Psychological functioning measures in patients with primary insomnia and sleep state misperception.

OBJECTIVE: Sleep state misperception (SSM) is a term used in the International Classification of Sleep Disorders to indicate people who mistakenly perceive their sleep as wakefulness. SSM is a form of primary insomnia. The aim of this study was to record psychological functioning measures (anxiety, depression, ability to feel pleasure, obsessive-compulsive traits) in a population of patients with primary insomnia and to evaluate the relationship between these measures and the patients' perception of their sleep. MATERIALS AND METHODS: Seventy-six consecutive patients with primary insomnia were enrolled: 34 men and 42 women, mean age 53.9 ± 13.1. Sleep study included the following: Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Berlin's Questionnaire and home-based polysomnography. Psychometric evaluation included the following: Self-Administered Anxiety Scale, Beck's Depression Inventory, Maudsley's Obsessive Compulsive Inventory, Snaith-Hamilton Pleasure Scale, Eating Attitude Test. RESULTS: All patients with insomnia had psychometric scores higher than the general population, but very few patients, in both groups, had anxiety or depression scores consistent with severe mood or anxiety disorders. Comparisons between subjective and objective scores confirmed that most sleep parameters were underestimated. Patients with SSM had lower anxiety scores as compared to patients without SSM. CONCLUSIONS: The study did not succeed in identifying any predictor of sleep misperception. We speculate that a group of patients, rather than being extremely worried by their insomnia, may have a sort of agnosia of their sleep.

Dysfunction of arousal systems in sleep-related migraine without aura.

Primary headaches are closely related to sleep. Modifications in the patterns of arousal during sleep have been reported in migraine, especially in the nights preceding a headache attack. We aimed at evaluating the pattern of arousal from sleep in a group of patients affected by sleep-related migraine. We enrolled 10 consecutive patients, three males and seven females, aged between 20 and 62 years, who presented frequent attacks of migraine without aura (more than five per month), closely related to sleep (more than one-half of the attacks occurred during sleep, causing an awakening). A control group was studied, matched for age and sex. Patients and controls underwent a full-night polysomnographic study, following adaptation; arousal pattern was studied by the scoring of the high-frequency EEG arousal and by the cyclic alternating pattern (CAP). Migraineurs showed a lower CAP rate in non-rapid eye movement (NREM) sleep and, in particular, a lower number of A1 phases (low-frequency, high-amplitude EEG bursts) compared with the controls. Migraineurs also showed a lower index of high-frequency EEG arousals during rapid eye movement (REM) sleep. The reduction in the CAP rate indicates a lower level of arousal fluctuation in NREM sleep. The reduced arousal index in REM suggests a dysfunction in neural structures involved in both the control of REM sleep and the pathophysiology of migraine, such as the hypothalamus and the brainstem.

A sleep study in cluster headache.

Cluster headache (CH) is a primary headache with a close relation to sleep. CH presents a circa-annual rhythmicity; attacks occur preferably during the night, in rapid eye movement (REM) sleep, and they are associated with autonomic and neuroendocrine modifications. The posterior hypothalamus is the key structure for the biological phenomenon of CH. Our aim is to describe a 55-year-old man presenting a typical episodic CH, in whom we performed a prolonged sleep study, consisting of a 9-week actigraphic recording and repeated polysomnography, with evaluation of both sleep macrostructure and microstructure. During the acute bout of the cluster we observed an irregular sleep-wake pattern and abnormalities of REM sleep. After the cluster phase these alterations remitted. We conclude that CH was associated, in this patient, with sleep dysregulation involving the biological clock and the arousal mechanisms, particularly in REM. All these abnormalities are consistent with posterior hypothalamic dysfunction.

Miller-Fisher syndrome mimicking intracranial hypertension following head trauma.

INTRODUCTION: Miller-Fisher syndrome (MFS) is a polyneuropathy with benign outcome characterized by ophthalmoplegia, limb ataxia and tendon areflexia. Impaired consciousness level and intracranial hypertension are very rare symptoms in MFS. CASE REPORT: We describe the case of a 5-year-old girl who showed intracranial hypertension, transient coma and respiratory failure after mild head injury; moreover the patient showed mild ataxia, areflexia, ophthalmoplegia and autonomic disturbances. These symptoms were suggestive of MFS. Electrophysiologic studies and laboratory tests confirmed the diagnosis and immunoglobulins and steroids were given. The child showed a progressive clinical improvement and the final outcome was good. CONCLUSION: This case, initially managed as trauma injury due to the presence of suggestive signs and clinical history, maskered an atypical presentation of Miller-Fisher syndrome, a rare disorder of central nervous system.

