Prevalence and incidence of multiple sclerosis in Turkey: A nationwide epidemiologic study.

BACKGROUND: Many studies on multiple sclerosis (MS) reveal different prevalence and epidemiologic results. OBJECTIVES: In this study, we aimed to determine the epidemiologic profile of MS using official health records in Turkey. METHODS: Patients diagnosed with MS from the official health data of the Ministry of Health, representing the entire population of Turkey, were included in the study. Prevalence and incidence calculations were performed using the data on gender, age, year of birth, city of residence, and year of diagnosis. RESULTS: As a result of the study, the number of patients with the ICD code G35 was determined as 201,061 and the number of patients with this code entered at least three times was determined as 82,225. The prevalence of MS in Turkey was calculated as 96.4 per 100,000 and the female/male ratio as 2.1/1. The incidence of MS in 2022 was 6.2 per 100,000 and the mean patient age was 43.1 ± 13.3 years (female: 43.0 ± 13.1 vs male: 43.2 ± 13.7) while the mean age at first diagnosis was 34.0 ± 13.0 (female: 33.6 ± 12.6 vs male: 34.9 ± 13.7). CONCLUSION: The research was conducted via Official Database of Turkey, which includes population of 85 million and provides valuable insights into the prevalence and incidence rates of this chronic disease.

EEG changes in intensive care patients diagnosed with COVID-19: a prospective clinical study.

INTRODUCTION: Coronavirus disease (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease was declared a pandemic on March 11th, 2020, by the World Health Organization (WHO). There has been a substantial increase in the epileptic seizures and status epilepticus reported in the pandemic period. In this context, it is aimed with this study to identify the electroencephalography (EEG) features of patients admitted to the intensive care unit with the diagnosis of COVID-19 and to look for any specific patterns in these features. MATERIAL AND METHOD: The material of this study primarily comprised the neurological evaluations and continuous EEG recordings of 87 intensive care patients who were diagnosed with COVID-19. In addition, demographic and clinical features and comorbid conditions of these patients were also analyzed, and any correlation thereof was investigated. RESULTS: The EEG data of 87 patients who were diagnosed with COVID-19 and were followed up in the intensive care unit were recorded and then analyzed. Abnormal EEG findings were detected in 93.1% (n = 81) of the patients, which were found to increase significantly with age (p < 0.001). The mean age of patients with specific epileptiform abnormalities on EEG was found to be significantly higher than those with non-specific abnormalities. Epileptiform discharges were seen in 37.9% (n = 33) of the patients. Nonconvulsive status epilepticus (NCSE) was detected in 5.7% of the patients, and antiepileptic drugs were started in 25 (28.7%) of the patients. DISCUSSION: Statistically significant EEG changes were observed in the continuous EEGs of the patients followed up in the intensive care unit due to COVID-19 infection. However, further studies are needed to associate the EEG changes observed in the COVID-19 patients with the epileptogenesis of COVID-19 infection.

Proximal sciatic neuropathy secondary to hamstring tendon avulsion.

We herein present the exceptional case of a patient, who injured a sciatic nerve due to avulsion of proximal hamstring tendon in a motorcycle accident. The 63-year-old man was diagnosed firstly with an incomplete fracture of distal femur. A foot drop on the right side was observed when the full-length cast was removed two months later. The patient was referred to the neurology clinic and was diagnosed with a sciatic nerve lesion at the proximal level of the biceps femoris. Magnetic resonance imaging of the thigh showed a proximal avulsion of hamstring muscles tendon. The patient did not improve by short-term physiotherapy and neurosurgical intervention. Sciatic nerve injury can be a result of proximal hamstring avulsion in events such as motorcycle accidents even in the absence of complete or major femur fracture.

Latent class cluster analysis identified hidden headache phenotypes in COVID-19: impact of pulmonary infiltration and IL-6.

