Trends in enzyme-inducing antiseizure medication use: A retrospective analysis among adults with epilepsy.

BACKGROUND: Enzyme-inducing antiseizure medications (EIASMs) were associated with drug interactions and long-term adverse effects. Therefore, it was suggested that epilepsy treatment should be started with non-EIASMs, and in patients treated with EIASMs, replacement with non-EIASMs should be evaluated OBJECTIVE: To assess potent EIASM use among patients with epilepsy at their first visit in our epilepsy outpatient clinic. METHODS: We retrospectively reviewed the computerized database and the medical records of all the patients who had their first visit in our outpatient epilepsy clinic during a 10-year period (2012-2021). Of 730 patients with ASM treated epilepsy, 243 (33%) were receiving potent EIASMs. RESULTS: The annual potent EIASM use decreased from 35.1 % in 2012 to 11.8 % in 2021. Most of the patients who received potent EIASM had their first visit during 2012-2015 compared to the following years (56.8 % vs 43.2 %) (p = 0.0001). Patients with epilepsy receiving potent EIASMs were older (44.3 vs 34.7) (p = 0.0001), more likely men (60.9 % vs 47.2 %) (p = 0.001), with longer disease duration (13 vs 9.3 y) (p = 0.0001), higher rate of neuropsychiatric comorbidity (37 % vs 27.9 %) (p = 0.014), and were treated with more ASMs (1.6 vs 1.3) (p = 0.0001) compared to patients receiving non-EIASMs. CONCLUSIONS: Potent EIASM use has been declining over the past decade. Additional efforts to further decrease EIASM use should be exerted among all patients with ASM-treated epilepsy, with emphasis on men with focal epilepsy and epilepsy duration > 10 years.

The yield of non-elective inpatient video-EEG monitoring in adults.

BACKGROUND: Inpatient video-EEG monitoring (VEM) can contribute to the diagnosis and treatment in many of the monitored patients. Most admissions to VEM are elective and are scheduled ahead before the monitoring session. PURPOSE: To retrospectively evaluate the yield of non-elective VEM sessions. METHODS: We retrospectively reviewed the VEM recordings and medical records of all the patients admitted to our one-bed VEM unit from June 2007 to June 2015. A VEM session was diagnostic when a seizure, an event or previously unreported interictal epileptiform discharges were recorded. RESULTS: The study group included 304 adults aged 18-92 years (mean 40.4 ± 17.4 years), 181 (59%) women. The diagnostic yield of non-elective and elective VEM session was similar (66 and 69%, respectively). In non-elective VEM, fewer patients had known epilepsy (p = 0.0001), session duration was shorter (p = 0.0001), and seizures and interictal epileptiform discharges were recorded less frequently compared to elective VEM (p = 0.005 and p = 0.0001, respectively). CONCLUSION: Non-elective VEM can provide useful information in patients admitted to the neurology department with recent neurological or behavioral events. A timely and correct diagnosis in these patients can potentially reduce unnecessary use of antiepileptic drugs in patients with psychogenic nonepileptic seizures and the morbidity and mortality associated with undiagnosed seizures.

How valuable is inpatient electroencephalogram for medical decision-making?

BACKGROUND: The electroencephalogram (EEG) can support the diagnosis of epilepsy, diagnose nonconvulsive status epilepticus and aid in the classification of epileptic seizures. Its contribution to the diagnosis of other medical conditions or to decision-making in other clinical situations was not established. Practically, EEG laboratories frequently encounter EEG referrals that are not based on current recommendations. OBJECTIVES: To assess the value of inpatient EEG in medical decision-making. METHODS: We retrospectively reviewed the inpatient computerized medical information management system and the EEG laboratory computerized database for all adult inpatient standard, sleep-deprived and bedside EEGs performed during a one-year period. Change in diagnosis and/or treatment and the clinical justification for ordering an EEG recording were determined. RESULTS: The study group included 584 patients, 313 (54%) men, aged 55·5 ± 20·8 years (range 18-95 years). The EEG was clinically justified in 372 (63·7%) and led to change in diagnosis and/or treatment in 47 (8%) patients. These patients were significantly more likely to be admitted to the neurology department (P = 0·033), have an admission and discharge diagnosis of seizure or epilepsy (P = 0·0001), have a clinically justified EEG (P = 0·0001) and have an EEG recording with electrographic seizures (P = 0·0001), interictal epileptiform discharges (P = 0·0001) and background abnormalities (P = 0·003). CONCLUSIONS: Inpatient EEG can mostly contribute to diagnosis and treatment in patients with a seizure or epilepsy. An informed use of the EEG can increase its yield and reduce the number of unnecessary referrals, thus shortening waiting time and enabling earlier diagnosis and treatment in yet undiagnosed patients.