Sleep disorders in Sanfilippo syndrome: a polygraphic study.

OBJECTIVE: A high prevalence of sleep disorders is reported in patients affected by Mucopolysaccharidosis III (Sanfilippo syndrome). These disorders have never been investigated by prolonged, objective, and instrumental evaluations. The present work is based on sleep duration and structure in Sanfilippo patients. STUDY DESIGN: The features of sleep/wake cycle in 6 Sanfilippo patients and 6 healthy controls were evaluated by means of sleep diaries and 48 hour ambulatory EEG and polygraphic recordings. Statistical analysis was performed by means of the U-test (Mann-Whitney). RESULTS: Four out of six Sanfilippo patients, the oldest patients in our sample, showed an extremely irregular sleep pattern, with several sleep episodes of inconstant duration, irregularly distributed along 24 hours. The two younger patients showed sleep maintenance insomnia with several nocturnal awakenings. CONCLUSIONS: These results suggest that sleep disruption in Sanfilippo syndrome consists of an irregular sleep/wake pattern, which at its onset might appear as a disorder of initiating or maintaining sleep. This could explain why same patients do not respond to conventional hypnotics. The present observation might suggest attempting therapies aimed at resynchronization, such as behavioral treatment, light therapy or melatonin.

Role of renal PGE2 in the adaptation from foetal to extrauterine life in term and preterm infants.

Urinary PGE(2) concentrations were assayed using a new EIA method, in 16 preterm and 18 term neonates at birth and 3 days later, since there is evidence that PGE(2) in urine are likely to reflect their renal generation and then could be correlated with kidney maturation or renal problems. PGE(2) concentrations were not different at birth (1.50+/-1.12 vs 1.56+/-1.94 ng/day), while resulted significantly higher in preterms, compared to terms, three days after birth (2.22+/-1.23 vs 1.39+/-0.79 ng/day). This increase in daily PGE(2) excretion observed only in preterm neonates could be due to an increased renal biosynthesis as a mechanism of compensatory response to prevent further decrements in renal plasma flow, since prostanoids play an important role in protecting the immature kidney from high levels of angiotensin II. Otherwise, the passive reabsorption of PGE(2) along the distal nephron could be altered because of kidney immaturity. The measurement of PGE(2) in urine of neonates, particularly prematures, could be useful to provide a better understanding of the homeostatic function of the kidney in the phase of adaptation to extra-uterine life.

El tratamiento con L-acetilcarnitina del comportamiento hiperactivo de pacientes con el síndrome X frágil / L-acetylcarnitine treatment on fragile patient hyperactive behaviour

Introducción. La hiperactividad es un problema significativo en casi todos los varones afectados por el síndrome X frágil (SXF), la enfermedad hereditaria más frecuente de retraso mental. Los enfoques terapéuticos se basan actualmente en estimulantes del sistema nervioso central (SNC), cuyos mecanismos de funcionamiento y su eficacia no están claramente definidos, a la vez que reducen el limitado tiempo de atención del paciente. Desarrollo. Un estudio piloto con 17 varones con SXF tratados con L-acetilcarnitina (LAC) durante un año demostró una reducción significativa en el comportamiento hiperactivo evaluado con el cuestionario Conners de padres y profesores. El uso de LAC en pacientes con SXF se deriva de la hipótesis que las propiedades bioquímicas y fisiológicas de esta sustancia pueden preservar la actividad cerebral. La LAC es una molécula pequeña hidrosoluble que se difunde fácilmente en el espacio extracelular y entra en cualquier célula del sistema nervioso por medio de un transportador específico. Las diferentes áreas del cerebro utilizan de forma diferente esta molécula para metabolizar la glucosa y lípidos para abastecer de ATP y la síntesis de neurotransmisores. El grupo acetilo presente en la LAC representa un elemento de señalización metabólica de gran importancia, posiblemente mediando su efecto en el SNC. La administración exógena de LAC puede afectar la actividad cerebral en el SXF por: modulación o administración de carburante para la producción de energía, que a nivel mitocondrial se asocia con el papel metabólico de la síntesis de neurotransmisores del ciclo de Krebs; remodelación de la membrana lipídica en función de la determinación activa, por parte de la LAC, de la producción de ácidos grasos polinsaturados, y efecto preferencial en el componente de atención del sistema colinérgico que depende de su peculiar modalidad de comunicación en el SNC. Un estudio explorativo, doblemente ciego, controlado con placebo y multicéntrico, se está llevando a cabo en función de estas premisas. Se incluirá una población total de 160 niños de nueve centros europeos. El objetivo del estudio es determinar el efecto de la LAC en el comportamiento hiperactivo de los niños con SXF de acuerdo con la evaluación del cuestionario Conners de padres y profesores (AU)

Seizures in an interferon-treated child.

