Retrospective analysis of effectiveness of fingolimod in real life setting in Turkey (REFINE).

BACKGROUND: During multiple sclerosis (MS) treatment different modes of action such as lateral (interferon beta to glatiramer acetate or glatiramer acetate to interferon beta) or vertical (interferon beta/glatiramer acetate to fingolimod) drug switch can be performed. This study aims to investigate the clinical effectiveness of switching from the first-line injectable disease modifying treatments (iDMTs) to fingolimod (FNG) compared to switching between first-line iDMTs. METHODS: This is a multicenter, observational and retrospective study of patients with relapsing-remitting MS who had lateral and vertical switch. The observation period included three key assessment time points (before the switch, at switch, and after the switch). Data were collected from the MS patients' database by neurologists between January 2018 and June 2019. The longest follow-up period of the patients was determined as 24 months after the switch. RESULTS: In 462 MS patients that were included in the study, both treatments significantly decreased the number of relapses during the postswitch 12 months versus preswitch one year while patients in the FNG group experienced significantly fewer relapses compared to iDMT cohort in the postswitch 12 months period. FNG cohort experienced fewer relapses than in the iDMT cohort within the postswitch 2 year. The mean time to first relapse after the switch was significantly longer in the FNG group. DISCUSSION: The present study revealed superior effectiveness of vertical switch over lateral switch regarding the improvement in relapse outcomes. Patients in the FNG cohort experienced sustainably fewer relapses during the follow-up period after the switch compared the iDMT cohort. Importantly, switching to FNG was more effective in delaying time to first relapse when compared with iDMTs.

Wernicke encephalopathy with epileptic seizures during pregnancy.

A 22-year-old woman was admitted to the emergency department with headache, dizziness, and numbness on the left side of the body. Neurologic examination revealed gaze-evoked nystagmus. Cranial magnetic resonance imaging, venous and arterial magnetic resonance angiography were normal. Generalized epileptogenic activity was observed in the electroencephalography. The erythrocyte thiamine transketolase levels were found to be 13 u/L. She received intravenous thiamine. On discharge, she had no neurologic sequelae. The diagnosis of Wernicke encephalopathy in our patient is based on increased thiamine requirement due to pregnancy, nystagmus, low transketolase level, and reversal of symptoms after thiamine replacement. .

Long-Term Effectiveness of Fingolimod for Multiple Sclerosis in a Real-World Clinical Setting.

INTRODUCTION: The primary aim of the present study was to evaluate the long-term efficacy of fingolimod in patients with multiple sclerosis (MS); secondary aims were to describe the safety of fingolimod with the evaluation of treatment satisfaction and impact on the quality of life in real life. METHODS: We collected clinical, demographical, neuroradiological, and treatment data, including pre- and posttreatment status health-related quality of life from 286 MS patients consecutively treated with fingolimod. Clinical assessment was based on the Expanded Disability Status Scale (EDSS), and quality of life assessment was performed with MS-related quality of life inventory (MSQOLI). The data were recorded at baseline and every 6 months for 2 years. RESULTS: One hundred and fourteen males and 172 females were enrolled. The annualized relapse rate and EDSS showed a statistically significant reduction during the observation period (p < 0.001). The patients also demonstrated substantial improvements in magnetic resonance imaging (MRI) outcomes (p < 0.001). Health-related quality of life scores improved significantly between baseline and 24-month visit (p < 0.001). No serious adverse events occurred. CONCLUSION: In our cohort, fingolimod treatment was associated with reduced relapse, MRI activity, and improved EDSS and MSQOLI scores. Additionally, fingolimod has been able to maintain its effectiveness over a considerable long period of treatment.

