Sleep microstructure is not altered in children with attention-deficit/hyperactivity disorder (ADHD).

The high rate of occurrence of sleep disturbances in children with attention-deficit/hyperactivity disorder (ADHD) prompted the idea that structural and neurotransmitter changes might give rise to specific sleep pattern abnormalities. The aim of this study was to evaluate the microstructure of sleep in children with ADHD who had no polysomnographically diagnosed sleep disorder, had never been treated for ADHD, and were free from any psychiatric comorbidity. Participants were 14 patients with ADHD (12 boys and 2 girls aged 7-12 years, mean age 9.6+/-1.6). ADHD was diagnosed according to DSM-IV criteria (Diagnostic and statistical manual of mental disorders). Psychiatric comorbidities were ruled out by detailed psychiatric examination. The patients underwent two consecutive overnight video-polysomnographic (PSG) recordings, with the sleep microstructure (cyclic alternating pattern - CAP) scoring during the second night. The data were compared with age- and sex-matched controls. Sleep microstructure analysis using CAP revealed no significant differences between the ADHD group and the controls in any of the parameters under study. In conclusions, no ADHD-specific alterations were found in the sleep microstructure.

Diagnosing narcolepsy with cataplexy on history alone: challenging the International Classification of Sleep Disorders (ICSD-2) criteria.

BACKGROUND AND PURPOSE: The second version of the International Classification of Sleep Disorders suggests narcolepsy with cataplexy can be diagnosed on history alone. PATIENTS: Five patients with a history supportive of narcolepsy/cataplexy. METHOD: Case review following clinical investigation. RESULTS: None of the five patients had a diagnosis of narcolepsy/cataplexy on the basis of objective testing using polysomnography (PSG) and multiple sleep latency testing (MSLT). CONCLUSION: PSG and MSLT should always be used in conjunction with a comprehensive history taken by an experienced sleep physician to support a diagnosis of narcolepsy with cataplexy and to exclude other conditions that may mimic narcolepsy.

Sleep disorders in Wilson's disease.

BACKGROUND: Wilson's disease (WD) is an autosomal recessive inherited disease with copper accumulation; neurodegeneration is associated with dopaminergic deficit. The aim of the study is to verify sleep co-morbidity by questionnaire and objective sleep examinations (polysomnography, multiple sleep latency test). METHODS: fifty-five patients with WD (22 hepatic, 28 neurological, five asymptomatic form) and 55 age- and sex-matched control subjects completed a questionnaire concerning their sleep habits, sleep co-morbidity, Epworth sleepiness scale (ESS), and answered screening questions for rapid eye movement (REM) behaviour disorder (RBD-SQ). Twenty-four patients with WD and control subjects underwent polysomnographic examination. RESULTS: unlike the controls, patients with WD were more prone to daytime napping accompanied by tiredness and excessive daytime sleepiness, cataplexy-like episodes and poor nocturnal sleep. Their mean ESS as well as RBD-SQ was higher than that of the controls. Total sleep time was lower, accompanied by decreased sleep efficiency and increased wakefulness. Patients with WD had lower latency of stage 1 and stage 2 of non-rapid eye movement (NREM) sleep and less amount of NREM sleep stage 2. One-third of the patients with WD were found to have short or borderline multiple sleep latency test (MSLT) values independent of nocturnal pathology (sleep apnoea, periodic leg movements and/or restless leg syndrome). CONCLUSIONS: patients with WD often suffer from sleep disturbances (regardless of the clinical form). The spectrum of sleep/wake symptoms raises the suspicion that altered REM sleep function may also be involved.

Arousals in nocturnal groaning.

