Melatonin: From Pharmacokinetics to Clinical Use in Autism Spectrum Disorder.

The role of melatonin has been extensively investigated in pathophysiological conditions, including autism spectrum disorder (ASD). Reduced melatonin secretion has been reported in ASD and led to many clinical trials using immediate-release and prolonged-release oral formulations of melatonin. However, melatonin's effects in ASD and the choice of formulation type require further study. Therapeutic benefits of melatonin on sleep disorders in ASD were observed, notably on sleep latency and sleep quality. Importantly, melatonin may also have a role in improving autistic behavioral impairments. The objective of this article is to review factors influencing treatment response and possible side effects following melatonin administration. It appears that the effects of exposure to exogenous melatonin are dependent on age, sex, route and time of administration, formulation type, dose, and association with several substances (such as tobacco or contraceptive pills). In addition, no major melatonin-related adverse effect was described in typical development and ASD. In conclusion, melatonin represents currently a well-validated and tolerated treatment for sleep disorders in children and adolescents with ASD. A more thorough consideration of factors influencing melatonin pharmacokinetics could illuminate the best use of melatonin in this population. Future studies are required in ASD to explore further dose-effect relationships of melatonin on sleep problems and autistic behavioral impairments.

Poor Sleep Quality Is Associated with Altered Taste Perception in Chinese Adults.

BACKGROUND: Small clinical studies have suggested that individuals with insufficient sleep could experience taste dysfunction. However, this notion has not been examined in a large-scale, population-based study. OBJECTIVE: This study aimed to examine whether overall sleep quality, as assessed by insomnia, daytime sleepiness, snoring, and sleep duration, was associated with the odds of having altered taste perception in a large population-based study. DESIGN: This was a cross-sectional study that used data from a subcohort of the Kailuan study, an ongoing multicenter cohort study that began in 2006 in Tangshan City, China. PARTICIPANTS/SETTING: The participants were 11,030 adults aged 25 years or older (mean age 53.7 ± 10.7 years), who were free of neurodegenerative diseases. All the participants had undergone questionnaire assessments and medical examinations at Kailuan General Hospital from June 2012 to October 2013. MAIN OUTCOME MEASURES: Altered taste and olfactory perception were assessed via a questionnaire with two questions regarding whether participants had any problems with sense of taste or smell for ≥3 months. STATISTICAL ANALYSES PERFORMED: The association between sleep quality and altered taste/olfactory perception was examined using a logistic regression model, adjusting for age, sex, lifestyle factors (eg, obesity, smoking, alcohol intake, and physical activity) and health status (eg, lipid profiles, blood pressure, modification use, and presence of chronic diseases). RESULTS: Poor overall sleep quality was associated with a higher risk of having altered taste perception (adjusted odds ratio for low vs high sleep quality 2.03, 95% CI 1.42 to 2.91; P < 0.001). Specifically, insomnia, daytime sleepiness, and short sleep duration, but not prolonged sleep duration and snoring, were significantly associated with altered taste perception. A significant association between overall sleep quality and the risk of having altered olfactory perception was also observed (adjusted odds ratio for low vs high sleep quality 2.17, 95% CI 1.68 to 2.80; P < 0.001). CONCLUSIONS: In this population-based study, poor sleep quality was associated with a high likelihood of altered taste perception.

Sleep disorders in anti-NMDAR encephalitis.