The efficacy of rituximab in patients with neuromyelitis optica spectrum disorder: A real-world study from Turkey.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are a group of antibody-mediated chronic inflammatory diseases of the central nervous system. Rituximab is a monoclonal antibody that leads to a reduction in disease activity. OBJECTIVE: To evaluate the efficacy of rituximab as monotherapy in NMOSD and to determine whether the efficacy varies depending on the presence of antibodies in this cohort. METHOD: This multicentre national retrospective study included patients with NMOSD treated with rituximab at least for 12 months from Turkey. The primary outcomes were the change in the annualised relapse rate, the Expanded Disability Status Scale (EDSS), the number of relapse and radiological activity-free patients. RESULTS: A total of 85 patients with NMOSD were included in the study. Of 85 patients, 58 (68.2%) were seropositive for anti-Aquaporin4-IgG (antI-AQP4-IgG). All patients were Anti-Myelin Oligodendrocyte Glycoprotein IgG (anti-MOG-IgG) negative. The median follow-up for rituximab treatment was 21 months (Q1 16-Q3 34.5). During rituximab treatment, the mean annualised relapse rate (ARR) significantly decreased from 1.45 ± 1.53 to 0.15 ± 0.34 (P < .001). In subgroup analyses, the mean ARR decreased from 1.61 ± 1.65 to 0.20 ± 0.39 in the seropositive group and 1.10 ± 1.19 to 0.05 ± 0.13 in the seronegative group. The mean EDSS improved from 3.98 ± 2.04 (prior to treatment onset) to 2.71 ± 1.59 (at follow-up) (P < .001). In the seropositive group, mean EDSS decreased from 3.94 ± 1.98 to 2.67 ± 1.54, and in the seronegative group, mean EDSS decreased from 4.07 ± 2.21 to 2.79 ± 1.73. There was no significant difference between anti-AQP4-IgG (+) and (-) groups in terms of ARR and EDSS. Sixty-four patients (75.2%) were relapse-free after the initiation of treatment. Seventy patients (82.3%) were radiological activity-free in the optic nerve, area postrema and brainstem. Additionally, 78 patients (91.7%) showed no spinal cord involvement after the treatment. CONCLUSION: Rituximab therapy is efficacious in the treatment of Turkish NMOSD patients independent of the presence of the anti-AQP4-IgG antibody.

Effectiveness, Safety, and Health-Related Quality of Life of Chronic Migraine Patients Treated with Onabotulinum Toxin A.

OBJECTIVE: The present study aims to describe the efficacy and safety of onabotulinum toxin A (BonT-A) with evaluation of treatment satisfaction and impact on quality of life in chronic migraine (CM) patients in real life. METHODS: This study was conducted in CM patients who were treated with BoNT-A with 12 months of follow-up. Data about outcome, adverse events, and patients' pre- and post-treatment status including health-related quality of life data were analyzed. Health-related quality of life scores were measured at baseline and months 6 and 12 after the beginning of BoNT-A administration. RESULTS: Of 42 enrolled patients, 30 were included in the analysis. At 12 months, all patients showed a reduction in number of headaches and analgesic use per month and none reported adverse events. After BoNT-A supplementation, health-related quality-of-life scores improved significantly. There was a direct association between health-related quality of life with reduction of headache days at the end of study. CONCLUSION: This study confirms that BoNT-A treatment is effective on CM and improves the functional well-being and quality of life of patients.

To Be or Not to Be Patent: The Relationship Between Migraine and Patent Foramen Ovale.

OBJECTIVE/BACKGROUND: Migraine is a common neurological disorder with an uncertain pathogenesis. A pathophysiological link has been proposed between the migraine headache and patent foramen ovale (PFO). However, the data about the association of migraine with the presence of PFO are conflicting. The study aims to prospectively investigate the prevalence of PFO in patients with migraine compared with that of control subjects. METHODS: A total of 203 migraineous patients and 212 control subjects with similar demographic characteristics to that of case subjects regarding age and gender were included in the study. Transthoracic echocardiography with agitated saline injection was used to evaluate the presence of PFO. PFO was judged to be present if any microbubble was seen in the left cardiac chambers within the first 5 cardiac cycles from the maximum right atrial opacification at rest or after provocative maneuvers. RESULTS: Mean age of the patients was 37.2 ± 9.8 years and 93% were female. Migraine with aura was present in 32% (n = 65) of the patients. The prevalence of PFO was similar in patients with migraine and the control subjects (42% vs 44%; odds ratio 0.90, 95% confidence interval 0.61-1.33, P = .61). Likewise, the prevalence of PFO was similar in migraineurs patients with or without aura (41% vs 42%; odds ratio 0.95, 95% confidence interval 0.51-1.76, P = .87). CONCLUSION: This study suggest that PFO is not more common in patients with migraine compared with healthy subjects. Therefore, our findings suggest that the relationship between migraine headache and the presence of PFO is questionable.

