- Email: [email protected]
P9-8 Validation of manual and automatic sleep scoring in normals and patients with neurodegenerative disorders
29th International Congress of Clinical Neurophysiology Results: HR and %LF were higher for the Task night than for the Notask night during both the waking state and the sleeping state. There was less amount of REM sleep especially in the first and fourth 2-hour periods on the Task night than on the No-task night. Amounts of slow wave sleep, wake time after sleep onset and movement time were not different between the two conditions. This might be related with small arousals which were so brief that they did not affect on the sleep architecture. Conclusion: The present study revealed that all-night sleep quality and sleep architecture in children can be affected by some exciting activities 1 hour before bedtime.
S155 Conclusions: SRED is likely to occur in young adult, and much more common in women than men. Judged from patients’ history and distribution of the symptom, SRED could be a severe symptomatic variant of AD, sometimes complicating NES. P9-7 Leg movement durations and periodicities in periodic limb movements of three patients with brain lesion, spinal cord lesion, and leg bone fractures M. Kodama1 Department of Neurology, Federation of National Public Service Personnel Mutual Aid Association, Hirakata Kohsai Hospital, Hirakata City, Osaka, Japan
P9-5 Transient and sustained activations of the brainstem around K-complexes in humans
1
S. Kohsaka1 , T. Sakai1 , M. Kohsaka2 , N. Fukuda3 Department of Pediatrics, Hokkaido University School of Medicine, Japan, 2 Ishikane Hospital, Sapporo, Japan, 3 Department of Health Sciences, Hokkaido University School of Medicine, Japan
Objective: The detail etiology of periodic limb movements in sleep (PLMS) and during wakefulness (PLMW) is unclear. Myoclonus differs the duration of electromyographical activity by the origin; short EMG durations in cortical myoclonus and long EMG durations in segmental spinal myoclonus. EMG durations may be a marker of etiology. We compared leg movement (LM) durations and periodic leg movement (PLM) periodicities of three patients with PLMS and PLMW; a patient with brain lesion, a patient with spinal cord lesion, and a patient with multiple leg bone fractures without any neurological deficits. Methods: We measured the durations and periodicities of LM and PLM events in a patient with epilepsy and restless legs syndrome, a sleep apnea syndrome (SAS) patient with post-polio syndrome, and a SAS patient with multiple bone fractures of right leg without any neurological deficits. We underwent polysomnography scored by the American Academy of Sleep Medicine Manual for the Scoring of Sleep and Associated Events (2007). Results: The brain lesion patient showed short LM durations during wakefulness and long LM durations in sleep. The patient with spinal cord lesion and the patient with leg bone fracture showed long LM durations during wakefulness and short LM durations in sleep, longer periodicities in sleep than those during wakefulness. PLM durations during wakefulness did not differ between three patients. The spinal cord patient showed shorter PLM durations in sleep than those during wakefulness. The brain lesion patient showed shorter LM and PLM durations during wakefulness than those of other two patients, longer LM and PLM durations in sleep than those of other two patients. Conclusions: The patient with brain lesion showed different tendency from the patient with spinal cord lesion or the patient with leg bone fractures in LM durations and periodicities between during wakefulness and in sleep.
