- Email: [email protected]
102 STRIATAL DOPAMINE SPECT IN RESTLESS LEGS SYNDROME
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099
Abstracts of 3rd International Congress of the Association of Sleep Medicine (WASM) / Sleep Medicine 10, Suppl. 2 (2009) S1–S83
IMPROVEMENT OF RESTLESS LEGS SYNDROME AFTER RENAL TRANSPLANTATION IN CHILEAN PATIENTS WITH CHRONIC RENAL FAILURE
C. Torres 1 , J. Santin 1 , N. Valencia 2 , G. Vidal 2 , S. Vilches 3 . 1 Pontificia Universidad Católica de Chile, Centro del Sueño; 2 Pontificia Universidad Católica de Chile; 3 Pontificia Universidad Católica, Unidad de Transplantes Introduction: Restless legs syndrome (RLS) is a common cause of sleep disturbance that is frequently experienced by patients on dialysis suffering from chronic renal failure (CRF). Previous studies have described a reduction in RLS symptomatology after successful renal transplantation. However, the underlying mechanism is not fully understood, and there are no local studies regarding this subject. Objective: This study aimed to evaluate the prevalence of RLS in patients with CRF on dialysis, to assess the improvement of symptoms after renal transplantation and to analyze laboratory parameters related to changes in symptomatology. Methods: We conducted a retrospective study on patients suffering from CRF on dialysis who were subjected to renal transplantation procedures. A standardized survey was applied for RLS diagnosis, according to the International RLS Study Group criteria, and the severity of the symptoms was evaluated before and after transplantation by use of ad-hoc intensity measurement scores. Multiple laboratory parameters were evaluated pre- and post-transplantation. Results: A total of 58 patients subjected to renal transplantation were evaluated, with an average age of 44 years (range, 18-72 years), of which 30 were males and 28 were females. Of these patients, 16 (28%), 5 females and 11 males with an average age of 45 years (range, 24-69 years), met the diagnostic criteria for RLS. The RLS mean severity score pre-transplantation was 23.7 (10-35) and 1.4 after transplantation (0-7) (p<0.001). Of the RLS group, 75% presented complete remission of symptoms after transplantation, and 25% (4/16) showed significant improvement. The average time in which this improvement was observed was 5.4 weeks. This reduction in symptomatology was related to an improvement in serum phosphate level and renal function (p<0.001); improvement was also seen for hematocrit and parathyroid hormone (PTH) levels (p<0.002 and p<0.05, respectively). Conclusions: Patients suffering from CRF treated with dialysis have a high prevalence of RLS. Patients with CRF and RLS subjected to renal transplantation showed a significant reduction of their symptomatology (100% in our series), and in most of the cases, complete recovery was observed. Similar to results described in international reports, this improvement after transplantation was associated with an improvement in hematocrit, renal function and serum levels of phosphate and PTH. Nevertheless, the specific biological process underlying this improvement is still not fully understood.
100
RESTLESS LEGS SYNDROME MAY BE ASSOCIATED WITH SMALL INTESTINAL BACTERIAL OVERGROWTH AND IMPROVED WITH ANTIBIOTIC TREATMENT
L. Weinstock. Specialists in Gastroenterology Introduction: Restless leg syndrome (RLS) etiology remains unclear, although alterations with dopamine and iron homeostasis may play a role. Small intestinal bacterial overgrowth (SIBO) is a common condition in which excessive levels of bacteria are present in the small intestine. A link between SIBO and RLS has recently been recognized. Dopamine agonists are standard therapy for RLS but may cause adverse effects; thus, new therapies are needed. Objectives: This study examined the prevalence of SIBO in patients with idiopathic RLS and the effect of rifaximin, a nonsystemic antibiotic, on RLS symptoms. Methods: Patients had RLS if they met all four international RLS criteria. Patients were screened for SIBO using a lactulose breath test (LBT). Patients with RLS and abnormal LBT results received 400 mg of rifaximin three times a day for ten days followed by 400 mg/d for 20 days. The LBT was repeated on day 12. On days 12, 20, and 30, general global assessments of RLS and gastrointestinal (GI) symptoms were conducted. The international RLS (IRLS) symptom scale (range, 0-40) was used to determined RLS severity. Results: Of 21 RLS patients, 15 (71%) had an abnormal LBT result. One patient with Helicobacter pylori infection was excluded. The 14 remaining patients reported having RLS symptoms for a mean of 6.8±7.5 years. Mean baseline IRLS symptom severity score was 23.1±6.2. Post-treatment, 9 patients
identified themselves as global RLS clinical responders (markedly, moderately, or slightly improved) and 5 subjects were identified as nonresponders (unchanged or slightly, moderately, or markedly worse). Mean IRLS severity scores for all patients were 23.1, 17.9, 16.2, and 14.8 at baseline, day 12, day 20, and day 30, respectively. At the same time points, mean IRLS scores for responders were 22.9, 14.6, 12.8, and 12.2, respectively, and for nonresponders, scores were 23.4, 23.8, 26.3, and 22.7, respectively. Percent change from baseline for the IRLS severity score was 40.2±0.44% in all patients (range, -55.0 to 100.0%), -5.7±32.0% in nonresponders (range, -55 to 20.7%), and 65.6±25.2% in responders (range, 31.0% to 100.0%). Two nonresponders who received additional combination antibiotics had substantial reductions in RLS symptoms. Conclusion: This pilot study supports the hypothesis that SIBO may contribute to RLS symptoms and suggests that antibiotics (e.g., rifaximin) may alleviate RLS symptoms.
