Excessive sleepiness and sleep patterns in patients with epilepsy: a case-control study.

The aim of this study was to assess excessive daytime sleepiness (EDS), sleep quality, and sleep disorders in a cohort of patients with epilepsy in the city of Florianopolis in southern Brazil. One hundred and forty patients diagnosed with epilepsy were assessed by questionnaires that included demographic and clinical variables, the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Stanford Sleepiness Scale (SSS), and the Fletcher & Luckett Adapted Questionnaire (FLAQ). These data were then compared to data from a control group (n=85). Compared to controls, patients with epilepsy (PWE) had significantly higher scores on the ESS (p=0.003), higher scores on the "daytime dysfunction" domain of the PSQI (p=0.002), and more symptoms that suggested obstructive sleep apnea in the FLAQ (p<0.001). By performing multiple linear regression models, we demonstrated that age, male gender, the presence of secondarily generalized seizures, and phenobarbital use were slightly to moderately correlated with PSQI (r=0.38) and FLAQ (r=0.51) but not with SSS scores. We concluded that PWE had more EDS, daytime dysfunction, and sleep disorders compared to a control group.

2023 Guidelines on the Diagnosis and Treatment of Insomnia in Adults - Brazilian Sleep Association.

Chronic insomnia disorder (simplified in this document as insomnia) is an increasingly common clinical condition in society and a frequent complaint at the offices of different areas of health practice (particularly Medicine and Psychology). This scenario has been accompanied by a significant evolution in treatment, as well as challenges in approaching patients in an appropriately way. This clinical guideline, coordinated by the Brazilian Sleep Association and the Brazilian Association of Sleep Medicine and counting on the active participation of various specialists in the area, encompasses an update on the diagnosis and treatment of insomnia in adults. To this end, it followed a structured methodology. Topics of interest related to diagnosis were written based on theoretical framework, evidence in the literature, and professional experience. As for the topics related to the treatment of insomnia, a series of questions were developed based on the PICO acronym (P - Patient, problem, or population; I - Intervention; C - Comparison, control, or comparator; O - Outcome). The work groups defined the eligible options within each of these parameters. Regarding pharmacological interventions, only the ones currently available in Brazil or possibly becoming available in the upcoming years were considered eligible. Systematic reviews were conducted to help prepare the texts and define the level of evidence for each intervention. The final result is an objective and practical document providing recommendations with the best scientific support available to professionals involved in the management of insomnia.

Socio-demographic and clinical characteristics of Brazilian patients with epilepsy who drive and their association with traffic accidents.

PURPOSE: To identify variables associated with driving in patients with epilepsy and their association with traffic accidents. METHODS: Binary logistic regression analysis was performed to determine the independent association between demographic and clinical variables and driving in 144 outpatients with epilepsy. Traffic accidents caused by seizures were also analyzed. RESULTS: Sixty-eight patients (47.2%) drove after the diagnosis of epilepsy. Among these patients, 67.6% drove in the last 12 months, 89% of whom did so in spite of uncontrolled seizures. Driving was independently associated with male sex, higher income, occurrence of simple partial seizures, age at epilepsy onset over 18 years and monotherapy treatment. Seventeen patients (only male) had accidents due to seizures, which were independently associated with lower education and age at epilepsy onset over 18 years. CONCLUSIONS: Identification of variables associated with driving and traffic accidents may help to minimize risks and improve the quality of life of patients with epilepsy.

MECP2-related conditions in males: A systematic literature review and 8 additional cases.

