- Email: [email protected]
MANIPULATING SLEEP DURATION ALTERS COGNITIVE AND EMOTIONAL FUNCTIONING IN CHILDREN
S14
Abstracts of 4th International Congress of WASM & 5th Conference of CSS / Sleep Medicine 12, Suppl. 1 (2011) S1–S130
SHORT-TERM PARTIAL SLEEP DEPRIVATION: EFFECTS ON EMOTION REGULATION OF HEALTHY ADULTS Nanette S. Danielsson 1 , Shane MacDonald 1 , Markus Jansson-Fröjmark 1 , Steven J. Linton 1 , Allison G. Harvey 2 . 1 Örebro University, Sweden; 2 University of California, United States Introduction and Objectives: Previous research has shown that sleep deprivation has negative effects on memory, cognitive, and physiological function. Sleep-deprived people also often show signs of emotionality. This study investigated risk posed by short-term partial sleep deprivation on the emotional regulation of healthy adults. Materials and Methods: We randomized 80 adults, ages 18-68, into sleep deprivation (3-nights with 5-hours in bed) and a control group. We used experimental emotion elicitation to examine group differences dependent on sleep conditions. We elicited negative emotions with music (MCI), visualization, and pictures (IAPS). We measured emotion regulation by levels of positive and negative emotion and affect; scores on discrete emotions (PANAS-X); levels of arousal, pleasure, emotion dominance (SAM, Affect Grid). We assessed within and between group differences with MANOVA, and group differences on discrete emotions with t-tests. Results: Following sleep-deprivation, people scored significantly lower on arousal, positive emotionality and affect compared to controls. In addition, they exhibited a negativity bias on discrete emotions, scoring positive (e.g., delighted, joyful) and neutral items (e.g., concentrating, attentive) lower and negative items (e.g., irritable, hostile) higher than controls. After emotion elicitation, both groups significantly reported increased negative emotion, arousal, displeasure, emotion dominance, and reduced positive emotion. The only significant differences between groups were on discrete emotions. The sleep-deprived group reported feeling significantly less fearless, more sluggish, tired, sleepy, and drowsy. Conclusion: Sleep-deprivation appears to pose risk to emotion regulation through reductions in positive emotionality and affect. This study supports prior research showing a negativity bias following sleep deprivation with participants scoring lower on positive and neutral items and higher on negative items. The results of this study provide an analog for how people with long-term sleep problems may be at increased risk for mood related disorders. Acknowledgements: Funding provided in part by Lars Hiertas Memorial Fund.
ASSOCIATION BETWEEN SLEEP HOMEOSTASIS AND A SYNAPTIC ADHESION MOLECULE 1
1
2
2
Janine El Helou , Erika Belanger Nelson , Stéphane Dorsaz , Thomas Curie , Paul Franken 2 , Valerie Mongrain 3 . 1 Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Coeur de Montréal, Canada; 2 Center for Integrative Genomics, University of Lausanne, Switzerland; 3 Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Coeur de Montréal, Psychiatry Departments, Université de Montréal, Canada Introduction and Objectives: Sleep need builds up during wakefulness and decays during sleep and this has been linked to changes in synaptic strength. Accordingly, sleep deprivation was shown to decrease NMDA receptors (NMDAr) functioning in different brain areas. NMDAr functioning is regulated by synaptic adhesion molecules (SAM), and one of these was shown to determine NMDAr synaptic localization. Here, we assessed the effect of sleep pressure on the expression of this SAM and its role in sleep regulation. Materials and Methods: 1) Male mice from 3 inbred strains were submitted or not to a 6h sleep deprivation (SD) by gentle handling starting at ZT0 (Zeitgeber time 0: lights on), and sacrificed at ZT6 for brain sampling. Total RNA was extracted and expression levels measured by microarray or qPCR. 2) AKR/J male mice were submitted to a 6h SD at ZT0, followed by protein extraction of brain cortical tissue and Western blot. 3) The EEG of mutant male mice not expressing the targeted SAM was recorded during 24h of baseline, during a 6h SD starting at ZT0 and 18h of recovery. Results: We observed that the mRNA expression of the targeted SAM was consistently decreased by SD in all inbred strains, whereas the SD-dependent decrease in its protein level was not significant for total cortical protein samples. Preliminary observations indicate that mice homozygote for the SAM mutation are much more difficult to keep awake during SD. Also, mutant and heterozygote mice had increased non-rapid eye movement
sleep time during baseline compared to wild-type litter mates. A similar trend was observed for recovery. Conclusion: Additional analyses are underway to assess the effect of this SAM on the dynamics of EEG markers of sleep pressure. Our preliminary data suggest a role for this SAM in sleep regulation. Acknowledgements: University of Lausanne, FNS (3100A0-111974), NSERC grants (386623-2010 and 390478-2010).