BACKGROUND AND OBJECTIVE: Nocturnal groaning (catathrenia) is a chronic sleep disorder classified as parasomnia with unclear effects on sleep and life quality. It is characterized by repeated episodes of monotonous vocalization in prolonged expiration (episodes of bradypnea) occurring mostly in REM sleep. We sought to assess its impact on sleep microstructure, i.e., the frequency of arousals relative to the groaning episodes. The frequency, duration and sleep-stage distribution of the groaning episodes were also studied. METHODS: Eight patients with nocturnal groaning (5 male, 3 female, age range 11-32 years, mean age 23+/-7.1) were evaluated. All underwent standard neurologic examination and nocturnal videopolysomnography for two consecutive nights. The second night polysomnography data were used to evaluate sleep parameters. The groaning episodes (bradypneic events) were counted separately, not as clusters. RESULTS: Sleep macrostructure revealed no specific changes. The number of groaning episodes/bradypneic events during the night varied from 40 to 182 (total number 725). The duration of bradypnea was from 2 to 46s (mean duration 12.5s). Groaning episodes prevailed in REM sleep (76.5%). The rate for NREM 2 was 21.5%, and only sporadic episodes were noted in delta sleep (1.9%); 63.3% of the events were associated with arousals, and in 94% of them an arousal occurred before or together with the onset of bradypnea. The arousal index was increased in 5 patients (mean 20.4). Bruxism was present in 4 cases, in 1 patient appearing in close association with groaning episodes. Ronchopathy was noted in 4 cases. CONCLUSION: Almost two-thirds of the groaning episodes were connected with arousals. Hypothetically, nocturnal groaning may well be a source of sleep disruption (mainly REM) in some cases. Because an arousal mostly preceded or coincided with groaning we believe that arousal mechanisms may be involved in the pathogenesis of nocturnal groaning.

Replication of restless legs syndrome loci in three European populations.

BACKGROUND: Restless legs syndrome (RLS) is associated with common variants in three intronic and intergenic regions in MEIS1, BTBD9, and MAP2K5/LBXCOR1 on chromosomes 2p, 6p and 15q. METHODS: Our study investigated these variants in 649 RLS patients and 1230 controls from the Czech Republic (290 cases and 450 controls), Austria (269 cases and 611 controls) and Finland (90 cases and 169 controls). Ten single nucleotide polymorphisms (SNPs) within the three genomic regions were selected according to the results of previous genome-wide scans. Samples were genotyped using Sequenom platforms. RESULTS: We replicated associations for all loci in the combined samples set (rs2300478 in MEIS1, p = 1.26 x 10(-5), odds ratio (OR) = 1.47, rs3923809 in BTBD9, p = 4.11 x 10(-5), OR = 1.58 and rs6494696 in MAP2K5/LBXCOR1, p = 0.04764, OR = 1.27). Analysing only familial cases against all controls, all three loci were significantly associated. Using sporadic cases only, we could confirm the association only with BTBD9. CONCLUSION: Our study shows that variants in these three loci confer consistent disease risks in patients of European descent. Among the known loci, BTBD9 seems to be the most consistent in its effect on RLS across populations and is also most independent of familial clustering.

[Wilson's disease]. / Wilsonova choroba.

Wilson's disease is an inherited disorder leading to accumulation of copper in tissues, mainly in the liver and brain. Genetic defect is in the gene coding ATPase type P (ATP7B). The inheritance is autosomal recessive. Up to now, more then 500 mutations causing Wilson's disease were described. The most frequent mutation in Central Europe is mutation H1069Q. The manifestation of Wilson's disease is usually hepatic or neurologic. Hepatic form is manifested by acute or chronic hepatitis, steatosis or cirrhosis. Neurologic involvement is manifested usually after 20 year of age by motor disturbances (tremor, disturbed speech, problems with writing), which could progress into severe extrapyramidal syndrome with tremor, rigidity, dysartria, dysfagia and muscle contracture. Diagnosis is based on clinical and laboratory examinations (neurologic symptoms, liver disease, low serum ceruloplasmin levels, elevated free copper concentration in serum, high urine copper excretion, and presence of Kayser-Fleischer rings). Confirmation of diagnosis is done by hepatic copper concentration in liver biopsy or by genetic examination. Untreated disease leads to the death of a patient. Treatment is based on chelating agents decreasing the copper content by excretion into urine (D-penicillamine, trientine) or on agents preventing absorption of copper from food (zinc, ammonium-tetrahiomolybdene). Patients with asymptomatic Wilson's disease have to be treated as well. In Czech Republic either penicillamine or zinc are used. Liver transplantation is indicated in patients with fulminant liver failure or decompensated cirrhosis. Screening in families of affected patients (all siblings) is obvious.

