Idiopathic hypersomnia years after the diagnosis.

Little attention has been paid to the long-term development of idiopathic hypersomnia symptoms and idiopathic hypersomnia comorbidities. The aim of this study was to describe the general health of patients with idiopathic hypersomnia years after the initial diagnosis, focusing on current subjective hypersomnolence and the presence of its other possible causes. Adult patients diagnosed with idiopathic hypersomnia ≥ 3 years ago at sleep centres in Prague and Kosice were invited to participate in this study. A total of 60 patients were examined (age 47.3 ± SD = 13.2 years, 66.7% women). In all participants, their hypersomnolence could not be explained by any other cause but idiopathic hypersomnia at the time of diagnosis. The mean duration of follow-up was 9.8 + 8.0 years. Fifty patients (83%) reported persisting hypersomnolence, but only 33 (55%) had no other disease that could also explain the patient's excessive daytime sleepiness and/or prolonged sleep. In two patients (3%), the diagnosis in the meantime had changed to narcolepsy type 2, and 15 patients (25%) had developed a disease or diseases potentially causing hypersomnolence since the initial diagnosis. Complete hypersomnolence resolution without stimulant treatment lasting longer than 6 months was reported by 10 patients (17%). To conclude, in a longer interval from the diagnosis of idiopathic hypersomnia, hypersomnolence may disappear or may theoretically be explained by another newly developed disease, or the diagnosis may be changed to narcolepsy type 2. Thus, after 9.8 years, only 55% of the examined patients with idiopathic hypersomnia had a typical clinical picture of idiopathic hypersomnia without doubts about the cause of the current hypersomnolence.

The sight of one's own body: Could qEEG help predict the treatment response in anorexia nervosa?

Aims of the study: The study aims to identify the differences in brain activity between participants with anorexia nervosa and healthy control using visual stimulus conditions combined with the quantitative dense-array EEG recording analysis method called Brain Activation Sequences (BAS). Materials and methods: 23 participants with anorexia nervosa and 21 healthy controls were presented with visual stimuli, including the subject's facial expressions and body images. The 128-channel EEG data were processed using BAS and displayed as activity in up to 66 brain regions. Subsequent cluster analysis was used to identify groups of participants exhibiting area-specific activation patterns. Results: Cluster analysis identified three distinct groups: one including all healthy controls (HC) and two consisting of all participants with anorexia (AN-I with 19 participants and AN-II with four participants). The AN-I and AN-II groups differed in their response to treatment. Comparisons of HC vs. AN confirmed the dominance of the right cerebral hemisphere in participants with anorexia nervosa in two of the three reported conditions. The facial expressions condition, specifically the facial reaction expressing disgust, indicates the existence of a social attentional bias toward faces, whereas emotions remained undetected in participants. High limbic activity, medial frontal gyrus involvement, low fusiform cortex activity, and milder visual cortex activity in healthy controls compared to participants indicate that the facial expression stimulus is perceived by healthy subjects primarily as an emotion, not as the face itself. In the body image condition, participants showed higher activity in the fusiform gyrus and right insula, indicating activation of the brain's "fear network." Conclusion: The study describes a specific pattern of brain activation in response to facial expression of disgust and body images that likely contributes to social-cognitive and behavioral impairments in anorexia. In addition, the substantial difference in the pattern of brain activation within the participants with AN and its association with treatment resistance deserves special attention because of its potential to develop a clinically useful prediction tool and identify potential targets for, for example, neuromodulatory treatments and/or individualized psychotherapy.

Idiopathic Hypersomnia-A Dynamic Simulation Model.