101
ANTIBIOTIC THERAPY IMPROVES RESTLESS LEG SYNDROME: A DOUBLE-BLIND, CONTROLLED STUDY OF A SHORT COURSE OF RIFAXIMIN
L.B. Weinstock 1 , A. Walters 2 , S. Duntley 3 , S. Zeiss 3 , N. Lewis 3 . 1 Washington University School of Medicine; 2 Vanderbuilt University School of Medicine; 3 Specialists in Gastroenterology Introduction: An association between restless leg syndrome (RLS) and small intestinal bacterial overgrowth (SIBO) has recently been recognized. Objective: We evaluated the efficacy of rifaximin, a nonsystemic antibiotic, for RLS treatment. Methods: Thirty-nine patients with idiopathic RLS (international RLS [IRLS] score ≥15 and ferritin level ≥20 ng/mL) and 27 healthy controls were screened for SIBO using a lactulose breath test (LBT). Patients with RLS and an abnormal LBT result received rifaximin 1650 mg/d or placebo for 10 days. IRLS scores were assessed at baseline and on days 11, 18, and 25. Results: Thirty patients (77%) and 7 controls (26%) had abnormal LBT results. Patients who received rifaximin (n=20; 11F/9M; mean age, 53.2±10.5 y) had a baseline IRLS score of 25.4±4.8 and suffered from RLS for a mean of 12.0±11.4 years. Within the rifaximin group, 10 patients (50%) had irritable bowel syndrome (IBS) and 16 (80%) had gastrointestinal (GI) symptoms. One patient in the placebo group (n=10) was excluded because of benzodiazepine use. The remaining patients who received placebo (n=9; 7F/2M; mean age, 60.9±14.4 y) had a baseline IRLS score of 22.7±5.3 and suffered from RLS for 10.9±14.3 years. In the placebo group, 1 patient was diagnosed with IBS, and 2 had GI symptoms. A similar percentage of patients in the rifaximin (30%) and placebo groups (33%) had low ferritin levels (20-50 ng/mL) at baseline. Eighteen days after initiation of rifaximin therapy, the mean change in IRLS score was -4.5±6.6 in the rifaximin group (n=20) vs. -0.6±8.0 in the placebo group (n=9; P=0.444). The percentage of IRLS responders (i.e., patients with a ≥6-point decrease from baseline in IRLS score) on day 18 was greater in the rifaximin group (50%) than in the placebo group (11%; P=0.096). A total of 4 patients in the rifaximin group and 2 in the placebo group experienced marked or moderate worsening of global RLS symptoms during treatment. Two of these 4 rifaximin patients had lower IRLS scores on days 11 and 18 than at baseline, but their IRLS scores exceeded baseline scores on day 25. Conclusion: GI symptoms and a positive LBT result, suggesting SIBO, are common in patients with idiopathic RLS. A short course of rifaximin 1650 mg/d led to decreased RLS severity. Further studies are warranted to determine the best dosing regimen of rifaximin in patients with RLS.
