Pattern-Reversal Visual Evoked Potential Parameters and Migraine in the Teenage Population.

Although migraine represents one of the most common form of primary headache in the teenage population, most neurophysiologic studies are only on the adulthood. We investigated 38 teenage patients with migraine with aura, 17 male and 21 female, with a mean age of 16.2 years, comparing them with gender- and age-matched patients with migraine without aura and healthy subjects. Also, characteristics of aura were correlated with pattern-reversal visual evoked potential parameters. There was a significant difference in left and right eye N2 wave latencies between migraine with aura and migraine without aura patients or healthy controls. In migraine with aura and migraine without aura, 26.3% of patients had abnormal wave latency. Reported tunnel vision during the aura was correlated with lower N1P1 and/or P1N2 wave amplitudes. Also, higher amplitude in patients with migraine with aura correlated with younger age and earlier disease onset, whereas longer aura duration correlated with prolonged wave latency. Findings suggest that migraine subtypes may be differentiated on the basis of N2 wave latency prolongation.

Nonlinear mixed effects modelling approach in investigating phenobarbital pharmacokinetic interactions in epileptic patients.

PURPOSE: The present study aimed to establish population pharmacokinetic model for phenobarbital (PB), examining and quantifying the magnitude of PB interactions with other antiepileptic drugs concomitantly used and to demonstrate its use for individualization of PB dosing regimen in adult epileptic patients. METHODS: In total 205 PB concentrations were obtained during routine clinical monitoring of 136 adult epilepsy patients. PB steady state concentrations were measured by homogeneous enzyme immunoassay. Nonlinear mixed effects modelling (NONMEM) was applied for data analyses and evaluation of the final model. RESULTS: According to the final population model, significant determinant of apparent PB clearance (CL/F) was daily dose of concomitantly given valproic acid (VPA). Typical value of PB CL/F for final model was estimated at 0.314 l/h. Based on the final model, co-therapy with usual VPA dose of 1000 mg/day, resulted in PB CL/F average decrease of about 25 %, while 2000 mg/day leads to an average 50 % decrease in PB CL/F. CONCLUSIONS: Developed population PB model may be used in estimating individual CL/F for adult epileptic patients and could be applied for individualizing dosing regimen taking into account dose-dependent effect of concomitantly given VPA.

Determinants of quality of life in people with epilepsy in Serbia.

PURPOSE: This study aimed at finding determinants of quality of life in people with epilepsy (PWE) living in Belgrade, Serbia. METHOD: In this study, we recruited consecutive adults with epilepsy attending our outpatient department. Adult patients (age range: 18-65years) of normal intelligence and without any progressive neurological disease or psychiatric disorder were included in the study. They completed the following questionnaires: QOLIE-31 Inventory (Serbian version), Beck's Depression Inventory-II, Beck's Anxiety Inventory, Symptom Check List-90, and Neurotoxicity Scale-II. Hierarchical multiple regression analysis was performed to assess the predictive effects of some factors on QOLIE-31 Inventory. RESULTS: The mean QOLIE-31 score of 203 patients who completed the questionnaires was 70.64±17.74. Sociodemographic factors (age, sex, education, and employment) did not significantly predict QOLIE-31 score. Significant determinants of quality of life were clinical characteristics - seizure severity and etiology of epilepsy - accounting for 30.9% of the variance, depressive and anxiety symptoms accounting for 42.8% of the variance, and cognitive effects of antiepileptic drugs, accounting for 1.5% above other variables. CONCLUSIONS: The results suggest that seizure severity and etiology of epilepsy, depressive and anxiety symptoms, and cognitive adverse medication effects are main determinants of quality of life in this population of PWE.

Pharmacokinetics of lamotrigine in paediatric and young adult epileptic patients--nonlinear mixed effects modelling approach.

