Convulsive status epilepticus management in adults and children: Report of the Working Group of the Polish Society of Epileptology.

INTRODUCTION: The Working Group was established at the initiative of the General Board of the Polish Society of Epileptology (PSE) to develop an expert position on the treatment of convulsive status epilepticus (SE) in adults and children in Poland. Generalized convulsive SE is the most common form and also represents the greatest threat to life, highlighting the importance of the choice of appropriate therapeutic treatment. AIM OF GUIDELINE: We present the therapeutic options separately for treatment during the early preclinical (>5-30min), established (30-60min), and refractory (>60min) SE phases. This division is based on time and response to AEDs, and indicates a practical approach based on pathophysiological data. RESULTS: Benzodiazepines (BZD) are the first-line drugs. In cases of ineffective first-line treatment and persistence of the seizure, the use of second-line treatment: phenytoin, valproic acid or phenobarbital is required. SE that persists after the administration of benzodiazepines and phenytoin or another second-line AED at appropriate doses is defined as refractory and drug resistant and requires treatment in the intensive care unit (ICU). EEG monitoring is essential during therapy at this stage. Anesthesia is typically continued for an initial period of 24h followed by a slow reversal and is re-established if seizures recur. Anesthesia is usually administered either to the level of the "burst suppression pattern" or to obtain the "EEG suppression" pattern. CONCLUSIONS: Experts agree that close and early cooperation with a neurologist and anesthetist aiming to reduce the risk of pharmacoresistant cases is an extremely important factor in the treatment of patients with SE. This report has educational, practical and organizational aspects, outlining a standard plan for SE management in Poland that will improve therapeutic efficacy.

Non-interventional surveillance study of adverse events in patients with epilepsy.

OBJECTIVES: Compare adverse events (AEs) in patients with epilepsy taking different antiepileptic drugs (AEDs) using standardized physician-completed questionnaires. MATERIALS AND METHODS: Multicenter, observational, cross-sectional study in epilepsy patients aged ≥4 , stable on 1-2 AED(s) for ≥3 months. RESULTS: One thousand and nineteen patients were evaluated: 28.7% took newer, 71.3% older (or older + newer) AED(s); 56.9% monotherapy; 43.1% polytherapy. Overall, 68.3% reported ≥1 AE (61.3% newer; 71.1% older AEDs), most commonly: cognitive function disturbances, sedation, psychological problems. Patients taking newer AEDs were significantly less likely to report ≥1 AE (OR [95% CI]: 0.64 [0.46-0.89], P = 0.008). Treatment/dose changed at study visit: 22.8% (17.5% newer; 24.9% older AEDs) because of (newer/older); lack of efficacy (6.2%/7.8%); AEs (4.1/8.4%); absence of seizures (3.8/4.0%). Patients receiving levetiracetam or lamotrigine were significantly less likely to report AEs/modify treatment. CONCLUSION: Patients taking newer AEDs were significantly less likely to report AEs, although the non-randomized study design does not allow the lower rate of AEs to be attributed with certainty to the use of newer AEDs. A standardized AE questionnaire appeared useful for monitoring AEs/optimizing AED therapy.

Myopathy as the first symptom of hypokalemic periodic paralysis--case report of a girl from a Polish family with CACNA1S (R1239G) mutation.

PURPOSE: Presenting the case of unusual onset hypokalemic periodic paralysis (HypoPP) where myopathy had developed two years before paralysis occurred. MATERIAL AND METHODS: A Polish three-generation family with HypoPP and mutation in CACNA1S (R1239G) has been investigated. Clinical presentation with unusual onset of the disease, biopsy results and genetic research in one family member were described. CONCLUSION: HypoPP is a rare disease it needs to be taken into consideration not only in cases of paroxysmal weakness but also when there is myopathy of unknown origin.

Neuropsychological assessment in newly diagnosed cryptogenic partial epilepsy in children--a pilot study.

