Karl Kesper

Quantification of tonic and phasic muscle activity in REM sleep behavior disorder.

Summary: REM sleep behavior disorder (RBD) is characterized by excessive tone of the chin muscle and limb movement during sleep. In the past, quantification of increased muscle tone in REM sleep has been performed visually, using no stringent criteria. The aim of this study was to develop an automatic analysis, allowing the quantification of muscle activity and its amplitude for all sleep stages, with a focus on REM sleep in patients with RBD. Forty-eight patients (27 male, 21 female) with RBD were included in the analysis. Twenty-one had idiopathic RBD; 28 had narcolepsy plus RBD. Twenty-five patients without confirmed sleep disorder served as control subjects. The amplitude of the EMG was generated from the difference of the upper and lower envelope of the mentalis muscle recordings. By smoothing the amplitude curve, a threshold curve was defined. Any muscle activity beyond the threshold curve was defined as motor activity. The means of the motor activity per second were summarized statistically and calculated for each sleep stage. Due to variable distribution of REM sleep, the latter was assigned to respective quartiles of the recorded night. Muscle activity was defined according to a histogram as short-lasting (<0.5 second) and long-lasting (>0.5 second) activity. No difference in the distribution of REM sleep/quartile and mean muscle tone throughout the sleep cycle could be found within the RBD groups and control subjects. Muscle activity was in the range of 200 ms. No clusters or regular distribution of muscle activity were found. Long muscle activity in the group with manifest clinical RBD was significantly higher than in control subjects, whereas it was nonsignificantly higher in subclinical RBD. The correlation between the frequency of long muscle activity in REM sleep and age was highly significant only for patients with idiopathic RBD. Automatic analysis of muscle activity in sleep is a reliable, easy method that may easily be used in the evaluation for REM sleep behavior disorder, creating indices of muscle activity similar to the indices for sleep apnea or PLMS. Together with the overt behavior, the analyses provides an important tool to get a deeper insight into the pathophysiology of RBD. Long movements appear to represent the motor disinhibition in REM sleep more distinct than short movements. The positive correlation of age and increased motor activity in REM sleep in idiopathic RBD highlights the idea of age dependant motor disinhibition as a continuum of a neurodegenerative disorder, which in narcolepsy patients with RBD only seems to happen as a single temporal event at onset of the disorder.

Peripheral arterial tonometry, oximetry and actigraphy for ambulatory recording of sleep apnea

Autonomous nervous functions change with sleep stages and show characteristic changes associated with sleep disorders. Therefore, continuous monitoring of autonomous nervous functions during sleep can be used for diagnostic purposes. Recently, the peripheral arterial tonometry (PAT) has been introduced to determine peripheral arterial vascular tone on the finger being determined by sympathetic activity. We investigate a new ambulatory recording system which uses PAT, oximetry and actigraphy (Watch-PAT) in order to detect sleep apnea and arousal. The Watch-PAT is battery operated and attached to the wrist and has two finger sensors. Twenty-one patients with suspected sleep apnea were recorded with cardiorespiratory polysomnography and the new system in parallel. Seventeen recordings could be evaluated. The correlation for the apnea/hypopnea index derived from the sleep laboratory and the respiratory disturbance index derived from the Watch-PAT was r = 0.89 (p < 0.01) and between arousals and the respiratory disturbance index was r = 0.77 (p < 0.01). The correlation for the total sleep time compared between the two systems was r = 0.15 (n.s.). The Watch-PAT detects apneas and hypopneas with a reasonable reliability and it is very sensitive to arousals. The number of Watch-PAT events lies between the sum of apneas plus hypopneas and arousals. Arousals are not unique to apnea events and therefore the specifity of the Watch-PAT is limited. In conclusion, the Watch-PAT is well suited to perform therapy control studies in patients suffering from sleep apnea and being treated.

Detection of sleep disordered breathing by automated ECG analysis

Sleep related breathing disorders are a highly prevalent disease associated with increased risk of cardiovascular complications like chronic arterial hypertension, myocardial infarction or stroke. Gold standard diagnostics (polysomnography) are complex and expensive; the need for simplified diagnostics is therefore obvious. As the ECG can be easily conducted during the night, the detection of sleep related breathing disorders by ECG analysis provides an easy and cheap approach. Using a combination of well known biosignals processing algorithms, we trained the algorithm on 35 pre-scored overnight recordings. We then applied the algorithm on 35 control recordings, achieving a diagnostic accuracy of 77%. We believe that with further improvements in ECG analysis this algorithm can be used for screening diagnostics of obstructive sleep apnea.

