Duration Of Antiepileptic Drug Therapy Research Articles

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

Serum Calcium, Vitamin D3 and Bone Specific Alkaline Phosphatase Levels in Nigerian Children Treated with Antiepileptic Drugs: A Comparative Study

Background and Aim of the Study: Studies have shown that serum 25-hydroxycholecalciferol, calcium and bone-specific alkaline phosphatase (B-ALP) are altered in children on antiepileptic drugs (AEDs), and these could result in poor bone mineralization. The study aimed to determine the serum 25-hydroxycholecalciferol, calcium, and B-ALP levels among children on AEDs attending the paediatric neurology clinic of the University of Port Harcourt Teaching Hospital (UPTH).
 Methods: This cross-sectional analytical study was carried out from January 2018 to April 2019 on 100 children on AEDs and 100 age- and gender-matched healthy controls, aged 1.5 - 17 years. Data on socio-demography, AED regimen, and clinical examination findings of the subjects, their serum 25-hydroxycholecalciferol, calcium, and B-ALP levels were obtained and entered into a proforma. Data obtained were analysed using IBM SPSS version 20. Statistical significance was set at p-value of < 0.05.
 Results: The subjects had significantly lower mean serum 25-hydroxycholecalciferol and calcium and higher mean serum B-ALP levels than the controls, respectively. The mean serum 25-hydroxycholecalciferol was significantly lower in children on AED polytherapy. There was negative correlation between the duration of drug therapy and all serum biochemical indices but this was only significant for serum 25-hydroxycholecalciferol level (p = 0.027). Age significantly impacted negatively on serum 25-hydroxycholecalciferol, p = 0.036 and calcium levels, p = 0.009, but not on B-ALP (p = 0.392).
 Conclusion: Children on antiepileptic drugs in UPTH had lower mean serum 25-hydroxycholecalciferol and calcium levels but higher mean serum BALP level than healthy controls, as well as inverse relationship between duration of AED therapy and 25, hydroxycholecalciferol, calcium and B-ALP. We therefore recommend children with epilepsy on antiepileptic drugs have their serum 25-hydroxycholecalciferol, calcium and B-ALP levels monitored to enable early detection of any abnormalities.

The attention networks in benign epilepsy with centrotemporal spikes: A long-term follow-up study

PurposeTo evaluate the long-term prognosis of attention deficit in children with newly diagnosed benign childhood epilepsy with centrotemporal spikes (BECTS). MethodsAttention network test (ANT) was performed over a period of 7 years on 42 patients who were newly diagnosed with BECTS, in the Department of Neurology of Anhui Provincial Children's Hospital. ResultsIn the patients’ group, the accuracy of ANT was lower (P = 0.000), the total response time was longer (P = 0.000), and the efficiency of orienting (P = 0.000) and alerting (P = 0.041) networks was lower than that of the control group. Accuracy was positively correlated with age of onset (b = 1.184) and negatively correlated with number of seizures (b = −1.321). After 7 years, there was no significant difference in the accuracy (P = 0.385); total response time (P = 0.661); and alerting (P = 0.797), orienting (P = 0.709), and executive control (P = 0.806) network efficiencies between the patients and controls. Accuracy was positively correlated with age of onset (b = 0.8583) and negatively correlated with number of seizures (b = −1.017) and duration of antiepileptic drugs therapy (b = −3.203). ConclusionsIn our study, the newly diagnosed BECTS patients had impaired attention network, mainly in the alerting and orienting domains. Age of onset, number of seizures, and time of antiepileptic treatment may affect the attention networks. With the remission of BECTS, the attention network dysfunction was reversed.

Non-Dose-Dependent Changes in Liver Enzyme Levels of Children With Epilepsy on Treatment With Sodium Valproate.

