Long-term Use Of Antiepileptic Drugs Research Articles

A - 160 Cognition over Time in Chronic sTBI with Non-Neurologic Comorbidities in Residential NeuroRehab.

Traumatic brain injury has been associated with increased risk of many comorbid neurologic and non-neurologic disorders (Masel & DeWitt, 2010). There is scant literature, however, to describe serial assessment of cognitive changes associated with comorbid non-neurologic disorders and sequelae in patients with chronic, severe traumatic brain injury (sTBI). A 60-year-old, right-handed, White male sustained an sTBI at age 15 secondary to a motor vehicle collision and subsequently developed behavioral and substance use problems, before being placed in a long-term residential neurorehabilitation program. He later developed kidney disease, believed to be the result of long-term use of anti-epileptic drugs (AEDs) that were prescribed to control seizures that developed following his brain injury. He continued to experience seizures, despite taking AEDs. Staff at his residential program reported concerns of declines in cognition and daily functioning over the past three years. Compared to results from two previous evaluations performed approximately four and six years prior, he demonstrated reductions in attention and working memory, processing speed, executive functioning, auditory and reading comprehension, and functional living skills. Expressive language, memory, and visuospatial skills were generally consistent with previous evaluations. Due to significant reductions across multiple cognitive domains, and multiple potential contributing factors, including ongoing seizures, late-stage kidney disease, and a possible superimposed neurodegenerative disorder, it was recommended that the patient continue to undergo serial neurocognitive testing to monitor for further decline and provide etiological clarification. The results were used by his therapists, residential program staff, and neurology providers to inform his treatment planning and care.

EPILEPSY IN WOMEN OF FERTILE AGE

Epilepsy in women is caused by the hypothalamic-pituitary-ovarian system, and women with epilepsy have a higher incidence of disorders such as menstrual irregularities, polycystic ovary syndrome, and infertility. The incidence of sexual dysfunction in the group of women with epilepsy ranges from 14 to 50%. It was found that epileptic seizures and long-term use of antiepileptic drugs (AEDs) lead to reproductive disorders of the female body, affecting the endocrine, hormonal, and sexual spheres of the female body.

A case report on anti-epileptic drugs associated cerebral palsy and rickets

Seizures are incredibly widespread all around the world, today. A seizure is often described as a transient alteration in the electrical activity of the brain. This required the treatment with antiepileptic drugs (AEDs). The majority of AEDs lower vitamin D levels. Vitamin D is found to be crucial for intestinal absorption of calcium, magnesium, and phosphate which helps to build and mineralize bones. Vitamin D deficiency has been seen to be a causative reason for cerebral palsy which is a neurological illness that affects movement and muscle coordination, permanently. It has been observed to manifest in infancy or early childhood due to vitamin D deficiency due to long term use of AEDs making it severe due to malnourishment. This case reports the use of antiepileptic drugs leading to cerebral palsy due to vitamin D deficiency. Therefore, by this case report we want to alert the readers and healthcare professionals about the possible adverse effects of AEDs and to be aware of them.

Research Progress of Febrile Seizures in Children

Febrile seizures (FS) are common neurological diseases in childhood. It is age-dependent and often occurs in children from 6 months to 5 years old. The etiology of FS is diverse and the mechanism is complex, which is not completely clear, but most children have a good prognosis. Through timely identification, symptomatic treatment and health guidance to patients’ families, we can get a good prognosis. In the treatment of FS, we should pay attention to finding the cause, and do a good job in the health education and guidance for children's families. At present, the long-term use of antiepileptic drugs is not recommended to prevent the recurrence and secondary epilepsy of FS. In the future, through the development of traditional Chinese medicine, the combination of Chinese and Western medicine can be considered in order to improve the therapeutic effect of FS. This paper reviews the relevant literature about the research progress of FS in recent years in China and abroad, to provide new ideas for the diagnosis and treatment of FS in children.