BACKGROUND AND OBJECTIVE: Clinical studies on COVID-19 headache are limited. This prospective study aimed to define headache characteristics, associated clinical and laboratory factors, and treatment response in COVID-19. METHODS: Cross-sectional study enrolled 287 patients diagnosed with COVID-19 and hospitalized on a regular ward during the pandemic. All patients were examined face to face and followed by a neurologist during their stay in the hospital. The characteristics, concomitant symptoms, treatment responses, and laboratory findings of COVID-19-associated headaches were recorded. RESULTS: Eighty-three COVID-19 patients reported headache (28.9%), in which 85.5% had no prior headaches. Mean age was 48.40 ± 15.90 and 58% was men. Compared to COVID-19 patients without headache (n = 204), patients with headache showed significantly higher frequency of pulmonary involvement (76%) and increased D-dimer levels. Fifty-nine percent of headaches responded iv paracetamol 1000 mg, and 85% of the paracetamol unresponsive headaches were relieved by greater occipital nerve (GON) blocks. Latent class cluster analysis identified 2 distinct class of bilateral, frontal, throbbing headaches: severe (VAS > 84), longer (> 14 h), frequent (> 7 headache days), paracetamol unresponsive-GON responsive headaches (85%), with pulmonary involvement (100%), and higher IL-6 levels (> 90 pg/mL) were classified in cluster 1. Cluster 2 included moderately affected patients (VAS > 54, > 6 h, > 4 days, 60% pulmonary involvement, > 20 pg/mL IL-6) and paracetamol responsive headaches (96%). VAS scores showed positive linear correlation with IL-6 levels (p < 0.001; r = 0.567). CONCLUSION: The intensity, duration, frequency, bilateral frontal location, and treatment response of COVID-19 headache was related to pulmonary involvement and IL-6 levels, which indicated a role of inflammation in determining the headache manifestations in moderately affected hospitalized patients. ROC curve cutoff values pointed that VAS > 70 severity, > 9 h duration, > 5 headache days, and IL-6 > 43 pg/mL levels can be diagnostic for COVID-19 headache. GON blocks can effectively abort headache when patients are unresponsive to paracetamol, and other NSAIDs are avoided during the SARS-CoV-2 infection.

Nation-wide analysis of the impact of Covid-19 pandemic on daily urology practice in Turkey.

OBJECTIVE: To present a nation-wide analysis of the workload of urology departments in Turkey week-by-week during Covid-19 pandemic. METHODOLOGY: The centres participating in the study were divided into three groups as tertiary referral centres, state hospitals and private practice hospitals. The number of outpatients, inpatients, daily interventions and urological surgeries were recorded prospectively between 9-March-2020 and 31-May-2020. All these variables were recorded for the same time interval of 2019 as well. The weekly change of the workload of urology during pandemic period was evaluated, also the workload of urology and the distributions of certain urological surgeries were compared between the pandemic period and the same time interval of the year 2019. RESULTS: A total of 51 centres participated in the study. The number of outpatients, inpatients, urological surgeries and daily interventions were found to be dramatically decreased by the 3rd week of pandemics in state hospitals and tertiary referral centres; however, the daily urological practice were similar in private practice hospitals throughout the pandemic period. When the workload of urology in pandemic period and the same time interval of the year 2019 were compared, a huge decrease was observed in all variables during pandemic period. However, temporary measures like ureteral stenting, nephrostomy placement and percutaneous cystostomy have been found to increase during Covid-19 pandemic compared with normal life. CONCLUSIONS: Covid-19 pandemic significantly affected the routine daily urological practice likewise other subspecialties and priority was given to emergent and non-deferrable surgeries by urologists in concordance with published clinical guidelines.

HMGB1, NLRP3, IL-6 and ACE2 levels are elevated in COVID-19 with headache: a window to the infection-related headache mechanism.

BACKGROUND AND AIM: Pathogenesis of COVID-19 -related headache is unknown, though the induction of the trigeminal neurons through inflammation is proposed. We aimed to investigate key systemic circulating inflammatory molecules and their clinical relations in COVID-19 patients with headache. METHODS: This cross-sectional study enrolled 88 COVID-19 patients, hospitalized on a regular ward during the second wave of the pandemic. Clinical characteristics of COVID-19 patients were recorded, and laboratory tests were studied. RESULTS: The mean ages of 48 COVID-19 patients with headache (47.71 ± 10.8) and 40 COVID-19 patients without headache (45.70 ± 12.72) were comparable. COVID-19 patients suffered from headache had significantly higher serum levels of HMGB1, NLRP3, ACE2, and IL-6 than COVID-19 patients without headache, whereas CGRP and IL-10 levels were similar in the groups. Angiotensin II level was significantly decreased in the headache group. COVID-19 patients with headache showed an increased frequency of pulmonary involvement and increased D- dimer levels. Furthermore, COVID-19 was more frequently associated with weight loss, nausea, and diarrhea in patients with headache. Serum NLRP3 levels were correlated with headache duration and hospital stay, while headache response to paracetamol was negatively correlated with HMGB1 and positively associated with IL-10 levels. CONCLUSION: Stronger inflammatory response is associated with headache in hospitalized COVID-19 patients with moderate disease severity. Increased levels of the circulating inflammatory and/or nociceptive molecules like HMGB1, NLRP3, and IL-6 may play a role in the potential induction of the trigeminal system and manifestation of headache secondary to SARS-CoV-2 infection.

