Disability burden of epilepsy in Türkiye: How does it differ from other newly industrialized countries?

INTRODUCTION: Epilepsy accounts for a substantial part of the global burden of disability. This study aimed to investigate the employment history of people with epilepsy in Türkiye, evaluate the role of education level in employment and epilepsy burden, and compare epilepsy employment data in different societies according to sociodemographic index data. METHODS: This prospective study included 420 people 16-76 years of age who were diagnosed with epilepsy according to the criteria of the International League Against Epilepsy. Socioeconomic, clinical, and employment data were collected using a questionnaire in face-to-face interviews. RESULTS: The study sample was 52 % women, the mean age was 34.2 ± 12.7 years (range: 16-76 years), and the mean disease duration was 17.2 ± 12.6 years. Only 26.7 % (n = 112) of the participants were actively working, 38.8 % had never worked, and 64.5 % had changed jobs at least twice (mean 2.45 job changes). The unemployment rate among the study sample was 7 times higher than in the general population. Female gender, low self and parental education levels, high seizure frequency, and the use of multiple anti-seizure medications were significantly associated with lower employment. CONCLUSION: We determined that the employment rates and education levels of people with epilepsy in Türkiye are low, the unemployment rate is high, and the burden of epilepsy is higher when compared with other low-middle income and newly industrialized countries and national population data. Education and employment opportunities for people with epilepsy in Türkiye should be improved to reduce the burden of epilepsy-related disability and thereby increase quality of life, welfare, and psychosocial well-being in this group.

EFHC1 gene mutation profile of Turkish JME patients and its association with disease risk.

OBJECTIVES: Juvenile myoclonic epilepsy (JME) is a common form of generalized epilepsy with an important genetic component. This cohort study aimed to examine the frequency of EFHC1 gene variants in Turkish JME patients and a healthy control group and evaluate the association between these mutations and disease risk. METHODS: We screened 72 JME patients with a mean age of 31.8 ± 9.9 (20-65) years and 35 controls with a mean age of 29.1 ± 7.6 (17-50) years from southern Turkey using direct sequencing analyses. RESULTS: EFCH1 single nucleotide variants were detected in 24 of 72 JME patients and 3 of 35 controls. The most common mutations were R182H in JME patients (p = 0.010) and 3'UTR in the control group (p < 0.001). The R182H mutation is a common variant in JME (95 % CI: 1.232-76.580, p = 0.031) and the 3'UTR mutation may be associated with lower risk of JME in the Turkish population (95 % CI: 13.89-166.67, p < 0.001). SIGNIFICANCE: Our results indicate that EFHC1 gene variants carry a risk for JME and the 3'UTR variant may have a protective role against JME in the Turkish population. Screening for other genes is needed to further clarify the genetic inheritance of JME in Turkish patients.

Which factors affect phenoconversion in isolated rapid eye movement sleep behavior disorder?

AIM: Isolated REM sleep behavior disorder (IRBD) is characterized by loss of the normal atonia of REM sleep. Patients with IRBD are at substantial risk of developing the synuclein-related neurodegenerative diseases (NDD). Few predictors of phenoconversion (from IRBD to NDD) have been identified such as age >65 years, hyposmia, constipation, elevated Epworth sleepiness scale (ESS). We aimed to detect rate and risk factors of phenoconversion. METHOD: The study designed as retrospectively. NDD was developed in 18 (27.27%) patients while NDD wasn't developed in 48 (72.73%) patients after ten years. The data of the first visit (age, gender, hyposmia, constipation, ESS, comorbidities, physical/neurological examinations, laboratory, and polysomnography) were compared between NDD (n:18) and IRBD (46) groups. The statistical program IBM SPSS Statistics Version 20.0 was used for all analyzes. The threshold for statistical significance for each test was set at 0.05. RESULTS: Although, most first-visit data (age, gender, hyposmia, constipation, ESS, laboratory, polysomnography) were not different between NDD (n:18) and IRBD (n:48) groups, diabetes mellitus (DM) frequency (p:0.021), mean duration of DM (0.027), chest circumference (p:0.017), and hip circumference (p:0.045) were found higher in NDD than IRBD. If the risk of phenoconversion calculated by logistic regression analysis was different only in terms of DM frequency (p:0.030) [odds ratio: 4.909 (1.17-20.19)]. CONCLUSION: The present study showed that the phenoconversion rate for ten years is 27.27%, and IRBD patients with diabetes mellitus increase the phenoconversion risk nearly five times.

