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.

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.

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.

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.

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.

Frequency of Restless Legs Syndrome in adults with epilepsy in Turkey.

BACKGROUND: Restless Legs Syndrome (RLS) is a common disorder characterized by an irresistible urge to move the legs particularly during rest in the evenings often leading to insomnia and daytime impairment. No prior studies estimate the prevalence of RLS in a diverse sample of adults with epilepsy using standard diagnostic criteria. MATERIAL AND METHOD: A total of 225 patients with epilepsy (61.8% female; mean age 33.3 ± 12.3 years) seen in the epilepsy clinic of Çukurova University Neurology Department were included. Restless Legs Syndrome diagnosis was based on structured interviews using internationally accepted criteria. Demographic and epilepsy-related variables were obtained through medical record review. RESULTS: The prevalence of RLS was 5.8% (n=13). Mean score on the International RLS Study Group rating scale for these subjects was 9.3 ± 3.6 (6-18). Ten (76.9%) patients with RLS scored in the mild range and the remainder in the moderate range of severity. Patients with RLS were not significantly different from others in terms of demographics, epilepsy classification or duration, treatment regimen (polytherapy vs. monotherapy), patient-reported sleep assessment, or relevant laboratory data. CONCLUSION: The prevalence of RLS in adults with epilepsy was similar to that observed in the adult general Turkish population (3.18-5.2%), although we excluded subjects with conditions associated with RLS, rendering ours a conservative estimate. While preliminary, these findings support the need for future studies exploring RLS in epilepsy given the potential impact of untreated sleep disorders and sleep deprivation on seizures and quality of life in people with epilepsy.

Fibromuscular Dysplasia and Intravenous Thrombolytic Treatment.

Fibromuscular dysplasia (FMD), which usually affects middle-aged and older women, is a non-atheromatous and non-inflammatory angiopathy. Definitive diagnosis is made only by angiography showing classic string-of-beads appearance. In this article, we present a patient with acute ischemic stroke due to FMD who was successfully treated with thrombolytic therapy as well as to revise the approach to FMD in the light of the literature.

Early left ventricular functional alterations in patients with obstructive sleep apnea syndrome.

BACKGROUND: The knowledge regarding myocardial alterations in patients with obstructive sleep apnea syndrome (OSAS) in the absence of any known cardiovascular disorders including hypertension is limited. The aim of this study was to assess the early alterations of left ventricular (LV) functions caused by OSAS before the development of hypertension and other cardiovascular manifestations of OSAS. METHODS: Eighty consecutive patients who underwent polysomnography (PSG) were enrolled in the study. Patients with hypertension, diabetes mellitus or any other known cardiac diseases were excluded from the study. Subjects were separated into two groups by their apnea/hypopnea index (AHI) (group 1: AHI < 15, and group 2: AHI ≥ 15). Fourty-three patients with normal polysomnographic examination or mild OSAS (group 1) and 37 patients with moderate to severe OSAS (group 2) were compared. After PSG examination, LV functions were assessed by using the conventional and tissue Doppler echocardiographic methods. RESULTS: The mean age was similar between the groups. The ratio of male patients was higher in group 2 (male/female: 31/12 in group 1 vs. 34/3 in group 2, p = 0.04). Body mass index was higher in group 2 (p = 0.05). Conventional echocardiography showed that interventricular septum thickness was 9.5 ± 1.1 mm in group 1, and 10.5 ± 1.4 mm in group 2 (p = 0.02). Mean left atrial diameter was 35.6 ± 4.1 mm in group 2, and 33.8 ± 3.1 mm in group 1 (p = 0.04). Ratio of early to late transmitral diastolic velocities was lower in group 2 (p = 0.01), indicating that impairment of diastolic function was more frequent in moderate to severe OSAS patients. Tissue Doppler echocardiography showed that early diastolic myocardial velocity was lower ingroup 2 (21.1 ± 5.6 cm/s in group 1 vs. 18.3 ± 5.3 cm/s in group 2, p = 0.01). CONCLUSIONS: Left ventricular diastolic dysfunction, LV hypertrophy and left atrial dilatationoccur in patients with OSAS even before the development of hypertension and other cardiovascular diseases.

The conduction block produced by oxcarbazepine in the isolated rat sciatic nerve: a comparison with lamotrigine.

