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Management of augmentation in restless legs syndrome with pramipexole extended-release
Abstracts / Sleep Medicine 14S (2013) e165–e238
and A rhythms and low values in the restfulness score. When a dayto-day time series analysis was performed instead of using the mean waveform, a significant improvement in the three CD markers was observed, although their values still were worse than those observed in diurnal workers. Conclusion: The ACM allows a reliable assessment of the degree of chronodisruption in shift workers, however, mathematical procedures based on day to day analysis should be mandatory to avoid bias derived from the irregular life styles associated to nocturnal shifts. Acknowledgements: To RETICEF (RD12/0043/0011), MINECO (BFU2010–21945-C02–01), and INNPACTO (IPT-2011–0833900000) with FEDER cofounding to JAM. http://dx.doi.org/10.1016/j.sleep.2013.11.456
Polysomnographic findings and respiratory management in leigh syndrome – A case report N. Madureira, M. Estevao, M. Ferreira, P. Garcia, M. Felix Laboratário do Sono e Ventilaão, Hospital Pedic trico, Centro Hospitalar e Universit, Portugal
Introduction: Leigh syndrome (LS) is a neurodegenerative disorder with symmetric necrotizing lesions mainly in the basal ganglia, thalamus and brainstem. Respiratory disturbances are a common feature, may have a fluctuating nature and vary from irregular breathing, deep sighing, hyperventilation or hiccups with lethargy to acute respiratory failure. Since this is a rare condition, there are few published descriptions of respiratory symptoms and polysomnographic (PSG) findings. The authors describe clinical and PSG data of a child with LS. Materials and methods: Case report with description of the clinical and PSG data of a recently diagnosed LS. The analysis of PSG data was based on the AASM guidelines. Post-sigh apnea (P-S apn) was defined as a pause of chest movements for >= 10 s. preceded by an augmented breath (>= 2x amplitude of the preceding stable respiration). Results: A 4 years-old boy was born uneventfully and developed normally until the age of three. He was admitted in a comatous state due to central hypoventilation during an acute respiratory infection. Five months before he had initiated ataxic gait, motor regression, irregular breathing, hiccups and sighs. On examination he had dysmorphic features, hypertrichosis, vertical gaze paralysis, squint, ataxia and tremor. MRI showed bilateral, symmetric focal hyperdensities in basal ganglia and thalamus. Biochemical study identified a complex IV deficiency in mitochondrial respiratory-chain. After respiratory stabilization, non invasive ventilation (NIV) was initiated during sleep. Some days later, he began to refuse it and, as desaturation and hypercapnia had subsided, NIV was suspended. During follow-up he maintained irregular breathing with periods of apneusislike breathing, frequent sighs and hiccups. PSG was performed six months after diagnosis. Sleep structure was normal with an arousal index of 7.2. Respiratory rhythm was very irregular, with clustered breathing on stage NREM 1/2.There were no obstructive events or isolated central apneas, sighs were very frequent (11/hour) and 40 P-S apn were observed (5/h). Mean SpO2 was 98 % (92–100), TcCO2 40-46 mmHg. During follow-up he maintained frequent sighs and hiccups. The parents were informed that the child should be admitted if irregular breathing with apnea was noticed. Conclusion: The PSG findings are consistent with those described in the rare literature for LS. The respiratory management in LS is challenging due to the fluctuation of the respiratory symptoms. http://dx.doi.org/10.1016/j.sleep.2013.11.457
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Obstructive sleep apnea syndrome in children younger than 2 years of age N. Madureira Laboratório do Sono e Ventilação, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Portugal
Introduction: Obstructive sleep apnea syndrome (OSAS) occurs in 1–3% of the pediatric population and may result in severe complications if left untreated. The prevalence of OSAS peaks at 3–7 years of age, when adenotonsillar hypertrophy (AH) is maximum. In infants and young toddlers, OSAS results frequently from craniofacial malformations and neurologic abnormalities; AH may be also related, isolated or in association to the previous conditions. In these cases, OSAS may be more severe and with a high recurrence or incomplete recovery rate after surgery. The authors characterize their clinical experience in OSAS in children younger than 2 years of age. Materials and methods: Retrospective analysis of clinical and polysomnographic (PSG) data of children younger than 2 years of age followed in a pediatric sleep laboratory between January/2007 and June/2013. The analysis of PSG data was based on the AASM guidelines. Results: Twenty-eight children younger than 2 years were studied, 67.9% were male and the median age of the onset of snoring was 7.5 months (0 – 23 months). Five patients (17.8%) had medical syndromes associated with increased risk of OSAS – Crouzon, Down, Goldenhar, polymalformative, chromosomopathy – and 17 (60.7%) had adenotonsillar hypertrophy grade 3 or 4. PSG showed moderate or severe OSAS in 78.5% patients. Median respiratory