Effect of the association of amantadine and quetiapine in the treatment of rem sleep behavior disorder: case report / Efeito da associação de amantadina e quetiapina no tratamento do distúrbio do comportamento do sono rem: relato de caso / Efecto de la asociación de amantadina y quetiapina en el tratamiento del trastorno del comportamiento del sueño rem: reporte de un caso

The aim was to report the case of a patient with REM sleep behavior disorder, unresponsive to standard treatment and with complete control of the condition after association of amantadine. Female patient, 45 years old, with systemic arterial hypertension and hypothyroidism, referred to neurological care, reporting frequent episodes of nocturnal agitation in the first hours of sleep, with walking and vocalization, waking up easily if called. She complains of drowsiness and anxiety, secondary to the impact of the RBD on her personal life. She mentions previous attempts at drug treatment with benzodiazepines (Bromazepam and Clonazepam), Zolpidem and Trazodone, all without clinical improvement, with Quetiapine being introduced at a low dose (not yet tried) 25mg, with a therapeutic target of 50mg with partial improvement only with 25mg. When trying 50mg, presenting a worsening of the picture. In a new follow-up, therapy with Amantadine 50 mg/day associated with Quetiapine 25 mg/day was started. The patient returned reporting a significant improvement in the condition, less frequent episodes associated with reduced nocturnal movement. After adaptation of the combined therapy, with adjustments in the dose of Amantadine, an increase of 50mg every 14 days up to 200 mg/day, with the possibility of using quetiapine 50mg (balance between the drugs), the patient evolved stable, with a great improvement in the quality of life and absence of new episodes of the sleep disorder.

O objetivo foi relatar o caso de uma paciente com transtorno comportamental do sono REM, sem resposta ao tratamento padrão e com completo controle do quadro após associação de amantadina. Paciente do sexo feminino, 45 anos, com hipertensão arterial sistêmica e hipotireoidismo, encaminhada a atendimento neurológico relatando episódios frequentes de agitação noturna nas primeiras horas de sono, com deambulo e vocalização, despertava facilmente se chamada. Queixa-se de sonolência e ansiedade, secundárias ao impacto do TCSREM em sua vida pessoal. Menciona tentativas prévias de tratamento medicamentoso com benzodiazepínicos (Bromazepam e Clonazepam), Zolpidem e Trazodona, todos sem melhora clínica, sendo introduzido Quetiapina em dose baixa (ainda não tentado) 25mg, com alvo terapêutico de 50mg com melhora parcial apenas com 25mg. Ao tentar 50mg, apresentando piora do quadro. Em novo retorno, iniciou-se terapia com Amantadina 50 mg/dia associada a Quetiapina 25 mg/dia. A paciente retornou referindo melhora significativa do quadro, episódios em menor frequência associados a redução na movimentação noturna. Após adaptação da terapia combinada, com ajustes da dose de Amantadina, aumento de 50mg a cada 14 dias até 200 mg/dia, sendo possível o uso da quetiapina 50mg (equilíbrio entre os fármacos) a paciente evoluiu estável, com grande melhora da qualidade de vida e ausência de novos episódios do distúrbio de sono.

El objetivo fue reportar el caso de un paciente con trastorno de conducta del sueño REM, que no responde al tratamiento estándar y con un control completo de la condición después de la asociación de amantadina. Paciente femenina, de 45 años de edad, con hipertensión arterial sistémica e hipotiroidismo, referida a atención neurológica, reportando episodios frecuentes de agitación nocturna en las primeras horas de sueño, con marcha y vocalización, despertándose fácilmente si se le llama. Se queja de somnolencia y ansiedad, secundarias al impacto de la RBD en su vida personal. Menciona intentos previos de tratamiento farmacológico con benzodiazepinas (Bromazepam y Clonazepam), Zolpidem y Trazodona, todos sin mejoría clínica, con la introducción de quetiapina a una dosis baja (aún no probada) de 25mg, con un objetivo terapéutico de 50mg con mejoría parcial solo con 25mg. Al intentar 50mg, presentando un empeoramiento de la imagen. En un nuevo seguimiento se inició tratamiento con 50 mg/día de amantadina asociado a 25 mg/día de quetiapina. El paciente retornó reportando una mejoría significativa en la condición, episodios menos frecuentes asociados a reducción del movimiento nocturno. Después de la adaptación de la terapia combinada, con ajustes en la dosis de Amantadina, un aumento de 50mg cada 14 días hasta 200 mg/día, con la posibilidad de utilizar quetiapina 50mg (equilibrio entre los fármacos), el paciente evolucionó estable, con una gran mejoría en la calidad de vida y ausencia de nuevos episodios del trastorno del sueño.