1
K-complexes (KCs) are one of the hallmarks for slow-wave sleep (SWS). Experimental studies suggest that slow inherent oscillations (<1 Hz) of the excitability change in the cortex underlie their generating mechanism. The excitability in the cortex between KCs is upregulated, and it is suggested that memories are consolidated in these upregulated periods. Here, we investigated the excitability change of the brainstem around KCs by sequentially analyzing brainstem auditory evoked potentials (BAEPs) in humans. Methods: The EEGs, including two channels for BAEPs, were recorded from 11 male volunteers during SWS while continuously delivering acoustic stimuli (80-dB binaural clicks at 20 times/s). The EEG data were sampled (10 kHz), and 12 to 30 KCs were selected in a case. We calculated 43 traces of BAEPs in the range from 3.0±0.4 s to 1.2±0.4 s by shifting the average area by 0.1 s. Two parameters (amplitude and area) of waveIII and -V were measured, and tested for the temporal change by one-way repeated measure ANOVA. Results: The parameters of wave-III exhibited a transient increase before the onset of KCs from 2.0±0.4 s to 1.5±0.4 s. The parameters of wave-V showed a sustained increase around KCs following the initial decrement in the range from 2.3±0.4 s to 1.7±0.4 s. Conclusion: The results suggest that KCs are triggered by the transient activation of the ventral brainstem, and that the upregulation in the cortex between KCs is provided by the sustained activation of the dorsal brainstem. P9-6 Clinical and videopolysomnographic characteristics of sleep-related eating disorder Y. Komada1,2 , A. Usui2,3 , Y. Inoue1,2 1 Department of Somnology, Tokyo Medical University, Japan, 2 Japan Somnology Center, Neuropsychiatric Research Institute, Japan, 3 The Faculty of Health Science Technology, Bunkyo Gakuin University, Japan Objective: Sleep-related eating disorder (SRED) is a recently described clinical entity that combines characteristics of both eating and sleep disorders. Nocturnal partial arousals are followed by rapid ingestion of food and subsequent poor memory for the episode. Clinical and videopolysomnographic characteristic have not been well elucidated. The aim of this study was to investigate the demographic, and clinical characteristics together with videopolysomnographic variables of SRED, and to compare these with arousal disorder (AD). Methods: A series of twenty-one consecutive patients with SRED and seventeen patients with AD was retrospectively investigated. We reviewed and compared the demographic variables, age at onset of the symptom, distribution of symptom episodes through the nocturnal sleep course, frequency of episodes, and PSG variables between the patients group with SRED and those with AD. Results: There was no significant difference in self reported mean age at onset, BMI at the investigation, and nocturnal distribution of the symptom between SRED and AD. However, percentage of women and frequency of episodes per week were significantly higher in SRED group than in AD group. There was no significant difference in PSG variables between the two groups. There were 7 cases out of 21 SRED patients having history of AD especially sleep walking in their younger ages. Nine cases were comorbid with nocturnal eating syndrome (NES) which clearly occurred after the onset of SRED.
P9-8 Validation of manual and automatic sleep scoring in normals and patients with neurodegenerative disorders P. Jennum1 , P. Jensen2 , H. Sorensen2 Danish Centre for Sleep Medicine, Denmark, 2 Danish Technical University, Electrical Engineering, Technical University of Denmark, Copenhagen, Denmark
1
Introduction: Reliable polysomnographic classification is the basis for evaluation of sleep disorders in neurological diseases. Aim: to develop a fully automatic sleep scoring algorithm on the basis of a reproduction of new international sleep scoring criteria from the American Academy of Sleep Medicine (AASM). Methods: A biomedical signal processing algorithm was developed, allowing for automatic sleep depth quantification of routine polysomnographic (PSG) recordings through feature extraction, supervised probabilistic Bayesian classification, and heuristic rule-based smoothing. The performance of the algorithm was tested using twenty-eight manually classified day-night PSGs from eighteen normal subjects and ten patients with Parkinson’s disease (PD) or multiple system atrophy (MSA). This led to quantification of automatic-versus-manual epoch-by-epoch agreement rates for both normal and abnormal recordings. Results: Resulting average agreement rates were 87.7% (Cohens Kappa: 0.79) and 68.2% (Cohens Kappa: 0.26) in the normal and abnormal group, respectively. Based on an observed reliability of the manual scorer of 92.5% (Cohens Kappa: 0.87) in the normal group and 85.3% (Cohens Kappa: 0.73) in the abnormal group. Conclusion: The developed algorithm was capable of scoring normal sleep with an accuracy around the manual inter-scorer reliability, it failed in accurately scoring abnormal sleep as encountered for the PD/MSA