disturbance index was 16.7 (1.7 – 280.8) and nadir SpO2 varied between 38% and 95% (median 81%). Twenty-two patients underwent adenotonsillectomy, 1 is waiting surgery, 3 are under medical treatment and 2 in non-invasive ventilation (syndromatic patients). In all patients, clinical symptoms resolved or improved after treatment. PSG was performed in ten patients 3 – 6 months after ENT surgery: 3 syndromatic and 7 with severe OSAS. Nine out of the 10 PSG were abnormal: upper airways resistance syndrome (7) and moderate OSAS (2). Median respiratory disturbance index after surgery was 4.5 (0.6 – 5.4) ) and nadir SpO2 after surgery varied between 89% and 97% (median 91%). Conclusion: The present series, although small, alerts medical attention to the possibility of precocious onset of OSAS and that in this age severe adenotonsillar hypertrophy may be associated. In spite of the clinical improvement, almost all PSG performed after surgery showed alterations, pointing to the need of post- treatment control of sleep parameters and follow-up in this age group. http://dx.doi.org/10.1016/j.sleep.2013.11.458
Management of augmentation in restless legs syndrome with pramipexole extended-release M. Maestri 1, S. Fulda 1, L. Ferini-Strambi 2, M. Zucconi 2, C. Bassetti 3, M. Manconi 1 1 Sleep and Epilepsy Center, Neurocenter of the Southern Switzerland, Civic Hospital of Lugano, Switzerland 2 Sleep Disorders Center, Division of Neuroscience, Università Vita-Salute San Raffaele, Milan, Italy 3 University Department of Neurology, Inselspital, Bern, Switzerland
Introduction: Dopamine agonists represent the first- line treatment in restless legs syndrome (RLS), however in the long term, a substantial portion of patients will develop augmentation, which is a severe drug-related exacerbation of symptoms and the main rea-
e194
Abstracts / Sleep Medicine 14S (2013) e165–e238
son of late therapy withdrawal. The mechanism underlining augmentation is unknown and no guidelines are available to treat it. Objective of the study was to evaluate the role of extended release dopaminoagonist in the management of augmentation. Materials and methods: Twenty-four consecutive RLS outpatients (10 M,14F, mean age 68.410 yrs) treated with immediate- release dopamine agonists (pramipexole 11 pts, ropinirole 7 pts, cabergoline 1 pts, levodopa 1 pts, combined DA treatment 4 pts) for a mean period of 6.7 yrs 5 were diagnosed as affected by severe, clinically relevant augmentation Since an inverse relationship between DA half-life and augmentation has been postulated we decided to switch the treatment to the long-acting extended release (ER) formula of pramipexole, given at 5 pm and progressively increased until a satisfactory control of the symptoms was achieved (at a mean dose of 0.75 mg, range 0.375–1.125 mg), accompanied by a complete withdrawal of the otherdopaminergic agents. Results: Resolution of augmentation was observed in all patients in 2–3 weeks and persisted so far for a mean follow- up interval of 7 months. Mean dose of dopamine agonist was not significanty different before and after the shift of therapy (pramipexole equivalent dosage during augmentation 0.84 mg0.51 vs. extended release pramipexole 0.67 mg0.28). RLS severity scale decreased from 324 to 169 (p < .001). Conclusion: Pramipexole extended release might represent an easy, safe and fast pharmacological option that needs to be evaluated with prospective and controlled investigations. The findings support the hypothesis that the duration of action of the drug plays a key role in the mechanism of augmentation. http://dx.doi.org/10.1016/j.sleep.2013.11.459
Macro and microstructure sleep changes in insomniacs with high dose abuse of BZ M. Maestri 1, R. Ferri 2, V. Bottasini 3, L. Ferini-Strambi 3,4, M. Manconi 1 1 Sleep and Epilepsy Center, Neurocenter of the Southern Switzerland, Civic Hospital of Lugano, Switzerland 2 Sleep Research Center, Department of Neurology I.C., Oasi Institute, Troina, Italy 3 Sleep Disorders Center, Division of Neuroscience, Università Vita-Salute San Raffaele, Milan, Italy 4 Miano, Neuroscience, Mental Health and Sense Organs Department, Chair of Pediatrics, Sleep Disorder Centre, La Sapienza University, II Faculty, Medicine, Rome, Italy
Introduction: Chronic and high-dosage intake of benzodiazepine (BZ) is a common problem in patients with insomnia. No data have been reported on the effects on PSG variables induced by high doses of BZ in patients with chronic insomnia. The aim of this study was to evaluate sleep architecture, microstructure (CAP) and EEG power spectra of patients with chronic primary insomnia and chronically treated with high-dose BZ, that were referred to the Sleep Center for drug discontinuation. Materials and methods: Consecutive enrolment of 20 subjects affected by primary insomnia (DSM-IV) and of 13 control subjects was carried out. All patients underwent a nocturnal polysomnographic recording. Sleep stages were scored following standard criteria on 30-s epochs while all CAP phases during NREM sleep were detected and classified into three subtypes (A1, A2, and A3) according to Terzano et al. (2001). Average relative power spectra were calculated using the sleep analysis software Hypnolab 1.2, by means of the Fast Fourier Transform, for frequencies between 0.5 and 25 Hz.