NIGHT-WORK SHIFTS AND INFLAMMATORY MARKERS Khosro Sadeghniiat-Haghighi, Omid Aminian. Center for Research on Occupational Diseases, Iran Introduction and Objectives: There are some certain side effects for shift workers. Sleep deprivation has been shown to be associated with an elevation in inflammatory markers such as IL-6, TNF-α and CRP; and also inflammation is associated with increased risk of cardiovascular disorders, inflammatory disorders, cerebrovascular disorders, and mortality which is seen in shift workers too. The purpose of the present study was investigation of the relationship between night work and inflammatory markers. Materials and Methods: After selecting 50 workers according to inclusion and exclusion criteria, we designed a cross over study and a specific shift schedule for them. They were divided randomly to 2 groups. Group 1 (25 persons) went on a schedule of 3 days as day-worker, one day off, and 3 days as night-worker. Group 2 were vice versa, 3 days as night-worker, one day off, and 3 days as day-worker.(cross over) Blood samples were obtained between 7 and 8 AM after the periods of day-work and night-work. IL6, TNF-α and CRP were assayed by ELISA, and WBC was measured by cell counter H1. Results: Night-work increased IL6, WBC, Neutrophils, Lymphocytes significantly, compared with day-work. TNF-α was increased but it was not statistically significant, and also changes in monocyte count was not significant. Conclusion: This study showed increased inflammatory markers after night work, which have been reported in some previous studies on sleep deprivation. No significant changes in Monocyte count were observed. The results showed the elevation in blood levels of inflammatory markers is due to increase in gene expression, not monocyte count. These results support the hypothesis that increase in inflammatory markers may have a relationship with night work side effects.
MANIPULATING SLEEP DURATION ALTERS COGNITIVE AND EMOTIONAL FUNCTIONING IN CHILDREN Jennifer Vriend 1 , Fiona Davidson 2 , Sunny Shaffner 1 , Penny Corkum 1 , Ben Rusak 1 . 1 Dalhousie University, Canada; 2 Mount Saint Vincent University, Canada Introduction and Objectives: Daytime consequences of sleep loss have been well documented in adults, but the pediatric literature includes mostly correlational studies, with few well-controlled, experimental studies. Some studies manipulated sleep experimentally in school-aged children to examine effects on cognitive functioning, but none has examined effects on emotional functioning. Materials and Methods: In this study, thirty 8-12 year-old children wore actigraphs for 3 weeks. During the baseline week, actigraphic data were used to estimate the child’s typical daily sleep duration. During the second week, the child was randomly assigned to go to bed either one hour earlier (sleep optimization) or one hour later (sleep restriction) than their typical bedtime. Each child then completed the opposite schedule during the third week of the study. After each of the 3 weeks, cognitive and emotional functioning were assessed using both objective and subjective measures. Results: A paired samples t-test revealed that the sleep manipulation was effective; the children slept longer in the sleep-optimized (M=9.29, SD=0.61) versus -restricted (M=8.06, SD=0.67) condition (t(29)=11.51, p<0.001). MANOVA revealed significant differences in performance between the sleep conditions (F(1, 29)=4.65, p=0.003), which authorized running paired samples t-tests. Results revealed that when sleep was restricted, compared to optimized, children showed poorer performance on verbal (t(29)=2.73, p=0.011) and visual (t(29)=2.20, p=0.036) memory tasks and expressed fewer positive emotions (t(29)=2.05, p=0.049) on an affective response task. Measures of parent-reported attention (t(29)=4.02, p<0.001) and emotion
Abstracts of 4th International Congress of WASM & 5th Conference of CSS / Sleep Medicine 12, Suppl. 1 (2011) S1–S130
regulation (t(29)=2.48, p=0.019) were also worse under sleep-restricted versus -optimized conditions. There were no significant differences in measures of attention or emotion regulation as self-reported by children. Conclusion: These results suggest that even a modest degree of chronic sleep restriction can have negative consequences for children’s daytime functioning. These findings support emphasizing the importance of promoting healthy sleep habits for children, and they have implications for understanding how inadequate sleep can affect cognitive and emotional development.
