Snoring was related to self-reported daytime sleepiness and tiredness in young adults performing compulsory conscript service.

STUDY OBJECTIVES: In young adults performing compulsory military service, fatigue and somnolence are common and presumably associated with objective or self-reported sleep deprivation. We aimed to find out whether objective sleep parameters from ambulatory polysomnography could explain their self-reported tiredness and sleepiness and whether habits were associated with sleep parameters or tiredness. METHODS: Seventy (67 male, age 18-24 years) participants had their sleep assessed with polysomnography. Their self-reported symptoms and demographic data were obtained from online survey including Epworth Sleepiness Scale, Beck's Depression Inventory, items from Basic Nordic Sleep Questionnaire, Internet Addiction Scale, and lifestyle questions. RESULTS: Snoring (audio recording, percentage of total sleep time) was associated with self-reported sleepiness (P = .010) and tiredness (P = .030) and snoring seemed to, partially, explain sleepiness (P = .029). Twenty-six percent of the conscripts had self-reported sleep deprivation (mismatch between reported need for sleep and reported sleep). Self-reported sleep deprivation was significantly associated with somnolence (P = .016) and fatigue (P = .026). Smartphone usage, both average time (P = .022) and frequency of usage (P = .0093) before bedtime, was associated with shorter total sleep time. On average, objective sleep time was rather short (7 hours, 6 minutes), sleep efficiency high (94.9%), proportion of N3 sleep high (27.7%), and sleep latency brief (9 minutes)-suggesting that many of the conscripts might have chronic partial sleep deprivation. CONCLUSIONS: Snoring might predispose to tiredness in presumably healthy young adults. Conscripts may have partial sleep deprivation. CITATION: Orjatsalo M, Toppila J, Heimola M, et al. Snoring was related to self-reported daytime sleepiness and tiredness in young adults performing compulsory conscript service. J Clin Sleep Med. 2023;19(2):243-251.

Misdiagnosis of narcolepsy caused by a false-positive orexin-A/hypocretin-1 enzyme immune assay.

The diagnosis of narcolepsy is based on clinical history, sleep studies, and, in some cases, cerebrospinal fluid orexin-A/hypocretin-1 measurement. The gold standard for orexin measurement is the radioimmunoassay but other commercial kits are also available, such as the enzyme immune assay (EIA). The specificity of orexin EIA in humans is unknown. We report four cases where orexin levels were measured by EIA and resulted in false positives and the misdiagnosis of narcolepsy. Therefore, orexin EIA measurement should be strongly discouraged in a clinical setting. CITATION: Sarkanen T, Sved G, Juujärvi M, Alakuijala A, Partinen M. Misdiagnosis of narcolepsy caused by a false-positive orexin-A/hypocretin-1 enzyme immune assay. J Clin Sleep Med. 2022;18(8):2075-2078.

Accuracy of Actigraphy Compared to Concomitant Ambulatory Polysomnography in Narcolepsy and Other Sleep Disorders.

Actigraphy provides longitudinal sleep data over multiple nights. It is a less expensive and less cumbersome method for measuring sleep than polysomnography. Studies assessing accuracy of actigraphy compared to ambulatory polysomnography in different sleep-disordered patients are rare. We aimed to compare the concordance between these methods in clinical setting. We included 290 clinical measurements of 281 sleep laboratory patients (mean age 37.9 years, 182 female). Concomitant ambulatory polysomnography and actigraphy were analyzed to determine the agreement in patients with obstructive sleep apnea, narcolepsy, periodic leg movement disorder, hypersomnia, other rarer sleep disorders, or no organic sleep disorder. Bland-Altman plots showed excellent accuracy, but poor precision in single night results between the two methods in the measurement of sleep time, sleep efficiency, and sleep latency. On average, actigraphy tended to overestimate sleep time by a negligible amount, -0.13 min, 95% confidence interval [-5.9, 5.6] min in the whole sample. Overestimation was largest, -12.8 [-25.1, -0.9] min, in patients with obstructive sleep apnea. By contrast, in patients with narcolepsy, actigraphy tended to underestimate sleep time by 24.3 [12.4, 36.1] min. As for sleep efficiency, actigraphy underestimated it by 0.18 [-0.99, 1.35] % and sleep latency by 11.0 [8.5, 13.6] min compared to polysomnography. We conclude that, in measuring sleep time, actigraphy is reasonably reliable and helpful to be used for a week or two to exclude insufficient sleep in patients with the suspicion of narcolepsy. However, the effectiveness of actigraphy in determining sleep seems to decrease in subjects with low sleep efficiencies.

