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1.
Am J Med Genet A ; 191(9): 2428-2432, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37462082

RESUMEN

Mitogen-activated protein kinase 8-interacting protein 3 gene (MAPK8IP3) encodes the c-Jun-amino-terminal kinase-interacting protein 3 (JIP3) and is involved in retrograde axonal transport. Heterozygous de novo pathogenic variants in MAPK8IP3 result in a neurodevelopmental disorder with or without brain abnormalities and possible axonal peripheral neuropathy. Whole-exome sequencing was performed on an individual presenting with severe congenital muscle hypotonia of neuronal origin mimicking lethal spinal muscular atrophy. Compound heterozygous rare variants (a splice and a missense) were detected in MAPK8IP3, inherited from the healthy parents. Western blot analysis in a muscle biopsy sample showed a more than 60% decrease in JIP3 expression. Here, we suggest a novel autosomal recessive phenotype of a lower motor neuron disease caused by JIP3 deficiency.


Asunto(s)
Atrofia Muscular Espinal , Enfermedades Musculares , Anomalías Musculoesqueléticas , Humanos , Hipotonía Muscular/diagnóstico , Hipotonía Muscular/genética , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/patología , Fenotipo , Mutación , Proteínas del Tejido Nervioso/genética , Proteínas Adaptadoras Transductoras de Señales/genética
2.
Ideggyogy Sz ; 66(3-4): 107-14, 2013 Mar 30.
Artículo en Húngaro | MEDLINE | ID: mdl-23750426

RESUMEN

INTRODUCTION: The only Hungarian video EEG laboratory where children of ages 0-18 can be continuously monitored for several days was opened 1 June 2001 at Department of Neurology of Bethesda Children's Hospital. OBJECTIVES: Summarizing our 10 years of experience with the video EEG monitoring (VEM) of children and defining the place of VEM in the treatment of childhood epilepsy in Hungary. PATIENTS AND METHODS: We have processed data from 597 monitoring sessions on 541 patients between June 1, 2001 and 31 May, 2011 based on our database and the detailed summaries of the procedures. RESULTS: 509 patients were under the age of 18. The average length of the sessions was 3.1 days. We have observed habitual episodes or episodes in question in 477 (80%) sessions. 241 (40%) sessions were requested with an epilepsy surgery indication, and 74 patients had 84 operations. 356 (60%) were requested with a differential diagnosis indication, and 191 (53%) cases of epilepsy were diagnosed. We most commonly diagnosed symptomatic generalized epilepsy (57 cases). In 165 sessions the episode in question was not diagnosed as epilepsy. Among the paroxysmal episodes we have identified events of psychogenic origin, movement disorders, sleep disorders and behavioral disorders. Only 3% of the differential diagnosis procedures brought no additional clinical information. DISCUSSION: The diagnostic efficiency in our VEM laboratory is in accordance with the data found in the literature. Besides epilepsy surgery VEM is recommended if suspected epileptic episodes occur and interictal epileptiform signs are not present or are not in accordance with the symptoms, if there is no explanation for therapy resistance and if paroxysmal episodes of non-epileptic origin are suspected but they cannot be identified based on the anamnesis. VEM is also helpful in diagnosing subtle seizures. The procedure has numerous additional benefits in patient care and in training the parents and hospital staff.


Asunto(s)
Electroencefalografía/métodos , Epilepsia/diagnóstico , Epilepsia/fisiopatología , Grabación en Video , Adolescente , Distribución por Edad , Niño , Preescolar , Diagnóstico Diferencial , Epilepsia/epidemiología , Epilepsia/cirugía , Femenino , Humanos , Hungría/epidemiología , Lactante , Masculino , Monitoreo Fisiológico , Estudios Retrospectivos , Adulto Joven
3.
Ideggyogy Sz ; 66(1-2): 53-7, 2013 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-23607230

