Polysomnographic and psychometric correlates of napping in primary insomnia patients.

Introduction: This study aims to evaluate napping in patients with insomnia compared with two control groups and to investigate the relationships between psychometric measures and napping habitude.Methods: Sixty-eight adult patients with chronic primary insomnia were enrolled; 27 men and 41 women, mean age 53.6 ± 13. All patients underwent 24 h ambulatory polysomnography (A-PSG). Prevalence of napping behavior in Insomnia Patients (I-group) was compared with Obstructive Sleep Apnea Syndrome (OSAS) patients (OSAS-group) and epilepsy patients (Ep-group). Patients were evaluated with Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and Berlin Questionnaire. Psychometric evaluation included Self-Administered Anxiety Scale (SAS #54), Beck Depression Inventory (BDI), Maudsley's Obsessive Compulsive Inventory (MOCI), Snaith-Hamilton Pleasure Scale (SHAPS), and Eating Attitude Test (EAT-26).Results: No significant differences resulted in prevalence and duration of naps in the three groups. In the comparison between nappers (N+, subject with at least one nap in A-PSG) and non-nappers (N-, subject with no naps in A-PSG) we observed significant differences in PSQI scores (N+ = 14.1 ± 2.7; N- =11.9 ± 3.3; Whitney U-test = 341.0; p = 0.004) and in EAT score (N+ = 9.8 ± 9.7; N- = 4.4 ± 5.6; Whitney U-test = 313.5, p = 0.0.14); no significant differences were measured in other psychometric parameters and in sleep macrostructural indexes.Conclusions: Our data are in accordance with previous findings outlining that N + insomniacs have higher PSQI scores than N-. Our results do not confirm the suggested association between napping and depressive or obsessive-compulsive symptoms. Conversely, we found a statistically significant difference (p = 0.0014) in EAT scores in N + and N-. Hyperarousal and REM sleep instability in insomniac patients may create an unbalance of the neuroendocrine hypothalamic regulation leading to an appetite alteration.

Heart rate and heart rate variability modification in chronic insomnia patients.

Chronic insomnia is highly prevalent in the general population, provoking personal distress and increased risk for psychiatric and medical disorders. Autonomic hyper-arousal could be a pathogenic mechanism of chronic primary insomnia. The aim of this study was to investigate autonomic activity in patients with chronic primary insomnia by means of heart rate variability (HRV) analysis. Eighty-five consecutive patients affected by chronic primary insomnia were enrolled (38 men and 47 women; mean age: 53.2 ± 13.6). Patients were compared with a control group composed of 55 healthy participants matched for age and gender (23 men and 32 women; mean age: 54.2 ± 13.9). Patients underwent an insomnia study protocol that included subjective sleep evaluation, psychometric measures, and home-based polysomnography with evaluation of HRV in wake before sleep, in all sleep stages, and in wake after final awakening. Patients showed modifications of heart rate and HRV parameters, consistent with increased sympathetic activity, while awake before sleep and during Stage-2 non-REM sleep. No significant differences between insomniacs and controls could be detected during slow-wave sleep, REM sleep, and post-sleep wake. These results are consistent with the hypothesis that autonomic hyper-arousal is a major pathogenic mechanism in primary insomnia, and confirm that this condition is associated with an increased cardiovascular risk.

Pain and the alpha-sleep anomaly: a mechanism of sleep disruption in facioscapulohumeral muscular dystrophy.