102
STRIATAL DOPAMINE SPECT IN RESTLESS LEGS SYNDROME
I.Y. Yoon, K.W. Kim, Y.K. Kim. Seoul National University Bundang Hospital Introduction: As dopamine (DA) precursors and DA agonists are highly effective in alleviating symptoms of restless legs syndrome (RLS), a dysfunction of DA system has been suggested as a pathophysiology of RLS. However, results of neuroimaging studies on RLS are inconclusive. Objectives: The aim of the current study was to investigate striatal presynaptic DA transporters (DAT) in elderly patients with RLS using β-CIT SPECT. We also studied the correlation between DAT density and RLS severity in the RLS patients. Methods: Sixteen drug-naïve patients with RLS and 16 healthy controls par-
Abstracts of 3rd International Congress of the Association of Sleep Medicine (WASM) / Sleep Medicine 10, Suppl. 2 (2009) S1–S83
ticipated in the study; β-CIT SPECT images were acquired from all the subjects. Standard regions of interest (ROIs) for the entire striatum, caudate and putamen were manually defined on β-CIT SPECT templates superimposed on standard MRI. The severity of RLS was defined as total score on the International RLS Study Group (IRLSSG) Severity Scale. Depressive symptoms were measured by means of the Geriatric Depression Scale (GDS). Results: Patients with RLS were older than healthy controls (79.8±9.0 vs. 70.6±5.7 yrs, p=0.002) with no difference in gender ratio. After adjusting for age, GDS and education level, no difference was observed in DAT densities of caudate, putamen or entire striatum between RLS patients and healthy controls. On the other hand, in partial correlation analysis controlling for age, GDS and education level, the score on the RLS severity scale was negatively correlated with DAT densities of caudate, anterior putamen, posterior putamen and striatum (r= -0.617, p=0.025; r=0.595, p=0.032; r= -0.637, p=0.019; r= -0.619, p=0.024). Conclusions: Two findings in the current study, that is, lack of differences in DAT densities in striatal SPECT between patients with RLS and healthy controls, and negative correlation between RLS severity and DAT density might be contradictory with regard to the involvement of the nigrostriatal DA system in RLS. Further studies are needed to define whether specific DA systems contribute to the pathogenesis of RLS.
103
EFFECTS OF DOPAMINE-AGONIST TREATMENT ON HEART RATE VARIABILITY DURING SLEEP IN RESTLESS LEGS SYNDROME
M. Manconi 1 , R. Ferri 2 , M. Zucconi 1 , F. Rundo 2 , A. Oldani 1 , L. Ferini-Strambi 1 . 1 Sleep Disorders Center, Department of Neuroscience, Scientific Institute and University Ospedale San Raffaele, Vita-Salute University, Milan; 2 Sleep Research Centre, Department of Neurology I.C., Oasi Institute (IRCCS), Troina, Italy Restless legs syndrome (RLS) is a sensory-motor disorder characterized by discomfort of and urge to move the legs, primarily during rest or inactivity, partial or total relief with movement, with presence or worsening exclusively in the evening. The majority of patients with RLS present periodic leg movements during sleep (PLMS) which are coupled with cortical and autonomic activations. Dopamine agonists are the first-line treatment in RLS; however, little is known on the impact of dopamine-agonist treatment on the autonomic function during sleep. For this reason, a prospective, polysomnographic, single-blind, placebo-controlled study was carried out in 23 patients with RLS. Basal spectral analysis of heart rate variability (HRV) and transient heart rate (HR) changes during PLMS in patients were compared with those of 10 healthy subjects and, subsequently, before and after pramipexole or placebo treatment, in the RLS group. Regarding basal sympathovagal balance outside of PLMS sequences, no differences were found between RLS and controls and, in the RLS group, before and after treatment. The mean amplitude of PLMS-related HR changes resulted significantly higher in patients than in controls. Pramipexole suppressed the number of PLMS and normalized the PLMS-related HR response in subjects with RLS. The repetitive abnormal autonomic response to PLMS might play a role in the increased cardiovascular risk observed in RLS patients. Pramipexole significantly reduced the number of PLMS and the autonomic response to the residual PLMS, without effects on the basal sympathovagal regulation during PLMS-free periods. D3 receptors in the sympathetic pre-ganglionic neurons of the spinal intermediolateral columns might represent the target of pramipexole. The normalization of the HR reaction to PLMS may be relevant in reducing the risk of cardiovascular diseases in RLS.