Folic acid supplementation in women of childbearing age with epilepsy: No association with type or number of antiepileptic drugs.

BACKGROUND: For over two decades, a daily folic acid (FA) supplementation has been recommended for women of childbearing age with epilepsy. This recommendation is based on evidence that FA administration before conception and during pregnancy can decrease the risk of fetal malformations in the general population, improve cognitive development, and reduce the risk of autistic traits in children exposed in utero to antiepileptic drugs (AEDs). OBJECTIVE: The aim of this study was to evaluate FA supplementation rate in nonpregnant women of childbearing age with epilepsy and its relation to AED type and number. METHODS: We retrospectively reviewed the computerized database and the medical records of all the women who had a first visit to our outpatient epilepsy clinic (Shamir-Assaf Harofeh Medical Center, Zerifin, Israel) during a 10-year period (2012-2021). RESULTS: Only 61 (22%) of 282 nonpregnant women of childbearing age with epilepsy treated with AEDs received FA supplementation. Ninety-two (33%) of the women were treated with AED polytherapy, and 41 (15%) received valproic acid in monotherapy or polytherapy. FA supplementation rate was higher in women aged ≤40 versus >40 (25% vs. 8.5%) (p = .004). No correlation was found between FA supplementation and AED type or number. CONCLUSIONS: FA supplementation rate was low and was unaffected by AED treatment. Patient and physician-targeted interventions should be implemented to increase FA prescription and patient adherence.

Quality of life in seizure-free patients with epilepsy on monotherapy.

Epilepsy is a multifaceted chronic disorder which has diverse and complex effects on the well-being of the patient. Although it is evident that seizure type and frequency play a critical role in the quality of life (QOL) of patients with epilepsy, it is less clear what the major determinants are that influence QOL in seizure-free patients receiving monotherapy. The aim of this study was to evaluate demographic, clinical, and socioeconomic factors influencing the QOL of seizure-free patients receiving monotherapy. All participants were patients from four medical centers who had epilepsy, were on monotherapy, and had been seizure-free for at least 1 year. Responders completed three questionnaires on demographic and clinical information, QOL, and antiepileptic drug (AED) side effects during routine follow-up visits in the epilepsy clinics. We present the data of 103 patients: 59 females (57.3%), mean age 37.75+/-13.66 years. Treatment side effects and unemployment (p<0.0001, p=0.037, respectively) were significant predictors for poor overall QOL, whereas age, gender, education, family status, comorbidity, seizure type, age of seizure onset, and epilepsy duration did not significantly affect overall QOL. There was no significant difference in side effects and QOL between patients receiving older versus newer AEDs. Ninety-four (92.2%) patients reported experiencing at least one side effect of AEDs when queried about specific symptoms, while only 11 (10.7%) patients replied affirmatively when asked whether they experienced "any" side effects. The most common side effects involved the central nervous system. In conclusion, this study reveals that the most significant factor influencing the QOL in seizure-free patients on monotherapy is AED side effects. QOL is a crucial component in the clinical care of patients with epilepsy, and physicians should take the time to ask specific questions on side effects of AEDs.

Phenytoin intoxication in a clozapine-related prolonged seizure.