Activating autoantibodies against G protein-coupled receptors in narcolepsy type 1.

STUDY OBJECTIVES: Narcolepsy type 1 is a rare hypersomnia of central origin, which is caused by loss of hypothalamic neurons that produce the neuropeptides hypocretin-1 and -2. Hypocretin-containing nerve terminals are found in areas known to play a central role in autonomic control and in pain signaling. Cholinergic M2 receptors are found in brain areas involved with the occurrence of hallucinations and cataplexy. In addition to classical symptoms of narcolepsy, the patients suffer frequently from autonomic dysfunction, chronic pain, and hypnagogic/hypnopompic hallucinations. We aimed to test whether narcolepsy type 1 patients have autoantibodies against autonomic ß2 adrenergic receptor, M2 muscarinic receptors, or nociception receptors. METHODS: We tested the serum of ten narcolepsy type 1 patients (five female) for activating ß2 adrenergic receptor autoantibodies, M2 muscarinic receptor autoantibodies, and nociception receptor autoantibodies. RESULTS: Ten of ten patients were positive for muscarinic M2 receptor autoantibodies (P < 0.001), 9/10 were positive for autoantibodies against nociception receptors (P < 0.001), and 5/10 were positive for ß2 adrenergic receptor autoantibodies (P < 0.001). CONCLUSIONS: Narcolepsy type 1 patients harbored activating autoantibodies against M2 muscarinic receptors, nociception receptors, and ß2 adrenergic receptors. M2 receptor autoantibodies may be related to the occurrence of cataplexy and, moreover, hallucinations in narcolepsy since they are found in the same brain areas that are involved with these symptoms. The occurrence of nociception receptor autoantibodies strengthens the association between narcolepsy type 1 and pain. The connection between narcolepsy type 1, autonomic complaints, and the presumed cardiovascular morbidity might be associated with the occurrence of ß2 adrenergic receptor autoantibodies. On the other hand, the presence of the autoantibodies may be secondary to the destruction of the hypocretin pathways.

Sleep Spindle Features and Neurobehavioral Performance in Healthy School-Aged Children.

PURPOSE: In adults, central fast-frequency sleep spindles are involved in learning and memory functions. The density of local spindles is higher than global spindles, emphasizing the importance of local plastic neural processes. In children, findings on the association of spindles with cognition are more variable. Hence, we aim to study whether the local spindles are also important for neurobehavioral performance in children. METHODS: We studied the correlations between local (occurring in only one channel: Fp1, Fp2, C3, or C4), bilateral, and diffuse (occurring in all four channels) spindles and neurobehavioral performance in 17 healthy children (median age 9.6 years). RESULTS: Local spindles were not as frequent as bilateral spindles (P-values < 0.05). Central spindle types had significant correlations with sensorimotor and language functions (e.g., the density of bilateral central spindles correlated positively with the Object Assembly in NEPSY, r = 0.490). Interestingly, frontopolar spindles correlated with behavior (e.g., the more bilateral the frontopolar spindles, the less hyperactive the children, r = -0.618). CONCLUSIONS: In children, the local spindles, but also more widespread central spindles, seem to be involved in the cognitive processes. Based on our findings, it is important that ageadjusted frequency limits are used in studies evaluating the frequencies of spindles in children.