RESUMEN

BACKGROUNDS AND PURPOSE: To correlate the extent of the leptomeningeal angiomatosis with clinical features in Sturge-Weber syndrome (SWS). METHODS: The study group consisted of 86 consecutive patients aged two months to 56 (mean 7.9 +/- 10.3) years with SWS and epilepsy. Clinical and MRI data were analyzed. RESULTS: Based on the extent of leptomeningeal angiomatosis, patients were divided into two subgroups: 43 patients had hemispheric angiomatosis and atrophy, whereas, another 43 had focal involvement. Nine of the 43 hemispherial patients (10%) showed bilateral involvement: all of these bilateral cases demonstrated dominance in a single side with hemispheric leptomeningeal angiomatosis and contralateral focal extension. Hemispheric and focal subgroups were clinically different. Patients with hemispheric SWS were younger at the age of epilepsy onset (p < 0.001) and age at MRI examination (p < 0.05). Neither gender, lateralization, duration of epilepsy, appearance of secondarily generalized seizures, nor seizure frequency revealed a significant difference between subgroups. CONCLUSION: Bilateral involvement is frequent and occurs in cases with a hemisperic involvement on one side. The age of epilepsy onset is related to the extent of leptomeningeal angiomatosis. Patients with hemispheric form of SWS presented with earlier age of seizure onset. Focal pial angiomatoses do not tend to progress (a longer duration is not associated with more frequent hemispheric involvement). Other variables including seizure frequency and secondary generalized tonic-clonic seizures are not associated with the extent of angiomatosis.


Asunto(s)
Angiomatosis/diagnóstico , Encéfalo/patología , Imagen por Resonancia Magnética , Convulsiones/etiología , Síndrome de Sturge-Weber/diagnóstico , Adolescente , Adulto , Edad de Inicio , Atrofia , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Radiografía , Síndrome de Sturge-Weber/diagnóstico por imagen , Síndrome de Sturge-Weber/patología , Síndrome de Sturge-Weber/fisiopatología
4.
J Neurosci ; 31(24): 8770-9, 2011 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-21677161

RESUMEN

Cortical electrical activity during nonrapid eye movement (non-REM) sleep is dominated by slow-wave activity (SWA). At larger spatial scales (∼2-30 cm), investigated by scalp EEG recordings, SWA has been shown to propagate globally over wide cortical regions as traveling waves, which has been proposed to serve as a temporal framework for neural plasticity. However, whether SWA dynamics at finer spatial scales also reflects the orderly propagation has not previously been investigated in humans. To reveal the local, finer spatial scale (∼1-6 cm) patterns of SWA propagation during non-REM sleep, electrocorticographic (ECoG) recordings were conducted from subdurally implanted electrode grids and a nonlinear correlation technique [mutual information (MI)] was implemented. MI analysis revealed spatial maps of correlations between cortical areas demonstrating SWA propagation directions, speed, and association strength. Highest correlations, indicating significant coupling, were detected during the initial positive-going deflection of slow waves. SWA propagated predominantly between adjacent cortical areas, albeit spatial noncontinuities were also frequently observed. MI analysis further uncovered significant convergence and divergence patterns. Areas receiving the most convergent activity were similar to those with high divergence rate, while reciprocal and circular propagation of SWA was also frequent. We hypothesize that SWA is characterized by distinct attributes depending on the spatial scale observed. At larger spatial scales, the orderly SWA propagation dominates; at the finer scale of the ECoG recordings, non-REM sleep is characterized by complex SWA propagation patterns.


Asunto(s)
Mapeo Encefálico , Ondas Encefálicas/fisiología , Corteza Cerebral/fisiopatología , Epilepsia Parcial Compleja/patología , Sueño/fisiología , Adolescente , Adulto , Electroencefalografía/métodos , Epilepsia Parcial Compleja/fisiopatología , Femenino , Humanos , Masculino , Red Nerviosa/fisiología , Dinámicas no Lineales , Estadísticas no Paramétricas
5.
Eur J Neurosci ; 33(3): 511-20, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21138489

RESUMEN

Sleep-associated memory consolidation is thought to rely on coordinated information transfer between the hippocampus and neocortex brought about during slow wave sleep (SWS) by distinct local field potential oscillations. Specifically, findings in animals have led to the concept that ripples originating from hippocampus combine with spindles to provide a fine-tuned temporal frame for a persistent transfer of memory-related information to the neocortex. The present study focused on characterizing the temporal relationship between parahippocampal ripple activity (80-140 Hz) and spindles recorded from frontal, parietal and parahippocampal cortices in 12 epilepsy patients implanted with parahippocampal foramen ovale electrodes. Overall, parietal and parahippocampal spindles showed closer relationships to parahippocampal ripple activity than frontal spindles, with the latter following parietal and parahippocampal spindles at a variable delay of up to 0.5 s. On a timescale of seconds, ripple activity showed a continuous increase before the peak of parietal and parahippocampal spindles, and decreased thereafter. At a fine timescale of milliseconds, parahippocampal ripple activity was tightly phase-locked to the troughs of these spindles. The demonstration of spindle phase-locked ripple activity in humans is consistent with the idea of a temporally fine-tuned hippocampus-to-neocortex transfer of information taking place during SWS.