PURPOSE: The purpose of the study was to examine and describe adjunctive lamotrigine (LTG) pharmacokinetics in paediatric and young adult patients using a nonlinear mixed effects modelling (NONMEM) approach. METHODS: The study included 53 patients (age range 3-35 years) who were concomitantly treated with carbamazepine (CBZ) and/or valproic acid (VPA). A total of 70 blood samples corresponding to trough levels were available for analysis. Data were modelled, and the final model was evaluated using NONMEM and auxiliary software tools. RESULTS: The final LTG population model included the effects of concomitant drugs and patient's weight (WT) which stratified the population into three groups: ≤25 kg, >25 to <60 kg and ≥60 kg. Based on the final model, the estimated LTG oral clearance (CL/F) for a typical patient weighing ≤25 kg, >25 to <60 kg or ≥60 kg who was concomitantly treated with CBZ was estimated to be 3.28, 4.23, or 7.15 l/h, respectively. If a patient was concomitantly treated with CBZ + VPA, the CL/F decreased on average by 69.5 % relative to LTG + CBZ co-therapy. VPA was found to decrease the LTG CL/F by 87.6 % compared to co-therapy with only CBZ. CONCLUSION: The LTG population pharmacokinetic model developed in this study may be a reliable method for individualising the LTG dosing regimen in paediatric and young adult patients on combination therapy during therapeutic drug monitoring.

[Visual vs. quantitative electroencephalographic analysis in patients with and without posttraumatic epilepsy].

INTRODUCTION: We investigated traces of EEG records from two groups of patients with brain trauma: with and without posttraumatic epilepsy (PTE) with respect to the control group by means of two methods: visual and quantitative EEG (QEEG) analysis. The aim of this study was to compare these methods in their sensibility for traumatic and epileptic alterations of the brain tissue in the two experimental conditions: after hyperventilation (HV) and after photo stimulation (FS), and in regard to the basic condition. MATERIAL AND METHODS: 36 patients with PTE and 33 without PTE, and the control group of 34 healthy subjects participated in this study. EEG was registered in three 1-min epochs: before activation, after HIV, and after FS on digital 32-channel EEG apparatus XLTEK. Mean amplitudes were calculated in 10 frequency ranges from 0 to 30 Hz on projections F7-C3, T5-O1, F8-C4 and T6-O2 from 16-s segments without artefacts. Data evaluation was performed using program package PERSYST Insight II (Persyst Development Co). Statistical package GRAPII-PAD was used for ANOVA test and Bonferroni post-test. RESULTS: Visual analysis used to distinguish between normal EEG, with pathological alterations, non-epileptiform and epileptiform transients showed that there was no statistically significant difference between patients with and without post-traumatic epilepsy. On the contrary, QEEG of registered epochs before activation, after HV and after FS showed statistically significant differences between the control group and the patients without PTE and with PTE. CONCLUSION: These results indicate that quantitative analysis provides more subtle data about el ectrophysiological alterations after traumatic brain injury, which leads to better classification of patients.

Psychometric evaluation of the Serbian version of the Quality of Life in Epilepsy Inventory-31 (QOLIE-31).

PURPOSE: To evaluate the psychometric properties of the Serbian-language version of the Quality of Life in Epilepsy Inventory-31 (QOLIE-31). METHODS: After undergoing a translation and cultural adaptation of its items in order to create a Serbian-language version of QOLIE-31, we assessed its psychometric properties-reliability, construct validity and criterion validity. The sample consisted of 203 adults with epilepsy. Reliability was tested both by assessing the internal consistency and by the test-retest method. Construct validity was assessed by factor analysis, multitrait-scaling analysis and method of known-groups validation. This was achieved by assessing the relationship between scales and external measures (socio-demographic characteristics, seizure severity and etiology of epilepsy). Criterion validity was assessed by correlation analysis between QOLIE-31 and Short form 36 health survey (SF-36) and Neurotoxicity scale-II. RESULTS: The domains showed high internal consistency (Cronbach's α 0.94). Test-retest reliability for Overall test score was 0.83 (Pearson's coefficient) indicating temporal stability. Seizure severity and etiology of epilepsy significantly influenced all QOLIE-31 domains except the Medication effect domain, with lowest scores in high seizure severity and symptomatic etiology groups. Employment status significantly influenced Overall quality of life, Emotional well-being, Social function and Overall score. Educational level was related to the Emotional well-being domain, with highest scores for students. The QOLIE-31 was highly positively correlated with SF-36 (rho=0.898) and strongly negatively correlated with Neurotoxicity scale-II (rho=-0.783). CONCLUSION: Serbian adaptation of the QOLIE-31 questionnaire is reliable and valid for assessing the quality of life in patients with epilepsy.