Aims of the study: Commonly used approach to illness assessment focuses on the patient's actual state supplemented by binary records of past events and conditions. This research project was designed to explain subjective experience in idiopathic hypersomnia (IH) patients influenced by their clinical symptoms and comorbidities. Material and Methods: Forty-three IH patients of both sexes (female 60.5%, male 39.5%) were assessed using a detailed structured examination. The interview covered neurologic, psychiatric, and internal medicine anamnesis, medication past and current, substance abuse, work impairment, detailed sleep-related data, specific sleep medication, and a full-length set of questionnaires including depression, quality of life, sleepiness, anxiety, fatigue, insomnia, and sleep inertia. The data were digitized and imported into statistical software (SPSS by IBM), and dynamic simulation software (Vensim by Ventana Systems Inc.) was used to build a causal loop diagram and stocks and flows diagram as a simulation structure. Results: The overall raw data and simulation-based patterns fit at 76.1%. The simulation results also identified the parameters that contribute the most to patients' subjective experience. These included sleep inertia, the refreshing potential of naps, the quality of nocturnal sleep, and the social aspects of the patient's life. Psychiatric disorders influence the overall pattern at a surprisingly low level. The influence of medication has been studied in detail. Although its contribution to the dynamics looks marginal at first sight, it significantly influences the contribution of other variables to the overall patient experience of the disease. Conclusion: Even the simplified dynamic structure designed by the research team reflects the real-life events in patients with IH at the acceptable level of 76.1% and suggests that a similar structure plays an important role in the course of the disease. Therapeutic focus on the parameters identified by the model should enhance the patients' subjective experience throughout illness duration and might even turn the progress from negative into positive. Further research is needed to understand the dynamics of idiopathic hypersomnia in greater detail to better understand the causes and design therapeutic approaches to improve patients' quality of life.

Idiopathic hypersomnia: a homogeneous or heterogeneous disease?

INTRODUCTION: Idiopathic hypersomnia (IH) is a rare orphan disease characterized by excessive daytime sleepiness, frequently accompanied by prolonged nocturnal sleep and difficulties awakening, termed sleep inertia or sleep drunkenness. Severe sleepiness usually causes a greater handicap than manifestations of narcolepsy. METHODS: Forty-three IH patients (17 male, mean age 42.8 ± SD 12.2 years, range 20-67), diagnosed in the past 20 years according to ICSD-2 or ICSD-3 criteria were invited for clinical examination to evaluate the course, manifestations and severity of the disease, as well as clinical comorbidities. The patients completed a set of questionnaires scoring sleepiness, sleep inertia, fatigue, depression, anxiety, circadian preference, and quality of life. RESULTS: IH patients were divided according to the duration of nocturnal sleep at the time of their diagnosis into two cohorts: (1) with normal sleep duration (n = 25, 58.1%) and (2) with long sleep duration (n = 18, 41.9%). The mean duration of ad libitum sleep per 22 h in the second cohort was 732.0 ± 115.4 min (range 603-1100), and women markedly prevailed (n = 14, 77.8%). Age at disease onset was younger in the group with long sleep duration (21.2 ± 11.4 years versus 28.1 ± 13.6 years, p = 0.028), their MSLT latency was longer (7.2 ± 3.7 min versus 5.1 ± 1.7 min, p = 0.005), a history of sleep inertia prevailed (p = 0.005), and daily naps were mostly non-refreshing (p = 0.014). Additionally, questionnaires in the group with long sleep duration showed more severe sleep inertia (p = 0.007), fatigue (p = 0.004), and a tendency towards evening chronotype (p = 0.001). CONCLUSIONS: IH patients with long sleep duration differ clinically as well as by objective measures at the time of diagnosis and in long-term follow up from IH patients without long 24-h sleep time. In our opinion they represent an independent clinical entity to be considered in the revised ICSD-3 criteria.

Emotion stimulus processing in narcolepsy with cataplexy.

Reported brain abnormalities in anatomy and function in patients with narcolepsy with cataplexy led to a project based on qualitative electroencephalography examination and analysis in an attempt to find a narcolepsy with cataplexy-specific brain-derived pattern, or a sequence of brain locations involved in processing humorous stimuli. Laughter is the trigger of cataplexy in these patients, and the difference between patients and healthy controls during the laughter should therefore be notable. Twenty-six adult patients (14 male, 12 female) suffering from narcolepsy with cataplexy and 10 healthy controls (five male, five female) were examined. The experiment was performed using a 256-channel electroencephalogram and then processed using specialized software built according to the scientific research team's specifications. The software utilizes electroencephalographic data recorded during elevated emotional states in participants to calculate the sequence of brain areas involved in emotion processing using non-linear and linear algorithms. Results show significant differences in activation (pre-laughter) patterns between the patients with narcolepsy and healthy controls, as well as significant similarities within the patients and the controls. Specifically, gyrus orbitalis, rectus and occipitalis inferior are active in healthy controls, while gyrus paracentralis, cingularis and cuneus are activated solely in the patients in response to humorous audio stimulus. There are qualitative electroencephalographic-based patterns clearly discriminating between patients with narcolepsy and healthy controls during laughter processing.