Reduced hypothalamic gray matter in narcolepsy with cataplexy.

OBJECTIVES: Narcolepsy with cataplexy is associated with a loss of hypocretin. The question is, if there is an autoimmune or neurodegenerative process selectively killing the hypothalamic hypocretin-containing neurons or if these cells survive but fail to produce hypocretin. To support one of these hypothesis we aimed to detect structural changes in the hypothalamus of narcoletic patients. MATERIALS AND METHODS: Nineteen narcoleptic patients were compared to 16 healthy controls. We used voxel-based morphometry (VBM), an unbiased MRI morphometric method with a high sensitivity for subtle changes in gray and white matter volumes to investigate hypothalamic region in this condition. RESULTS: Classical MRI protocol revealed no structural abnormalities, but using VBM we found significant reduction in hypothalamic gray matter volumes between patients and controls. CONCLUSIONS: VBM showed hypothalamic gray matter loss in narcolepsy with cataplexy. This suggest that functional abnormalities of hypocretin neurons in narcolepsy are associated with structural changes of hypothalamus.

[Heart rate variability during sleep]. / Variabilita srdecní frekvence ve spánku.

BACKGROUND: Changes in the tone of the autonomic nervous system during sleep occur and characterize individual sleep stages and probably also sleep cycles. The spectral analysis of the heart rate variability (SA HRV) is a tool for exact assessment of autonomic nervous activity giving us precise information on the activity of the autonomic nervous system--on its sympathetic and parasympathetic component. METHODS AND RESULTS: All night polysomnographic recording was performed in 11 healthy subjects, during which the SA HRV was carried out. The total spectral power of the heart rate variability and relative values of its individual components were evaluated: the very low frequency component (VLF), the low frequency component (LF), and high frequency component (HF). The absolute value of the RR-interval duration was assessed. The LF spectral band in normalized units was significantly higher during REM sleep than in non-REM sleep. On the other hand, the HF spectral band in normalized units was significantly higher during non-REM sleep compared to REM sleep. The LF/HF ratio, which reflects the sympathovagal balance, had a maximal value during REM sleep and reached its minimum in non-REM sleep. A gradual lengthening of the RR-interval and lowering of the LF/HF ratio during night was observed. CONCLUSIONS: The SA HRV showed to be a sensitive method for detection of activity of the autonomic nervous system during sleep. The sympathovagal balance was shifted to prevailing sympathetic activity in REM sleep. On the contrary, during non-REM sleep this balance was shifted towards prevailing parasympathetic influence. A gradual increase of parasympathetic influence during night was also observed.

[Alternating hemiplegia of childhood (AHC)]. / Alternující hemiplegie v detství--longitudinální studie.

BACKGROUND: Alternating hemiplegia of childhood (AHC) is a rare neurological disease of unknown aetiology characterized by recurrent paroxysmal attacks of side-alternating hemiplegias of variable duration associated with other paroxysmal dysfunctions. Paroxysmal attacks start in infants but neurological deficits become progressive with the age. METHODS AND RESULTS: During the last 20 years 8 patients (5 boys, 3 girls) with AHC were followed. Mean age at the time of diagnosis was 2.75 years, age range 2-5 years; mean follow up period 13.9 years (range 1 month-20 years) The diagnosis was based on clinical history and neurological findings, completed by neurophysiological and neuroimaging methods (SPECT, PET), and results of psychological and biochemical findings. Paroxysmal phenomena (occulo-motor, tonic, choreo-athetotic, autonomic) appearing at the age of 4.1 +/- 2.2 months and followed by repeated attacks of hemiplegia (age onset 16.3 +/- 13.0 months) were the first symptoms. Progressive neurological impairment covering spasticity, dyskinetic syndrome, cerebellar ataxia and intellectual deficit was present in all cases, epileptic seizures in 7 out of 8 patients. On ictal SPECT/PET examination hypoperfusion/glucose hypometabolism were demonstrated above affected hemispheres including basal ganglia, both thalami and cerebellar hemispheres. Improvement of hemiparesis was illustrated by nocturnal videomonitoring. CONCLUSIONS: AHC is a chronic disease with progressive neurological deficit. A flunarizine therapy has a favorable effect on frequency and severity of paroxysmal attacks, but does not prevent a progressive neurological impairment.