Contenido onírico en diferentes trastornos del sueño: síndrome de apnea e hipopnea del sueño, insomnio primario, trastorno de la conducta del sueño REM idiopático y narcolepsia de tipo 1 / Dream content in different sleep disorders: sleep apnoea and hypopnoea syndrome, primary insomnia, idiopathic REM sleep behaviour disorder and narcolepsy type 1

Objetivo: Determinar si existen diferencias en el contenido onírico en diferentes trastornos del sueño y describir sus características. Pacientes y métodos: Estudiamos cuatro trastornos del sueño: síndrome de apnea e hipopnea del sueño (SAHS), insomnio primario (IP), trastorno de conducta del sueño REM idiopático (TCSRI) y narcolepsia de tipo 1. Se solicitó a cada paciente que llenara un diario de sus sueños durante dos semanas. El contenido de los diarios fue transcrito y analizado en longitud, contenido mental, complejidad y amenaza. Los resultados se compararon para establecer diferencias. Resultados: Se estudió a 89 pacientes: 23 con SAHS sin presión positiva continua de la vía aérea (CPAP) que tuvieron la mayor cantidad de sueños con participación en amenazas (32,5%); 19 con SAHS tratados con CPAP que tuvieron la mayor cantidad de sueños con objetos (64,8%), elementos descriptivos (38%) y de más alta complejidad (9,5%); 22 con insomnio primario con la mayor cantidad de sueños con eventos amenazantes al ámbito social (57,7%); 12 con TCSRI que tuvieron en sus sueños la más alta cantidad de fracasos (14%) y menor complejidad (71,7%), y 13 con narcolepsia de tipo 1 que tuvieron la mayor cantidad de sueños relacionados con actividades (84,3%) y amenazas hacia la vida (41,4 %). Estas diferencias fueron estadísticamente significativas (p < 0,05). Conclusiones: Los distintos trastornos del sueño sí se asocian a contenidos oníricos diferentes que traducirían distintos procesos neurológicos subyacentes. Estos hallazgos deberían replicarse en estudios que analicen más pacientes y añadan un grupo control sin trastornos del sueño.(AU)

Aim: The aim of this study is to determine whether there are any differences in the dream content in different sleep disorders and to describe their characteristics. Patients and methods: We studied four sleep disorders: sleep apnoea and hypopnoea syndrome (SAHS), primary insomnia (PI), idiopathic REM sleep behaviour disorder (IRBD) and narcolepsy type I. Each patient was asked to keep a dream diary for two weeks. The content of the diaries was transcribed and analysed for length, mental content, complexity and threat. The results were compared to establish differences. Results: Eighty-nine patients were studied: 23 with SAHS without continuous positive airway pressure (CPAP) who had the highest number of dreams involving threats (32.5%); 19 with SAHS treated with CPAP who had the highest number of dreams involving objects (64.8%), descriptive elements (38%) and higher complexity (9.5%); 22 with primary insomnia who had the highest number of dreams with threatening events in the social sphere (57.7%); 12 with IRBD who had the highest number of dreams with failures (14%) and lower complexity (71.7%); and 13 with narcolepsy type I who had the highest number of dreams related to activities (84.3%) and threats to life (41.4%) These differences were statistically significant (p <0.05). Conclusions: Different sleep disorders are associated with different dream contents, which would be translating different underlying neurological processes. These findings should be replicated in studies that analyse more patients and add a control group without sleep disorders.(AU)

Enfermedad de Willis-Ekbom a propósito de un caso / Willis-Ekbom's disease a case report

