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.

Potential feasibility of a remote first visit in the epilepsy clinic.

BACKGROUND: Since the beginning of coronavirus disease (COVID-19) epidemic in Israel in early 2020, follow-up visits through phone consultations were available only for patients treated in our outpatient epilepsy clinic. OBJECTIVE: To assess the potential feasibility of phone consultation instead of in-person first visit in the outpatient epilepsy clinic. METHODS: The computerized database and medical records of all the patients who had an in-person first visit in our outpatient epilepsy clinic during a 4-year period (2018-2021) were retrospectively reviewed. Potential feasibility of a remote visit was assessed for all visits and was deemed possible when physical examination or vagal nerve stimulator (VNS) examination or parameter adjustment was not reported in the visit summary. RESULTS: The study group included 462 patients who had an in-person first visit in the outpatient epilepsy clinic during the study period. A remote first visit was deemed potentially feasible in 404 (87%) patients. Those in whom a remote first visit was deemed potentially infeasible were older (p = 0.0001), with longer disease duration (p = 0.001) and higher rates of antiseizure medication polytherapy (p = 0.0001), VNS and additional symptoms (p = 0.0001). CONCLUSIONS: A remote visit may be potentially feasible for most patients who are scheduled for a first visit in the epilepsy clinic. An in-person visit may remain the preferred option for patients with additional neurological symptoms or a VNS, and may also be considered in older patients and those with longer disease duration or antiseizure medication polytherapy.

Tolerability and efficacy of perampanel in children with refractory epilepsy.

AIM: There are few reports on the tolerability and efficacy of perampanel, a new antiepileptic drug with a novel mechanism of action, in children and adolescents. We aimed to describe our experience with perampanel add-on and mono-therapy in children with refractory epilepsy. METHOD: Computerized medical records of children treated with perampanel in the paediatric neurology clinic from December 2012 to October 2015 were reviewed. RESULTS: Twenty-four children treated with perampanel (15 females, 9 males) aged 1 year 6 months to 17 years (mean 10y, standard deviation [SD] 4y 5mo) were identified. Adverse events were more common in children aged 12 years or older (89%) compared to younger children (53%), and were mainly behavioural. Ten (42%) children had 50 per cent or higher seizure reduction, two (8%) children had 33 per cent seizure reduction, and seizures were less severe in one (4%) child. Perampanel was discontinued in 13 (54%) children mostly due to adverse events. The mean duration of follow-up in the remaining 11 children was 8.1 months (SD 5.2) (range 1.3-17mo). INTERPRETATION: Perampanel is associated with a relatively high rate of behavioural adverse events mostly in adolescents with refractory epilepsy.

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.

Genetic risk factors for antiepileptic drug-induced hypersensitivity reactions in Israeli populations.

The human leukocyte antigen (HLA) alleles B*15:02 and A*31:01 have been identified as predictive markers of adverse cutaneous effects of carbamazepine and phenytoin in Asian and North European populations, respectively. Our aim was to estimate the distribution of these alleles in Jewish and Arab populations in Israel. The HLA-B*15:02 and HLA-A*31:01 carrier rate was estimated based on data from the Hadassah Bone Marrow Registry. Data on Stevens-Johnson syndrome (SJS)- and toxic epidermal necrolysis (TEN)-related hospitalizations were obtained from the Israeli Ministry of Health (MOH) registries and from four Israeli medical centers. Of 83,705 Jewish and Arab-Muslim donors, 81 individuals of known origin carried the HLA-B*15:02. Among them, 66 were Jews of India-Cochin descent. Of the Cochin Jewish donors, 12.7% were B*15:02 carriers. HLA-A*31:01 carrier incidence among Arab and Jewish Israeli populations (3.5% and 2.2%, respectively) was within the range reported in other countries. We did not identify SJS- or TEN-related hospitalizations of Jews of Indian descent. Yet, this population should be considered at greater risk for antiepileptic drug-induced SJS and TEN. Until further data on actual risk are available, such patients should be typed for HLA-B before treatment with carbamazepine or phenytoin.

Postural stability in patients with different types of head and neck trauma in comparison to healthy subjects.