[Periodic limb movements in sleep: polysomnographic and actigraphic methods for their detection]. / Periodické pohyby koncetinami ve spáinku a jejich vysetrování pomocí polygrafie a aktigrafie.

BACKGROUND: The aim of our study was to compare the results obtained by simultaneous polysomnographic and actigraphic recording and thus to estimate the specificity and sensitivity of actigraphic evaluation of periodic leg movements in sleep (PLMS). As a standard method, PLMS are detected by means of polysomnography, including superficial EMG of anterior tibial muscles. Since 1995, there have been efforts to detect PLMS by means of actigraphy, which is more convenient for both patient and investigator. METHODS AND RESULTS: Recordings were done during 44 nights in 42 patients (10 women, mean age 49.2, SD 13.1 years) in our sleep laboratory. The same criteria for periodic leg movements and the cut-off periodic leg movements index (PLMI > 5) were used in both methods. For the actigraphic way of PLMS detection, we found a specificity of 90%, sensitivity 60%, positive predictive value 88.2%, negative predictive value 64.3 % and total diagnostic accuracy of 73.3%. A close correlation (Spearman's coefficient rho > 0.64, p < 0.0001) between PLMI resulting from either method of recording was observed, though the PLMI actigraph proved to be significantly lower (Sign test--p < 0.01). CONCLUSIONS: Our study has proven good specificity a negative predictive value of the actigraphic recording. To improve its sensitivity, we suggest to reduce the threshold of significant presence PLMS, as expressed by PLMI, from 5 to 3. Actigraphy seems to be a suitable method from PLMS screening in the general population for both clinical and research purposes.

[Spectral analysis of the variations in heart rate and cardiac activation on waking up in sleepwalking]. / Análisis espectral de la variabilidad del ritmo cardíaco y activación cardíaca durante el despertar en el sonambulismo.

INTRODUCTION: In sleepwalking, a disorder that is characterised by partial waking, the subject experiences an alteration of the microstructure of sleep that can affect autonomous activity during sleep and the waking state. AIMS: In order to evaluate any possible upset in the regulation of autonomous functioning in sleepwalkers during sleep and the waking state, we conducted a spectral analysis of their heart rate variability (HRV) during both sleep and the waking state. SUBJECTS AND METHODS: Spectral analysis of HRV was conducted in the group of 10 sleepwalkers and 10 normal controls during sleep and during the waking state in both the horizontal and vertical positions. Their pattern of cardiac activation was also analysed during different types of arousal. RESULTS: There were no differences between the group of sleepwalkers and the control group in the parameters used in the spectral analysis of HRV during sleep and in the horizontal position during the waking state. Sleepwalkers showed a greater shift in the sympathovagal balance in favour of sympathetic activity, as a response to standing. During the 5-minute sequences immediately before the start of pathological arousal in sleepwalkers, the total energy in the spectral analysis of HRV was seen to increase. No differences were found between the patterns of cardiac activation displayed by the groups of patients and normal subjects during several different types of arousal. CONCLUSIONS: Autonomous reactivity was seen to be altered as a response to the orthostatic load in sleepwalkers, which could be the consequence of the instability of these patients' sleep. The increase in the total energy in the spectral analysis of HRV immediately before pathological arousal during NREM 4 sleep in sleepwalkers suggests that autonomous activation precedes cortical arousal.

