Objective and Subjective Sleep Patterns in Adults With Maturity-Onset Diabetes of the Young (MODY).

OBJECTIVE: To examine sleep patterns in adults with maturity-onset diabetes of the young (MODY). RESEARCH DESIGN AND METHODS: Adults with glucokinase (GCK)-MODY and transcription factor (TF)-related MODY (HNF1A, HNF1B, HNF4A) were recruited (n = 24; age 46.0 years, 79% women, BMI 24.7 kg/m2) from The University of Chicago's Monogenic Diabetes Registry. Sleep patterns were assessed by 2-week wrist actigraphy (total 315 nights), one night of a home sleep apnea test, and validated surveys. RESULTS: Overall, compared with established criteria, 29% of participants had sleep latency ≥15 min, 38% had sleep efficiency ≤85%, 46% had wake after sleep onset >40 min, all indicating poor objective sleep quality. Among all participants, 54% had a sleep duration below the recommended minimum of 7 h, 88% reported poor sleep quality, 58% had obstructive sleep apnea, and 71% reported insomnia. Compared with GCK-MODY, participants with TF-related MODY had poorer objective sleep quality and increased night-to-night variability in sleep patterns. CONCLUSIONS: Sleep disturbances appear to be common in adults with MODY despite absent traditional risk factors for sleep disorders. Future research investigating the sleep-diabetes relationship is warranted in this population.

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.

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.

Risk factors for sleep quality disturbances in patients with lumbar spinal stenosis before operation.

PURPOSE: We aimed to explore the risk factors of preoperative sleep quality in patients with lumbar spinal stenosis (LSS) and the association of sleep-related beliefs with sleep quality in these patients. METHODS: Sleep quality and related risk factors of sleep quality disturbances in patients with LSS preoperatively were assessed by questionnaires. Pittsburgh Sleep Quality Index (PSQI) for sleep quality, Oswestry Disability Index (ODI) for clinical outcomes, Visual Analog Scale for Pain (VAS Pain), Self-Rating Anxiety Scale (SAS) for anxiety level, and Dysfunctional Beliefs and Attitudes about Sleep (DBAS-16) for sleep-related beliefs were assessed. Bivariate logistic regression analysis was used to assess the risk factors of sleep quality disturbances. RESULTS: A total of 227 patients were enrolled, mean age 64 years (SD 13.1), 119 women (52%). The incidence of sleep quality disturbances in patients was 37% (83/227). Increased DBAS-16 scores (OR = 0.781; 95% CI, 0.725-0.841; p < 0.001) significantly decreased the probability of developing sleep quality disturbances, while increased anxiety levels (OR = 1.241; 95% CI, 1.152-1.337; p < 0.001) significantly increased the probability of developing sleep quality disturbances in patients. Factors including educational level, increased age, sex, preoperative length of stay, VAS Pain scores, and ODI scores showed no significant association and were therefore excluded from the model. CONCLUSIONS: High levels of anxiety and mistaken sleep-related beliefs were risk factors of sleep quality disturbances in patients with LSS before surgery. The more mistaken sleep-related beliefs were, the greater the probability of sleep disturbances.

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.

Abnormal nocturnal behavior due to hypoglycemia: A case report.