PURPOSE: Cryptogenic epilepsy (CE) is defined as a partial or generalized epilepsy syndromes in which we can not point out any underlying cause. The role of neuropsychological assessment of "non-lesional" epilepsies is crucial not only to better control of different medical treatment but also to understanding the role of epilepsy for cognitive functions. The aim of the study was to compare the intellectual and cognitive functions between children with newly diagnosed cryptogenic partial epilepsy (CPE) children and the control healthy group. MATERIAL AND METHODS: 184 participants, 89 patients with cryptogenic partial epilepsy and 95 healthy children and adolescents, with ages ranging from 6-16 years were assessed on neuropsychological tests of general intellectual functioning and selected cognitive skills. RESULTS: There were significant differences found between groups for four examined functions. Children with CPE scored significantly lower in verbal and categorial fluency, visuoconstructional tasks, learning and memory than group of healthy children. There was no differences in general IQ level. CONCLUSIONS: Study of neuropsychological profile in newly diagnosed CPE can get us an information of influence of stable, related to illness factors and the paroxysmal activity on cognitive function. Neurological follow-up of children with CPE at the very beginning of diagnosis should include screening evaluation of cognitive functions to provide appropriate intervention.

The sleep habits and sleep disorders in children with headache.

PURPOSE: The study was conducted to examine the sleep habits and sleep disorders in children and adolescents with headache. MATERIAL AND METHODS: Three hundred children with headache were qualified to a headache group (HG) and 284 children from schools and kindergartens without headache to a control group (CG). RESULTS: In our study, 27.7% children of the HG slept together with other person in the bed; 18.7% of the CG. In the HG, 11.7% of children had physical contact with parents when falling asleep, in the CG 19.7%. In the HG, watching TV and listening to the radio when falling asleep occurred more frequently. About 20% of parents in the HG read aloud to children before putting them to sleep, in the CG 32.4%. Day naps occurred in 32.7% of the HG children and in 20.1% of the CG. Sleep disorders reported in the study group as parasomnia symptoms included: sleep talking 48.3% (CG 38.7%); bruxism 23.3% (CG 16.5%); leg movement 20.3% (CG 18.0%); nightmares 16.7% (CG 7.4%) and sleep breathing disorder symptoms like snoring 27.3% in the HG group (CG 19.0%) and breathing pauses 5.7% (CG 1.4%). Awakenings from the night sleep were observed in 43.7% children of the HG and in 36.4% children of the CG. CONCLUSIONS: Sleep habits in children with headache were considerably different from sleep habits in the CG. The prevalence of sleep disorder symptoms like: snoring, sleep talking, bruxism, sleep terror, nightmares, breathing pauses and awaking from night sleep was higher in the HG group than in the CG.

The symptomatology of tic disorders and concomitant sleep habits in children.

INTRODUCTION: The aim of study was to analyze the clinical symptoms of tic disorders (TG) and sleep habits in children. The sleep habits were compared with those of a control group (CG). MATERIALS AND METHODS: The study included 84 children with TG. The diagnoses were verified according to DSM-IVR criterion. CG included 156 healthy children. The parents filled in a questionnaire developed by the authors--TG's parents filled in a part concerning the symptomatology of tic disorders and sleep habits, CG's parents only the second part. RESULTS: There were 78.6% of male and 21.4% of female in TG respectively, and 53.8% and 46.2% in CG. The simple and complex motor tics were observed in 98.8% and 39.3% of patients, vocal tics--64.3%, sensory tics--20.2%. ADHD and OCD symptoms were noticed respectively in 73.8% and 35.7% of children. The most common simple and complex motor tics were respectively: blinking--9.0%, jumping and touching--20.2% of patients. Vocal tics were presented in 64.3%. 23.8% of TG slept together with another person in bed, and 69% of them in one room with other members of family; in CG it was respectively 58.1% and 19.2%. 33.3% of TG fell asleep and woke up in the same position in bed, in the CG 75.6% of children slept calmly. The bed-time stories were seldom read by the parents in TG--3.6% vs CG--31.4%. CONCLUSIONS: Quote frequently TG are connected with other behavioral symptoms, in particular ADHD and OCD. Sleep habits are different in TG than in CG.