Narcolepsy and other Hypersomnia
104
SPECT FINDINGS IN A PATIENT WITH KLEINE-LEVIN SYNDROME
M.O. Adolfo 1 , S.M. Valiensi 2 , M.F. Maria Fernanda Verdaguer 1 , D. Martino 1 , M.C. Fitzsimons 1 . 1 Hospital Britanico de Buenos Aires; 2 Hospital Italiano de Buenos Aires Introduction: Kleine-Levin syndrome (KLS) is a severe form of hypersomnia with onset during adolescence. It is characterized by relapsing-remitting
S29
episodes of hypersomnia and cognitive and behavioral changes. During episodes, patients display hypersomnia, cognitive disturbances, feeling of derealization, hyperphagia and hypersexuality. Each event lasts for 1 or 2 weeks, and patients are asymptomatic between episodes. The etiopathogenesis is unknown. A diencephalic dysfunction was proposed. Brain SPECT changes have been reported in patients with KLS. Objectives: To show SPECT findings in a case of KLS. The study was done during the symptomatic episode. Methods: A 28 year-old man with frequent episodes of hypersomnia, confusion and hyperphagia since adolescence, who has 3-4 attacks per year, was studied. The brain MRI was normal. The EEG showed generalized slow waves. During one episode, 99mTc-ethylcysteinate dimer brain single photon emission computed tomography (SPECT) was performed. Results: SPECT showed a severe hypoperfusion in the thalamus, basal ganglia, and left frontal and temporal lobes. Conclusion: These findings suggest a diencephalic alteration during a symptomatic episode in a case of KLS.
105
QUALITY OF LIFE IN PORTUGUESE PATIENTS WITH NARCOLEPSY
A. David, T. Paiva, F. Constantino, J. Moutinho. CENTRO HOSPITALAR DE COIMBRA Introduction: Narcolepsy is a chronic sleep disorder (AASM, 2005) that has a major impact on health-related quality of life (HRQoL). Similar to others European Countries, 47 per 100,000 inhabitants are affected in Portugal (Ohayon et al., 2002). Objectives: The aim of this study was to evaluate the health-related quality of life in Portuguese patients with narcolepsy and to compare the data obtained in this study with data from other national surveys. Methods: A transversal study was performed, and the final sample population consisted of 51 adult patients aged between 18 and 80 years old (mean=43.35±5.32), with an equal gender distribution of 26 males and 25 females. Quality of life was measured using the Medical Outcome Study - 36 item Short-From Survey (MOS SF-36). Results: HRQoL domains were significantly lower than National surveys, except for Physical Function (PF) and Bodily Pain (BP) (p-values from 0.0000.006). The SF-36 presented lowest score for Vitality (39.93). Deterioration was significantly higher in the Physical Role (p=0.006), Vitality (p=0.011), and Mental Health (p=0.008) in the women and in PF (p=0.003) and BP (p=0.045) in the elderly subjects. Narcoleptics with cataplexy had a worse health profile for both PF (p=0.020) and General Health (GH) (p=0.032), and those with a longer disease duration had worse scores in PF (p=0.048), BP (p=0.015) and GH (p=0.044). Those individuals with higher literacy had a better PF (p=0.046). There was no correlation between accidents and marital status, professional activity and situation, or the symptoms of narcolepsy (except cataplexy). Conclusions: The HRQoL showed a significant deterioration in narcoleptics, affecting all dimensions except physical function and bodily pain when compared with the general Portuguese population. Keywords: narcolepsy, quality of life, sleep disorders.