OBJECTIVE: To measure the presence of the alpha-sleep anomaly in facioscapulohumeral muscular dystrophy (FSHD) and to evaluate the association between the sleep electroencephalogram (EEG) pattern and the presence of musculoskeletal pain. DESIGN: Cross-sectional study. SETTING: Sleep laboratory. SUBJECTS: Fifty-five consecutive adult FSHD patients, 26 women and 29 men, age 49.6 ± 15.1 years (range 18-76). INTERVENTIONS: Questionnaires and polysomnography. OUTCOME MEASURES: Patients were asked to indicate if in the 3 months before the sleep study they presented persisting or recurring musculoskeletal pain. Patients who reported pain were asked to fill in the Italian version of the Brief Pain Inventory and the McGill Pain questionnaire, and a 101-point visual analog scale (VAS) for pain intensity. Polysomnographic recordings were performed. EEG was analyzed by means of Fast Fourier Transform. Four power spectra bands (δ 0-4 Hz, θ 4-8 Hz, α 8-14 Hz, ß 14-32 Hz) were computed. Sleep macrostructure parameters and alpha/delta EEG power ratio during non rapid eye movement (NREM) sleep were compared between patients with and without pain. RESULTS: Forty-two patients in our sample reported chronic pain. VAS mean score was 55.2 ± 23.8 (range 10-100), pain rating index score was 13.8 ± 10.2, and present pain intensity was 2.5 ± 0.8. The statistical analysis documented an increased occurrence of the alpha and beta rhythms during NREM sleep in FSHD patients with pain. Significant correlations were observed between the alpha/delta power ratio during NREM sleep and pain measures. CONCLUSIONS: Chronic musculoskeletal pain is frequent in FSHD patients, and it represents a major mechanism of sleep disruption.

Migraine, arousal and sleep deprivation: comment on: "sleep quality, arousal and pain thresholds in migraineurs: a blinded controlled polysomnographic study".

We discuss the hypothesis proposed by Engstrom and coworkers that Migraineurs have a relative sleep deprivation, which lowers the pain threshold and predispose to attacks. Previous data indicate that Migraineurs have a reduction of Cyclic Alternating Pattern (CAP), an essential mechanism of NREM sleep regulation which allows to dump the effect of incoming disruptive stimuli, and to protect sleep. The modifications of CAP observed in Migraineurs are similar to those observed in patients with impaired arousal (narcolepsy) and after sleep deprivation. The impairment of this mechanism makes Migraineurs more vulnerable to stimuli triggering attacks during sleep, and represents part of a more general vulnerability to incoming stimuli.

Heart rate variability in facioscapulohumeral muscular dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD) is the third most frequent form of muscular dystrophy. Heart rate variability (HRV) analysis is a means of evaluating the activity of the autonomic nervous system. The aim of this study was to evaluate HRV in FSHD patients. Fifty-five consecutive FSHD patients were enrolled (31 men, age 26-72 years). Muscular impairment was measured using a clinical severity scale (CSS). Patients were compared with a control group of 55 healthy subjects, matched for age and sex. HRV was analyzed in the time domain and in the frequency domain. Patients showed increased spectral power of the low-frequency band. Spectral power of the high-frequency band was inversely correlated with CSS score. FSHD is associated with a slight increase in sympathetic output and with a decrease in parasympathetic output. These modifications become more evident with the progression of the disease and could increase the risk of arrhythmias and other cardiovascular events.

Abnormal sexual behavior during sleep.

INTRODUCTION: Automatic, uncontrolled, and unaware sexual behaviors during sleep have occasionally been described. The clinical and polysomnographic features of nocturnal sexual behavior allow it to be considered a distinct parasomnia named "sexsomnia". Recently, abnormal sexual behaviors during sleep have been evaluated in the forensic medical context because violent behaviors can be associated with this parasomnia. AIM: To describe the clinical and polysomnographic findings in three patients who referred to our sleep laboratory for sleep disorders and who reported episodes of sleep-related sexual activation. MAIN OUTCOME MEASURES: We analyzed video-polysomnographic recordings, sleep structure, sleep microstructure, and sleep-related respiratory events. METHODS: The patients were three males aged 42, 32, and 46 years. All had unremarkable medical, neurological, and psychiatric histories. All underwent full-night polysomnography. RESULTS: Each patient presented a distinct sleep disorder: one had severe obstructive sleep apnea syndrome (OSAS), one presented clinical and polysomnographic features of non-rapid eye movement (NREM) sleep parasomnia (somnambulism), and the third presented clinical and polysomnographic features of rapid eye movement behavior disorder. CONCLUSIONS: In our patients, the clinical and polysomnographic findings suggest that abnormal nocturnal sexual behavior can occur in association with distinct sleep disorders, characterized by different pathophysiologic mechanisms and distinctive treatments. Abnormal sexual behaviors during sleep should be investigated with polysomnography in order to define their pathophysiology and to establish appropriate treatments.