Electrophysiological Evaluation of Dysphagia in the Mild or Moderate Patients with Multiple Sclerosis: A Concept of Subclinical Dysphagia.

Swallowing mechanism and neurogenic dysphagia in MS have been rarely studied by electromyographical (EMG) methods. This study aims to evaluate the presence of subclinical dysphagia in patients with mild multiple sclerosis (MS) using electrophysiological methods. A prospective study of 51 patients with relapsing remitting multiple sclerosis and 18 age-matched healthy adults was investigated. We used electromyography to measure the activity of the submental muscles during swallowing. Electrophysiological recordings of patients were obtained during relapse, after relapse, and at any time in remission period. Clinical dysphagia was found in 12% of MS patients, while electrophysiological swallowing abnormalities were encountered in 33% of patients. Subclinical dysphagia was determined in 35% of patients during an MS relapse, in 20% of patients after a relapse, and in 25% of all 51 patients in the remission period based on EMG findings. Duration of swallowing signal of submental muscles in all MS patients was found to be longer than in normal subjects (p = 0.001). During swallowing of 50 ml of sequential water, the compensatory respiratory cycles occurred more often in MS patients than normal subjects, especially during a relapse (p = 0.005). This is the first study investigating swallowing abnormalities and subclinical dysphagia from the electrophysiological aspect in MS patients with mild disability. The electrophysiological tests described in this study are useful to uncover subclinical dysphagia since they have the advantage of being rapid, easy to apply, non-invasive, and without risk for the patients.

Intracranial hemorrhages related with warfarin use and comparison of warfarin and acetylsalicylic acid.

BACKGROUND: Acetylsalicylic acid (ASA) and warfarin are used to prevent ischemic cerebrovascular events. They have serious complications including intracranial hemorrhages (ICHs). Warfarin-related intracerebral hemorrhage (ich) incidence is .2%-5% in population that accounts for 10%-12% of all ichs. In this article, we investigated the profile of ASA and warfarin-related spontaneous ICHs in comparison with ICHs without any drug use (WADU) with their clinical, radiological, and biochemical properties. METHODS: In all, 486 patients aged 18-101 years with spontaneous ICHs were included. Patients constituted 4 separate groups: users of warfarin, ASA, ASA + warfarin, and WADU. Clinical, neurological, etiological, and radiological data of these patients were compared. RESULTS: There were 32 patients in warfarin, 58 patients in ASA, and 7 in warfarin + ASA group. Most of the patients were in no drug group (389 patients). The most frequent type of hemorrhage was supratentorial intraparenchymal hemorrhage. The most common accompanying disease was hypertension. The number of female patients was statistically significant in the warfarin group. Glasgow Coma Scale (GCS), accompanying diseases, opening of the hematoma to the ventricle, localization of the hemorrhage, age of the patient, and activated partial thromboplastin time level are all related to the outcome of patients. Warfarin users had worst mortality rate. CONCLUSIONS: Use of warfarin, low GCS score, opening to ventricle, older age, accompanying diabetes, and/or hypertension were worse prognostic factors. It is possible that patients with these unfavorable prognostic factors cannot survive.

Clinical and demographic characteristics of late-onset multiple sclerosis: LOMS-TR study.