106
EFFECT OF SODIUM OXYBATE ON THE NEURO-ENDOCRINE AXIS IN A SINGLE-CENTER, OPEN LABEL, FLEXIBLE-DOSE STUDY
H. Gaelle. CHU de Liege Introduction: Sodium oxybate is a salt of γ-hydroxybutyrate and is indicated for the treatment of narcolepsy with cataplexy in adult patients. Data on the effects of γ-hydroxybutyrate on the neuro-endocrine axis are contradictory in animal models. Data in humans are limited. Methods: This single-center, open label, flexible dose study was designed to evaluate the effect of sodium oxybate during 12 week treatment for endocrine changes with a focus on the hypothalamic pituitary axis. Twenty-five subjects (13 male, 12 female) with clinically definite narcolepsy with cataplexy were included. As a primary endpoint concentrations of insulin-like growth factor (IGF-1) were measured at baseline and after 1 and 3 months. Secondary endpoints included the circadian rhythm of growth hormone (GH) and cortisol, plasma concentrations of ACTH, DHEA-S, TSH, T4 and variations of electrolytes and osmolality at baseline, 1 and 3 months. Results: ITT-analysis showed no significant change in IGF-1 as compared to baseline. Growth hormone blood concentration increased significantly
099
Abstracts of 3rd International Congress of the Association of Sleep Medicine (WASM) / Sleep Medicine 10, Suppl. 2 (2009) S1–S83
IMPROVEMENT OF RESTLESS LEGS SYNDROME AFTER RENAL TRANSPLANTATION IN CHILEAN PATIENTS WITH CHRONIC RENAL FAILURE
C. Torres 1 , J. Santin 1 , N. Valencia 2 , G. Vidal 2 , S. Vilches 3 . 1 Pontificia Universidad Católica de Chile, Centro del Sueño; 2 Pontificia Universidad Católica de Chile; 3 Pontificia Universidad Católica, Unidad de Transplantes Introduction: Restless legs syndrome (RLS) is a common cause of sleep disturbance that is frequently experienced by patients on dialysis suffering from chronic renal failure (CRF). Previous studies have described a reduction in RLS symptomatology after successful renal transplantation. However, the underlying mechanism is not fully understood, and there are no local studies regarding this subject. Objective: This study aimed to evaluate the prevalence of RLS in patients with CRF on dialysis, to assess the improvement of symptoms after renal transplantation and to analyze laboratory parameters related to changes in symptomatology. Methods: We conducted a retrospective study on patients suffering from CRF on dialysis who were subjected to renal transplantation procedures. A standardized survey was applied for RLS diagnosis, according to the International RLS Study Group criteria, and the severity of the symptoms was evaluated before and after transplantation by use of ad-hoc intensity measurement scores. Multiple laboratory parameters were evaluated pre- and post-transplantation. Results: A total of 58 patients subjected to renal transplantation were evaluated, with an average age of 44 years (range, 18-72 years), of which 30 were males and 28 were females. Of these patients, 16 (28%), 5 females and 11 males with an average age of 45 years (range, 24-69 years), met the diagnostic criteria for RLS. The RLS mean severity score pre-transplantation was 23.7 (10-35) and 1.4 after transplantation (0-7) (p<0.001). Of the RLS group, 75% presented complete remission of symptoms after transplantation, and 25% (4/16) showed significant improvement. The average time in which this improvement was observed was 5.4 weeks. This reduction in symptomatology was related to an improvement in serum phosphate level and renal function (p<0.001); improvement was also seen for hematocrit and parathyroid hormone (PTH) levels (p<0.002 and p<0.05, respectively). Conclusions: Patients suffering from CRF treated with dialysis have a high prevalence of RLS. Patients with CRF and RLS subjected to renal transplantation showed a significant reduction of their symptomatology (100% in our series), and in most of the cases, complete recovery was observed. Similar to results described in international reports, this improvement after transplantation was associated with an improvement in hematocrit, renal function and serum levels of phosphate and PTH. Nevertheless, the specific biological process underlying this improvement is still not fully understood.
100
RESTLESS LEGS SYNDROME MAY BE ASSOCIATED WITH SMALL INTESTINAL BACTERIAL OVERGROWTH AND IMPROVED WITH ANTIBIOTIC TREATMENT
L. Weinstock. Specialists in Gastroenterology Introduction: Restless leg syndrome (RLS) etiology remains unclear, although alterations with dopamine and iron homeostasis may play a role. Small intestinal bacterial overgrowth (SIBO) is a common condition in which excessive levels of bacteria are present in the small intestine. A link between SIBO and RLS has recently been recognized. Dopamine agonists are standard therapy for RLS but may cause adverse effects; thus, new therapies are needed. Objectives: This study examined the prevalence of SIBO in patients with idiopathic RLS and the effect of rifaximin, a nonsystemic antibiotic, on RLS symptoms. Methods: Patients had RLS if they met all four international RLS criteria. Patients were screened for SIBO using a lactulose breath test (LBT). Patients with RLS and abnormal LBT results received 400 mg of rifaximin three times a day for ten days followed by 400 mg/d for 20 days. The LBT was repeated on day 12. On days 12, 20, and 30, general global assessments of RLS and gastrointestinal (GI) symptoms were conducted. The international RLS (IRLS) symptom scale (range, 0-40) was used to determined RLS severity. Results: Of 21 RLS patients, 15 (71%) had an abnormal LBT result. One patient with Helicobacter pylori infection was excluded. The 14 remaining patients reported having RLS symptoms for a mean of 6.8±7.5 years. Mean baseline IRLS symptom severity score was 23.1±6.2. Post-treatment, 9 patients
identified themselves as global RLS clinical responders (markedly, moderately, or slightly improved) and 5 subjects were identified as nonresponders (unchanged or slightly, moderately, or markedly worse). Mean IRLS severity scores for all patients were 23.1, 17.9, 16.2, and 14.8 at baseline, day 12, day 20, and day 30, respectively. At the same time points, mean IRLS scores for responders were 22.9, 14.6, 12.8, and 12.2, respectively, and for nonresponders, scores were 23.4, 23.8, 26.3, and 22.7, respectively. Percent change from baseline for the IRLS severity score was 40.2±0.44% in all patients (range, -55.0 to 100.0%), -5.7±32.0% in nonresponders (range, -55 to 20.7%), and 65.6±25.2% in responders (range, 31.0% to 100.0%). Two nonresponders who received additional combination antibiotics had substantial reductions in RLS symptoms. Conclusion: This pilot study supports the hypothesis that SIBO may contribute to RLS symptoms and suggests that antibiotics (e.g., rifaximin) may alleviate RLS symptoms.