A prospective clinical study of detailed neurological manifestations in patients with COVID-19.

BACKGROUND: COVID-19 is a virus pandemic. According to the first obtained data, COVID-19 has defined with findings such as cough, fever, diarrhea, and fatigue although neurological symptoms of patients with COVID-19 have not been investigated in detail. This study aims to investigate the neurological findings via obtained face-to-face anamnesis and detailed neurological examination in patients with COVID-19. METHODS: Two hundred thirty-nine consecutive inpatients with COVID-19, supported with laboratory tests, were evaluated. Detailed neurological examinations and evaluations of all patients were performed. All evaluations and examinations were performed by two neurologists who have at least five-year experience. RESULTS: This study was carried out 239 patients (133 male + 106 female) with diagnosed COVID-19. Neurological findings were present in 83 of 239 patients (34.7%). The most common neurological finding was a headache (27.6%). D-dimer blood levels were detected to be significantly higher in patients with at least one neurological symptom than patients without the neurological symptom (p < 0.05). IL-6 level was found to be significantly higher in patients with headache than without headache (p < 0.05). Creatine kinase (CK) level was detected to be significantly higher in patients with muscle pain (p < 0.05). CONCLUSION: Neurological symptoms are often seen in patients with COVID-19. Headache was the most common seen neurological symptom in this disease. Dizziness, impaired consciousness, smell and gustation impairments, cerebrovascular disorders, epileptic seizures, and myalgia were detected as other findings apart from the headache. It is suggested that determining these neurological symptoms prevents the diagnosis delay and helps to prohibit virus spread.

Using Objective Speech Analysis Techniques for the Clinical Diagnosis and Assessment of Speech Disorders in Patients with Multiple Sclerosis.

Multiple sclerosis (MS) is one of the chronic and neurodegenerative diseases of the central nervous system (CNS). It generally affects motor, sensory, cerebellar, cognitive, and language functions. It is thought that identifying MS speech disorders using quantitative methods will make a significant contribution to physicians in the diagnosis and follow-up of MS patients. In this study, it was aimed to investigate the speech disorders of MS via objective speech analysis techniques. The study was conducted on 20 patients diagnosed with MS according to McDonald's 2017 criteria and 20 healthy volunteers without any speech or voice pathology. Speech data obtained from patients and healthy individuals were analyzed with the PRAAT speech analysis program, and classification algorithms were tested to determine the most effective classifier in separating specific speech features of MS disease. As a result of the study, the K-nearest neighbor algorithm (K-NN) was found to be the most successful classifier (95%) in distinguishing pathological sounds which were seen in MS patients from those in healthy individuals. The findings obtained in our study can be considered as preliminary data to determine the voice characteristics of MS patients.

Correction: Sonkaya et al. Using Objective Speech Analysis Techniques for the Clinical Diagnosis and Assessment of Speech Disorders in Patients with Multiple Sclerosis. Brain Sci. 2024, 14, 384.

In the original publication [...].

Exploring the impact of wearing-off phenomenon in ocrelizumab-treated multiple sclerosis patients: Insights from a comprehensive study.

BACKGROUND: Ocrelizumab (OCR) effectively modifies the disease course in multiple sclerosis (MS) patients but may cause a preinfusion "wearing-off phenomenon" (WoP). This study explored the prevalence, timing, and severity of this phenomenon in MS patients using the OCR, as well as the associated symptoms and treatment satisfaction. METHODS: We conducted a prospective multicenter study across 11 MS centers involving MS patients aged 18-70 years who had received at least two OCR doses. The study employed a questionnaire addressing demographic, clinical, and radiological data; symptom progression; and treatment satisfaction. RESULTS: Of the 409 patients included in the study, 406 participated. A significant portion experienced varying degrees of WoP: 39.2% sometimes, 25.9% usually, and 14.3% always, with 55.9% noting symptom onset over four weeks prior to their next dose. Common symptoms included fatigue, walking difficulties, and pain. Subgroup analysis of 334 patients revealed that 78.1% of patients experienced these effects, which correlated with shorter disease durations, a longer delay between the two doses before the last dose, and a greater rate of relapse (P>0.05). CONCLUSION: The WoP of the OCR is prevalent and significant among MS patients and is influenced by the dosing interval, disease duration, and relapse rate. These insights underscore the need for personalized treatment schedules and more research into factors affecting MS management.

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.].

Greater occipital nerve block efficacy in COVID­19 associated headache: a preliminary study.