What is the effect of selective serotonin reuptake inhibitors on temperament and character in patients with fibromyalgia?

OBJECTIVE: The purpose of the present study was to assess a group of patients with fibromyalgia (FM) and control subjects using the personality questionnaire proposed by Cloninger and to determine possible changes in the Italian version of the Temperament and Character Inventory-Revised patterns of patients with FM after therapy with serotoninergic antidepressants (selective serotonin reuptake inhibitors [SSRIs]). METHODS: Sixty patients with FM filled out the Temperament and Character Inventory-Revised and Beck Depression Inventory before and after 6-month therapy with SSRIs (escitalopram 10 mg, fluoxetine 20 mg, or paroxetine 20 mg). A total of 80 age-, sex-, and education level-matched healthy subjects were selected as a control group. RESULTS: Both in the pretreatment and posttreatment period, patients were found to have higher harm avoidance and lower self-directedness scores than healthy controls. In addition, harm avoidance and self-directedness were state and trait dependent. CONCLUSIONS: Depressive symptoms in patients with FM can be significantly decreased by treatment with SSRIs. A careful clinical assessment and study of personality profile is needed to identify patients with FM who may benefit from antidepressant pharmacologic therapy and specific psychotherapeutic interventions.

Abnormal Circadian Modification of Aδ-Fiber Pathway Excitability in Idiopathic Restless Legs Syndrome.

Restless legs syndrome (RLS) is characterized by unpleasant sensations generally localized to legs, associated with an urge to move. A likely pathogenetic mechanism is a central dopaminergic dysfunction. The exact role of pain system is unclear. The purpose of the study was to investigate the nociceptive pathways in idiopathic RLS patients. We enrolled 11 patients (mean age 53.2 ± 19.7 years; 7 men) suffering from severe, primary RLS. We recorded scalp laser-evoked potentials (LEPs) to stimulation of different sites (hands and feet) and during two different time conditions (daytime and nighttime). Finally, we compared the results with a matched control group of healthy subjects. The Aδ responses obtained from patients did not differ from those recorded from control subjects. However, the N1 and the N2-P2 amplitudes' night/day ratios after foot stimulation were increased in patients, as compared to controls (N1: patients: 133.91 ± 50.42%; controls: 83.74 ± 34.45%; p = 0.016; Aδ-N2-P2: patients: 119.15 ± 15.56%; controls: 88.42 ± 23.41%; p = 0.003). These results suggest that RLS patients present circadian modifications in the pain system, which are not present in healthy controls. Both sensory-discriminative and affective-emotional components of pain experience show parallel changes. This study confirms the structural integrity of Aδ nociceptive system in idiopathic RLS, but it also suggests that RLS patients present circadian modifications in the pain system. These findings could potentially help clinicians and contribute to identify new therapeutic approaches.

Effect of levetiracetam on depression and anxiety in adult epileptic patients.

BACKGROUND: Interictal depression is common in patients with epilepsy and it significantly impacts quality of life. Some studies indicate that levetiracetam (LEV) may have mood stabilizing properties. METHODS: Twenty-five adults with uncontrolled partial seizures and concomitant depressive symptoms were treated with LEV. Patients were evaluated for depression and anxiety with several psychometric measures, including: Montgomery and Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HDRS), Zung Self-rating Scale for Depression (Z-SDS), Hamilton Anxiety Rating Scale (HARS), Zung Self-rating Scale for Anxiety (Z-SAS). RESULTS: Evaluations after 5 weeks and after 3 months of LEV treatment demonstrated significant improvement in depression and anxiety. CONCLUSIONS: This uncontrolled study suggests that treatment with LEV may also improve depression and anxiety in patients with partial seizures. However, the sample of patients is limited and the possibility of a placebo effect cannot be excluded. These findings must be considered preliminary and should be replicated under placebo-controlled conditions.