Chronotype as self-regulation: morning preference is associated with better working memory strategy independent of sleep.

Study Objectives: We set out to examine how chronotype (diurnal preference) is connected to ability to function in natural conditions where individuals cannot choose their sleep schedule. We conducted a cross-sectional study in military conscript service to test the hypothesis that sleep deprivation mediates the adverse effects of chronotype on cognitive functioning. We also examined the effects of time of day. Methods: One hundred forty participants (ages 18-24 years) completed an online survey, including the Morningness-Eveningness Questionnaire and a Cambridge Neuropsychological Test Automated Battery. Most (n = 106) underwent an actigraphy recording. After bivariate analyses, we created a mediation model (self-reported sleepiness and sleep deprivation mediating effect of chronotype on cognition) and a moderation model (synchrony between most alert time and testing time). Results: Reaction times in inhibition task correlated negatively with sleep efficiency and positively with sleep latency in actigraphy. There was no relation to ability to inhibit responses. More significantly, spatial working memory performance (especially strategicness of performance) correlated positively with morning preference and negatively with sleep deprivation before service. Synchrony with most alert time of the day did not moderate these connections. No other cognitive task correlated with morningness or sleep variables. Conclusions: In line with previous research, inhibitory control is maintained after insufficient sleep but with a tradeoff of slower performance. The connection between morning preference and working memory strategy is a novel finding. We suggest that diurnal preference could be seen as an adaptive strategy, as morningness has consistently been associated with better academic and health outcomes.

Self-reported view on work capacity predicts abnormal Oxford Sleep Resistance Test results in patients with obstructive sleep apnea.

STUDY OBJECTIVES: The Oxford Sleep Resistance Test is an objective vigilance test based on behavior. It is a modified version of the maintenance of wakefulness test and is considered less burdensome and less expensive than the maintenance of wakefulness test. Although professional drivers with obstructive sleep apnea in Europe must be assessed for their ability to maintain adequate wakefulness on a yearly basis, Oxford Sleep Resistance Test results are usually normal in this population. In this retrospective observational study, we searched for predictive factors of abnormal Oxford Sleep Resistance Test sleep latency. METHODS: We included 1,071 Oxford Sleep Resistance Test results of patients with obstructive sleep apnea (95% men, aged 21-74 years). Mean sleep latency < 40 minutes was considered abnormal. RESULTS: Sleep latency was abnormal in 12.0% of tests. Participants at risk for abnormal test results self-reported as being sleepy, depressed, on sick leave, unemployed, or retired or considered themselves unable to work. In a logistic regression model, the self-reported view on work capacity was the most important predictor of abnormal Oxford Sleep Resistance Test sleep latency (odds ratio, 3.5). Ongoing sick leave was also an important predictor for abnormal test results. CONCLUSIONS: A self-reported good ability to work predicts that a patient with sleep apnea can maintain wakefulness in a vigilance test. This may help in reducing the increasing challenge with frequent tests.

Heart Rate Variability in Head-Up Tilt Tests in Adolescent Postural Tachycardia Syndrome Patients.

Introduction: Postural tachycardia syndrome (POTS) is a suspected dysautonomia with symptoms of orthostatic intolerance and abnormally increased heart rate while standing. We aimed to study cardiac autonomic nervous system functioning in head-up tilt (HUT) in adolescents with POTS to find out if parasympathetic tone is attenuated in the upright position. Methods: We compared characteristics of a group of 25 (females 14/25; 56%) adolescents with POTS and 12 (females 4/12; 34%) without POTS aged 9-17 years. We compared heart rate variability with high- and low-frequency oscillations, and their temporal changes in HUT. Results: The high-frequency oscillations, i.e., HF, attenuated in both groups during HUT (p < 0.05), but the attenuation was bigger in POTS (p = 0.04). In the beginning of HUT, low-frequency oscillations, i.e., LF, increased more in POTS (p = 0.01), but in the end of HUT, an attenuation in LF was seen in the POTS group (p < 0.05), but not in the subjects without POTS. There were no associations of previous infections or vaccinations with POTS. Subjects with POTS were sleepier and their overall quality of life was very low. Conclusion: The results imply to an impaired autonomic regulation while standing in POTS, presenting as a lower HF and higher LF in the beginning of HUT and an attenuated LF in the prolonged standing position.

