fingolimod, natalizumab, and ocrelizumab were included. Data for relapses, Expanded Disability Status Scale (EDSS) scores, and brain magnetic resonance imaging (MRI) scans were collected. Patients were matched using propensity scores. Annualized relapse rates (ARR), time to first relapse, and disability accumulation were compared. RESULTS: Propensity score matching retained 736 patients in the fingolimod versus 370 in the natalizumab groups, 762 in the fingolimod versus 434 in the ocrelizumab groups, and 310 in the natalizumab versus 310 in the ocrelizumab groups for final analyses. Mean ARR decreased markedly from baseline after treatment in all three treatment groups. Mean on-treatment ARR was lower in natalizumab-treated patients (0.09, 95% confidence interval (CI), 0.07-0.12) than in those treated with fingolimod (0.17, 0.15-0.19, p<0.001), ocrelizumab (0.08, 0.06-0.11), and fingolimod (0.14, 0.12-0.16, p=0.001). No significant difference was observed in mean on-treatment ARR between patients treated with natalizumab (0.08, 0.06-0.11) and ocrelizumab (0.09, 0.07-0.12, p=0.54). Compared to fingolimod, the natalizumab and ocrelizumab groups exhibited a higher percentage of relapse-free patients and a lower percentage of MRI-active patients at year 1. No significance differences in disability accumulation were determined between the therapies. CONCLUSION: Natalizumab and ocrelizumab exhibited similar effects on relapse control, and both were associated with better relapse control than fingolimod. The effects of the three therapies on disability outcomes were similar.

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.

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.

Positive effects of ocrelizumab in patients with familial mediterranean fever and coexistent multiple sclerosis.

OBJECTIVES: This study aims to evaluate the effects of ocrelizumab (OCZ) on familial Mediterranean fever (FMF) attacks in multiple sclerosis (MS) patients with FMF (MS+FMF patients). PATIENTS AND METHODS: This retrospective observational study included 11 patients (2 males, 9 females; mean age 46.6±9.2; range, 22 to 55 years) with MS+FMF hospitalized between January 2016 and July 2019. Demographic, clinical, and laboratory parameters and patient reported outcomes were analyzed in patients treated with OCZ for 18 months. RESULTS: Combining OCZ with colchicine in MS+FMF patients significantly reduced the frequency of FMF attacks (p=0.003) and the frequency of joint attacks (p=0.002). Consistent with the clinical improvement, the maximum serum C-reactive protein levels were significantly decreased after combination therapy compared to before combination therapy (p=0.003). MS+FMF patients reported that FMF disease activity improved after OCZ therapy (Visual Analog Scale [VAS] 74±9.6 vs. VAS 46.5±8.1 mm, p=0.003). CONCLUSION: Ocrelizumab therapy led to a prominent decrease in the frequency of FMF attacks, alleviated functional impairment, and improved quality of life in MS+FMF patients.

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.

Efficacy and Tolerability of Interferon Gamma in Treatment of Friedreich's Ataxia: Retrospective Study.

Friedreich's Ataxia (FRDA) is the most common form of autosomal recessive ataxia. The disease primarily results from a GAA trinucleotide repeat expansion within the FXN gene in up to 97% of patients. The clinical presentation begins approximately between the ages of 5 and 15. The major clinical findings of FRDA are progressive extremity and gait ataxia. Although it is known that the disease is caused by low levels of functional protein in the target tissues, there is no effective treatment available for this pathology. However, significant improvements have been achieved in the research into pharmacological treatments for FRDA in recent years. Interferon-gamma (IFN-γ) has been shown to induce frataxin production in many cell types. In this study, the clinical features, tolerability, and the prognosis of individuals with FRDA to whom IFN-γ was administered in a university hospital were evaluated retrospectively and the results were discussed. To the best of our knowledge, this is the first study conducted in our country to evaluate the effect of IFN gamma on this patient group.

Diffusion tensor imaging of the median nerve healing. Preliminary results.

AIMS: This study aimed to examine the correlation between DTI, clinical assessment, and electromyography results in patients who underwent primary median nerve repair. METHODS: Ten patients who underwent primary repair of the complete median nerve transection were included. Study assessments were performed on both the traumatized and non-traumatized extremities and patients were followed up for a minimum duration of 11 months. Clinical assessments, (Tinnel test, static 2-point discrimination test, motor and quality of life assessments), electromyography and DTI were performed. RESULTS: None of the clinical or electromyographic parameters correlated significantly with any of the diffusion tensor imaging parameters, i.e. fractional anisotropy (FA) or apparent diffusion coefficient (ADC) (p>0.05 for all). In addition, The Disabilities of the Arm, Shoulder and Hand (DASH) scores did not correlate with either FA (r=0.55, p=0.098) or ADC (r=0.40, p=0.260) values. However, Tinnel positive cases (n=3) had lower relative FA when compared to Tinnel negative cases (n=7) (-0.11±0.19 vs. 0.05±0.04, p=0.033). CONCLUSION: Our findings do not support the presence of relations between DTI parameters and electromyographic or most of the clinical parameters. Further MRI studies with larger numbers of patients with complete transection of the median nerve using the novel imaging parameters are warranted. KEY WORDS: Diffusion Tensor Imaging (DTI), Electromyography (EMG), Median nerve, Nerve injury, Nerve repair.

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.

Nasu Hakola Disease: A Rare Cause of Dementia and Cystic Bone Lesions, Report of a New Turkish Family.

The differential diagnosis of young-onset progressive dementia is an issue that requires effort. Recording the family history and careful clinical evaluation are useful tools in the diagnosis. In case of genetic bases, definitive diagnosis requires molecular analysis. We report consanguineous two patients presenting with young-onset progressive dementia characterized by behavioral changes and with bone cysts. Concomitant bone pathology and inheritance pattern directed us to investigate TREM2 gene, for differential diagnosis, which resulted with the identification of a causative mutation that confirmed the diagnosis of Nasu Hakola disease. The mutation (c.113A>G) is the same for a Turkish family with Nasu Hakola disease reported before. But the presence of bone cysts and absence of epilepsy in our patients are the different findings. Molecular analysis should be considered in patients with young age onset behavioral and cognitive deficits, with white matter lesions in brain magnetic resonance imaging, if especially associated with cystic bone lesions.

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.

A rare entity in ED: posterior reversible encephalopathy syndrome.

Posterior reversible encephalopathy syndrome is a clinico-neuroradiologic entity with typical symptoms and symmetric high-signal intensity lesions in the bilateral parietooccipital lobes on T2-weighted or fluid-attenuated inversion recovery magnetic resonance imaging. In this presentation, we report a case of posterior reversible encephalopathy syndrome who was admitted to our emergency department because of seizure and deterioration of consciousness. The aim of this presentation is to alert the emergency physicians about one of the hypertensive emergencies with neurologic symptoms associated with hypertension.