Different fates of excessive daytime sleepiness: survival analysis for remission.

BACKGROUND: Excessive daytime sleepiness (EDS) is a symptom frequently presented in sleep clinics. Only a paucity of data has addressed clinical courses of sleep disorders with EDS. Therefore, we sought to compare clinical outcomes of patients presenting EDS. METHODS: A retrospective observational study was performed in the setting of sleep laboratory and outpatient department in a university hospital. One hundred and eight patients who presented EDS underwent polysomnography and multiple sleep latency test. Each patient was diagnosed as one of the following four categories: (1) narcolepsy with cataplexy (N + C; n = 29); (2) narcolepsy without cataplexy (N - C; n = 22); (3) idiopathic hypersomnia (IH; n = 24); and (4) subjective hypersomnolence (SH; n = 33) with mean sleep latency >8 min. Remission of EDS and treatment response were determined based on clinical evaluation. Kaplan-Meier survival analysis was performed. RESULTS: Remission rates were significantly different (P < 0.001, overall log-rank test) among four groups except those between N - C and IH (P = 0.489). While N + C showed no remission, predicted remission rates of N - C and IH group were 44.6% at 5 years and 32.5% at 5.5 years after diagnosis. The predicted remission rate of SH group was 71.7% at 3 years after diagnosis. CONCLUSIONS: The similarity of clinical courses between N - C and IH suggests that N - C may be more related to IH compared to N + C. Considering different clinical courses among EDS patients, thorough evaluation of EDS should be warranted before starting treatment.

Comparison of the efficacies of oral iron and pramipexole for the treatment of restless legs syndrome patients with low serum ferritin.

BACKGROUND AND PURPOSE: It is not clear which is preferred between iron supplement and a dopamine agonist in the treatment of restless legs syndrome (RLS) with iron deficiency. The efficacies of oral iron supplementation and pramipexole for treatment of RLS with low-normal serum ferritin (15-50 ng/ml) were compared. METHODS: Thirty RLS patients who took either oral iron or pramipexole for 12 weeks and were followed at 2, 4, 8 and 12 weeks after treatment commencement were enrolled. Severities of RLS symptoms were assessed using the international RLS study group rating scale for severity (IRLS) at every visit. Treatment response was defined as a decrease in IRLS score of at least 50% from baseline. RESULTS: The 30 subjects were assigned equally to an iron or pramipexole group. At baseline, IRLS scores and serum ferritin levels were similar between these two groups. After 12 weeks, IRLS scores were lower than those at baseline in both groups (iron -9.1 ± 7.07, P < 0.001; pramipexole -8.7 ± 8.31, P = 0.001) and similar between the two groups. Changes in IRLS scores from baseline were similar between the two groups at each visit. The response rates of the groups were identical at 46.7%. CONCLUSIONS: Pramipexole was not different from oral iron in terms of efficacy and improvement speed in RLS patients with a low-normal serum ferritin, but response rate of either oral iron or pramipexole alone was moderate. Some proportion of RLS patients with iron deficiency might benefit from combined use of oral iron and dopamine agonists.

Increased striatal dopamine transporter density in moderately severe old restless legs syndrome patients.

BACKGROUND AND PURPOSE: Dopamine dysregulation in restless legs syndrome (RLS) may be varied by the severity of RLS, which could contribute to the conflicting results from previous functional neuroimaging studies on the central dopaminergic neurotransmission of RLS. The aim of this study was to observe whether reduced striatal dopaminergic neurotransmission is associated with moderate to moderately severe RLS. METHODS: Thirteen elderly patients with RLS and 12 normal elderly controls were enrolled in the study. All the subjects were dopaminergic-drug naïve and twelve patients with RLS had the severity of moderate to moderately severe degree based on the International Restless Legs Syndrome Study Group (IRLSSG) Severity Scale. We compared dopamine transporter density (DAT) availability and D2 receptor density in the striatum between patients with RLS and controls using [(123)I]2ß-carbomethoxy-3ß-(4-iodophenyl)tropane single-photon emission computed tomography (SPECT) and [(123)I]iodobenzamide SPECT. RESULTS: Dopamine transporter density of patients with RLS was increased in the caudate (P = 0.037), posterior putamen (P = 0.041), and entire striatum (P = 0.046) compared with that of normal controls. DAT density was higher in the anterior putamen of patients with RLS than controls, although statistically not significant (P = 0.079). There was no difference in the D2 receptor density between patients with RLS and normal controls in the whole striatum or any of subregions. CONCLUSIONS: Dysregulation rather than simple upregulation or downregulation of central dopaminergic neurotransmission may underlie the pathogenesis of RLS, and decreased dopaminergic neurotransmission may cause moderate to moderately severe RLS in the elderly.