Los trastornos del sueño REM, son de alta prevalencia en nuestro medio, se manifiestan por lo general en comorbilidad con trastornos afectivos como la ansiedad y la depresión. Dependiendo de la sintomatología del paciente la afectación puede afectar su calidad de vida, en nuestro medio son frecuentes las crisis de pánico y trastornos del sueño reconocidos culturalmente como provenientes de embrujos o maleficios, que al no ser tratados con buenos resultados, buscan una respuesta en el ámbito médico postergando la intervención en el caso evaluado. El presente caso describe los síntomas experimentados por un adulto de sexo masculino, con un cuadro que impresiona por su descripción sintomatológica de origen netamente urológico, que fue valorado en integridad con sus respectivos resultados laboratoriales y de gabinete es referido a diferentes especialidades y finalmente a psiquiatría donde se llega a la conclusión diagnostica de enfermedad de Willis-Ekbom, trastorno del sueño REM y Trastorno de ansiedad generalizada con crisis de pánico, se realiza tratamiento específico, con resultados favorables y seguimientos periódicos. Se presenta el caso clínico de un paciente de sexo masculino de 61 años como se describe en la presentación.

REM sleep disorders, are of high prevalence in our environment, are usually manifested in comorbidity with affective disorders such as anxiety and depression. Depending on the symptomatology of the patient, the affectation can affect their quality of life, in our environment there are frequent panic crises and sleep disorders culturally recognized as coming from spells or curses, which, when not being treated with good results, seek an answer in the medical field postponing the intervention in the case evaluated. The present case describes the symptoms experienced by a male adult, with a picture that impresses with his symptomatic description of a purely urological origin, which was assessed in integrity with their respective laboratory and laboratory results. It refers to different specialties and finally to psychiatry. where the diagnostic conclusión of Willis-Ekbom disease, REM sleep disorder and generalized anxiety disorder with panic crisis is reached, specific treatment is performed, with favorable results and periodic follow-up.

Conditions associated with REM sleep behaviour disorder: Description of a hospital series. / Patologías asociadas al trastorno de conducta de sueño REM. Descripción de una serie hospitalaria.

INTRODUCTION: REM sleep behaviour disorder (RBD) is characterised by violent behaviours (screaming, kicking, vivid dreams) during REM sleep. It has a prevalence of 1% to 2% of the general population and is especially frequent in men and the population older than 60. In the last decade, RBD has been suggested to be a prodrome of neurodegenerative disease. We analysed associated neurological diseases and responses to drug treatment in 33 patients with RBD treated in the multidisciplinary sleep disorders unit at Hospital Infanta Sofía. PATIENTS AND METHODS: We conducted an observational descriptive retrospective analysis of patients diagnosed with RBD and treated in our multidisciplinary sleep disorders unit between October 2012 and December 2015. We recorded age, sex, associated diseases, and treatments administered to these patients. RESULTS: A total of 365 patients were attended at our unit, including 33 with RBD: 13 women (40%) and 20 men (60%). Mean age was 62.72 years. An associated disorder was identified in 48%, with the most common being mild cognitive impairment (69%). The percentage of patients with RBD and an associated disorder among patients older than 60 was 68%. Eighty-two percent of the patients required treatment. The most commonly used drug was clonazepam (76%), followed by melatonin (9%), gabapentin (6%), and trazodone (3%). DISCUSSION: In our series, 48% of the patients had an associated disorder. The likelihood of detecting an associated disorder increases with patients' age. The vast majority of patients required drug treatment due to symptom severity; the most frequently administered drug was clonazepam (76%).