Asunto(s)
Hipocampo/fisiología , Memoria/fisiología , Neocórtex/fisiología , Sueño/fisiología , Adulto , Electroencefalografía , Epilepsia/fisiopatología , Humanos , Persona de Mediana Edad
6.
Brain ; 133(9): 2814-29, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20656697

RESUMEN

Brain electrical activity is largely composed of oscillations at characteristic frequencies. These rhythms are hierarchically organized and are thought to perform important pathological and physiological functions. The slow wave is a fundamental cortical rhythm that emerges in deep non-rapid eye movement sleep. In animals, the slow wave modulates delta, theta, spindle, alpha, beta, gamma and ripple oscillations, thus orchestrating brain electrical rhythms in sleep. While slow wave activity can enhance epileptic manifestations, it is also thought to underlie essential restorative processes and facilitate the consolidation of declarative memories. Animal studies show that slow wave activity is composed of rhythmically recurring phases of widespread, increased cortical cellular and synaptic activity, referred to as active- or up-state, followed by cellular and synaptic inactivation, referred to as silent- or down-state. However, its neural mechanisms in humans are poorly understood, since the traditional intracellular techniques used in animals are inappropriate for investigating the cellular and synaptic/transmembrane events in humans. To elucidate the intracortical neuronal mechanisms of slow wave activity in humans, novel, laminar multichannel microelectrodes were chronically implanted into the cortex of patients with drug-resistant focal epilepsy undergoing cortical mapping for seizure focus localization. Intracortical laminar local field potential gradient, multiple-unit and single-unit activities were recorded during slow wave sleep, related to simultaneous electrocorticography, and analysed with current source density and spectral methods. We found that slow wave activity in humans reflects a rhythmic oscillation between widespread cortical activation and silence. Cortical activation was demonstrated as increased wideband (0.3-200 Hz) spectral power including virtually all bands of cortical oscillations, increased multiple- and single-unit activity and powerful inward transmembrane currents, mainly localized to the supragranular layers. Neuronal firing in the up-state was sparse and the average discharge rate of single cells was less than expected from animal studies. Action potentials at up-state onset were synchronized within +/-10 ms across all cortical layers, suggesting that any layer could initiate firing at up-state onset. These findings provide strong direct experimental evidence that slow wave activity in humans is characterized by hyperpolarizing currents associated with suppressed cell firing, alternating with high levels of oscillatory synaptic/transmembrane activity associated with increased cell firing. Our results emphasize the major involvement of supragranular layers in the genesis of slow wave activity.


Asunto(s)
Mapeo Encefálico , Encéfalo/fisiología , Electroencefalografía , Análisis Espectral/métodos , Potenciales de Acción/fisiología , Análisis de Varianza , Animales , Encéfalo/citología , Encéfalo/fisiopatología , Electrofisiología/métodos , Epilepsia/patología , Epilepsia/fisiopatología , Humanos , Neuronas/fisiología , Periodicidad
7.
Ideggyogy Sz ; 64(5-6): 187-92, 2011 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-21688720

RESUMEN

PURPOSE: Zonisamide is licensed in the European Union for adjunctive therapy for partial epilepsy, but its efficacy in generalized epilepsy was less explored. METHODS: This prospective observational study included 47 patients (mean age 29 years, range 3-50) with different resistant generalized epilepsy syndromes: idiopathic generalized syndromes (IGE) 15 patients, (juvenile myoclonic epilepsy four, absence epilepsy four, myoclonic absence two, unclassified IGE five), progressive myoclonic epilepsy type 1 (PME1) four, severe myoclonic epilepsy of infancy (SMEI) three, borderline SMEI three, Lennox-Gastaut syndrome/secondary generalized epileptic encephalopties 23 patients. All patients were followed up for at least six months. The mean dose given was 367 mg/day (range 100-600 mg/day), the patients received at least one and no more than two concomitant AE. Response was defined as more than 50% seizure reduction or seizure freedom. RESULTS: The best effect was achieved in PME one, all the patients were responders. Myoclonic seizures were reduced 80%, none of the patients had generalized tonic clonic (GTC) seizures. In two of the four patients all other antiepileptics were tapered of (including piracetam), so they were GTC seizure and almost myoclonia free on zonisamide only. Responder rates were in GEFS +/- SME 62.5%, in resistant IGE 62.5%, and in epileptic encephalopathies 33.3% patients. Tolerance after initial efficacy developed in six patients. Adverse effects were mild: weight loss, somnolence and confusion were repeatedly reported. Three patients reported cognitive improvement. CONCLUSION: Clinical benefit of a broad spectrum antiepileptic zonisamide extends across seizure types, ages and epilepsy syndromes. The efficacy in PME proved to be excellent.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Epilepsia Generalizada/tratamiento farmacológico , Isoxazoles/uso terapéutico , Adolescente , Adulto , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/efectos adversos , Niño , Preescolar , Confusión/inducido químicamente , Trastornos de Somnolencia Excesiva/inducido químicamente , Resistencia a Medicamentos , Epilepsias Mioclónicas/tratamiento farmacológico , Epilepsia Tipo Ausencia/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Humanos , Lactante , Isoxazoles/administración & dosificación , Isoxazoles/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Espasmos Infantiles/tratamiento farmacológico , Resultado del Tratamiento , Pérdida de Peso , Zonisamida
8.
Epilepsia ; 51(2): 214-20, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19780800

