A clinical efficacy experience of Lacosamide on sleep quality in patients with Nocturnal Frontal Lobe Epilepsy (NFLE).

BACKGROUND: Nocturnal frontal lobe epilepsy (NFLE) is a focal epilepsy with seizures arising mainly during sleep and characterized by complex motor behavior or sustained dystonic posturing. First described in 1981, it was considered a motor disorder of sleep and was indicated as nocturnal paroxysmal dystonia (NPD). The debated on epileptic origin of this condition was demonstrated in 1990 and the term NFLE was introduced. Since then it has been demonstrated that the heterogeneous aspects of morpheic seizures were responsive to antiepileptic drugs (AED's) with sodium blocking action mechanism, especially the carbamazepine (CBZ). Aim of Work and Methods: We report a clinical experience of NFLE patients associated with sleep disorders treated with Lacosamide, AED's with a novel mechanism of action. In vitro electrophysiology studies have shown that lacosamide selectively boosts the slow inactivation of the sodium-voltage-dependent channels, resulting in a stabilization of the hypersensitive neuronal membranes. RESULTS AND CONCLUSION: On the treated patients we observed a positive clinical response to lacosamide therapy without significant side effects. In particular, the effective clinical response to the pharmacological treatment was obtained at a dose of 200 mg/day.

When restless legs syndrome turns malignant.

Usually symptoms of restless legs syndrome (RLS) respond well to treatment with dopaminergic drugs, opiates, or anticonvulsant medications. Yet sometimes symptoms can be severe and become refractory, even to high-dose combination therapy. Here we present two cases of familial RLS with rigorous and unusual motor and sensory symptoms in the form of episodes of myoclonic hyperkinesias and painful sensations in addition to more characteristic features of RLS. Stepwise reduction of all RLS-and antidepressant medication down to opiate monotherapy-and subsequent opiate rotation led to an improvement of symptoms. Yet in both cases, reintroduction of low-dose dopaminergic drugs was necessary to achieve satisfactory treatment effect. We have termed this form of RLS refractory to multiple combinations of all classes of commonly used drugs malignant RLS. Therapeutically simplification and reduction of the drug scheme and opiate rotation should be considered in malignant RLS.

Oxcarbazepine in children with nocturnal frontal-lobe epilepsy.

Nocturnal frontal-lobe epilepsy is characterized by paroxysmal arousals, motor seizures with dystonic or hyperkinetic features, and episodic nocturnal wanderings. Carbamazepine is effective for seizure control in some of these patients, but seizures may be refractory to multiple antiepileptic drugs. We report on eight children between ages 4-16 years with nocturnal frontal-lobe epilepsy who had a dramatic response to oxcarbazepine at standard recommended doses, some of whom were refractory to previous antiepileptic medications. Brain magnetic resonance imaging, routine electroencephalogram, and prolonged, continuous video-electroencephalogram telemetry were performed in all children. Nocturnal frontal-lobe epilepsy was diagnosed by demonstrating ictal electroencephalogram changes originating from the frontal lobes. The children were followed for response of seizures to oxcarbazepine, side effects, and routine blood tests, including serum 10-monohydroxide derivative levels. The mean oxcarbazepine dose was 30.4 mg/kg/day +/- 11.7 (mean +/- SD); the mean 10-monohydroxide level was 23.1 microg/mL +/- 8.6 (mean +/- SD). Seizures improved within 4 days of oxcarbazepine initiation in six children, whereas two children required higher doses. Their follow-up has ranged from 12 to 24 months, without seizure recurrence or serious side effects. Our patients demonstrate the efficacy of oxcarbazepine for nocturnal hyperkinetic seizures in children with nocturnal frontal-lobe epilepsy.

Non-REM sleep instability in patients with major depressive disorder: subjective improvement and improvement of non-REM sleep instability with treatment (Agomelatine).

OBJECTIVE: To assess the importance of non-rapid eye movement (NREM) sleep disturbance in major depressive disorder (MDD) patients using cyclic alternating pattern (CAP) analysis, and to determine the usefulness of CAP analysis in evaluating treatment effect. METHODS: Baseline sleep-staging data and CAP analysis of NREM sleep was compared in 15 MDD patients (Hamilton depression scale score>20) and normal controls. Longitudinal evaluation of sleep changes using similar analysis during a treatment trial was also performed. ANALYSIS: A single-blinded researcher scored and analyzed the sleep of MDD and age-matched normal controls at baseline and during a treatment trial using the international scoring system as well as CAP analysis. RESULTS: MDD patients had evidence of disturbed sleep with both analyses, but CAP analysis revealed more important changes in NREM sleep of MDD patients at baseline than did conventional sleep staging. There was a significant decrease in CAP rate, time, and cycle and disturbances of phase A subtype of CAP. NREM abnormalities, observed by CAP analysis, during the treatment trial paralleled subjective responses. Analysis of subtype A phase of CAP demonstrated better sleep improvement. CONCLUSION: CAP analysis demonstrated the presence of more important NREM sleep disturbances in MDD patients than did conventional sleep staging, suggesting the involvement of slow wave sleep (SWS) in the sleep impairment of MDD patients. Improvement of NREM sleep paralleled subjective mood improvement and preceded REM sleep improvement. CAP analysis allowed objective investigation of the effect of treatment on sleep disturbances.