Narcolepsy with and without cataplexy, idiopathic hypersomnia with and without long sleep time: a cluster analysis.

BACKGROUND: The successive editions of the International Classification of Sleep Disorders (ICSD) reflect the evolution of the concepts of various sleep disorders. This is particularly the case for central disorders of hypersomnolence, with continuous changes in terminology and divisions of narcolepsy, idiopathic hypersomnia, and recurrent hypersomnia. According to the ICSD 2nd Edition (ICSD-2), narcolepsy with cataplexy (NwithC), narcolepsy without cataplexy (Nw/oC), idiopathic hypersomnia with long sleep time (IHwithLST), and idiopathic hypersomnia without long sleep time (IHw/oLST) are four, well-defined hypersomnias of central origin. However, in the absence of biological markers, doubts have been raised as to the relevance of a division of idiopathic hypersomnia into two forms, and it is not yet clear whether Nw/oC and IHw/oLST are two distinct entities. With this in mind, it was decided to empirically review the ICSD-2 classification by using a hierarchical cluster analysis to see whether this division has some relevance, even though the terms "with long sleep time" and "without long sleep time" are inappropriate. RESULTS: The cluster analysis differentiated three main clusters: Cluster 1, "combined monosymptomatic hypersomnia/narcolepsy type 2" (people initially diagnosed with IHw/oLST and Nw/oC); Cluster 2 "polysymptomatic hypersomnia" (people initially diagnosed with IHwithLST); and Cluster 3, narcolepsy type 1 (people initially diagnosed with NwithC). CONCLUSIONS: Cluster analysis confirmed that narcolepsy type 1 and polysymptomatic hypersomnia are independent sleep disorders. People who were initially diagnosed with Nw/oC and IHw/oLST formed a single cluster, referred to as "combined monosymptomatic hypersomnia/narcolepsy type 2."

Brain activation sequences.

OBJECTIVE: Reported brain abnormalities in anatomy and function in psychiatric and neurological patients led to a project based on qualitative electroencephalography examination and analysis in an attempt to find specific brain derived pattern--or sequence of brain locations involved in processing various stimuli--both visual and auditory. METHODS: Specialized software called Brain Activation Sequences was built according to our team member specifications (M.S.). The software utilizes event related potentials recorded during cognitive/emotion processing in participants (healthy controls, neurological patients and psychiatric patients) to calculate the sequence of brain areas using nonlinear and linear algorithms. RESULTS: Results show significant differences in activation patterns between patients and healthy controls as well as significant similarities within the groups of patients and controls in both performed testing experiments.

Hippocampal but not amygdalar volume loss in narcolepsy with cataplexy.

OBJECTIVE: Narcolepsy with cataplexy (NC) and narcolepsy without cataplexy (NwoC) are lifelong neurological disorders characterized primarily by excessive daytime sleepiness. Emotional events such as laughter are a trigger of cataplexy in NC. METHODS: We compared the volumes of key limbic structures, the amygdala and hippocampus, in 53 NC, 23 NwoC and 37 control subjects. MRI volumetry was performed in FreeSurfer (FS) and by manual delineation. RESULTS: We found no differences in amygdalar volume in the three groups, however, hippocampal volume was significantly smaller in the NC group than in other groups. Amygdalar and hippocampal volumes assessed by FS were significantly greater, but strong positive correlation between manual and FS results were observed. Thus, both methods are suitable for amygdalar and hippocampal volumetry.

Past and present in drug treatment of sleep disorders.

Sleep disorders are frequent and disturbing, mostly chronic conditions. Despite the fact practice of sleep medicine is a young field. Sleep disorders were reduced to insomnia and even insomnia was not well studied until 1960ies. This article maps amazing development of sleep disorders treatment from the beginning till current date. The text covers both scientific and clinical perspectives on most frequent sleep related disorders including insomnias, hypersomnias, parasomnias, sleep related movement and breathing disorders, restless legs syndrome and circadian rhythm sleep disorders.

