Pathomechanism of nocturnal paroxysmal dystonia in autosomal dominant sleep-related hypermotor epilepsy with S284L-mutant α4 subunit of nicotinic ACh receptor.

To study the pathomechanism and pathophysiology of nocturnal paroxysmal dystonia of autosomal dominant sleep-related hypermotor epilepsy (ADSHE), this study determined functional abnormalities in thalamic hyperdirect pathway from reticular thalamic nucleus (RTN), motor thalamic nuclei (MoTN), subthalamic nucleus (STN) to substantia nigra pars reticulata (SNr) of transgenic rats (S286L-TG) bearing S286 L missense mutation of rat Chrna4 gene, which corresponds to the S284 L mutation in the human CHRNA4 gene. The activation of α4ß2-nAChR in the RTN increased GABA release in MoTN resulting in reduced glutamatergic transmission in thalamic hyperdirect pathway of wild-type. Contrary to wild-type, activation of S286L-mutant α4ß2-nAChR (loss-of-function) in the RTN relatively enhanced glutamatergic transmission in thalamic hyperdirect pathway of S286L-TG via impaired GABAergic inhibition in intra-thalamic (RTN-MoTN) pathway. These functional abnormalities in glutamatergic transmission in hyperdirect pathway contribute to the pathomechanism of electrophysiologically negative nocturnal paroxysmal dystonia of S286L-TG. Therapeutic-relevant concentration of zonisamide (ZNS) inhibited the glutamatergic transmission in the hyperdirect pathway via activation of group II metabotropic glutamate receptor (II-mGluR) in MoTN and STN. The present results suggest that S286L-mutant α4ß2-nAChR induces GABAergic disinhibition in intra-thalamic (RTN-MoTN) pathway and hyperactivation of glutamatergic transmission in thalamic hyperdirect pathway (MoTN-STN-SNr), possibly contributing to the pathomechanism of nocturnal paroxysmal dystonia of ADSHE patients with S284L mutant CHRNA4. Inhibition of glutamatergic transmission in thalamic hyperdirect pathway induced by ZNS via activation of II-mGluR may be involved, at least partially, in ZNS-sensitive nocturnal paroxysmal dystonia of ADSHE patients with S284L mutation.

Nocturnal motor events in epilepsy: Is there a defined physiological network?

OBJECTIVE: Paroxysmal nocturnal movements in epilepsy are a recognised phenomenon, however, the mechanisms that produce them and the effect of the underlying epilepsy still remains elusive. In this study, 10 patients were studied to define the cerebral networks corresponding to these movements and explore how epileptiform activity modulated them. METHODS: We compared the change in power of the 25-250 Hz frequency band using event-related synchronization of all stereo-EEG electrodes implanted, during a baseline segment, during nocturnal movements and seizures. RESULTS: The underlying network activated during these paroxysmal movements comprised the insula, anterior cingulate, premotor areas and orbitofrontal regions. Three groups emerged, (1) complete overlap, (2) no overlap and (3) partial overlap of ERS changes of the epileptogenic zone within the proposed network and correlation of semiology between nocturnal movements and seizures. CONCLUSION: We conclude that nocturnal movements are due to a complex interplay within this physiological network of defined anatomical regions. Epileptic activity had significant impact on nocturnal movements but was not required for generation. SIGNIFICANCE: Where the semiology of the first clinical sign of a seizure consistently matches a patient's nocturnal movements, we suggest that the underlying epileptogenic zone is potentially located within this defined network.

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.

Discinesias paroxísticas / Paroxysmal dystonia

RESUMEN Existen enfermedades y condiciones que se presentan con movimientos involuntarios hipercinéticos de aparición súbita y remisión espontanea (episódicas). Dichas condiciones generan dificultades diagnósticas ya que por su carácter intermitente, en ocasiones no pueden ser evaluadas por el clínico.