RATIONALE: Hypoglycemia, which is characterized mainly by palpitations, dizziness, and sweating, is common and easy to identify. However, some other symptoms, such as mental disorder or abnormal behavior, are atypical, which may lead to a misdiagnosis of epilepsy, sleepwalking, infarction, or mental disorder, among others. PATIENT CONCERNS: We report a case of a patient with type 2 diabetes who presented with abnormal nocturnal behavior due to hypoglycemia. DIAGNOSIS: Hypoglycemia was diagnosed based on a blood glucose level of 2.1 mmol/L when the patient turned up disoriented unresponsive, unable to understand what was said to him, and producing nonsensical speech. After the patient ate a piece of chocolate, his consciousness returned to normal and all mental symptoms disappeared. Polysomnography (PSG) was synchronously performed. The results of the PSG did not show any signs of abnormality during nonrapid eye movement (NREM) or rapid eye movement (REM) sleep. INTERVENTIONS: We regulated his dose of insulin. OUTCOMES: No additional episodes occurred during the 3-month follow-up. Therefore, the abnormal nocturnal behavior of this patient was determined to be due to hypoglycemia, while the cause of the hypoglycemia was insulin overuse. LESSONS: For physicians, if the cause of abnormal behavior cannot be detected, hypoglycemia should be suspected. Long-term persistent hypoglycemia may cause brain dysfunction and even result in permanent brain damage.

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.

Correlation between allopregnanolone levels and depressive symptoms during late menopausal transition and early postmenopause.

OBJECTIVES: This observational, cross-sectional study included 140 women with climacteric symptoms. The aim of the study was to evaluate the correlation between the presence and severity of depressive symptoms and allopregnanolone levels in women during late menopausal transition and early postmenopause. METHODS: The study group was divided into two groups: 45 women in late menopausal transition and 95 early postmenopausal women. We evaluated Kupperman index, Hamilton scale and serum follicle-stimulating hormone, luteinizing hormone, 17ß-estradiol, prolactin, total testosterone, dehydroepiandrosterone sulfate and allopregnanolone levels. RESULTS: We found that serum allopregnanolone concentration was lower in early postmenopausal women compared to women in late menopausal transition; that there was a correlation between serum allopregnanolone levels in early postmenopausal women and time since last menstruation, intensity of climacteric symptoms, and intensity of depression symptoms and that there was a correlation between serum allopregnanolone levels and several depression symptoms presence (shallow sleep and symptoms of the digestive tract in women during late menopause transition; feelings of guilt, sleep disorders and general somatic symptoms in early postmenopausal women). CONCLUSION: We concluded that reproductive aging is characterized by a reduction of allopregnanolone circulating levels that correlate to Hamilton depression index in early postmenopause and presence of specific depressive symptoms during late menopausal transition and early postmenopause.

Adjunctive low-dose docosahexaenoic acid (DHA) for major depression: An open-label pilot trial.

OVERVIEW: Whilst the majority of evidence supports the adjunctive use of eicosapentaenoic acid (EPA) in improving mood, to date no study exists using low-dose docosahexaenoic acid (DHA) alone as an adjunctive treatment in patients with mild to moderate major depressive disorder (MDD). METHODS: A naturalistic 8-week open-label pilot trial of low-dose DHA, (260 mg or 520 mg/day) in 28 patients with MDD who were non-responsive to medication or psychotherapy, with a Hamilton Depression Rating Scale (HAM-D) score of greater than 17, was conducted. Primary outcomes of depression, clinical severity, and daytime sleepiness were measured. RESULTS: After 8 weeks, 54% of patients had a ≥50% reduction on the HAM-D, and 45% were in remission (HAM-D ≤ 7). The eta-squared statistic (0.59) indicated a large effect size for the reduction of depression (equivalent to Cohen's d of 2.4). However confidence in this effect size is tempered due to the lack of a placebo. The mean score for the Clinical Global Impression Severity Scale was significantly improved by 1.28 points (P < 0.05). Despite a significant reduction in the HAM-D score for middle insomnia (P = 0.02), the reduction in excessive daytime somnolence on the total Epworth Sleepiness Scale (ESS) did not reach significance. No significant adverse reactions to DHA were found. CONCLUSION: Within the major limits of this open-label pilot study, the results suggest that DHA may provide additional adjunctive benefits in patients with mild- to -moderate depression.