Rotigotine's effect on PLM-associated blood pressure elevations in restless legs syndrome: An RCT

Objective: This double-blind, placebo-controlled, interventional trial was conducted to investigate the effects of rotigotine patch on periodic limb movement (PLM)–associated nocturnal systolic blood pressure (SBP) elevations. Methods: Patients with moderate to severe restless legs syndrome (RLS) were randomized to rotigotine (optimal dose [1–3 mg/24 h]) or placebo. Continuous beat-to-beat blood pressure (BP) assessments were performed during polysomnography at baseline and at the end of 4-week maintenance. Primary outcome was change in number of PLM-associated SBP elevations (defined as slope of linear regression ≥2.5 mm Hg/beat-to-beat interval over 5 consecutive heartbeats [≥10 mm Hg]). Additional outcomes were total SBP elevations, PLM-associated and total diastolic BP (DBP) elevations, periodic limb movements index (PLMI), and PLM in sleep arousal index (PLMSAI). Results: Of 81 randomized patients, 66 (37 rotigotine, 29 placebo) were included in efficacy assessments. PLM-associated SBP elevations were significantly reduced with rotigotine vs placebo (least squares mean treatment difference [95% confidence interval (CI)] −160.34 [−213.23 to −107.45]; p < 0.0001). Rotigotine-treated patients also had greater reduction vs placebo in total SBP elevations (−161.13 [−264.47 to −57.79]; p = 0.0028), PLM-associated elevations (−88.45 [−126.12 to −50.78]; p < 0.0001), and total DBP elevations (−93.81 [−168.45 to −19.16]; p = 0.0146), PLMI (−32.77 [−44.73 to −20.80]; p < 0.0001), and PLMSAI (−7.10 [−11.93 to −2.26]; p = 0.0047). Adverse events included nausea (rotigotine 23%; placebo 8%), headache (18% each), nasopharyngitis (18%; 8%), and fatigue (13%; 15%). Conclusions: Further investigation is required to determine whether reductions in nocturnal BP elevations observed with rotigotine might modify cardiovascular risk. Classification of evidence: This study provides Class I evidence that for patients with moderate to severe RLS, rotigotine at optimal dose (1–3 mg/24 h) reduced PLM-associated nocturnal SBP elevations.

FDG PET, Dopamine Transporter SPECT, and Olfaction: Combining Biomarkers in REM Sleep Behavior Disorder

Idiopathic REM sleep behavior disorder is a prodromal stage of Parkinsons disease and dementia with Lewy bodies. Hyposmia, reduced dopamine transporter binding, and expression of the brain metabolic PD‐related pattern were each associated with increased risk of conversion to PD. The objective of this study was to study the relationship between the PD‐related pattern, dopamine transporter binding, and olfaction in idiopathic REM sleep behavior disorder.

Significant association between systolic and diastolic blood pressure elevations and periodic limb movements in patients with idiopathic restless legs syndrome

OBJECTIVE A new and unique methodology was developed to evaluate the association between periodic limb movements (PLMs) and nocturnal blood pressure (BP) excursions in patients with restless legs syndrome (RLS). METHODS All data were collected at baseline of the ENCORE (Effects of Neupro on Cardiovascular Observations in Patients with Restless Legs Syndrome) study, a placebo-controlled polysomnographic study of rotigotine in patients with idiopathic RLS. Continuous beat-by-beat BP and heart rate assessments were performed during a full night of polysomnography. All BP elevations occurring with and without PLMs were systematically identified and analyzed. RESULTS Patients (n = 89) had a mean total of 508.9 ± 405.7 PLMs, 788.4 ± 261.9 systolic BP elevations, and 349.7 ± 242.9 diastolic BP elevations during the night. Higher time-adjusted frequencies of systolic BP elevations [mean difference (95% confidence interval, CI): 543.0 (487.2, I); p <0.0001] and diastolic BP elevations (205.8 (169.3, I); p <0.0001) were observed with PLMs than without PLMs. A peak in the frequency of PLM onset coincided with BP elevation onset. CONCLUSION Our methodology allowed the first evaluation of the total number of nocturnal PLM-associated BP elevations occurring in patients with RLS. Our data clearly indicate an interdependence between BP elevations and PLMs, and they have clinical relevance as BP variability is a potential cardiovascular risk factor.

Analysis of Sleep Fragmentation and Sleep Structure in Patients With Sleep Apnea and Normal Volunteers

Sleep disorders have a high prevalence. Sleep disorders are recognized first by the complaint of non-restorative sleep. A quantification of the disorder is done by the investigation in a sleep laboratory. The investigation in the sleep laboratory examines the EEG, EOG and EMG to derive sleep stages. This is a labor intensive sleep scoring after the polysomnography investigation. Usually the time course of the sleep stages is quantified in terms of percentages of stages related to total sleep time and the latencies for the individual stages. The additional feature of transitions between sleep stages and the disruption of sleep, which corresponds to periods of wakefulness during sleep are not evaluated systematically. We have evaluated these transitions using a statistical approach. We have detected systematic differences in the distributions of sleep stages and wake states during sleep. This differences were investigated in normal subjects and patients with sleep apnea. Then these differences were investigated in different species. The difference in the distributions can be explained only by fundamentally different regulation of sleep and wakefulness