OBJECTIVE: To describe the sleep disorders in anti-NMDA receptor encephalitis (anti-NMDARe). METHODS: Patients recovering from anti-NMDARe were invited to participate in a prospective observational single-center study including comprehensive clinical, video-polysomnography (V-PSG) sleep assessment, and neuropsychological evaluation. Age- and sex-matched healthy participants served as controls. RESULTS: Eighteen patients (89% female, median age 26 years, interquartile range [IQR] 21-29 years) and 21 controls (81% female, median age 23 years, IQR 18-26 years) were included. In the acute stage, 16 (89%) patients reported insomnia and 2 hypersomnia; nightmares occurred in 7. After the acute stage, 14 (78%) had hypersomnia. At study admission (median 183 days after disease onset, IQR 110-242 days), 8 patients still had hypersomnia, 1 had insomnia, and 9 had normal sleep duration. Patients had more daytime sleepiness than controls (higher Barcelona Sleepiness Index, p = 0.02, and Epworth Sleepiness Score, p = 0.04). On V-PSG, sleep efficiency was similar in both groups, but patients more frequently had multiple and longer confusional arousals in non-REM (NREM) sleep (videos provided). In addition, 13 (72%) patients had cognitive deficits; 12 (67%) had psychological, social, or occupational disability; and 33% had depression or mania. Compared with controls, patients had a higher body mass index (median 23.5 [IQR 22.3-30.2] vs 20.5 [19.1-21.1] kg/m2; p = 0.007). Between disease onset and last follow-up, 14 (78%) patients developed hyperphagia, and 6 (33%) developed hypersexuality (2 requiring hospitalization), all associated with sleep dysfunction. CONCLUSIONS: Sleep disturbances are frequent in anti-NMDARe. They show a temporal pattern (predominantly insomnia at onset; hypersomnia during recovery), are associated with behavioral and cognitive changes, and can occur with confusional arousals during NREM sleep.

Pediatric polysomnography-A review of indications, technical aspects, and interpretation.

Polysomnography is an elaborate diagnostic test composed of numerous data-collecting sensors working concomitantly to aid in the evaluation of varied sleep disorders in all age groups. Polysomnography is the study of choice for the assessment of pediatric sleep-disordered breathing, including obstructive sleep apnea syndrome, central apnea, and hypoventilation disorders, and is used to help determine treatment efficacy. Beyond the purview of snoring and breathing pauses, polysomnography can elucidate the etiology of hypersomnolence, when associated with a multiple sleep latency test, and abnormal movements or events, whether nocturnal seizure or complex parasomnia, when a thorough patient history cannot provide clear answers. This review will highlight the multitudinous indications for pediatric polysomnography and detail its technical aspects by describing the multiple neurophysiologic and respiratory parametric sources. Knowledge of these technical aspects will provide the practitioner with a thoughtful means to understand the limitations and interpretation of polysomnography.

Hyper-serotonergic state determines onset and progression of idiopathic Parkinson's disease.

Despite decades of research on Parkinson's disease (PD), the etiology of this disease remains unclear. The present manuscript introduces a new hypothesis proposing a hyper-serotonergic state as the main mechanism leading to axonal impairment both in dopaminergic and serotonergic neurons in PD. The strong serotonergic connection between the raphe nuclei and the dorsal raphe nuclei with the basal ganglia, all important brain structures associated with the pathophysiology of PD, emphasize a potential role for this neurotransmitter in PD. Importantly, a hyper-serotonergic state can lead to axonal growth impairment, an effect that seems to be selective to axons that can respond to this neurotransmitter. Serotonin seems to be a promising candidate to explain several of the poorly understood early symptoms of PD, including sleep impairment, anxiety, altered gastrointestinal motility and hallucinations. The hypothesis proposed here emphasizes that a hyper-serotonergic state would initially cause disruption of axonal transportation, an acute state in which axonal changes are reversible and the neurodegenerative process can be halted. As the hyper-serotonergic state persists, the accumulation of neurotoxic products and a sustained impairment in axonal transportation would lead to axonal death and culminate in an irreversible neurodegenerative process. The potential implications of this hypothesis are discussed, as well as how future research can be employed to further elucidate the role of serotonin on PD progression.

Effects of sleep disruption on stress, nigrostriatal markers, and behavior in a chronic/progressive MPTP male mouse model of parkinsonism.