S156 patients, which is due to the abnormal mictro- and macrostructure pattern in these patients P9-9 The clinical significance of PLMS in REM sleep behavior disorder T. Sasai1 , Y. Inoue1,2 1 Japan Somnology Center, Neuropsyhiatric Reseaech Institute, Japan, 2 Department of Somnology, Tokyo Medical University, Japan Objective: Periodic leg movements during sleep (PLMS) is frequently observed in rapid eye movement (REM) sleep behavior disorder (RBD) especially during REM sleep period. However, clinical significance of PLMS in patients with RBD remains unclear. This study was conducted to elucidate the clinical significance and the underlying mechanism for the existence of PLMS in RBD. Methods: Consecutive 54 patients with idiopathic RBD without PLMS (iRBD w/o PLMS, 65.9±6.9 yrs), 27 patients with iRBD with PLMS (iRBD-PLMS, 67.7±7.1 yrs), and 31 patients with idiopathic PLMS (iPLMS, 63.5±5.9 yrs) were enrolled. Scores of Epworth Sleepiness Scale (ESS) were compared among the three patients groups. PLMS index, mean duration of PLMS, and inter-PLMS interval were calculated during both NREM sleep period and REM sleep period respectively, and compared among the three patient groups. Correlation analysis between ratio of PLMS related arousal index to PLMS index (PLMAI/PLMI) and proportion of REM sleep without atonia to total REM sleep (RWA/REM) were performed in the iRBD-PLMS group. The associated factor for the presence of PLMS during REM sleep period was also investigated in the subject iRBD group. Results: The iRBD-PLMS group showed significantly lower ESS score than the iPLMS w/o PLMS group did. PLMAI/PLMI was negatively correlated with RWA/REM. The iRBD-PLMS group showed significantly higher PLMS index, longer duration of PLMS, and shorter inter-PLMS interval than the iPLMS group did. RWA/REM was extracted as a significantly associated factor for the presence of PLMS during REM sleep period among the iRBD patients. Conclusions: RWA could be associated with suppression of arousal response to PLMS possibly leading to lower daytime sleepiness in iRBD. The association between the presence of PLMS during REM sleep period and the amount of RWA suggested that PLMS during this sleep period could become an important disease process marker of iRBD. P9-10 REM sleep behaviour disorder in patients with narcolepsy is associated with hypocretin-1 deficiency S. Knudsen1 , S. Gammeltoft2 , P. Jennum1 1 Danish Center for Sleep Medicine, Department of Clinical Neurophysiology, Glostrup Hospital, University of Copenhagen, Denmark, 2 Department of Clinical Biochemistry, Glostrup Hospital, University of Copenhagen, Denmark Objectives: REM sleep behaviour disorder (RBD) is characterized by dream-enacting behaviour and impaired motor inhibition during REM sleep. RBD is commonly associated with neurodegenerative disorders, but also reported in narcolepsy with cataplexy (NC). Most NC patients lack the sleep-wake and REM sleep motor-regulating hypocretin neurons in the lateral hypothalamus. In contrast, RBD and hypocretin deficiency are rare in narcolepsy without cataplexy (NwC). We hypothesized that RBD coexists with cataplexy in narcolepsy due to hypocretin deficiency. Methods: RBD was diagnosed by ICSD-2 criteria in 63 narcolepsy patients with or without cataplexy. Main outcome measures: RBD symptoms, short and long muscle activations/hour REM and non-REM (NREM) sleep, periodic (PLMs) and non-periodic limb movements (LMs)/hour REM and NREM sleep. Outcome variables were analyzed in relation to cataplexy and hypocretin deficiency in uni- and multivariate logistic/linear regression models, controlling for possible RBD biasing factors (age, gender, disease duration, previous anti-cataplexy medication). Results: Only hypocretin deficiency independently predicted RBD symptoms (RR = 3.69, P = 0.03), long muscle activations/hour REM (lncoefficient = 0.81, P < 0.01) and short muscle activations/hour REM (ln-coefficient = 1.01, P < 0.01). Likewise, PLMs/hour REM and NREM were only associated with hypocretin deficiency (P < 0.01). A significant association between hypocretin deficiency and cataplexy was confirmed (P < 0.01). In sub-analysis, hypocretin deficiency suggested the association of PLMs and RBD outcomes (symptoms, non-periodic short and long muscle activity) in REM sleep.