The influence of drug-drug interaction and patients' characteristics on valproic acid's clearance in adults with epilepsy using nonlinear mixed effects modeling.

Monitoring valproic acid (VPA) concentrations is especially challenging due to its highly variable pharmacokinetics (PK) and complex interactions with other antiepileptic drugs. We used sparse routine therapeutic drug monitoring data (n=200) from 129 adults with epilepsy to develop a population PK model of VPA, and determine the factors that influence its clearance (CL/F). Patients were on mono VPA therapy, or were concomitantly treated with carbamazepine, phenobarbital, topiramate (TPR), lamotrigine or benzodiazepines. A one-compartment model with first-order absorption and elimination was used to fit the concentration-time VPA data. Estimates generated by NONMEM indicated that VPA CL/F was influenced by the patients' body weight (increases with the 0.556 exponent), VPA daily dose (if it is greater than 1000 mg/day, CL/F increases by 43%), and co-therapy with TPR (lowering CL/F for 23%). The interindividual variability in VPA CL/F was modeled with exponentional error model. The estimated coefficient of variation was 31.9%, while the residual variability was 23.8% for the proportional and 13.2mg/l for the additive component. The model was validated in a separate set of 24 patients, and the predictive performance was evaluated, that indicated unbias and acceptable precision. This study confirms the interaction of VPA with TPR, which is presumably dependent on VPA dose.

Autonomic status epilepticus in Panayiotopoulos syndrome and other childhood and adult epilepsies: a consensus view.

PURPOSE: To discuss and propose a definition of autonomic status epilepticus (SE), describe its clinical and EEG features, and review what is known about its epidemiology, pathophysiology, differential diagnosis, and management. METHODS: An international consortium of established researchers in the field was identified from their published work, agreed the purpose of the project, searched the literature, and, by use of e-mail communication, agreed the consensus document. RESULTS: Autonomic SE is a condition lasting at least 30 min and characterized by epileptic activity causing altered autonomic function of any type at seizure onset or in which manifestations consistent with altered autonomic function are prominent (quantitatively dominant or clinically important) even if not present at seizure onset. It is best described, and probably most commonly encountered in children, with Panayiotopoulos syndrome. However, it also occurs in children with symptomatic epilepsies and, exceptionally, in adults. Its pathogenesis and most appropriate management are poorly understood. CONCLUSIONS: It is hoped that this document will help clinical recognition of Autonomic SE, reduce misdiagnosis, and promote further interest and studies into what has been a relatively neglected area.

Epileptic encephalopathy with bilateral continuous spike-waves during slow sleep in a child with vacuolating megalencephalic leukoencephalopathy.

This case report describes the clinical evolution of a symptomatic epileptic encephalopathy with bilateral continuous spike-waves during slow wave sleep (BCSWS) in a 3-year-old girl. Her epilepsy with focal motor seizures during sleep was later complicated by myoclonic, atonic and clonic seizures culminating in BCSWS. The clinical picture, clinical course and magnetic resonance imaging findings were characterstic of primary white matter disease, probably, vacuolated megalencephalic leukoencephalopathy with subcortical cysts (MLC). To the best of our knowledge, this is the first reported case of BSCWS in a patient with leukodystrophies or MLC. This case report indicates that epileptic encephalopathy with BSCWS may be a cause of neurological or neuropsychological deterioration in MLC.