Birth outcomes in pregnant women with epilepsy: A Nationwide multicenter study from Türkiye.

OBJECTIVE: The present study was aimed at investigating the effects of anti-seizure medications (ASMs), patient demographic characteristics, and the seizure type and frequency on the development of congenital malformations (CMs) in the infants of pregnant women with epilepsy (PWWE). METHODS: PWWE followed up at the neurology outpatient clinic of 21 centers between 2014 and 2019 were included in this prospective study. The follow-up of PWWE was conducted using structured, general pregnant follow-up forms prepared by the Pregnancy and Epilepsy Study Committee. The newborns were examined by a neonatologist after delivery and at 1 and 3 months postpartum. RESULTS: Of the infants of 759 PWWE, 7.2% had CMs, with 5.6% having major CMs. Polytherapy, monotherapy, and no medications were received by 168 (22.1%), 548 (72.2 %), and 43 (5.7 %) patients, respectively. CMs were detected at an incidence of 2.3% in infants of PWWE who did not receive medication, 5.7% in infants of PWWE who received monotherapy, and 13.7% in infants of PWWE who received polytherapy. The risk of malformation was 2.31-fold (95% confidence interval (CI): 1.48-4.61, p < .001) higher in infants of PWWE who received polytherapy. Levetiracetam was the most frequently used seizure medication as monotherapy, with the highest incidence of CMs occurring with valproic acid (VPA) use (8.5%) and the lowest with lamotrigine use (2.1%). The incidence of CMs was 5% at a carbamazepine dose <700 mg, 10% at a carbamazepine dose ≥700 mg, 5.5% at a VPA dose <750 mg, and 14.8% at a VPA dose ≥750 mg. Thus the risk of malformation increased 2.33 times (p = .041) in infants of PWWE receiving high-dose ASMs. SIGNIFICANCE: Birth outcomes of PWWE receiving and not receiving ASMs were evaluated. The risk of CMs occurrence was higher, particularly in infants of PWWE using VPA and receiving polytherapy. The incidence of CMs was found to be lower in infants of PWWE receiving lamotrigine.

Seizures in COVID-19: the relationship between biomarkers and prognosis.

OBJECTIVE: To assess the prevalence of seizure, associated risk factors, and prognosis in patients with SARS-CoV-2 infection and identify predictive biomarkers in SARS-CoV-2 patients with seizure. METHODS: A cohort of 17,806 patients with SARS-CoV-2 infection admitted to two university hospitals in Adana between March 11, 2020 and January 1, 2021 was analyzed retrospectively. The patients' demographic characteristics, laboratory findings, and systemic and neurological symptoms at admission and on the day of seizure onset were evaluated. RESULTS: Neurological findings were detected in 877 of the 17,806 patients. Of these, 45 patients (0.25%) had seizure (status epilepticus in 4/45 patients, 8.9%). Patients with seizure had a mean age of 55.3 years (range 17-88) and 57.8% were male. Seizure was more common in the 18-44 (24.4%) and ≥ 65 age groups (44.4%) and in those with multiple comorbidity. The case fatality rate for patients with seizure among all SARS-CoV-2 patients was 0.135% (95% CI 80.86-188.71). However, no patient with a previous diagnosis of epilepsy died during SARS-CoV-2 infection. High neutrophil, platelet, and ferritin levels and low lymphocyte and calcium levels on the day of seizure development compared to admission were associated with higher mortality (p = 0.004, 0.008, 0.028, 0003, and 0.002, respectively). CONCLUSIONS: Seizures are not uncommon during SARS-CoV-2 infection, with a higher risk of mortality in older patients and those with higher inflammatory markers.

Prognostic indicators of non-convulsive status epilepticus in intensive care unit.

