Michael Saletu

Structural and serum surrogate markers of cerebrovascular disease in obstructive sleep apnea (OSA): association of mild OSA with early atherosclerosis.

AbstractThere is increasing evidence of a causal interaction between obstructive sleep apnea (OSA) and cerebrovascular disease. The aim of the study was to elucidate the relationship between the polysomnographically (PSG) measured severity of OSA and carotid atherosclerosis determined by ultrasonography and serum surrogate markers. 147 patients (102 males, 45 females) referred to our sleep laboratory for evaluation of snoring and sleep–disordered breathing were investigated. Carotid atherosclerosis was evaluated by serum analysis of high-sensitivity C–reactive protein (hs–CRP) and fibrinogen and four sonographic indices: intima–media thickness (IMT) of the common carotid artery (CCA), IMT from bulb to internal carotid artery (Bulb–ICA), combined IMT measurements from all segments and a plaque score (PlaS). Pearson correlation analysis, intergroup comparison (ANOVA), covariance analysis and a multiple regression were performed to assess the association between surrogate markers and respiratory variables. 44 patients had no OSA (apnea–hypopnea index AHI < 5/h), 27 mild (AHI 5–15), 25 moderate (AHI 15–30) and 51 severe OSA (AHI > 30). After adjusting for potential confounders, significant differences between the controls and all three OSA groups were observed in the CCA–IMT (p = 0.032) and in the PlaS between the controls and the severe group (p = 0.034). Multiple regression revealed the AHI as an independent predictor of CCA–IMT (p = 0.001) and combined IMT (p = 0.001), whereas the percentage of total sleep time with an oxygen saturation below 90 % was associated with Bulb–ICA IMT (p = 0.018) and hs–CRP (p = 0.015). OSA is associated with higher surrogate levels of cerebrovascular disease. Even mild OSA seems to predispose to early atherosclerosis.

Low-resolution brain electromagnetic tomography (LORETA) identifies brain regions linked to psychometric performance under modafinil in narcolepsy

Low-resolution brain electromagnetic tomography (LORETA) showed a functional deterioration of the fronto-temporo-parietal network of the right hemispheric vigilance system in narcolepsy and a therapeutic effect of modafinil. The aim of this study was to determine the effects of modafinil on cognitive and thymopsychic variables in patients with narcolepsy and investigate whether neurophysiological vigilance changes correlate with cognitive and subjective vigilance alterations at the behavioral level. In a double-blind, placebo-controlled crossover design, EEG-LORETA and psychometric data were obtained during midmorning hours in 15 narcoleptics before and after 3 weeks of placebo or 400 mg modafinil. Cognitive investigations included the Pauli Test and complex reaction time. Thymopsychic/psychophysiological evaluation comprised drive, mood, affectivity, wakefulness, depression, anxiety, the Symptom Checklist 90 and critical flicker frequency. The Multiple Sleep Latency Test (MSLT) and the Epworth Sleepiness Scale (ESS) were performed too. Cognitive performance (Pauli Test) was significantly better after modafinil than after placebo. Concerning reaction time and thymopsychic variables, no significant differences were observed. Correlation analyses revealed that a decrease in prefrontal delta, theta and alpha-1 power correlated with an improvement in cognitive performance. Moreover, drowsiness was positively correlated with theta power in parietal and medial prefrontal regions and beta-1 and beta-2 power in occipital regions. A less significant correlation was observed between midmorning EEG LORETA and the MSLT; between EEG LORETA and the ESS, the correlation was even weaker. In conclusion, modafinil did not influence thymopsychic variables in narcolepsy, but it significantly improved cognitive performance, which may be related to medial prefrontal activity processes identified by LORETA.

Subjective Evaluation of Sleep Apnea Is Not Sufficient in Stroke Rehabilitation

Abstract Objective: Sleep apnea (SA) is common in stroke patients and is associated with poor functional outcome. Therefore, we studied the clinical value of the Berlin Questionnaire (BQ), a subjective screening method to detect stroke patients with SA in a neurorehabilitation care unit, and compared it with respirographic sleep studies. Another aim was to explore the association of SA with functional status in the subacute phase after stroke. Methods: Sixty-eight stroke patients were subjected to respirographic sleep studies to determine their apnea-hypopnea index (AHI). Subjective evaluation was performed by means of the BQ. Functional outcome was assessed by the Barthel Index (BI). Sensitivity and specificity of the BQ for detecting SA in stroke patients were calculated. Results: Respirographic sleep studies showed a high prevalence of moderate and severe sleep apnea in 56% of stroke patients. Sensitivity and specificity of the BQ for SA (AHI > 15) were 0.69 and 0.15, respectively. The area under the receiver operating characteristics (ROC) curve for detection of SA was 0.58. The AHI correlated significantly with the BI (r = -0.57, P ≤ .001). Conclusion: As the BQ demonstrated low diagnostic utility in stroke rehabilitation, screening for SA should not be based solely on clinical interviews. SA is linked to poor functional status in the subacute phase post stroke.

