Adjunctive Madopar for ultrarefractory epilepsy? Preliminary observations.

BACKGROUND: The optimum drug treatment for ultrarefractory epilepsy after failure of seven prior antiepileptic drugs (AEDs) remains uncertain. Prompted by reports that adjunctive amantadine or l-dopa has been useful for children with refractory absence seizures and Lennox-Gastaut syndrome, we studied the utility of dopaminergic agents for adults with ultrarefractory epilepsy. METHODS: We assessed seizure control following adjunctive treatment for up to 12 months with the dopaminergic agent Madopar© in three adult patients with ultrarefractory epilepsy following brain injury or with Lennox-Gastaut syndrome, who had not achieved sustained seizure remission during past treatment with at least seven lifetime AEDs. FINDINGS: The adjunctive use of Madopar was associated with a reduction or remission of tonic-clonic seizures in two patients. However, Madopar seemed to have aggravated absence seizures in the patient with Lennox-Gastaut syndrome. INTERPRETATION: Although our preliminary observations do not and cannot establish the efficacy or safety of adjunctive Madopar, it may be an option for treatment of ultrarefractory focal seizures in adults if confirmed by randomized controlled trials.

Biperiden for treatment of somnambulism in adolescents and adults with or without epilepsy: clinical observations.

BACKGROUND: Sleepwalking in adolescents and adults may lead to serious injuries and require treatment. Anecdotal treatment recommendations include benzodiazepines (which also work in focal seizures of the frontal lobe that are an important differential diagnosis), imipramine and amitriptyline. METHODS: We assessed in a follow-up study of 4 years (medium, range: 2-7 years) the usefulness of the antiparkinsonian drug biperiden (Akineton©), an acetylcholine antagonist with high affinity for muscarinic M1-type receptors, in four consecutive cases of arousal disorder with sleepwalking and confusional behavior in adolescents and adults with or without epilepsy who did not respond to diazepam, clonazepam or amitriptyline. FINDINGS: The adjunctive use of biperiden was associated with reduction or remission of sleepwalking episodes in four consecutive treatment-refractory cases of arousal disorder with sleepwalking and confusional behavior. In contrast, biperiden showed no effect in a patient with REM behavioral disorder. INTERPRETATION: Although our observations do not and cannot establish the efficacy or safety of biperiden, it may be useful to consider biperiden for treatment of sleepwalking, if needed. A putative cholinergic mechanism of arousal disorders, including sleepwalking, provides a reasonable hypothesis why the anticholinergic agent biperiden might work. Evidence for efficacy and safety from randomized controlled trials is needed to confirm our preliminary observations.

Long-term efficacy and safety of eslicarbazepine acetate: results of a 1-year open-label extension study in partial-onset seizures in adults with epilepsy.

PURPOSE: To evaluate the long-term efficacy and safety of once daily eslicarbazepine acetate (ESL) as adjunctive therapy for partial-onset seizures in adults with epilepsy. METHODS: One-year open-label treatment extension with ESL in patients who completed a placebo-controlled pivotal study (Epilepsia 2009; 50: 454-463). Starting dose was 800 mg once daily, for 4 weeks; thereafter, dose could be titrated up or down. Doses of concomitant antiepileptic drugs were to be kept stable. RESULTS: Overall, 314 patients were enrolled. The intent-to-treat population consisted of 312 patients, and 239 (76.6%) completed 1 year of treatment. ESL median dose was 800 mg once daily. Compared to baseline, median seizure frequency decreased by 39% during the first 4 weeks and between 48% and 56% thereafter. The responder rate (≥50% seizure reduction) was 41% during weeks 1-4 and, thereafter ranged between 48% and 53%. The proportion of seizure-free patients per 12-week interval ranged between 8.7% and 12.5%. Quality of life, as measured by the Quality of Life in Epilepsy Inventory-31 (QOLIE-31), and depressive symptoms, as measured by the Montgomery Asberg Depression Rating Scale (MADRS), improved significantly compared to baseline. Treatment-emergent adverse events (TEAEs) were reported by 51% of patients. The most frequent TEAEs were headache (10%), dizziness (10%), diplopia (5%), and nasopharyngitis (5%). TEAEs were mostly (97%) of mild to moderate intensity. Eleven patients (3.5%) discontinued due to TEAEs. There were no results of laboratory tests raising safety concerns. DISCUSSION: Sustained therapeutic effect, favorable tolerability and safety, and an improvement in quality of life and depressive symptoms were observed during long-term add-on treatment of partial-onset seizures in adults with once daily ESL.

Dream recall after night awakenings from tonic/phasic REM sleep.

Eleven healthy subjects, 9 females and 2 males aged 21-23, were submitted to all night polygraphic recording and awaken in REM (Rapid Eye Movements) sleep, randomly upon tonic or phasic REM. Immediately upon awakening subjects were asked about possible dreaming according to the standardized questionnaire. Seventy-seven dreams, i.e. 79% of all 97 REM awakenings, were reported and analyzed. There were no significant differences in reported frequency of dreamings after awakening, mood and dream content due to phasic/tonic REM sleep. Dreams from phasic REM were a bit more colorful. Predictor of morning remembering of dreams was meaninglessness, not meaningfulness of dreams, and, in lesser extent, good mood, colorfulness, dreams with words and phasic REM sleep.

[Epilepsy--an ongoing challenge]. / Epilepsija--izazov koji traje.

Epilepsy is a sequel of depolarizing neuronal event with recurrent seizures. Neuronal membrane disorder is the main cause of epileptogenesis. The epileptic process is initiated and progressing due to the membrane inability to maintain balanced changing of the electrochemical gradient, which is physiologically necessary for intracerebral signal transfer. Membrane ion channels are deranged, which may be congenital or acquired. To date, only a few specific genetically caused ion channel aberrations in some less common epileptic syndromes have been identified, however, the main pathophysiologic sequence of events at the cellular level remains obscure. Synaptic dysregulation of epileptic neuronal groups with unbalanced inter-relationship of excitatory and inhibitory complements within the epileptic focus has been only partly elucidated. Therefore, the treatment of epilepsy remains fortuitous to a great extent because idopathic epileptogenesis is stochastically unpredictable. We do not yet know why, how and when the epileptic process begins, and vice versa, why the process may occasionally be completely silent in a continuously overstrained interaction system. What link in the excitation neuronal system is weakest: membrane instability, neurotransmitter incoordination, or something else? Yet, in two thirds of the individuals prone to epilepsy, monotherapy with so-called channel antiepileptics with selective action on membrane ion exchange and/or antiepileptics with neurotransmitter modulation will stop the manifestation of epilepsy but not the longterm proneness to epileptogenesis. In the remaining one third of sufferers the epilepsy is refractory to any therapeutic attempts. Therefore, antiepileptic treatment is a highly complex, individualized procedure in which only the observational predictors have been positively defined to date, i.e. clinical manifestation and electroencephalography specificity. They make the basis for balanced evaluation of the real extent of action of the antiepileptics available.