BACKGROUND: To determine the rate of non-convulsive status epilepticus with/without prominent motor phenomena (SE-PM/ NCSE) and predictive value of electroclinical findings of continious electroencephalography (cEEG) monitoring of these patients and its association with prognosis in intensive care units (ICU). METHODS: We retrospectively collected data of 218 patients whose cEEG was performed in ICU between 2016 and 2018. The cEEG for NCSE diagnosis was evaluated according to Salzburg Consensus Criteria (SCC). RESULTS: The mean age of patients was 57.09 ± 18.9 (16-95) years and 49.1% (107) were female. Of 218 patients, 32 (14.7%) had SE-PM/NCSE. According to SCC the rate of NCSE (NCSE + possible NCSE) was 9.6% (n = 21). Prior to cEEG recording, 38.9% (n = 85) of overall patients had a history of seizure/convulsion, and 22.7% (n = 21) of these patients diagnosed with NCSE based on cEEG. The mortality rates in critically ill patients were 41.3% (30.8%, 42.8%; for SE-PM and NCSE respectively). Prognosis was associated with age, epilepsy diagnosis, having convulsion/seizure history on follow-up, GCS, need for ventilation, kind of drugs, sepsis diagnosis, and minimum frequency of background activity of the cEEG (p = 0.001, 0.002, 0.001, 0.020, 0.001, 0.001, 0.001, 0.0001 respectively). CONCLUSIONS: NCSE findings are mostly found in patients who were comatose and had seizure/convulsion history on follow-up. Mortality is higher in patients diagnosed with NCSE followed in the ICU compared to SE-PM.

Frequency and economic burden of psychogenic non-epileptic seizures in patients applying for disability benefits due to epilepsy.

BACKGROUND: Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures and are often misdiagnosed as epilepsy. OBJECTIVE: To investigate the frequency of PNES and to calculate the economic burden of the patients who admitted to video-electroencephalographicmonitoring (VEM) to obtain a diagnosis of epilepsy in order to apply for disability retirement. METHODS: The present retrospective study included 134 patients who required disability reports between 2013 and 2019 and had their definite diagnoses after VEM. Following VEM, the patients were divided into three groups: epilepsy, PNES, and epilepsy + PNES. RESULTS: In total, 22.4% (n = 30) of the patients were diagnosed with PNES, 21.6% (n = 29) with PNES and epilepsy, and 56% (n = 75), with epilepsy. The frequency of PNES among all patients was of 44% (n = 59). In patients with PNES alone, the annual cost of using anti-seizure medication was of 160.67 ± 94.04 dollars; for psychostimulant drugs, it was of 148.3 ± 72.48 dollars a year; and the mean direct cost for diagnostic procedures was of 582.9 ± 330.0 (range: 103.52-1601.3) dollars. CONCLUSIONS: Although it is challenging to determine the qualitative and quantitative total cost in these patient groups, early diagnosis and sociopsychological support will reduce the additional financial burden on the health system and increase the quality of life of the patients.

ANTECEDENTES: As crises psicogênicas não epilépticas (CPNE) se assemelham a crises epilépticas, e muitas vezes são diagnosticadas erroneamente como epilepsia. OBJETIVO: Investigar a frequência de CPNE e calcular o impacto econômico dos pacientes internados para serem submetidos a monitoramento videoencefalográfico (MVE) para obter um diagnóstico de epilepsia e requerer aposentadoria por invalidez. MéTODOS: Este estudo retrospectivo incluiu 134 pacientes que solicitaram laudo médico de incapacidade entre 2013 e 2019, e obtiveram seus diagnósticos definitivos após serem submetidos a MEV. Os pacientes foram divididos em três grupos: epilepsia, CPNE, e epilepsia + CPNE. RESULTADOS: Após o MEV, 22,4% (n = 30) dos pacientes foram diagnosticados com CPNE, 21,6% (n = 29), com CPNE + epilepsia, e 56%, com epilepsia. A frequência de CPNE entre todos os pacientes foi de 44% (n = 59). Em pacientes somente com CPNE, o custo anual do uso de anticonvulsivantes foi de US$ 160,67 ± 94,04; para os psicoestimulantes, o custo anual foi de US$ 148,3 ± 72,48; e a média do custo direto de procedimentos diagnósticos foi de US$ 582,9 ± 330,0 (variação: 103,52­1601,3). CONCLUSõES: Embora seja um desafio determinar o custo total qualitativo e quantitativo nesses grupos de pacientes, o diagnóstico precoce e o apoio sociopsicológico reduzirão o impacto financeiro adicional ao sistema de saúde e aumentarão a qualidade de vida dos pacientes.