Background:Sodium valproate (VPA) is considered as the drug of choice for the treatment of generalized epilepsy in children. Sodium Valproate may be hepatotoxic.Aim:To assess the level of derangement of liver enzymes in children with epilepsy on treatment with sodium valproate.Methods:A cohort study. One hundred fifty-three children, comprising 51 with epilepsy on treatment with VPA (group I), 51 with epilepsy on treatment with other antiepileptic drugs (AEDs) but not VPA (group II), and 51 with nonconvulsive disorders (group III) had liver function tests performed for them. Data were analyzed by SPSS version 23.0.Results:There were 85 males and 68 females, aged 6 months to 14 years (median = 7.0 years). There was no significant difference in the mean plasma levels of alanine transaminase (ALT), alkaline phosphatase, and gamma glutamyl transferase across the three groups of children. The mean aspartate transaminase level was significantly higher in children in group III. There was a statistically significant negative correlation between the duration of AED therapy and the mean serum level of AST (r = −0.266, P = 0.016). The serum ALT level showed a statistically significant positive correlation with the duration of AED therapy (r = 0.268, P = 0.015).Conclusion:Sodium valproate monotherapy does not appear to be associated with significant hepatotoxicity in children in our cohort.

Concentrations of the Selected Biomarkers of Endothelial Dysfunction in Response to Antiepileptic Drugs: A Literature Review.

Epilepsy is a disease arising from morphological and metabolic changes in the brain. Approximately 60% of patients with seizures can be controlled with 1 antiepileptic drug (AED), while in others, polytherapy is required. The AED treatment affects a number of biochemical processes in the body, including increasing the risk of cardiovascular diseases (CVDs). It is indicated that the duration of AED therapy with some AEDs significantly accelerates the process of atherosclerosis. Most of AEDs increase levels of homocysteine (HCys) as well as may affect concentrations of new, nonclassical risk factors for atherosclerosis, that is, asymmetric dimethylarginine (ADMA) and homoarginine (hArg). Because of the role of these parameters in the pathogenesis of CVD, knowledge of HCys, ADMA, and hArg concentrations in patients with epilepsia treated with AED, both pediatric and adult, appears to be of significant importance.

Comparison of Phenytoin versus Levetiracetam in Early Seizure Prophylaxis after Traumatic Brain Injury, at a Tertiary Care Hospital in Karachi, Pakistan.

Aims:The aim of the study was to compare the efficacy of phenytoin and levetiracetam for seizure prophylaxis in patients with severe traumatic brain injury (TBI).Subjects and Methods:A randomized controlled trial was conducted over a period of 6 months, at a tertiary health care center in Karachi, Pakistan. Patients with TBI were divided into two groups. Patients in Group A were given phenytoin, whereas Group B patients received levetiracetam. The first dose of the drugs was given within 24 h of injury and continued for 7 days. Data were collected using a predesigned pro forma. All the patients who were in a state of persistent coma, had altered mental status, or had clinical signs of seizures underwent a 1-h electroencephalographic (EEG) recording to observe the seizures, the first EEG was done on the 1st day posttrauma and a second one was done on day 7 of drug use, both the EEGs were compared for changes. We also analyzed the patients according to their duration of antiepileptic drug therapy, length of hospital stay, and complications during therapy.Results:One hundred and forty (117 males and 23 females) patients who presented with TBI having a mean age of 29.48 ± 16.24 years were part of the study. The most prevalent cause of brain injury was road traffic accidents in 72.85% patients. There was no significant relationship between the antiepileptic drug used with the initial EEG (P = 0.313) and seizure activity (P = 0.502). However, a significant correlation of the antiepileptic drug used was found with EEG (P = 0.002) and seizure activity (P = 0.014) on follow-up. Patients who took levetiracetam had decreased the incidence of abnormal EEG and seizure activity on follow-up. There was not any correlation between GCS both initially (P = 0.845) and on follow-up (P = 0.104) with the antiepileptic drug used.Conclusion:The incidence of abnormal EEGs and seizure activity in patients with TBI is the same for both levetiracetam and phenytoin for the initial 7 days post-TBI; however, the incidence of seizures is lower for patients who used levetiracetam on the subsequent follow-up.