RESUMEN

PURPOSE: Upper extremity automatisms are considered to be an ipsilateral seizure lateralizing sign in temporal lobe epilepsy (TLE). Herein we describe different types of contralateral upper extremity automatisms (CUEAs). METHODS: One hundred ninety-three video-(electroencephalography) EEG recordings of 59 patients were reviewed. Other than two patients who refused surgery, all patients underwent standardized temporal lobectomy with favorable postoperative outcome. Fifty-seven seizures of 21 patients were selected with CUEAs. We evaluated their electroclinical characteristics and their relation to other lateralizing motor symptoms. RESULTS: Two types of CUEAs were observed. Nonmanipulative, proximal upper extremity automatisms were seen unilaterally and contralaterally to the operated side. These automatisms were rhythmic; repetitive; and often occurred with a circulatory component resembling waving, flaunting, circling, or stirring movements. They occurred in 29 seizures (15%) of 11 patients (19%), in most seizures in the first half of the seizure, and never postictally, in various time sequences and combined with dystonic/tonic posturing or limb immobility. Manipulative/distal type of CUEAs occurred in 11 seizures (6%) of 7 patients (12%) on the unexpected contralateral side. These CUEAs were seen in all phases of the seizures, including in the postictal state. DISCUSSION: Nonmanipulative unilateral proximal upper extremity automatism is a reliable lateralizing sign to the contralateral hemisphere in TLE. This sign may be pathophysiologically related to dystonic/tonic posturing. Manipulative distal automatisms have less lateralizing value.


Asunto(s)
Automatismo/diagnóstico , Epilepsia del Lóbulo Temporal/fisiopatología , Lateralidad Funcional/fisiología , Extremidad Superior/fisiopatología , Adolescente , Adulto , Lobectomía Temporal Anterior , Automatismo/clasificación , Automatismo/fisiopatología , Niño , Distonía/fisiopatología , Electroencefalografía/estadística & datos numéricos , Epilepsia del Lóbulo Temporal/diagnóstico , Epilepsia del Lóbulo Temporal/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Grabación en Video
9.
Eur J Paediatr Neurol ; 27: 37-42, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32456992

RESUMEN

INTRODUCTION: Spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by a homozygous deletion of the survival motor neuron (SMN) 1 gene. Nusinersen is an antisense oligonucleotide enhancing the production of the SMN protein. It has received approval by the European Medicines Agency (EMA) in 2017, based on the clinical trials demonstrating the effectiveness of nusinersen in several types of SMA. In Hungary, the first patient received nusinersen treatment in April 2018. Our aim is to summarize our experience regarding the efficacy, safety and tolerability of nusinersen in our patients. METHODS: Data were collected retrospectively in all types of SMA patients (type 1-3) starting treatment with nusinersen in Hungary between April 2018 and December 2019. Motor functions were evaluated at baseline, at the fourth and all following injections. RESULTS: By 31st December 2019, nusinersen therapy was initiated in 54 patients at either of the two Hungarian treatment centres. Mean age of the patients at the start of the treatment was 6.3 years (±5,4 range 0.4-17.9). 13 patients are type 1 (mean 0.78 ± 0.27, range 0.4-1.5 yrs), 21 patients are type 2 (mean 4.5 ± 3.3, range 1.3-12 yrs), 23 patients are type 3 (mean 10.9 ± 5.2, range 2.9-17.9 yrs). Fourteen patients had severe scoliosis, four of them underwent spine stabilizing surgery. During the study period 340 injections were administered without any new safety concerns emerging. The data of 38 patients, who had completed the first six treatments, were included in the final statistical analysis. Motor function has improved in most of the children. By the 307th day visit, on average, a 14.9 (±5,1) point improvement was measured on the CHOP INTEND scale in type 1 patients (p = 0.016). All patients with type 1 SMA who performed the motor evaluation (7/10) have improved by more than four (7-21) points. Regarding type 2 patients, a 7.2 (range -2- 17) point increase from baseline (p < 0.001) on the Hammersmith Functional Motor Scale Expanded (HFMSE) and 4.3 (range: 2-9) point increase (p = 0.031) on the Revised Upper Limb Module (RULM) were found. The distance of the 6 min walk test also increased by 33.9 m on average (range -16 - 106), in type 3 patients. CONCLUSION: According to our results nusinersen has the same safety and tolerability profile as in the clinical trials. In a heterogenic patient population of SMA type 1 and 2, nusinersen showed similar efficacy as seen in the pivotal studies. A clinically and statistically significant improvement of motor functions was also detectable in type 3 patients with heterogeneous age distribution.