Sleep complaints are an early clinical symptom of neurodegenerative disorders. Patients with Parkinson's disease (PD) experience sleep disruption (SD). The objective of this study was to determine if preexisting, chronic SD leads to a greater loss of tyrosine hydroxylase (TH) within the striatum and the substantia nigra following chronic/progressive exposure with the neurotoxin, 1-methyl-2-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Male mice underwent chronic SD for 4 weeks, then injected with vehicle (VEH) or increasing doses of MPTP for 4 weeks. There was a significant decrease in the plasma corticosterone levels in the MPTP group, an increase in the SD group, and a return to the VEH levels in the SD+MPTP group. Protein expression levels for TH in the striatum (terminals) and substantia nigra pars compacta (dopamine [DA] cell counts) revealed up to a 78% and 38% decrease, respectively, in the MPTP and SD+MPTP groups compared to their relevant VEH and SD groups. DA transporter protein expression increased in the striatum in the MPTP versus VEH group and in the SN/midbrain between the SD+MPTP and the VEH group. There was a main effect of MPTP on various gait measures (e.g., braking) relative to the SD or VEH groups. In the SD+MPTP group, there were no differences compared to the VEH group. Thus, SD, prior to administration of MPTP, has effects on serum corticosterone and gait but more importantly does not potentiate greater loss of TH within the nigrostriatal pathway compared to the MPTP group, suggesting that in PD patients with SD, there is no exacerbation of the DA cell loss.

Case of Childhood Absence Epilepsy with Focal Spikes.

BACKGROUND: Childhood absence epilepsy is a common generalized epilepsy syndrome characterized by childhood onset of frequent sporadic absence seizures. During onset, the electroencephalogram exhibits bilateral, symmetric, and synchronous discharges of approximately 3 Hz of generalized spike-and-wave complexes. Focal spikes are often found in children with focal epilepsy but are not common in absence epilepsy. CASE DESCRIPTION: In the case patient, focal spikes were observed during active onset of absence epilepsy and at 5 years after the first hospital visit, at which time absence epilepsy was controlled and medication was withdrawn without focal seizure attack in the interim. CONCLUSIONS: This case demonstrates that focal spikes associated with childhood absence epilepsy do not require specific treatment in the absence of focal seizures.

REM sleep fragmentation associated with depressive symptoms and genetic risk for depression in a community-based sample of adolescents.

INTRODUCTION: Fragmented REM sleep may impede overnight resolution of distress and increase depressive symptoms. Furthermore, both fragmented REM and depressive symptoms may share a common genetic factor. We explored the associations between REM sleep fragmentation, depressive symptoms, and a polygenic risk score (PRS) for depression among adolescents. METHODS: About 161 adolescents (mean age 16.9 ±â€¯0.1 years) from a birth cohort underwent a sleep EEG and completed the Beck Depression Inventory-II the same day. We calculated PRSes for depressive symptoms with PRSice 1.25 software using weights from a recent genome-wide association study for dimensions of depressive symptoms (negative emotion, lack of positive emotion and somatic complaints). REM fragmentation in relation to entire REM duration was manually calculated from all REM epochs. REM latency and density were derived using SomnoMedics DOMINO software. RESULTS: PRSes for somatic complaints and lack of positive emotions were associated with higher REM fragmentation percent. A higher level of depressive symptoms was associated with increased percent of REM fragmentation and higher REM density, independently of the genetic risks. Belonging to the highest decile in depressive symptoms was associated with a 2.9- and 7.6-fold risk of belonging to the highest tertile in REM fragmentation and density. In addition, higher PRS for somatic complaints had an independent, additive effect on increased REM fragmentation. LIMITATION: A single night's sleep EEG was measured, thus the night-to-night stability of the REM fragmentation-depressive symptom link is unclear. CONCLUSION: Depressive symptoms and genetic risk score for somatic complaints are independently associated with more fragmented REM sleep. This offers new insights on the quality of sleep and its relation to adolescents' mood.

Objective and Subjective Sleep Efficiency in Adult Patients with Cystic Fibrosis and Impact on Quality of Life.