Diagnosis and management of central hypersomnias.

Central hypersomnias are diseases manifested in excessive daytime sleepiness (EDS) not caused by disturbed nocturnal sleep or misaligned circadian rhythms. Central hypersomnias includes narcolepsy with and without cataplexy, recurrent hypersomnia, idiopathic hypersomnia, with and without long sleep time, behaviorally induced insufficient sleep syndrome, hypersomnia and narcolepsy due to medical conditions, and finally hypersomnia induced by substance intake. The Epworth Sleepiness Scale is a subjective tool mostly used for EDS assessment, while the Multiple Sleep Latency Test serves as an objective diagnostic method for narcolepsy and idiopathic hypersomnias. As for symptomatic therapy of EDS, the central nervous system stimulants modafinil and methylphenidate seem to work well in most cases and in narcolepsy and Parkinson's disease; sodium oxybate also has notable therapeutic value.

Sleepiness in patients with obstructive sleep apnoea - daytime course and impact of nocturnal respiratory events.

BACKGROUND: Obstructive sleep apnoea (OSA) is a condition leading to excessive daytime sleepiness. The aim of the study was a) to study course of daytime sleepiness in patients with OSA and b) to find the most important nocturnal polysomnography parameters influencing daytime sleepiness in OSA. METHODS: The cohort consisted of forty-five patients (6 women, 39 men) diagnosed with OSA. All patients underwent polysomnography, Multiple Sleep Latency Test (MSLT) and rated subjectively their daytime tendency to sleep with the Epworth Sleepiness Scale. RESULTS: Sleep latency was significantly longer at 15:00 and at 17:00 hours compared to previous tests. A significant negative correlation was found between the mean of the MSLT sleep latency and a number of awakenings, the apnoea/hypopnoea index and oxygen desaturation index values. CONCLUSIONS: The study showed the sleep latency prolongation at 15:00 and 17:00 hours respectively and confirmed connection of excessive daytime sleepiness to fragmentation of nocturnal sleep and OSA severity.

Dissociative symptoms and interregional EEG cross-correlations in paranoid schizophrenia.

Recent findings indicate that binding and synchronization of distributed activities are crucial for the mechanism of consciousness, and there is increased evidence that disruptions in feature binding produce disintegration of consciousness in schizophrenia. These data suggest that the disrupted binding and disintegration of consciousness could be related to dissociation, which is historically linked to Bleuler's concept of splitting in schizophrenia. In the present study we aimed to investigate relations among electroencephalogram (EEG) activities of cortical sites and used psychometric measures of positive and negative schizophrenia symptoms (Positive and Negative Syndrome Scale) and the Dissociative Experiences Scale (DES) in 58 patients with paranoid schizophrenia. The results show statistically significant Spearman correlations of the DES with cross-correlation function in nine (of 16) EEG pairs. Positive symptoms display significant Spearman correlation with mean of cross-correlation function in only one EEG pair (F4-C4). Results of the Mann-Whitney test between patients with higher (DES > or = 30) and lower dissociation show statistically significant differences between the groups for cross-correlations in nine EEG pairs. The results of this study provide the first supportive evidence for a negative relationship between cross-correlation indices and symptoms of dissociation in schizophrenia.

Traumatic stress, dissociation, and limbic irritability in patients with unipolar depression being treated with SSRIs.

Recent evidence suggests that stressful experiences may be related to deficits in inhibitory functions and temporo-limbic epileptic-like activity. The latter may produce psychosensory seizure-like symptoms that may also appear in nonepileptic conditions. This study assesses whether the increased presence of the seizure-like symptoms in 113 unipolar depressive patients treated with SSRIs is associated with significantly more severe symptoms of depression, traumatic stress, and dissociation in comparison with 86 healthy controls. Results indicate that seizure-like symptoms in depressive patients have significant association with depression, symptoms of dissociation, and traumatic stress. This association suggests that processess generating seizure-like symptoms may be related to symptoms of depression, traumatic stress, and dissociation.