Análisis espectral de la variabilidad del ritmo cardíaco y activación cardíaca durante el despertar en el sonambulismo / Spectral analysis of the variations in heart rate and cardiac activation on waking up in sleepwalking

Introducción. En el sonambulismo, un trastorno caracterizado por un despertar parcial, se refiere una alteración de la microestructura del sueño que puede influir en la actividad autónoma durante el sueño y la vigilia. Objetivo. Para evaluar una posible desregulación autónoma en los pacientes con sonambulismo durante el sueño y la vigilia, realizamos un análisis espectral de la variabilidad del ritmo cardíaco (VRC) durante el sueño y la vigilia. Sujetos y métodos. En el grupo de 10 sonámbulos y de 10 sujetos normales se realizó el análisis espectral de la VRC durante el sueño y durante la vigilia en la posición horizontal y vertical, y un análisis del patrón de la activación cardíaca durante varios tipos de despertar. Resultados. El grupo de sonámbulos y el grupo de control no difirieron en los parámetros del análisis espectral de la VRC durante el sueño y en la posición horizontal durante la vigilia. En los sonámbulos se demostró un mayor cambio del equilibrio simpaticovagal en beneficio de la actividad simpática, en respuesta a la verticalización. Durante las secuencias de 5 minutos inmediatamente anteriores al inicio del despertar patológico en los sonámbulos, se observó el incremento de la energía total del análisis espectral de la VRC. El patrón de la activación cardíaca durante varios tipos de despertar no difirió entre los pacientes y los sujetos normales. Conclusiones. Se evidenció una alteración de la reactividad autónoma en respuesta a la carga ortostática en sonámbulos, lo que puede ser la consecuencia de la inestabilidad del sueño en estos pacientes. El incremento de la energía total del análisis espectral de la VRC, inmediatamente antes del despertar patológico durante el sueño NREM 4 en sonámbulos, sugiere que la activación autónoma precede el despertar cortical (AU)

Introduction. In sleepwalking, a disorder that is characterised by partial waking, the subject experiences an alteration of the microstructure of sleep that can affect autonomous activity during sleep and the waking state. Aims. In order to evaluate any possible upset in the regulation of autonomous functioning in sleepwalkers during sleep and the waking state, we conducted a spectral analysis of their heart rate variability (HRV) during both sleep and the waking state. Subjects and methods. Spectral analysis of HRV was conducted in the group of 10 sleepwalkers and 10 normal controls during sleep and during the waking state in both the horizontal and vertical positions. Their pattern of cardiac activation was also analysed during different types of arousal. Results. There were no differences between the group of sleepwalkers and the control group in the parameters used in the spectral analysis of HRV during sleep and in the horizontal position during the waking state. Sleepwalkers showed a greater shift in the sympathovagal balance in favour of sympathetic activity, as a response to standing. During the 5-minute sequences immediately before the start of pathological arousal in sleepwalkers, the total energy in the spectral analysis of HRV was seen to increase. No differences were found between the patterns of cardiac activation displayed by the groups of patients and normal subjects during several different types of arousal. Conclusions. Autonomous reactivity was seen to be altered as a response to the orthostatic load in sleepwalkers, which could be the consequence of the instability of these patients’ sleep. The increase in the total energy in the spectral analysis of HRV immediately before pathological arousal during NREM 4 sleep in sleepwalkers suggests that autonomous activation precedes cortical arousal (AU)

Hypocretin deficiency in Prader-Willi syndrome.

Four patients with clinically and genetically confirmed Prader-Willi syndrome (PWS) underwent nocturnal polysomnograpy (PSG), multiple sleep latency test (MSLT), human leukocyte antigens (HLA) typing and estimation of cerebrospinal fluid (CSF) hypocretin-1 (Hcrt-1) level to investigate if a role of hypothalamic dysfunction and sleep disturbance might be functionally connected through the hypocretin (orexin) system. In all four patients physical examination confirmed extreme obesity (increasing with age) with dysmorphogenetic features. Excessive daytime sleepiness (EDS) was manifested in only two subjects without any imperative feature. None of the patients under study suffered from cataplexy. Nocturnal PSG revealed fragmented sleep with low efficiency, the hypopnea and apnea indexes increasing from borderline up to very high values in direct proportion to the patients' age. MSLT latency was shortened in two patients with clinically expressed EDS, only one sleep onset rapid eye movements (REM) period (SOREM) was found. HLA typing showed DQB1*0602 positivity in two patients; the further two were negative. Mean value of CSF Hcrt-1 in the patients group was down to 164 +/- 46.8 pg/ml (in comparison with 265.8 +/- 48.8 pg/ml in 10 young healthy subjects, P=0.02). The deficiency of CSF Hcrt-1 level correlated in PWS patients with their EDS severity.