CORRELATION BETWEEN THE DURATION OF ANTI-EPILEPTIC DRUGS THERAPY AND VITAMIN D LEVEL IN EPILEPTIC CHILDREN

Long-term use of antiepileptic drugs (AEDs) for epilepsy causes a decrease in vitamin D levels due to the activation of liver cytochrome P450 enzymes. The novelty of this study is due to researching about correlation between the duration of anti-epileptic drugs therapy and vitamin d level in epileptic children This cross-sectional study was conducted from October - December 2021in children with epilepsy aged 1 month to 18 years admitted to pediatric neurology polyclinic of DR Wahidin Sudirohusodo. They were divided into two groups: epileptic children receiving AEDs treatment ≤ 1 year and epileptic children receiving AEDs treatment 1 year. Statistical analysis showed no significant relationship between the duration of AEDs use and the incidence of vitamin D deficiency in children with epilepsy.Keywords: Vitamin D Deficiency; Antiepileptic Drugs; Epilepsy

Evaluation of the risk factors for recurrence and the development of epilepsy in patients with febrile seizure.

Although febrile seizure (FS) is generally considered benign and self-limiting, there are differences regarding the risk factors, the prognosis, and the development of epilepsy. To examine the clinical and sociodemographic characteristics of patients diagnosed with FS, and to determine the risks of recurrence and the development of epilepsy. Between 2015 and 2019, we performed a retrospective evaluation of 300 patients with FS followed for at least 24 months. The first episode of FS was simple in 72.7% of the patients and complex in 27.3%, and it recurred in 40%. Age under 12 months in the first FS, complex FS, and neurodevelopmental delay were found to statistically increase the risk of recurrence (p < 0.05). A total of 7% of the patients developed epilepsy, and this rate was found to be higher in patients with neurodevelopmental delay and long-term use of antiepileptic drugs (p < 0.001). The development of epilepsy was also observed in 77.8% of the patients with abnormal electroencephalogram (EEG). Epilepsy developed more frequently in those with abnormal EEG (p<0.001). Neurodevelopmental delay was an important risk factor for FS recurrence and the development of epilepsy. Abnormality in the EEG is an important risk factor for the development of epilepsy. We found that the long-term prophylactic treatment did not cause decreases in the recurrence of FS nor in the development of epilepsy.

Assessment of asymmetric dimethylarginine and homocysteine in epileptic children receiving antiepileptic drugs

BackgroundEpilepsy is a neurological disease that requires long-term antiepileptic drugs (AEDs). The old generation of AEDs may affect serum homocysteine and asymmetric dimethylarginine (ADMA) and disturb lipid levels. The aim of the study was to evaluate serum ADMA, homocysteine, lipid profile, and carotid intima-media thickness (CIMT) in epileptic children.MethodsThis study was implemented on 159 epileptic children who were subdivided into 3 subgroups, with 53 receiving sodium valproate, 53 receiving levetiracetam, and 53 receiving polytherapy, for over 6 months and 53 healthy children.ResultsLow-density lipoprotein, triglycerides, and cholesterol levels were increased in epileptic children (p < 0.001), which were higher in those receiving multidrug followed by a valproate receiver. While high-density lipoprotein was lower in those receiving multidrug more than those receiving valproate. ADMA and homocysteine levels increased in epileptic patients than in controls (p < 0.001). Higher ADMA was also observed in the multidrug receiver (5.78 ± 0.62), followed by the levetiracetam group (5.56 ± 0.61). Homocysteine levels were significantly higher in multidrug and valproate-treated children than those treated with levetiracetam. CIMT was significantly higher in multidrug and valproate-treated patients (p < 0.001).ConclusionsLong-term use of AEDs, especially old-generation polytherapy, can elevate lipid profiles, homocysteine, ADMA levels, and carotid intima-media thickness compared to the minimal effect of new AEDs.ImpactThe long-term use of antiepileptic drugs, especially old-generation polytherapy, can increase lipid profiles, homocysteine levels, ADMA, and carotid intima thickness compared to the minimal effect of new antiepileptic generation.A routine follow-up of these markers and a lifestyle modification are recommended to avoid cerebrovascular events as much as possible.