OBJECTIVES: Multiple sclerosis (MS), which is known as a young-adult age disease, is called late-onset MS (LOMS) when it occurs at the age of 50 and older. In our study, we aimed to analyse the clinical and demographic characteristics, comorbidities, diagnostic and treatment challenges and prognosis of LOMS. METHODS: In a retrospective analysis of 136 patients diagnosed with multiple sclerosis (MS) after the age of 50, based on the 2017 McDonald criteria, and who were under observation in eight distinct MS centers across Turkey; demographic information, clinical characteristics of the disease, oligoclonal band (OCB) status, initial and current Expanded Disability Status Scale (EDSS) values, administered treatments, and the existence of spinal lesions on magnetic resonance imaging (MRI) were investigated. RESULTS: The mean age of the 136 patients was 60.96±6.42 years (51-79), the mean age at diagnosis was 54.94±4.30 years, and 89 (65.4 %) of the patients were female. Most of the cases, 61.1 % (83) had at least one comorbidity. In 97 patients who underwent lumbar puncture (LP), OCB positivity was observed in 63.6 %. In 114 patients (83.8 %), spinal lesions were detected on MRI. Eighty-seven patients had relapsing-remitting MS (RRMS) (64 %), 27 patients had secondary progressive MS (SPMS) (19.9 %), and 22 patients had primary progressive MS (PPMS) (16.2 %). The mean EDSS at the time of diagnosis was 2.44±1.46, and the mean current EDSS was 3.15±2.14. CONCLUSIONS: In LOMS patients, the rates of delay in the diagnostic process, treatment disruption and progressive disease are higher than in the general MS population. The high rates of LP applying and OCB positivity of this study may indicate the habit of looking for clear evidences in advanged age in our country. This situation and comorbidities may cause a delay in diagnosis and eliminates the window of opportunity for early diagnosis. Although the high number of spinal lesions is a known marker for progressive disease, it is an issue that needs to be discussed whether the increased frequency of progressive course at older ages is due to the nature of the disease or immune aging itself.

The Effect of Smoking on Inactivated and mRNA Vaccine Responses Applied to Prevent COVID-19 in Multiple Sclerosis.

Introduction: Coronavirus disease 2019 (COVID-19) is the biggest health challenge of recent times. Studies so far reveal that vaccination is the only way to prevent this pandemic. There may be factors that decrease or increase vaccine effectiveness. In multiple sclerosis (MS), some of these factors may cause changes in the effectiveness of the vaccine, depending on the nature of the disease and disease-modifying treatments (DMT). In this study, we aimed to investigate the relationship between antibody titer and smoking in non-treated and DMT-treated MS patients who received inactivated vaccine (Sinovac) and messenger RNA BNT162b2 (BioNTech) mRNA vaccines. Method: Vaccine antibody responses were measured between 4-12 weeks after two doses of inactivated vaccine and mRNA vaccines. Patients were separated into 6 groups as: patients with MS without treatment PwMS w/o T, ocrelizumab, fingolimod, interferons (interferon beta-1a and interferon beta-1b), dimethyl fumarate, and teriflunomide. Antibody titers of smokers and non-smokers were compared for both vaccines and for each group. Results: The study included 798 patients. In the mRNA vaccine group, smokers (n=148; 2982±326 AU/mL) had lower antibody titers compared to the non-smokers (n=244; 5903±545 AU/mL) in total (p=0.020). In the inactivated vaccine group, no significant difference was detected between smokers (n=136; 383±51 AU/mL) and non-smokers (n=270; 388±49 AU/mL) in total (p=0.149). In both vaccine groups, patients receiving ocrelizumab and fingolimod had lower antibody titers than those receiving other DMTs or PwMS w/o T. In untreated MS patients, antibody levels in smokers were lower than in non-smokers in the mRNA vaccine group. No difference was found between antibody levels of smokers and non-smokers in any of the inactivated vaccine groups. Conclusion: Ocrelizumab and fingolimod have lower antibody levels than PwMS w/o T or other DMTs in both mRNA and inactivated vaccine groups. Smoking decreases antibody levels in the mRNA vaccine group, while it has no effect in the inactivated vaccine group.