OBJECTIVE: To present a cohort of 8 males and perform a systematic review of all published cases with a single copy of MECP2 carrying a pathogenic variant. METHODS: We reviewed medical records of males with a single copy of MECP2 carrying a pathogenic variant. We searched in Medline (Pubmed) and Embase to collect all articles which included well-characterized males with a single copy of MECP2 carrying a pathogenic or likely pathogenic variant in MECP2 (1999-2020). RESULTS: The literature search yielded a total of 3,185 publications, of which 58 were included in our systematic review. We were able to collect information on 27 published patients with severe neonatal encephalopathy, 47 individuals with isolated or familial mental retardation X-linked 13 (XLMR13), as well as 24 individuals with isolated or familial Pyramidal signs, parkinsonism, and macroorchidism (PPM-X). In our cohort, we met eight individuals aged 4 to 19-year-old at the last evaluation. Three MECP2-associated phenotypes were seen in male carriers of a single copy of the gene: severe neonatal encephalopathy (n = 5); X-linked intellectual deficiency 13 (n = 2); and pyramidal signs, parkinsonism, and macroorchidism (PPM-X) (n = 1). Two novel de novo variants [p.(Gly252Argfs∗7) and p.(Tyr132Cys)] were detected. CONCLUSION: In males, the MECP2 pathogenic variants can be associated with different phenotypes, including neonatal severe encephalopathy, intellectual deficiency, or late-onset parkinsonism and spasticity. The typical RS phenotype is not expected in males, except in those with Klinefelter syndrome or somatic mosaicism for MECP2.

[The newer sedative-hypnotics]. / Novos sedativos hipnóticos.

There has been a search for more effective and safe hypnotic drugs in the last decades. Zolpidem, zaleplon, zopiclone, eszopiclone (the z-drugs) and indiplon are GABA-A modulators which bind selectively α1 subunits, thus, exhibiting similar mechanisms of action, although recent evidence suggests that eszopiclone is not as selective for α1 subunit as zolpidem is. Ramelteon and tasimelteon are new chrono-hypnotic agents, selective for melatonin MT1 and MT2 receptors. On the other hand, the consumption of sedative antidepressant drugs is significantly increasing for the treatment of insomnia, in the last years. As an experimental drug, eplivanserin is being tested as a potent antagonist of serotonin 2-A receptors (ASTAR) with a potential use in sleep maintenance difficulty. Another recent pharmacological agent for insomnia is almorexant, which new mechanism of action involves antagonism of hypocretinergic system, thus inducing sleep. Finally we also discuss the potential role of other gabaergic drugs for insomnia.

Donepezil improves obstructive sleep apnea in Alzheimer disease: a double-blind, placebo-controlled study.

BACKGROUND: There is an association between Alzheimer disease and sleep-disordered breathing. Donepezil is the drug most frequently used to treat cognitive symptoms in Alzheimer disease. This study evaluates the effects of donepezil on obstructive sleep apnea in patients with Alzheimer disease. METHODS: Randomized, double-blind, placebo-controlled design. Twenty-three patients with mild-to-moderate Alzheimer disease and apnea-hypopnea index (AHI) > 5/h were allocated to two groups: donepezil treated (n = 11) and placebo treated (n = 12). Polysomnography and cognitive evaluation using Alzheimer disease assessment scale-cognitive (ADAS-cog) subscale were performed at baseline and after 3 months. Cognitive and sleep data were analyzed using analysis of variance. RESULTS: AHI and oxygen saturation improved significantly after donepezil treatment compared to baseline and placebo (p < 0.05). Rapid eye movement (REM) sleep duration increased after donepezil treatment (p < 0.05). ADAS-cog scores improved after donepezil treatment, although they did not correlate with REM sleep increase and sleep apnea improvement (p < 0.01). CONCLUSIONS: Donepezil treatment improved AHI and oxygen saturation in patients with Alzheimer disease. Treatment also increased REM sleep duration and reduced ADAS-cog scores. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00480870.

How do people with drug-resistant mesial temporal lobe epilepsy sleep? A clinical and video-EEG with EOG and submental EMG for sleep staging study.

This study aimed to assess subjective and objective sleep parameters in a homogeneous group of drug-resistant mesial temporal lobe epilepsy (MTLE) patients through internationally validated clinical questionnaires, video-electroencephalographic (VEEG) and polysomnographic (PSG) studies. Fifty-six patients with definite diagnosis of MTLE who were candidates for epilepsy surgery underwent a detailed clinical history, the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Stanford Sleepiness Scale (SSS), neurological examination, 1.5 T brain magnetic resonance imaging, VEEG and PSG. Sixteen percent of patients reported significant daytime sleepiness as measured by ESS and 27% reported low levels of sleep quality as measured by PSQI. Patients with medically resistant epilepsy by MTLE showed increased wakefulness after sleep onset (WASO) with mean ± standard deviation of 17.4 ± 15.6, longer non-rapid eye movement (NREM) 1 (7.5 ± 4.6%) and NREM3 sleep (26.6 ± 11.8%), abnormal rapid eye movement (REM) latency in 30/56 patients, shorter REM sleep (16.7 ± 6.6%), and abnormal alpha delta patterns were observed in 41/56 patients. The analysis of interictal epileptic discharges (IEDs) evidenced highest spiking rate during NREM3 sleep and higher concordance with imaging data when IEDs were recorded in sleep, mainly during REM sleep. We concluded that patients with MTLE showed disrupted sleep architecture that may result in daytime dysfunction and sleep complaints. Furthermore, NREM sleep activated focal IEDs and them - when recorded during sleep - had higher localizing value.