Risk of Microangiopathy in Patients with Epilepsy under Long-term Antiepileptic Drug Therapy.

Long-term antiepileptic drug (AED) therapy is considered a risk factor of atherosclerosis. Furthermore, the duration of therapy contributes to acceleration of large-vessel atherosclerosis. Therefore, in this study, we tested the hypothesis that long-term AED therapy plays a crucial role in the pathogenesis of microangiopathy in patients with epilepsy. We recruited 120 patients with epilepsy (age, 18-60 years) and 40 healthy controls. Optical coherence tomography (OCT) was used to measure the central macular thickness and diameters of the retinal artery and vein to evaluate atherosclerotic retinopathy; microalbumin and creatinine levels in urine were assessed to evaluate atherosclerotic nephropathy. In addition, high-sensitivity C-reactive protein (hs-CRP), lipid profiles, homocysteine, folate, uric acid, and body mass index were determined. The ratio of urine albumin to creatine and OCT findings showed that patients with epilepsy had higher abnormal microalbuminuria and narrowing retinal vein diameters, respectively. Multiple linear regression analysis showed that increased triglyceride and hs-CRP levels might contribute to microalbuminuria. In addition, serum creatinine, duration of AED therapy, enzyme-inducing AED therapy, and duration of enzyme-inducing AED therapy were candidate risk factors for retinal vein narrowing. Patients with epilepsy are at a higher risk for microangiopathy presented as retinopathy and nephropathy. Long-term AED therapy, particularly with enzyme-inducing AEDs; high triglyceride levels, and inflammatory processes play an important role in the development of microangiopathy in patients with epilepsy.

Association of Serum Homocysteine and hs-CRP with Idiopathic Generalised Epilepsy and Duration of Antiepileptic Drug Therapy

Association of Serum Homocysteine and hs-CRP with Idiopathic Generalised Epilepsy and Duration of Antiepileptic Drug Therapy

Serum calcium deficiency and bone mineral density in patients on long-term anti-epileptic therapy

Introduction: Epilepsy is a common chronic neurological disorder, usually requiring long-term treatment with anti-epileptic drugs (AEDs). AED therapy is associated with metabolic bone disease and is a major iatrogenic risk factor for fractures. There remains uncertainty about the type(s) of bone disease due to AED treatment and the pathogenesis of AED-associated fractures. The fracture rate in patients with epilepsy is 2–6 times higher than the rate observed in the general population. Only a few studies in India have studied the prevalence of osteopenia in patients on long-term AEDs. Purpose of Study: The purpose of this study is to find out the prevalence of osteoporosis and osteopenia and to correlate serum calcium levels with bone mineral density (BMD) by bone densitometer in patients with epilepsy on long-term AED therapy. Materials and Methods: The study was carried out at Government Medical College and Hospital where 50 cases having epilepsy of more than or equal to 2 years duration and 50 age- and sex-matched healthy controls were taken by comparing BMD and associated parameters. Results: Mean BMD value was low in cases as compared to controls in all age groups with a significant decrease in young age group and as the duration of AED therapy increased the mean BMD decreased.

Hyperhomocysteinaemia in children receiving phenytoin and carbamazepine monotherapy: a cross-sectional observational study

ObjectiveLong-term therapy with phenytoin and carbamazepine is known to cause hyperhomocysteinaemia. We evaluated the prevalence of hyperhomocysteinaemia in North Indian children receiving phenytoin or carbamazepine monotherapy for >6 months duration...