Parasomnias en Pediatría: Una visión clínica / Parasomnia in Pediatrics: A clinical view

Resumen Un motivo frecuente de consulta, en la práctica pediátrica, son los trastornos del sueño que pueden afectar hasta al 30% de la población infantil, con repercusiones negativas tanto en el aspecto cognitivo como conductual y físico (Meijer et al. 2000). Dentro de estas manifestaciones se encuadran las denominadas parasomnias que son fenómenos o manifestaciones anormales, molestas o displacenteras, que se presentan durante las etapas del sueño y se pueden acompañar de cambios siológicos cardiovasculares y/o motores. Constituyen un tercio de todos los trastornos del sueño con causas relacionadas al neurodesarrollo o a patrones familiares y desencadenantes similares (medicamentos, ebre, trastornos respiratorios y stress). Particularmente cuando coexisten con trastornos neurológicos o del neurodesarrollo, pudiendo confundirse con otras patologías tal como la epilepsia, lo que conlleva un desafío diagnóstico para el Neuropediatra. Corresponden a la tercera causa de alteraciones de sueño en la infancia con origen tanto en factores genéticos con patrones ligados a la herencia y otras se asociadas al neurodesarrollo del SNC. Se las clasifica, según en qué etapa del sueño se presentan en: Trastornos del Alertamiento, Trastornos de la Transición sueño/vigilia, Trastornos asociados al sueño REM y otras parasomnias. Existen cada vez más evidencias acerca de los efectos de la inadecuada higiene se sueño y problemas del neurodesarrollo que nos obligan a echar más luz sobre esta problemática para corregir y evitar problemas futuros asociadas a ello, siendo el propósito de este trabajo el realizar una revisión sobre los conocimientos actuales sobre el tema en cuestión.

Abstract A frequent chief complaint in pediatric practice are sleep disorders, which may affect up to 30% of the pediatric population. These may have harmful e ects on cognition, behavior and physical development (Meijer et al. 2000). These sleep disorders include parasomnias, unpleasant abnormal phenomena that occur during sleep and may be accompanied by cardiovascular and/or motor manifestations. These make up one third of all sleep disorders caused by disturbances of neural development or family patterns, with similar triggering factors, such as medication, fever, respiratory disorders and stress. When they coincide with neurological or neural development disorders they may be confused with other disease conditions, such as epilepsy, and be a diagnostic challenge for the pediatric neurologist. Parasomnias are the third cause of sleep disorders of childhood, originating in both hereditary genetic factors and others pertaining to neural development of the CNS. They are classified according to the stage of sleep they affect: disorders of waking, disorders of the sleep/waking transition, REM sleep associated disorders and other parasomnias. A growing body of evidence points to the effects of inadequate sleep hygiene and disorders of neural development, requiring, therefore, further research. This paper reviews current knowledge on the subject.

Modelo in vitro para el estudio del papel de la unión mesopontina en la generación del sueño de movimientos oculares rápidos y la vigilia / In vitro model for the study of the role of the mesopontine region in rapid eye movement (REM) sleep and wakefulness / Modelo in vitro para o estudo do papel da união mesopontina na geração de sono de movimentos oculares rápidos e da vigília

El estudio de las estrategias neurales para la organización del comportamiento en vertebrados constituye un desafío mayor para la Neurociencia. El avance del conocimiento en este campo depende de manera crítica de la utilización de modelos experimentales adecuados que admitan múltiples niveles de análisis (p.ej: comportamental, circuital, celular, sináptico, molecular) y abordajes multitécnicos. Nos propusimos analizar in vitro una red neural de la unión mesopontina del tronco encefálico críticamente implicada en el control del sueño de movimientos oculares rápidos (S-REM). Pese al cúmulo de evidencias que apoyan el papel desempeñado por esta red en relación al S-REM, los mecanismos celulares y sinápticos que subyacen a este control son poco conocidos y continúan siendo objeto de intensa investigación. Para avanzar en el conocimiento de estos mecanismos, se llevó a cabo la caracterización morfológica y funcional de una rodaja de tronco encefálico de la rata, en la que las estructuras críticas para el control del S-REM, i.e.: núcleos tegmentales laterodorsal y pedúnculopontino, y su proyección al núcleo reticular pontis oralis (PnO), están presentes y son operativas. La inclusión del núcleo motor del trigémino en la rodaja permitió detectar cambios de la excitabilidad de las motoneuronas ante manipulaciones farmacológicas del PnO, representativos de los cambios del tono muscular asociados a maniobras similares realizadas in vivo. La utilización de este modelo in vitro de S-REM, permitirá aportar a la dilucidación de las estrategias neurales que operan en niveles intermedios de organización del SN en mamíferos para la generación y regulación de un estado comportamental.