Alteration of the in vivo nicotinic receptor density in ADNFLE patients: a PET study.

Nicotinic acetylcholine receptors (nAChRs) are involved in a familial form of frontal lobe epilepsy, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). In several ADNFLE families, mutations were identified in the nAChR alpha4 or beta2 subunit, which together compose the main cerebral nAChR. Electrophysiological assessment using in vitro expression systems indicated a gain of function of the mutant receptors. However the precise mechanisms by which they contribute to the pathogenesis of a focal epilepsy remain obscure, especially since alpha4beta2 nAChRs are known to be widely distributed within the entire brain. PET study using [18F]-F-A-85380, a high affinity agonist at the alpha4beta2 nAChRs, allows the determination of the regional distribution and density of the nAChRs in healthy volunteers and in ADNFLE patients, thus offering a unique opportunity to investigate some in vivo consequences of the molecular defect. We have assessed nAChR distribution in eight non-smoking ADNFLE patients (from five families) bearing an identified mutation in nAChRs and in seven age-matched non-smoking healthy volunteers using PET and [(18)F]-F-A-85380. Parametric images of volume of distribution (Vd) were generated as the ratio of tissue to plasma radioactivities. The images showed a clear difference in the pattern of the nAChR density in the brains of the patients compared to the healthy volunteers. Vd values revealed a significant increase (between 12 and 21%, P < 0.05) in the ADNFLE patients in the mesencephalon, the pons and the cerebellum when compared to control subjects. Statistical parametric mapping (SPM) was then used to better analyse subtle regional differences. This analysis confirmed clear regional differences between patients and controls: patients had increased nAChR density in the epithalamus, ventral mesencephalon and cerebellum, but decreased nAChR density in the right dorsolateral prefrontal region. In five patients who underwent an additional [(18)F]-fluorodeoxyglucose (FDG) PET experiment, hypometabolism was observed in the neighbouring area of the right orbitofrontal cortex. The demonstration of a regional nAChR density decrease in the prefrontal cortex, despite the known distribution of these receptors throughout the cerebral cortex, is consistent with a focal epilepsy involving the frontal lobe. We also propose that the nAChR density increase in mesencephalon is involved in the pathophysiology of ADNFLE through the role of brainstem ascending cholinergic systems in arousal.

Pharmacokinetic interactions of carbamazepine with some antiepileptic drugs during epilepsy treatment in children and adolescents.

PURPOSE: The aim of the study was to obtain pharmacokinetic data for carbamazepine (CBZ) and its fractions not bound with proteins in bitherapy with lamotrigine (LTG), topiramate (TPM), vigabatrin (VGB) or valproic acid (VPA) in children and adolescents treated for epilepsy. MATERIAL AND METHODS: The participants of the presented investigations were fifty-five patients with epilepsy who were under control of The Department of Developmental Neurology, University of Medical Sciences in Poznaf. All of patients were treated with CBZ in bitherapy with LTG, TPM, VGB or VPA. The blood samples were taken under steady-state conditions, before the morning dose and subsequently every 3 or 2 for 24 h. The plasma levels of CBZ were determined using TDX analyzer (Abbott Diagnostic Division, USA). Free CBZ fraction was isolated with the use of ultrafiltration system (Amicon, USA). For pharmacokinetic calculations of total and free CBZ, one-compartment model was used according to standardized procedure. RESULTS: No significant differences in pharmacokinetic parameters of unbound CBZ in four groups of patients on bitherapy with CBZ and LTG, TPM, VGB or VPA were found. The changes in pharmacokinetics of total CBZ were related with difference in CBZ concentrations, area under curve (AUC), L/D/kg ratios and clearance (Cl)/kg. CBZ+VGB bitherapy led to higher total CBZ concentrations. In the group on bitherapy with CBZ+VPA, no increase in unbound CBZ was detected. CONCLUSIONS: Pharmacokinetic interactions of CBZ with LTG, TPM, VGB or VPA in children are associated only with the changes in total CBZ parameters.