L: Restless Legs Syndrome (RLS) and Movement Disorders in Sleep
IRON DEFICIENT ANEMIA POPULATION: PRELIMINARY REPORT ON PREVALENCE AND CHARACTERISTICS OF RESTLESS LEGS SYNDROME Michael Auerbach 1 , Richard Allen 2 , Christopher Earley 2 . 1 Auerbach Hematology Oncology Associates, United States; 2 Johns Hopkins University, Dept. of Neurology, United States
S15
Results: RLS Patients showed higher connectivity than controls in the thalamus, basal ganglia and red nucleus regardless of symptom period (night or morning), while less connectivity was observed in the parietal lobe, frontal and the temporal gyrus. The connectivity of the nigrostriatal dopaminergic pathway was increased. Conclusion: RLS patients may have hyper-connections among dopaminergic motor-control circuits, but also hypo-connections between sensory integration areas in cortex. This is consistent with putative dopamine dysfunction in RLS patients and could explain why RLS patients show unconscious sensations that are hard to describe. The results indicate RLS patients may have deficits in controlling and managing sensory information. Acknowledgements: Many thanks to Dr. Richard P. Allen and Christopher J. Earley, who helped our study.
BEHAVIORAL CHARACTERIZATION OF BTBD9 KNOCKOUT MICE - A POTENTIAL MODEL OF RESTLESS LEGS SYNDROME Mark DeAndrade 1 , Li Zhang 1 , Thomas van Groen 2 , Russell Johnson 2 , Karen Gamble 2 , Yuqing Li 1 . 1 University of Florida, United States; 2 University of Alabama at Birmingham, United States
Introduction and Objectives: Iron deficiency plays a major role in Restless Legs Syndrome (RLS) and in two small studies has been reported to occur for about 40% of the patients with iron deficiency anemia (IDA). This study documents prevalence, severity and morbidity of RLS in a clinical IDA population referred for iron treatment. It also contrasts the iron and IDA morbidity (sleep and energy) for those with and without IDA. Materials and Methods: All patients referred for treatment of IDA at a large clinical practice completed clinical forms including the CHRLSq-13 (validated for RLS diagnosis) and questions about sleep and energy. Results: Preliminary data from 38 consecutive cases included 15 (38%) with definite RLS, and 13 (34%) not RLS. Ten reported some but not all RLS symptoms. Definite RLS compared to not RLS were younger (avr±SD: 47±12.6 vs. 62±19.2, t=2.3, p=0.03), and had higher EPO (avr±SD 125.7±73.9 vs. 57.1±48.7, t=2.1, p=0.058), greater difficulty returning to sleep (mean rank 10-point scale 7.5 vs. 3, U=0, p=0.005) and shorter total sleep times (avr±SD hours 6.0±0.8 vs. 7.4±0.5). There were no other significant differences. Definite RLS reported symptoms occurring more than twice a week, 66% reported daily occurrence. The symptoms were moderate to severely distressing for 73%. Conclusion: RLS occurs commonly with IDA (39%) causing moderate to severe distress in 28% of the IDA population. RLS was associated with shorter sleep and more difficulty returning to sleep. These patients may benefit from RLS treatments, but none were being treated. The iron status in general did not differ between RLS and not RLS except for an elevated EPO possibly indicating greater hypoxic pathway activation for the RLS patients.