Left thalamomegaly in a patient with partial epilepsy.

Temporal lobe epilepsy (TLE) is associated with modification in thalamic structure and function. In particular, thalamic atrophy and hypometabolism can occur, affecting ipsilateral, contralateral thalami or both. We describe a 28-year-old epileptic woman, who presented peculiar neuroimaging findings, with enlargement of the thalamus contralateral to the epileptic focus. The patient was born from dystocic delivery, she presented partial motor seizures in the left side of the body, followed by generalisation, and the EEG showed a right temporal epileptic focus. Serial CT and MRI scan, performed along 11 years, showed a non-evolutive left thalamomegaly. 18-FDG PET showed reduced metabolic activity in the upper right temporal gyrus and in the ipsilateral thalamus. Thalamic asymmetry in our patient could be an occasional finding.

Bipolar disorder and epilepsy: a bidirectional relation? Neurobiological underpinnings, current hypotheses, and future research directions.

A number of studies have demonstrated that affective disorders in epilepsy represent a common psychiatric comorbidity; however, most of the classic neuropsychiatric literature focuses on depression, which is actually prominent, but little is known about bipolar depression, and very little about mania, in epilepsy. Biochemical, structural, and functional abnormalities in primary bipolar disorder could also occur secondary to seizure disorders. The kindling paradigm, invoked as a model for understanding seizure disorders, has also been applied to the episodic nature of bipolar disorder. In bipolar patients, changes in second-messenger systems, such as G-proteins, phosphatidylinositol, protein kinase C, myristoylated alanine-rich C kinase substrate, or calcium activity have been described, along with changes in c-fos expression. Common mechanisms at the level of ion channels might include the antikindling and the calcium-antagonistic and potassium outward current-modulating properties of antiepileptic drugs. All these lines of research appear to be converging on a richer understanding of neurobiological underpinnings between bipolar disorder and epilepsy. Mania, which is the other side of the coin in affective disorders, may represent a privileged window into the neurobiology of mood regulation and the neurobiology of epilepsy itself. Future research on intracellular mechanisms might become decisive for a better understanding of the similarities between these two disorders.

Omega-3 fatty acids and antioxidants in neurological and psychiatric diseases: an overview.

RATIONALE: Omega-3 fatty acids are known to play a role in nervous system activity, cognitive development, memory-related learning, neuroplasticity of nerve membranes, synaptogenesis and synaptic transmission. The brain is considered abnormally sensitive to oxidative damage, and aging is considered one of the most significant risk factors for degenerative neurological disorders. Recently, clinical trials of several neurodegenerative diseases have increasingly targeted the evaluation of the effectiveness of various antioxidants. OBJECTIVES: The effects of omega-3 fatty acids and antioxidants on the anatomic and functional central nervous system development and their possible therapeutical use in some neurological and psychiatric pathologies are evaluated. RESULTS: A number of critical trials have confirmed the benefits of dietary supplementation with omega-3 fatty acids not only in several psychiatric conditions, but also in inflammatory and autoimmune and neurodegenerative diseases. Many evidences indicate that antioxidants are also essential in maintaining a correct neurophysiology. CONCLUSIONS: Omega-3 fatty acids could be useful in the prevention of different pathologies, such as cardiovascular, psychiatric, neurological, dermatological and rheumatological disorders. A number of studies suggest that antioxidants can prevent the oxidation of various macromolecules such as DNA, proteins, and lipids. The ideal use of antioxidants should be a prophylactic and continue treatment before aging.

Sleep quality in Facioscapulohumeral muscular dystrophy.