Results: A significant difference was found for Time in Bed, REM sleep latency and percentage of sleep stage 1 which were increased in BZ patients. Total CAP rate was dramatically decreased (8%) in patients (especially during sleep stage 2 and slow-wave sleep) because of the significant decrease in the number of CAP A1 and A2 subtypes. As concern power spectra, during NREM sleep, BZ patients show a clear decrease in the relative power of the delta band of NREM sleep, accompanied by a relative increase of the sigma and beta bans. A time-dependent general decrease of the delta power was observed for control subjects, but not for patients during sleep stage 2 and SWS. Conclusion: Macrostructure of sleep seems to be quite preserved in BZ patients, while sleep instability is decreased to severe pathological values, lower than any other reduction that has been previously reported. This reduction could be responsible for the low sleep quality and the cognitive deficits usually reported. Also power spectral analysis confirm the reduction in slow wave activity and the loss of its dynamic regulation. BZ overuse and insomnia seem to interact both leading to a sleep whose continuity parameters are conserved, but whose organization and microstructure is completely altered. http://dx.doi.org/10.1016/j.sleep.2013.11.460
Serial electrical stimulations of hypothalamic orexin-containing neuronal regions lead to elevation of CSF OrexinA concentration and fasten the recovery of sleep-wakefulness cycle from experimentally induced comatose state N. Maglakelidze, E. Chkhartishvili, S. Dzadzamia, E. Chijavadze, M. Babilodze, N. Nachkebia Lab. Neurobiology of Sleep-Wakefulness Cycle, I. Beritashvili Center of Experimental Biomedicine, Georgia
Introduction: Study is aimed at assessing the Hypothalamic Orexinergic system as the neuronal substrate that increases the speed of regulation of disturbed sleep homeostasis and wakefulness recovery from some pathological conditions, namely from experimental comatose state. Pre-clinical evidences on this topic is sparse and we are studying this question for the first time. Materials and methods: Using white wild rats, (n = 12) modeling of semi-chronic experimental comatose state was induced by kainic and/or ibotenic acid lesion of intra-collicular layers. EEG registration was started immediately, lasting continuously for 72 h. 30 min after comatose state, serial electrical stimulations (8–12v, 200c/s, 0.1 ms) of dorsal, lateral, posterior and perifornical Hypothalamic Orexincontaining neurons began. Stimulation periods, lasting for 1 h, with 5 min intervals between subsequent stimulation, were applied in turn to the left and to the right side hypothalamic regions. CSF OrexinA concentration was measured by ELISA method. Statistical processing was made by Students’ t-test. Results: Kainic and/or ibotenic lesioning of intra-collicular layers wholly disrupts cyclic alternation of sleep-wakefulness cycle (SWC) behavioral states. Isolated forebrain falls into comatose state and pathological pattern of electrical activity (exaggerated spindle activity with strongly desynchronized inter-spindle periods) takes the dominant position in neo- and paleo-cortical structures. Dominance of this pathological pattern of EEG activity takes approximately 30 h and then the first sighns for spontaneous normalization appears. Spontaneous recovery from comatose state starts by restoration of light slow wave sleep EEG picture, taking approximately 40 h after lesioning. Serial electrical stimulations of dorsal, lateral, posterior and perifornical hypothalamic Orexin- containing neurons significantly speed up light slow wave sleep recovery, taking 30–35 h after comatose state. Deep slow wave sleep
and A rhythms and low values in the restfulness score. When a dayto-day time series analysis was performed instead of using the mean waveform, a significant improvement in the three CD markers was observed, although their values still were worse than those observed in diurnal workers. Conclusion: The ACM allows a reliable assessment of the degree of chronodisruption in shift workers, however, mathematical procedures based on day to day analysis should be mandatory to avoid bias derived from the irregular life styles associated to nocturnal shifts. Acknowledgements: To RETICEF (RD12/0043/0011), MINECO (BFU2010–21945-C02–01), and INNPACTO (IPT-2011–0833900000) with FEDER cofounding to JAM. http://dx.doi.org/10.1016/j.sleep.2013.11.456
Polysomnographic findings and respiratory management in leigh syndrome – A case report N. Madureira, M. Estevao, M. Ferreira, P. Garcia, M. Felix Laboratário do Sono e Ventilaão, Hospital Pedic trico, Centro Hospitalar e Universit, Portugal