Depression, traumatic stress and interleukin-6.

BACKGROUND: Recent evidence indicates that various types of interactions between nervous and immune system are important in pathogenesis of depression. These findings show that a significant role in developing depression play pro-inflammatory cytokines that may mediate its psychological, and neurobiological manifestations. Great importance among these cytokine molecules plays interleukin-6 (IL-6). There is growing evidence that this inflammatory process related to depression may be influenced by psychological stress as well as organic inflammatory conditions. These findings suggest that specific influences related to traumatic stress and dissociation could be found in close relationship to increased level of cytokine IL-6. METHODS: In the present study we have performed psychometric measurement of depression (BDI-II), traumatic stress symptoms (TSC-40) and dissociation (DES, SDQ-20), and immunochemical measure of serum IL-6 in 40 inpatients with unipolar depression (mean age 42.3+/-6.8). RESULTS: The results show that IL-6 is significantly correlated to BDI-II (Spearman R=0.47, p<0.01), TSC-40 (Spearman R=0.32, p<0.05), SDQ-20 (Spearman R=0.34, p<0.05) but not to DES (Spearman R=0.25, p=0.11). CONCLUSION: The findings of the present study indicate that increased level of IL-6 in depression could be directly related to symptoms of traumatic stress and somatoform dissociation.

Sensitization, epileptic-like symptoms and local synchronization in patients with paranoid schizophrenia.

Recent findings indicate that changes in synchronization of neural activities underlying sensitization and kindling could be more comprehensively understood using nonlinear methods. With this aim we have examined local synchronization using novel measure of coarse-grained information rate (CIR) in 8 EEG signals recorded at different cortical areas in 44 patients with paranoid schizophrenia. The values of local synchronization that could reflect sensitization related changes in EEG activities of cortical sites were then related to psychometric measures of epileptic-like symptoms and positive and negative schizophrenia symptoms (PANSS). While no significant correlations between CIR and positive and negative symptoms have been found, statistically significant relationships described by Spearman correlation coefficients between CIR indices and results of LSCL-33 have been observed in 7 (of 8) EEG channels (r in the range from 0.307 to 0.374, p<0.05). Results of this study provide first supportive evidence for the relationship between local synchronization measured by CIR and epileptic-like symptoms in schizophrenia.

Brain wave P300: a comparative study of various forms of criminal activity.

BACKGROUND: This comparative and comprehensive study builds on a previous study comparing the P300 wave of impulsively violent delinquents and a non-impulsive non-delinquent group. The purpose was to investigate changes in P300 cognitive evoked potentials, especially the amplitude and latency at the Pz electrode site. MATERIAL/METHODS: The P300 parameters of perpetrators of various types of criminal offences and those of a control group matched for age, gender, and educational status were compared (N=80). There were 20 subjects with impulsively aggressive delinquent behavior. The observed parameters were compared with the neuropsychophysiological correlates of a group of 20 subjects with deliberately (i.e. non-impulsive) violent behavior, a group of 20 delinquents sentenced for property crimes (theft), and 20 non-delinquent non-impulsive nonviolent persons. To differentiate these groups, Eysenck's IVE questionnaire and a structured interview according to DSM IV criteria conducted by a certified forensic psychiatrist were used. RESULTS: The results showed a significantly lower P300 wave amplitude in the impulsively aggressive individuals than in the other groups. No significant differences were found in terms of latency. The results confirm the results of previous studies. CONCLUSIONS: The results suggest the possibility of a neuropsychophysiological correlate of impulsively aggressive individuals behaving in a socially dangerous way. This opens a discussion on the subject of expert evaluation of criminal acts within the context of "uncontrolled affect".

Chaotic patterns of autonomic activity during hypnotic recall.

Chaotic neural dynamics likely emerge in cognitive processes and may present time periods that are extremely sensitive to influences affecting the neural system. Recent findings suggest that this sensitivity may increase during retrieval of stressful emotional experiences reflecting underlying mechanism related to consolidation of traumatic memories. In this context, hypnotic recall of anxiety memories in 10 patients, simultaneously with ECG measurement was performed. The same measurement was performed during control cognitive task in 8 anxiety patients and 22 healthy controls. Nonlinear data analysis of ECG records indicates significant increase in the degree of chaos during retrieval of stressful memory in all the patients. The results suggest a role of chaotic neural dynamics during processing of anxiety-related stressful memories.