OBJECTIVE: Dizziness is a common complaint in patients following mild head or neck trauma, but neurological signs are usually rare or absent. The aim of the study was to compare postural control in patients with different types of head and neck trauma to healthy subjects. METHODS: Balance function was evaluated by computerized dynamic platform posturography (CDPP) in 57 dizzy patients with whiplash injury (n = 11), mild head trauma without loss of consciousness (HTNLC) (n = 23), whiplash injury and mild head trauma without loss of consciousness (WHTNLC) (n = 12) and mild head trauma with loss of consciousness (n = 11) and in 14 healthy subjects. RESULTS: Compared to healthy subjects and after adjustment for inter-group age differences, sway index (SI) was significantly higher in patients with WHTNLC in three of the tests. There were no significant differences within the patient group according to type of injury. When time following the injury was considered, the SI was non-significantly higher within the first week after trauma compared to other time intervals. CONCLUSION: The severity of the postural abnormality in patients with head and/or neck trauma is not uniform and is influenced by the type of trauma.

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.

Primary treatment gap among adults with epilepsy: A cross-sectional analysis.

OBJECTIVE: Despite recommendations to initiate antiseizure medication treatment once the diagnosis of epilepsy is confirmed, a certain proportion of patients with epilepsy who should receive antiseizure medication treatment remain untreated. We aimed to evaluate the rate of and the reasons for the treatment gap in patients with epilepsy who were referred to their first visit in our epilepsy clinic. METHODS: We retrospectively reviewed the computerized database and the medical records of all the patients with epilepsy who had their first visit in our outpatient epilepsy clinic during a 10-year period (2012-2021). RESULTS: Forty-nine (6.5%) of 746 patients with epilepsy were not treated with antiseizure medications: 27 (3.6%) were nonadherent to treatment, 12 (1.6%) patients were not definitively diagnosed with epilepsy prior to their first epilepsy clinic visit, and in 10 (1.3%) patients antiseizure medication treatment was not recommended. Untreated patients had shorter epilepsy duration compared to patients treated with antiseizure medications (p = .003). At last follow-up, 77% of the untreated patients at first visit were receiving antiseizure medications compared to 97% of the initially treated group, and fewer were receiving antiseizure medication polytherapy (p = .0001). SIGNIFICANCE: Although the rate of treatment gap was relatively low, we believe that it should be further reduced. Efforts may focus on addressing individual causes of nonadherence to antiseizure medication treatment and on promoting knowledge of diagnosis and treatment of epilepsy among healthcare professionals.

Guidelines and epilepsy practice: Antiseizure medication initiation following an unprovoked first seizure in adults.

OBJECTIVES: Adherence rate to evidence-based clinical practice guidelines is relatively low and the impact of guidelines on clinical practice in epilepsy is variable. The 2015 practice guideline on the management of an unprovoked first seizure in adults specifies clinical variables associated with increased risk of seizure recurrence and the impact of immediate antiseizure medication (ASM) treatment on seizure outcome. We aimed to evaluate the impact of the evidence-based guideline for the management of an unprovoked first seizure in adults on clinical practice in our adult neurology department. METHODS: We retrospectively reviewed the computerized database of 169 adult patients admitted to the adult neurology department at Shamir-Assaf Harofeh Medical Center following a first unprovoked seizure between October 2011 and October 2018. RESULTS: ASMs were initiated in 86% of patients with a first unprovoked seizure pre- and in all patients admitted post- guideline publication. Monotherapy and use of old generation ASMs were more common in both groups and a combination of old- and new generation ASMs - among the pre-guideline group. The pre-guideline decision to initiate ASM treatment was significantly influenced only by epileptiform discharges in the electroencephalogram (EEG). DISCUSSION: This is the first study to evaluate the impact of the 2015 practice guideline on the initiation of ASM treatment after a first unprovoked seizure in adults. Further studies are needed to assess the global contribution of the guideline to clinical practice and its impact on patient outcomes.

[Epilepsy in pregnancy].