Availability of brain serotonin transporters in patients with restless legs syndrome.

BACKGROUND: Selective serotonin reuptake inhibitors have been associated with the risk of restless legs syndrome (RLS), suggesting that dysregulation of serotonergic neurotransmission may provoke or exacerbate RLS. METHODS: We compared the availability of serotonin transporter (SERT) between 16 drug-naïve patients with RLS and 16 healthy controls. SERT was measured in the pons and medulla via [(123)I]-2beta-carbomethoxy-3beta-(4-iodophenyl) tropane (beta-CIT) SPECT. A ratio of specific to nonspecific brain uptake (V(3)'') was used for all comparisons. RLS was diagnosed according to the criteria proposed by the National Institute of Health, and its severity was measured using the International RLS Study Group (IRLSSG) Severity Scale. RESULTS: The availability of SERT was similar in the RLS group and the control group with regards to the pons (1.24 +/- 0.31 vs 1.24 +/- 0.25, p > 0.1) and the medulla (0.99 +/- 0.25 vs 1.00 +/- 0.23, p > 0.1). However, IRLSSG Severity Scale scores increased with decrease of SERT availability in both the pons (beta = -0.50, t = -3.19, p = 0.009) and the medulla (beta = -0.42, t = -2.44, p = 0.03). CONCLUSIONS: Although serotonin transporter (SERT) availability in pons and medulla was similar in the restless legs syndrome (RLS) group and the control group, the severity of RLS symptoms increased as the availability of SERT decreased. These data partially support the hypothesis that an increase of serotonergic neurotransmission in the brainstem may exacerbate RLS, possibly via dual modulations on striatal dopaminergic neurotransmission and on the activities of spinal motor and sensory neurons.

The implication of nigrostriatal dopaminergic degeneration in the pathogenesis of REM sleep behavior disorder.

BACKGROUND AND PURPOSE: The pathogenesis of rapid eye movement (REM) sleep behavior disorder (RBD) is not clear despite its frequent association with Parkinson's disease (PD). We investigated whether the nigrostriatal dopaminergic system is involved in the development of idiopathic RBD. METHODS: Fourteen patients with RBD, 14 patients with PD and 12 normal controls were included in the study. The diagnosis of RBD was confirmed on polysomnography. All the participants performed single-photon emission computed tomography imaging 3 h after injection of [(123)I]FP-CIT. During REM sleep of the RBD patients, each 30-s epoch was rated as 'tonic' when there was at least 50% of tonically maintained chin electromyography (EMG) activity in the epoch. Phasic EMG activities were calculated as the percentage of 3-s mini-epoch containing phasic EMG events (leg and chin, separately). RESULTS: The RBD patients showed a trend of lower binding in the striatum than the normal controls (P = 0.07), and the significance was revealed in the putamen (P = 0.02). However, in 11 individual cases of the 14 RBD patients, the dopamine transporter (DAT) densities in the putamen still remained within the normal range. In the RBD patients, there was no correlation between EMG activities and DAT densities. CONCLUSIONS: Nigrostriatal dopaminergic degeneration could be a part of the pathogenesis of RBD, but not essential for the development of RBD. The lack of correlation between RBD severity and DAT densities suggests that another pathogenic process not related to nigrostriatal dopaminergic transmission may be implicated in RBD.

Erectile dysfunction and disease-specific quality of life in patients with obstructive sleep apnea.