OBJECTIVE: Oxcarbazepine is an antiepileptic drug widely used for the treatment of neuropathic pain. In the present study, the effects of oxcarbazepine and lamotrigine on conduction properties in the rat sciatic nerves were examined. METHODS: The experiments were conducted with in vitro sucrose-gap technique on the isolated wistar rat sciatic nerves. The compound action potentials were obtained by tonic (single) and phasic (10, 40, and 100 Hz) stimulation. RESULTS: Oxcarbazepine produced a significant concentration- and frequency-dependent reduction in the compound action potential amplitude. When the two drugs were applied at concentrations that produced equal levels of tonic (i.e., non-frequency-dependent) conduction block, oxcarbazepine produced the greatest phasic (i.e., frequency-dependent) conduction block, followed by lamotrigine. Oxcarbazepine and lamotrigine reduced the 4-aminopyridine-induced amplitude of delayed depolarization; however, oxcarbazepine had a significantly greater effect than lamotrigine. CONCLUSION: These results suggest that oxcarbazepine produces more potent frequency-dependent conduction block than lamotrigine, and suppresses the delayed depolarization which contributes to sensory signaling and may play a role in neuropathic pain. The findings provide insight into the mechanisms of action of oxcarbazepine and lamotrigine and may help in the development of novel therapies for neuropathic pain.

Can neural network able to estimate the prognosis of epilepsy patients according to risk factors?

The aim of this study is to evaluate the underlying etiologic factors of epilepsy patients and to predict the prognosis of these patients by using a Multi-Layer Perceptron Neural Network (MLPNN) according to risk factors. 758 patients with epilepsy diagnosis are included in this study. The MLPNNs were trained by the parameters of demographic properties of the patients and risk factors of the disease. The results show that the most crucial risk factor of the epilepsy patients was constituted by the febrile convulsion (21.9%), the kinship of parents (22.3%), the history of epileptic relatives (21.6%) and the history of head injury (18.6%). We had 91.1 % correct prediction rate for detection of the prognosis by using the MLPNN algorithm. The results indicate that the correct prediction rate of prognosis of the MLPNN model for epilepsy diseases is found satisfactory.

The effect of electrophysiological and neuroimaging findings on the prognosis of juvenile myoclonic epilepsy proband.

BACKGROUND: Juvenile myoclonic epilepsy (JME) is a well-defined idiopathic generalized epileptic syndrome, and diagnostic criteria for JME are to have a normal brain imaging and clinical evidence of typical epileptic seizures. The aim of this study is to evaluate electrophysiological and neuroimaging findings of JME and determine their relationship with prognosis. METHODS: Thirty-two patients (23 women and nine men) with a mean age of 22 (16-37) years were included in this study. Interictal electroencephalography (EEG), magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) were carried out in all patients. RESULTS: Analysis of premedication EEGs revealed primary generalized pattern activity in 75% (n=24) and focal abnormalities in 18.75% (n=6). MRI was abnormal in seven (21.88%) patients (two with arachnoid cyst, two with mild cerebral atrophy, two with ventricular enlargement and one with single gliotic lesion), and SPECT imaging detected hypoperfusion in 15 (47%) patients. Hypoperfusion was mostly found on the parietal lobe. CONCLUSION: We found that, after medication, only 6.25% of EEGs had primary generalized pattern activity (p<0.0001); nevertheless, the prognosis was good in patients who had typical EEG findings (p=0.106). The prognosis of patients with MRI abnormalities was grave (p=0.023). Twenty percent of the patients who had SPECT abnormalities were seizure free, and 80% of them had been partially controlled (p=0.059). There were no correlations between MRI abnormalities, EEG and SPECT findings.

Lyme disease presenting as subacute transverse myelitis.

Lyme disease (borreliosis) is a systemic illness resulting from infection with the spirochete Borrelia burgdorferi. It is transmitted to humans by the bites of infected ticks belonging to several species of the genus Ixodes. After the bacteria enter the body via the dermis, most patients develop the early, localised form of Lyme disease, which is characterised by erythema migrans and influenza-like symptoms. This disease may also affect the heart, nervous system and joints. The neurological findings of this disease may include peripheral and central nervous system signs. A 21-year-old woman attended a family medicine outpatient clinic complaining of unexplained pain and muscle power loss in her lower extremities. The problem had started in her right leg 3 months earlier and worsened in the last week. She had a neurology consultation and was hospitalised. Her neurological examination revealed bilateral facial paralysis and sensory impairment. Immunoglobulin M antibody to B. burgdorferi was positive on Western blotting in both serum and cerebrospinal fluid. The patient was diagnosed with subacute neuroborreliosis and treated.