Frequency and economic burden of psychogenic non-epileptic seizures in patients applying for disability benefits due to epilepsy / Frequência e impacto econômico das crises psicogênicas não epilépticas em pacientes requerentes de aposentadoria por invalidez devido a epilepsia

Abstract Background Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures and are often misdiagnosed as epilepsy. Objective To investigate the frequency of PNES and to calculate the economic burden of the patients who admitted to video-electroencephalographicmonitoring (VEM) to obtain a diagnosis of epilepsy in order to apply for disability retirement. Methods The present retrospective study included 134 patients who required disability reports between 2013 and 2019 and had their definite diagnoses after VEM. Following VEM, the patients were divided into three groups: epilepsy, PNES, and epilepsy + PNES. Results In total, 22.4% (n = 30) of the patients were diagnosed with PNES, 21.6% (n = 29) with PNES and epilepsy, and 56% (n = 75), with epilepsy. The frequency of PNES among all patients was of 44% (n = 59). In patients with PNES alone, the annual cost of using anti-seizure medication was of 160.67 ± 94.04 dollars; for psychostimulant drugs, it was of 148.3 ± 72.48 dollars a year; and the mean direct cost for diagnostic procedures was of 582.9 ± 330.0 (range: 103.52-1601.3) dollars. Conclusions Although it is challenging to determine the qualitative and quantitative total cost in these patient groups, early diagnosis and sociopsychological support will reduce the additional financial burden on the health system and increase the quality of life of the patients.

Resumo Antecedentes As crises psicogênicas não epilépticas (CPNE) se assemelham a crises epilépticas, e muitas vezes são diagnosticadas erroneamente como epilepsia. Objetivo Investigar a frequência de CPNE e calcular o impacto econômico dos pacientes internados para serem submetidos a monitoramento videoencefalográfico (MVE) para obter um diagnóstico de epilepsia e requerer aposentadoria por invalidez. Métodos Este estudo retrospectivo incluiu 134 pacientes que solicitaram laudo médico de incapacidade entre 2013 e 2019, e obtiveram seus diagnósticos definitivos após serem submetidos a MEV. Os pacientes foram divididos em três grupos: epilepsia, CPNE, e epilepsia + CPNE. Resultados Após o MEV, 22,4% (n = 30) dos pacientes foram diagnosticados com CPNE, 21,6% (n = 29), com CPNE + epilepsia, e 56%, com epilepsia. A frequência de CPNE entre todos os pacientes foi de 44% (n = 59). Em pacientes somente com CPNE, o custo anual do uso de anticonvulsivantes foi de US$ 160,67 ± 94,04; para os psicoestimulantes, o custo anual foi de US$ 148,3 ± 72,48; e a média do custo direto de procedimentos diagnósticos foi de US$ 582,9 ± 330,0 (variação: 103,52-1601,3). Conclusões Embora seja um desafio determinar o custo total qualitativo e quantitativo nesses grupos de pacientes, o diagnóstico precoce e o apoio sociopsicológico reduzirão o impacto financeiro adicional ao sistema de saúde e aumentarão a qualidade de vida dos pacientes.

Loss-of-function variants in the KCNQ5 gene are implicated in genetic generalized epilepsies.

BACKGROUND: De novo missense variants in KCNQ5, encoding the voltage-gated K+ channel KV7.5, have been described to cause developmental and epileptic encephalopathy (DEE) or intellectual disability (ID). We set out to identify disease-related KCNQ5 variants in genetic generalized epilepsy (GGE) and their underlying mechanisms. METHODS: 1292 families with GGE were studied by next-generation sequencing. Whole-cell patch-clamp recordings, biotinylation and phospholipid overlay assays were performed in mammalian cells combined with homology modelling. FINDINGS: We identified three deleterious heterozygous missense variants, one truncation and one splice site alteration in five independent families with GGE with predominant absence seizures; two variants were also associated with mild to moderate ID. All missense variants displayed a strongly decreased current density indicating a loss-of-function (LOF). When mutant channels were co-expressed with wild-type (WT) KV7.5 or KV7.5 and KV7.3 channels, three variants also revealed a significant dominant-negative effect on WT channels. Other gating parameters were unchanged. Biotinylation assays indicated a normal surface expression of the variants. The R359C variant altered PI(4,5)P2-interaction. INTERPRETATION: Our study identified deleterious KCNQ5 variants in GGE, partially combined with mild to moderate ID. The disease mechanism is a LOF partially with dominant-negative effects through functional deficits. LOF of KV7.5 channels will reduce the M-current, likely resulting in increased excitability of KV7.5-expressing neurons. Further studies on network level are necessary to understand which circuits are affected and how this induces generalized seizures. FUNDING: DFG/FNR Research Unit FOR-2715 (Germany/Luxemburg), BMBF rare disease network Treat-ION (Germany), foundation 'no epilep' (Germany).