Modafinil improves information processing speed and increases energetic resources for orientation of attention in narcoleptics: Double-blind, placebo-controlled ERP studies with low-resolution brain electromagnetic tomography (LORETA)

BACKGROUND AND PURPOSE Recent neuroimaging studies in narcolepsy discovered significant gray matter loss in the right prefrontal and frontomesial cortex, a critical region for executive processing. In the present study, event-related potential (ERP) low-resolution brain electromagnetic tomography (LORETA) was used to investigate cognition before and after modafinil as compared with placebo. PATIENTS AND METHODS In a double-blind, placebo-controlled cross-over design, 15 patients were treated with a 3-week fixed titration scheme of modafinil and placebo. The Epworth Sleepiness Scale (ESS), Maintenance of Wakefulness Test (MWT) and auditory ERPs (odd-ball paradigm) were obtained before and after the 3 weeks of therapy. Latencies, amplitudes and LORETA sources were determined for standard (N1 and P2) and target (N2 and P300) ERP components. RESULTS The ESS score improved significantly from 15.4 (+/- 4.0) under placebo to 10.2 (+/- 4.1) under 400mg modafinil (p=0.004). In the MWT, latency to sleep increased nonsignificantly after modafinil treatment (11.9+/-6.9 versus 13.3+/-7.1 min). In the ERP, N2 and P300 latencies were shortened significantly. While ERP amplitudes showed only minor changes, LORETA revealed increased source strengths: for N1 in the left auditory cortex and for P300 in the medial and right dorsolateral prefrontal cortex. CONCLUSION LORETA revealed that modafinil improved information processing speed and increased energetic resources in prefrontal cortical regions, which is in agreement with other neuroimaging studies.

Sleepiness and atherosclerosis in sleep apnea

In their Atherosclerosis article in press (published online on ugust 19th) Drager et al. reported a high prevalence (63%) of bstructive sleep apnea (OSA) in patientswith a recent diagnosis of etabolic syndrome (MS) [1]. In amultiple linear regression analyis theapnoea–hyponea index (AHI), abdominal circumference, and ystolic blood pressure (R2 =0.42) were found to be independently ssociated with intima media thickness (IMT). An interesting findng is that in consecutive patients with MS, two thirds of patients ith OSA did not present any significant subjective daytime sleepiess evaluated by the Epworth Sleepiness Scale (ESS). I was rather surprised that the authors discussed their findings s consistentwith thoseof previous studies in the literature that did ot find an association between OSA and excessive daytime sleepiess in patients with established cardiovascular disease. However, t is not clear if subjects with a clinical event (e.g. stroke) were xcluded in their study. This comment in their discussion is evenmore interesting in the ight of the fact that we obtained quite different results published n a recent issue of the same journal that were not mentioned by he authors in their discussion [2]. In our study we investigated the relation between sleepiness valuated by the Epworth Sleepiness Scale and the classical risk actors of atherosclerosis, sleep-related respiratory variables, IMT nd surrogate markers of inflammation (hs-CRP and fibrinogen. leepiness increased with OSA severity and was further associted with all respiratory variables, obesity and diabetes. In our egression analysis age, systolic blood pressure and the ESS were ound tobe independentpredictors of IMT.After including the three espiratory variables AHI, sleep time spent with an oxygen saturaion <90%, the respiratory arousal index (post-polysomnographic

P0015 Low-resolution brain electromagnetic tomography (LORETA) identifies brain regions linked to psychometric performance under modafinil in narcolepsy

Low-resolution brain electromagnetic tomography (LORETA) showed a functional deterioration of the fronto-temporo-parietal network of the right hemispheric vigilance system in narcolepsy and a therapeutic effect of modafinil. The aim of this study was to determine the effects of modafinil on cognitive and thymopsychic variables in patients with narcolepsy and investigate whether neurophysiological vigilance changes correlate with cognitive and subjective vigilance alterations at the behavioral level. In a double-blind, placebo-controlled crossover design, EEG-LORETA and psychometric data were obtained during midmorning hours in 15 narcoleptics before and after 3 weeks of placebo or 400 mg modafinil. Cognitive investigations included the Pauli Test and complex reaction time. Thymopsychic/psychophysiological evaluation comprised drive, mood, affectivity, wakefulness, depression, anxiety, the Symptom Checklist 90 and critical flicker frequency. The Multiple Sleep Latency Test (MSLT) and the Epworth Sleepiness Scale (ESS) were performed too. Cognitive performance (Pauli Test) was significantly better after modafinil than after placebo. Concerning reaction time and thymopsychic variables, no significant differences were observed. Correlation analyses revealed that a decrease in prefrontal delta, theta and alpha-1 power correlated with an improvement in cognitive performance. Moreover, drowsiness was positively correlated with theta power in parietal and medial prefrontal regions and beta-1 and beta-2 power in occipital regions. A less significant correlation was observed between midmorning EEG LORETA and the MSLT; between EEG LORETA and the ESS, the correlation was even weaker. In conclusion, modafinil did not influence thymopsychic variables in narcolepsy, but it significantly improved cognitive performance, which may be related to medial prefrontal activity processes identified by LORETA.