Osteogenic Effect of Pregabalin in Human Primary Mesenchymal Stem Cells, Osteoblasts, and Osteosarcoma Cells.

Seventy million patients worldwide are suffering from epilepsy. The long-term use of antiepileptic drugs causes the alteration of the bone tissue and its metabolism, thus increasing the risk of fractures. Clinical and pre-clinical studies have highlighted conflicting data on the influence of the relatively new antiepileptic drug pregabalin (Lyrica®). The objective of the present study was therefore to investigate its cytotoxicity in primary human osteoblasts (hOB). HOB and human mesenchymal stem cells (hMSC) were isolated from patients. The human osteosarcoma cells MG63 were included as established cell line. Cells were incubated with pregabalin at concentrations ranging from 0 to 40 μg/mL. Time-dependent cell proliferation was measured by automatic cell counting, and metabolism was determined by XTT assay and osseous differentiation by alkaline phosphatase (ALP) activity. Histological examinations of calcium deposit were performed with ALP, Alizarin Red, and von Kossa staining. A concentration-dependent increase in the proliferation of hOB and hMSC was observed after treatment with pregabalin. All cells showed a significant increase in cell metabolism. The osteogenic differentiation, confirmed by the increase of calcium deposit, was promoted by the administration of pregabalin. This effect was already significant at the therapeutic plasma concentration of pregabalin (10 μg/mL). In contrast to the other antiepileptic drugs, pregabalin showed no osteocatabolic effects. Conflicting in-vivo data must therefore be attributed to systemic effects of pregabalin.

Effect of Antiepileptic Drugs on Serum Lipid Profile among Children with Epilepsy at a Tertiary Care Hospital, Chennai, India

Introduction: An arsenal of Antiepileptic Drugs (AED) is used in the management of childhood seizure disorders. Most of them are taken long-term. These drugs have the potential to cause hyperlipidemia by inducing the P450 enzyme system. The alteration in lipid profile caused by long-term use of antiepileptic drugs in children needs to be studied to reduce the risk of future atherosclerosis. Aim: To analyse the effect of antiepileptic drugs on serum lipid profile in children with epilepsy in a tertiary care. Materials and Methods: This prospective descriptive study was conducted in the Outpatient and Inpatient Wards of the Department of Paediatrics and Neurology, Institute of Child Health and Hospital for Children, Chennai, Tamil Nadu, India, from February 2017 to September 2017. The study involved a total of 155 children, who were on monotherapy antiepileptic drugs for atleast 6 months (33 on phenytoin, 42 on phenobarbitone, 20 on levetiracetam, 20 on carbamazepine, 40 on sodium valproate). A corresponding numbers of children, who attended the General Outpatient Department for acute upper respiratory tract and were otherwise healthy, were included as controls. A blood sample (3 mL) was drawn after an overnight fast for serum glucose, liver enzymes, total cholesterol, High Density Lipoprotein-Cholesterol (HDL-C), Low Density LipoproteinCholesterol (LDL-C), Very Low Density Lipoprotein (VLDL) cholesterol and Triglycerides (TG) measurement. Chi-square test was performed to find out the significance of association and independent t-test was used to compare the mean between various groups. Results: Cytochrome P450 (CYP) enzyme inducers like carbamazepine, phenytoin and phenobarbitone significantly modified serum lipids in epileptic children when compared to healthy controls. In children on long-term phenytoin monotherapy, mean cholesterol levels were significantly higher in the cases compared to controls (156.73±31.93 mg/dL vs 105.03±8.60 mg/dL, p-value &lt;0.0001), significantly elevated triglycerides (123.48±25.99 mg/dL vs 87.88±12.16 mg/dL, p-value &lt;0.0001), and HDL-C level was significantly lower (44.52±10.14 mg/ dL vs 56.73±12.56 mg/dL, p-value &lt;0.0001) than in controls. Phenobarbitone use was associated with significantly higher levels of cholesterol (164.97±34.41 mg/dL vs 107.76±9.28 mg/dL, p-value &lt;0.0001), LDL (155.27±28.55 mg/dL vs 93.36±6.81 mg/ dL, p-value &lt;0.0001), and triglycerides (125.55±42.19 mg/dL vs 86.30±8.12 mg/dL, p-value &lt;0.001) and lower HDL (46.30±9.47 mg/dL vs 57.73±14.41 mg/dL, p-value &lt;0.0001). Levetiracetam was not associated in significant alteration in both liver enzymes and lipid profile (p-value &gt;0.05). Carbamazepine monotherapy was associated with higher levels of cholesterol (180.50±28.06 mg/dL vs 112.15±13.55 mg/dL, p-value &lt;0.0001), LDL (138.85±22.55 mg/dL vs 82.45±12.12 mg/dL, p-value&lt;0.0001) and triglycerides (142.80±9.48 mg/dL vs 85.40±6.29 mg/dL, p-value &lt;0.0001) when compared to healthy controls. There was no alteration in lipid profile in valproate monotherapy. Valproate monotherapy was associated with significant increase in levels of SGOT and SGPT when compared to mean levels (40.35±11.208 (IU/L), and 40.70±8.809 (IU/L), respectively) observed in other AEDs and significant increase in SGPT levels when compared to healthy controls (36.50±10.61(IU/L) in cases vs 40.70±8.81 (IU/L) in controls). Conclusion: Levetiracetam did not produce significant changes in the serum lipid profile and liver enzymes and appears to be safe to use in children for long-term epilepsy management especially in children with baseline deranged lipid profile.