Posters Conclusion: Our results support that hypocretin deficiency is independently associated with RBD in narcolepsy. Thus, hypocretin deficiency is linked to the two major disturbances of REM sleep motor regulation in narcolepsy: RBD and cataplexy. Hypocretin deficiency is also significantly associated with PLMs in REM and NREM sleep, and provides a possible pathophysiological link between RBD and PLMs in narcolepsy. The study supports the hypothesis that an impaired hypocretin system causes a general instability of motor regulation during wakefulness, REM and NREM sleep in human narcolepsy. P9-11 Validation of the ICSD-2 criteria for CSF hypocretin-1 measurements in the diagnosis of narcolepsy in the Danish population S. Knudsen1 , P. Jennum1 , J. Alving2 , S. Sheikh4 , S. Gammeltoft3 Danish Center for Sleep Medicine, Department of Clinical Neurophysiology, Glostrup Hospital, University of Copenhagen, Denmark, 2 Danish Epilepsy Centre, Dianalund, Denmark, 3 Department of Clinical Biochemistry, University of Copenhagen, Glostrup Hospital, Denmark, 4 Department of Biochemistry, Pharmacology & Genetics, University of Southern Denmark, Odense Hospital, Denmark 1
Objectives: The International Classification of Sleep Disorders (ICSD-2) criteria for low CSF hypocretin-1 levels (CSF hcrt-1) still need validation as a diagnostic tool for narcolepsy in different populations because inter-assay variability and different definitions of hypocretin deficiency complicate direct comparisons of study results. Methods: Interviews, polysomnography, multiple sleep latency test, HLAtyping and CSF hcrt-1 measurements in Danish patients with narcolepsy with cataplexy (NC) and narcolepsy without cataplexy (NwC), CSF hcrt-1 measurements in other hypersomnias, neurological and normal controls. Comparisons of hypocretin deficiency and frequency of HLA-DQB1*0602positivity in the Danish and eligible NC and NwC populations (included via MEDLINE search), by (re)calculation of study results using the ICSD-2 criterion for low CSF hcrt-1 (<30% of normal mean). Results: In Danes, low CSF hcrt-1 was present in 40/46 NC, 3/14 NwC and 0/106 controls (p < 0.0001). 39/41 NC and 4/13 NwC patients were HLA-DQB1*0602-positive (p < 0.01). Hypocretin-deficient NC patients had higher frequency of cataplexy, shorter mean sleep latency, more sleep onset REM periods (p < 0.05) and more awakenings (NS) than did NC patients with normal CSF hcrt-1. Across populations, low CSF hcrt-1 and HLA-DQB1*0602-positivity characterized the majority of NC (80 100%, p = 0.53; 80 100%, p = 0.11) but a minority of NwC patients (11 29%, p = 0.75; 29 89%, p = 0.05). Conclusion: The study provides evidence that hypocretin deficiency causes a more severe NC phenotype. The ICSD-2 criterion for low CSF hcrt-1 (<30% of normal mean) is valid for diagnosing NC, but not NwC. HLA-typing should precede CSF hcrt-1 measurements because hypocretin deficiency is rare in HLA-DQB1*0602-negative patients. P9-12 Neurophysiologic approach to the complex organization in spine: a study on FWD and cutaneous silent period in primary restless legs patients B. Isak1 , K. Uluc1 , C. Salcini1 , K. Agan1 , T. Tanridag1 , O. Us1 Marmara University Hospital, Department of Neurology, Istanbul, Turkey
1
Objective: F-wave duration (FWD) and cutaneous silent period (CSP) are considered to be influenced by the central excitability and/or diminished central inhibition. The aim of this study was to define the RLS patients with the help of FWD and/or CSP parameters. Methods: Twenty four patients of primary RLS were compared with thirty one age- and sex-matched controls. The subjects were evaluated with nerve conduction studies (NCS), F-wave parameters (minimummaximum-mean latencies, chronodispersion, persistence, duration and the ratio of mean FWD to compound muscle action potential [CMAP] duration), CSPs (latency, duration and the ratio of durations from lower and upper extremities, respectively), expiration to inspiration ratio (E/I) and sympathetic skin responses (SSR). Results: There was no significant difference between patients and controls for NCS, E/I and SSR. However, FWDs were prolonged and CSP parameters were shortened significantly in the lower extremities of the patient group (P < 0.0001). Conclusions: Since both the NCSs and the autonomic tests were in normal ranges, the abnormalities of FWD and CSP parameters were referred to