The study of the neural basis of behavior is a major challenge in Neuroscience. Advancing our knowledge in this field depends, critically, on the use of experimental paradigms that provide multiple levels of analysis, as well as powerful techniques. We have selected, as a model of a neural plan that organizes a complex behavior, a neural network located in the mesopontine junction. This region is thought to be both necessary and sufficient for the generation of rapid eye movement (REM) sleep, although the cellular and synaptic mechanisms involved in the control of this behavioral state at the mesopontine level are still under debate and remain poorly understood. As part of a long term effort to gain insight into these mechanisms, we carried out the morphological and functional characterization of a slice preparation of rat brainstem and we demonstrate that critical structures for the control of REM sleep - the laterodorsal and pedunculopontine tegmental nuclei and their projection to the oral part of the pontine reticular nucleus (PnO) - are present and are operational. The presence of the trigeminal motor nucleus in the slice sought to include in the experimental model a structure capable of expressing changes of the excitability of the motorneurons caused by pharmacological manipulations of the PnO, representative of changes of muscle tone associated with similar maneuvers performed in vivo. The use of this in vitro model of REM sleep will provide critical information to elucidate neural strategies that operate at intermediate levels of central nervous system organization in mammals to control behavioral states.

O estudo de estratégias neurais para a organização do comportamento em vertebrados constitui um desafio maior para a Neurociencia. O avanço do conhecimento nessa área depende criticamente da utilização de modelos experimentais adequados que suportem múltiplos níveis de análise (por exemplo: comportamental, circuital, celular, sináptico e molecular) e abordagens por múltiplas técnicas. Decidiu-se analisar in vitro uma rede neural da união mesopontina do tronco encefálico criticamente envolvida no controle do sono de movimentos oculares rápidos (S-REM). Apesar da riqueza de provas que sustentam o papel desta rede em relação ao S-REM, os mecanismos celulares e sinápticos subjacentes a este controle são pouco conhecidos e permanecem sob intensa investigação. Para avançar no conhecimento desses mecanismos, caracterizou-se morfológica e funcionalmente uma fatia de tronco encefálico de rato, na qual as estruturas críticas para o controle do S-REM, i.e.: núcleos tegmentais laterodorsal e pedunculopontino, e sua projeção para o núcleo reticular pontis oralis (PnO) estão presentes e operantes. A inclusão do núcleo motor do trigêmeo na fatia permitiu detectar mudanças da excitabilidade das motoneuronas provocadas por manipulações farmacológicas do PnO, representativas das alterações do tônus muscular associados com operações semelhantes quando realizados in vivo. A utlização deste modelo in vitro de S-REM permitirá contribuir para a elucidação de estratégias neurais que operam em níveis intermedios de organização do SN de mamíferos para a geração e regulação de um estado comportamental.

Association between REM sleep behaviour disorder and impulse control disorder in patients with Parkinson's disease. / Relación entre el trastorno de conducta del sueño REM y el trastorno de control de impulsos en pacientes con enfermedad de Parkinson.

INTRODUCTION: The relationship between impulse control disorder (ICD) and REM sleep behaviour disorder (RBD) has not yet been clarified, and the literature reports contradictory results. Our purpose is to analyse the association between these 2 disorders and their presence in patients under dopaminergic treatment. METHODS: A total of 73 patients diagnosed with Parkinson's disease and treated with a single dopamine agonist were included in the study after undergoing clinical assessment and completing the single-question screen for REM sleep behaviour disorder and the short version of the questionnaire for impulsive-compulsive behaviours in Parkinson's disease. RESULTS: Mean age was 68.88 ± 7.758 years. Twenty-six patients (35.6%) were classified as probable-RBD. This group showed a significant association with ICD (P=.001) and had a higher prevalence of non-tremor akinetic rigid syndrome and longer duration of treatment with levodopa and dopamine agonists than the group without probable-RBD. We found a significant correlation between the use of oral dopamine agonists and ICD. Likewise, patients treated with oral dopamine agonists demonstrated a greater tendency toward presenting probable-RBD than patients taking dopamine agonists by other routes; the difference was non-significant. CONCLUSIONS: The present study confirms the association between RBD and a higher risk of developing symptoms of ICD in Parkinson's disease.