Several reports have suggested a high incidence of erectile dysfunction (ED) among patients with obstructive sleep apnea syndrome (OSAS). The aim of this study was to investigate the correlation between OSAS and ED, or disease-specific quality of life (QOL) in patients with OSAS. In addition, we analyzed specific polysomnographic (PSG) parameters in predicting ED in OSAS patients. In total, 32 patients with OSAS and 27 normal controls were asked to complete the Korean versions of the International Index of Erectile Function questionnaire (KIIEF-5) and the Calgary Sleep Apnea Quality of Life Index (SAQLI). All patients then underwent a full-night in-laboratory PSG examination. Patients were diagnosed with OSAS if they had clinical symptoms suggestive of OSAS for at least 1 year and an apnea-hypopnea index (AHI) of more than 10 in PSG. Nineteen patients (59.3%) in the OSAS group showed ED, which was significantly higher than in the control group (8 patients, 29.6%, P=0.012). In addition, SAQLI scores worsened as AHI increased (r=0.327, P=0.011) and as the lowest oxygen saturation level decreased (r=0.420, P=0.001). ED was not significantly correlated with AHI (r=0.061, P=0.649); however, it was significantly correlated with the lowest oxygen saturation decreased (r=0.338, P=0.009). When the cutoff value for the lowest oxygen saturation level to predict ED was set at 77%, its positive predictive value was 88.9% (sensitivity=0.70, specificity=0.62). Thus, all male patients with OSAS should be screened for erectile dysfunction and more comprehensive consultation is needed, especially, if their lowest oxygen saturation levels are below 77%.

Prevalence of narcolepsy-cataplexy in Korean adolescents.

BACKGROUND: Narcolepsy typically begins between adolescence and early adulthood causing severe neuropsychiatric impairments, but few prevalence studies are available on adolescent narcoleptics. In the present study, we investigated the prevalence of narcolepsy-cataplexy in adolescents. METHODS: In total 20,407 students, aged 14-19 years, participated in this study. Ullanlinna Narcolepsy Scale (UNS) was applied to all subjects and those with a UNS score of > or =14 were contacted by phone for semi-structured interview. Subjects then suspected of having narcolepsy participated in a laboratory investigation, which included polysomnography and HLA typing, or were interviewed in detail by telephone. RESULTS: Three subjects were finally diagnosed as narcolepsy with cataplexy and seven subjects might be diagnosed as narcolepsy without cataplexy. Among three narcoleptics with cataplexy, two subjects were HLA-DQB1*0602 and DRB1*1501 positive, but one subject had no test of HLA typing. The prevalence of narcolepsy with cataplexy in Korean adolescence was thus determined to be 0.015% (95% confidence interval = 0.0-0.0313%). CONCLUSION: This epidemiologic study is the first of its type on adolescent narcolepsy to use the International Classification of Sleep Disorders, 2nd edition (ICSD-2) diagnostic criteria. Considering those cases with an onset after adolescence were not included, the prevalence of narcolepsy with cataplexy determined in the present study is comparable with that of other studies in adults.

Degree of arousal is most correlated with blood pressure reactivity during sleep in obstructive sleep apnea.

We investigated blood pressure (BP) reactivity of obstructive sleep apnea (OSA) during rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep. The influences on BP reactivity of degree of arousal, the lowest O2 saturation (SaO2), and respiratory disturbance (RD) duration were compared. Ten normotensive or borderline hypertensive patients with OSA were studied with one-night polysomnography including non-invasive beat-to-beat BP monitoring (Finapres). We compared baseline BP, pre-apneic BP, and post-apneic BP during both REM and NREM sleep. Also, relationships between delta BP (post-apneic BP minus pre-apneic BP) and degree of arousal, the lowest SaO2, and RD duration were examined. During both REM and NREM sleep, pre-apneic BP was elevated compared with baseline BP. Post-apneic BP elevation was noted compared with pre-apneic BP. The degree of arousal was more significantly correlated with delta BP than the lowest SaO2. RD duration was hardly correlated with delta BP. Pre-apneic BP elevation seems to result from cumulation of sympathetic activation and sympathetic nervous system resetting. The correlation between delta BP and degree of arousal suggests that sympathetic activation causing post-apneic BP elevation may result mainly from an arousal response regardless of hypoxia.