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.

Neurocognitive impairment in multiple sclerosis and its association with thiol-disulfide homeostasis and ischemia-modified albumin.

This study aimed to assess the possible association between cognitive impairment and two important biochemical biomarkers of oxidative stress, thiol-disulfide homeostasis (TDH), and ischemia-modified albumin (IMA) in patients with multiple sclerosis (MS). This study included 85 patients with MS (38 treatment-naïve relapsing-remitting MS (RRMS), 31 RRMS on fingolimod therapy, and 16 secondary progressive MS (SPMS)) and 33 healthy controls. Cognitive evaluation was carried out by applying the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) test battery and the scores were adjusted for age and years of education. Plasma TDH was assessed using an automated method and plasma IMA levels were determined using the cobalt-albumin binding assay. Plasma native thiol and total thiol levels were significantly decreased in patients with SPMS when compared with the naïve patients and healthy controls. Cognitive impairment was detected in 47.4% of naïve patients, 64.5% of patients on fingolimod therapy, and 80% of patients with SPMS. Naïve patients or patients on fingolimod therapy who were cognitively impaired had significantly decreased levels of native thiol and total thiol compared to the cognitively normal patients. Logistic regression analysis revealed total thiol and native thiol to be significantly associated with cognitive impairment in naïve patients and patients on fingolimod therapy. Significant correlations were determined between BICAMS scores, TDH, IMA, clinical indices of disease severity (EDSS and MSSS), and magnetic resonance imaging parameters. This study has shown for the first time that plasma TDH parameters are associated with cognitive impairment in MS.

The Turkish experience of COVID-19 infection in people with NMOSD and MOGAD: A milder course?

BACKGROUND: COVID-19 is a multisystemic infection with variables consequences depending on individual and comorbid conditions. The course and outcomes of COVID-19 during neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) are not clearly known. OBJECTIVE/METHODS: The aim of this study was to examine the features and outcomes of COVID-19 infection in NMOSD and MOGAD patients. The patients' demographic and clinical factors, disease modifying treatment (DMT) used and disease information of COVID-19 infection were recorded. Conditions leading to hospitalization and severe exposure to COVID-19 infection were also analyzed. RESULTS: The study included 63 patients from 25 centers. Thirty-two patients (50.8%) belong to AQP-4 seropositive group, 13 (20.6%) and 18 (28.6%) were in MOG-positive and double-seronegative groups, respectively. Risk factors for severe COVID-19 infection and hospitalization were advanced age, high disability level and the presence of comorbid disease. Disease severity was found to be high in double-seronegative NMOSD and low in MOGAD patients. No statistically significant effect of DMTs on disease severity and hospitalization was found. CONCLUSION: In NMOSD and MOGAD patients, advanced age, high disability and presence of comorbid disease pose risks for severe COVID-19 infection. There was no direct significant effect of DMTs for COVID-19 infection.

Sarcopenia in patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune neurodegenerative disease of the central nervous system. Sarcopenia, which is characterized by the loss of physical performance and poor outcomes, has recently become the focus of research. However, the relationship between sarcopenia and MS has not yet been investigated. This study aims to determine the prevalence of sarcopenia in MS patients and investigate the factors associated with sarcopenia. METHODS: One hundred and one MS patients who can walk without assistance and 55 healthy controls were included. Handgrip strength (HGS) and gait speed tests were applied to all participants. Additionally, anterior thigh muscle thickness (anterior TMT) and skeletal muscle mass index (SSMI) were estimated by ultrasound and bioelectrical impedance analysis (BIA), respectively. According to these tests, MS patients were grouped as either sarcopenic or non-sarcopenic. The groups were compared using clinical and laboratory data, handgrip strength and performance test, Modified Fatigue Impact Scale (MFIS), and the Godin leisure-time exercise questionnaire (GLTEQ). RESULTS: HGS, gait speed, fat free mass (FFM), SMMI, anterior TMT, and sonographic thigh adjustment ratio (STAR) values in patients with MS were significantly lower than healthy controls for both sexes (for female, p:0.001, p:0.001, p:0.010, p:0.049, p:0.001, and p:0.101, respectively; for male, all p:0.001). Compared with healthy controls, MS patients had a significantly lower GLTEQ score (p:0.001), while the MFIS score (p:0.001) was higher. According to STAR, HGS, and gait speed, sarcopenia was diagnosed in 12 (17.64%) female and 7 (21.21%) male patients with MS. Whole-body sarcopenia was diagnosed in only 11 (10.9%) of the patients by BIA. HGS, gait speed, FFM, anterior TMT, and STAR values in sarcopenic MS patients were significantly lower than in non-sarcopenic for females (p:0.001, p:0.001, p:0.004, p:0.001, and p:0.001, respectively) and males (p:0.001, p:0.001, p:0.011, p:0.003, and p:0.001, respectively). MFIS score was significantly higher in sarcopenic patients than non-sarcopenic for both females (p:0.001) and males (p:0.036), but only the physical fatigue subscale was significantly higher. While the physical fatigue score was negatively correlated with GLTEQ in MS patients (r:-0.276, p:0.005), it was positively correlated with the expanded disability status scale (r:0.409, p:0.001). CONCLUSION: We detected that approximately one-fifth of MS patients have sarcopenia. Regional sarcopenia was more prevalent than whole body sarcopenia. We found a high degree of fatigue and lack of exercise in sarcopenic MS patients.