S155 Conclusions: SRED is likely to occur in young adult, and much more common in women than men. Judged from patients’ history and distribution of the symptom, SRED could be a severe symptomatic variant of AD, sometimes complicating NES. P9-7 Leg movement durations and periodicities in periodic limb movements of three patients with brain lesion, spinal cord lesion, and leg bone fractures M. Kodama1 Department of Neurology, Federation of National Public Service Personnel Mutual Aid Association, Hirakata Kohsai Hospital, Hirakata City, Osaka, Japan
P9-5 Transient and sustained activations of the brainstem around K-complexes in humans
1
S. Kohsaka1 , T. Sakai1 , M. Kohsaka2 , N. Fukuda3 Department of Pediatrics, Hokkaido University School of Medicine, Japan, 2 Ishikane Hospital, Sapporo, Japan, 3 Department of Health Sciences, Hokkaido University School of Medicine, Japan
Objective: The detail etiology of periodic limb movements in sleep (PLMS) and during wakefulness (PLMW) is unclear. Myoclonus differs the duration of electromyographical activity by the origin; short EMG durations in cortical myoclonus and long EMG durations in segmental spinal myoclonus. EMG durations may be a marker of etiology. We compared leg movement (LM) durations and periodic leg movement (PLM) periodicities of three patients with PLMS and PLMW; a patient with brain lesion, a patient with spinal cord lesion, and a patient with multiple leg bone fractures without any neurological deficits. Methods: We measured the durations and periodicities of LM and PLM events in a patient with epilepsy and restless legs syndrome, a sleep apnea syndrome (SAS) patient with post-polio syndrome, and a SAS patient with multiple bone fractures of right leg without any neurological deficits. We underwent polysomnography scored by the American Academy of Sleep Medicine Manual for the Scoring of Sleep and Associated Events (2007). Results: The brain lesion patient showed short LM durations during wakefulness and long LM durations in sleep. The patient with spinal cord lesion and the patient with leg bone fracture showed long LM durations during wakefulness and short LM durations in sleep, longer periodicities in sleep than those during wakefulness. PLM durations during wakefulness did not differ between three patients. The spinal cord patient showed shorter PLM durations in sleep than those during wakefulness. The brain lesion patient showed shorter LM and PLM durations during wakefulness than those of other two patients, longer LM and PLM durations in sleep than those of other two patients. Conclusions: The patient with brain lesion showed different tendency from the patient with spinal cord lesion or the patient with leg bone fractures in LM durations and periodicities between during wakefulness and in sleep.
1
K-complexes (KCs) are one of the hallmarks for slow-wave sleep (SWS). Experimental studies suggest that slow inherent oscillations (<1 Hz) of the excitability change in the cortex underlie their generating mechanism. The excitability in the cortex between KCs is upregulated, and it is suggested that memories are consolidated in these upregulated periods. Here, we investigated the excitability change of the brainstem around KCs by sequentially analyzing brainstem auditory evoked potentials (BAEPs) in humans. Methods: The EEGs, including two channels for BAEPs, were recorded from 11 male volunteers during SWS while continuously delivering acoustic stimuli (80-dB binaural clicks at 20 times/s). The EEG data were sampled (10 kHz), and 12 to 30 KCs were selected in a case. We calculated 43 traces of BAEPs in the range from 3.0±0.4 s to 1.2±0.4 s by shifting the average area by 0.1 s. Two parameters (amplitude and area) of waveIII and -V were measured, and tested for the temporal change by one-way repeated measure ANOVA. Results: The parameters of wave-III exhibited a transient increase