Valeriana en el tratamiento a largo plazo del insomnio / Use of Valerian in the Long-Term Treatment of Insomnia

Introducción: La valeriana se ha utilizado desde la antigua Grecia y China para inducir el sueño, debido a sus propiedades ansiolíticas. Hoy en día, aun cuando no es un producto aprobado por la Agencia de Administración de Drogas y Alimentos de Estados Unidos (FDA) para el tratamiento del insomnio, se utiliza en diferentes países con esta finalidad. Objetivo: Llevar a cabo una revisión que permita determinar la eficacia de la valeriana en el tratamiento a largo plazo del insomnio y considerarla una alternativa terapéutica posible a las benzodiazepinas y los agonistas benzodiazepínicos. Resultados: Son pocos los estudios controlados realizados con valeriana; no obstante, los resultados disponibles sugieren que su empleo facilita la reestructuración de la arquitectura del sueño después de varias semanas de tratamiento y consigue así mejorar su calidad. También hay indicios que señalan que desempeña un papel importante en la disminución del estrés y la ansiedad en aquellos pacientes donde esta condición interfi ere con el inicio y mantenimiento del sueño, así como en el tratamiento coadyuvante en la discontinuación del uso prolongado de benzodiazepinas. Conclusiones: El principal punto a favor de la valeriana es su capacidad para disminuir la latencia del sueño de ondas lentas y aumentar su porcentaje, sin provocar efectos secundarios de importancia ni dependencia; sin embargo, aún no se dispone de suficientes estudios controlados a largo plazo que permitan establecer conclusiones definitivas.

Introduction: Valerian has been used for centuries to induce drowsiness due to its anxiolytic properties. It was fi rst described being used in ancient cultures, i.e., Greece and China. Nowadays, even though it is not officially approved by the US Food and Drug Administration Agency (FDA) as a treatment for insomnia, it is widely used in different latitudes for such a purpose. Objective: To carry out an extensive review in order to establish the levels of effectiveness of valerian in the long term treatment of patients suffering from sleeplessness and consider it an alternative to the use of benzodiazepines and benzodiazepinic agonists. Results: There are very few controlled studies on the effects of valerian. Nonetheless, the available data might indicate that the use of valerian helps to restructure sleep architecture after several weeks of treatment and helps to improve sleep quality. There are also papers suggesting that valerian plays a key role in diminishing stress and anxiety in cases where these conditions disturb normal sleep patterns and is useful in discontinuing long treatments based on benzodiazepines. Conclusions: The key advantage of valerian is its capability to reduce the slow wave sleep latency and increase its percentage without causing relevant secondary effects or dependence. Still, we do not have sufficient data from long term controlled studies in order to support conclusive results.

Epilepsia y sueño / Epilepsy and sleep

Existe una interacción importante entre la epilepsia y el sueño, ya que este último tiene influencia en el momento de iniciación, la frecuencia y las características de las crisis, así como los hallazgos electroencefalográficos. La privación del sueño también desempeña un papel fundamental de otra parte, la epilepsia y los medicamentos anticonvulsivantes alteran el patrón de sueño. Sin embargo, se desconocen los mecanismos neurofisiológicos que intervienen en esta interacción y su esclarecimiento es de vital importancia para controlar las crisis y mejorar la calidad de vida de los pacientes. En este escrito se describen los diferentes tipos de crisis, su relación con las etapas del sueño y sus patrones electroencefalográfico.

There is a significant interaction between epilepsy and sleep, since the latter has influence in the onset, frequency and characteristics of the seizures, as well as EEG findings, and sleep deprivation also plays an important role; on the other hand, epilepsy and anticonvulsant drugs alter the pattern of sleep. However, neurophysiological mechanisms involved in this interaction are yet unknown and its clarification is vital to control seizures and improve the quality of life of patients. In this paper are described the different types of seizures, their relationship with the stages of sleep, and their electroencephalographic patterns.