INTRODUCTION: Poor sleep quality and excessive daytime sleepiness are common in patients with cystic fibrosis (CF), and both are negatively correlated with health-related quality of life (HRQoL). The objective of our study was to evaluate subjective and objective sleep quality in adult CF patients and its effect on HRQoL. MATERIALS AND METHODS: This was a descriptive, prospective, cross-sectional study of CF patients > 18 years of age. Patients underwent nocturnal polysomnography (PSG) and were administered the Pittsburgh Sleep Quality Index questionnaire (PSQI) and the Cystic Fibrosis Quality of Life Questionnaire (CFQR 14 + Spain). RESULTS: The study included 23 patients, 14 women (61%). The mean age of the participants was 32 + 18 years. The mean PSQI score was 5.57 + 3.55; 13 (56.5%) of the patients were poor sleepers, and 13% reported poor sleep quality; seven (30%) had sleep latency > 30 min, 10 (43.5%) had sleep efficiency < 85%. Nineteen underwent polysomnography. According to PSG measurements, sleep efficiency was less than 90% in 61% of the patients. Pathological values were found for the following parameters: intra-sleep wakefulness in 12 patients (63%); microarousal index in 12 patients (63%); and apnea-hypopnea index (AHI) in 2 patients. The desaturation time with SpO2 < 90% (T90) was > 30% in 3 patients. We observed a significant correlation between PSQI and all dimensions of CFQR 14. CONCLUSIONS: Subjective and objective sleep efficiency decreases in adult CF patients. Sleep quality has an impact on HRQoL. The PSQI questionnaire was able to discriminate sleep quality.

Posttraumatic stress disorder diagnosis is associated with reduced parasympathetic activity during sleep in US veterans and military service members of the Iraq and Afghanistan wars.

Study Objectives: To determine whether high-frequency heart rate variability (HF-HRV) during sleep differs between those with and without posttraumatic stress disorder (PTSD) as a function of sleep type (non-rapid eye movement [NREM] vs. rapid eye movement [REM]), and to explore this relationship across successive sleep cycles. Participants with PTSD were hypothesized to have lower HF-HRV across both REM and NREM sleep. Methods: Sixty-two post-9/11 military veterans and service members completed self-report measures of sleep quality, insomnia severity, and disruptive nocturnal behaviors. Participants then completed a laboratory-based polysomnographic study night with concurrent HRV assessment. Results: Participants with PTSD (N = 29) had lower HF-HRV in overall NREM sleep relative to those without PTSD (N = 33) (F(1, 54) = 4.24, p = .04). Groups did not differ on overall HF-HRV during REM sleep. HF-HRV increased over the night for the sample as a whole during both NREM and REM sleep. PTSD status did not moderate the association between HF-HRV and sleep cycles. However, the PTSD group had lower HF-HRV in the first t(155) = 2.67, p = .008, and fourth NREM cycles, t(155) = 2.11, p = .036, relative to participants without PTSD. Conclusions: Findings suggest blunted parasympathetic modulation during NREM sleep in a young cohort of military veterans and service-members with PTSD. Findings are concerning considering the increased risk of incident cardiovascular events associated with impaired parasympathetic nervous system function. Reduced parasympathetic modulation may be one mechanism underlying the increased prevalence of cardiovascular disease (CVD) among veterans with PTSD.

An evening milk drink can affect word recall in Indonesian children with decreased sleep efficiency: A randomized controlled trial.

STUDY OBJECTIVES: Sleep is important for memory consolidation in children. This study intended to find out whether an evening milk-based drink could influence sleep efficiency and memory recall in a group of Indonesian children (5-6 years old) with sleep deprivation. METHODS: Children were randomly allocated to one of three interventions: Reference product, satiety-stimulating product, and a relaxing product. The intervention lasted for 6 weeks and children consumed two servings per day of each 200 ml, the serving in the morning being the same for all children. All measurements took place at baseline and at the end of the intervention. Sleep parameters were studied using actigraphy and a sleep diary during three consecutive days. Memory consolidation was tested using a 20 word-pair list, which was memorized the evening before being recalled the next morning at home-base. Anthropometry was measured using standard equipment. RESULTS: The Satiety group showed a significant decrease in word recall, and a significant increase in nocturnal awakenings that was inversely associated with sleep efficiency at the end of the intervention. Sleep efficiency did not differ between the three groups being 75.5 ± 8.6% and 75.7 ± 6.3% at baseline and end of the intervention, respectively. Despite the lower energy intake in the Standard (reference) group, this condition showed the highest increase in weight. DISCUSSION: Evening growing-up milks can affect memory recall, sleep characteristics, and growth. However, to correct sleep efficiency and sleep duration, improvement of parental behavior may be the most important factor with nutrition providing a supplementary effect.