Asunto(s)
Actividad Motora/efectos de los fármacos , Atrofia Muscular Espinal/tratamiento farmacológico , Oligonucleótidos/uso terapéutico , Adolescente , Niño , Preescolar , Femenino , Humanos , Hungría , Lactante , Masculino , Recuperación de la Función/efectos de los fármacos , Estudios Retrospectivos , Resultado del Tratamiento
10.
Ideggyogy Sz ; 62(9-10): 319-25, 2009 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-19835273

RESUMEN

OBJECTIVES: To investigate interhemispheric propagation of mesial temporal lobe epilepsy seizures in patients undergoing long-term video-EEG monitoring with combined scalp and foramen ovale electrodes. AIM OF THE STUDY: To reveal possible interhemispheric propagation patterns in mesial temporal lobe epilepsy, to improve presurgical evaluation of temporal epileptic patients. METHODS: Sixty-five seizures from 20 patients were analyzed. We defined two contralateral seizure propagation patterns: Type I for those seizures that spread to the contralateral foramen ovale electrodes earlier than to the contralateral scalp electrodes, and type II for the opposite. PARTICIPANTS: Twenty drug resistant epileptic patients were investigated in frame of their presurgical evaluation. RESULTS: The majority of seizures (80%) were classified as type I. Inter-foramen ovale electrode propagation time was significantly shorter for type I compared to type II seizures. Ninety percent of patients had either type I or type II seizures only. Patients with type I seizures significantly more often had mesiotemporal structural alterations evident on magnetic resonance imaging scans, and became more often seizure-free after surgery compared to patients with type II seizures whose surgical outcome was less favorable or surgery could not be indicated because of independent bilateral ictal seizure-onset. CONCLUSIONS: The two types of contralateral propagation patterns we are describing seem to represent two subtypes of mesial temporal lobe epilepsy with different morphological and prognostic features. The predominance of type I over type II seizures together with shorter propagation times for type I seizures indicate a role of a more direct and dominant interhemispheric pathway in mesial temporal lobe epilepsy.


Asunto(s)
Electroencefalografía , Epilepsia del Lóbulo Temporal/patología , Epilepsia del Lóbulo Temporal/fisiopatología , Imagen por Resonancia Magnética , Adolescente , Adulto , Edad de Inicio , Femenino , Humanos , Masculino , Convulsiones/clasificación , Convulsiones/patología , Convulsiones/fisiopatología , Adulto Joven
12.
Epilepsia ; 49(7): 1174-9, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18479387

RESUMEN

PURPOSE: Incidental paradoxical antiepileptic effect of levetiracetam has been described. The aim of the present study was to identify the epilepsy patients at risk. METHODS: We performed a retrospective analysis in 207 patients treated with levetiracetam. This entailed evaluation of patient notes and patient interviews. A paradoxical effect was defined as an increased seizure frequency or the experience of more severe seizures including generalized tonic-clonic seizures (GTCS) within 1 month after starting levetiracetam (LEV). RESULTS: Thirty patients (14%) experienced a paradoxical effect. Eight of them (4%) developed de novo GTCS. We could not demonstrate any association between the paradoxical effect of levetiracetam and type of epilepsy or the antiepileptic comedication used. However we found that the paradoxical effect developed preferentially (p < 0.001) in mentally retarded patients. CONCLUSION: Because there is an increased risk of worsening epilepsy when starting levetiracetam treatment of mentally retarded epileptic patients, there is a need for caution and close observation during the first weeks of therapy.