Bilateral facial nerve palsy in the course of neuroborreliosis in children-dynamics, laboratory tests and treatment.

PURPOSE: Presentation of four patients with bilateral peripheral facial nerve palsy as a clinical manifestation of neuroborreliosis in children--diagnostic, treatment and prognosis. MATERIAL AND METHODS: In 2002-2004 in The Chair and Department of Developmental Neurology, 24 children from the Wielkopolska region were admitted with diagnosis of borreliosis. Among all the children with borreliosis, confirmed by serologic examination, 4 (16.7%) demonstrated bilateral peripheral facial palsy (PFP). We investigated the presence of IgM class and IgG class specific antibodies in the sera and cerebrospinal fluid (CSF) of 4 patients with bilateral PFP. (Detected by immunoenzymatic methods--ELISA.) RESULTS: Before the occurrence of PFP all the children manifested unspecified systemic symptoms such as headaches, muscle and articulation pains, weakness and in two cases a mood depression. At first all patients demonstrated elevated IgM antibodies and proper levels of IgG antibodies. Control tests administered within 2-14 months later reduction of antibodies was indicated. Two patients demonstrated significant pleocytosis in CSF test, (without the meningeal symptoms). All children were treated with physiotherapeutic procedures and were administered antibiotic intravenously. CONCLUSIONS: PFP is one of the most frequent neurological symptoms of borreliosis in children. In case of acute PFP and especially the bilateral form of PFP, neuroborreliosis is the most probable diagnosis. All children reported PFP at one side first and after several weeks the paresis of the facial nerve on the opposite side usually appeared. The clinical state of children started to improve after the introduction of physiotherapy and this process usually lasted several months.

[Intractable epilepsy of childhood and its treatment]. / Padaczka lekooporna wieku rozwojowego i jej leczenie.

This paper discusses the concept of epilepsy intractability as the criterium qualifying for the administration of polytherapy, inclusion of new antiepileptic drugs /AEDs/ and application of neurosurgical treatment. There were also diagnostic criteria and complication discussed. To define the concept of epilepsy intractability correctly and to administer appropriate treatment, it is necessary to classify the kind of seizures and their possible reasons, to apply suitable AEDs, their doses and to treat patients with them for a suitable period of time. Intractable forms of epilepsy are diagnosed at about 20-30% of patients with suitable treatment. The disease prevalence is different at particular age groups and depends also on seizure type or epileptic syndrome. Therefore, Ohtahar syndrome, West, Lennox and Gastaut syndromes, epilepsia partialis continua belong to intractable epileptic syndromes at children. There is the biggest risk of psychic disorders appearance among patients resistant to antiepileptic treatment. Moreover, long-term application of AEDs may be associated with the induction of epileptic seizures, occurrence of side and toxic symptoms. Great interest in intractable epilepsy is connected with huge progress in treatment of this disease which has resulted in introduction of many new AEDs for the last few years. Its inclusion into treatment, first as add--on therapy, and then, due to clinical examinations, also as a monotherapy, enables the improvement in seizure control and in the quality of patients' life.

[Therapeutic antiepileptic drug monitoring: thirteen years of experience in the Laboratory of Clinical Neuropharmacology in the Chair and Department of Developmental neurology]. / Monitorowanie stezen leków przeciwpadaczkowych--trzynascie lat doswiadczen w Pracowni Neurofarmakologii Klinicznej Katedry i Kliniki Neurologii Wieku Rozwojowego.