Sleep disruption in chronic rhinosinusitis.

INTRODUCTION: Chronic rhinosinusitis (CRS) is a common disease of the upper airways and paranasal sinuses with a marked decline in quality of life (QOL). CRS patients suffer from sleep disruption at a significantly higher proportion (60 to 75%) than in the general population (8-18 %). Sleep disruption in CRS causes decreased QOL and is linked to poor functional outcomes such as impaired cognitive function and depression. Areas covered: A systematic PubMed/Medline search was done to assess the results of studies that have investigated sleep and sleep disturbances in CRS. Expert commentary: These studies reported sleep disruption in most CRS patients. The main risk factors for sleep disruption in CRS include allergic rhinitis, smoking, and high SNOT-22 total scores. The literature is inconsistent with regard to the prevalence of sleep-related disordered breathing (e.g. obstructive sleep apnea) in CRS patients. Although nasal obstruction is linked to sleep disruption, the extent of sleep disruption in CRS seems to expand beyond that expected from physical blockage of the upper airways alone. Despite the high prevalence of sleep disruption in CRS, and its detrimental effects on QOL, the literature contains a paucity of studies that have investigated the mechanisms underlying this major problem in CRS.

[No motor signs in Parkinson's disease]. / Les signes non moteurs de la maladie de Parkinson.

In Parkinson's disease, motor signs have long been the main targets of the management of the disease. In recent years, non-motor disorders have elicited increasing interest. These disorders are under diagnosed and managed more difficultly than motor signs and are sometimes perceived as more disturbing by the patients. These signs are polymorphous, sometimes occurring before the motor symptoms but increase with the disease duration and complicating always the late stages. They may fluctuate as the motor signs, while being under the control of dopaminergic pathways, or be linked to the degeneration of other neuronal circuits. These clinical manifestations, whether or not fluctuating are classified into three major categories: psycho-cognitive including sleep disorders, autonomic and sensory.

Sex Hormones and Sleep in Men and Women From the General Population: A Cross-Sectional Observational Study.

CONTEXT AND OBJECTIVES: Associations between sex hormones and sleep habits originate mainly from small and selected patient-based samples. We examined data from a population-based sample with various sleep characteristics and the major part of sex hormones measured by mass spectrometry. DESIGN, SETTING, AND PARTICIPANTS: We used data from 204 men and 213 women of the cross-sectional Study of Health in Pomerania-TREND. MAIN OUTCOME AND MEASURES: Associations of total T (TT) and free T, androstenedione (ASD), estrone, estradiol (E2), dehydroepiandrosterone-sulphate, SHBG, and E2 to TT ratio with sleep measures (including total sleep time, sleep efficiency, wake after sleep onset, apnea-hypopnea index [AHI], Insomnia Severity Index, Epworth Sleepiness Scale, and Pittsburgh Sleep Quality Index) were assessed by sex-specific multivariable regression models. RESULTS: In men, age-adjusted associations of TT (odds ratio 0.62; 95% confidence interval (CI) 0.46-0.83), free T, and SHBG with AHI were rendered nonsignificant after multivariable adjustment. In multivariable analyses, ASD was associated with Epworth Sleepiness Scale (ß-coefficient per SD increase in ASD: -0.71; 95% CI: -1.18 to -0.25). In women, multivariable analyses showed positive associations of dehydroepiandrosterone-sulphate with wake after sleep onset (ß-coefficient: .16; 95% CI 0.03-0.28) and of E2 and E2 to TT ratio with Epworth Sleepiness Scale. Additionally, free T and SHBG were associated with AHI in multivariable models among premenopausal women. CONCLUSIONS: The present cross-sectional, population-based study observed sex-specific associations of androgens, E2, and SHBG with sleep apnea and daytime sleepiness. However, multivariable-adjusted analyses confirmed the impact of body composition and health-related lifestyle on the association between sex hormones and sleep.