101
ANTIBIOTIC THERAPY IMPROVES RESTLESS LEG SYNDROME: A DOUBLE-BLIND, CONTROLLED STUDY OF A SHORT COURSE OF RIFAXIMIN
L.B. Weinstock 1 , A. Walters 2 , S. Duntley 3 , S. Zeiss 3 , N. Lewis 3 . 1 Washington University School of Medicine; 2 Vanderbuilt University School of Medicine; 3 Specialists in Gastroenterology Introduction: An association between restless leg syndrome (RLS) and small intestinal bacterial overgrowth (SIBO) has recently been recognized. Objective: We evaluated the efficacy of rifaximin, a nonsystemic antibiotic, for RLS treatment. Methods: Thirty-nine patients with idiopathic RLS (international RLS [IRLS] score ≥15 and ferritin level ≥20 ng/mL) and 27 healthy controls were screened for SIBO using a lactulose breath test (LBT). Patients with RLS and an abnormal LBT result received rifaximin 1650 mg/d or placebo for 10 days. IRLS scores were assessed at baseline and on days 11, 18, and 25. Results: Thirty patients (77%) and 7 controls (26%) had abnormal LBT results. Patients who received rifaximin (n=20; 11F/9M; mean age, 53.2±10.5 y) had a baseline IRLS score of 25.4±4.8 and suffered from RLS for a mean of 12.0±11.4 years. Within the rifaximin group, 10 patients (50%) had irritable bowel syndrome (IBS) and 16 (80%) had gastrointestinal (GI) symptoms. One patient in the placebo group (n=10) was excluded because of benzodiazepine use. The remaining patients who received placebo (n=9; 7F/2M; mean age, 60.9±14.4 y) had a baseline IRLS score of 22.7±5.3 and suffered from RLS for 10.9±14.3 years. In the placebo group, 1 patient was diagnosed with IBS, and 2 had GI symptoms. A similar percentage of patients in the rifaximin (30%) and placebo groups (33%) had low ferritin levels (20-50 ng/mL) at baseline. Eighteen days after initiation of rifaximin therapy, the mean change in IRLS score was -4.5±6.6 in the rifaximin group (n=20) vs. -0.6±8.0 in the placebo group (n=9; P=0.444). The percentage of IRLS responders (i.e., patients with a ≥6-point decrease from baseline in IRLS score) on day 18 was greater in the rifaximin group (50%) than in the placebo group (11%; P=0.096). A total of 4 patients in the rifaximin group and 2 in the placebo group experienced marked or moderate worsening of global RLS symptoms during treatment. Two of these 4 rifaximin patients had lower IRLS scores on days 11 and 18 than at baseline, but their IRLS scores exceeded baseline scores on day 25. Conclusion: GI symptoms and a positive LBT result, suggesting SIBO, are common in patients with idiopathic RLS. A short course of rifaximin 1650 mg/d led to decreased RLS severity. Further studies are warranted to determine the best dosing regimen of rifaximin in patients with RLS.