Ullanlinna Narcolepsy Scale in diagnosis of narcolepsy.

STUDY OBJECTIVES: To validate Ullanlinna Narcolepsy Scale (UNS) as a screening tool for narcolepsy in a clinical population and to compare it with Swiss Narcolepsy Scale (SNS) and Epworth Sleepiness Scale (ESS). METHODS: UNS questionnaires of 267 participants visiting Helsinki Sleep Clinic were analyzed. The diagnoses of the participants were narcolepsy type 1 (NT1, n = 89), narcolepsy type 2 (NT2, n = 10), other hypersomnias (n = 24), sleep apnea (n = 37), restless legs syndrome or periodic limb movement disorder (n = 56), and other sleep-related disorders (n = 51). In addition, ESS and SNS scores in a subset of sample (total N = 167) were analyzed and compared to UNS. RESULTS: Mean UNS score in NT1 was 22.0 (95% confidence interval [CI] = 20.4 to 23.6, range 9-43), which was significantly higher than in other disorders, including NT2 (mean 13.7, 95% CI = 10.3 to 17.1, range 7-21, p = .0013). Sensitivity and specificity of UNS in separating NT1 from other disorders were 83.5% and 84.1%, respectively. Positive and negative predictive values were 82.5% and 85.1%, respectively. Sensitivities of SNS and ESS in NT1 were 77.2% and 88.6%, and specificities 88.6% and 45.5%, respectively. There were no differences in receiver operating characteristic curves between UNS and SNS. UNS had moderate negative correlation with hypocretin-1 levels (rs = -.564, p < .001), and mean sleep latency in multiple sleep latency test (rs= -.608, p < .001). CONCLUSIONS: UNS has high specificity and sensitivity for NT1 in a sleep clinic setting. UNS scores below 9 strongly suggest against the diagnosis of narcolepsy.

Narcolepsy Associated with Pandemrix Vaccine.

PURPOSE OF REVIEW: After the connection between AS03-adjuvanted pandemic H1N1 vaccine Pandemrix and narcolepsy was recognized in 2010, research on narcolepsy has been more intensive than ever before. The purpose of this review is to provide the reader with current concepts and recent findings on the Pandemrix-associated narcolepsy. RECENT FINDINGS: After the Pandemrix vaccination campaign in 2009-2010, the risk of narcolepsy was increased 5- to 14-fold in children and adolescents and 2- to 7-fold in adults. According to observational studies, the risk of narcolepsy was elevated for 2 years after the Pandemrix vaccination. Some confounding factors and potential diagnostic biases may influence the observed narcolepsy risk in some studies, but it is unlikely that they would explain the clearly increased incidence in all the countries where Pandemrix was used. An increased risk of narcolepsy after natural H1N1 infection was reported from China, where pandemic influenza vaccination was not used. There is more and more evidence that narcolepsy is an autoimmune disease. All Pandemrix-associated narcolepsy cases have been positive for HLA class II DQB1*06:02 and novel predisposing genetic factors directly linking to the immune system have been identified. Even though recent studies have identified autoantibodies against multiple neuronal structures and other host proteins and peptides, no specific autoantigens that would explain the disease mechanism in narcolepsy have been identified thus far. There was a marked increase in the incidence of narcolepsy after Pandemrix vaccination, especially in adolescents, but also in young adults and younger children. All vaccine-related cases were of narcolepsy type 1 characterized by hypocretin deficiency in the central nervous system. The disease phenotype and the severity of symptoms varied considerably in children and adolescents suffering from Pandemrix-associated narcolepsy, but they were indistinguishable from the symptoms of idiopathic narcolepsy. Narcolepsy type 1 is most likely an autoimmune disease, but the mechanisms have remained elusive.