Carbamazepine-Induced Hematological and Immunological Alterations in Egyptian Children with Idiopathic Generalized Seizures

AbstractCarbamazepine (CBZ) is one of the oldest antiepileptic drugs (AEDs) that is still used for the treatment of tonic-clonic seizures in children. Long-term use of AEDs induces potential toxic effects that may remain undetermined for a long time. Earlier studies have revealed a wide spectrum of hematological toxicities associated with CBZ. This study was conducted to unveil the toxic effects of carbamazepine as an antiepileptic monotherapy on hematological and immunological parameters in a group of Egyptian pediatric patients using it for different durations. Fifty pediatric epileptics of either sex were enrolled; 38 were taking CBZ as antiepileptic monotherapy for ≥ 6 months and 12 were newly diagnosed untreated patients. Hematological and immunological parameters studied were compared with their age and sex-matched 15 controls and among groups. CBZ was found more toxic for total leukocyte count, lymphocyte count, serum IgA and IgM levels (p &lt; 0.001, 0.001, &lt; 0.001, &lt; 0.001, respectively). Hemoglobin level, platelets count, serum C4 level and IgA were negatively correlated with serum CBZ level (Spearman's rho = – 0.62, – 0.42, – 0.34, – 0.13; p &lt; 0.001, 0.008, 0.04, 0.44, respectively). CBZ treatment duration associated inversely with platelets, lymphocyte, and eosinophil counts (p &lt; 0.001, 0.03, 0.01, respectively). Epileptic children on CBZ monotherapy had their hematologic and immunologic systems affected, which mandates routine monitoring of these children.

Correlation of Vitamin D and Calcium Levels in Children in New Diagnosed Epilepsy and Minimal 6 Months After Therapy

