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O0020 Sleepiness and fatigue in major depressive disorder and therapeutic effects of a sedating antidepressant
Oral Platform Presentations / Sleep Medicine 8 Suppl. 1 (2007) S49–S66 of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
O0018 Quantitative thermal sensory testing and sympathetic skin response in primary restless legs syndrome – a prospective study of 57 Indian patients G. Shukla *, S. Singh, V. Goyal, A. Srivastava, M. Behari. Department of Neurology, All India Institute of Medical Sciences, New Delhi, India Background: Patients with Restless legs syndrome (RLS) present with predominantly sensory manifestations, which often resemble and sometimes are mistaken as those of peripheral neuropathy. There are very few studies on the prevalence of sensory abnormalities and evidence of peripheral neuropathy in patients with primary RLS. Aim: We conducted this study to assess the prevalence of electrophysiological and psychophysiological evidence of involvement of small peripheral nerve fibers in consecutive patients of primary RLS. Methods: Over a period of 3 years, all consecutive patients fulfilling the IRLSSG criteria of RLS attending Neurology services, were evaluated for evidence of pregnancy or any medical, hematological or neurological disorders. All patients in whom all such disorders could be ruled out and those who did not have known peripheral neuropathy formed the patient population. Detailed nerve conduction studies on one upper limb and one lower limb, quantitative thermal sensory testing (QST) by method of limits and sympathetic skin response (SSR) were carried out in all patients. Results: A total of 105 patients (52 males, 53 females) with RLS were seen from September 2003 to August 2006. Among these 57 patients (38 females, 19 males) with an average age of 43+14.5 years could be classified as primary RLS. The average duration of symptoms in lower limbs was 5.4 years. All patients revealed no abnormality on detailed medical and neurological examination. Nerve conduction studies were found normal in all patients. QST could be performed in 50 patients and revealed abnormal thresholds for at least one modality of sensation (cold or warm) in 33 patients (66%). Fifteen patients (30%) among these (all of whom had abnormalities on QST) also showed a non-recordable SSR. Conclusion: This study reveals that a large proportion, almost two-thirds, of patients with primary RLS demonstrate evidence of possible involvement of small peripheral nerve fibers with abnormal thermal thresholds and SSR.
O0019 Periodic limb movement in chronic renal failure: an actigraph evaluation M. Bhatia1 , S.B. Nandeeshwara2 , A.K. Bhalla3 , D.S. Rana3 . 1 Sleep Medicine, 2 Clinical Neurophysiology, 3 Nephrology Department, Sir Ganga Ram Hospital, New Delhi, India The objective was to study the prevalence of Periodic Leg Movements in patients with Chronic Renal Failure using an actigraph. The study group included 50 Chronic Renal Failure (CRF) patients, enrolled from Nephrology Unit, Sir Ganga Ram Hospital, New Delhi. All were evaluated by clinical history and a pre-designed questionnaire, comprising of patients demographic details, and RLS symptoms. All participants were given an actigraph (PAM-RL version 7.6.0, IM systems) for one night. The recorded data was downloaded and PLM/hr was noted. PLM/hr was considered significant if it was >5. There were 39 males, 11 females, with mean± SD age 52.60±15.26 yr. The disease duration in patients ranged from 2 to 14 years, mean(SD) 4.31(3.465) years. Sleep related complaints were reported by 25 (50%) patients. Complaints included: difficulty in falling asleep − 17 patients (34%), frequent awakening − 19 (38%), restless feelings in legs relieved by movement − 13 (26%), increased sleep in 6 (12%), abnormal behavior in sleep − 12 (24%); 17 patients (34%) had an urge to move legs with abnormal sensation. Increased motor activity to relieve these symptoms was observed in 12 patients (24%). Various methods to obtain relief included: walking (1), pressing legs (5), rubbing (5), tying with cloth (1), touch on cold surface (1), change in position (2) and shaking the legs (2). In 8 (16%), bed partners noticed increased movements in sleep. 40 (80%) patients were given actigraph and 22 patients (55%) had PLM rate >5.