Moderate Changes in the Circadian System of Alzheimer's Disease Patients Detected in Their Home Environment.

Alzheimer's disease (AD) is a neurodegenerative disease often accompanied with disruption of sleep-wake cycle. The sleep-wake cycle is controlled by mechanisms involving internal timekeeping (circadian) regulation. The aim of our present pilot study was to assess the circadian system in patients with mild form of AD in their home environment. In the study, 13 elderly AD patients and 13 age-matched healthy control subjects (the patient's spouses) were enrolled. Sleep was recorded for 21 days by sleep diaries in all participants and checked by actigraphy in 4 of the AD patient/control couples. The samples of saliva and buccal mucosa were collected every 4 hours during the same 24 h-interval to detect melatonin and clock gene (PER1 and BMAL1) mRNA levels, respectively. The AD patients exhibited significantly longer inactivity interval during the 24 h and significantly higher number of daytime naps than controls. Daily profiles of melatonin levels exhibited circadian rhythms in both groups. Compared with controls, decline in amplitude of the melatonin rhythm in AD patients was not significant, however, in AD patients more melatonin profiles were dampened or had atypical waveforms. The clock genes PER1 and BMAL1 were expressed rhythmically with high amplitudes in both groups and no significant differences in phases between both groups were detected. Our results suggest moderate differences in functional state of the circadian system in patients with mild form of AD compared with healthy controls which are present in conditions of their home dwelling.

Heightened Delta Power during Slow-Wave-Sleep in Patients with Rett Syndrome Associated with Poor Sleep Efficiency.

Sleep problems are commonly reported in Rett syndrome (RTT); however the electroencephalographic (EEG) biomarkers underlying sleep dysfunction are poorly understood. The aim of this study was to analyze the temporal evolution of quantitative EEG (qEEG) biomarkers in overnight EEGs recorded from girls (2-9 yrs. old) diagnosed with RTT using a non-traditional automated protocol. In this study, EEG spectral analysis identified high delta power cycles representing slow wave sleep (SWS) in 8-9h overnight sleep EEGs from the frontal, central and occipital leads (AP axis), comparing age-matched girls with and without RTT. Automated algorithms quantitated the area under the curve (AUC) within identified SWS cycles for each spectral frequency wave form. Both age-matched RTT and control EEGs showed similar increasing trends for recorded delta wave power in the EEG leads along the antero-posterior (AP). RTT EEGs had significantly fewer numbers of SWS sleep cycles; therefore, the overall time spent in SWS was also significantly lower in RTT. In contrast, the AUC for delta power within each SWS cycle was significantly heightened in RTT and remained heightened over consecutive cycles unlike control EEGs that showed an overnight decrement of delta power in consecutive cycles. Gamma wave power associated with these SWS cycles was similar to controls. However, the negative correlation of gamma power with age (r = -.59; p<0.01) detected in controls (2-5 yrs. vs. 6-9 yrs.) was lost in RTT. Poor % SWS (i.e., time spent in SWS overnight) in RTT was also driven by the younger age-group. Incidence of seizures in RTT was associated with significantly lower number of SWS cycles. Therefore, qEEG biomarkers of SWS in RTT evolved temporally and correlated significantly with clinical severity.

Ambulatory blood pressure monitoring in diabetes for the assessment and control of vascular risk.

The diagnosis of hypertension and the clinical decisions regarding its treatment are usually based on daytime clinic blood pressure (BP) measurements. However, the correlation between BP levels and target organ damage, cardiovascular (CV) risk, and long-term prognosis, is higher for ambulatory (ABPM) than clinic measurements, both in the general population as well as in patients with diabetes. Moreover, there is consistent evidence in numerous studies that the asleep BP better predicts CV events than either the awake or 24h means. The prevalence of abnormal BP pattern and sleep-time hypertension is extensive in diabetes, often leading to inaccurate diagnoses of hypertension and its therapeutic control in the absence of complete and careful assessment of the entire 24h, i.e., daytime and night-time, BP pattern. Accordingly, ABPM should be the preferred method to comprehensively assess and decide the optimal clinical management of patients with diabetes directed to properly reduce elevated sleep-time BP, which might also lead to a significant reduction of CV events.