Introduction and Objectives: Restless Legs Syndrome (RLS) is a disorder that is manifested at rest with unpleasant sensations deep inside the legs that are relieved partially with movement. Family and twin studies have strongly support a genetic contribution. Two independent studies published recently suggest that the BTBD9 gene plays a role in RLS. The goal of this project is to understand the function of BTBD9 protein and model RLS in mice. Materials and Methods: We have generated a knockout of the Btbd9 gene, the mouse homolog of the BTBD9 gene, using a gene-trap. Furthermore, we have characterized the Btbd9 knockout mice using an array of behavioral and physiological experiments, including open field observation for total activity, wheel running for measurement of voluntary activity across a 24 hour period, tail flick for sensation, polysomnography for sleep analysis, and serum iron analysis. Results: In heterozygous interbreeding Btbd9 knockout mice were not produced as predicted by Mendelian ratio suggesting the knockout is partially lethal. The adult Btbd9 knockout mice showed several interesting phenotypes including alterations in pain sensitivity, iron metabolism, sleep pattern, and open field activity. Conclusion: The KO mice hold the promise to be the first mammalian genetic model of RLS having several key characteristic of an RLS phenotype in mouse. Experiments will be conducted in the future to test the response of these mice to dopaminergic agonist, which are common treatments for restless legs syndrome patients. Acknowledgements: Mark P. DeAndrade, Li Zhang, Thomas van Groen, Russell Johnson Jr., Karen L. Gamble, and Yuqing Li. Funding by NIH (NS37409, NS47466, NS47692, NS54246, NS57098, NS65273, NS72872, and NS74423) and startup funds from the Department of Neurology (UAB).
THALAMO-CORTICAL AND SUBCORTICAL CONNECTIVITY IN RESTLESS LEGS SYNDROME: A RESTING STATE CONNECTIVITY STUDY USING FMRI
RELATIONSHIP BETWEEN INTERLEUKIN, IRON LEVELS AND RESTLESS LEG SYNDROME IN MARATHON RUNNERS
Yong Won Cho 1 , Do Hyung Kim 1 , HyukWon Chang 2 , Jeonghun Ku 3 . 1 Department of Neurology, Dongsan Medical Center, Keimyung University School of Medicine, Korea (South); 2 Department of Radiology, Dongsan Medical Center, Keimyung University School of Medicine, Korea (South); 3 Department of Biomedical Engineering, Dongsan Medical Center, Keimyung University School of Medicine, Korea (South)
Sayonara Beatriz Ranciaro Fagundes, Derlei João Leite Fagundes, André L.L. Bachi, Luciane Bizari Coin Carvalho, João Eduardo C. Carvalho, Lucila B. Fernandes Prado, Mauro Vaisberg, Gilmar Fernandes Prado. UNIFESP, Brazil
Introduction and Objectives: There have been few fMRI studies of RLS. We conducted a resting state connectivity study using fMRI to evaluate the functional connectivity in RLS. Materials and Methods: Resting state fMRIs were obtained from 15 idiopathic RLS patients not on RLS medications (10 female; mean age ± sd 53.27±9.94, 10 (67%) female) and 13 controls (mean age ± sd 52.38±9.06, 8 (61.5%) female), both during the night when RLS symptoms are expressed and in the morning when RLS symptoms are generally absent. Resting state connectivity was measured by a seed based method using AFNI software. Bilateral thalamus (ventral posterolateral nucleus) were selected as a seed. Connectivity characteristics of RLS patients with and without symptoms were compared to controls.