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.

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.].

mRNA versus inactivated virus COVID-19 vaccines in multiple sclerosis: Humoral responses and protectivity-Does it matter?

BACKGROUND: COVID-19 vaccines are recommended for people with multiple sclerosis (pwMS). Adequate humoral responses are obtained in pwMS receiving disease-modifying therapies (DMTs) after vaccination, with the exception of those receiving B-cell-depleting therapies and non-selective S1P modulators. However, most of the reported studies on the immunity of COVID-19 vaccinations have included mRNA vaccines, and information on inactivated virus vaccine responses, long-term protectivity, and comparative studies with mRNA vaccines are very limited. Here, we aimed to investigate the association between humoral vaccine responses and COVID-19 infection outcomes following mRNA and inactivated virus vaccines in a large national cohort of pwMS receiving DMTs. METHODS: This is a cross-sectional and prospective multicenter study on COVID-19-vaccinated pwMS. Blood samples of pwMS with or without DMTs and healthy controls were collected after two doses of inactivated virus (Sinovac) or mRNA (Pfizer-BioNTech) vaccines. PwMS were sub-grouped according to the mode of action of the DMTs that they were receiving. SARS-CoV-2 IgG titers were evaluated by chemiluminescent microparticle immunoassay. A representative sample of this study cohort was followed up for a year. COVID-19 infection status and clinical outcomes were compared between the mRNA and inactivated virus groups as well as among pwMS subgroups. RESULTS: A total of 1484 pwMS (1387 treated, 97 untreated) and 185 healthy controls were included in the analyses (male/female: 544/1125). Of those, 852 (51.05%) received BioNTech, and 817 (48.95%) received Sinovac. mRNA and inactivated virus vaccines result in similar seropositivity; however, the BioNTech vaccination group had significantly higher antibody titers (7.175±10.074) compared with the Sinovac vaccination group (823±1.774) (p<0.001). PwMS under ocrelizumab, fingolimod, and cladribine treatments had lower humoral responses compared with the healthy controls in both vaccine types. After a mean of 327±16 days, 246/704 (34.9%) of pwMS who were contacted had COVID-19 infection, among whom 83% had asymptomatic or mild disease. There was no significant difference in infection rates of COVID-19 between participants vaccinated with BioNTech or Sinovac vaccines. Furthermore, regression analyses show that no association was found regarding age, sex, Expanded Disability Status Scale score (EDSS), the number of vaccination, DMT type, or humoral antibody responses with COVID-19 infection rate and disease severity, except BMI Body mass index (BMI). CONCLUSION: mRNA and inactivated virus vaccines had similar seropositivity; however, mRNA vaccines appeared to be more effective in producing SARS-CoV-2 IgG antibodies. B-cell-depleting therapies fingolimod and cladribine were associated with attenuated antibody titer. mRNA and inactive virus vaccines had equal long-term protectivity against COVID-19 infection regardless of the antibody status.

The effect of cognitive performance on self-management behavior of multiple sclerosis patients.