The cholinergic system may play a role in the pathophysiology of residual excessive sleepiness in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a prevalent condition characterized by momentary cessations in breathing during sleep due to intermittent obstruction of the upper airway. OSA has been frequently associated with a number of medical comorbidities. CPAP (continuous positive airway pressure) is the gold standard treatment and is known to improve OSA symptoms, including excessive sleepiness. However, 12-14% of CPAP-treated patients continue to complain of sleepiness despite normalization of ventilation during sleep, and 6% after exclusion of other causes of EDS. This is of great concern because EDS is strongly associated with systemic health disorders, lower work performance, and a high risk of accidents. We hypothesized that decreased central cholinergic activity plays a role in the pathophysiology of residual excessive sleepiness in patients with OSA treated with CPAP. Acetylcholine (Ach) plays a large role in wakefulness physiology, and its levels are reduced in sleepiness. Herein, we discuss the potential role of the cholinergic system in this new clinical condition.

Beneficial effect of donepezil on obstructive sleep apnea: a double-blind, placebo-controlled clinical trial.

INTRODUCTION/OBJECTIVES: Previous publications have shown beneficial effects of cholinergic medication on obstructive sleep apnea (OSA) in Alzheimer's disease (AD) patients. We hypothesized that cholinergic medication could also improve OSA in non-AD patients. The present study evaluated the effects of donepezil on OSA in non-AD patients. METHODS: A randomized, double-blind, placebo-controlled study was conducted. The final sample consisted of 21 male patients with mild to severe OSA and AHI >10 divided into two groups, a donepezil-treated group (n=11) and a placebo-treated group (n=10). The dosage was one tablet/day (5 mg) for the first two weeks and two tablets/day (10 mg) for the last two weeks. Polysomnography and sleepiness evaluations were performed at baseline and after one month of treatment. Groups were compared using two-way ANOVA for repeated measures with treatment-group and treatment-time as the main factors and time-treatment as an interaction effect. RESULTS: Considering the effect of the interaction with time-treatment, there was a significant improvement in the obstructive apnea/hypopnea index, desaturation index, percentage of time with O(2) saturation ≤3% lower than baseline, lowest oxygen saturation, and the Epworth Sleepiness Scale (ESS) scores with donepezil treatment (p<0.05). Sleep efficiency significantly decreased (p<0.01). CONCLUSIONS: Donepezil treatment improved obstructive sleep apnea index, oxygen saturation, and sleepiness in parallel with a reduction in sleep efficiency. Our findings support the concept that cholinergic transmission may influence breathing regulation in OSA patients.

Seizure precipitants and inhibiting factors in mesial temporal lobe epilepsy.

Epileptic seizures may be triggered by both nonspecific facilitating factors and specific reflex epileptic mechanisms. These consist of sensory or cognitive inputs activating neural networks that, due to some functional instability, may respond with an epileptic discharge. The aim of this study was to determine the prevalence and nature of self-perceived seizure-inducing and -inhibiting factors in patients with mesial temporal lobe epilepsy (MTLE) followed from March 3rd to December 8th, 2009 at the Centro de Epilepsia de Santa Catarina Outpatient Clinic of the Hospital Governador Celso Ramos in Florianópolis, Brazil and their relation to demographics, epilepsy-related variables and anxiety level. Of the 71 patients, 60 (84.5%) patients identified at least one seizure trigger, and 36 (50.7%) patients identified inhibiting factors. In order of frequency, the most freely recalled precipitants were nervousness (58.8%), worrying (21.6%) and menstruation (19.6%), while the precipitants that were most frequently identified from a list were worrying (73.2%), anxiety (66.2%) and anger (53.5%). Knowledge of precipitant factors may have implications on the treatment and seizure control of patients.