Prevalence of primary headaches in children from Belgrade, Serbia.

The aim of our study is to estimate the prevalence of migraine and tension-type headaches in 7-12-year-old school children from Belgrade. The sample was drawn from a total of 1259 school children from randomly selected primary schools. The diagnosis was made on the basis of a clinical interview combined with the neurological examination. The prevalence of migraine increases with age from 0.5% at the age of seven, to 6.8% at the age of 12. Female to male ratio inverts with age: males predominate at age 7-9, but females predominate at age 10-12. The estimated prevalence of tension-type headache increases with age from 0.5% in 7-year olds to 2.4% in 12-year olds. Statistically, the onset of migraine occurs significantly earlier than that of tension-type headache. Migraine and tension-type headache are frequent headache types and have different demographic characteristics among children.

Preventing depression in adolescents with epilepsy.

PURPOSE: The goal of the work described in this article was to test the possibility of preventing depression among adolescents with epilepsy. METHODS: Adolescents with newly diagnosed epilepsy (104 patients) were screened for depression. The risk for depression was increased in 30 (28.8%) patients (mean age 17.4, 60% females) who were randomized into two equal treatment groups: (1) cognitive-behavioral intervention (CBI) group and (2) treatment with counseling as usual (TAU) group. The Beck Depression Inventory (BDI), Center for Epidemiological Study on Depression (CES-D) scale, Hamilton Depression Scale (HAMD), and Quality of Life in Epilepsy Inventory (QOLIE-31) were administered at baseline and during the 9-month follow-up. RESULTS: Initial BDI and HAMD scores for the two groups were comparable. Depression was diagnosed during follow-up in three patients in the TAU group. Subthreshold depressive disorder significantly improved at follow-up in the BCI group compared with the TAU group (P<0.05). QOLIE-31 Total scores significantly correlated with both mood improvement and seizure-free state.

Social competence of children and adolescents with epilepsy.

BACKGROUND: This study compared children and adolescents with epilepsy with their healthy peers on measures of social competence. METHODS: Children and adolescents with epilepsy (70 subjects aged 11-18 years; 47.1% girls) and their healthy peers in control group (95 subjects aged 11-18 years; 50.9% girls) were compared on measures of social competence from the Child Competence Checklist (part of Child Behavior Check List). The questionnaires were completed by the parents. All participants were of normal intelligence. RESULTS: The difference of means of total T scores for subscales of sociabilitiy and activities in the epilepsy group and in the control group were statistically significant (p<0.05). The results showed that 5.7% of children and adolescents with epilepsy were in the clinical range compared to 2.1% of subjects in control group. The girls with epilepsy demonstrated greater problems with social competence (45.8+/-8.27) than boys with epilepsy (48.1+/-8.27) and this difference was statistically significant (p<0.05). Multiple analysis of variance of T scores for social competence subscales related to neurobiological variables in the group of participants with epilepsy demonstrated a statistically significant association of reduced sociability with multiple generalized seizure types (F=4,405; d.f.=2; p<0.05). CONCLUSIONS: The study clearly shows that epilepsy is a limiting factor for social competence of children and adolescents.

Seizures associated with intoxication and abuse of tramadol.

PURPOSE: To assess the frequency of seizures and patient characteristics associated with tramadol intoxication and abuse in young addicts. METHODS: Patients with history of tramadol abuse and intoxication were prospectively studied during a 3-year period. The characterstics of patients with seizures and those without seizures were compared. RESULTS: Fifty-seven patients (mean age 22.3 years [range 16-43 years], 47 males) were included. Tonic/clonic seizures occurred in 31 (54.4%) patients, (26 males and 5 females): single in 14 (45%), multiple in 17 (55%) patients after a tramadol dose ranging from 250-2500 mg. Seizures occurred within 24 h after tramadol intoxication in 26 (84%) patients, and later in 5 (16%) patients. Compared to addicts without seizures, the abusers with seizures were younger (p < 0.05). Both epileptiform and nonepileptiform electroencephalographic patterns were more common in patients with seizures than in patients without seizures, but the differences did not reach statistical significance. CONCLUSION: The neurotoxicity of tramadol commonly manifests as generalized tonic-clonic seizures occurring most frequently within 24 h after tramadol intake. Seizures were more common in younger abusers with a longer duration of exposure to tramadol and with the combined use of tramadol with alcohol.