COVID­19 is an infection caused by the new coronavirus SARS­CoV­2. Headache is one of the most common neurological findings. In the treatment of various chronic headaches, the greater occipital nerve (GON) block is often used as a safe and effective method. The aim of our study was to investigate the effectiveness of the GON block in the treatment of headaches observed in COVID­19 patients. Between March and May 2020, 27 patients (with laboratory­confirmed 2019­nCoV infection by next­generation sequencing confirmation of real­time PCR) that had moderate or severe headache associated with COVID­19 and treated with a single session of GON block were retrospectively analyzed. The visual analogue scale (VAS) values and the number of analgesic usage of patients were recorded before and after the blockade on the 1st and 10th days. Fifteen (55.6%) patients included in the study were male and twelve (44.4%) were female. In terms of VAS values, the difference between pre­treatment and post­treatment values on the 1st and 10th days was found statistically significant. Likewise, the difference between analgesic use before and after the procedure was statistically significant. GON block appears to be an effective pain management method in COVID­19 related headache, and it revealed promising reductions in pain scores and analgesic usage. As well as we know, this is the first study of "COVID­19 associated headache treated with GON blockade". More long term and well­designed prospective studies with more participants are needed to better define this headache and develop effective treatment strategies.

Cerebral Hemodynamic Changes During Migraine Attacks and After Triptan Treatments.

INTRODUCTION: Migraine has been known for many years, but its mechanism remains unclear. Different cerebral hemodynamic changes have been observed at different stages of a migraine attack. Published results on cerebral hemodynamics are contradictory. For this reason, we aimed to investigate cerebral hemodynamic changes during attacks as well as the effects of frovatriptan and rizatriptan. METHODS: Forty migraine patients with aura using rizatriptan (n=20) and frovatriptan (n=20) and 20 healthy individuals were included in our study. Cerebral blood flow velocities and breath-holding indices were recorded bilaterally from middle and posterior cerebral arteries. All procedures were repeated one hour after treatments and one week after attacks. RESULTS: We observed similar values of cerebral blood flow velocities and breath holding indices in all patients with migraine during the attack-free period compared to the control group. All cerebral vascular structures in migraine patients had significantly lower cerebral blood flow velocities and higher values in breath-holding indices during attacks. After taking rizatriptan and frovatriptan for an attack, the changes in hemodynamics disappeared. CONCLUSION: During attacks of migraineurs with aura, vasodilatation develops. In addition, higher vasomotor reactivity during attacks supports hypersensitivity in migraine pathophysiology. Triptans, acting as vasoconstrictor agents, were able to stop over-vasodilatation during attacks. In other words, it is possible that triptans show their effects by eliminating vascular hypersensitivity during acute attacks.

Familial Mediterranean Fever and Multiple Sclerosis Successfully Treated With Interferon Beta-1a: A Case Report.

Multiple sclerosis (MS) is the most common demyelinating disease in Turkey while familial Mediterranean fever (FMF) is the most common periodic fever syndrome worldwide. In this article, we report a 37-year-old male patient admitted with complaint of difficulty in walking. He had been taking colchicine at admission for 27 years. Despite this therapy, he had been experiencing twice monthly severe FMF attacks. After systemic and neurological examinations, laboratory tests and cranial and spinal magnetic resonance imaging, he was diagnosed as MS. Interferon (IFN) beta-1a was initiated three times/weekly subcutaneously for MS treatment. He stopped colchicine treatment after five months of IFN treatment because he did not suffer from any FMF attacks. He is still attack free for both diseases for a follow-up duration of 12 months. IFN beta is one of the most preferred agents for MS treatment but not one of the agents used for the treatment of FMF. Interferon beta can be a treatment of choice in patients with coincident FMF and MS and can be used in colchicine-resistant patients after being studied in systematic clinical studies.

Evaluation of cognitive functions in migraineurs treated with topiramate.

Topiramate for the treatment of migraine prophylaxis may cause side effects such as cognitive dysfunction. We aimed to investigate the topiramate's efficacy in migraineours and effect on cognitive functions. 24 migraine patients (Group 1) and 24 healthy participants (Group 2) were included. In both groups event-related potentials P300 Latency, Amplitude and N200 Latency, Amplitude's were evaluated. Topiramate treatment was ordered to group 1. Two months after treatment, the same parameters were evaluated. Monthly number of attacks, painful days, analgesic-triptan use and VAS scores were compared before and 2 months after treatment. Evaluation between group 1 and group 2 showed no difference. Group1's before and after treatment values were compared; all parameters after treatment were statistically significantly better. Group 1's number of attacks in a month, the number of painful days in a month, VAS score, the number of analgesic use, the number of triptan use had all decreased after treatment. 100 mg topiramate was effective in the treatment of migraine. However, electrophysiological studies showed that cognitive functions are also affected adversely.