before the onset of KCs from 2.0±0.4 s to 1.5±0.4 s. The parameters of wave-V showed a sustained increase around KCs following the initial decrement in the range from 2.3±0.4 s to 1.7±0.4 s. Conclusion: The results suggest that KCs are triggered by the transient activation of the ventral brainstem, and that the upregulation in the cortex between KCs is provided by the sustained activation of the dorsal brainstem. P9-6 Clinical and videopolysomnographic characteristics of sleep-related eating disorder Y. Komada1,2 , A. Usui2,3 , Y. Inoue1,2 1 Department of Somnology, Tokyo Medical University, Japan, 2 Japan Somnology Center, Neuropsychiatric Research Institute, Japan, 3 The Faculty of Health Science Technology, Bunkyo Gakuin University, Japan Objective: Sleep-related eating disorder (SRED) is a recently described clinical entity that combines characteristics of both eating and sleep disorders. Nocturnal partial arousals are followed by rapid ingestion of food and subsequent poor memory for the episode. Clinical and videopolysomnographic characteristic have not been well elucidated. The aim of this study was to investigate the demographic, and clinical characteristics together with videopolysomnographic variables of SRED, and to compare these with arousal disorder (AD). Methods: A series of twenty-one consecutive patients with SRED and seventeen patients with AD was retrospectively investigated. We reviewed and compared the demographic variables, age at onset of the symptom, distribution of symptom episodes through the nocturnal sleep course, frequency of episodes, and PSG variables between the patients group with SRED and those with AD. Results: There was no significant difference in self reported mean age at onset, BMI at the investigation, and nocturnal distribution of the symptom between SRED and AD. However, percentage of women and frequency of episodes per week were significantly higher in SRED group than in AD group. There was no significant difference in PSG variables between the two groups. There were 7 cases out of 21 SRED patients having history of AD especially sleep walking in their younger ages. Nine cases were comorbid with nocturnal eating syndrome (NES) which clearly occurred after the onset of SRED.
P9-8 Validation of manual and automatic sleep scoring in normals and patients with neurodegenerative disorders P. Jennum1 , P. Jensen2 , H. Sorensen2 Danish Centre for Sleep Medicine, Denmark, 2 Danish Technical University, Electrical Engineering, Technical University of Denmark, Copenhagen, Denmark
1
Introduction: Reliable polysomnographic classification is the basis for evaluation of sleep disorders in neurological diseases. Aim: to develop a fully automatic sleep scoring algorithm on the basis of a reproduction of new international sleep scoring criteria from the American Academy of Sleep Medicine (AASM). Methods: A biomedical signal processing algorithm was developed, allowing for automatic sleep depth quantification of routine polysomnographic (PSG) recordings through feature extraction, supervised probabilistic Bayesian classification, and heuristic rule-based smoothing. The performance of the algorithm was tested using twenty-eight manually classified day-night PSGs from eighteen normal subjects and ten patients with Parkinson’s disease (PD) or multiple system atrophy (MSA). This led to quantification of automatic-versus-manual epoch-by-epoch agreement rates for both normal and abnormal recordings. Results: Resulting average agreement rates were 87.7% (Cohens Kappa: 0.79) and 68.2% (Cohens Kappa: 0.26) in the normal and abnormal group, respectively. Based on an observed reliability of the manual scorer of 92.5% (Cohens Kappa: 0.87) in the normal group and 85.3% (Cohens Kappa: 0.73) in the abnormal group. Conclusion: The developed algorithm was capable of scoring normal sleep with an accuracy around the manual inter-scorer reliability, it failed in accurately scoring abnormal sleep as encountered for the PD/MSA