Introduction and Objectives: Introduction Long distance street running is emerging as a popular sport in Western industrialized countries. Hours after an inflammatory stimulus, hepcidin levels greatly increase, and studies indicate that hepcidin inhibits intestinal iron absorption, placental iron transport and release of recycled iron from macrophages, decreasing the delivery of iron to maturing erythrocytes in the bone marrow. The acute induction of hepticidin is mediated in large part by interleukin-6 (IL-6). Restless Legs Syndrome (RLS) is a sensorimotor disorder and studies have indicated that low brain iron concentrations and dysfunction of iron metabolism and intracellular iron may play key role in the pathogenesis of RLS. Objective Our goal was to describe iron and IL-6 concentrations in RLS marathon runners vs no RLS marathon runners and its association with RLS. Materials and Methods: Participants included in this study were participating in the São Paulo Marathon. We investigated 33 recreational runners who finished the marathon (42.195Km) in less than 4 h. We collected venous
Abstracts of 4th International Congress of WASM & 5th Conference of CSS / Sleep Medicine 12, Suppl. 1 (2011) S1–S130
SHORT-TERM PARTIAL SLEEP DEPRIVATION: EFFECTS ON EMOTION REGULATION OF HEALTHY ADULTS Nanette S. Danielsson 1 , Shane MacDonald 1 , Markus Jansson-Fröjmark 1 , Steven J. Linton 1 , Allison G. Harvey 2 . 1 Örebro University, Sweden; 2 University of California, United States Introduction and Objectives: Previous research has shown that sleep deprivation has negative effects on memory, cognitive, and physiological function. Sleep-deprived people also often show signs of emotionality. This study investigated risk posed by short-term partial sleep deprivation on the emotional regulation of healthy adults. Materials and Methods: We randomized 80 adults, ages 18-68, into sleep deprivation (3-nights with 5-hours in bed) and a control group. We used experimental emotion elicitation to examine group differences dependent on sleep conditions. We elicited negative emotions with music (MCI), visualization, and pictures (IAPS). We measured emotion regulation by levels of positive and negative emotion and affect; scores on discrete emotions (PANAS-X); levels of arousal, pleasure, emotion dominance (SAM, Affect Grid). We assessed within and between group differences with MANOVA, and group differences on discrete emotions with t-tests. Results: Following sleep-deprivation, people scored significantly lower on arousal, positive emotionality and affect compared to controls. In addition, they exhibited a negativity bias on discrete emotions, scoring positive (e.g., delighted, joyful) and neutral items (e.g., concentrating, attentive) lower and negative items (e.g., irritable, hostile) higher than controls. After emotion elicitation, both groups significantly reported increased negative emotion, arousal, displeasure, emotion dominance, and reduced positive emotion. The only significant differences between groups were on discrete emotions. The sleep-deprived group reported feeling significantly less fearless, more sluggish, tired, sleepy, and drowsy. Conclusion: Sleep-deprivation appears to pose risk to emotion regulation through reductions in positive emotionality and affect. This study supports prior research showing a negativity bias following sleep deprivation with participants scoring lower on positive and neutral items and higher on negative items. The results of this study provide an analog for how people with long-term sleep problems may be at increased risk for mood related disorders. Acknowledgements: Funding provided in part by Lars Hiertas Memorial Fund.
ASSOCIATION BETWEEN SLEEP HOMEOSTASIS AND A SYNAPTIC ADHESION MOLECULE 1
1
2
2
Janine El Helou , Erika Belanger Nelson , Stéphane Dorsaz , Thomas Curie , Paul Franken 2 , Valerie Mongrain 3 . 1 Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Coeur de Montréal, Canada; 2 Center for Integrative Genomics, University of Lausanne, Switzerland; 3 Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Coeur de Montréal, Psychiatry Departments, Université de Montréal, Canada Introduction and Objectives: Sleep need builds up during wakefulness and decays during sleep and this has been linked to changes in synaptic strength. Accordingly, sleep deprivation was shown to decrease NMDA receptors (NMDAr) functioning in different brain areas. NMDAr functioning is regulated by synaptic adhesion molecules (SAM), and one of these was shown to determine NMDAr synaptic localization. Here, we assessed the effect of sleep pressure on the expression of this SAM and its role in sleep regulation. Materials and Methods: 1) Male mice from 3 inbred strains were submitted or not to a 6h sleep deprivation (SD) by gentle handling starting at ZT0 (Zeitgeber time 0: lights on), and sacrificed at ZT6 for brain sampling. Total RNA was extracted and expression levels measured by microarray or qPCR. 2) AKR/J male mice were submitted to a 6h SD at ZT0, followed by protein extraction of brain cortical tissue and Western blot. 3) The EEG of mutant male mice not expressing the targeted SAM was recorded during 24h of baseline, during a 6h SD starting at ZT0 and 18h of recovery. Results: We observed that the mRNA expression of the targeted SAM was consistently decreased by SD in all inbred strains, whereas the SD-dependent decrease in its protein level was not significant for total cortical protein samples. Preliminary observations indicate that mice homozygote for the SAM mutation are much more difficult to keep awake during SD. Also, mutant and heterozygote mice had increased non-rapid eye movement
sleep time during baseline compared to wild-type litter mates. A similar trend was observed for recovery. Conclusion: Additional analyses are underway to assess the effect of this SAM on the dynamics of EEG markers of sleep pressure. Our preliminary data suggest a role for this SAM in sleep regulation. Acknowledgements: University of Lausanne, FNS (3100A0-111974), NSERC grants (386623-2010 and 390478-2010).