Asunto(s)
Anticonvulsivantes/efectos adversos , Epilepsia/tratamiento farmacológico , Epilepsia/epidemiología , Discapacidad Intelectual/epidemiología , Piracetam/análogos & derivados , Adolescente , Adulto , Anciano , Anticonvulsivantes/uso terapéutico , Niño , Trastornos de Somnolencia Excesiva/inducido químicamente , Trastornos de Somnolencia Excesiva/epidemiología , Mareo/inducido químicamente , Mareo/epidemiología , Interacciones Farmacológicas , Femenino , Humanos , Genio Irritable/efectos de los fármacos , Levetiracetam , Masculino , Persona de Mediana Edad , Piracetam/efectos adversos , Piracetam/uso terapéutico , Estudios Retrospectivos , Factores de Riesgo
13.
Epileptic Disord ; 10(2): 156-61, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18539568

RESUMEN

We report on three women and a review of the literature on absence status epilepticus over the age of 50 years. Our aim was to characterize the male-female ratio in this condition. Out of 16 studies on absence status epilepticus over the age of 50, including our cases, a female dominance was found in 15. We found altogether, 104 (71%) females and 42 (29%) males. This gender difference is highly significant (p < 0.00001). We conclude that absence status epilepticus over the age of 50 is predominantly a female disorder.


Asunto(s)
Epilepsia Tipo Ausencia/fisiopatología , Estado Epiléptico/fisiopatología , Factores de Edad , Edad de Inicio , Anticonvulsivantes/uso terapéutico , Electroencefalografía , Epilepsia Tipo Ausencia/epidemiología , Epilepsia Tipo Ausencia/patología , Epilepsia Generalizada/epidemiología , Epilepsia Generalizada/patología , Epilepsia Generalizada/fisiopatología , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Factores Sexuales , Estado Epiléptico/epidemiología , Estado Epiléptico/patología
15.
Br J Pharmacol ; 142(8): 1332-42, 2004 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-15265808

RESUMEN

Serotonin-2 receptor antagonists, like ritanserin, greatly enhance deep slow wave sleep (SWS-2) and low-frequency EEG power in humans and rodents. 5-HT(2A) and 5-HT(2C) receptors may be involved in these effects, but the role of the 5-HT(2B) receptor is still unclear. To investigate the role of the 5-HT(2B) receptor in regulation of the sleep-wake cycle, the subtype-selective antagonist SB-215505 (0.1, 0.3 and 1.0 mg kg(-1) i.p.) was administered to Sprague-Dawley rats at light onset (beginning of passive phase). EEG, EMG and motor activity were recorded during the subsequent 8 h. SB-215505 dose-dependently increased wakefulness (W) at the expense of the intermediate stage of sleep, paradoxical sleep (PS) and SWS-2 in the first hour. Parallel to increased W, significantly increased motor activity was found. Spectral analysis of the EEG in W showed a dose-dependent decrease in power density in the 3-8 Hz frequency range (maximum effect at 6 Hz). In light slow wave sleep and SWS-2, the drug reduced low-frequency (<8 Hz) EEG power, suggesting decreased sleep intensity after SB-215505 treatment. In PS, the drug dose-dependently decreased EEG power solely in the theta (6-9 Hz) band, primarily affecting the peak power value (7 Hz). The well-known SWS-2 enhancing effect of 5-HT(2) receptor antagonists is mediated by 5-HT(2A) and/or 5-HT(2C) receptors. In contrast, blockade of 5-HT(2B) receptors increases motor activity and W along with decreased theta activity during W and PS. Activation of 5-HT(2B) receptors may contribute to initiation of sleep and to theta generation during W and PS under physiological conditions.


Asunto(s)
Indoles/farmacología , Actividad Motora/efectos de los fármacos , Quinolinas/farmacología , Antagonistas del Receptor de Serotonina 5-HT2 , Ritmo Teta/efectos de los fármacos , Vigilia/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Masculino , Actividad Motora/fisiología , Ratas , Receptor de Serotonina 5-HT2B/fisiología , Antagonistas de la Serotonina/farmacología , Vigilia/fisiología
16.
Psychopharmacology (Berl) ; 173(3-4): 296-309, 2004 May.
Artículo en Inglés | MEDLINE | ID: mdl-15083265