Most women with epilepsy will need to continue antiepileptic drugs prior to and during pregnancy. Pre-conception counseling should be available to all wormen with epilepsy who are considering pregnancy, and should address obstetrical complications, change in seizure frequency, and adverse pregnancy outcome. Supplementation with folic acid. 0.4-5 mg/day, is recommended for all women with epilepsy of childbearing potential, especially 3 months prior to conception and throughout the first trimester. It is advisable to obtain serum drug concentrations before pregnancy, when seizure control is optimal, in order to establish a baseline. Serum concentration should be performed each trimester among patients with good seizure control, and monthly in patients with complicated epilepsy, breakthrough seizures, significant side effects, and those treated with lamotrigine or oxcarbazepine. The incidence of major congenital malformations in offspring of women treated with antiepileptic drugs has ranged from 4 to 10%, corresponding to a two-fold increase from the expected incidence in the general population. Malformation rates are higher with valproate, lower with carbamazepine and lamotrigine, and dose-effect relationship has been shown for teratogenicity especially with valproate. An expert morphological assessment, targeted at the neural axis, heart and face, should be performed at 11-13 weeks and 18-22 weeks. There is generally no contraindication to breast feeding among mothers with epilepsy, but further studies are needed to establish the safety of newer antiepileptic drugs.

Reasons for delayed treatment initiation in Guillain-Barre syndrome.

OBJECTIVE: The goal of this study was to analyze the reasons for delayed diagnosis of Guillain-Barre syndrome (GBS). METHODS: We retrospectively reviewed the records of all adult patients with GBS treated at Shamir Medical Center (SMC) from 2006 to 2018. We divided the patients into two groups: those with early initiation of treatment (within 24 h of arrival to ED), and those with later initiation of treatment (>24 h after arrival). We extracted epidemiological and clinical data regarding those groups, and compared them. RESULTS: 100 patients with GBS were treated between 2006 and 2018 at SMC. 50 patients were treated within 24 h of arrival, and in 50 - treatment was initiated later. Of those with delayed treatment, 9 had mild disease, but did receive a working diagnosis of GBS. 41 patients were not diagnosed initially as a clear-cut GBS, and alternative diagnoses were considered, the most common were orthopedic (11/41), vascular (7/41) or nutritional deficiency (6\41). Findings that increased the likelihood for alternative diagnoses to be considered first were severe limb or back pain (26/41); intact or brisk reflexes (17/41); and an atypical pattern of weakness (7\41). CONCLUSIONS: GBS is a challenging diagnosis. Acknowledging the heterogeneity of its presentation and knowing its pitfalls is crucial for the prompt and accurate diagnosis of the disease.

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.

[Epilepsy in the elderly].

Elderly persons with epilepsy are expected to be an increasing larger group among patients with epilepsy in view of population aging and the higher onset of epilepsy in the elderly as compared to any other age group. Cerebrovascular disease is the most common cause of seizures in the elderly, and complex partial seizures (CPS) are the most common seizure type in this age group. CPS semiology is often different in the elderly compared to young adults, since strokes usually involve extratemporal regions. The absence of familiar clinical characteristics of seizures, such as aura and automatisms, can delay the correct diagnosis of epilepsy or Lead to misdiagnosis. As a result of age-related pharmacokinetic changes, the clearance of most old and new antiepileptic drugs (AEDs] is reduced by 20-40% in elderly persons compared to younger adults, and there may be a longer elimination half-life of certain AEDs. In addition to measurements of serum AED concentration, it is important to monitor clinical response, since age-related pharmacodynamic changes can alter the relationship between serum AED concentration and pharmacological effects. Newer AEDs have a lower potential for drug interactions and are better tolerated by the elderly compared to old generation AEDs. Monotherapy is the preferred therapeutic strategy for initial treatment of seizures due to fewer adverse events, decreased risk of drug interactions, improved adherence and lower treatment costs. Elderly patients with epilepsy are more likely to remain seizure-free on AED treatment than younger age groups. Elderly patients with refractory epilepsy and precise localization of the seizure focus can be appropriate surgical candidates, and a favorable prognosis is expected with curative surgical procedures.

Therapeutic levetiracetam monitoring during pregnancy: "mind the gap".