Phenytoin is a first-line drug for the treatment of status epilepticus. We report a case of phenytoin intoxication after intravenous phenytoin loading in a patient with clozapine-related seizures. To our knowledge, this is the first description of phenytoin intoxication due to CYP2C9 inhibition by clozapine. This case report is important because it supports the use of a lower intravenous loading dose of phenytoin in patients with clozapine-related status epilepticus.

Delayed post-ictal event-related potentials do not differentiate between generalized tonic-clonic seizures and syncope.

BACKGROUND: The differentiation between generalized tonic-clonic seizure (GTCS) and syncope is an important clinical problem. Corroborative investigations, which are requested when history is unclear or insufficient, have limited diagnostic value. The aim of our study was to determine whether auditory event-related potentials (ERPs) can be utilized in post-event differentiation between GTCS and syncope. MATERIALS AND METHODS: ERPs were recorded in 18 patients with a single seizure and in 21 patients following syncope, either on one or two occasions. ERP latencies and amplitudes were compared between groups and sessions. RESULTS: No significant differences of P3, N2, P2 and N1 latencies and P3, N2 and P2 amplitudes were found between patients following a single GTCS as compared to patients following syncope on either session. CONCLUSION: Post-event ERPs are insufficient to differentiate between GTCS and syncope. Further investigations are needed to evaluate the influence of different post-event intervals and ERP paradigms on ERP parameters in patients with GTCS.

Antiepileptic Drug Treatment in Community-Dwelling Older Patients with Epilepsy: A Retrospective Observational Study of Old- Versus New-Generation Antiepileptic Drugs.

INTRODUCTION: The use of antiepileptic drugs (AEDs) in older patients with epilepsy is challenged by polypharmacy and decreased drug elimination. Newer AEDs have a lower potential for drug interactions and are reported to be better tolerated by the elderly than old-generation AEDs. OBJECTIVE: The objective of this study was to evaluate AED use and the related adverse event rate in an outpatient cohort of older patients with epilepsy. METHODS: We retrospectively reviewed the computerized database and medical records of all the patients aged ≥60 years who visited our epilepsy outpatient clinic (Assaf Harofeh Medical Center, Zerifin, Israel) during a 4-year period from February 2012 to February 2016. In this study, phenytoin, valproic acid, carbamazepine, phenobarbital, clobazam, and clonazepam were defined as old-generation AEDs. Gabapentin, levetiracetam, lamotrigine, topiramate, oxcarbazepine, lacosamide, and perampanel were defined as new-generation AEDs. RESULTS: The study group included 115 patients aged 60-90 years (mean 70.5 ± 7.8 years), 70 (61%) of whom were men. Co-morbidities were present in 98.3% of the patients, including neuropsychiatric illnesses in 21.2%. Present medical treatment included new-generation AEDs in 49 (44.5%) and both old- and new-generation AEDs in 20 (18.2%) patients. The most commonly used current AEDs were phenytoin, gabapentin, levetiracetam, and lamotrigine. Adverse reactions mainly included fatigue and CNS-related symptoms, and were more frequent among patients treated with new-generation AEDs than in those treated with old-generation AEDs or a combination of old- and new-generation AEDs; however, these reactions were mostly related to levetiracetam treatment. The likelihood of levetiracetam-related adverse events was increased by slow levetiracetam titration [defined as a weekly dose increase of ≤250 mg/day in this study; odds ratio (OR) 16.35, 95% confidence interval (CI) 2.94-90.98], and by low- (OR 5.68, 95% CI 1.40-22.95) and high (OR 4.24, 95% CI 1.28-14.02) levetiracetam dosages compared with patients treated with lamotrigine or gabapentin. CONCLUSIONS: New-generation AEDs were administered to most of the patients in this outpatient clinic-based cohort of older patients with epilepsy. In order to decrease levetiracetam-related adverse events in this age group, we suggest that a slower titration rate (e.g., an increase of ≤125 mg/day each week) and lower maximal dosage (e.g., 1500 mg/day) of the drug should be considered.

Palpitations: could they be neurogenic? A case report.