Incidence of narcolepsy after H1N1 influenza and vaccinations: Systematic review and meta-analysis.

An increased incidence of narcolepsy was seen in many countries after the pandemic H1N1 influenza vaccination campaign in 2009-2010. The H1N1 vaccine - narcolepsy connection is based on observational studies that are prone to various biases, e.g., confounding by H1N1 infection, and ascertainment, recall and selection biases. A direct pathogenic link has, however, remained elusive. We conducted a systematic review and meta-analysis to analyze the magnitude of H1N1 vaccination related risk and to examine if there was any association with H1N1 infection itself. We searched all articles from PubMed, Web of Science and Scopus, and other relevant sources reporting the incidence and risk of post-vaccine narcolepsy. In our paper, we show that the risk appears to be limited to only one vaccine (Pandemrix®). During the first year after vaccination, the relative risk of narcolepsy was increased 5 to 14-fold in children and adolescents and 2 to 7-fold in adults. The vaccine attributable risk in children and adolescents was around 1 per 18,400 vaccine doses. Studies from Finland and Sweden also appear to demonstrate an extended risk of narcolepsy into the second year following vaccination, but such conclusions should be interpreted with a word of caution due to possible biases. Benefits of immunization outweigh the risk of vaccination-associated narcolepsy, which remains a rare disease.

Autonomic Nervous System Functioning Related to Nocturnal Sleep in Patients With Chronic Fatigue Syndrome Compared to Tired Controls.

STUDY OBJECTIVES: Autonomic nervous system (ANS) dysfunction is common in chronic fatigue syndrome (CFS). One of the main complaints in CFS is unrefreshing sleep. We aimed to study the nocturnal cardiac ANS in different sleep stages in patients filling the 2015 Institute of Medicine CFS diagnostic criteria. METHODS: In this case series study, the nocturnal heart rate variability and blood pressure (BP) variables in polysomnography were studied in groups of patients with CFS (n = 8) and tired controls (n = 8) aged 16-49 years. Five of the patients with CFS and controls were female. The heart rate variability and BP parameters and heart rate were studied in all sleep stages and wake. RESULTS: The amount of low-frequency oscillations of the electrocardiography R-R-intervals spectra (LF; predominantly reflects sympathetic activity) was higher for patients with CFS in all sleep stages compared to controls (P < .001). During wake, the amount of LF was lower for the patients with CFS (P < .05). The amount of high-frequency oscillations (HF; reflects parasympathetic activity) was lower in stage N3 sleep in the patients with CFS than for the controls (P < .0001), but, in total, HF was higher in patients with CFS (P < .001). Patients with CFS had higher overall nocturnal systolic and mean BP (P < .0001) and lower heart rate (P < .0001) than controls. No significant differences were found in sleep stage distributions. CONCLUSIONS: The results suggest a nocturnal dysfunction of the cardiac ANS in CFS, presenting as lower parasympathetic tone in deep sleep and higher sympathetic tone asleep.

Clinical course of H1N1-vaccine-related narcolepsy.

