Žarko Martinović

Impact of age, weight and concomitant treatment on lamotrigine pharmacokinetics

What is known and Objective:  Lamotrigine metabolism may be substantially altered with concomitant administration of valproic acid and/or carbamazepine. Such alterations may require the adjustment of lamotrigine dose to ensure optimal treatment efficacy and safety.

Pattern-reversal visual evoked potentials recorded in children with generalized epilepsy.

Visual potentials evoked by pattern reversal (PRVEPs) were studied in 64 normal subjects (age range 7 to 15 years) and in 15 patients with primary generalized epilepsy (age range 8 to 13 years), 10 of whom were without anticonvulsant medication. Most of them were studied during sodium valproate (VPR) therapy and some during carbamazepine (CBZ) medication. A Quadristim set (Alvar) was used to present checkerboard patterns on a TV monitor, to amplify the EEG signals and to average and plot the evoked potentials. The potentials were elicited by binocular full-field 2/s checkerboard reversals, recorded from an electrode 4 cm above the inion, and analyzed for latency, amplitude and waveform. Our PRVEP measurements examined peak latency of positive P2 (or P100) component and trough-to-peak amplitude on N1P2 wave complex. The degree of similarity between pairs of PRVEP plots were determined by Pearson correlation coefficient r for an analysis time of 150 ms. In most of our patients, no pronounced influence of the disease itself on the parameters and waveform of the normal PRVEP pattern was demonstrated if anticonvulsant drugs were not taken. In patients who were under complete seizure control, the anticonvulsant did not change the PRVEP morphology as well. The PRVEP abnormality was most pronounced in patients who were taking anticonvulsant medication, but whose seizures were poorly controlled. This pattern distortion can be revealed by the correlation coefficient, but not by other PRVEP parameters. Therefore, this coefficient may be useful as a sensitive and objective measure both of PRVEP distortion and PRVEP improvement. Our results give further evidence that nondemyelinating disorders, but with synaptic transmission defects, can produce measurable changes in PRVEP morphology.

Topography of visual EEG reactivity in school-age children

In order to quantify the visual reactivity of EEG to opening the eyes, the topography of EEG power spectra for a sample of 72 healthy subjects of age ranging from 7 to 15 years was investigated. The EEGs were recorded from 16 scalp sites with eyes open (EOP) and eyes closed (ECL). Ln-transformed absolute EEG powers, acquired under these two states, were tested with Wilcoxons paired test for differences between the powers. The absolute powers in alpha band and in total, were significantly higher in all derivations, under the ECL, as compared with the EOP, condition. Absolute powers in theta band under the ECL condition were also significantly higher than those under the EOP condition, except for frontal derivations. Changes in delta power were insignificant. Beta 1 band activity, when eyes were closed, was maximal in posterior and minimal in anterior derivations. When the eyes were open, the greatest beta 1 power was found in the frontal derivations. Beta 2 was the only band in which a frequent increase in power took place with eyes opening. Eyes opening appeared to decrease significantly, the beta 1 and beta 2 powers only in posterior derivations. The results showed that the visual blocking of EEG was mostly due to a higher degree of EEG desynchronization for the subjects aged 7-5 years.

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 (Cronbachs α 0.94). Test-retest reliability for Overall test score was 0.83 (Pearsons 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.

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), Becks Depression Inventory-II, Becks 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.

Computerized EEG topography of normal preadolescent twins—Correlating similarity of background activity with genetic relatedness

SummaryThe influence of genetic relatedness on the similarity degree of topographical EEG parameters was studied in a sample of 26 sets of monozygotic (MZ) and 46 sets of dizygotic (DZ) twins. All 144 subjects were healthy, primary school children, aged 7–15 years, 69 boys and 75 girls. Correlation coefficients were calculated for 50 quantitative EEG parameters of paired values obtained at each of 16 active electrode sites, in four groups of paired tracings: 1. MZ twins, 2. DZ twins, 3. The autocorrelated (A) group formed by correlating the spectral parameters from the same subjects in two different analyzed sequences, 4. The random (R) control group of 1200 unrelated pairs formed from DZ twin pairs. Sets of MZ twins and A group showed the highest degrees of similarity of spectral parameters over all brain areas except for significant differences only for some background features over posterior regions. In contrast, highly significant differences in topographic parameters were evident in comparison of MZ sets with DZ sets, particularly when MZ sets were compared with DZ subsets of opposite sex. Both number and degree of significant differences increased progressively in comparisons with groups 3 vs 2,1 vs 4, and 3 vs 4. The data gave strong evidence for a complex polygenic determination of normal human EEG topography.