BACKGROUND: Difficulties of self-management in people with MS (pwMS) is considered as one of the most important factors contributing to low rehabilitation efficacy, more severe long-term complications and increase in healthcare costs. Despite the emergence of research in the last decade documenting causes, types, and course of cognitive difficulties in MS disease subtypes, limited evidence is available in the literature for direct comparison of self-management and cognitive deficits. In this study we aimed to investigate the relationship between cognitive performance and self-management in pwMS. METHODS: PwMS who applied to neurology out-patient clinics of seven different centers were included into study. Multiple Sclerosis Self-Management Scale- Revised (MSSM-R) was used for the assessment of self-management behaviors and Multiple Sclerosis inventory cognition scale (MUSIC) was used for the assessment of cognitive performance and fatigue. RESULTS: In this study, 194 (144 female and 50 male) pwMS participated (mean age = 38.9 years). The course of the disease was RRMS in 173 patients and mean EDSS was 2.0. 68.5% of the participants were married, 32.5% were employed, and 57.2% had secondary education. The MSSM-R mean score of the study group was 42.6 ± 10.4 (1-81). There was a positive correlation between MSSM-R and MUSIC-cog scores (r = 0.21, p = 0.003). A hierarchical multiple regression revealed that income level (ß = 0.196, t = 2.692, p = 0.008) and cognitive performance (ß = 0.167, t = 2.063, p = 0.041) together with control variables (gender, age, educational status, employment status, duration of disease, EDSS and fatigue) explained 5.5% of the variance in self-management. CONCLUSION: Cognitive performance is a predictor of self-management in pwMS. Better self-management behavior is also related with employment and income level in pwMS. Studies evaluating patients' cognitive abilities and evaluating the effectiveness of adapted self-management training programs are needed.

The Socioeconomic and Psychological Impact of the COVID-19 Pandemic on People with Multiple Sclerosis in Turkey.

Introduction: Various restrictions due to the coronavirus infection have affected working life globally. People with multiple sclerosis (pwMS) have several difficulties in social life, patient follow-up, and receiving treatments. In this study, we aimed to evaluate the experiences of pwMS during the COVID-19 pandemic. Method: We developed a 50-question survey aiming to determine fears, anxieties, and the problems experienced by patients regarding their diseases and social lives during the COVID-19 pandemic. The questionnaire was released online via the Turkish MS Society website, local MS societies websites, and social media accounts. Only the answers of the patients who filled out the questionnaire completely were evaluated. Results: In total, 6008 patients took the survey, and 3255 of them completed the questionnaire. Among all, 378 patients (11.6%) were positive for COVID-19. The most common COVID-19-related symptom was fatigue (48.4%). The routine medical follow-up was interrupted in 61.4% and the medication was discontinued in 14% of the patients. Approximately 25% of the patients reported different symptoms related to relapse activity. The main concern of the patients related to the COVID-19 pandemic was the disruption of the health of the ones they loved. Among all the patients, 4.4% lost their jobs. Conclusion: Our data showed that the COVID-19 pandemic strongly affected the working lives of pwMS. Also, the pandemic changed the attitudes of patients and neurologists. Therefore, the long-term effects of the COVID-19 pandemic on disease approach, patient follow-up, social conditions, and working life should be monitored.

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.

Mitochondrial Mutations in Multiple Sclerosis Patients with Atypical Optic Neuropathy.

BACKGROUND: Multiple sclerosis-related optic neuritis is mostly associated with good recovery. The aim of this study was to investigate the causes of progressive visual worsening in multiple sclerosis patients despite treatment. METHODS: We retrospectively reviewed the medical records of multiple sclerosis patients with optic neuritis admitted to the ward of our Neurology Department between 2001 and 2020. The patients with unilateral/bilateral progressive visual loss or non-substantial recovery of visual acuity were screened for genetic testing for Leber's hereditary optic neuropathy. RESULTS: Of 1014 multiple sclerosis patients, 411 (39%) reported having optic neuritis. During follow-up, 11 patients manifested atypical characteristics of multiple sclerosis-related optic neuritis (presence of one of the following clinical findings: bilateral simultaneous or sequential eye involvement, progressive visual loss, or no response to corticosteroids during hospitalization), while others presented with typical multiple sclerosis-related optic neuritis. Those multiple sclerosis patients with atypical characteristics of optic neuritis were screened for other possible etiologies of optic neuropathy. We found pathogenic mitochondrial mutations in 5 patients with multiple sclerosis in our study group. CONCLUSION: In our study group, the prevalence of mitochondrial mutations among all multiple sclerosis patients with optic neuritis was 0.12%. We strongly recommend investigating Leber's hereditary optic neuropathy mutations in MS patients if they suffer from severe or bilateral visual loss without recovery during follow-up. Because Leber's hereditary optic neuropathy mitochondrial mutations indicate relatively poor visual prognosis and have important implications for genetic counseling.