BACKGROUND: Epilepsy is one of the most common chronic neurological conditions and its treatment during pregnancy is challenging. Levetiracetam (LEV) is an antiepileptic medication frequently used during pregnancy. Only a few small studies have been published on LEV monitoring during pregnancy, demonstrating decreased serum LEV levels during the first and second trimester; however, the most significant decrease was observed during the third trimester of pregnancy. In this study we aimed to evaluate LEV pharmacokinetics during different stages of pregnancy. METHODS: We followed up and monitored serum levels of pregnant women treated with LEV for epilepsy. RESULTS: Fifty-nine women with 66 pregnancies during the study period were included. The lowest raw LEV serum concentrations were observed during the first trimester. Compared with the pre-pregnancy period, raw serum concentration was lower by 5.76 mg/L [95% confidence interval (CI) (2.78, 8.75), p = 0.039] during the first trimester. Comparing the decrease in the first trimester with either the second or the third, no significant changes were observed (p = 0.945, p = 0.866). Compared with pre-pregnancy measurements, apparent clearance was increased by 71.08 L/day [95%CI (16.34, 125.83), p = 0.011] during the first trimester. About 30% of LEV serum levels during pregnancy were below the laboratory quoted reference range. CONCLUSIONS: Raw LEV serum levels tend to decrease during pregnancy, mainly during the first trimester contrary to previous reports. Monitoring of LEV serum levels is essential upon planning pregnancy and thereafter if pre-pregnancy LEV levels are to be maintained. However, more studies are needed to assess the correlation with clinical outcome.

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.

[Genetic aspects of epilepsy].

The progress in genetic research in epilepsy mainly concerns two important aspects of the disease--identification of genetic etiology and drug therapy. Genetically, epilepsies can be divided according to the mode of inheritance. Epilepsies with simple or Mendelian inheritance, maintain Mendel's laws of inheritance, which determine that each gene is responsible for a certain trait. Several genetic and environmental factors are involved in epilepsies with complex inheritance. In the past few years, several idiopathic generalized epilepsies were ascribed to voltage and ligand-dependent channels, such as potassium, sodium, and chloride channels and the GABA receptor. Monogenic inheritance was also reported in several localization-related epilepsies. Nearly half of the patients with epilepsy continue to have refractory epilepsy and side effects of drug therapy. Genetic factors related to the pharmacokinetics and pharmacodynamics of antiepileptic drugs are deemed important. The pharmacogenetic approach to drug therapy will enable early identification of potential side effects and lack of efficacy before treatment initiation, based on the patient's genotype. The epilepsy-related genetic information accumulated in the past decade entails new diagnostic and treatment opportunities for patients with epilepsy. However, its moral and social implications on the patients and their families should be carefully examined.

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.

Quantitative EEG After Brain Stimulation and Cognitive Training in Alzheimer Disease.

PURPOSE: Medications are the currently accepted symptomatic treatment of Alzheimer disease (AD), but their impact on delaying the progression of cognitive deficits and functional impairment is limited. The authors aimed to explore long-term electrophysiological effects of repetitive transcranial magnetic stimulation interlaced with cognitive training on quantitative electroencephalography (EEG) in patients with AD. METHODS: Quantitative EEG was assessed on non-repetitive transcranial magnetic stimulation interlaced with cognitive training treatment days before treatment and after each treatment phase in seven patients with mild AD. RESULTS: After 4.5 months (54 sessions) of treatment, a significant increase of delta activity over the temporal region was found compared with pretreatment values. Nonsignificant increases of the log EEG power were found for alpha band over the frontal and temporal regions, beta band over the frontal region, theta band over the frontal, temporal, and parieto-occipital regions, and delta band over the frontal and parieto-occipital regions. Nonsignificant decreases were found for alpha over the parieto-occipital region, and for beta over the temporal and parieto-occipital regions. A positive correlation was found between log alpha power over the frontal and temporal regions at 6 weeks and Mini-Mental State Examination (MMSE) scores at 6 weeks and 4.5 months, and between log alpha power over the parieto-occipital regions and MMSE scores at 6 weeks. A negative correlation was found between log alpha power over the frontal and temporal regions at 6 weeks and baseline Alzheimer's Disease Assessment Scale-cognitive subscale scores. CONCLUSIONS: Repetitive transcranial magnetic stimulation interlaced with cognitive training has long-term effects on quantitative EEG in patients with mild AD. Further research on the quantitative EEG long-term effects of transcranial magnetic stimulation interlaced with cognitive training is required to confirm the authors' data.