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A large no. (50%) of patients with CRF have sleep related complaints, Insomnia & RLS being the most common. Actigraph detected presence of PLMS in 55% though these were not obtained on history. Contributed support: The authors are grateful to Dr. W. Hening, Dr. R. Allen and IM systems for providing the Actigraph. O0020 Sleepiness and fatigue in major depressive disorder and therapeutic effects of a sedating antidepressant J. Shen *, C.M. Shapiro. Sleep Research Unit, Department of Psychiatry, UHN and University of Toronto, Toronto, Canada Objectives: To compare the severity of sleepiness and fatigue between MDD patients and normal individuals, to investigate therapeutic effects of a sedating antidepressant and to observe clinical correlations between mood state and the measurements of sleepiness and fatigue. Methods: The Multiple Sleep Latency Test (MSLT) and the Epworth Sleepiness Scale (ESS) were used to measure daytime sleepiness; the Fatigue Severity Scale (FSS) and the Fatigue Impact Scale (FIS) were used to measure fatigue; and the Center for Epidemiological Study-Depression Scale (CES-D) and the Beck Depression Inventory (BDI) were used to measure mood state. Student t-test, repeated measures analysis of variance (rMANOVA) and Pearson’ correlation test were used for data analyses. Results: This study included 74 subjects. There was no different (P = 0.169) on age between patient group (43.9±12.5; n = 42) and control group (39.7±13.4; n = 32). There were significant group differences on the ESS (8.4±4.7 vs. 4.8±3.4; P = 0.001), the FSS (5.1±1.4 vs. 2.5±1.2; P < 0.001) and the FIS (82.2±40.8 vs. 13.9±13.1; P < 0.001). After baseline assessments, 16 MDD patients took mirtazapine for 58 days. There was a linear effect on the MSLT (F=3.215, P = 0.011), the ESS (F=3.675, P = 0.021) and the FIS (F=5.796, P = 0.002). Correlations were high between the FIS and the mood measurements, moderate between the other subjective sleepiness and fatigue measurements and the mood measurements. Conclusion: Sleepiness and fatigue are severer in MDD patients than in normal population. Mirtazapine decreased the severity of sleepiness and fatigue. Mood state correlates with those subjective sleepiness and fatigue measurements. O0021 The effects of low iron on adenosine and dopamine receptors S. Gulyani1 , M. Gleichmann2 , B. Martin2 , M.P. Mattson2 , R.P. Allen1 , C.J. Earley1 *. 1 Neurology, Johns Hopkins University, Baltimore, MD, USA, 2 National Institute on Aging Intramural Research Program, Baltimore, MD, USA Restless legs syndrome (RLS) is associated with low brain iron and altered dopaminergic signaling. Binding studies show that iron deficient (ID) rats have decrease D2 receptor (D2R) levels. As iron has no known direct effect on D2R protein translation or transcription, we explored the effects of ID on parallel systems that might directly impact the dopaminergic system. Stimulation of the adenosine A2a receptor (A2aR) has been shown to alter the affinity of D2R for its agonists. In order to explore the possibility that ID may affect A2aR, which then secondarily affects D2R, we studied the effects of ID on A2aR and D2R protein levels in a transfected human neuroblastoma cell line, striatal primary neurons in culture and C57BL/6 mice. ID was induced in the cultured cells by addition of the iron chelator desferroxamine. Protein lysates were made for western blot analysis. Male mice were made ID by placing them on a low (4 ppm) iron diet (control diet was 48 ppm), starting at day 21 of age for 65 days, following which the striatum and midbrain were dissected and protein lysates were made for western blots. With increasing doses of desferroxamine both cell lines showed increasing amounts of transferrin receptor, indicating progressive cellular iron deficiency. Under low-iron conditions, both cell lines showed an increase in A2aR and a decrease in D2R protein levels. In the mice ID, as demonstrated by decreased hemoglobin, was also associated with increased A2aR and decreased D2R in both striatum and midbrain. Although our results do not allow us to understand the mechanism behind the changes, the literature does suggest a reciprocal antagonistic interaction exists between A2aR and D2R. Future studies will be needed to address