Determining antiepileptic drug (AED) concentration in biological fluids and calculating its dosage on this basis is a long-term method in the treatment of epilepsy. This facilitates the treatment and increases the safety of patients in the aspect of suitable seizure control and reduced risk of side effects. This report presented the range and the number of antiepileptic drug concentration determined during thirteen years activity of Laboratory of Clinical Neuropharmacology in the Department of Developmental Neurology. There was also a number of drug concentrations particularly often determined presented, compared and discussed. Moreover, there were also analyses of subtherapeutic, therapeutic and potentially toxic concentration decomposition presented for subsequent AEDs. The frequency of conventional drug and of slow released forms for VPA and CBZ was compared. VPA appeared to be the most frequently monitored drug and CBZ occurred to be the next one. The concentrations of PHT, PB, PRM and ETH were more rarely determined. In the observed period of time the number of LPP concentration determined in the therapeutic range amounted to 69%, the least frequently the potentially toxic levels were determined--11%. Normal concentrations i.e. therapeutic ones were most often determined for CBZ (77%) and subtherapeutic levels were determined mostly for PHT.

[Carbamazepine presence in plasma lipoproteins]. / Dyspozycja karbamazepiny w lipoproteinach osocza.

The aim of this study was to define the disposition of carbamazepine (CBZ) in serum lipoproteins. The examination was conducted using the serum of 51 patients treated with carbamazepine the concentration of which was monitored 51 patients, 22 women and 29 men, 1.5-35 years old/mean 13.0 +/- 6.7 years/weighing 10.2-90.0 kg/mean 46.5 +/- 23.6/participated in the study. Every patient received carbamazepine in an individual oral dose. Concentrations of cholesterol, triglicerides, proteins and CBZ were determined. Lipoprotein fractions (VLDL, LDL, HDL and LPDS) were separated by ultracentrifugation of serum. Carbamazepine concentrations were measured by fluorescence polarization immunoassay technique on a TD x analyzer. Cholesterol, triglicerides and proteins levels were measured on Bayer--Technicon apparaturs. Carbamazepine is distributed in plasma lipoproteins, mainly in HDL fraction (mean 45.2 +/- 9.0%) and in LPDS (mean 43.2 +/- 9.3%) fraction. Ratio of carbamazepine concentration to cholesterol (RcCH), triglicerides (RcTG) and proteins concentration (RcP) and carbamazepine concentration (%) to cholesterol (R% CH), triglicerides (R% TG) and proteins concentration (%/R% P) are different in different fractions. The obtained results suggest that the disposition of CBZ in lipoprotein fractions may have a significant importance in the therapy and fat metabolism disorders make the changes of drug dose urgent.

[Diagnostic value of sleep deprivation as the EEG activation method in diagnosis of epilepsy in developmental age]. / Wartosc diagnostyczna deprywacji snu jako metody aktywacji EEG w rozpoznawaniu padaczki w wieku rozwojowym.

The paper presented the significance of EEG activation in diagnosing epilepsy in children and adolescents. EEG records of 108 patients between 3-19 years of age with the occurrence of various types of paroxysmal disorders who were admitted to Chair and Department of Developmental Neurology University of Medical Sciences in Poznan were analysed. Standard EEG was administered to all children twice: the first examination at rest with hyperventilation (HV) and photostimulation (FS) and the second one after total or partial sleep deprivation (DS). At awaking state normal records were stated in 57% of cases, in 15% paroxysmal changes in HV or FS appeared, in the rest of cases (28%) generalised paroxysmal disorders, localised changes, lateralised or diffused were noted. Among EEG activation methods DS occurred to be the most effective after it, 52 patients (48%) were diagnosed for generalised paroxysmal changes, 20% for localised, 3% lateralised and for 6% for diffused changes. Normal EEG were recorded in 22% of examined children and adolescents. The epilepsy were diagnosed in 59 (55%) of patients mostly with generalised seizures (28) partial secondarily generalised (16) and partially complex (11). In 49 (45%) children were diagnosed with other paroxysmal disorders.