Bone Mineral Changes in Epilepsy Patients During Initial Years of Antiepileptic Drug Therapy

Antiepileptic drug (AED) therapy is associated with decreased bone mineral density; however, the time course for this development is unclear. The aim of this study was to evaluate bone mineral changes during the initial years of AED therapy in AED-naive, newly diagnosed epilepsy patients compared with non-AED users. In 49 epilepsy patients newly started on AEDs and in 53 non-AED users of both genders, bone mineral density (BMD) and bone mineral content were measured using dual-energy X-ray absorptiometry at baseline (within the first year of therapy) and at least 1 yr later. Bone changes between the 2 assessments, adjusted for age, height, and weight, were calculated as the annual rate of change. The median duration of AED therapy was 3.5 mo at baseline and 27.6 mo at follow-up. No overall difference was found in mean BMD and bone mineral content measures between user and nonuser cohorts in both cross-sectional baseline and the annual rate of change (p > 0.05). However, users on carbamazepine monotherapy (n = 11) had an increased annual rate of total hip (−2.1% vs −0.8%, p = 0.020) and femoral neck BMD loss (−2.1% vs −0.6%, p = 0.032) compared to nonusers. They also had a marginally higher rate of femoral neck BMD loss (−2.1%, p = 0.049) compared with valproate (−0.1%, n = 13) and levetiracetam users (+0.6%, n = 13). During the initial years of AED treatment for epilepsy, no difference was found in bone measures between AED users as a group and nonuser cohorts. However, the data suggested that carbamazepine monotherapy was associated with increased bone loss at the hip regions, compared to users of levetiracetam or valproate and nonusers. Larger studies of longer duration are warranted to better delineate the bone effects of specific AEDs, with further consideration of the role of early dual-energy X-ray absorptiometry scanning and careful AED selection in potentially minimizing the impact on bone health in these patients.

Changes in balance function with chronic antiepileptic drug therapy: A twin and sibling study.

To investigate cross-sectional and longitudinal differences in static and dynamic standing balance measures and lower limb muscle strength in patients who are treated chronically with antiepileptic drugs (AEDs). Twenty-six AED exposure-discordant same-gender twin and sibling pairs were studied. Clinical and laboratory balance examinations were conducted twice, separated by at least 1 year. The mean within-pair differences in balance measures were calculated cross-sectionally at baseline and follow-up, and longitudinally. No significant mean within-pair difference was found at baseline in age (44 years), weight, and height (p > 0.05). Between study assessments, the median (interquartile range [IQR]) interval was 3.0 (2.1-4.3) years in users and 2.9 (2.0-4.4) years in nonusers. The median duration of AED therapy was 19 (11-21) years. At baseline and follow-up, cross-sectional sway measures from posturography (Chattecx Balance System) and clinical static balance tests showed poorer performance in users compared to nonusers on several test conditions (p = 0.002-0.032). At follow-up, the users took longer than nonusers to complete the Four-Square-Step Test (p = 0.005) and Five-Times-Sit-to-Stand Test (p = 0.018). A greater annual rate of deterioration in sway was found in users compared to nonusers using posturography on the anteroposterior tilting platform task with distraction (p = 0.032). In both groups, higher baseline sway predicted greater annual deterioration in sway in all platform conditions (β = 0.3-0.5, p < 0.001-0.013). The annual change in measures did not differ between groups in the clinical balance and lower limb strength assessments. In this longitudinal twin and sibling study, chronic AED users had poorer standing balance compared to nonusers. Users showed greater deterioration in postural sway with one dynamic platform condition. AEDs may progressively impair balance mechanisms, although this requires further investigations. Repeated dynamic posturography could provide a basis for preventive trials for maintaining or improving balance.

THU0383 Osteoporosis in Epilepsy and Multiple Sclerosis Patients.

BackgroundOsteoporosis is the most common type of bone disease. There is recent mounting evidence indicating that patients with multiple sclerosis (MS) and epilepsy (EP) have decreasing bone mineral density (BMD)...