OBJECTIVE: To evaluate the subjective sleep quality, the prevalence of daytime sleepiness and the risk of sleep-related upper airways obstruction in patients with genetically proven Facioscapulohumeral muscular dystrophy (FSHD). FSHD is an autosomal dominant myopathy, characterized by an early involvement of facial and scapular muscles with eventual spreading to pelvic and lower limb muscles. PATIENTS AND METHODS: Forty-six patients were enrolled, 27 women and 19 men, mean age 43.6+/-14.1 years. Study protocol included: a Clinical Severity Scale (CSS) for FSHD, Pittsburgh Sleep Quality Index (PSQI), Italian version of the Epworth Sleepiness Scale (ESS) and the search for clinical predictors of sleep-related airways obstruction. RESULTS: Twenty-seven patients presented snoring, 12 reported respiratory pauses during sleep. One half (23/46) had PSQI scores above the normal threshold (=5). Correlations were found between the CSS and: the total PSQI score, the components C1 sleep quality, C5 sleep disturbances, C7 daytime dysfunction. CONCLUSION: Our data support the hypothesis that patients with FSHD have an impaired sleep quality, and that this impairment is directly related to the severity of the disease. A systematic polysomnographic evaluation of these patients will be necessary to confirm the presence of sleep disruption and to clarify its pathogenesis.

Biological and environmental factors affecting ultrasound-induced hemolysis in vitro: 5. Temperature.

This research project tested the hypothesis that cold-equilibrated (approximately 0 degrees C) human erythrocytes in vitro in the presence of an ultrasound contrast agent (Albunex) will undergo greater ultrasound-induced hemolysis than physiologically equilibrated (37 degrees C) human erythrocytes in vitro because of a temperature-related transition in membrane fluidity leading to increased fragility. First, it was shown that cold-equilibrated erythrocytes are more susceptible to mechanically induced hemolysis than physiologically equilibrated erythrocytes. Second, when adjustments were made for (1) temperature-dependent efficiencies of a 1-MHz transducer (200 micros pulse length, 20 ms interpulse interval, 30 s exposure duration) such that when cold or physiological temperatures were employed, there were equivalent acoustic outputs in terms of peak negative pressure (MPa P-) and (2) comparable viscosities of the 0 and 37 degrees C blood plasmas, the cold (approximately 0 degrees C) erythrocytes displayed substantially greater amounts of ultrasound-induced hemolysis than the physiological (37 degrees C) erythrocytes. The data supported the hypothesis.

Dissociated changes of somatosensory evoked low-frequency scalp responses and 600 Hz bursts after single-dose administration of lorazepam.

Electrical stimulation of upper limb nerves allows one to record two types of scalp responses, that is conventional low-frequency somatosensory evoked potentials (SEPs), and bursts of high-frequency (about 600 Hz) wavelets. To further clarify the functional meaning of both types of responses, we investigated whether changes of GABAergic drive could cause significant modifications of conventional as well as high-frequency SEPs. We recorded median nerve SEPs from six healthy volunteers before and after a single oral administration of lorazepam. In order to explain scalp SEP distribution before and after lorazepam administration, we performed the brain electrical source analysis of raw data. After lorazepam administration, conventional scalp SEPs showed a significant amplitude decrease of all cortical components including the primary N20/P20 response, while the subcortical P14 response remained substantially unchanged. Similarly, dipolar analysis showed a significant strength decrease of all cortical dipoles, whereas the strength of both subcortical dipoles (possibly located at the level of the brainstem and thalamus, respectively) remained unchanged. By contrast, no significant changes of high-frequency SEPs were induced by drug intake. Therefore, our findings suggest that the inhibitory effect induced by lorazepam mainly affects intracortical circuitry. Tonic increase of the inhibitory drive, possibly mediated by GABAA receptors, can account for the reduced activity of first order deep spiny neurons generating the primary N20/P20. Conversely, intrinsic firing properties of the cell population generating high-frequency SEP responses are unaffected by the increase of GABAergic drive. This finding lends further substance to the hypothesis that conventional and high-frequency SEPs are generated by different cell populations.

Biological and environmental factors affecting ultrasound-induced hemolysis in vitro: medium tonicity.