S156 patients, which is due to the abnormal mictro- and macrostructure pattern in these patients P9-9 The clinical significance of PLMS in REM sleep behavior disorder T. Sasai1 , Y. Inoue1,2 1 Japan Somnology Center, Neuropsyhiatric Reseaech Institute, Japan, 2 Department of Somnology, Tokyo Medical University, Japan Objective: Periodic leg movements during sleep (PLMS) is frequently observed in rapid eye movement (REM) sleep behavior disorder (RBD) especially during REM sleep period. However, clinical significance of PLMS in patients with RBD remains unclear. This study was conducted to elucidate the clinical significance and the underlying mechanism for the existence of PLMS in RBD. Methods: Consecutive 54 patients with idiopathic RBD without PLMS (iRBD w/o PLMS, 65.9±6.9 yrs), 27 patients with iRBD with PLMS (iRBD-PLMS, 67.7±7.1 yrs), and 31 patients with idiopathic PLMS (iPLMS, 63.5±5.9 yrs) were enrolled. Scores of Epworth Sleepiness Scale (ESS) were compared among the three patients groups. PLMS index, mean duration of PLMS, and inter-PLMS interval were calculated during both NREM sleep period and REM sleep period respectively, and compared among the three patient groups. Correlation analysis between ratio of PLMS related arousal index to PLMS index (PLMAI/PLMI) and proportion of REM sleep without atonia to total REM sleep (RWA/REM) were performed in the iRBD-PLMS group. The associated factor for the presence of PLMS during REM sleep period was also investigated in the subject iRBD group. Results: The iRBD-PLMS group showed significantly lower ESS score than the iPLMS w/o PLMS group did. PLMAI/PLMI was negatively correlated with RWA/REM. The iRBD-PLMS group showed significantly higher PLMS index, longer duration of PLMS, and shorter inter-PLMS interval than the iPLMS group did. RWA/REM was extracted as a significantly associated factor for the presence of PLMS during REM sleep period among the iRBD patients. Conclusions: RWA could be associated with suppression of arousal response to PLMS possibly leading to lower daytime sleepiness in iRBD. The association between the presence of PLMS during REM sleep period and the amount of RWA suggested that PLMS during this sleep period could become an important disease process marker of iRBD. P9-10 REM sleep behaviour disorder in patients with narcolepsy is associated with hypocretin-1 deficiency S. Knudsen1 , S. Gammeltoft2 , P. Jennum1 1 Danish Center for Sleep Medicine, Department of Clinical Neurophysiology, Glostrup Hospital, University of Copenhagen, Denmark, 2 Department of Clinical Biochemistry, Glostrup Hospital, University of Copenhagen, Denmark Objectives: REM sleep behaviour disorder (RBD) is characterized by dream-enacting behaviour and impaired motor inhibition during REM sleep. RBD is commonly associated with neurodegenerative disorders, but also reported in narcolepsy with cataplexy (NC). Most NC patients lack the sleep-wake and REM sleep motor-regulating hypocretin neurons in the lateral hypothalamus. In contrast, RBD and hypocretin deficiency are rare in narcolepsy without cataplexy (NwC). We hypothesized that RBD coexists with cataplexy in narcolepsy due to hypocretin deficiency. Methods: RBD was diagnosed by ICSD-2 criteria in 63 narcolepsy patients with or without cataplexy. Main outcome measures: RBD symptoms, short and long muscle activations/hour REM and non-REM (NREM) sleep, periodic (PLMs) and non-periodic limb movements (LMs)/hour REM and NREM sleep. Outcome variables were analyzed in relation to cataplexy and hypocretin deficiency in uni- and multivariate logistic/linear regression models, controlling for possible RBD biasing factors (age, gender, disease duration, previous anti-cataplexy medication). Results: Only hypocretin deficiency independently predicted RBD symptoms (RR = 3.69, P = 0.03), long muscle activations/hour REM (lncoefficient = 0.81, P < 0.01) and short muscle activations/hour REM (ln-coefficient = 1.01, P < 0.01). Likewise, PLMs/hour REM and NREM were only associated with hypocretin deficiency (P < 0.01). A significant association between hypocretin deficiency and cataplexy was confirmed (P < 0.01). In sub-analysis, hypocretin deficiency suggested the association of PLMs and RBD outcomes (symptoms, non-periodic short and long muscle activity) in REM sleep.