A radial basis function neural network model for classification of epilepsy using EEG signals.

Epilepsy is a disorder of cortical excitability and still an important medical problem. The correct diagnosis of a patient's epilepsy syndrome clarifies the choice of drug treatment and also allows an accurate assessment of prognosis in many cases. The aim of this study is to evaluate epileptic patients and classify epilepsy groups such as partial and primary generalized epilepsy by using Radial Basis Function Neural Network (RBFNN) and Multilayer Perceptron Neural Network (MLPNNs). Four hundred eighteen patients with epilepsy diagnoses according to International League against Epilepsy (ILAE 1981) were included in this study. The correct classification of this data was performed by two expert neurologists before they were executed by neural networks. The neural networks were trained by the parameters obtained from the EEG signals and clinic properties of the patients. Experimental results show that the predictions of both neural network models are very satisfying for learning data sets. According to test results, RBFNN (total classification accuracy = 95.2%) has classified more successfully when compared with MLPNN (total classification accuracy = 89.2%). These results indicate that RBFNN model may be used in clinical studies as a decision support tool to confirm the classification of epilepsy groups after the model is developed.

Epileptic seizures triggered by the use of a powered toothbrush.

BACKGROUND: Reflex epilepsy is characterized by seizures that are triggered in response to a specific stimulus and tooth-brushing epilepsy is an extremely rare form of reflex epilepsy in which the seizures are mainly induced by the act of tooth brushing. In this report, we describe an epilepsy patient whose seizures were exclusively triggered by the use of a powered toothbrush. METHODS AND RESULTS: A 31-year old female had been treated for partial epilepsy of left temporal or frontal lobe for 20 years and she did not have seizures for the last 3 years. However, she experienced periods of auras, partial complex seizures, and nocturnal generalized seizures after she started using a powered toothbrush. The interictal electroencephalography revealed slow wave paroxysm over the left temporal or frontal lobe. CONCLUSIONS: This case report is, to our knowledge, the first report of reflex epilepsy in which the seizures were triggered by the use of a powered toothbrush. Possible mechanisms to explain the novel type of this rare disorder are discussed.

The actions of lamotrigine and levetiracetam on the conduction properties of isolated rat sciatic nerve.

The purpose of this study was to investigate the actions of lamotrigine and levetiracetam on the conduction properties of isolated rat sciatic nerves in-vitro. Compound action potentials from rat sciatic nerves were recorded using a sucrose-gap technique with single and repetitive stimulation. Lamotrigine, at 0.01 to 1 mM, reduced the amplitude of compound action potentials (3.9+/-0.6% to 47.9+/-2.4%) and produced at high frequency dependent (phasic) and independent (tonic) conduction block. Lamotrigine extended the peak time of the compound action potentials significantly without changing the half falling-time (P<0.05). Lamotrigine reduced the amplitude of the delayed depolarization, which was more pronounced than that of the amplitude of the compound action potentials in the presence of 4-aminopyridine. With tonic and phasic stimulation, 0.1 to 10 mM of levetiracetam did not alter the amplitude, peak time and half falling time of the compound action potentials. In addition, levetiracetam did not change the amplitude of the delayed depolarization and the area of the compound action potentials following application of 4-aminopyridine. These results indicate that lamotrigine produces a powerful tonic block with delayed depolarization, whereas it produces a weaker phasic block in rat sciatic nerve. Levetiracetam has no effect on peripheral nerve conduction even at high concentrations. These results may have the relevance to our understanding of the peripheral effects of lamotrigine and levetiracetam.

Transient parkinsonism: induced by progesterone or pregnancy?

We report on the development of transient parkinsonism after progesterone injection in a pregnant patient with a risk of abortion. Etiological possibilities are discussed, including pregnancy itself, possible toxic effects of the dead fetus, and progesterone injection. Progesterone-induced parkinsonism seems the most likely diagnosis in this case.