Single nucleotide variants around the connective tissue growth factor (CTGF/CCN2) gene and their association with multiple sclerosis risk, disability scores, and rate of disease progression.

BACKGROUND: This study aimed to explore the possible association of single nucleotide polymorphisms (SNPs) in the upstream (rs9402373) and downstream regions (rs9399005 and rs12526196) of the gene encoding connective tissue growth factor (CTGF/CCN2) with relapsing-remitting multiple sclerosis (RRMS) risk and clinical parameters including disability scores and rate of disability progression. MATERIALS AND METHODS: In total, 200 patients with RRMS and 305 controls were genotyped using real-time PCR (rs1252696 C/T and rs9402373 G/C) or PCR-RFLP (rs9399005 C/T) methods. Furthermore, the association between these genotypes and clinical parameters including Expanded Disability Status Scale (EDSS) score, Multiple Sclerosis Severity Score (MSSS), age at onset, duration of disease, duration of treatment, and presence of contrast-enhancing lesions was analyzed. RESULTS: rs9399005 genotypes TT and CT in the dominant model were significant predictors of RRMS vs. control status by logistic regression analysis (OR = 1.45, 95% CI = 1.01-2.08, P = .04). Moreover, these genotypes for rs9399005 were associated with a MSSS ≥ 2.4 (OR = 3.54, 95% CI = 1.56-8.05, P = .003). In addition, MSSS was lower in patients who had at least one rs12526196C allele than in the corresponding patients with the TT genotype (P = .02). CONCLUSION: To our knowledge, this is the first evidence of the involvement of variants around the CTGF gene in MS risk and disability progression.

More continuous flow, better learning? The effect of aortic valve opening in patients with left ventricular assist device.

PURPOSE: The aim of this study was to analyze neurocognitive function in patients who underwent continuous flow left ventricular assist device (LVAD) implantation. MATERIAL AND METHOD: This cross-sectional study included three groups: LVAD (n = 31), heart failure patients (n = 26), and healthy volunteers (n = 27). The Rey Auditory-Verbal Learning Test (RAVLT), Judgement of Line Orientation Test (JLOT), Trail Making Test (TMT), Stroop Color-Word Interference Test (SCWIT), Verbal Fluency Test (VFT), Symbol-Digit Modality Test (SDMT) were used to assess the neurocognitive functions. Data were analyzed at a median 12 (3-47) months after LVAD implantation. The LVAD patients were also divided by aortic valve opening (AVO) into three subgroups as "closed" (n = 9), "1-6" (n = 8) and "7-10" (n = 14) opening per ten beats and data were re-analyzed accordingly. RESULTS: There was no significant difference among the groups according to SCWIT, JLOT, SDMT, TMT, and VFT scores. Post-hoc analyzes of RAVLT scores showed significant differences between the LVAD and the other two groups in favor of the LVAD group. Also, the patients with AVO "7-10" the response times were longer and learning scores were found to be lower than those without AVO. CONCLUSION: With continuous-flow LVAD, neurocognitive functions were not impaired. The learning performance was better in cases where there was no AVO and flow was completely device dependent. We may speculate that neurocognitive functions are not worsening with continuous cerebral blood flow and even it may improve learning performance.

Effects of continuous-flow left ventricular assist devices on cerebral hemodynamics.