Ambulatory Recording of Sleep Apnea Using Peripheral Arterial Tonometry

Sleep related breathing disorders are common. A reliable diagnosis with relatively simple and portable methods is still needed. One approach is to make use of autonomous nervous system changes which accompany disordered breathing during sleep. The peripheral arterial tonometry (PAT) determines the peripheral arterial vascular tone using a plethysmographic method on the finger. The peripheral arterial tone is modulated by sympathetic activity, by peripheral blood pressure, and by the peripheral resistance of the vessels. We investigate a new ambulatory recording device which uses PAT, oximetry and actigraphy in order to detect sleep apnea. For this purpose we performed a comparative study on 21 patients referred to our sleep laboratory due to suspected sleep apnea. Of these 17 valid recordings were compared. The Watch-PAT was used in parallel with cardiorespiratory polysomnography and the validity was determined. The new system is able to detect apneas and hypopneas with a high reliability (r=0.89). It is very sensitive to arousals (r=0.77). Since arousal are not specific to sleep apnea the specifity of the new system could not be finally clarified in this study. We conclude that the new system is very well suited to perform control studies in patients with sleep apnea which are under therapy and require regular follow-up investigations to maintain a high CPAP compliance.

Problems in automatic sleep scoring applied to sleep apnea

Automatic sleep analysis is used in the daily work of sleep centers working with digital polysomnography. Automatic sleep analysis has a limited accuracy in the sleep of healthy volunteers with approximately 80% conformance depending on definition. The problem of limited accuracy is even more severe in sleep disorders. Sleep apnea is a sleep disorder with a high prevalence which requires polysomnography for diagnosis and starting therapy. About 70% of all sleep studies in Germany are related to this disorder. The problems which occur with automatic sleep staging in sleep apnea are related to a large number of movement artifacts, repetitive arousal, severe sleep fragmentation with rapid changes of sleep stages, distorted slow wave sleep and distorted rapid-eye-movement (REM) sleep. These problems are discussed and the limitations of current visual analysis and automatic analysis are pointed out.

[Obstructive sleep apnea in neurological diseases: specially as a risk factor for stroke].

ZusammenfassungPatienten mit neurologischen Erkrankungen haben häufig schlafbezogene Atmungsstörungen als Begleiterkrankungen. Umgekehrt werden bei Patienten mit obstruktiver Schlafapnoe (OSA) gehäuft Erkrankungen des zerebro- und kardiovaskulären Systems gefunden. Epidemiologische Studien haben gezeigt, dass die unbehandelte OSA ein unabhängiger Risikofaktor für das Auftreten eines Schlaganfalls, einer arteriellen Hypertonie oder einer kardiovaskulären Erkrankung ist. Pathogenetisch bedeutsam sind apnoeassoziierte Faktoren wie die arterielle Hypertonie, das Auftreten von Vorhofflimmern, ein erhöhter Sympathikotonus, die intermittierende Hypoxie sowie eine vaskuläre Dysfunktion. Frühzeitige Diagnosestellung und Therapieeinleitung der schlafbezogenen Atmungsstörungen bei neurologischen Erkrankungen führen zu einem verbesserten Behandlungsergebnis der neurologischen Erkrankung und zu einer Reduktion zerebro- und kardiovaskulärer Folgeerkrankungen.SummaryNeurological diseases are frequently associated with sleep-related breathing disorders. In contrast patients with obstructive sleep apnea (OSA) suffer more often from cerebrovascular and cardiovascular diseases. Epidemiological studies have shown that OSA is common among patients with stroke, arterial hypertension or cardiovascular disease. In particular apnea-associated arterial hypertension, atrial fibrillation, activation of the sympathetic nervous system, recurrent hypoxemia and vascular inflammatory response should be considered as risk factors for the vascular system. Early diagnosis and treatment of sleep-related breathing disorders in neurological diseases are required to reduce the risk of subsequent cerebrovascular and cardiovascular diseases.Neurological diseases are frequently associated with sleep-related breathing disorders. In contrast patients with obstructive sleep apnea (OSA) suffer more often from cerebrovascular and cardiovascular diseases. Epidemiological studies have shown that OSA is common among patients with stroke, arterial hypertension or cardiovascular disease. In particular apnea-associated arterial hypertension, atrial fibrillation, activation of the sympathetic nervous system, recurrent hypoxemia and vascular inflammatory response should be considered as risk factors for the vascular system. Early diagnosis and treatment of sleep-related breathing disorders in neurological diseases are required to reduce the risk of subsequent cerebrovascular and cardiovascular diseases.