Early‐onset absence epilepsy: SLC2A1 gene analysis and treatment evolution

To determine the prevalence of SLC2A1 mutations in children with early-onset absence epilepsy (EOAE) and to investigate whether there were differences in demographic and electroclinical data between patients who became seizure-free with anti-epileptic drug (AED) monotherapy (group I) and those who needed add-on treatment of a second AED (group II). We reviewed children with EOAE attending different Italian epilepsy centers. All participants had onset of absence seizures within the first 3 years of life but otherwise conformed to a strict definition of childhood absence epilepsy. Mutation analysis of SLC2A1 was performed in each patient. Eighty-four children (57 in group I, 27 in group II) fulfilled the inclusion criteria. No mutation in SLC2A1 was found. There were no statistical differences between the two groups with regard to F/M ratio, age at onset of EOAE, early history of febrile seizures, first-degree family history for genetic generalized epilepsy, duration of AED therapy at 3 years after enrollment, use of AEDs at 3 years, failed withdrawals at 3 years, terminal remission of EOAE at 3 years, and 6-month follow-up EEG data. Mean duration of seizures/active epilepsy was significantly shorter in group I than in group II (P = 0.008). We demonstrate that in a large series of children with rigorous diagnosis of EOAE, no mutations in SLC2A1 gene are detected. Except for duration of seizures/active epilepsy, no significant differences in demographic and electroclinical aspects are observed between children with EOAE who responded well to AED monotherapy and those who became seizure-free with add-on treatment of a second AED.

Homocysteine, folic acid and vitamin B12 levels in serum of epileptic children

The relationship between increased homocysteine (Hcy) level and epileptic seizure remains controversial in human, despite a growing evidence of the pro-convulsive effect of the hyperhomocysteinemia (HHcy) observed in the animal studies. The mechanism of this association with epileptogenesis has not been clearly understood, although there is emerging evidence to support the unfavorable effects of some anti-epileptic drugs (AEDs) on the plasma homocysteine (Hcy) concentrations. The aim of this study was to uncover the relationship between the levels of homocysteine (Hcy), the cofactors involved in its metabolism as folic acid and vitamin B12 and anti-epileptic drugs (AEDs) in epileptic patients. Serum level of homocysteine (Hcy), folic acid and vitamin B12 was measured in 60 patients with idiopathic epilepsy; and its level was compared to 30 healthy children serving as control group. No significant difference was found regarding the plasma homocysteine (Hcy) levels between patients (both receiving anti-epileptics and non anti-epileptic drug users) and controls. Epileptic patients on polytherapy showed higher mean serum levels of homocysteine (Hcy) and lower mean serum levels of folic acid compared to those on monotherapy. However, the mean serum levels of homocysteine (Hcy), vitamin B12 and folic acid showed non significant differences between patients using valproic acid (VPA) or carbamazepine (CBZ). Duration of AED therapy showed a significant positive correlation with mean serum levels of homocysteine (Hcy) and a significant negative correlation with mean serum levels of folic acid. To conclude; AEDs upset the homeostatic balance of homocysteine (Hcy) and its cofactors and cause abnormalities in their serum levels.

Effects of long‐term antiepileptic drug monotherapy on vascular risk factors and atherosclerosis