O0018 Quantitative thermal sensory testing and sympathetic skin response in primary restless legs syndrome – a prospective study of 57 Indian patients G. Shukla *, S. Singh, V. Goyal, A. Srivastava, M. Behari. Department of Neurology, All India Institute of Medical Sciences, New Delhi, India Background: Patients with Restless legs syndrome (RLS) present with predominantly sensory manifestations, which often resemble and sometimes are mistaken as those of peripheral neuropathy. There are very few studies on the prevalence of sensory abnormalities and evidence of peripheral neuropathy in patients with primary RLS. Aim: We conducted this study to assess the prevalence of electrophysiological and psychophysiological evidence of involvement of small peripheral nerve fibers in consecutive patients of primary RLS. Methods: Over a period of 3 years, all consecutive patients fulfilling the IRLSSG criteria of RLS attending Neurology services, were evaluated for evidence of pregnancy or any medical, hematological or neurological disorders. All patients in whom all such disorders could be ruled out and those who did not have known peripheral neuropathy formed the patient population. Detailed nerve conduction studies on one upper limb and one lower limb, quantitative thermal sensory testing (QST) by method of limits and sympathetic skin response (SSR) were carried out in all patients. Results: A total of 105 patients (52 males, 53 females) with RLS were seen from September 2003 to August 2006. Among these 57 patients (38 females, 19 males) with an average age of 43+14.5 years could be classified as primary RLS. The average duration of symptoms in lower limbs was 5.4 years. All patients revealed no abnormality on detailed medical and neurological examination. Nerve conduction studies were found normal in all patients. QST could be performed in 50 patients and revealed abnormal thresholds for at least one modality of sensation (cold or warm) in 33 patients (66%). Fifteen patients (30%) among these (all of whom had abnormalities on QST) also showed a non-recordable SSR. Conclusion: This study reveals that a large proportion, almost two-thirds, of patients with primary RLS demonstrate evidence of possible involvement of small peripheral nerve fibers with abnormal thermal thresholds and SSR.
O0019 Periodic limb movement in chronic renal failure: an actigraph evaluation M. Bhatia1 , S.B. Nandeeshwara2 , A.K. Bhalla3 , D.S. Rana3 . 1 Sleep Medicine, 2 Clinical Neurophysiology, 3 Nephrology Department, Sir Ganga Ram Hospital, New Delhi, India The objective was to study the prevalence of Periodic Leg Movements in patients with Chronic Renal Failure using an actigraph. The study group included 50 Chronic Renal Failure (CRF) patients, enrolled from Nephrology Unit, Sir Ganga Ram Hospital, New Delhi. All were evaluated by clinical history and a pre-designed questionnaire, comprising of patients demographic details, and RLS symptoms. All participants were given an actigraph (PAM-RL version 7.6.0, IM systems) for one night. The recorded data was downloaded and PLM/hr was noted. PLM/hr was considered significant if it was >5. There were 39 males, 11 females, with mean± SD age 52.60±15.26 yr. The disease duration in patients ranged from 2 to 14 years, mean(SD) 4.31(3.465) years. Sleep related complaints were reported by 25 (50%) patients. Complaints included: difficulty in falling asleep − 17 patients (34%), frequent awakening − 19 (38%), restless feelings in legs relieved by movement − 13 (26%), increased sleep in 6 (12%), abnormal behavior in sleep − 12 (24%); 17 patients (34%) had an urge to move legs with abnormal sensation. Increased motor activity to relieve these symptoms was observed in 12 patients (24%). Various methods to obtain relief included: walking (1), pressing legs (5), rubbing (5), tying with cloth (1), touch on cold surface (1), change in position (2) and shaking the legs (2). In 8 (16%), bed partners noticed increased movements in sleep. 40 (80%) patients were given actigraph and 22 patients (55%) had PLM rate >5.