INTRODUCTION. Children with epilepsy should take long-term anti-epileptic drugs. Long-term use of anti-epileptic drugs can reduce vitamin D levels. Low vitamin D will lead to low blood calcium levels. This study aims to analyze the relationship between vitamin D and calcium levels in newly diagnosed epileptic children and ≥6 months after therapy. METHOD. These was an analytical observational study with cross sectional research design. The vitamin D examination instrument uses the ELFA method (enzyme linked fluorescent assay) with the Vidas instrument from bioMerieux. Samples were collected during June - August 2018 from Inpatient and Outpatient Clinics. The samples were divided into new diagnosis of epilepsy group and 6 months after therapy group. Each group was measured for vitamin D and serum calcium levels. The relationship between the two parameters were analyzed using T-Test independent. RESULTS. From the 19 new diagnosis of epilepsy, there were 57.9% low vitamin D and 10.5% low calcium levels. From the 20 subjects 6 months after therapy, 70% low vitamin D and 25% low calcium levels. There were a relationship between vitamin D and calcium levels in patients with newly diagnosed and ≥6 months after therapy. DISCUSSION. Low vitamin D and low calcium levels were found more in the anti-epileptic therapy group than the new diagnosis group of epilepsy. Low vitamin D levels can be caused by the use of long-term antiepileptic drugs that will affect serum calcium levels. CONCLUSION. This study showed a significant relationship between vitamin D and serum calcium levels in patients with newly diagnosed epilepsy and 6 months after therapy. Vitamin D and calsium serum examination should be done in every patient who gets long term therapy of antiepileptic drugs. KEY WORDS. Vitamin D, calcium, epilepsy, ELFA.

Biomarkers Obtained by Transcranial Magnetic Stimulation of the Motor Cortex in Epilepsy.

Epilepsy is associated with numerous neurodevelopmental disorders. Transcranial magnetic stimulation (TMS) of the motor cortex coupled with electromyography (EMG) enables biomarkers that provide measures of cortical excitation and inhibition that are particularly relevant to epilepsy and related disorders. The motor threshold (MT), cortical silent period (CSP), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long interval intracortical inhibition (LICI) are among TMS-derived metrics that are modulated by antiepileptic drugs. TMS may have a practical role in optimization of antiepileptic medication regimens, as studies demonstrate dose-dependent relationships between TMS metrics and acute medication administration. A close association between seizure freedom and normalization of cortical excitability with long-term antiepileptic drug use highlights a plausible utility of TMS in measures of anti-epileptic drug efficacy. Finally, TMS-derived biomarkers distinguish patients with various epilepsies from healthy controls and thus may enable development of disorder-specific biomarkers and therapies both within and outside of the epilepsy realm.

Clinical features and long-term outcomes of seizures associated with autoimmune encephalitis: A follow-up study in East China

PurposeTo evaluate the clinical characteristics, treatment outcomes, prognosis and potential risk factors of patients in East China with seizure secondary to autoimmune encephalitis. MethodsFrom February 2014 to June 2016, 113 patients diagnosed with autoimmune encephalitis in Huashan Hospital, Fudan University, were enrolled in our study. After at least two years of follow-up, we retrospectively analyzed the patients’ clinical details, electroencephalograph performance, brain MRI findings, and the therapeutic outcome. Patients underwent clinical evaluation every 3 months. We compared the clinical characteristics and epileptic prognosis of autoimmune encephalitis per antibody type. The association of the epileptic prognosis and EEG abnormalities was evaluated. GTE (Grand Total EEG) Score was used to evaluate EEG abnormalities. Statistic methods included ANOVA, Bonferroni correction test. ResultsTreatment outcomes were assessabled in 103 patients (10 patients died or withdrew), including anti-GABABR encephalitis (11), anti-LGI1 encephalitis (16), anti-NMDAR encephalitis (73), Caspr2 antibody encephalitis (3). 83 patients had seizures, who underwent both immunotherapy and anti-epileptic drugs therapy. In terms of seizure type, 57 (68.7%) patients exhibited focal to bilateral tonic-clonic seizure (FBTCS), 51 (61.4%) patients exhibited focal-impaired awareness seizure (FIAS) or focal aware seizure (FAS). 18 (21.7%) patients developed to status epilepticus. 30 (36%) patients had multiple types of seizures. 39 (47%) patients had daily seizures. 80.7% (67/83) of patients with epilepsy had seizure remission. During the 24 months of follow-up, 11 (11%) patients had clinical relapses. GTE scores were significantly different between the group with seizure reduction < 75% and the group with seizure remission (p = 0.009). Imaging abnormalities existed in 53% of the patients in our cohort, but lacked specificity during the acute phase. ConclusionAutoimmune encephalitis (AE) presents with large seizure burden with differing seizure semiology among different antibody types. Except for anti-GABAb receptor encephalitis, it may not be necessary for other AE types to apply long-term use of anti-epileptic drugs (AEDs). The GTE Score can be used to evaluate the EEG abnormalities and may be a predictor of seizure outcomes. MRI findings during the acute phase are non-specific. Long-term follow-up MRIs may be much more meaningful in evaluating prognosis.