Introduction: Leigh syndrome (LS) is a neurodegenerative disorder with symmetric necrotizing lesions mainly in the basal ganglia, thalamus and brainstem. Respiratory disturbances are a common feature, may have a fluctuating nature and vary from irregular breathing, deep sighing, hyperventilation or hiccups with lethargy to acute respiratory failure. Since this is a rare condition, there are few published descriptions of respiratory symptoms and polysomnographic (PSG) findings. The authors describe clinical and PSG data of a child with LS. Materials and methods: Case report with description of the clinical and PSG data of a recently diagnosed LS. The analysis of PSG data was based on the AASM guidelines. Post-sigh apnea (P-S apn) was defined as a pause of chest movements for >= 10 s. preceded by an augmented breath (>= 2x amplitude of the preceding stable respiration). Results: A 4 years-old boy was born uneventfully and developed normally until the age of three. He was admitted in a comatous state due to central hypoventilation during an acute respiratory infection. Five months before he had initiated ataxic gait, motor regression, irregular breathing, hiccups and sighs. On examination he had dysmorphic features, hypertrichosis, vertical gaze paralysis, squint, ataxia and tremor. MRI showed bilateral, symmetric focal hyperdensities in basal ganglia and thalamus. Biochemical study identified a complex IV deficiency in mitochondrial respiratory-chain. After respiratory stabilization, non invasive ventilation (NIV) was initiated during sleep. Some days later, he began to refuse it and, as desaturation and hypercapnia had subsided, NIV was suspended. During follow-up he maintained irregular breathing with periods of apneusislike breathing, frequent sighs and hiccups. PSG was performed six months after diagnosis. Sleep structure was normal with an arousal index of 7.2. Respiratory rhythm was very irregular, with clustered breathing on stage NREM 1/2.There were no obstructive events or isolated central apneas, sighs were very frequent (11/hour) and 40 P-S apn were observed (5/h). Mean SpO2 was 98 % (92–100), TcCO2 40-46 mmHg. During follow-up he maintained frequent sighs and hiccups. The parents were informed that the child should be admitted if irregular breathing with apnea was noticed. Conclusion: The PSG findings are consistent with those described in the rare literature for LS. The respiratory management in LS is challenging due to the fluctuation of the respiratory symptoms. http://dx.doi.org/10.1016/j.sleep.2013.11.457
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Obstructive sleep apnea syndrome in children younger than 2 years of age N. Madureira Laboratório do Sono e Ventilação, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Portugal
Introduction: Obstructive sleep apnea syndrome (OSAS) occurs in 1–3% of the pediatric population and may result in severe complications if left untreated. The prevalence of OSAS peaks at 3–7 years of age, when adenotonsillar hypertrophy (AH) is maximum. In infants and young toddlers, OSAS results frequently from craniofacial malformations and neurologic abnormalities; AH may be also related, isolated or in association to the previous conditions. In these cases, OSAS may be more severe and with a high recurrence or incomplete recovery rate after surgery. The authors characterize their clinical experience in OSAS in children younger than 2 years of age. Materials and methods: Retrospective analysis of clinical and polysomnographic (PSG) data of children younger than 2 years of age followed in a pediatric sleep laboratory between January/2007 and June/2013. The analysis of PSG data was based on the AASM guidelines. Results: Twenty-eight children younger than 2 years were studied, 67.9% were male and the median age of the onset of snoring was 7.5 months (0 – 23 months). Five patients (17.8%) had medical syndromes associated with increased risk of OSAS – Crouzon, Down, Goldenhar, polymalformative, chromosomopathy – and 17 (60.7%) had adenotonsillar hypertrophy grade 3 or 4. PSG showed moderate or severe OSAS in 78.5% patients. Median respiratory disturbance index was 16.7 (1.7 – 280.8) and nadir SpO2 varied between 38% and 95% (median 81%). Twenty-two patients underwent adenotonsillectomy, 1 is waiting surgery, 3 are under medical treatment and 2 in non-invasive ventilation (syndromatic patients). In all patients, clinical symptoms resolved or improved after treatment. PSG was performed in ten patients 3 – 6 months after ENT surgery: 3 syndromatic and 7 with severe OSAS. Nine out of the 10 PSG were abnormal: upper airways resistance syndrome (7) and moderate OSAS (2). Median respiratory disturbance index after surgery was 4.5 (0.6 – 5.4) ) and nadir SpO2 after surgery varied between 89% and 97% (median 91%). Conclusion: The present series, although small, alerts medical attention to the possibility of precocious onset of OSAS and that in this age severe adenotonsillar hypertrophy may be associated. In spite of the clinical improvement, almost all PSG performed after surgery showed alterations, pointing to the need of post- treatment control of sleep parameters and follow-up in this age group. http://dx.doi.org/10.1016/j.sleep.2013.11.458