BACKGROUND: Palpitations usually occur in patients with arrhythmias of cardiac origion, in conditions associated with increased catecholamine levels, and in psychiatric disorders. A rare etiology of palpitations is seizures with autonomic features. REVIEW SUMMARY: We report a 24-year-old man with a several-week history of episodic palpitations, weakness, dizziness, and presyncopal phenomena. Subsequent events included loss of consciousness, with postevent confusion and tonic movements. A low-grade astrocytoma was diagnosed in the right frontal lobe. CONCLUSION: This case emphasizes the importance of detailed history in the diagnosis of epilepsy.

[Epilepsy surgery].

Epilepsy consists of recurrent seizures, which are not caused by reversible or transient metabolic or toxic etiologies. Approximately a third of the patients have medical refractory epilepsy and experience a decreased quality of life. In addition, these patients are subjected to increased risks of physical injury and death. Epilepsy surgery may be a therapeutic option in some of the patients with refractory epilepsy. The surgical outcome depends on optimal selection of the surgical candidates, the type of surgical procedure, and early surgical intervention during the course of the disease.

Feasibility of sleep-deprived EEG in children.

BACKGROUND: Non-sedated EEG recording in children can be technically challenging, particularly when behavioral disorders are present. We aimed to assess the feasibility and the efficacy of non-sedated sleep-deprived EEG in children with behavioral disorders and in young children. METHODS: We retrospectively reviewed the EEG recordings and computerized medical records of all pediatric inpatients at least 2-month-old that had a sleep-deprived EEG during a 5-year period between 2009 and 2014. RESULTS: We present the data of 261 children, 142 (54%) boys, mean age 7.9 ± 4.9 years, 67 (26%) aged 0.5-4 years. Behavioral disorders were reported in 38 (15%) of the patients. Mean recording duration was 50.8 ± 12.5 min, and mean sleep duration- 31.8 ± 15.2 min. Thirty-seven (14%) patients slept less than 15 min during the EEG, including 19 (7%) patients with no sleep during the recording. Sleep duration and the presence of interictal epileptiform discharges did not significantly differ between children with/without behavioral disorders and in those younger/older than 4 years. Patients that did not fall asleep during the EEG did not differ from the others regarding presence of behavioral disorders or age. CONCLUSIONS: These results suggest that non-sedated sleep-deprived EEG is feasible in young children and in those with behavioral disorders. Further studies are needed in order to better characterize the etiologies of sleepless pediatric sleep-deprived EEG recordings.

The effects of immediate and short-term retest on the latencies and amplitudes of the auditory event-related potentials in healthy adults.

OBJECTIVE: To evaluate the immediate and short-term effects of repeated within session trials on N1, P2, N2 and P3 latencies and P2, N2 and P3 amplitudes in healthy adults. MATERIALS AND METHODS: ERPs were elicited by the auditory oddball paradigm and recorded over Fz, Cz and Pz in 18 healthy adults over two sessions, one to three days apart, and two within session trials with one to three minutes trial-retrial interval. The ERPs' latencies and amplitudes were blindly calculated and were analyzed by Analysis of Variance (ANOVA) with repeated measures. RESULTS: Significant decreases of N2 amplitude at Fz, P3 amplitude at Cz and P3 latency at Pz were recorded in the second-compared to the first within session trial (p=0.034, 0.041, 0.046, respectively). There were no significant inter-session differences regarding N1, P2, N2 and P3 latencies or amplitudes. There was no significant interaction between session and trial. A statistically significant difference was found between the first session's mental count errors (p=0.039) but there were no significant differences between the second session's trials (p=0.581) or between sessions (p=0.328). CONCLUSIONS: N1, P2, N2 and P3 latencies and amplitudes are stable at short-term intervals of one to three days, but one to three minutes' retrial interval may affect P3 latency and N2 and P3 amplitudes. We suggest that when primary novelty-induced cognitive processes are evaluated, single trial sessions or more than three-minute inter-trials interval should be employed in order to mitigate habituation.