Interferon-treated patients can present seizures, which in most paediatric cases are related to fever. The case of chronic hepatitis C is described in which Interferon probably disclosed a latent epilepsy. The hypothesis is advanced that seizures can be provoked by Interferon therapy in subjects with a low convulsant threshold and, in those cases in which it cannot be substituted with another drug, antiepileptic therapy should be started after the first episode.

[L-acetylcarnitine treatment on fragile X patients hyperactive behaviour]. / El tratamiento con L-acetilcarnitina del comportamiento hiperactivo de pacientes con el síndrome X frágil.

Hyperactivity is a significant problem for almost all young males affected by fragile X syndrome (FXS), the most common inherited disease causing mental retardation. Therapeutical approaches are actually based on Central Nervous System (CNS) stimulants lacking a well defined rationale and efficacy while they further decrease the patient's limited attention span. A pilot study on 17 fragile X male treated with L-acetylcarnitine (LAC) over one year, showed a significant reduction of their hyperactivity behaviour tested by the Conners Abbreviated Parent-Teacher Questionnaire. LAC use in FXS patients derives from the hypothesis that the biochemical and physiological properties this substance has may preserve brain activity. LAC is a small, hydrosoluble molecule that easily diffuses in the extracellular space and enters any cell in the nervous system through specific transporters. Different cerebral areas use this molecule differently to metabolize glucose and lipids to provide for ATP and neurotrasmitters synthesis. The acetyl group LAC carriers represents a key metabolic signaling element possibly mediating its effect in the CNS. The exogenous administration of LAC may affect brain activity in FXS by: I) modulation of fuel partitioning for energy production, which at the mithocondrial level is associated with the Kreb's cycle metabolic role in neurotransmitter synthesis; II) remodelling of lipid membrane in terms of LAC actively determining the production of polyunsaturated fatty acids; III) preferential effect on the attention component of the cholinergic system which relies on its peculiar modality of communication in the CNS. Based on the above premises an explorative, double-blind, placebo controlled, multicenter study is ongoing. A total population of 160 children from nine European centers will be enrolled. The objective of this study is to determine the effect of LAC on the hyperactive behaviour of FXS children as evaluated by the administration of the Conners Abbreviated Parent Questionnaire.

Is ESES/CSWS a strictly age-related disorder?

OBJECTIVES: We report on a case of ESES/CSWS observed in a patient of 21 years and still persisting at the age of 25. Cases of ESES/CSWS have never been previously described in adult patients. ESES/CSWS is considered to be related to the degree of maturation of the central nervous system, and therefore strictly age-related. METHODS: Our case of ESES/CSWS was observed in a 2 1 year old woman referred for cognitive and behavioral disorders. She had previously had epileptic fits, but was seizure free at that time. The patient underwent a full-night polygraphic recording , which showed typical ESES/CSWS pattern, with a Spike-and-Wave Index >8 5%. Polysomnography was repeated 9 times in a 4 year follow-up, during which the ESES/CSWS condition persisted, despite the pharmacological treatments. The patient also underwent cerebral magnetic resonance imaging and fludeoxyglucose F 18 positron emission tomography (PET). RESULTS: The PET study revealed reduced metabolic activity within the lower gyrus of the right parietal lobe, but no significant difference between subcortical structures and cortical mantle was seen. MRI scans were normal. CONCLUSIONS: This observation suggests that ESES/CSWS might not always be an age-related condition. Sleep EEG recordings should always be performed in patients with behavioral disorders and a history of epileptic fits.

Growth and developmental retardation, ocular ptosis, cardiac defect, and anal atresia: confirmation of the ROCA-Wiedemann syndrome.

We report on a girl with growth and mental retardation, peculiar face with ptosis, epicanthus, broad nasal bridge, low-set and abnormal ears, cleft uvula, congenital heart defect, and anal atresia. A similar condition was reported previously by Wiedemann et al. [1982: An atlas of characteristic syndromes: a visual aid to diagnosis, 2nd ed. p 114-115]. We confirm the existence of this condition that, although similar to Ohdo syndrome, seems to be an independent clinical entity. We propose that, based on the principal clinical manifestations, this condition should be identified with the acronym ROCA (retardation of growth and development, ocular ptosis, cardiac defect, and anal atresia).