Panayiotopoulos syndrome: a consensus view.

The aim of this paper is to promote the correct classification of, and provide guidelines on, the diagnosis and management of Panayiotopoulos syndrome (PS). An international consortium of established researchers in the field collaborated to produce a consensus document. The resulting document defines PS, characterizes its electro-clinical features, considers its likely pathogenesis, and provides guidance on appropriate management. We conclude that PS is a common idiopathic, benign seizure disorder of childhood, which should be classified as an autonomic epilepsy, rather than an occipital epilepsy.

[Comorbidity of migraine and somatic diseases].

INTRODUCTION: A 5-year prospective follow-up study was performed at the Institute of Mental Health in Belgrade, and it included adult patients diagnosed with migraine. MATERIAL AND METHODS: A protocol for prospective follow-up of comorbiditiy of migraine and somatic diseases was designed, whereas data were analyzed using standard statistical methods. RESULTS: The study comprised 381 patients, mean age 35.8 (range 19-60) years, 60 (15.8%) males and 321 (84.2%) females. The mean duration of migraine history before the first visit to the doctor was 7.7 (0-36) years. There was no concomitant disease in 50.5% of examinees. The most common concomitant diseases in the study population were: spondylosis (15.9%), head injury (12.9%), gynecological disorders (11.6% of female subgroup), hypotension (8.8%), hypertension (8.5%), allergy and asthma (5.8%), various cardiovascular diseases (4%) and epilepsy (3%). The incidence of the majority of diseases is in accordance with known epidemiological data for general population (except for head injury and epilepsy). In the subgroup of patients with comorbidity, almost 70% of patients reported more than one migraine attack per month, compared to 35% of patients without concomitant diseases, and about 60% of them had a higher intensity of headache in comparison with 35% of those without comorbidity. CONCLUSION: Present results indicate an increased severity of migraine attacks in patients with comorbidity. Therefore, it is necessary to assess how good management of comorbid diseases can alleviate the course and intensity of migraine headaches.

Antiepileptic, behavioral, and antidepressant effects of adjuvant lamotrigine therapy in drug-resistant epilepsy.

AIM: To evaluate the behavioral effects of lamotrigine as add-on therapy in treatment-resistant epilepsy. METHODS: An open, prospective, long-term study of lamotrigine as adjuvant therapy was performed in 56 patients with drug-resistant epilepsy (female/male ratio 35/21, age range 16-51 years). All the patients kept seizure diaries, and electroencephalograms were recorded at baseline and during 24 months of the treatment. Quality of life questionnaire, Hamilton depression scale (HMD), Beck depression scale (BDI), and Hamilton anxiety scale (HMA) were used before and during lamotrigine therapy. Comparative assessments were made in an age- and sex-matched control group treated with other antiepileptic drugs. RESULTS: Overall, seizure control was improved in 55.3% of the patients, remained unchanged in 39.3%, and deteriorated in 5.4%. Improvement in some quality of life measures occurred in 50% of the patients. The HMD subscales and BDI scale showed significant improvement in lamotrigine treated patients compared to the control group (ANOVA, p < 0.01). Negative behavioral effects occurred in 10.7% of the patients. CONCLUSION: Lamotrigine demonstrated significant antiepileptic long-term efficacy, and its positive effects on the mood and quality of life, which surpassed the negative behavioral effects, and contributed highly to the favorable treatment outcome.