Continuous-flow left ventricular assist devices (LVADs) reduce peak systolic flow, increase diastolic flow, and eliminate pulsatility of circulation. Altered blood flow may lead to a change in end-organ perfusion. Analysis of the flow dynamics of the arteries of end organs, such as the brain, may indicate whether an organ is perfused sufficiently. The aim of this study is to evaluate and identify the flow pattern changes of carotid (CA) and middle cerebral arteries (MCA) in LVAD patients and to compare with heart failure patients and healthy volunteers. Eighty-nine individuals were included in this cross-sectional study. Participants were divided into three groups: LVAD patients (n = 31), heart failure patients (n = 26), and healthy volunteers (n = 27). Carotid and transcranial Doppler ultrasonography were performed for all study groups for peak systolic velocity (PSV), end-diastolic velocity (EDV), pulsatility (PI), and resistive (RI) indices of CA and MCA. Flow dynamics were compared between the groups. Doppler ultrasonographic data were analyzed at a median 12 (3-47) months after LVAD implantation. CA-PSV was lower in LVAD group compared with the other two groups (P < .001), MCA-PSV of LVAD and heart failure groups were similar and lower than healthy volunteers (P < .05). The highest values for CA-EDV were found in the LVAD group (P < .05). MCA-EDV values were found to be lowest in heart failure group (P < .05). For PI and RI, in all CA and MCA, the LVAD group had lower indices compared with the other two groups (P < .001). In addition, MCA flow analysis in patients with LVADs was identified for the first time with this study.

Serum asymmetric dimethylarginine and nitric oxide levels in Turkish patients with acute ischemic stroke.

BACKGROUND: Nitric oxide synthase (NOS) is present in the brain and cerebral arteries and it enables the synthesis of nitric oxide (NO), which plays a critical role in brain perfusion. Asymmetrical dimethylarginine (ADMA) is an endogenous NOS inhibitor. OBJECTIVES: The aim of this study was to evaluate serum ADMA levels, which are an indicator of endothelial dysfunction of the renal functions in patients with acute ischemic stroke, and to determine whether there is a possible correlation between ADMA and NO levels and the l-arginine-to-ADMA ratio. MATERIAL AND METHODS: Fifty-two patients (22 male and 30 female; mean age: 75.2 ±10.1 years) with a diagnosis of acute ischemic stroke in the first 24 h post-stroke and 48 healthy individuals (controls; 13 male and 35 female; mean age: 60.1 ±7.92 years) were included in this study. The risk factors recorded and evaluated were age and gender of the patients, serum lipid levels, serum ADMA levels, nitrate-to-nitrite ratios, l-arginine, l-arginine-to-ADMA ratios, sedimentation rate, C-reactive protein (CRP), urea and creatinine levels, and glomerular filtration ratio (eGFR). RESULTS: The mean serum ADMA level was 0.48 ±0.23 µM for the patients and 0.36 ±0.18 µM for the controls. The mean NO level was 2.78 ±0.59 µM for the patient group and 4.49 ±2.84 µM for the controls. The ADMA levels for the patient group were significantly higher than for the control group (p = 0.011); the NO levels for the patients were significantly lower than for the controls (p < 0.001). The logistic regression method demonstrated that ADMA and NO levels may be independent risk factors for the patient group, and the receiver operating characteristic (ROC) curve analysis showed that both of these variables were discriminative risk factors. CONCLUSIONS: An increased serum level of the NOS inhibitor ADMA was found to be a possible independent risk factor for ischemic stroke.

Analysis of multiple sclerosis patients with electrophysiological and structural tests.

We aimed to analyze the effects of progressive myelin loss and neurodegeneration seen in patients with multiple sclerosis (MS) on visual tract with electrophysiological and structural tests. Fifty-one patients diagnosed with MS in the Neurology Department were followed up in neuro-ophthalmology outpatient clinic irrespective of their visual symptoms, and were included in our study. The patients were classified as the ones with the history of optic neuritis (group II) and ones without the history (group I) of optic neuritis. The data, including clinical presentation, retinal nerve fiber layer thickness (RNFLT) measurements, pattern visual evoked potential (pVEP) and flash electro retino grams (ERG) test results, were recorded. In our study, comparison of pVEP test latencies of groups I and II with each other, and with those of healthy subjects revealed statistically significant differences (p < 0.05). The analysis of rod functions on ERG did not show any significant changes (p > 0.05). However, both groups showed significantly decreased cone b-wave amplitudes, elongation of latencies, and decreased flicker amplitudes on cone and flicker potentials obtained after light adaptation (p < 0.05). There was significant thinning in RNFLT of the both groups when compared to the normal standards. The difference between two groups was statistically significant (p < 0.05). Axon loss is seen in the optic nerve with subclinical or acute optic neuritis in patients with MS. RNFLT analysis and electrophysiological tests are of great importance in diagnosis of MS, as well as to determine progression and to direct neuroprotective therapy in patients diagnosed with MS. Objective analysis methods gain more importance in the diagnosis and follow-up of MS patients, parallel to technological advancements.