Management of augmentation in restless legs syndrome with pramipexole extended-release M. Maestri 1, S. Fulda 1, L. Ferini-Strambi 2, M. Zucconi 2, C. Bassetti 3, M. Manconi 1 1 Sleep and Epilepsy Center, Neurocenter of the Southern Switzerland, Civic Hospital of Lugano, Switzerland 2 Sleep Disorders Center, Division of Neuroscience, Università Vita-Salute San Raffaele, Milan, Italy 3 University Department of Neurology, Inselspital, Bern, Switzerland
Introduction: Dopamine agonists represent the first- line treatment in restless legs syndrome (RLS), however in the long term, a substantial portion of patients will develop augmentation, which is a severe drug-related exacerbation of symptoms and the main rea-
e194
Abstracts / Sleep Medicine 14S (2013) e165–e238
son of late therapy withdrawal. The mechanism underlining augmentation is unknown and no guidelines are available to treat it. Objective of the study was to evaluate the role of extended release dopaminoagonist in the management of augmentation. Materials and methods: Twenty-four consecutive RLS outpatients (10 M,14F, mean age 68.410 yrs) treated with immediate- release dopamine agonists (pramipexole 11 pts, ropinirole 7 pts, cabergoline 1 pts, levodopa 1 pts, combined DA treatment 4 pts) for a mean period of 6.7 yrs 5 were diagnosed as affected by severe, clinically relevant augmentation Since an inverse relationship between DA half-life and augmentation has been postulated we decided to switch the treatment to the long-acting extended release (ER) formula of pramipexole, given at 5 pm and progressively increased until a satisfactory control of the symptoms was achieved (at a mean dose of 0.75 mg, range 0.375–1.125 mg), accompanied by a complete withdrawal of the otherdopaminergic agents. Results: Resolution of augmentation was observed in all patients in 2–3 weeks and persisted so far for a mean follow- up interval of 7 months. Mean dose of dopamine agonist was not significanty different before and after the shift of therapy (pramipexole equivalent dosage during augmentation 0.84 mg0.51 vs. extended release pramipexole 0.67 mg0.28). RLS severity scale decreased from 324 to 169 (p < .001). Conclusion: Pramipexole extended release might represent an easy, safe and fast pharmacological option that needs to be evaluated with prospective and controlled investigations. The findings support the hypothesis that the duration of action of the drug plays a key role in the mechanism of augmentation. http://dx.doi.org/10.1016/j.sleep.2013.11.459
Macro and microstructure sleep changes in insomniacs with high dose abuse of BZ M. Maestri 1, R. Ferri 2, V. Bottasini 3, L. Ferini-Strambi 3,4, M. Manconi 1 1 Sleep and Epilepsy Center, Neurocenter of the Southern Switzerland, Civic Hospital of Lugano, Switzerland 2 Sleep Research Center, Department of Neurology I.C., Oasi Institute, Troina, Italy 3 Sleep Disorders Center, Division of Neuroscience, Università Vita-Salute San Raffaele, Milan, Italy 4 Miano, Neuroscience, Mental Health and Sense Organs Department, Chair of Pediatrics, Sleep Disorder Centre, La Sapienza University, II Faculty, Medicine, Rome, Italy
Introduction: Chronic and high-dosage intake of benzodiazepine (BZ) is a common problem in patients with insomnia. No data have been reported on the effects on PSG variables induced by high doses of BZ in patients with chronic insomnia. The aim of this study was to evaluate sleep architecture, microstructure (CAP) and EEG power spectra of patients with chronic primary insomnia and chronically treated with high-dose BZ, that were referred to the Sleep Center for drug discontinuation. Materials and methods: Consecutive enrolment of 20 subjects affected by primary insomnia (DSM-IV) and of 13 control subjects was carried out. All patients underwent a nocturnal polysomnographic recording. Sleep stages were scored following standard criteria on 30-s epochs while all CAP phases during NREM sleep were detected and classified into three subtypes (A1, A2, and A3) according to Terzano et al. (2001). Average relative power spectra were calculated using the sleep analysis software Hypnolab 1.2, by means of the Fast Fourier Transform, for frequencies between 0.5 and 25 Hz.