The effects of topiramate therapy on cerebral metabolism in migraine with aura patients.

AIM: Topiramate is an antiepileptic drug with multiple mechanisms of action that is also used for migraine prophylaxis. This study aimed to investigate the efficacy of topiramate therapy for migraine prophylaxis, based on vasomotor reactivity ([VMR] an indicator of cerebral autoregulation), and to identify changes in cerebral hemodynamics during the treatment. MATERIAL AND METHODS: We included 20 migraine (with aura) patients (group 1) and 20 healthy controls (group 2) in the study. Transcranial Doppler monitoring was performed in both groups with patients in the supine and resting position. Using a two-sided temporal window at depths of 45-60 mm for the middle cerebral artery (MCA) and depths of 60-70 mm for the posterior cerebral artery (PCA), basal flow rates and VMR values were measured. Group 1 initially received 25 mg/d of topiramate orally, and then the dose was increased 25 mg every week. At the fourth week; the optimal dose was increased to 50 mg b.i.d. and the treatment was continued at this dose. Transcranial Doppler parameters were re-evaluated 2 months after treatment. In addition, the number of attacks per month, duration of pain, and visual analog scale (VAS) scores obtained before the treatment and 2 months after the treatment in group 1 were compared. RESULTS: Basal flow rates and VMR values recorded from the right and left MCA in group 1 were significantly higher than those in the control group (P < 0.05). Flow velocities obtained from the right and left MCA, and the VMR values in group 1 after topiramate treatment did not differ significantly from those in the control group (P > 0.05). In addition, the number of attacks, duration of pain, and VAS scores in group 1 were significantly lower after the treatment than before the treatment (P < 0.05). CONCLUSION: Topiramate is an effective prophylactic treatment in migraine with aura patients and appeared to play a positive role in the regulation of cerebrovascular autonomic control.

Effects of Subchronic Treatment with Ibuprofen and Nimesulide on Spatial Memory and NMDAR Subunits Expression in Aged Rats.

Several studies point to an important function of cyclooxygenase (COX) and prostaglandin signaling in models of synaptic plasticity which is associated with N-methyl-D-aspartate receptors (NMDARs). Cyclooxygenase gene is suggested to be an immediate early gene that is tightly regulated in neurons by NMDA dependent synaptic activity. Nonsteroid Antiinflammatory Drugs (NSAIDs) exert their antiinflammatory effect by the inhibion of COX have controversial effects on learning and memory. We administered ibuprofen as a non-selective COX-2 inhibitor and nimesulide as a selective COX-2 inhibitor for 8 weeks for determining the cognitive impact of subchronic administration of NSAIDs to aged rats. Wistar albino rats (16 mo, n = 30) were separated into control (n = 10), ibuprofen (n = 10) and nimesulide (n = 10) treated groups. First we evaluated hippocampus-dependent spatial memory in the radial arm maze (RAM) and than we evaluated the expression of the NMDAR subunits, NR2A and NR2B by western blotting to see if their expressions are effected by subchronic administration with these drugs. Ibuprofen and nimesulide treated rats completed the task in a statistically significant shorter time when compared with control group (p < 0.01), but there was no statistically significant difference between groups about choice accuracy data in RAM. Furthermore, no statistically significant difference was detected for the protein expressions of NR2A and NR2B of the subjects. Oral administration of ibuprofen and nimesulide for 8 weeks showed no impairment but partly improved spatial memory.

The efficacy of botulinum toxin in patients with cervicogenic headache: a placebo-controlled clinical trial.

OBJECTIVE: Botulinum toxin type-A (BoNTA) has been considered a treatment option for CH. The aim of this study was to assess the effectiveness of BoNTA treatment in patients with medically resistant CH. MATERIALS AND METHODS: Forty patients with CH were included in the study. Patients in the BoNTA group (n=20) were administered 10 U of BoNTA bilaterally to the frontal muscles, 20 U to the temporal muscles, 15 U to the semispinalis capitis, 15 U to the splenius capitis, and 15 U to the trapezius muscles (total: 150 U). Patients in the placebo group (n=20) received 0.2 mL of saline administrated to the same sites. All participations were evaluated 6 and 12 weeks after treatment; side effects, the number of painful days, severity (by visual analogue scale, VAS) and frequency of pain were evaluated. RESULTS: In the BoNTA group, the severity and frequency of pain 6 and 12 weeks post treatment were significantly lower than pre-treatment levels (p<0.05). At 12 weeks post treatment, the severity and frequency of pain in the BoNTA group were lower than in the placebo group (p<0.05). CONCLUSION: The findings suggest that BoNTA was an effective treatment for CH.