Long-term seizure outcome in patients with status epilepticus due to acute encephalitis

PurposeTo investigate the long-term seizure outcome in patients with convulsive status epilepticus (CSE) due to acute encephalitis and identify early predictors for terminal seizure remission. MethodsBased on a prospective registry of CSE, consecutive patients with CSE due to acute encephalitis were enrolled from July 2009 to November 2017, with follow-up ending in November 2018. Variables during hospital stay, seizure outcomes within 1 month after status epilepticus (SE), and seizure outcomes within 3 months after acute phase of encephalitis were assessed for predicting terminal seizure freedom. ResultsAfter a median 58-month observation period, 77 patients were included in this study. Twenty-eight (36%) patients died within 3 months, 22 (29%) patients had recurrent seizures after acute phase of encephalitis, and 27 (35%) patients attained terminal seizure freedom after acute phase of encephalitis. Patients with CSE due to autoimmune encephalitis had a higher rate of terminal seizure freedom than those with viral and other encephalitis. Among all living patients (n = 49), 26 (53%) patients were on anti-epileptic medication at the end of follow-up. STESS score on admission, seizure freedom throughout 1 month after SE, and seizure freedom throughout 3 months after acute phase were found to be independently associated with terminal seizure freedom. ConclusionsOur study proposed a dynamic assessment system to identify patients for whom long-term use of anti-epileptic drugs (AEDs) might not be necessary. Our findings filled a gap in treatment decision on how long AEDs should be continued for patients with CSE due to acute encephalitis.

Osteopathic correction effect on anxiety and depression level according to HADS scale in children with various forms of epilepsy

Introduction.Epilepsy is a chronic brain disease, which treatment consists of relieving the seizures with the help of constant long-term use of anti-epileptic drugs. This, in turn, can cause various negative effects on the body. Epilepsy is not a single disease with various attacks, it is a whole spectrum associated with comorbid conditions, including anxiety and depression. Additional medication is suggested to correct this. Therefore, developing the effective drug-free methods with the help of osteopathic treatment to correct anxiety and depression in epilepsy complex therapy received priority.Goal of research— to study the osteopathic treatment potential to reduce anxiety and depression levels in children with various forms of epilepsy.Materials and methods.The study included 72 children with various forms of epilepsy, aged from 7 to 17 years, 35 girls, 37 boys. The selection criteria were as follows: at least 1 year of epilepsy course duration, no status or serial course of epileptic seizures, no motor and cognitive deteriorations, all children studied in public schools. All children received osteopathic treatment for 2 months, along with medical treatment. Before and after treatment, each patient′s anxiety and depression levels were assessed according to the Hospital Anxiety and Depression Scale (HADS), along with an osteopathic examination.Results.All children taken in the study revealed a range of somatic dysfunctions of craniosacral system, skull and reciprocal tension membranes, with biomechanical abnormality. By initial testing, anxiety and depression average values according to HADS scale were above normal in all children. After osteopathic treatment, a statistically signifi cant decrease in anxiety and depression levels was found.Conclusion. Osteopathic treatment is effi cient for epilepsy complex therapy in children. It helps to reduce drug load in correction of anxiety and depression that accompany the underlying disease.

Characteristics of Seizure and Antiepileptic Drug Utilization in Outpatients With Autoimmune Encephalitis.