Results: A significant difference was found for Time in Bed, REM sleep latency and percentage of sleep stage 1 which were increased in BZ patients. Total CAP rate was dramatically decreased (8%) in patients (especially during sleep stage 2 and slow-wave sleep) because of the significant decrease in the number of CAP A1 and A2 subtypes. As concern power spectra, during NREM sleep, BZ patients show a clear decrease in the relative power of the delta band of NREM sleep, accompanied by a relative increase of the sigma and beta bans. A time-dependent general decrease of the delta power was observed for control subjects, but not for patients during sleep stage 2 and SWS. Conclusion: Macrostructure of sleep seems to be quite preserved in BZ patients, while sleep instability is decreased to severe pathological values, lower than any other reduction that has been previously reported. This reduction could be responsible for the low sleep quality and the cognitive deficits usually reported. Also power spectral analysis confirm the reduction in slow wave activity and the loss of its dynamic regulation. BZ overuse and insomnia seem to interact both leading to a sleep whose continuity parameters are conserved, but whose organization and microstructure is completely altered. http://dx.doi.org/10.1016/j.sleep.2013.11.460
Serial electrical stimulations of hypothalamic orexin-containing neuronal regions lead to elevation of CSF OrexinA concentration and fasten the recovery of sleep-wakefulness cycle from experimentally induced comatose state N. Maglakelidze, E. Chkhartishvili, S. Dzadzamia, E. Chijavadze, M. Babilodze, N. Nachkebia Lab. Neurobiology of Sleep-Wakefulness Cycle, I. Beritashvili Center of Experimental Biomedicine, Georgia
Introduction: Study is aimed at assessing the Hypothalamic Orexinergic system as the neuronal substrate that increases the speed of regulation of disturbed sleep homeostasis and wakefulness recovery from some pathological conditions, namely from experimental comatose state. Pre-clinical evidences on this topic is sparse and we are studying this question for the first time. Materials and methods: Using white wild rats, (n = 12) modeling of semi-chronic experimental comatose state was induced by kainic and/or ibotenic acid lesion of intra-collicular layers. EEG registration was started immediately, lasting continuously for 72 h. 30 min after comatose state, serial electrical stimulations (8–12v, 200c/s, 0.1 ms) of dorsal, lateral, posterior and perifornical Hypothalamic Orexincontaining neurons began. Stimulation periods, lasting for 1 h, with 5 min intervals between subsequent stimulation, were applied in turn to the left and to the right side hypothalamic regions. CSF OrexinA concentration was measured by ELISA method. Statistical processing was made by Students’ t-test. Results: Kainic and/or ibotenic lesioning of intra-collicular layers wholly disrupts cyclic alternation of sleep-wakefulness cycle (SWC) behavioral states. Isolated forebrain falls into comatose state and pathological pattern of electrical activity (exaggerated spindle activity with strongly desynchronized inter-spindle periods) takes the dominant position in neo- and paleo-cortical structures. Dominance of this pathological pattern of EEG activity takes approximately 30 h and then the first sighns for spontaneous normalization appears. Spontaneous recovery from comatose state starts by restoration of light slow wave sleep EEG picture, taking approximately 40 h after lesioning. Serial electrical stimulations of dorsal, lateral, posterior and perifornical hypothalamic Orexin- containing neurons significantly speed up light slow wave sleep recovery, taking 30–35 h after comatose state. Deep slow wave sleep