Headache in idiopathic/genetic epilepsy: Cluster analysis in a large cohort.

OBJECTIVE: The link between headache and epilepsy is more prominent in patients with idiopathic/genetic epilepsy (I/GE). We aimed to investigate the prevalence of headache and to cluster patients with regard to their headache and epilepsy features. METHODS: Patients aged 6-40 years, with a definite diagnosis of I/GE, were consecutively enrolled. The patients were interviewed using standardized epilepsy and headache questionnaires, and their headache characteristics were investigated by experts in headache. Demographic and clinical variables were analyzed, and patients were clustered according to their epilepsy and headache characteristics using an unsupervised K-means algorithm. RESULTS: Among 809 patients, 508 (62.8%) reported having any type of headache; 87.4% had interictal headache, and 41.2% had migraine. Cluster analysis revealed two distinct groups for both adults and children/adolescents. In adults, subjects having a family history of headache, ≥5 headache attacks, duration of headache ≥ 24 months, headaches lasting ≥1 h, and visual analog scale scores > 5 were grouped in one cluster, and subjects with juvenile myoclonic epilepsy (JME), myoclonic seizures, and generalized tonic-clonic seizures (GTCS) were clustered in this group (Cluster 1). Self-limited epilepsy with centrotemporal spikes and epilepsy with GTCS alone were clustered in Cluster 2 with the opposite characteristics. For children/adolescents, the same features as in adult Cluster 1 were clustered in a separate group, except for the presence of JME syndrome and GTCS alone as a seizure type. Focal seizures were clustered in another group with the opposite characteristics. In the entire group, the model revealed an additional cluster, including patients with the syndrome of GTCS alone (50.51%), with ≥5 attacks, headache lasting >4 h, and throbbing headache; 65.66% of patients had a family history of headache in this third cluster (n = 99). SIGNIFICANCE: Patients with I/GE can be clustered into distinct groups according to headache features along with seizures. Our findings may help in management and planning for future studies.

Evaluation of the effects of shift work on parasomnia prevalence.

Shift work is increasingly common in industrialized countries but is associated with numerous health problems, especially sleep disorders. This study compared the frequency of NREM (confusional arousal, sleep terrors, sleepwalking, sleep-related eating disorder), REM parasomnias (REM sleep behavior disorder, nightmare disorder), and isolated symptoms/normal variants (sleeptalking) between shift workers and daytime workers. A total of 1473 participants in 3 different professional groups and working different shift schedules (daytime, night, or rotating shifts) were included. Participants completed a questionnaire consisting of 132 questions about parasomnia, occupational stress, history of occupational and traffic accidents, depression, and other sleep disorders. The lifetime parasomnia prevalence was 43.7% and the 1-year parasomnia prevalence was 24.4% overall. The 1-year parasomnia prevalence was 27.5% among shift workers and 13% among daytime workers. This rate was highest among rotating shift workers (27.9%), followed by night shift workers (21.2%), and lowest in daytime workers (13%) (P < .001). The most common parasomnias reported were sleep terrors, confusional arousals, and sleeptalking. Parasomnia prevalence rates among workers with and without a history of occupational accidents were 43.7% and 24.2%, while those of workers with and without a history of car accidents were 47.4% and 23.8%, respectively (P < .001). Shift work was associated with higher parasomnia prevalence. Working rotating shifts in particular was an independent risk factor for parasomnia. The parasomnias most frequently associated with shift work were confusional arousal, sleeptalking, and sleep terrors. It should be kept in mind that higher parasomnia rates may increase the risk of occupational and traffic accidents in this population.