OBJECTIVE: To follow and analyze the clinical course and quality of life of Pandemrix H1N1-vaccine-related narcolepsy (pNT1). METHODS: Twenty-six drug-naïve confirmed pNT1 subjects completed Epworth Sleepiness Scale (ESS), Ullanlinna Narcolepsy Scale (UNS), Swiss Narcolepsy Scale (SNS), Rimon's Brief Depression scale (RDS), and WHO-5 Well-being index questionnaires near the disease onset and in a follow-up a minimum of two years later. The number of cataplexies and body mass index (BMI) were recorded. The effects of hypocretin-1 levels and sleep recording results were analyzed. The findings at the follow-up visit were compared with 25 non-vaccine-related type 1 narcolepsy (NT1) subjects. RESULTS: In pNT1, RDS score decreased significantly (mean 10.2, SD 4.7 vs mean 6.7, SD 4.5, p = 0.003). Median of BMI increased from 20.8 kg m(-2) to 23.4 kg m(-2), p <0.001. There were no significant differences in other sleep scores. However, deviation and range in questionnaire scores at the follow-up were wide. Subjects with very low or undetectable hypocretin-1 levels had worse scores in UNS (mean 26.4, SD 6.95 vs mean 19.1, SD 3.83, p = 0.006) and ESS (mean 17.9, SD = 4.29 vs mean 14.1, SD = 3.70, p = 0.047) than those with hypocretin-1 levels of 20-110 pg/mL. Most disabling symptoms were excessive daytime sleepiness and disturbed sleep. There were no significant differences between the scores in pNT1 and NT1. CONCLUSIONS: Clinical course of pNT1 is heterogeneous but the evolution of pNT1 seems similar to NT1. Lower hypocretin levels in pNT1 are associated with a more severe phenotype.

Predicting Obstructive Sleep Apnea with Periodic Snoring Sound Recorded at Home.

STUDY OBJECTIVES: The cost-effectiveness of diagnosing obstructive sleep apnea (OSA) could be improved by using a preliminary screening method among subjects with no suspicion of other sleep disorders. We aimed to evaluate the diagnostic value of periodic snoring sound recorded at home. METHODS: We included 211 subjects, aged 18-83 (130 men), who were referred to our laboratory for suspicion of OSA, and had a technically successful overnight polygraphy, measured with the Nox T3 Sleep Monitor (Nox Medical, Iceland) with a built-in microphone. We analyzed the percentage of periodic snoring during the home sleep apnea study. RESULTS: Apnea-hypopnea index (AHI) ranged from 0.1 to 116 events/h and the percentage of periodic snoring from 1% to 97%. We found a strong positive correlation (r = 0.727, p < 0.001) between periodic snoring and AHI. The correlation was slightly stronger among female, younger, and obese subjects. The best threshold value of the periodic snoring for predicting an AHI > 15 events/h with as high sensitivity as possible was found to be 15%. There, sensitivity was 93.3%, specificity 35.1%, and negative predictive value 75.0%. CONCLUSIONS: According to our results, it is possible to set a periodic snoring threshold (15% or more) for the subject to advance to further sleep studies. Together with medical history and prior to more expensive studies, measuring periodic snoring at home is a simple and useful method for predicting the probability of OSA, in particular among women who are often unaware of their apnea-related snoring.

Hypocretin-1 Levels Associate with Fragmented Sleep in Patients with Narcolepsy Type 1.

STUDY OBJECTIVES: We aimed to analyze nocturnal sleep characteristics of patients with narcolepsy type 1 (narcolepsy with cataplexy) measured by actigraphy in respect to cerebrospinal fluid hypocretin-1 levels of the same patients. METHODS: Actigraphy recording of 1-2 w and hypocretin-1 concentration analysis were done to thirty-six unmedicated patients, aged 7 to 63 y, 50% female. Twenty-six of them had hypocretin-1 levels under 30 pg/mL and the rest had levels of 31-79 pg/mL. RESULTS: According to actigraphy, patients with very low hypocretin levels had statistically significantly longer sleep latency (P = 0.033) and more fragmented sleep, indicated by both the number of immobile phases of 1 min (P = 0.020) and movement + fragmentation index (P = 0.049). There were no statistically significant differences in the actual sleep time or circadian rhythm parameters measured by actigraphy. CONCLUSIONS: Actigraphy gives additional information about the stabilization of sleep in patients with narcolepsy type 1. Very low hypocretin levels associate with more wake intruding into sleep.