RESUMEN

RATIONALE: Despite the well documented neurochemical actions of 3,4-methylenedioxymethamphetamine (MDMA), acute effects in rats previously exposed to the drug have not been extensively explored. OBJECTIVE: To examine motor activity and vigilance effects of MDMA in drug-naive rats and in rats exposed to the drug 3 weeks earlier. METHODS: MDMA (15 mg/kg, i.p.) was administered to Dark Agouti rats. Motor activity, wakefulness, light slow wave sleep (SWS-1), deep slow wave sleep (SWS-2) and paradoxical sleep (PS), sleep and PS latencies were measured. Acrophases and amplitudes of the 24 h cycles were calculated by cosinor analysis. In parallel groups, local cerebral glucose utilization (lCMRglu) and (3H)-paroxetine binding were measured in motor areas of the brain. RESULTS: In drug-naive rats MDMA caused marked increases in motor activity and wakefulness for at least 5-6 h. Circadian patterns of motor activity and sleep/vigilance parameters were altered up to 5 days after treatment. Despite most parameters tending to return to normal, there were still significant effects of MDMA on motor activity, wakefulness, and SWS-2 28 days later. Acute MDMA administration caused significant increases in lCMRglu, but after 3 weeks lCMRglu was decreased in the same brain areas. No significant change in [3H]paroxetine binding was observed in motor areas, although significant reductions were seen elsewhere (neocortex -81%). In rats exposed to MDMA 3 weeks earlier, most acute effects induced by MDMA administration were similar to those in drug-naive rats, but shorter duration of the acute effects were found in motor activity and vigilance. CONCLUSIONS: Our findings provide evidence that MDMA use can lead to long-term changes in regulation of circadian rhythms, motor activity and sleep generation.


Asunto(s)
Ritmo Circadiano/efectos de los fármacos , Actividad Motora/efectos de los fármacos , N-Metil-3,4-metilenodioxianfetamina/farmacología , Sueño/efectos de los fármacos , Animales , Autorradiografía , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Glucosa/metabolismo , Masculino , N-Metil-3,4-metilenodioxianfetamina/administración & dosificación , Ensayo de Unión Radioligante , Ratas , Vigilia/efectos de los fármacos
17.
Brain Res ; 943(1): 105-11, 2002 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-12088844

RESUMEN

Parallel effects of a single injection of the 5-HT(2) receptor antagonist ritanserin on EEG power spectra, sleep and motor activity were measured for a 20-h period in freely moving Sprague-Dawley rats. Ritanserin (0.3 mg/kg, i.p.), administered at light onset (passive phase), caused an immediate transient increase in the EEG power density in the low frequency range (0.25-6 Hz, mainly delta activity) and a depression in the high frequency range (27-30 Hz) accompanied by a decrease in vigilance and light slow wave sleep (SWS-1), intermediate stage of sleep and increase in deep slow wave sleep (SWS-2) compared to control treatment. All these effects were over 8 h after the injection. Twelve hours after the injection, at dark onset (active phase), there was a marked increase in vigilance and motor activity and decrease in SWS-1 and spindle frequency activity in the control animals, but all these changes were diminished by ritanserin treatment. These effects resulted in a significant relative increase in the intermediate band (peak: 12-15 Hz) of the EEG power spectra and thus, a relative increase in thalamo-cortical synchronization caused by ritanserin at dark onset. Because ritanserin is a selective 5-HT(2) receptor antagonist, we conclude that under physiological conditions serotonin increases EEG desynchronization and produces an increase in vigilance level and motor activity by tonic activation of 5-HT(2) receptors. This regulatory mechanism plays an important role in the waking process, and the appearances of its effects in the light and dark phase are markedly different.


Asunto(s)
Ritmo Circadiano/efectos de los fármacos , Oscuridad , Electroencefalografía/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Receptores de Serotonina/fisiología , Ritanserina/farmacología , Antagonistas de la Serotonina/farmacología , Sueño/efectos de los fármacos , Animales , Ritmo Circadiano/fisiología , Masculino , Actividad Motora/fisiología , Fotoperiodo , Ratas , Ratas Sprague-Dawley , Sueño/fisiología
18.
Brain Res ; 1008(2): 236-44, 2004 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-15145761