Gabapentin in the treatment of migraine and epilepsy comorbid with mood and anxiety disorders

Abstract This open prospective study assessed the use of gabapentin in migraine and epilepsy comorbid with mood and anxiety disorders. After a 4-week baseline period, gabapentin was used as adjunctive treatment in 14 adult patients with both epilepsy and migraine disorders for 3 months. The outcomes were compared with a control group of 14 sex-matched patients with the same disorders, not treated with gabapentin. Both groups were assessed on the Cornell dysthymia rating scale (CDRS), Beck depression inventory (BDI), and Hamilton anxiety scale. A total of 8 (57%) gabapentin-treated patients showed a significant improvement in migraine vs. 3 (21.4%) of the controls. In comparison with controls, the gabapentin-treated group had a significant decrease in CDRS and BDI scores (p<0.05). The results suggest a particular role for gabapentin in the treatment of patients with both epilepsy and migraine comorbid with mood and anxiety disorders.

18. The electroencephalogram (EEG) in patients with Lennox–Gastaut syndrome continuing into adulthood

Purpose: To study the long-term clinical and EEG evolution of Lennox–Gastaut syndrome, a chronic and severe epileptic encephalopathy. Methods: Patients presenting with seizure types and EEG discharges typical of LGS were diagnosed at the age 2–7years and included in the follow-up extended to adulthood. Results: The study sample consisted of 23 patients (9 females and 14 males, mean age at onset 3.6years, average follow-up period 19.8years). Three main clinical and EEG stages were found: 1. Full-blown stage with intractable seizures or epileptic status and long bilateral slow spike-wave discharge, 2. Diminished seizure frequency and short, irregular EEG discharges, and 3. Seizure remission with low amplitude and slow EEG activity. At the end of follow-up, 5 patients were still in full-blown stage, 7 reached second stage, while a stable remission with persistent cognitive and mental disorders occurred in 11 patients. Long-lasting BSSWC episodes remitted at an earlier age than bilateral tonic spike discharges during sleep. Conclusion: Severe epileptiform EEG abnormalities were concomitant with high seizure frequency and severity, while scanty and slow EEG activity with rare or absent epileptiform abnormalities was associated with severe sequels of LGS.

11.The role of electroencephalographic follow-up in tuberous sclerosis complex

disorder). PSG is indicated for the diagnosis and follow up of sleep related breathing disorder (SRBD) and titration of CPAP; diagnosis of narcolepsy followed by MSLT; evaluation of atypical or injurious behaviors usually in seizures and parasomnias (e.g., RBD); evaluation of periodic limb movements in sleep (PLMS) or insomnia resistant to therapy; PSG is not routinely indicated: if there is a clear diagnosis of typical and non-injurious parasomnia; seizure disorders with no signs and symptoms consistent with a sleep disorder; in the diagnosis, and treatment of restless legs syndrome; for the diagnosis of circadian rhythm sleep disorders; PSG and MSLT are not routinely indicated for the diagnosis of depression.

14.Long-term EEG evolution in focal epilepsy syndromes with a childhood onset

Benign epilepsies of infancy are entities for which is not easy to make a diagnosis. In 1963 Fukuyama first proposed the benign epilesy of infancy characterized by onset before the age of 2 years and benign course. Later publications in 80s and 90s specified localization and semiology, familial and nonfamilial characteristics and final outcome. The International classification of epilepsies and epileptic syndromes (Engel, 2001) comprises only familial and non-familial benign infantile seizures. Specchio and Vigevano (2006) described semiology and onset, family history, ictal and interictal EEG pattern, prognosis and final outcome of benign seizures in infancy. They divided them into the following groups: Benign non-familial infantile seizures, Benign familial infantile seizures (BFIS), BFIS associated with other neurological symptoms, Benign familial neonatalinfantile seizures (BFNIS), Benign infantile seizures associated with mild gastroenteritis (BIS with MG), Benign infantile focal epilepsy with midline spikes and waves during sleep (BIMSE). The aim of this review is to describe these entities and discuss similarities and difference between them. We pointed out significance of video EEG recording in dramatic appearance of seizures in clusters, lasting few days, which can also occured in benign epilepsy of infancy.