Long-term therapy with antiepileptic drugs (AEDs) has been associated with metabolic consequences that lead to an increase in risk of atherosclerosis in patients with epilepsy. We compared the long-term effects of monotherapy using different categories of AEDs on markers of vascular risk and the atherosclerotic process. One hundred sixty adult patients who were receiving AED monotherapy, including two enzyme-inducers (carbamazepine, CBZ; and phenytoin, PHT), an enzyme-inhibitor (valproic acid, VPA), and a noninducer (lamotrigine, LTG) for more than 2 years, and 60 controls were enrolled in this study. All study participants received measurement of common carotid artery (CCA) intima media thickness (IMT) by B-mode ultrasonography to assess the extent of atherosclerosis. Other measurements included body mass index, and serum lipid profile or levels of total homocysteine (tHcy), folate, uric acid, fasting blood sugar, high sensitivity C-reactive protein (hs-CRP), or thiobarbituric acid reactive substances (TBARS). Long-term monotherapy with older-generation AEDs, including CBZ, PHT, and VPA, caused significantly increased CCA IMT in patients with epilepsy. After adjustment for the confounding effects of age and gender, the CCA IMT was found to be positively correlated with the duration of AED therapy. Patients with epilepsy who were taking enzyme-inducing AED monotherapy (CBZ, PHT) manifested disturbances of cholesterol, tHcy or folate metabolism, and elevation of the inflammation marker, hs-CRP. On the other hand, patients on enzyme-inhibiting AED monotherapy (VPA) exhibited an increase in the levels of uric acid and tHcy, and elevation of the oxidative marker, TBARS. However, no significant alterations in the markers of vascular risk or CCA IMT were observed in patients who received long-term LTG monotherapy. Patients with epilepsy who were receiving long-term monotherapy with CBZ, PHT, or VPA exhibited altered circulatory markers of vascular risk that may contribute to the acceleration of the atherosclerotic process, which is significantly associated the duration of AED monotherapy. This information offers a guide for the choice of drug in patients with epilepsy who require long-term AED therapy, particularly in aged and high-risk individuals.

Balance impairment in chronic antiepileptic drug users: A twin and sibling study

Patients taking antiepileptic drugs (AEDs) have an increased incidence of fractures. This study investigated chronic AED use and physical contributors to falls risk using an AED-discordant, twin and sibling matched-pair approach, and assessed clinically relevant subgroups: AED polytherapy; longer-duration AED; and falls history. Twenty-nine same-sex (mean age 44.9 years, 59% female), ambulatory, community-dwelling twin and sibling pairs, discordant for AED exposure (and AED-indication), were recruited. Validated clinical and laboratory tests of strength, gait, and balance were performed. Relevant AED levels, and fasting serum samples for 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D [1,25(OH)(2)D], and immunoreactive parathyroid hormone (iPTH) levels were taken. There were significant mean within-pair differences in tests of static and dynamic balance, with the AED user having poorer balance function than the AED nonuser. No difference was seen in lower limb strength or gait measures. Increased duration of AED therapy and AED polytherapy were independent predictors of increased sway. No significant within-pair differences were seen in fasting serum levels of 1,25(OH)(2)D, 25OHD and iPTH after Bonferroni correction. Balance performance is impaired in AED users compared to their matched nonuser siblings. Pairs where the AED users took AED polytherapy, or had a longer duration of AED use, had more impaired balance performance. These balance deficits may contribute to the increased rate of fractures in this population.

Long‐term antiepileptic drug therapy contributes to the acceleration of atherosclerosis

Long-term antiepileptic drug (AED) therapy has been associated with an increase in risk of atherosclerosis. At issue is whether this risk is related to the duration of AED therapy. We evaluated the hypothesis that the cumulative effect of long-term exposure to AEDs plays a pivotal role in the pathogenesis of atherosclerosis in patients with epilepsy. One hundred ninety-five patients under long-term AED therapy and 195 healthy age- and sex-matched control subjects received measurement of intima media thickness (IMT) at the far wall of the common carotid artery (CCA) by B-mode ultrasonography to assess the extent of atherosclerosis. Other measurements included body mass index (BMI) and blood lipid profile or homocysteine, folic acid, uric acid, fasting blood sugar, high sensitivity C-reactive protein (hs-CRP), thiobarbituric acid reactive substances (TBARS), and total reduced thiols. CCA IMT was significantly increased in patients with epilepsy, with male subjects exhibiting thicker IMT than their female counterparts. Whereas BMI, homocysteine, hs-CRP, and TBARS were significantly elevated, folic acid and thiols were significantly reduced in patients with epilepsy. Multiple linear regression analysis further revealed that duration of AED therapy, age, gender, and TBARS level (index for oxidative stress) were independently associated with CCA IMT. In addition, the log-transformed CCA IMT increased linearly with duration of AED therapy after adjustments for age, gender, and TBARS level. The duration of AED therapy is significantly associated with the acceleration of atherosclerosis in patients with epilepsy, alongside independent contributions of age, gender, and oxidative stress to the atherosclerotic process.