Posters Conclusion: Our results support that hypocretin deficiency is independently associated with RBD in narcolepsy. Thus, hypocretin deficiency is linked to the two major disturbances of REM sleep motor regulation in narcolepsy: RBD and cataplexy. Hypocretin deficiency is also significantly associated with PLMs in REM and NREM sleep, and provides a possible pathophysiological link between RBD and PLMs in narcolepsy. The study supports the hypothesis that an impaired hypocretin system causes a general instability of motor regulation during wakefulness, REM and NREM sleep in human narcolepsy. P9-11 Validation of the ICSD-2 criteria for CSF hypocretin-1 measurements in the diagnosis of narcolepsy in the Danish population S. Knudsen1 , P. Jennum1 , J. Alving2 , S. Sheikh4 , S. Gammeltoft3 Danish Center for Sleep Medicine, Department of Clinical Neurophysiology, Glostrup Hospital, University of Copenhagen, Denmark, 2 Danish Epilepsy Centre, Dianalund, Denmark, 3 Department of Clinical Biochemistry, University of Copenhagen, Glostrup Hospital, Denmark, 4 Department of Biochemistry, Pharmacology & Genetics, University of Southern Denmark, Odense Hospital, Denmark 1
Objectives: The International Classification of Sleep Disorders (ICSD-2) criteria for low CSF hypocretin-1 levels (CSF hcrt-1) still need validation as a diagnostic tool for narcolepsy in different populations because inter-assay variability and different definitions of hypocretin deficiency complicate direct comparisons of study results. Methods: Interviews, polysomnography, multiple sleep latency test, HLAtyping and CSF hcrt-1 measurements in Danish patients with narcolepsy with cataplexy (NC) and narcolepsy without cataplexy (NwC), CSF hcrt-1 measurements in other hypersomnias, neurological and normal controls. Comparisons of hypocretin deficiency and frequency of HLA-DQB1*0602positivity in the Danish and eligible NC and NwC populations (included via MEDLINE search), by (re)calculation of study results using the ICSD-2 criterion for low CSF hcrt-1 (<30% of normal mean). Results: In Danes, low CSF hcrt-1 was present in 40/46 NC, 3/14 NwC and 0/106 controls (p < 0.0001). 39/41 NC and 4/13 NwC patients were HLA-DQB1*0602-positive (p < 0.01). Hypocretin-deficient NC patients had higher frequency of cataplexy, shorter mean sleep latency, more sleep onset REM periods (p < 0.05) and more awakenings (NS) than did NC patients with normal CSF hcrt-1. Across populations, low CSF hcrt-1 and HLA-DQB1*0602-positivity characterized the majority of NC (80 100%, p = 0.53; 80 100%, p = 0.11) but a minority of NwC patients (11 29%, p = 0.75; 29 89%, p = 0.05). Conclusion: The study provides evidence that hypocretin deficiency causes a more severe NC phenotype. The ICSD-2 criterion for low CSF hcrt-1 (<30% of normal mean) is valid for diagnosing NC, but not NwC. HLA-typing should precede CSF hcrt-1 measurements because hypocretin deficiency is rare in HLA-DQB1*0602-negative patients. P9-12 Neurophysiologic approach to the complex organization in spine: a study on FWD and cutaneous silent period in primary restless legs patients B. Isak1 , K. Uluc1 , C. Salcini1 , K. Agan1 , T. Tanridag1 , O. Us1 Marmara University Hospital, Department of Neurology, Istanbul, Turkey
1
Objective: F-wave duration (FWD) and cutaneous silent period (CSP) are considered to be influenced by the central excitability and/or diminished central inhibition. The aim of this study was to define the RLS patients with the help of FWD and/or CSP parameters. Methods: Twenty four patients of primary RLS were compared with thirty one age- and sex-matched controls. The subjects were evaluated with nerve conduction studies (NCS), F-wave parameters (minimummaximum-mean latencies, chronodispersion, persistence, duration and the ratio of mean FWD to compound muscle action potential [CMAP] duration), CSPs (latency, duration and the ratio of durations from lower and upper extremities, respectively), expiration to inspiration ratio (E/I) and sympathetic skin responses (SSR). Results: There was no significant difference between patients and controls for NCS, E/I and SSR. However, FWDs were prolonged and CSP parameters were shortened significantly in the lower extremities of the patient group (P < 0.0001). Conclusions: Since both the NCSs and the autonomic tests were in normal ranges, the abnormalities of FWD and CSP parameters were referred to