[Evaluation and treatment of sleep problems in children diagnosed with attention deficit hyperactivity disorder: an update of the evidence]. / Evaluacion y tratamiento de los problemas de sueño en niños diagnosticados de trastorno por deficit de atencion/hiperactividad: actualizacion de la evidencia.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) affects approximately 5% of all children and adolescents, and these patients frequently suffer from sleep problems. The association between sleep disorders and ADHD, however, is multifaceted and complex. AIMS: To explore the relationship between sleep disorders and ADHD. DEVELOPMENT: Sleep problems in children with ADHD include altered sleep and specific disorders per se or that may be due to comorbid psychiatric disorders or to the stimulants they receive as treatment for their ADHD. Today, an evaluation of the sleep conditions in children with ADHD is recommended before starting pharmacological treatment. The first step in managing their sleep problems is good sleep hygiene and cognitive-behavioural psychotherapy. Another option is to consider modifying the dosage and formulation of the stimulants. Atomoxetine and melatonin are therapeutic alternatives for children with ADHD and more severe sleep problems. Specific treatments exist for respiratory and movement disorders during sleep. CONCLUSIONS: It is important to evaluate sleep in children who present symptoms suggestive of ADHD, since problems during sleep can play a causal role or exacerbate the clinical features of ADHD. Correct evaluation and treatment of sleep disorders increase the family's and the child's quality of life and can lessen the severity of the symptoms of ADHD.

TITLE: Evaluacion y tratamiento de los problemas de sueño en niños diagnosticados de trastorno por deficit de atencion/hiperactividad: actualizacion de la evidencia.Introduccion. El trastorno por deficit de atencion/hiperactividad (TDAH) afecta aproximadamente al 5% de los niños y adolescentes, y los problemas del sueño son comunes en estos pacientes. Sin embargo, la asociacion entre los trastornos del sueño y el TDAH es multifacetica y compleja. Objetivo. Explorar la relacion entre los trastornos del sueño y el TDAH. Desarrollo. Los problemas del sueño en niños con TDAH incluyen alteraciones del sueño y trastornos especificos per se o debidos a trastornos psiquiatricos comorbidos o a los farmacos estimulantes para el TDAH. Actualmente se recomienda la evaluacion de las condiciones del sueño en niños con TDAH antes de la iniciacion del tratamiento farmacologico. La primera linea de actuacion para el manejo de los problemas de sueño es la higiene del sueño y la psicoterapia cognitivo-conductual. Otra opcion es considerar la modificacion de la posologia y formulacion de los farmacos estimulantes. La atomoxetina y la melatonina son alternativas terapeuticas para los niños con TDAH y problemas del sueño mas graves. Para los trastornos respiratorios y del movimiento en el sueño existen tratamientos especificos. Conclusiones. Es importante evaluar el sueño en los niños que presentan sintomas sugestivos de TDAH, ya que los problemas en el sueño pueden desempeñar un papel causal o exacerbar la clinica del TDAH. Una correcta evaluacion y tratamiento de los trastornos del sueño aumentan la calidad de vida de la familia y del niño y pueden disminuir la gravedad de los sintomas del TDAH.

[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.

Work-family conflict and sleep disturbance: the Malaysian working women study.

This study aimed at assessing effect of the four dimensions of work-family conflicts (strain and time-based work interference into family and family interference into work) on sleep disturbance in Malaysian working women. This cross-sectional study was conducted among 325 Malaysian married working women. Multiple-stage simple random sampling method was used to recruit women from public service departments of Malaysia. Self-administrated questionnaires were used to measure the study variables and data were analyzed using SPSS version 21. We found that high level of the four dimensions of work-family conflicts significantly increase sleep disturbance. Our analyses also revealed an age-dependent effect of the work-family conflict on sleep disturbance. Women in their 20 to 30 yr old suffer from sleep disturbance due to high level of time-based and strain-based work-interference into family. However, the quality of sleep among women aged 30-39 were affected by strain-based family-interference into work. Finally, women older than 40 yr had significantly disturbed sleep due to strain-based work-interference into family as well as time-based family interference into work. Our findings showed that sleep quality of working women might be disturbed by experiencing high level of work-family conflict. However, the effects of inter-role conflicts on sleep varied among different age groups.