Autoimmune encephalitis (AE) is one kind of encephalitis that associates with specific neuronal antigens. Most patients with AE likely suffer from seizures, but data on the characteristics of seizure and antiepileptic drugs (AEDs) utilization in this patient group remains limited. This study aimed to report the clinical status of seizure and AEDs treatment of patients with AE, and to evaluate the relationship between AEDs discontinuation and seizure outcomes. Patients with acute neurological disorders and anti-N-methyl-D-aspartate receptor (NMDAR), γ-aminobutyric acid B receptor (GABABR), leucine-rich glioma inactivated 1, or contactin-associated protein-like 2 (CASPR2) antibodies were included. As patients withdrew from AEDs, they were divided into the early withdrawal (EW, AEDs used ≤3 months) and late withdrawal (LW, AEDs used >3 months) groups. Seizure remission was defined as having no seizures for at least 1 year after the last time when AEDs were administered. Seizure outcomes were assessed on the basis of remission rate. The factors affecting the outcomes were assessed through Spearman analysis. In total, we enrolled 75 patients (39 patients aged <16 years, male/female = 39/36) for follow-up, which included 67 patients with anti-NMDAR encephalitis, 4 patients with anti-GABABR encephalitis, 2 patients with anti-voltage-gated potassium channel encephalitis, and 2 patients with coexisting antibodies. Among the 34 enrolled patients with anti-NMDAR encephalitis who were withdrawn from AEDs, only 5.8% relapse was reported during the 1-year follow-up, with no significant difference in the percentage of relapse between the EW and LW groups (P = 0.313). Fifteen patients (an average age of 6.8, 14 patients with anti-NMDAR encephalitis and 1 patient with anti-CASPR2 encephalitis) presented seizure remission without any AEDs. Seventy five percent of patients with anti-GABABR antibodies developed refractory seizure. Other risk factors which contributed to refractory seizure and seizure relapse included status epilepticus (P = 0.004) and cortical abnormalities (P = 0.028). Given this retrospective data, patients with AE have a high rate of seizure remission, and the long-term use of AEDs may not be necessary to control the seizure. Moreover, seizures in young patients with anti-NMDAR encephalitis presents self-limited. Patients with anti-GABABR antibody, status epilepticus, and cortical abnormalities are more likely to develop refractory seizure or seizure relapse.

Antiepileptic drugs are associated with central hypothyroidism.

Studies in children have shown an increased frequency of central hypothyroidism (CH) with long-term use of antiepileptic drugs (AEDs). The aim of this study was to search for CH in adults treated with AEDs and find whether the type of AEDs used matters. Adult epileptic patients treated at the neurology outpatient clinic at Landspitali University Hospital (LSH) from 1998 to 2011 were included. Patients were invited for a blood test if serum levels for TSH (s-TSH) or free-T4 (s-fT4 ) had not already been obtained. CH was defined as s-fT4 below the reference range (12-22pmol/L) and normal s-TSH levels (0.30-4.20mIU/L). Data were analyzed using logistic regression and Mann-Whitney test. We identified 165 patients (92 women), mean age 45.6 (±15.5, range: 20-92) years. The mean s-fT4 -level in our group was 14.2 (±2.9, range: 8.1-24.4) pmol/L compared with 16.9 (±6.1) pmol/L in a sample of 13248 measurements at LSH during one year (LSH-group) (P<0.001). The difference in s-fT4 -level between men and the LSH-group was significant and also for women (P<0.001 and P<0.001, respectively). Thirty-five patients (21%) had CH. A significant association with the use of carbamazepine or oxcarbazepine was found, odds ratio for women 15.0 (95% CI: 4.6-49.5) and 1.8 (95% CI: 0.4-8.3) for men. 21% of patients treated with AEDs had CH, more often patients taking carbamazepine or oxacarbazepine, and more often women. The s-fT4 -level was lower among patients treated with AEDs.