NIGHT-WORK SHIFTS AND INFLAMMATORY MARKERS Khosro Sadeghniiat-Haghighi, Omid Aminian. Center for Research on Occupational Diseases, Iran Introduction and Objectives: There are some certain side effects for shift workers. Sleep deprivation has been shown to be associated with an elevation in inflammatory markers such as IL-6, TNF-α and CRP; and also inflammation is associated with increased risk of cardiovascular disorders, inflammatory disorders, cerebrovascular disorders, and mortality which is seen in shift workers too. The purpose of the present study was investigation of the relationship between night work and inflammatory markers. Materials and Methods: After selecting 50 workers according to inclusion and exclusion criteria, we designed a cross over study and a specific shift schedule for them. They were divided randomly to 2 groups. Group 1 (25 persons) went on a schedule of 3 days as day-worker, one day off, and 3 days as night-worker. Group 2 were vice versa, 3 days as night-worker, one day off, and 3 days as day-worker.(cross over) Blood samples were obtained between 7 and 8 AM after the periods of day-work and night-work. IL6, TNF-α and CRP were assayed by ELISA, and WBC was measured by cell counter H1. Results: Night-work increased IL6, WBC, Neutrophils, Lymphocytes significantly, compared with day-work. TNF-α was increased but it was not statistically significant, and also changes in monocyte count was not significant. Conclusion: This study showed increased inflammatory markers after night work, which have been reported in some previous studies on sleep deprivation. No significant changes in Monocyte count were observed. The results showed the elevation in blood levels of inflammatory markers is due to increase in gene expression, not monocyte count. These results support the hypothesis that increase in inflammatory markers may have a relationship with night work side effects.
MANIPULATING SLEEP DURATION ALTERS COGNITIVE AND EMOTIONAL FUNCTIONING IN CHILDREN Jennifer Vriend 1 , Fiona Davidson 2 , Sunny Shaffner 1 , Penny Corkum 1 , Ben Rusak 1 . 1 Dalhousie University, Canada; 2 Mount Saint Vincent University, Canada Introduction and Objectives: Daytime consequences of sleep loss have been well documented in adults, but the pediatric literature includes mostly correlational studies, with few well-controlled, experimental studies. Some studies manipulated sleep experimentally in school-aged children to examine effects on cognitive functioning, but none has examined effects on emotional functioning. Materials and Methods: In this study, thirty 8-12 year-old children wore actigraphs for 3 weeks. During the baseline week, actigraphic data were used to estimate the child’s typical daily sleep duration. During the second week, the child was randomly assigned to go to bed either one hour earlier (sleep optimization) or one hour later (sleep restriction) than their typical bedtime. Each child then completed the opposite schedule during the third week of the study. After each of the 3 weeks, cognitive and emotional functioning were assessed using both objective and subjective measures. Results: A paired samples t-test revealed that the sleep manipulation was effective; the children slept longer in the sleep-optimized (M=9.29, SD=0.61) versus -restricted (M=8.06, SD=0.67) condition (t(29)=11.51, p<0.001). MANOVA revealed significant differences in performance between the sleep conditions (F(1, 29)=4.65, p=0.003), which authorized running paired samples t-tests. Results revealed that when sleep was restricted, compared to optimized, children showed poorer performance on verbal (t(29)=2.73, p=0.011) and visual (t(29)=2.20, p=0.036) memory tasks and expressed fewer positive emotions (t(29)=2.05, p=0.049) on an affective response task. Measures of parent-reported attention (t(29)=4.02, p<0.001) and emotion
Abstracts of 4th International Congress of WASM & 5th Conference of CSS / Sleep Medicine 12, Suppl. 1 (2011) S1–S130
regulation (t(29)=2.48, p=0.019) were also worse under sleep-restricted versus -optimized conditions. There were no significant differences in measures of attention or emotion regulation as self-reported by children. Conclusion: These results suggest that even a modest degree of chronic sleep restriction can have negative consequences for children’s daytime functioning. These findings support emphasizing the importance of promoting healthy sleep habits for children, and they have implications for understanding how inadequate sleep can affect cognitive and emotional development.