Chaos in schizophrenia associations, reality or metaphor?

There is evidence that schizophrenic associations display "chaotic", random-like behavior and decreased predictability. The evidence suggests a hypothesis that the "chaotic" mental disorganization could be explained within the concept of nonlinear dynamics and complexity in the brain that may cause chaotic neural organization. Testing of the hypothesis in the present study was performed using nonlinear analysis of bilateral electrodermal activity (EDA) during resting state and an association test in 56 schizophrenic patients and 44 healthy participants. EDA is a suitable measure of brain and autonomic activity reflecting neurobiological changes in schizophrenia that may indicate changes in nonlinear neural dynamics related to associative process. The results show that quantitative indices of chaotic dynamics (the largest Lyapunov exponents) calculated from EDA signals recorded during rest and the association test are significantly higher in schizophrenia patients than in the control group and increase during the test in comparison to the resting state. The difference was confirmed by statistical methods and using surrogate data testing that rejected an explanation within the linear statistical framework. The results provide supportive evidence that pseudo-randomness of schizophrenic associations and less predictability could be linked to increased complexity of nonlinear neural dynamics, although certain limitations in data interpretation must be taken into account.

Dissociation, cognitive conflict and nonlinear patterns of heart rate dynamics in patients with unipolar depression.

Recent findings in cognitive neuroscience indicate that activation of anterior cingulate cortex (ACC) is related to detecting cognitive conflict. Conflict related ACC activation elicits responses in central autonomic network which can be assessed by psychophysiological measures such as heart rate variability (i.e. beat to beat R-R intervals--RRI). Recent findings in neuroscience also suggest that cognitive conflict is related to specific nonlinear chaotic changes of the signal generated by the neural systems. The present study used Stroop word-colour test as an experimental approach to the study of cognitive conflict in connection with RRI measurement, psychometric measurement of dissociation (DES) and calculation of largest Lyapunov exponents in nonlinear data analysis of RRI time series in 40 patients with unipolar depression and 35 healthy controls. Significant correlation 0.58 (p<0.01) between largest Lyapunov exponents and DES found in depressive patients indicate that cognitive conflict related neural interference during conflicting Stroop task is closely related to dissociative processes. These results present first supportive evidence that degree of chaos could be related to dissociation.

Dissociative symptoms and neuroendocrine dysregulation in depression.

BACKGROUND: Dissociative symptoms are traditionally attributed to psychological stressors that produce dissociated memories related to stressful life events. Dissociative disorders and dissociative symptoms including psychogenic amnesia, fugue, dissociative identity-disorder, depersonalization, derealization and other symptoms or syndromes have been reported as an epidemic psychiatric condition that may be coexistent with various psychiatric diagnoses such as depression, schizophrenia, borderline personality disorder or anxiety disorders. According to recent findings also the somatic components of dissociation may occur and influence brain, autonomic and neuroendocrine functions. At this time there are only few studies examining neuroendocrine response related to dissociative symptoms that suggest significant dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis. The aim of the present study is to perform examination of HPA axis functioning indexed by basal cortisol and prolactin and test their relationship to psychic and somatoform dissociative symptoms. MATERIAL/METHODS: Basal cortisol and prolactin and psychic and somatoform dissociative symptoms were assessed in 40 consecutive inpatients with diagnosis of unipolar depression mean age 43.37 (SD=12.21). RESULTS: The results show that prolactin and cortisol as indices of HPA axis functioning manifest significant relationship to dissociative symptoms. Main results represent highly significant correlations obtained by simple regression between psychic dissociative symptoms (DES) and serum prolactin (R=0.55, p=0.00027), and between somatoform dissociation (SDQ-20) and serum cortisol (R=-0.38, p=0.015). CONCLUSIONS: These results indicate relationship between HPA-axis reactivity and dissociative symptoms in unipolar depressive patients that could reflect passive coping behavior and disengagement.