[The atypical developments of rolandic epilepsy are predictable complications]. / Las evoluciones atipicas de la epilepsia rolandica son complicaciones predecibles.

INTRODUCTION: The development of atypical features in rolandic epilepsy is part of a clinical spectrum of phenotypes that are variable, idiopathic and age-dependent, as well as having a genetically determined predisposition. AIM: To study the electroclinical characteristics suggesting an atypical development in rolandic epilepsy. PATIENTS AND METHODS: A retrospective search was performed in 133 children diagnosed with atypical benign focal epilepsy (ABFE), Landau-Kleffner syndrome and continuous spike-wave during sleep (CSWS). Nine patients were selected, all of whom presented atypical clinical features and an electroencephalogram (EEG) pattern of electrical status epilepticus during sleep (ESES) in the course of their rolandic epilepsy. RESULTS: The average age at onset of rolandic epilepsy was 5 years. Patients showed a deterioration of both their clinical features and their EEG recording one and a half years later, on average. ABFE was observed in three of them and CSWS in six. No cases of Landau-Kleffner syndrome were found. The EEG in wakefulness showed the focus to be in the left centrotemporal region in six patients and in three of them it was on the right-hand side. All the patients presented ESES in the EEG during sleep. An atypical pattern was observed in the regional ESES in three of the patients. Moreover, cognitive and behavioural disorders were detected due to deficits in specific learning areas, such as language, memory, attention and restlessness. CONCLUSIONS: The early onset of rolandic epilepsy, the appearance of new seizures with an increased frequency and the frontocentrotemporal focus in the EEG, which increases in frequency, both in wakefulness and in sleep, are all electroclinical characteristics of an atypical development.

TITLE: Las evoluciones atipicas de la epilepsia rolandica son complicaciones predecibles.Introduccion. Las evoluciones atipicas de la epilepsia rolandica son parte de un espectro clinico de fenotipos variables, idiopaticos, dependientes de la edad y con una predisposicion geneticamente determinada. Objetivo. Estudiar las caracteristicas electroclinicas sugestivas de una evolucion atipica en la epilepsia rolandica. Pacientes y metodos. Se realizo una busqueda retrospectiva de 133 niños diagnosticados de epilepsia focal benigna atipica (EFBA), sindrome de Landau-Kleffner y epilepsia de punta-onda continua durante el sueño (POCS). Se seleccionaron nueve pacientes que, en el trascurso de su epilepsia rolandica, presentaron un cuadro clinico atipico y un patron electroencefalografico (EEG) de estado epileptico electrico durante el sueño (ESES). Resultados. El inicio de la epilepsia rolandica fue, en promedio, a los 5 años. Los pacientes presentaron un empeoramiento clinico y del EEG año y medio mas tarde en promedio. En tres pacientes se observaron caracteristicas de EFBA, y en seis, de POCS. No se encontraron casos de sindrome de Landau-Kleffner. El EEG en vigilia mostro una focalidad centrotemporal izquierda en seis pacientes, y derecha, en tres. Todos los pacientes presentaron un ESES en el EEG de sueño. En tres de ellos se observo un patron atipico de ESES regional. Ademas, se detectaron alteraciones cognitivas y conductuales por deficits en areas especificas del aprendizaje, como lenguaje, memoria, atencion e inquietud. Conclusiones. El inicio precoz de la epilepsia rolandica, la aparicion de nuevas crisis con un incremento en su frecuencia y una focalidad frontocentrotemporal en el EEG, que aumenta en frecuencia, tanto en vigilia como en sueño, son caracteristicas electroclinicas sugerentes de una evolucion atipica.