Polysomnographic and actigraphic characteristics of patients with H1N1-vaccine-related and sporadic narcolepsy.

OBJECTIVE: After the pandemic H1N1 influenza ASO3-adjuvanted vaccine, Pandemrix©, was used in late 2009 and early 2010, the incidence of narcolepsy increased in many European countries. This incidence mainly increased in children and adolescents and, to a lesser degree, in adults. PATIENTS/METHODS: 125 unmedicated patients, aged 4 to 61 years, were included in this case-series study. Of these, 69 were diagnosed to have an H1N1-vaccine-related narcolepsy and 57 had sporadic narcolepsy. Most of these patients had: an actigraphy recording of 1-2 weeks, polysomnography, a Multiple Sleep Latency Test (MSLT), and cerebrospinal fluid hypocretin-1 concentration analysis. RESULTS: Patients with H1N1-vaccine-related narcolepsy had shorter diagnostic delays, lower periodic leg movement index during sleep, earlier sleep-wake rhythm, and were younger in age at diagnosis, compared with sporadic cases. They also had shorter sleep latency and more sleep onset REM periods in MSLT, but these results were strongly age-dependent. Actigraphy showed quantitatively less sleep and more sleep fragmentation than polysomnography. CONCLUSION: Regarding polysomnographic and actigraphic characteristics, there were no dramatic deviations between H1N1-vaccine-related and sporadic narcolepsy. Circadian rhythms indicated some interesting new findings with respect to the H1N1-vaccine-related disease. An actigraphy recording of 1-2 weeks is useful when studying the nocturnal aspects of narcolepsy and sleep-wake rhythms of narcoleptic patients.

The Oxford Sleep Resistance test (OSLER) and the Multiple Unprepared Reaction Time Test (MURT) detect vigilance modifications in sleep apnea patients.

STUDY OBJECTIVES: The Oxford Sleep Resistance Test (OSLER) is a behavioral test that measures a subject's ability to maintain wakefulness and assesses daytime vigilance. The multiple unprepared reaction time (MURT) test measures a subject's reaction time in response to a series of visual or audible stimuli. METHODS: We recruited 34 healthy controls in order to determine the normative data for MURT. Then we evaluated modifications in OSLER and MURT values in 192 patients who were referred for suspicion of sleep apnea. We performed OSLER (three 40-min sessions) and MURT (two 10-min sessions) tests at baseline. Of 173 treated OSA patients, 29 professional drivers were retested within six months of treatment. RESULTS: MURT values above 250 ms can be considered abnormal. The OSLER error index (the number of all errors divided by the duration of the session in hours) correlated statistically significantly with sleep latency, MURT time, and ESS. Treatment improved OSLER sleep latency from 33 min 4 s to 36 min 48 s, OSLER error index from 66/h to 26/h, and MURT time from 278 ms to 224 ms; these differences were statistically significant. CONCLUSIONS: OSLER and MURT tests are practical and reliable tools for measuring improvement in vigilance due to sleep apnea therapy in professional drivers.

A dose-ranging study of pramipexole for the symptomatic treatment of restless legs syndrome: polysomnographic evaluation of periodic leg movements and sleep disturbance.

