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.

Is multiple sclerosis a risk factor for atherosclerosis?

BACKGROUND: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. We aimed to discuss possible predisposing factors to atherosclerosis such as carotid intima-media thickness (CIMT) and high-sensitivity C-reactive protein (Hs-CRP) levels in MS. METHODS: Thirty-five ambulatory patients with relapsing-remitting MS (RRMS) (22 females and 13 males) and 34 healthy controls (21 females and 13 males) with similar demographic variables were included. Blood cell counts, cholesterol levels, vitamin D and B12, Hs-CRP levels, body mass index (BMI), history of smoking, and CIMT of both groups, Expanded Disability Status Scale (EDSS) scores, and disease duration of patients were recorded. Patients with a history of other vascular diseases such as hypertension, diabetes mellitus, peripheral artery disease, and acute relapses were excluded. RESULTS: Sixty-nine participants were included. The mean age of the study population was 35.8±7.1 years. Right CIMT was significantly greater in the patient population (P<0.001). Spearman's correlation coefficient between age and right CIMT was r=0.41, P=0.01. When we compared the Hs-CRP with a cut-off value of ≤3, the right, left, and mean CIMT levels were not statistically significant (P=0.17; P=0.22; P=0.15). The mean serum vitamin D levels were higher in the patient group and this was statistically significant (P<0.001). The statistically significant factors identified with univariate analysis with P<0.2 were further entered into multivariate modelling. CONCLUSION: CIMT seems to be affected in patients with MS by means of the disease itself and age. Thus, CIMT might reflect the predisposition to subclinical atherosclerosis more than Hs-CRP. Further investigation in a large MS population is still needed.

Methylation of cation-chloride cotransporters NKCC1 and KCC2 in patients with juvenile myoclonic epilepsy.

The etiology of juvenile myoclonic epilepsy (JME) is still unknown and the process of elaboration of multiple genetic mechanisms is ongoing. The aim of this study was to investigate the potential role of NKCC1 (SCL12A2) and KCC2 (SCL12A5) in JME by comparing their DNA methylation status in patients with JME versus healthy controls. Forty-nine patients with JME and 39 healthy individuals were compared for DNA methylation at the 5CpG islands. A total of 71 (81%) samples were found to have methylation in the NKCC1 gene, 36 (73%) from patients and 35 (90%) from healthy individuals. Out of the KCC2 samples, 50 (57%) were found to have methylation, 33 (67%) from patients and 17 (44%) from healthy individuals. In patients with JME, methylation of NKCC1 (73%) was lower than its methylation in the controls (90%) (p = 0.047). On the other hand, methylation of KCC2 in patients with JME (67%) was greater than the methylation in the controls (44%) (p = 0.022). Twenty-eight patients were treated with VPA and ongoing medications were not found to be associated with methylation (p > 0.05). In the present study, we determined significantly lower NKCC1 DNA methylation and significantly higher KCC2 DNA methylation levels in patients with JME compared with the healthy controls. This implies that NKCC1 expression can be higher and KCC2 expression can be reduced in affected people. Further studies that investigate the potential effect of DNA methylation mechanisms regulating gene expression on seizure activity and how they change JME network activity will be helpful.

The methylation status of NKCC1 and KCC2 in the patients with refractory temporal lobe epilepsy.

BACKGROUND AND PURPOSE: Methylation is a key epigenetic modification of DNA and regarding its impact on epilepsy, it is argued that "DNA methylation may play an important role in seizure susceptibility and maintenance of the disorder". DNA methylation status of KCC2 (SCL12A5) and NKCC1 (SCL12A2) associated with refractory temporal lobe epilepsy was investigated in our study. METHODS: Thirty-eight patients with temporal lobe epilepsy (TLE) who were diagnosed by video EEG monitoring and 32 healthy control subjects were included in the study. Twenty-three patients in TLE group were men and the remaining 15 were women. Among them, 27 had unilateral temporal focus (9 with right; 18 with left) and 11 patients had bilateral TLE. We analyzed promoter region methylation status of the KCC2 (SCL12A5) and NKCC1 (SCL12A2) genes in the case and control groups. Gene regions of interest were amplified through PCR and sequencing was accomplished with pyro-sequencing. RESULTS: We found a significant relationship between TLE and methylation on the NKCC1. However, there was no association between TLE and methylation on the KCC2 gene. Also, we found no association between right or left and unilateral or bilateral foci of TLE. There was no relationship between TLE and methylation on the NKCC1and KCC2 genes in terms of mesial temporal sclerosis in cranial MRI, head trauma or febrile convulsions. CONCLUSION: The methylation of NKCC1 can be a mecha-nism of refractory temporal lobe epilepsy. There are limited findings about DNA methylation in TLE. Therefore, further studies with large sample sizes are necessary.