102
STRIATAL DOPAMINE SPECT IN RESTLESS LEGS SYNDROME
I.Y. Yoon, K.W. Kim, Y.K. Kim. Seoul National University Bundang Hospital Introduction: As dopamine (DA) precursors and DA agonists are highly effective in alleviating symptoms of restless legs syndrome (RLS), a dysfunction of DA system has been suggested as a pathophysiology of RLS. However, results of neuroimaging studies on RLS are inconclusive. Objectives: The aim of the current study was to investigate striatal presynaptic DA transporters (DAT) in elderly patients with RLS using β-CIT SPECT. We also studied the correlation between DAT density and RLS severity in the RLS patients. Methods: Sixteen drug-naïve patients with RLS and 16 healthy controls par-
Abstracts of 3rd International Congress of the Association of Sleep Medicine (WASM) / Sleep Medicine 10, Suppl. 2 (2009) S1–S83
ticipated in the study; β-CIT SPECT images were acquired from all the subjects. Standard regions of interest (ROIs) for the entire striatum, caudate and putamen were manually defined on β-CIT SPECT templates superimposed on standard MRI. The severity of RLS was defined as total score on the International RLS Study Group (IRLSSG) Severity Scale. Depressive symptoms were measured by means of the Geriatric Depression Scale (GDS). Results: Patients with RLS were older than healthy controls (79.8±9.0 vs. 70.6±5.7 yrs, p=0.002) with no difference in gender ratio. After adjusting for age, GDS and education level, no difference was observed in DAT densities of caudate, putamen or entire striatum between RLS patients and healthy controls. On the other hand, in partial correlation analysis controlling for age, GDS and education level, the score on the RLS severity scale was negatively correlated with DAT densities of caudate, anterior putamen, posterior putamen and striatum (r= -0.617, p=0.025; r=0.595, p=0.032; r= -0.637, p=0.019; r= -0.619, p=0.024). Conclusions: Two findings in the current study, that is, lack of differences in DAT densities in striatal SPECT between patients with RLS and healthy controls, and negative correlation between RLS severity and DAT density might be contradictory with regard to the involvement of the nigrostriatal DA system in RLS. Further studies are needed to define whether specific DA systems contribute to the pathogenesis of RLS.
103
EFFECTS OF DOPAMINE-AGONIST TREATMENT ON HEART RATE VARIABILITY DURING SLEEP IN RESTLESS LEGS SYNDROME
M. Manconi 1 , R. Ferri 2 , M. Zucconi 1 , F. Rundo 2 , A. Oldani 1 , L. Ferini-Strambi 1 . 1 Sleep Disorders Center, Department of Neuroscience, Scientific Institute and University Ospedale San Raffaele, Vita-Salute University, Milan; 2 Sleep Research Centre, Department of Neurology I.C., Oasi Institute (IRCCS), Troina, Italy Restless legs syndrome (RLS) is a sensory-motor disorder characterized by discomfort of and urge to move the legs, primarily during rest or inactivity, partial or total relief with movement, with presence or worsening exclusively in the evening. The majority of patients with RLS present periodic leg movements during sleep (PLMS) which are coupled with cortical and autonomic activations. Dopamine agonists are the first-line treatment in RLS; however, little is known on the impact of dopamine-agonist treatment on the autonomic function during sleep. For this reason, a prospective, polysomnographic, single-blind, placebo-controlled study was carried out in 23 patients with RLS. Basal spectral analysis of heart rate variability (HRV) and transient heart rate (HR) changes during PLMS in patients were compared with those of 10 healthy subjects and, subsequently, before and after pramipexole or placebo treatment, in the RLS group. Regarding basal sympathovagal balance outside of PLMS sequences, no differences were found between RLS and controls and, in the RLS group, before and after treatment. The mean amplitude of PLMS-related HR changes resulted significantly higher in patients than in controls. Pramipexole suppressed the number of PLMS and normalized the PLMS-related HR response in subjects with RLS. The repetitive abnormal autonomic response to PLMS might play a role in the increased cardiovascular risk observed in RLS patients. Pramipexole significantly reduced the number of PLMS and the autonomic response to the residual PLMS, without effects on the basal sympathovagal regulation during PLMS-free periods. D3 receptors in the sympathetic pre-ganglionic neurons of the spinal intermediolateral columns might represent the target of pramipexole. The normalization of the HR reaction to PLMS may be relevant in reducing the risk of cardiovascular diseases in RLS.