Fasciculations in brain death.

OBJECTIVES: Brain death is the colloquial name for human death determined by tests showing irreversible cessation of the clinical functions of the brain. Spontaneous and reflex movements have been described in brain death. The aim of this report is to describe a brain-dead patient with unusual motor movements. DESIGN AND SETTING: The patient was followed and her motor movements were videotaped. PATIENT: We report the presence of extensive and long-lasting fasciculations in a patient who fulfilled the criteria for brain death. MEASUREMENTS AND MAIN RESULTS: We describe and show on videotape a brain-dead patient with rare motor movements. CONCLUSION: We suggest that fasciculations outlined in this study has to be accepted as motor symptoms in brain death patients.

Clinical and radiologic correlations of small and large centrum ovale infarcts.

BACKGROUND: Acute centrum ovale (CO) infarction confined to the territory of perforating long medullary arteries is rarely reported. This study was designed to investigate the full spectrum of clinical findings, topography, and pathogenesis of patients with acute CO infarct. METHODS: A total of 64 patients with CO infarct were recorded. Risk factors such as age, hypertension, diabetes mellitus, hypercholesterolemia, smoking, and cardiopathy were recorded. RESULTS: The average age of the patients was 64.2 years. There were 46 patients (71.8%) in large-infarct group and 18 patients (28.1%) in small-infarct group. The most frequent risk factor was hypertension (89.1%). Other risk factors included smoking (39%), diabetes mellitus (29.7%), hyperlipidemia (28.1%), transient ischemic attack (15%), carotid stenosis (9%), atrial fibrillation (21%), other potential cardiac source of embolism (39%), and myocardial infarct (4%). The main clinical feature was faciobrachiocrural paralysis associated dysarthria (51.6%). Other clinical characteristics were facial, upper and lower extremity paralysis with sensorial deficits and/or dysarthria (26.6%), hemiparesis including face (12.5%), and either facial and upper or upper and lower extremity paralysis with hemisensorial deficit (9.4%). The baseline Barthel index was found to be less than 50 in 22 patients (34.4%) and greater than 50 in 42 patients (65.6%) for the entire group whereas 72% of patients were independent at discharge. CONCLUSION: In this article, risk factors, clinical spectrum, and features of CO infarcts were correlated in a large patient group. The majority of CO infarcts were large and had a poorer outcome compared to previous reports.

Blood pressure changes in migraine patients before, during and after migraine attacks.

Migraine attacks are characterized by headaches associated with neurological, gastrointestinal, and autonomic symptoms. A relationship between migraine and hypertension or hypotension is controversial. In this study, we aimed to determine if blood pressure changes were related to migraine attacks. From the outpatient clinic of our neurology department, 62 normotensive migraine patients with and without aura were chosen for study in accordance with the International Headache Society 2004 criteria. A questionnaire including general and specific questions was given to the patients to be filled out during 6 consequent migraine attacks. The patients received a fully automatic digital brachial upper arm sphygmomanometer (Omron M 4-1) to measure the changes in their blood pressure during attacks. The patients were asked to record their blood pressure changes 3 times: (1) just before or very early, (2) during (when headache peaks), and (3) 1 hour after the attack. Twenty-three of the 62 patients (57 women, 5 men) had migraine with aura (22 women and 1 man), and 39 of them did not have aura (35 women and 4 men). There was no statistically significant difference between systolic and diastolic values obtained before or very early, during the peak level, and 1 hour after the end of the attacks (P > 0.05). Although diastolic hypotensive values were not different statistically between groups, when all the patients were considered, diastolic hypotensive values were detected in a considerable number of patients (a total of 115 measurements). In this normotensive migrainous population, we observed that diastolic hypotension before or very early, during, and after migraine attack was the most significant result (5.1%). Although it was not statistically significant, the total number of hypotensive values was remarkable.