RESUMEN

The present study was conducted to investigate the effects of two noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists, GYKI 52466 and GYKI 53405 (the racemate of talampanel) on the generation of spike-wave discharges (SWD) parallel with the vigilance and behavioral changes in the genetic absence epilepsy model of WAG/Rij rats. Intraperitoneal (i.p.) administration of GYKI 52466 (1-[4-aminophenyl]-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine; 3, 10 and 30 mg/kg, i.p.), the prototypic compound of the 2,3-benzodiazepine family, caused a fast dose-dependent increase in the number and cumulative duration of SWD. These changes were accompanied by dose-dependent increase in duration of light slow wave sleep (SWS1) and passive awake, vigilance states associated with the presence of SWD. In addition a short, transient behavioral activation occurred that was followed by strong ataxia and immobility, decrease of active wakefulness and increase in deep slow wave sleep. GYKI 53405 (7-acetyl-5-(4-aminophenyl)-8-methyl-8,9-dihydro-7H-1,3-dioxolo[4,5-b][2,3]benzodiazepine, the racemate of talampanel, 16 mg/kg, i.p.) failed to affect any measure of SWD and vigilance. When used as a pretreatment, GYKI 52466 (10 mg/kg) slightly attenuated SWD-promoting effects of the 5-HT1A receptor agonist 8-OH-DPAT, it decreased cumulative duration and average time of paroxysms. In conclusion, AMPA receptors play moderate role in regulation of epileptic activity, and some of these effects are connected to their effects on vigilance in this model.


Asunto(s)
Nivel de Alerta/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Benzodiazepinas/farmacología , Epilepsia Tipo Ausencia/fisiopatología , Epilepsia Tipo Ausencia/psicología , Antagonistas de Aminoácidos Excitadores/farmacología , Receptores AMPA/antagonistas & inhibidores , 8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , Animales , Relación Dosis-Respuesta a Droga , Electroencefalografía , Electromiografía , Epilepsia Tipo Ausencia/genética , Masculino , Ratas , Agonistas de Receptores de Serotonina/farmacología , Sueño/efectos de los fármacos , Vigilia/efectos de los fármacos
19.
Neurosci Lett ; 359(1-2): 45-8, 2004 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-15050708

RESUMEN

Recent studies have provided evidence that activation of 5-HT1A receptors increases epileptic activity in the WAG/Rij rat model of absence epilepsy, and additional data have suggested the involvement of 5-HT7 receptors as well. Therefore, we have tested the effects of the selective 5-HT1A receptor antagonist WAY-100635 and the selective 5-HT7 receptor antagonist SB-258719 on spontaneous epileptic activity. In general, both compounds reduced epileptic activity compared to vehicle. Significant decreases were found in the number of paroxysms and the cumulative and average duration of spike-wave discharges (SWDs), although the time courses of these effects induced by the two compounds were clearly different. These results provide evidence that activation of 5-HT1A and 5-HT7 receptors plays a significant role in regulating SWD activity in this animal model of absence epilepsy.


Asunto(s)
Modelos Animales de Enfermedad , Epilepsia Tipo Ausencia/tratamiento farmacológico , Receptores de Serotonina/fisiología , Antagonistas del Receptor de Serotonina 5-HT1 , Antagonistas de la Serotonina/uso terapéutico , Animales , Epilepsia Tipo Ausencia/fisiopatología , Masculino , Ratas , Ratas Wistar , Receptor de Serotonina 5-HT1A/fisiología
20.
Neurosci Lett ; 350(1): 56-60, 2003 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-12962916

RESUMEN

Platelet serotonin (5-HT) concentrations in a headache-free period during the mid-follicular phase and the serotonin transporter gene regulatory region polymorphism (5-HTTLPR) were measured in female migraine patients without aura (n = 64) and healthy controls (n = 42). High-pressure liquid chromatography (HPLC) was used to determine the platelet 5-HT concentration and genetic polymorphism was determined by polymerase chain reaction. Significantly lower platelet 5-HT concentrations were found in migraine patients compared to controls. Concerning the 5-HTTLPR polymorphism, the S/S genotype was associated with a significantly higher platelet 5-HT concentration (P = 0.027) in the whole study population. This association between the 5-HTTLPR genotypes and platelet 5-HT concentrations was independent of the diagnosis. In addition, the platelet 5-HT concentration was lower in migraineurs in all genotypes (S/S, S/L, L/L). In conclusion, 5-HTTLPR variants may have an effect on the platelet 5-HT concentrations, but the lower 5-HT concentrations in migraine patients seem to be determined by other factors.


Asunto(s)
Proteínas Portadoras/genética , Glicoproteínas de Membrana/genética , Proteínas de Transporte de Membrana , Trastornos Migrañosos/genética , Proteínas del Tejido Nervioso , Polimorfismo Genético , Secuencias Reguladoras de Ácidos Nucleicos , Serotonina/sangre , Adulto , Alelos , Análisis de Varianza , Plaquetas/metabolismo , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Cromatografía Líquida de Alta Presión , Femenino , Variación Genética , Genotipo , Humanos , Trastornos Migrañosos/sangre , Reacción en Cadena de la Polimerasa , Proteínas de Transporte de Serotonina en la Membrana Plasmática
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