Intellectual impairment in patients with epilepsy in Ile-Ife, Nigeria

Epilepsy is the most common non-infectious neurologic disease in developing countries such as Africa, including Nigeria. This study was designed to assess the intellectual performance of patients with epilepsy (PWE) in Nigeria hoping that the result will serve as the basis for educational, vocational, and social counseling. Forty-one PWE were studied along with 41 age-, sex- and education-matched healthy controls. A questionnaire was developed and applied to all subjects and history was taken from patients and eyewitness. The intellectual function of each subject was assessed with the aid of Wechsler Adult Intelligence Scale adapted for Nigerians. All patients subsequently had electroencephalography (EEG) performed and the EEG findings were noted. SPSS statistical package was used to analyze the data. The PWE performed poorly on the verbal IQ, performance IQ, and full scale IQ scores when compared with controls (P < 0.05) and 20% of PWE had mental retardation. Long duration of epilepsy, long duration of antiepileptic drug therapy, younger age at onset of epilepsy, increased frequency of seizures, and low educational status were found to have negative impacts on intellectual performance in PWE (P < 0.05) while seizure types and type of antiepileptic drugs (carbamazepine or phenytoin) did not influence intellectual performance. This study shows that PWE had significant intellectual impairment when compared with controls. In addition, long duration of epilepsy, long duration of AED therapy, earlier age of onset, increased seizure frequency, and low educational status had a negative impact on intellectual functioning in PWE.

Re: Drug-Induced Psychosis with Levetiracetam

Dear Editor: We read with much interest the letter by Dr Bayerlein and others (1) describing a patient who developed an acute psychotic episode during treatment with levetiracetam (LEV). In their report, the authors quoted one of our works on psychiatric adverse events (PAEs) related to LEV (2), stating that lamotrigine (LTG) cotherapy was a risk factor for the occurrence of PAEs. We wish to point out that, in our paper, we showed that this combination was a favourable one and that patients taking LTG were less likely to develop PAEs (OR 0.40; 95%CI, 0.17 to 0.92)-probably because of its antidepressant properties. A previous study showed the same findings with other antiepileptic drugs (AEDs) such as topiramate (3). Regarding the case presented by the authors, we regret to note that forced normalization (FN) was not taken into account among the possible hypotheses. Although this is a well-described phenomenon (4) with an increasing literature investigating its biological basis (5), some psychiatrists do not consider its occurrence in patients with epilepsy. This particular case is typical of one where FN may play a role. The phenomenon has been described with several AEDs, suggesting that it is more likely to be related to the clinical phenotype of the patient than to be a characteristic of the drug. In his original report, Landolt suggested that a subgroup of subjects with idiopathic generalized epilepsy could be at risk (4), and Tellenbach described alternative psychosis in patients with myoclonic epilepsy (6) like the case presented by Dr Bayerlein. Interestingly, we noted the same association in a previous study investigating the role of FN in topiramate-associated psychopathology (7). Moreover, in the presented case, seizures improved remarkably, although they were not completely suppressed. This is enough to consider that the hypothesis is plausible, according to recently suggested guidelines (8). Alternative psychoses are characterized by rapid onset and highly flourished symptoms with a short duration (usually, 1 week) followed by an almost complete remission after seizure reoccurrence or AED dosage reduction. There is no relation to the duration of AED therapy; it is seen mainly with an increase in dosage or a change in the AED regime. Thus patients who have been taking the drug for a long time may develop FN with the same drug, owing to such changes. In conclusion, the patient described by Dr Beyerlein and colleagues has several features that may make FN a reasonable hypothesis. We hope that clinicians will be more interested in this phenomenon to lead to a correct diagnosis, prognosis, and therapy of psychosis in epilepsy and to identify patients who may be studied in further research into the pathophysiology of psychosis in general and the psychosis of epilepsy in particular.