L: Restless Legs Syndrome (RLS) and Movement Disorders in Sleep
IRON DEFICIENT ANEMIA POPULATION: PRELIMINARY REPORT ON PREVALENCE AND CHARACTERISTICS OF RESTLESS LEGS SYNDROME Michael Auerbach 1 , Richard Allen 2 , Christopher Earley 2 . 1 Auerbach Hematology Oncology Associates, United States; 2 Johns Hopkins University, Dept. of Neurology, United States
S15
Results: RLS Patients showed higher connectivity than controls in the thalamus, basal ganglia and red nucleus regardless of symptom period (night or morning), while less connectivity was observed in the parietal lobe, frontal and the temporal gyrus. The connectivity of the nigrostriatal dopaminergic pathway was increased. Conclusion: RLS patients may have hyper-connections among dopaminergic motor-control circuits, but also hypo-connections between sensory integration areas in cortex. This is consistent with putative dopamine dysfunction in RLS patients and could explain why RLS patients show unconscious sensations that are hard to describe. The results indicate RLS patients may have deficits in controlling and managing sensory information. Acknowledgements: Many thanks to Dr. Richard P. Allen and Christopher J. Earley, who helped our study.
BEHAVIORAL CHARACTERIZATION OF BTBD9 KNOCKOUT MICE - A POTENTIAL MODEL OF RESTLESS LEGS SYNDROME Mark DeAndrade 1 , Li Zhang 1 , Thomas van Groen 2 , Russell Johnson 2 , Karen Gamble 2 , Yuqing Li 1 . 1 University of Florida, United States; 2 University of Alabama at Birmingham, United States
Introduction and Objectives: Iron deficiency plays a major role in Restless Legs Syndrome (RLS) and in two small studies has been reported to occur for about 40% of the patients with iron deficiency anemia (IDA). This study documents prevalence, severity and morbidity of RLS in a clinical IDA population referred for iron treatment. It also contrasts the iron and IDA morbidity (sleep and energy) for those with and without IDA. Materials and Methods: All patients referred for treatment of IDA at a large clinical practice completed clinical forms including the CHRLSq-13 (validated for RLS diagnosis) and questions about sleep and energy. Results: Preliminary data from 38 consecutive cases included 15 (38%) with definite RLS, and 13 (34%) not RLS. Ten reported some but not all RLS symptoms. Definite RLS compared to not RLS were younger (avr±SD: 47±12.6 vs. 62±19.2, t=2.3, p=0.03), and had higher EPO (avr±SD 125.7±73.9 vs. 57.1±48.7, t=2.1, p=0.058), greater difficulty returning to sleep (mean rank 10-point scale 7.5 vs. 3, U=0, p=0.005) and shorter total sleep times (avr±SD hours 6.0±0.8 vs. 7.4±0.5). There were no other significant differences. Definite RLS reported symptoms occurring more than twice a week, 66% reported daily occurrence. The symptoms were moderate to severely distressing for 73%. Conclusion: RLS occurs commonly with IDA (39%) causing moderate to severe distress in 28% of the IDA population. RLS was associated with shorter sleep and more difficulty returning to sleep. These patients may benefit from RLS treatments, but none were being treated. The iron status in general did not differ between RLS and not RLS except for an elevated EPO possibly indicating greater hypoxic pathway activation for the RLS patients.