Two-year results of carotid artery stenting.

OBJECTIVES: The effectiveness of carotid artery stenting (CAS) for primary and secondary prevention of ischemic stroke has been demonstrated. The aim of our study was the clinical and radiological evaluation of the reliability of the CAS procedure over a two-year follow-up period. STUDY DESIGN: This study included 120 patients (mean age, 68 (48-86) years) admitted to our hospital between December 2010 and March 2013 for whom CAS was decided in the neurology, cardiovascular surgery and cardiology council. Symptomatic cases with more than 50% stenosis by angiography and asymptomatic patients with stenosis of more than 70% were included in the study. 80% of the asymptomatic patients were those detected during the screening before the coronary bypass surgery. RESULTS: The success rate of the procedure was found as 97.5%. No mortality or myocardial infarction was observed in any of the patients in whom CAS was applied successfully. In 1 symptomatic patient (0.8%), ischemic cerebrovascular event with sequelae was observed 24 hours after the procedure. In total, transient ischemic attack was observed in 2 patients (1.7%) 6 and 11 months after the procedure. Asymptomatic restenosis was detected in 3 patients (2.5% of the total, with 2 in the asymptomatic and 1 in the symptomatic group). Symptomatic restenosis was not observed. None of the patients experienced hyperperfusion syndrome. CONCLUSION: We believe the CAS procedure can be performed safely in symptomatic and asymptomatic patients with low complication and high success rates.

Early and late-onset nonconvulsive status epilepticus after stroke.

BACKGROUND: Nonconvulsive status epilepticus (NCSE) is a condition that needs timely diagnosis and treatment. It has insignificant clinical features and presents high risk of misdiagnosis. OBJECTIVE: To investigate NCSE among patients with stroke, given that stroke plays an important role in the etiology of NCSE. METHODS: In this retrospective study, acute stroke patients who were admitted and followed up at a stroke outpatient clinic between January 2013 and March 2016 were included. Patients with previous histories of epilepsy, brain tumor, head trauma, hypertensive encephalopathy, arteriovenous malformation, subarachnoid hemorrhage or cerebral venous thrombosis were excluded. Demographic properties, stroke etiology, imaging method, EEG findings, stroke severity according to the NIHSS score, functional disability and modified Rankin Scale were recorded for all patients. RESULTS: Thirty-nine out of 792 stoke patients experienced NCSE. The mean age of the study population was 70±1.2 years (min-max: 46‒90). The study population was composed of 28 females (71.8%) and 11 males (28.2%). NCSE had early onset in 23 patients (59%) and late onset in 16 (41%). The early-onset NCSE patients were older and this was statistically significant between the groups (early onset: 73.5±11.5; late onset: 65.9±12.1; p=0.04). A history of previous stroke was more frequent in the late-onset NCSE group (14; 87,5%) than in the early-onset group (11; 47.8%) (p=0.01). The prognosis was worse in the early-onset group, but without statistical significance. CONCLUSION: Changes in mental status in the early stages of stroke are mostly attributed to stroke itself, but NCSE should be suspected in the right clinical setting, such as in older patients with suspicious anatomical and clinical associations.

Colour vision in juvenile myoclonic epilepsy.

To determine the integrity of colour perception, related to photic sensitivity, in patients with juvenile myoclonic epilepsy. Twenty-four patients with photoparoxysmal response, 27 patients without photoparoxysmal response, and 32 healthy individuals were investigated using the Farnsworth Munsell-100 Hue test to calculate error scores for total colour, blue/yellow, and red/green. No significant differences were observed regarding blue/yellow, red/green or total error score between juvenile myoclonic epilepsy patients with or without photoparoxysmal response. However, the data for all three scores were significantly higher in both patient groups compared to the healthy control group. In both patient groups, the blue/yellow error score was significantly higher than the red/green error score. We were unable to identify a relationship between photoparoxysmal response and colour vision in patients with juvenile myoclonic epilepsy. We believe that the underlying reason why juvenile myoclonic epilepsy patients had significantly higher blue/yellow, red/green, and total error score compared to the healthy control group may be due to GABA dysfunction, which is considered to play a role in the pathophysiology of this disease as well as the physiology of colour vision.

Reversible Splenial Lesion Syndrome After Intravenous Immunoglobulin Treatment for Guillain-Barre Syndrome.