Clinical and polysomnographic features of patients with Restless Legs Syndrome.

OBJECTIVE: To reveal clinical and polysomnographic features in patients treated for restless leg syndrome, and to examine the compatibility of sleep data and clinical features. METHODS: The study was conducted at the Department of Neurology, Ankara Numune Training and Education Hospital, Ankara, Turkey, and comprised patients who presented to the outpatient clinic between January and July 2014 who were diagnosed with restless leg syndrome based on the International RestIess Leg Syndrome Study Group criteria. Patients underwent polysomnography test in spontaneous sleep in a single room. SPSS 18 was used for statistical analyses. RESULTS: Of the 18 patients, 13(72%)were females and 5(28%)were males. Overall mean age was 51.56±11.57years (range: 23-66 years). Fourteen (77.8%) patients reported insomnia; 10(55.5%) patients had excessive daytime sleepiness; 13(72.2%) reported snoring; and 3(17%) had apnoea. Mean International Restless Legs Syndrome Study Group Rating Scale score was 26.11±7.9 (range: 16-40).Mean Epworth Sleepiness Scale score was 9.17±5.1 (range: 0-20). CONCLUSIONS: Restless leg syndrome was more common in women and the most common complaint was insomnia.

The association of IL-18 gene promoter polymorphisms and the levels of serum IL-18 on the risk of multiple sclerosis.

OBJECTIVES: Multiple sclerosis is an inflammatory condition of the central nervous system whose etiology is influenced by immunologic, genetic, and environmental factors. Aim of the present study was to determine if any relation exists between IL-18 -137C/G and -607C/A gene promoter polymorphisms on the individual susceptibility of multiple sclerosis and also to investigate the possible effect of IL-18 activity regarding this kind of polymorphism and MS. PATIENTS AND METHODS: 113 patients with clinically definite MS and 135 ethnically-matched controls were participated in this study. IL-18 -137C/G and -607C/A gene promoter polymorphisms were analyzed by Sequence Specific Polymerase Chain Reaction (SS-PCR), while levels of serum IL-18 were measured by Enzyme Linked Immunoassay Assay (ELISA) in patients with MS and healthy controls. RESULTS: Our results showed that the IL-18 -607AA genotype indicated 6 times higher risk in the development of MS (OR=6.883; 3.17-14.96; p<0.001). According to our findings, smoking seems to be an important confounding factor in MS patients with carrying IL-18 -607 AA and CA+AA genotypes. However, no meaningful association was found with IL-18 -137C/G gene promoter polymorphism. CONCLUSION: In conclusion, we suggest that IL-18 -607C/A gene promoter polymorphism is a major genetic factor for determining individual susceptibility to MS, where smoking status also increases the risk of MS.

The impact of detoxifying and repair gene polymorphisms on oxidative stress in ischemic stroke.

Stroke is a multifactorial disease caused by the combination of certain risk factors and genetic factors. There are possible risk factors having important role in the pathogenesis of stroke. The most important environmental factors are cigarette smoking and oxidative stress which have different sources. GST (M1, T1, P1) have major roles in detoxification of the products of oxidative stress and they are polymorphic. DNA damages can also be repaired by repair enzymes such as OGG1 and XRCC1 which are highly polymorphic and have pivotal roles in repair systems. In the present study, we investigated that polymorphisms in genes involved in detoxification and DNA-repair pathways might modify the individual's risk for ischemic stroke. Furthermore, the products of oxidative stress and antioxidant capacity were measured and the impact of gene polymorphism on them was evaluated. Our data showed that OGG1 Ser326Cys and XRCC1 Arg399Gln gene polymorphisms had impacts on the development of stroke.

Is there an association between the Expanded Disability Status Scale and inflammatory markers in multiple sclerosis?