Botulinum-A toxin in the treatment of painful post-stroke nocturnal paroxysmal dystonia triggered by periodic limb movements of sleep: case report / Toxina botulínica tipo A no tratamento da distonia paroxística noturna dolorosa pós-isquemia cerebral desencadeada por movimentos periódicos do sono: relato de caso

INTRODUCTION: Sleep disorders presenting involuntary movements may be very annoying to patients, apart from their negative influence on sleep. OBJECTIVE: To report the use of botulinum type-A toxin (BoNT-A) to manage the case of a patient whose sleep was severely disrupted by episodes of dystonic posturing of the right lower limb triggered by periodic limb movements of sleep (PLMS). METHOD: A 79-year-old woman with mild post-stroke right hemiparesis presented with recurrent painful episodes of dystonia of the right lower limb, which disrupted her sleep. The dystonic episodes could also be voluntarily triggered by extension of the right hallux. Polysomnography confirmed that the dystonic episodes were triggered by PLMS. Twenty units of BoNT-A (20U/500U vial) were injected into her right extensor hallucis longus. RESULTS: Shortly after BoNT-A was injected, the dystonic symptoms abated, and the patient achieved better sleep efficiency. CONCLUSION: The PLMS-related involuntary extension of the hallux was probably triggering the nocturnal post-stroke lower limb dystonic paroxysms. BoNT-A injection into the right extensor hallucis longus was effective in managing this condition and thus resolved the associated disruption of sleep.

INTRODUÇÃO: Desordens do sono apresentando movimentos involuntários podem ser bastante perturbadoras aos pacientes, além de sua influência negativa no sono. OBJETIVO: Descrever o uso da toxina botulínica tipo-A (BoNT-A) no manejo do caso de um paciente cujo sono estava gravemente fragmentado por episódios de distonia do membro inferior direito, desencadeados por movimentos periódicos do sono (MPS). MÉTODO: Uma paciente com 79 anos portadora de hemiparesia direita leve seqüelar a isquemia cerebral (AVCI) procurou-nos por episódios dolorosos recorrentes de distonia noturna de seu membro inferior direito, os quais fragmentavam seu sono. Os episódios de distonia também podiam ser desencadeados voluntariamente, por extensão do hálux direito. Uma polisonografia confirmou que os episódios distônicos eram desencadeados pelos MPS. Vinte unidades de BoNT-A (20 U/frasco de 500 U) foram injetadas no seu extensor longo do hálux. RESULTADOS: Alguns dias após a injeção de BoNT-A os sintomas distônicos regrediram, e o sono da paciente tornou-se eficiente. CONCLUSÃO: As extensões involuntárias do hálux relacionadas aos movimentos periódicos do sono estavam provavelmente desencadeando os paroxismos distônicos noturnos pós-AVCI. A injeção de BoNT-A no extensor longo do hálux foi eficaz no manejo desta condição, resolvedo assim a fragmentação do sono.

Botulinum-A toxin in the treatment of painful post-stroke nocturnal paroxysmal dystonia triggered by periodic limb movements of sleep: case report.

INTRODUCTION: Sleep disorders presenting involuntary movements may be very annoying to patients, apart from their negative influence on sleep. OBJECTIVE: To report the use of botulinum type-A toxin (BoNT-A) to manage the case of a patient whose sleep was severely disrupted by episodes of dystonic posturing of the right lower limb triggered by periodic limb movements of sleep (PLMS). METHOD: A 79-year-old woman with mild post-stroke right hemiparesis presented with recurrent painful episodes of dystonia of the right lower limb, which disrupted her sleep. The dystonic episodes could also be voluntarily triggered by extension of the right hallux. Polysomnography confirmed that the dystonic episodes were triggered by PLMS. Twenty units of BoNT-A (20U/500U vial) were injected into her right extensor hallucis longus. RESULTS: Shortly after BoNT-A was injected, the dystonic symptoms abated, and the patient achieved better sleep efficiency. CONCLUSION: The PLMS-related involuntary extension of the hallux was probably triggering the nocturnal post-stroke lower limb dystonic paroxysms. BoNT-A injection into the right extensor hallucis longus was effective in managing this condition and thus resolved the associated disruption of sleep.

Treatment of periodic leg movements with a dopaminergic agonist in subjects with total spinal cord lesions.

OBJECTIVE: To investigate the effect of L-dopa on the PLM/h index of spinal cord injured subjects. SETTING: São Paulo, Brazil. METHODS: Thirteen male volunteers with spinal cord section between T7 - T12, and mean age of 31.6+/-8.3 years participated in the study. L-dopa or placebo were administered for 30 days, 1 h before the volunteers went to sleep, in a double blind, crossover design. Polysomnographic recordings were performed on ten occasions: Phase 1: Basal night, following an adaptation night at the sleep laboratory; phase 2: after 1, 7, 21 and 30 days of L-dopa administration; phase 3: first night of L-dopa or placebo withdrawal; phase IV: 1, 7, 21 and 30 days after placebo ingestion. RESULTS: The index of PLM/h on the first night of L-dopa or placebo withdrawal (phase III) was lower than on both the basal night and the first night of L-dopa treatment. At the time of polysomnographic analysis, volunteers were divided into two groups: index of PLM/h below five and those whose index was above five. Comparison between L-dopa and placebo treatments revealed that only those volunteers with an index above five revealed a reduction in PLM in L-dopa. CONCLUSION: These results indicate that despite the spinal cord lesions, L-dopa treatment is capable of minimizing PLM during sleep.