SUMMARY During the last years, several drugs has been tried to try to diminish the impact of this condition and improve quality of life the people who suffer from dystonia. Oral therapy alone or in combination generates only partial symptom relief and most of the cases end up requiring other more invasive therapies.

Diferente evolución de la fibrilación auricular tras el primer episodio documentado / Different evolution of atrial fibrillation after the first documented episode

No disponible

Nocturnal paroxysmal dystonia - case report.

Nocturnal paroxysmal dystonia describes a syndrome consisting of recurrent motor episodes of dystonic-dyskinetic features arising from non-rapid eye movement (NREM) sleep. In the article, the authors present female case of nocturnal paroxysmal dystonia. The patient has had attacks since her childhood and was eventually diagnosed at the age of 48. Therapy with carbamazepine considerably reduced the frequency and entent of seizures. The present case evidences that nocturnal paroxysmal dystonia still is a diagnostic challenge for clinicians. Especially, we emphasize the importance of polysomnography in the verification of the diagnosis.

Trastornos paroxísticos no epilépticos durante el sueño / Non-epileptic paroxysmal sleep disorders

Los trastornos paroxísticos no epilépticos durante el sueño son un gran reto para el clínico. Por ello, es importante conocer las diferentes manifestaciones clínicas que permitan llevar a cabo un diagnóstico diferencial adecuado, ya que las alteraciones, sobre todo motoras en el sueño, son parte de estos trastornos. En el presente trabajo se describen las fases del sueño normal y sus características electroencefalográficas, así como datos básicos de la polisomnografía. Las confusiones, sobre todo con la epilepsia nocturna del lóbulo frontal, son frecuentes y provocan que se administren fármacos innecesarios, así como una carga emocional en los padres o cuidadores del paciente, que resulta del diagnóstico de epilepsia. Se enuncian las posibles causas de los errores de diagnóstico (AU)

Non-epileptic paroxysmal disorders during sleep are a great challenge for the clinician. It is important to know the various clinical manifestations for appropriate differential diagnosis, since alterations in sleep, mostly motor, are part of these disorders. Our paper describes the normal sleep stages and electroencephalographic characteristics and polysomnography basic data. The confusions especially with nocturnal frontal lobe epilepsy are frequent and cause unnecessary drugs administered, the emotional burden of the parents or caretakers, which is the diagnosis of epilepsy. We discuss the possible causes of diagnostic errors (AU)

[Non-epileptic paroxysmal sleep disorders]. / Trastornos paroxísticos no epilépticos durante el sueño.

Non-epileptic paroxysmal disorders during sleep are a great challenge for the clinician. It is important to know the various clinical manifestations for appropriate differential diagnosis, since alterations in sleep, mostly motor, are part of these disorders. Our paper describes the normal sleep stages and electroencephalographic characteristics and polysomnography basic data. The confusions especially with nocturnal frontal lobe epilepsy are frequent and cause unnecessary drugs administered, the emotional burden of the parents or caretakers, which is the diagnosis of epilepsy. We discuss the possible causes of diagnostic errors.

TITLE: Trastornos paroxisticos no epilepticos durante el sueño.Los trastornos paroxisticos no epilepticos durante el sueño son un gran reto para el clinico. Por ello, es importante conocer las diferentes manifestaciones clinicas que permitan llevar a cabo un diagnostico diferencial adecuado, ya que las alteraciones, sobre todo motoras en el sueño, son parte de estos trastornos. En el presente trabajo se describen las fases del sueño normal y sus caracteristicas electroencefalograficas, asi como datos basicos de la polisomnografia. Las confusiones, sobre todo con la epilepsia nocturna del lobulo frontal, son frecuentes y provocan que se administren farmacos innecesarios, asi como una carga emocional en los padres o cuidadores del paciente, que resulta del diagnostico de epilepsia. Se enuncian las posibles causas de los errores de diagnostico.

Effects of antiepileptic treatment on sleep and seizures in nocturnal frontal lobe epilepsy.