MDS-UPDRS to assess non-motor symptoms after STN DBS for Parkinson's disease.

OBJECTIVE: To determine if the non-motor sections of the Movement Disorder Society's (MDS) version of the Unified Parkinson's Disease Rating Scale (UPDRS) could supplement the original UPDRS as a patient completed assessment of changes in non-motor symptoms in Parkinson's disease (PD) patients after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS). METHODS: Thirty PD patients who underwent bilateral STN DBS were assessed using the total UPDRS and the non-motor sections of the MDS-UPDRS prior to surgery and one year following surgery. This study focuses on non-motor symptoms as assessed by Part I of the UPDRS and Part 1A and 1B of the MDS-UPDRS. RESULTS: One year following surgery, no individual non-motor symptoms or the total mentation score of the UPDRS were significantly changed. In comparison, the MDS-UPDRS showed significant improvements in sleep and urinary problems and a trend towards improvement in anxiety, constipation, daytime sleepiness, fatigue and pain. CONCLUSIONS: This study provides evidence that the MDS-UPDRS non-motor sections, when completed by the patients, can supplement the original version of the UPDRS as an effective method of measuring changes in non-motor symptoms after DBS. It also reinforces the benefits of bilateral STN DBS on non-motor symptoms of PD.

[Sluggish cognitive tempo: an updated review]. / Tempo cognitivo lento: una revision actualizada.

INTRODUCTION: The study of sluggish cognitive tempo (SCT) arose largely from research carried out on attention deficit hyperactivity disorder (ADHD). This construct is defined by a range of behavioural symptoms such as the appearance of drowsiness, daydreaming, physical hypoactivity, little initiative, lethargy and apathy. DEVELOPMENT: The construct of SCT is reviewed by means of recently published papers on its clinical characteristics, associated symptoms, evaluation, prevalence, aetiology, comorbidity, neuropsychological profiles and treatment. The latest studies propose that SCT should be understood as a cluster of symptoms that is distinct from ADHD. Although there is no clear consensus on the matter, the evidence is becoming increasingly more consistent and endows SCT with a high degree of external validity, associating it with internalising symptoms. CONCLUSIONS: We believe the different subtypes of ADHD must be grounded in attentional conceptual models. Hence, the attentional guidance network would be related with SCT, the vigilance or sustained attention network would be linked with the inattentive subtype of ADHD, and executive attention would be involved in the combined subtype of ADHD. The evidence obtained to date, including this review, supports the idea that SCT is an attention disorder distinct from ADHD but, like any dimensional disorder, it can overlap with it in around half the cases.

TITLE: Tempo cognitivo lento: una revision actualizada.Introduccion. El estudio del tempo cognitivo lento (TCL) surgio en gran parte de las investigaciones del trastorno por deficit de atencion/hiperactividad (TDAH). Este constructo se define con una gama de sintomas conductuales, como apariencia de somnolencia, soñar despierto, hipoactividad fisica, pobre iniciativa, letargo y apatia. Desarrollo. Se revisa el constructo de TCL a traves de articulos recientemente publicados al respecto sobre caracteristicas clinicas, sintomas asociados, evaluacion, prevalencia, etiologia, comorbilidad, perfiles neuropsicologicos y tratamiento. Los trabajos mas actuales proponen entender el TCL como un cluster de sintomas distintivo del TDAH. Aunque no hay un consenso claro, los datos son cada vez mas consistentes y dotan de gran validez externa al TCL, asociandolo con sintomas internalizantes. Conclusiones. Consideramos necesario anclar los diferentes subtipos de TDAH en modelos conceptuales atencionales. Asi, la red de orientacion atencional se relacionaria con el TCL, la red de vigilancia o atencion sostenida con el TDAH subtipo inatento, y la atencion ejecutiva seria la implicada en el TDAH subtipo combinado. La evidencia hasta la fecha, incluyendo esta revision, apoya la idea de que el TCL es un trastorno de atencion diferenciado del TDAH, pero que, como cualquier trastorno dimensional, puede solaparse con el aproximadamente en la mitad de los casos.