Evaluation of long-term antiepileptic drug use in patients with temporal lobe epilepsy: Assessment of risk factors for drug resistance and polypharmacy

PurposeTo evaluate risk factors for drug resistance and polypharmacy in patients with temporal lobe epilepsy. MethodsPatients with temporal lobe epilepsy, treated for more than 5 years, completed questionnaires on antiepileptic drug use and effect. Logistic regression models were used for analysis of risk factors. ResultsOf 135 patients included in the study, 65% were classified as drug resistant and 41% identified as using polypharmacy. Poor effects associated with first-choice antiepileptic drug were reported by 59% of the patients, and 70% reported poor effects of second-line treatment. The most frequently used first-generation antiepileptic drugs had a similar mean effect to those of second-generation. Univariate regression analyses showed a significant association between drug resistance and mesial temporal sclerosis, seizure onset below 18 years, and lack of family history of epilepsy. However, multivariate regression analysis showed no association with any demographic or clinical features. Unsuccessful treatment with the first antiepileptic drug increased the risk of drug resistance by 18 times, and the risk of poor effect from the second antiepileptic drug by 9 times. Disease duration was associated with annual risk for drug resistance of 7% and for polypharmacy of 5%. ConclusionsA poor effect from initial pharmacotherapy is the only early risk factor for drug resistance found in this study. Long disease duration increases the risk of drug resistance and polypharmacy. Second-generation antiepileptic drugs provide no additional effect for poor responders to first-generation drugs.

Seizure outcomes in patients with anti‐NMDARencephalitis: A follow‐up study

To evaluate the long-term seizure outcome and potential factors associated with seizure outcome in patients with anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. In the setting of a prospective, single-center, longitudinal cohort study, 109 patients were evaluated with ongoing follow-up. Patients underwent clinical evaluation every 3 months. Seizure outcomes and the potential risk factors were assessed with a median follow-up of 24 months (6-60 months). Of 109 patients (47 men; 62 women) with anti-NMDAR encephalitis, 88 patients (80.7%) had reported seizures at acute phase, including single seizure (17/88, 19.3%), repetitive seizures (27/88, 30.7%), nonrefractory status epilepticus (22/88, 25%), refractory status epilepticus (SE; 13/88, 14.8%), and super refractory status epilepticus (9/88, 10.2%). Seizure was more likely to recur in patients with tumor presence, status epilepticus (SE) development, coma, or intensive care unit (ICU) admission in the acute phase (p < 0.05). Seizure freedom was achieved within 2 years in all patients. More than 80% of the whole cohort with acute seizures had their last seizure within 6 months of disease onset. Seizure is a common feature in the acute stage of anti-NMDAR encephalitis but not thereafter. The presence of tumor, SE, coma, and/or ICU admission in the acute phase predicts early seizure occurrence after the acute phase. Seizure freedom was typically achieved in our follow-up, and long-term use of antiepileptic drugs may not be necessary.

Potential risk factors for vitamin D levels in medium- and long-term use of antiepileptic drugs in childhood

Antiepileptic drugs (AED) have potential side effects through vitamin-D. Prevalence of vitamin D insufficiency and potential risk factors for the longitudinal changes of vitamin D levels compared to its baseline levels under AED treatment were investigated in this study. This retrospective study includes patients whose AED therapy were started in only autumn months, between 2000 and 2014. Detailed assessment of neurologic diagnosis and brain MRI findings, ambulatory status, types and durations of AED treatment, and baseline bone health blood tests (vitamin-D, alkaline phosphatase, calcium, and phosphate levels) were obtained on all patients. Vitamin-D deficiency was defined as 25(OH)D <20ng/mL, while vitamin-D insufficiency was defined as 25(OH)D between 21 and 29ng/mL. A total of 172 children (mean age 9.6±4.3years) were followed up 5.3years in average (range 1-14.7). The mean baseline 25(OH)D level was decreased from 24.4±11.6 to 19.6±10.7ng/mL at the last follow up. The mean change in the vitamin-D levels (ΔD-vitamin) was -4.8ng/mL (p=0.003). The rate of vitamin-D deficiency was 54% and insufficiency was 25%. Multivariate logistic regression analysis identified only long-term use of AEDs as a risk factor for the longitudinal decrease. Monotherapy with valproic acid (n=45), carbamazepine (n=20), levetiracetam (n=10) and phenobarbital (n=12) was compared with each other. There was no difference in terms of longitudinal changes in 25(OH)D levels. In the treatment of childhood epilepsy, 25(OH)D levels should be monitored, especially when long-term AED used, in order to prevent D-hypovitaminosis.