[Neuropsychological aspects of cognitive functioning in epileptic children and adolescents treated with lamotrigine]. / Wybrane neuropsychologiczne aspekty funkcjonowania poznawczego dzieci i mlodziezy z padaczka leczonych lamotrigina.

The aim of our study was to examine the influence of long term lamotrigine (LTG) add-on therapy on higher nervous function in patients at the developmental age with epilepsy and to analyse the correlation between changes in EEG and cognitive parameters as a consequence of applying LTG in bi- or polytherapy with conventional antiepileptic drugs (AEDs). There were 25 patients (pts), 8-18 years of age with epilepsy stated as "difficult to treat" with partial (12 pts) and generalised (13 pts) seizures. The frequency of seizures was estimated as one or more per month last year (before LTG treatment). The mean age of the patients who had the first seizure was 4.7 yrs. Doses of LTG were adjusted individually (depending on conventional AEDs) according to the recommendation of the producer. The serum levels of conventional AEDs were checked during LTG therapy. Psychological examination was administered three times: before introduction of LTG (as add-on drug) to the therapy, after 3- and after 16 months of the treatment. We measured the level of intelligence, short-term memory, attention, visuomotor integration and abilities of learning. EEG was recorded by Ceegraph (Biologic, USA) after 3 and 12 months of LTG treatment. After the treatment no statistically significant differences in Intelligence Quotient (IQ): global, verbal, nonverbal were noticed. Statistical significance has been stated in parameters of short-term memory. The number of seizures decreased more than 50% in 12 pts. EEG records improved in 6 pts (normalisation of background activity), minimising of epileptform discharges has been noticed in 3 pts. LTG introduced into polytherapy of epilepsy in children and adolescents modified EEG and had minimal influence on cognitive functions.

[The Landau-Kleffner syndrome. SPECT and EEG investigations]. / Zespól Landaua i Kleffnera. badania SPECT i EEG.

Four children (three boys and one girl) with acquired epileptic aphasia (the Landau-Kleffner syndrome) have been observed in the Department of Developmental Neurology University of Medical Sciences in Poznan. We present the dynamic of clinical symptoms and fluctuations in EEG studies. The changes in the brain in single photon emission computed tomography (SPECT) during remission of clinical symptoms are discussed.

Clinical and pharmacokinetic observations on valproate: a 3 year follow-up study in 100 children with generalized epilepsy.

The results of a 36 month observation of therapeutic effects of various schemes of long-term monitored treatment of primary generalized epilepsy with Valproate (VPA) derivatives is presented. A hundred children and adolescents aged 5-15 constituted the experimental group. In each of 3 groups the drug was administered in individually assessed doses. An optimal antiepileptic clinical effect of VPA was achieved thanks to therapeutic monitoring, especially pharmacokinetic studies.

[Early changes in the visual system in subacute sclerosing panencephalitis]. / Wczesne zmiany w ukladzie wzrokowym w podostrym stwardniejacym zapaleniu mózgu.

This paper presents our observations of changes in the visual system in the early period of SSPE in the group of 23 children at the age of 3 to 17 years (18 boys and 5 girls). The most frequent changes were papillary stasis (9 patients). Decreased visual acuity with no changes in the optic fundus or with chorioretinitis and simple atrophy of the optic nerve were observed in 8 children. Convergent squint, visual hallucinations and visual agnosia were additional symptoms in single cases. Changes in the visual system which appeared in early period of the disease as single clinical symptom usually create serious diagnostic problems. The greatest problem appeared when papillary stasis coexisted with other symptoms of increased intracranial pressure. Neuroradiological examinations were decisive in these cases. Diagnosis of SSPE was confirmed by further course of the disease and others additional and typical results.