Narcolepsy and other Hypersomnia
104
SPECT FINDINGS IN A PATIENT WITH KLEINE-LEVIN SYNDROME
M.O. Adolfo 1 , S.M. Valiensi 2 , M.F. Maria Fernanda Verdaguer 1 , D. Martino 1 , M.C. Fitzsimons 1 . 1 Hospital Britanico de Buenos Aires; 2 Hospital Italiano de Buenos Aires Introduction: Kleine-Levin syndrome (KLS) is a severe form of hypersomnia with onset during adolescence. It is characterized by relapsing-remitting
S29
episodes of hypersomnia and cognitive and behavioral changes. During episodes, patients display hypersomnia, cognitive disturbances, feeling of derealization, hyperphagia and hypersexuality. Each event lasts for 1 or 2 weeks, and patients are asymptomatic between episodes. The etiopathogenesis is unknown. A diencephalic dysfunction was proposed. Brain SPECT changes have been reported in patients with KLS. Objectives: To show SPECT findings in a case of KLS. The study was done during the symptomatic episode. Methods: A 28 year-old man with frequent episodes of hypersomnia, confusion and hyperphagia since adolescence, who has 3-4 attacks per year, was studied. The brain MRI was normal. The EEG showed generalized slow waves. During one episode, 99mTc-ethylcysteinate dimer brain single photon emission computed tomography (SPECT) was performed. Results: SPECT showed a severe hypoperfusion in the thalamus, basal ganglia, and left frontal and temporal lobes. Conclusion: These findings suggest a diencephalic alteration during a symptomatic episode in a case of KLS.
105
QUALITY OF LIFE IN PORTUGUESE PATIENTS WITH NARCOLEPSY
A. David, T. Paiva, F. Constantino, J. Moutinho. CENTRO HOSPITALAR DE COIMBRA Introduction: Narcolepsy is a chronic sleep disorder (AASM, 2005) that has a major impact on health-related quality of life (HRQoL). Similar to others European Countries, 47 per 100,000 inhabitants are affected in Portugal (Ohayon et al., 2002). Objectives: The aim of this study was to evaluate the health-related quality of life in Portuguese patients with narcolepsy and to compare the data obtained in this study with data from other national surveys. Methods: A transversal study was performed, and the final sample population consisted of 51 adult patients aged between 18 and 80 years old (mean=43.35±5.32), with an equal gender distribution of 26 males and 25 females. Quality of life was measured using the Medical Outcome Study - 36 item Short-From Survey (MOS SF-36). Results: HRQoL domains were significantly lower than National surveys, except for Physical Function (PF) and Bodily Pain (BP) (p-values from 0.0000.006). The SF-36 presented lowest score for Vitality (39.93). Deterioration was significantly higher in the Physical Role (p=0.006), Vitality (p=0.011), and Mental Health (p=0.008) in the women and in PF (p=0.003) and BP (p=0.045) in the elderly subjects. Narcoleptics with cataplexy had a worse health profile for both PF (p=0.020) and General Health (GH) (p=0.032), and those with a longer disease duration had worse scores in PF (p=0.048), BP (p=0.015) and GH (p=0.044). Those individuals with higher literacy had a better PF (p=0.046). There was no correlation between accidents and marital status, professional activity and situation, or the symptoms of narcolepsy (except cataplexy). Conclusions: The HRQoL showed a significant deterioration in narcoleptics, affecting all dimensions except physical function and bodily pain when compared with the general Portuguese population. Keywords: narcolepsy, quality of life, sleep disorders.
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EFFECT OF SODIUM OXYBATE ON THE NEURO-ENDOCRINE AXIS IN A SINGLE-CENTER, OPEN LABEL, FLEXIBLE-DOSE STUDY
H. Gaelle. CHU de Liege Introduction: Sodium oxybate is a salt of γ-hydroxybutyrate and is indicated for the treatment of narcolepsy with cataplexy in adult patients. Data on the effects of γ-hydroxybutyrate on the neuro-endocrine axis are contradictory in animal models. Data in humans are limited. Methods: This single-center, open label, flexible dose study was designed to evaluate the effect of sodium oxybate during 12 week treatment for endocrine changes with a focus on the hypothalamic pituitary axis. Twenty-five subjects (13 male, 12 female) with clinically definite narcolepsy with cataplexy were included. As a primary endpoint concentrations of insulin-like growth factor (IGF-1) were measured at baseline and after 1 and 3 months. Secondary endpoints included the circadian rhythm of growth hormone (GH) and cortisol, plasma concentrations of ACTH, DHEA-S, TSH, T4 and variations of electrolytes and osmolality at baseline, 1 and 3 months. Results: ITT-analysis showed no significant change in IGF-1 as compared to baseline. Growth hormone blood concentration increased significantly