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease characterized by inflammation of white matter in the central nervous system. It has been indicated that this inflammation causes increased levels of proinflammatory cytokines. Therefore, we aimed to evaluate if there is a possible association between inflammatory markers and the Expanded Disability Status Scale (EDSS) score in patients with MS. METHODS: We reviewed the data of 127 patients (91 women and 36 men) who were retrospectively diagnosed as MS according to the revised Mc Donald's criteria who were seen at our facility between January 2007 and December 2012. Patients were divided into two groups according to EDSS score: Group 1, EDSS < 5; and Group 2, EDSS ≥ 5. The risk factors that were evaluated included age and sex of the patients, duration of MS, drugs, thyroid function tests, vitamin B12 levels, homocysteine levels, immunoglobulins (Ig) A, G, and M, rheumatoid factor, complement 3 and 4, antistreptolysin O, C reactive protein (CRP), white blood cell count, and neutrophile-lymphocyte ratio (NLR). RESULTS: There was a statistically significant difference between the groups in terms of age, duration of the disease, drug received, Ig M, free T3, serum homocysteine levels, CRP, and NLR (p < 0.05). Pearson's correlation analysis showed a significant correlation between age, duration of MS, IgM, serum homocysteine levels, CRP, and NLR. According to the receiver operating characteristic curve analysis, IgM and NLR were discriminative factors in patients in Group 2. CONCLUSION: According to this study, inflammation may have a role in the pathogenesis of MS and in patients with EDSS > 5. Additionally, NLR and CRP levels may be discriminative factors of adverse clinical outcomes.

Comparison of Cognitive Functions Between Obstructive Sleep Apnea Syndrome and Simple Snoring Patients: OSAS May Be a Modifiable Risk Factor for Cognitive Decline.

By comparing neurocognitive test results from patients with obstructive sleep apnea syndrome (OSAS) and those from patients with simple snoring, we aimed to establish whether OSAS negatively influences cognition. Patients with mild-to-severe OSAS (n = 29) and nonhypoxic simple-snoring patients (n = 30) were admitted to the study. All participants in both groups were evaluated with polysomnography and neurocognitive tests, including the Stroop Test, Rey Auditory Verbal Learning Test, Judgment of Line Orientation, Trail-Making Test, and Symbol Digit Modalities Test (SDMT). Significant differences were identified between the groups for test scores on the Rey 1, SDMT, and Stroop tests. We propose that accurate OSAS diagnosis and treatment might help to prevent cognitive decline.

The effects of lipoprotein(a) and homocysteine on prognosis and risk factors in acute ischemic stroke.

The role of atherosclerosis in ischemic stroke has been intensively investigated in recent years, and homocysteine (Hcy) and lipoprotein(a) Lp(a) were found to have roles during the process. This study aims to investigate the relationship between acute ischemic stroke and Lp(a) and Hcy levels and to determine the prognosis and functional disability. Forty-one patients with acute ischemic stroke and 33 controls were included in the study. Lp(a) and Hcy levels were examined in both groups. The modified Rankin scale (MRS) scores at discharge and in the first and third months were determined to establish the functional disability and prognosis of stroke patients. In patients with acute ischemic stroke, Hcy levels were significantly higher than the controls (p = 0.003). There was no significant difference between Lp(a) levels in patients with acute ischemic stroke and controls (p = 0.150). Because there was a significant difference in terms of Hcy levels between the groups, it will be suitable to routinely monitor the Hcy levels of individuals who are known to have risk factors for stroke. Neither Lp(a) nor Hcy levels had any correlations with functional disability; therefore, it can be concluded that the Lp(a) and Hcy levels are inexpressive in predicting the functional disability and prognosis for ischemic stroke patients.

What happens in the other eye? Blink reflex alterations in contralateral side after facial palsy.

Alterations in blink reflex excitability may occur in the contralateral side (CLS) and in the symptomatic side after peripheral facial palsy (PFP). In this study, the alterations of blink reflex in CLS were evaluated in cases with PFP who showed "three different types" of recovery. For this purpose, the R2 response area and recovery curve of the blink reflex were evaluated. The study included 51 patients suffering from PFP and 20 age- and sex-matched healthy controls. Cases with PFP were divided into three groups: patients with PFP with partially cured and accompanied by synkinesis (postfacial syndrome), patients with PFP with residual weakness, and patients who suffered from recurrent PFP. All three groups' R2 values of CLS were compared with the values of controls and patients who had synkinesis. The CLS of all three groups' R2 area values were found to be significantly higher when compared with controls. These values were found to be highest in patients who suffered from recurrent PFP. Hyperexcitability occurs in CLS after PFP and this is highest in patients who suffer from recurrent PFP. It suggested that the contralateral reorganization caused by peripheral nerve damage correlates with the severity of the lesion and the recurrence of axon damage enhances the excitability of the reflex cycle, which affects the contralateral facial nucleus.