[Transient global amnesia: A descriptive study of 12 Polynesian patients]. / Ictus amnésique: étude descriptive de 12 patients polynésiens.

INTRODUCTION: According to the criteria of Hodges and Warlow, transient global amnesia is defined by sudden onset of isolated anterograde amnesia of spontaneous resolution within one to twenty-four hours. Its pathophysiological mechanisms are still uncertain. METHODS: In a retrospective study, we have analyzed epidemiological, clinical and MRI data from twelve patients admitted to the only neurological department of French Polynesia for transient global amnesia corresponding to the criteria of Hodges and Warlow between January 2010 and December 2013. RESULTS: The median age of the cohort was 61.5 (53-72), the sex ratio was 1. Ten patients had one or more cardiovascular risk factors, 3 had migraine headaches and 3 had anxiodepressive disorders. Among triggers found, the occurrence during the rest was noted in one case. Retrograde amnesia was observed in 42% of cases, repetitive questioning in 75% of cases, anxious bewilderment in 67% of cases and disorientation in 33% of cases. The median episode duration was 9 hours and the duration of hospitalization was 3 days. Three patients had a recurrence. MRI was abnormal in all patients and showed diffusion-weighted hyperintensities in right (n=8), left (n=3) and bilateral (n=1) hippocampi. CONCLUSION: Epidemiological, clinical and MRI data from our cohort are similar to those from the literature except for the highest prevalence of cardiovascular risk factors and the most frequent right hippocampus involvement. Transient global amnesia occurring exceptionally while sleeping was also observed in one of our patients.

Clinical and Neurologic Manifestation of Minimal Hepatic Encephalopathy and Overt Hepatic Encephalopathy.

Hepatic encephalopathy (HE) shows a wide spectrum of neuropsychiatric manifestations. A combined effort with neuropsychological and psychometric evaluation has to be performed to recognize the syndrome, whereas minimal HE (MHE) is largely under-recognized. Subtle symptoms of MHE can only be diagnosed through specialized neuropsychiatric testing. Early diagnosis and treatment may drastically improve the quality of life for many cirrhotic patients. Further research to gain better insight into the pathophysiology and diagnostic accuracy of HE will help determine future management strategies.

[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.

A prospective study of adverse drug reactions to antiepileptic drugs in children.

OBJECTIVES: To prospectively determine the nature and rate of adverse drug reactions (ADRs) in children on antiepileptic drugs (AEDs) and to prospectively evaluate the effect of AEDs on behaviour. SETTING: A single centre prospective observational study. PARTICIPANTS: Children (<18 years old) receiving one or more AEDs for epilepsy, at each clinically determined follow-up visit. PRIMARY AND SECONDARY OUTCOMES: Primary outcome was adverse reactions of AEDs. Behavioural and cognitive functions were secondary outcomes. RESULTS: 180 children were recruited. Sodium valproate and carbamazepine were the most frequently used AEDs. A total of 114 ADRs were recorded in 56 of these children (31%). 135 children (75%) were on monotherapy. 27 of the 45 children (60%) on polytherapy had ADRs; while 29 (21%) of those on monotherapy had ADRs. The risk of ADRs was significantly lower in patients receiving monotherapy than polytherapy (RR: 0.61, 95% CI 0.47 to 0.79, p<0.0001). Behavioural problems and somnolence were the most common ADRs. 23 children had to discontinue their AED due to an ADR. CONCLUSIONS: Behavioural problems and somnolence were the most common ADRs. Polytherapy significantly increases the likelihood of ADRs in children. TRAIL REGISTRATION NUMBER: EudraCT (2007-000565-37).