Spectral analysis of the heart rate variability in sleep.

Spectral analysis of heart rate variability (HRV) during overnight polygraphic recording was performed in 11 healthy subjects. The total spectrum power, power of the VLF, LF and HF spectral bands and the mean R-R were evaluated. Compared to Stage 2 and Stage 4 non-REM sleep, the total spectrum power was significantly higher in REM sleep and its value gradually increased in the course of each REM cycle. The value of the VLF component (reflects slow regulatory mechanisms, e.g. the renin-angiotensin system, thermoregulation) was significantly higher in REM sleep than in Stage 2 and Stage 4 of non-REM sleep. The LF spectral component (linked to the sympathetic modulation) was significantly higher in REM sleep than in Stage 2 and Stage 4 non-REM sleep. On the contrary, a power of the HF spectral band (related to parasympathetic activity) was significantly higher in Stage 2 and Stage 4 non-REM than in REM sleep. The LF/HF ratio, which reflects the sympathovagal balance, had its maximal value during REM sleep and a minimal value in synchronous sleep. The LF/HF ratio significantly increased during 5-min segments of Stage 2 non-REM sleep immediately preceding REM sleep compared to 5-min segments of Stage 2 non-REM sleep preceding the slow-wave sleep. This expresses the sympathovagal shift to sympathetic predominance occurring before the onset of REM sleep. A significant lengthening of the R-R interval during subsequent cycles of Stage 2 non-REM sleep was documented, which is probably related to the shift of sympathovagal balance to a prevailing parasympathetic influence in the course of sleep. This finding corresponds to a trend of a gradual decrease of the LF/HF ratio in subsequent cycles of Stage 2 non-REM sleep.

[Excessive daytime somnolence and its psychosocial sequelae]. / Nadmerná denní spavost a její psychosociální dusledky.

Excessive daytime sleepiness arises frequently as a consequence of insufficient or shortened nocturnal sleep, or as a result of poor sleeps hygiene. One of the most common dyssomnias with imperative sleepiness is narcolepsy. Narcolepsy is a chronic disease that greatly affects quality of life. The present study of 57 patients shows that the negative assessment is partly due to the subjective views exhibited by the narcoleptic personality prone to underestimation, negative self-image and depressive disposition. The personality traits may be due to an adaptation reaction to the disease but also to the biological predisposition. Comparison with population data for our Republic brought no evidence of progress at education or family life being adversely affected by narcolepsy, however, decreased assertion in employment and limitation in self-realization in free time was an explicit consequence of the disease. All 57 patients reported excessive daytime sleepiness as the most discomforting symptom that in 40% of them was responsible for career curtailment in a productive age and for living on partial or full disability.

Electromagnetic field of mobile phones affects visual event related potential in patients with narcolepsy.

The effects of the mobile phone (MP) electromagnetic fields on electroencephalography (EEG) and event-related potentials (ERP) were examined. With regard to the reported effects of MP on sleep, 22 patients with narcolepsy-cataplexy were exposed or sham exposed for 45 min to the MP (900 MHz, specific absorption rate 0.06 W/kg) placed close to the right ear in a double blind study. There were no changes of the EEG recorded after the MP exposure. A subgroup of 17 patients was studied on visual ERP recorded during the MP exposure. Using an adapted "odd-ball" paradigm, each patient was instructed to strike a key whenever rare target stimuli were presented. There were three variants of target stimuli (horizontal stripes in (i) left, (ii) right hemifields or (iii) whole field of the screen). The exposure enhanced the positivity of the ERP endogenous complex solely in response to target stimuli in the right hemifield of the screen (P < 0.01). The reaction time was shortened by 20 ms in response to all target stimuli (P < 0.05). In conclusion, the electromagnetic field of MP may suppress the excessive sleepiness and improve performance while solving a monotonous cognitive task requiring sustained attention and vigilance.