Reversible corpus callosum splenial (CCS) lesions have been described in patients with varied etiologies. The most common causes of previously reported reversible focal lesions of the CCS are viral encephalitis, antiepileptic drug toxicity/withdrawal, and metabolic disorders. Intravenous immunoglobulin (IVIG) therapy is used for different immune-mediated diseases. It is generally safe, and serious adverse reactions are uncommon. We presented a rare case of disturbed consciousness with reversible CCS lesions after IVIG therapy for Guillain-Barre syndrome in an adult woman. In this case, we believe that IVIG therapy caused reversible CCS lesions with encephalopathy and probably result of cytotoxic edema and/or cerebral arterial vasospasm.

Early and late-onset nonconvulsive status epilepticus after stroke / Estado de mal epiléptico não convulsivo de ocorrência precoce e tardia após acidente vascular cerebral

ABSTRACT Background: Nonconvulsive status epilepticus (NCSE) is a condition that needs timely diagnosis and treatment. It has insignificant clinical features and presents high risk of misdiagnosis. Objective: To investigate NCSE among patients with stroke, given that stroke plays an important role in the etiology of NCSE. Methods: In this retrospective study, acute stroke patients who were admitted and followed up at a stroke outpatient clinic between January 2013 and March 2016 were included. Patients with previous histories of epilepsy, brain tumor, head trauma, hypertensive encephalopathy, arteriovenous malformation, subarachnoid hemorrhage or cerebral venous thrombosis were excluded. Demographic properties, stroke etiology, imaging method, EEG findings, stroke severity according to the NIHSS score, functional disability and modified Rankin Scale were recorded for all patients. Results: Thirty-nine out of 792 stoke patients experienced NCSE. The mean age of the study population was 70±1.2 years (min-max: 46‒90). The study population was composed of 28 females (71.8%) and 11 males (28.2%). NCSE had early onset in 23 patients (59%) and late onset in 16 (41%). The early-onset NCSE patients were older and this was statistically significant between the groups (early onset: 73.5±11.5; late onset: 65.9±12.1; p=0.04). A history of previous stroke was more frequent in the late-onset NCSE group (14; 87,5%) than in the early-onset group (11; 47.8%) (p=0.01). The prognosis was worse in the early-onset group, but without statistical significance. Conclusion: Changes in mental status in the early stages of stroke are mostly attributed to stroke itself, but NCSE should be suspected in the right clinical setting, such as in older patients with suspicious anatomical and clinical associations.

RESUMO Introdução: O Estado de Mal Não-Convulsivo (EMNC) é uma condição que necessita de diagnóstico e tratamento oportunos. Possui características clínicas insignificantes e apresenta alto risco de diagnóstico incorreto. Objetivo: Investigar o EMNC entre pacientes com acidente vascular cerebral (AVC), visto que ele desempenha um papel importante na etiologia do EMNC. Métodos: Neste estudo retrospectivo, pacientes com AVC agudo que foram admitidos e acompanhados em um ambulatório de AVC entre janeiro de 2013 e março de 2016 foram incluídos. Pacientes com história prévia de epilepsia, tumor cerebral, traumatismo cranioencefálico, encefalopatia hipertensiva, malformação arteriovenosa, hemorragia subaracnóidea ou trombose venosa cerebral foram excluídos. Propriedades demográficas, etiologia do AVC, método de imagem, achados de EEG, gravidade do AVC pela escala NIHSS, incapacidade funcional e escala de Rankin modificada foram registrados para todos os pacientes. Resultados: Um total de 39 dos 792 pacientes com AVC experimentaram EMNC. A idade média da população do estudo foi de 70±1,2 anos (mín-máx: 46‒90). A população do estudo foi composta por 28 mulheres (71,8%) e 11 homens (28,2%). O EMNC teve início precoce em 23 pacientes (59%) e início tardio em 16 (41%). Os pacientes com EMNC de início precoce eram mais velhos, o que foi estatisticamente significativo entre os grupos (início precoce: 73,5±11,5; início tardio: 65,9±12,1; p=0,04). Um histórico de AVC prévio foi mais frequente no grupo com EMNC de início tardio (14; 87,5%) do que no grupo de início precoce (11; 47,8%) (p=0,01). O prognóstico foi pior no grupo de início precoce, mas sem significância estatística. Conclusão: As alterações no estado mental nos estágios iniciais do AVC são atribuídas principalmente ao próprio AVC, mas deve-se suspeitar de EMNC com diagnóstico clínico correto, como em pacientes mais velhos com associações anatômicas e clínicas suspeitas.