OBJECTIVE: To study the effects of antiepileptic treatment on sleep parameters and video-polysomnography (VPSG) seizures in nocturnal frontal lobe epilepsy (NFLE). METHODS: Twenty patients with a clinical and VPSG diagnosis of NFLE (baseline polysomnography [PSG]) underwent a clinical follow-up and performed a second VPSG after effective antiepileptic treatment lasting for at least 6 months. Conventional sleep measures, cyclic alternating pattern (CAP) parameters, and objective VPSG seizures were assessed in NFLE patients before and after treatment and were compared with the results of 20 age- and gender-matched control subjects. RESULTS: Antiepileptic treatment determined a partial reduction of objective VPSG seizures of approximately 25% compared to baseline condition. Alterations of most conventional sleep measures recovered normal values, but nonrapid eye movement (NREM) sleep instability remained pathologically enhanced (CAP rate, +26% compared to controls) and was associated with persistence of daytime sleepiness. CONCLUSIONS: Residual epileptic events and high levels of unstable NREM sleep can define a sort of objective resistance of both seizures and disturbed arousal system to the therapeutic purpose of the antiepileptic drugs in NFLE. This finding could determine the need for new therapeutic options in this particular form of epilepsy.

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.

Del inicio de una epilepsia parcial continua al diagnóstico y tratamiento del síndrome de Rasmussen / From the beginning of a continuous partial epilepsy to the diagnosis and treatment of Rasmussen's syndrome

La epilepsia parcial continua es una forma de estatus epiléptico parcial, que se caracteriza por la presencia de mioclonías repetidas que afectan a un grupo muscular. Su origen es cortical y pueden prolongarse durante horas, días, semanas y excepcionalmente años. Dentro de estas formas de epilepsia podemos diferenciar 2 grupos: el primer grupo o síndrome de Kojewnikow clásico, comprende a niños con una lesión conocida en la región rolándica (cuya etiología es también conocida) y existe un daño neurológico estable (salvo si la lesión aumenta, como por ejemplo, los tumores). Consiste en la presencia de crisis parciales motoras, a veces seguidas por períodos de mioclonías bien localizadas. El segundo grupo o síndrome de Rasmussen se caracteriza por inicio de crisis en pacientes previamente sanos, comenzando con crisis parciales motoras a las cuales rápidamente se asocian mioclonías que pueden afectar distintas zonas corporales. La evolución es progresiva, con deterioro neurológico. Describimos el caso de un niño de 7 años de edad estudiado por crisis convulsivas parciales y degeneración progresiva de funciones superiores. Se le practican estudios de imagen, neurofisiológicos y pruebas de laboratorio, siendo diagnosticado de síndrome de Rasmussen. Finalmente, se le realiza una hemisferectomía paliativa, confirmándose el diagnóstico de encefalitis de Rasmussen mediante biopsia(AU)

Continuous partial epilepsy is a form of partial status epilepticus, which is characterized by the presence of repeated myoclonus affecting a muscle group. Its origin is cortical and it can last for hours, days, weeks and exceptionally, years. Within these forms of epilepsy we can distinguish two groups: the first group or Kojewnikow classic syndrome includes children with a known lesion in the rolandic region (the etiology is also known) and there is a stable neurological damage (unless the injury increases, e.g., tumors). This disease is characterized by the presence of motor partial seizures, sometimes they are followed by periods of well-localized myoclonus. The second group or Rasmussen syndrome is characterized by onset of seizures in previously healthy patients, starting with partial motor seizures, that later can be combined with myoclonus that affect different areas of the body. It is a progressive disease that leads to neurological damage. A case is presented of a 7-year-old patient investigated due to having partial seizures and progressive neurological degeneration. After performing imaging studies, neuropsychological studies, and laboratory tests, he was diagnosed with Rasmussen's syndrome. Finally, a palliative hemispherectomy was performed and the diagnosis was confirmed by a biopsy(AU)

Differential diagnoses of nocturnal fear and movement paroxysm: a case report.