S53
A large no. (50%) of patients with CRF have sleep related complaints, Insomnia & RLS being the most common. Actigraph detected presence of PLMS in 55% though these were not obtained on history. Contributed support: The authors are grateful to Dr. W. Hening, Dr. R. Allen and IM systems for providing the Actigraph. O0020 Sleepiness and fatigue in major depressive disorder and therapeutic effects of a sedating antidepressant J. Shen *, C.M. Shapiro. Sleep Research Unit, Department of Psychiatry, UHN and University of Toronto, Toronto, Canada Objectives: To compare the severity of sleepiness and fatigue between MDD patients and normal individuals, to investigate therapeutic effects of a sedating antidepressant and to observe clinical correlations between mood state and the measurements of sleepiness and fatigue. Methods: The Multiple Sleep Latency Test (MSLT) and the Epworth Sleepiness Scale (ESS) were used to measure daytime sleepiness; the Fatigue Severity Scale (FSS) and the Fatigue Impact Scale (FIS) were used to measure fatigue; and the Center for Epidemiological Study-Depression Scale (CES-D) and the Beck Depression Inventory (BDI) were used to measure mood state. Student t-test, repeated measures analysis of variance (rMANOVA) and Pearson’ correlation test were used for data analyses. Results: This study included 74 subjects. There was no different (P = 0.169) on age between patient group (43.9±12.5; n = 42) and control group (39.7±13.4; n = 32). There were significant group differences on the ESS (8.4±4.7 vs. 4.8±3.4; P = 0.001), the FSS (5.1±1.4 vs. 2.5±1.2; P < 0.001) and the FIS (82.2±40.8 vs. 13.9±13.1; P < 0.001). After baseline assessments, 16 MDD patients took mirtazapine for 58 days. There was a linear effect on the MSLT (F=3.215, P = 0.011), the ESS (F=3.675, P = 0.021) and the FIS (F=5.796, P = 0.002). Correlations were high between the FIS and the mood measurements, moderate between the other subjective sleepiness and fatigue measurements and the mood measurements. Conclusion: Sleepiness and fatigue are severer in MDD patients than in normal population. Mirtazapine decreased the severity of sleepiness and fatigue. Mood state correlates with those subjective sleepiness and fatigue measurements. O0021 The effects of low iron on adenosine and dopamine receptors S. Gulyani1 , M. Gleichmann2 , B. Martin2 , M.P. Mattson2 , R.P. Allen1 , C.J. Earley1 *. 1 Neurology, Johns Hopkins University, Baltimore, MD, USA, 2 National Institute on Aging Intramural Research Program, Baltimore, MD, USA Restless legs syndrome (RLS) is associated with low brain iron and altered dopaminergic signaling. Binding studies show that iron deficient (ID) rats have decrease D2 receptor (D2R) levels. As iron has no known direct effect on D2R protein translation or transcription, we explored the effects of ID on parallel systems that might directly impact the dopaminergic system. Stimulation of the adenosine A2a receptor (A2aR) has been shown to alter the affinity of D2R for its agonists. In order to explore the possibility that ID may affect A2aR, which then secondarily affects D2R, we studied the effects of ID on A2aR and D2R protein levels in a transfected human neuroblastoma cell line, striatal primary neurons in culture and C57BL/6 mice. ID was induced in the cultured cells by addition of the iron chelator desferroxamine. Protein lysates were made for western blot analysis. Male mice were made ID by placing them on a low (4 ppm) iron diet (control diet was 48 ppm), starting at day 21 of age for 65 days, following which the striatum and midbrain were dissected and protein lysates were made for western blots. With increasing doses of desferroxamine both cell lines showed increasing amounts of transferrin receptor, indicating progressive cellular iron deficiency. Under low-iron conditions, both cell lines showed an increase in A2aR and a decrease in D2R protein levels. In the mice ID, as demonstrated by decreased hemoglobin, was also associated with increased A2aR and decreased D2R in both striatum and midbrain. Although our results do not allow us to understand the mechanism behind the changes, the literature does suggest a reciprocal antagonistic interaction exists between A2aR and D2R. Future studies will be needed to address