OBJECTIVE: To evaluate, both polysomnographically and by subjective scales, the efficacy and safety profile of pramipexole for restless legs syndrome (RLS) via a 3-week, double-blind, placebo-controlled, parallel-group, dose-ranging study. METHODS: At baseline and after 3 weeks, periodic limb movements (PLM) and sleep parameters were assessed by polysomnography, and patients self-assessed their sleep disturbance and overall RLS severity using the international RLS study group rating scale (IRLS). Four pramipexole doses were evaluated: 0.125, 0.25, 0.50, and 0.75mg/d. Data from 107 patients were included in the intent-to-treat (ITT) analysis. RESULTS: For pramipexole recipients, the primary outcome measure, PLM per hour in bed asleep or awake (the PLM index, or PLMI), decreased by a median of -26.55 to -52.70 depending on dosage group, vs. -3.00 for placebo (p<0.01 or 0.001 for each group vs. placebo; Wilcoxon-Mann-Whitney test). Improvements in the secondary endpoints of PLM while asleep and while awake were also significantly superior for pramipexole. At 3 weeks, all pramipexole doses reduced the median for PLM while asleep to levels considered normal (<5PLM/h). Except for delta-sleep time and awakenings/arousals, sleep parameters remained unchanged or favored pramipexole. Median sleep latency was reduced by -5.00 to -11.75min in the pramipexole groups, vs. -2.00 for placebo (p<0.05 for all groups except 0.25mg/d). Median total sleep time increased by 25.75-66.75min, vs. 25.50 (p<0.05 for 0.50mg/d), and median time in stages 2-4/rapid eye movement (REM) sleep increased by 37.00-68.00min, vs. 26.75 (p<0.05 for 0.50mg/d). By subjective IRLS ratings, all pramipexole doses were significantly superior to placebo. Safety analysis demonstrated no dose-dependent increase in adverse events, and no drug-related increase in daytime somnolence was observed. CONCLUSIONS: Pramipexole is effective and well tolerated in RLS, most notably among objective measures, for reducing PLM and decreasing sleep latency. Although other sleep parameters showed lesser, usually insignificant change, patients' subjective ratings of RLS severity and sleep disturbance were significantly improved (p0.0023).

A proGDNF-related peptide BEP increases synaptic excitation in rat hippocampus.

The glial cell-derived neurotrophic factor (GDNF) precursor contains several putative sites for prohormone convertase-mediated excision of short peptides. Here, we show that one of the predicted peptides, named BEP (brain excitatory peptide), induces a substantial increase in the synaptic excitability in rat CA1 pyramidal neurons. The excitation is sensitive to N-ethylmaleimide, suggesting involvement of a G-protein-coupled receptor.

Open-label study of the long-term efficacy and safety of pramipexole in patients with Restless Legs Syndrome (extension of the PRELUDE study).

BACKGROUND AND OBJECTIVE: To demonstrate the long-term efficacy and safety of pramipexole for Restless Legs Syndrome (RLS) using physician and patient RLS ratings, along with subjective assays of sleep parameters, in a 26-week, open-label trial. PATIENTS AND METHODS: Among 107 Finnish adults with moderate to severe RLS, pramipexole initiated at 0.125 mg/day was titrated to a maximum 0.75 mg/day. Efficacy evaluations included the International RLS Study Group Rating Scale (IRLS), Patient Global Impression (PGI) scale, Clinical Global Impressions-Improvement (CGI-I) scale, Epworth Sleepiness Scale (ESS), and Short Form-36 (SF-36) Health Survey. Subjective Sleep Quality was assessed by patient ratings of sleep and morning tiredness. Safety was documented by Adverse Events reported in >5% of patients. RESULTS: The mean reduction in IRLS score was 73.5% (P<0.05). The IRLS responder rate, defined by score reduction of >or= 50%, was 81.3%. On the PGI scale, 89.7% of patients rated themselves as "very much" or "much" better. By CGI-I assessment, 94.8% of patients were considered either "very much" or "much" improved. Mean ESS score showed a modest but statistically significant reduction (P<0.05) within the normal range, indicating that long-term pramipexole did not increase daytime sleepiness. On the SF-36 all 8 domains showed improvement, 5 of them statistically significant (P<0.05) and 4 of these 5 (role-physical, bodily pain, vitality, and role-emotional) by >10 points on a 100-point scale. Subjective Sleep Quality also improved. The most frequent Adverse Events were influenza (17.8%), headache (15.0%), and fatigue (10.3%). CONCLUSION: Pramipexole is well tolerated and effective for long-term treatment of RLS.