Whole human anticoagulated blood in vitro underwent controlled plasma replacement with either isotonic (0.9%) or hypotonic (0.5%) saline to 1. restore the blood to its original volume (which resulted in different hematocrits) or 2. bring the blood to a singular hematocrit (40%). The hypotonic cell MCVs were, on average, considerably larger than their isotonic counterpart by a ratio of 1.4:1. The blood samples were then subjected to two tests, one of mechanical fragility, the other to ultrasound (US)-induced hemolysis. The US exposure metrics were: 1.0-MHz center frequency, 200-micros pulse duration, 20-ms interpulse interval, exposure durations of 10 to 30 s in the presence of Albunex, as a control on blood gas nucleation, and exposure vessel rotation at 200 rpm. In all instances, the hypotonic blood displayed higher levels of hemolysis than the corresponding isotonic treatment. The highest ratio of US-induced hemolysis for the hypotonic:isotonic regimens was 2.2. In some instances, the ratio was somewhat less but appeared to be related to differences in whole blood viscosities among the regimens or other factors. The data supported the a priori hypothesis that hypotonicity will result in an increased tension on the cell membrane and render it more susceptible to shear-induced hemolysis, including exposure to US under conditions known to foster the occurrence of inertial cavitation. There was no temperature increase during the insonations of the blood.

Comparative hemolytic effectiveness of 1 MHz ultrasound on human and rabbit blood in vitro.

This project continued testing of the general working hypothesis that cell size is a physical determinant in extent of ultrasound (US)-induced hemolysis, the larger the cell the greater the lysis. For this project, the specific hypothesis tested was that human erythrocytes, being larger than rabbit erythrocytes, would be the more sensitive to sonolysis induced by inertial cavitation in the presence of Albunex, a US contrast agent. The rationale behind this hypothesis was 1. an earlier-published analytic construct indicating an inverse relation between particle size and the shear force required for deformation, and 2. a number of independent demonstrations that, among sized populations of erythrocytes, an inverse relation exists between erythrocyte volume and mechanically-induced shear forces in the cell-bathing medium; namely, the larger the cell, the less shear force required to rupture the cell's membrane. The present data support the hypothesis; over six independent trials, the mean corpuscular volumes of human (H) and rabbit (R) erythrocytes were 89.5 and 64.1 microm(3), respectively, H > R (p << 0.001), and the ratio of US-induced hemolysis in H to R blood in vitro was 1.12:1.0 (p < 0.004).

Biological and environmental factors affecting ultrasound-induced hemolysis in vitro: 1. HIV macrocytosis (cell size).

This paper reports the results of a further test of the hypothesis that the extent of ultrasound (US)-induced cell lysis in the presence of a US contrast agent to enhance cavitational effects is a function of cell size. The present data support the hypothesis. Human adult erythrocytes in vitro derived from patients with HIV (n = 15) and apparently healthy individuals (n = 15) were compared for US-induced hemolysis in vitro. The anticoagulated whole blood from patients with HIV and macrocytic erythrocytes had significantly greater (p <0.0001) mean corpuscular volume (MCV) and a significantly greater (p <0.03) extent of US-induced hemolysis in vitro relative to blood from apparently normal, healthy individuals. As a control to determine if disease state (i.e., HIV infection per se) might be a contributing factor in US-induced hemolysis in vitro, the blood from patients with HIV and apparently normal MCVs (n = 15) was also tested against an additional population of apparently normal, healthy individuals (n = 15); there were no statistically significant differences in MCVs or US-induced hemolysis between the two groups (p >> 0.05). There were also no statistically significant differences in viscosities or hematocrits of the whole blood or plasma in vitro from HIV-macrocytic or apparently healthy individuals but, for all blood types, a pooled correlation existed between hematocrit and whole blood viscosity.

Benign neonatal sleep myoclonus: case report and follow-up of four members of an affected family.

Benign neonatal sleep myoclonus (BNSM), characterized by myoclonic jerks of the extremities only in non-REM sleep, occurs in the first months of life with spontaneous disappearance within 3-4 months. We examined five siblings with typical BNSM, at the 3-10 years follow-up neurological examination. Psychomotor development, cognitive functions and EEG were completely normal. These cases confirm that BNSM is a self limited and nonepileptic disorder.