Recurrent nocturnal behavioural and movement paroxysms are a diagnostic challenge for the clinical pediatrician. We report on an adolescent girl who presents recurrent stereotypical nightmare-like episodes occurring during non-REM sleep stages 1-2 (N1 and N2). We discuss the differential diagnoses between epileptic and nonepileptic events and between nocturnal frontal and temporal seizures. The pathophysiological and unusual electroencephalographical features are discussed with respect to clinical features and results of interictal FDG-PET. Conclusion In case of stereotypical nightmare-like episodes in children or adolescents, an epileptic origin has to be ruled out before a parasomnia is diagnosed. In addition, a normal awake EEG or interictal sleep EEG in the diagnostic workup may not exclude an epileptic disorder. In case of nightly stereotypic motor or affective events, an epileptic disorder should be discussed.

Insular-opercular seizures manifesting with sleep-related paroxysmal motor behaviors: a stereo-EEG study.

PURPOSE: Sleep-related complex motor seizures are a common feature of nocturnal frontal lobe epilepsy. Nevertheless, recent studies also suggest that sleep-related hypermotor seizures can originate in the insula. The present study describes the electroclinical features of eight drug-resistant epileptic patients with insular-opercular seizures manifesting with nocturnal complex motor seizures. METHODS: Patients underwent a comprehensive presurgical evaluation, which included history, interictal electroencephalography (EEG), scalp video-EEG monitoring, high-resolution magnetic resonance imaging (MRI), and intracerebral recording by stereo-EEG. KEY FINDINGS: Almost all patients reported an initial sensation consisting of viscerosensitive or somatosensory symptoms. Ictal clinical signs were represented by tonic-dystonic asymmetric posturing and/or hyperkinetic automatisms, including bimanual/bipedal activity and ballistic movements. Some patients exhibited dysarthric speech, hypersalivation, and apnea. Interictal and ictal EEG provided lateralizing information in the majority of patients. In three patients, MRI showed a focal anatomical abnormality in the insular-opercular region. Stereo-EEG ictal recordings demonstrated that the epileptic discharge involved simultaneously the insular cortex and the opercular region. Complex motor manifestations appeared when the ictal discharge showed an extrainsular spreading to frontomesial regions (cingulum, superior frontal gyrus, and supplementary motor area) and/or to internal and neocortical temporal lobe structures. Six patients received an insular-opercular cortical resection; three of them are seizure free (minimum follow-up 24 months) and in one a marked reduction in seizure frequency was obtained. Two patients have been operated on recently. Histology revealed a focal cortical dysplasia in three patients. One patient excluded from surgery died for sudden unexpected death in epilepsy during sleep. SIGNIFICANCE: Our data strengthen the concept that sleep-related complex motor attacks can originate in the insula, and provide useful electroclinical information to differentiate this localization from those with similar clinical characteristics. Furthermore, this study indicates that in these drug-resistant patients, surgical treatment represents a highly effective treatment option.

[Ion channel dysfunction in pathogenesis of idiopathic epilepsies]. / Zaburzenia czynnosci kanalów jonowych w patogenezie padaczek idiopatycznych.

Despite advances in diagnostics, the cause of epilepsy has still not been unequivocally determined in 60-65% of patients. In this group of patients, genetic factors probably play the main role. It is thought that genetic predisposition is responsible for the occurrence of so-called "idiopathic" forms of epilepsy in about 40% of patients. The genetic basis of epilepsy has been substantiated by numerous examples of familial forms of epileptic syndromes. Among these, autosomal dominant nocturnal frontal lobe epilepsy and juvenile myoclonic epilepsy can be mentioned. Mutations in the neuronal nicotinic acetylcholine receptor subunit genes are responsible for both these epilepsies. Recent advances in molecular genetics have provided the means for better understanding of human epileptogenesis at a molecular level, which facilitates clinical diagnosis and provides a more rational basis for therapy and prevention of this form of epilepsy.