Distrofia miotônica tipo 1: um relato de caso / Myotonic dystrophy type 1: a case report

A distrofia miotônica tipo I (DM1) é considerada aforma mais comum de miopatia em adultos, sendo caracterizadaclinicamente por fraqueza muscular, evidênciasclínicas de miotonia e uma história familiarpositiva. Apresenta, no entanto, uma grande variabilidadefenotípica, podendo ser encontradas manifestaçõesclínicas multissistêmicas (cardíacas, endócrinas,gastrointestinais, oftalmológicas e cognitivas) que podemdificultar seu diagnóstico. Relato de caso: pacientemasculino de 26 anos iniciou há 10 anos com quadrode fraqueza em membros superiores e inferiores. Apósanos sem melhora clínica, confirmou-se o diagnósticode DM1. Neste relato de caso ressalta-se a importânciada história clínica e exame físico do paciente para odiagnóstico de DM1.

Myotonic dystrophy type 1 (dystrophic myotonia type1 or DM1) is a muscle disorder, inherited in an autosomaldominant fashion, characterized by muscle wastingand weakness associated with myotonia and a numberof other systemic abnormalities, including cardiological,endocrine, gastroenterological, ophthalmological anddevelopmental impairment. A 26-year-old male patient,started 10 years ago with progressive superior and inferiorlimb weakness, associated with agoraphobia. Initiallyhe received the diagnosis of panic disorder and he wastreated with antidepressants. After years without clinicalimprovement, the diagnosis of DM1 was confirmed.Few diseases are as easy to recognize as DM1 once thediagnosis is considered. Conversely, misdiagnosis occurswhen the presenting complaint may be unrelated to thebasic problem, with patients presenting themselves tomany different specialists.

Novos sedativos hipnóticos / The newer sedative-hypnotics

Nas últimas décadas houve um esforço para o desenvolvimento de hipnóticos mais seguros e eficazes. Zolpidem, zaleplona, zopiclona, eszopiclona (drogas-z) e indiplona são moduladores do receptor GABA-A, os quais agem de forma seletiva na subunidade α1, exibindo, desta forma, mecanismos similares de ação, embora evidências recentes sugiram que a eszopiclona não seja tão seletiva para a subunidade α1 quanto o zolpidem. Ramelteon e tasimelteon são novos agentes crono-hipnóticos seletivos para os receptores de melatonina MT1 e MT2. Por outro lado, nos últimos anos, o consumo de drogas antidepressivas sedativas tem aumentado significativamente no tratamento da insônia. Como droga experimental, a eplivanserina tem sido testada como um potente agonista inverso do subtipo 5-HT2A da serotonina, com um uso potencial na dificuldade da manutenção do sono. Outro agente farmacológico para o tratamento da insônia é o almorexant, o qual apresenta um novo mecanismo de ação envolvendo antagonismo do sistema hipocretinérgico, desta forma levando à indução do sono. Finalmente, também discutiremos o potencial papel de outras drogas gabaérgicas no tratamento da insônia.

There has been a search for more effective and safe hypnotic drugs in the last decades. Zolpidem, zaleplon, zopiclone, eszopiclone (the z-drugs) and indiplon are GABA-A modulators which bind selectively α1 subunits, thus, exhibiting similar mechanisms of action, although recent evidence suggests that eszopiclone is not as selective for α1 subunit as zolpidem is. Ramelteon and tasimelteon are new chrono-hypnotic agents, selective for melatonin MT1 and MT2 receptors. On the other hand, the consumption of sedative antidepressant drugs is significantly increasing for the treatment of insomnia, in the last years. As an experimental drug, eplivanserin is being tested as a potent antagonist of serotonin 2-A receptors (ASTAR) with a potential use in sleep maintenance difficulty. Another recent pharmacological agent for insomnia is almorexant, which new mechanism of action involves antagonism of hypocretinergic system, thus inducing sleep. Finally we also discuss the potential role of other gabaergic drugs for insomnia.