Introduction and Objectives: Restless Legs Syndrome (RLS) is a disorder that is manifested at rest with unpleasant sensations deep inside the legs that are relieved partially with movement. Family and twin studies have strongly support a genetic contribution. Two independent studies published recently suggest that the BTBD9 gene plays a role in RLS. The goal of this project is to understand the function of BTBD9 protein and model RLS in mice. Materials and Methods: We have generated a knockout of the Btbd9 gene, the mouse homolog of the BTBD9 gene, using a gene-trap. Furthermore, we have characterized the Btbd9 knockout mice using an array of behavioral and physiological experiments, including open field observation for total activity, wheel running for measurement of voluntary activity across a 24 hour period, tail flick for sensation, polysomnography for sleep analysis, and serum iron analysis. Results: In heterozygous interbreeding Btbd9 knockout mice were not produced as predicted by Mendelian ratio suggesting the knockout is partially lethal. The adult Btbd9 knockout mice showed several interesting phenotypes including alterations in pain sensitivity, iron metabolism, sleep pattern, and open field activity. Conclusion: The KO mice hold the promise to be the first mammalian genetic model of RLS having several key characteristic of an RLS phenotype in mouse. Experiments will be conducted in the future to test the response of these mice to dopaminergic agonist, which are common treatments for restless legs syndrome patients. Acknowledgements: Mark P. DeAndrade, Li Zhang, Thomas van Groen, Russell Johnson Jr., Karen L. Gamble, and Yuqing Li. Funding by NIH (NS37409, NS47466, NS47692, NS54246, NS57098, NS65273, NS72872, and NS74423) and startup funds from the Department of Neurology (UAB).
THALAMO-CORTICAL AND SUBCORTICAL CONNECTIVITY IN RESTLESS LEGS SYNDROME: A RESTING STATE CONNECTIVITY STUDY USING FMRI
RELATIONSHIP BETWEEN INTERLEUKIN, IRON LEVELS AND RESTLESS LEG SYNDROME IN MARATHON RUNNERS
Yong Won Cho 1 , Do Hyung Kim 1 , HyukWon Chang 2 , Jeonghun Ku 3 . 1 Department of Neurology, Dongsan Medical Center, Keimyung University School of Medicine, Korea (South); 2 Department of Radiology, Dongsan Medical Center, Keimyung University School of Medicine, Korea (South); 3 Department of Biomedical Engineering, Dongsan Medical Center, Keimyung University School of Medicine, Korea (South)
Sayonara Beatriz Ranciaro Fagundes, Derlei João Leite Fagundes, André L.L. Bachi, Luciane Bizari Coin Carvalho, João Eduardo C. Carvalho, Lucila B. Fernandes Prado, Mauro Vaisberg, Gilmar Fernandes Prado. UNIFESP, Brazil
Introduction and Objectives: There have been few fMRI studies of RLS. We conducted a resting state connectivity study using fMRI to evaluate the functional connectivity in RLS. Materials and Methods: Resting state fMRIs were obtained from 15 idiopathic RLS patients not on RLS medications (10 female; mean age ± sd 53.27±9.94, 10 (67%) female) and 13 controls (mean age ± sd 52.38±9.06, 8 (61.5%) female), both during the night when RLS symptoms are expressed and in the morning when RLS symptoms are generally absent. Resting state connectivity was measured by a seed based method using AFNI software. Bilateral thalamus (ventral posterolateral nucleus) were selected as a seed. Connectivity characteristics of RLS patients with and without symptoms were compared to controls.
Introduction and Objectives: Introduction Long distance street running is emerging as a popular sport in Western industrialized countries. Hours after an inflammatory stimulus, hepcidin levels greatly increase, and studies indicate that hepcidin inhibits intestinal iron absorption, placental iron transport and release of recycled iron from macrophages, decreasing the delivery of iron to maturing erythrocytes in the bone marrow. The acute induction of hepticidin is mediated in large part by interleukin-6 (IL-6). Restless Legs Syndrome (RLS) is a sensorimotor disorder and studies have indicated that low brain iron concentrations and dysfunction of iron metabolism and intracellular iron may play key role in the pathogenesis of RLS. Objective Our goal was to describe iron and IL-6 concentrations in RLS marathon runners vs no RLS marathon runners and its association with RLS. Materials and Methods: Participants included in this study were participating in the São Paulo Marathon. We investigated 33 recreational runners who finished the marathon (42.195Km) in less than 4 h. We collected venous