Low cerebrospinal fluid hypocretin (Orexin) and altered energy homeostasis in human narcolepsy.

Hypocretins (orexins) are hypothalamic neuropeptides involved in sleep and energy homeostasis. Hypocretin mutations produce narcolepsy in animal models. In humans, narcolepsy is rarely due to hypocretin mutations, but this system is deficient in the cerebrospinal fluid (CSF) and brain of a small number of patients. A recent study also indicates increased body mass index (BMI) in narcolepsy. The sensitivity of low CSF hypocretin was examined in 38 successive narcolepsy-cataplexy cases [36 human leukocyte antigen (HLA)-DQB1*0602-positive] and 34 matched controls (15 controls and 19 neurological patients). BMI and CSF leptin levels were also measured. Hypocretin-1 was measurable (169 to 376 pg/ml) in all controls. Levels were unaffected by freezing/thawing or prolonged storage and did not display any concentration gradient. Hypocretin-1 was dramatically decreased (<100 pg/ml) in 32 of 38 patients (all HLA-positive). Four patients had normal levels (2 HLA-negative). Two HLA-positive patients had high levels (609 and 637 pg/ml). CSF leptin and adjusted BMI were significantly higher in patients versus controls. We conclude that the hypocretin ligand is deficient in most cases of human narcolepsy, providing possible diagnostic applications. Increased BMI and leptin indicate altered energy homeostasis. Sleep and energy metabolism are likely to be functionally connected through the hypocretin system.

[Analysis of the most frequent mutations in girls with Rett syndrome]. / Analýza nejcastejsích mutací u dívek s Rettovým syndromem.

BACKGROUND: Rett syndrome is an X-linked dominant neurodevelopmental disorder affecting 1 from 10,000 to 15,000 females worldwide. The responsible gene, encoding methyl-CpG binding protein 2 was recently identified. Methyl-CpG binding protein 2 is thought to act as a global transcriptional repressor. In the methyl-CpG binding protein 2 gene are known 5 prevalent mutations that cause Rett syndrome. Four of them are detectable by restriction analysis. In this study we present the results of the molecular study of four prevalent mutations in the gene for methyl-CpG binding protein 2 in Czech and Slovak patients with Rett syndrome. METHODS AND RESULTS: 22 females with Rett syndrome were investigated by methods of molecular biology. Restriction analysis and direct sequencing of PCR products revealed in methyl-CpG binding protein 2 gene 3 different mutations (T158M, R168X, R270X) in six unrelated patients with Rett syndrome. Mutation R306C, frequent in Great Britain and Sweden, was not detected in our group of patients with Rett syndrome. CONCLUSIONS: The diagnosis of Rett syndrome and genetic counselling in affected families should go out from the close cooperation of the pediatric, neurologic, and genetic departments with the specialized laboratories dealing with the molecular biological diagnosis.

Increased REM density in narcolepsy-cataplexy and the polysymptomatic form of idiopathic hypersomnia.

The present work is focused on REM sleep density in patients with primary hypersomnia in comparison with non-hypersomnia subjects. 28 unmedicated patients with narcolepsy-cataplexy (NC) and 10 unmedicated patients suffering from the polysymptomatic form of idiopathic hypersomnia (IH) and their age- and sex-matched controls were included in the study. The clinical diagnosis was confirmed by MSLT and nocturnal PSG, HLA typing was performed in a respective group of narcoleptic patients. Polygraphical recordings were visually scored with particular regard to the two most characteristic phasic features of REM sleep: the number of rapid eye movements (REMs) and chin muscle twitches (Tws) per minute. These events were evaluated according to recognized criteria; a closer look was taken at both their frequency and their distribution across all the nocturnal REM periods (REMPs). The following main differences between hypersomniac patients (of both groups examined) and healthy controls were found in terms of phasic activity: (I) REM density (expressed in REMs/min and Tws/min in each REM period) was significantly increased in the hypersomniac patients in comparison with the controls. (p>0.05).(II) The intra-night phasic activity distribution was found rising more conspicuously in the hypersomniacs than in the controls.