Home Sleep Apnea Testing is a Feasible and Accurate Method to Diagnose Obstructive Sleep Apnea in Stroke Patients During In-Hospital Rehabilitation

STUDY OBJECTIVES To study the feasibility and accuracy of home sleep apnea testing (HSAT) in the diagnosis of obstructive sleep apnea (OSA) in a stroke rehabilitation unit. METHODS Stroke patients referred to a neurorehabilitation center underwent OSA screening by means of HSAT within the Home Polygraphic Recording with Telemedicine Monitoring for Diagnosis and Treatment of Sleep Apnea in Stroke, or HOPES study (ClinicalTrials.gov identifier: NCT02748681). Feasibility was determined by evaluating the acceptability of recording quality. Patients in whom moderate OSA was diagnosed subsequently underwent unattended polysomnography (PSG) confirmation. Accuracy was studied by comparing the respiratory event index (REI)/monitoring time (MT) of screening HSAT with the apnea-hypopnea index (AHI)/total sleep time (TST) obtained during subsequent PSG with Bland-Altman plots. The influence of PSG-evaluated wake time and arousals on OSA classification was studied by comparing the AHI and REI of the same night. RESULTS A total of 265 patients (58 ± 9 years, 70% male) were screened. A total of 92% of HSAT studies were performed with acceptable recording quality. In total, 33 patients (63 ± 5 years, 58% male) with moderate OSA (REI ≥ 15 to < 30 events/h) were included in the HSAT/PSG comparison. The Bland-Altman plot shows acceptable limits of agreement from -19.5 to +16.4, with a mean difference of -1.33. The REI detected in the PSG night demonstrated no significant differences to the AHI and a high correlation (r = .97; P < .001). The 95% confidence interval of the Bland-Altman plots varied from -7.61 to +4.80. CONCLUSIONS These findings confirm a good feasibility and sufficient accuracy of HSAT attached in a stroke rehabilitation unit. Therefore, the authors suggest that American Academy of Sleep Medicine recommendations for HSAT should include stroke patients.

Home polygraphic recording with telemedicine monitoring for diagnosis and treatment of sleep apnoea in stroke (HOPES Study): study protocol for a single-blind, randomised controlled trial

Introduction Meta-analyses report that more than 50% of patients who had a stroke suffer from moderate to severe sleep apnoea (SA), with adherence rates to positive airway pressure (PAP) therapy of only 30%. The primary objective of this study is to determine whether PAP adherence in patients who had a stroke with obstructive sleep apnoea (OSA) can be improved by a PAP training strategy during inhospital rehabilitation combined with a telemedicine monitoring system after discharge. Further objectives are (1) to compare the validity of a non-attended level-III polygraphy with that of a level-II polysomnography (PSG) in the diagnosis of SA, (2) to compare the validity of an apnoea-hypopnoea index (AHI) yielded by the PAP device with that obtained during PSG, (3) to determine changes in nocturnal systolic blood pressure (BP) due to PAP therapy with the pulse transit time (PTT) method and (4) to assess the impact of telemonitored PAP therapy on neurorehabilitation outcome parameters. Methods and analyses Single-blind, monocentre, randomised controlled trial. It includes 55 patients who had a subacute stroke, aged 19–70 years, with moderate to severe OSA, who have undergone successful PAP training and titration at the neurorehabilitation unit. Patients are randomised to either a standard care group or a telemedicine group. PAP adherence, sleep and respiratory variables, subjective and objective sleep quality, systolic BP (PTT method) of the two groups are compared after 3 months and 1 year as well as cognitive and motor neurorehabilitation outcome parameters, quality of life and PAP satisfaction. Additionally, intranight AHI/total sleep time versus AHI/time in bed and night-to-night variability of the AHI are assessed. Ethics and dissemination Before screening, all participants will be provided with oral and written information. The study will be disseminated by peer-reviewed publications and conference presentations. Trial registration number NCT02748681; Pre-results.

YIP06 [O0012] Is excessive daytime sleepiness a predictor of carotid atherosclerosis in sleep apnea?

OBJECTIVE To elucidate the relationship between excessive daytime sleepiness (EDS) in obstructive sleep apnea (OSA) and carotid atherosclerosis determined by ultrasonography and serum surrogate markers. METHODS One hundred and forty-seven patients (102 males) with snoring and sleep-disordered breathing were investigated. Carotid atherosclerosis was evaluated by serum analysis of high-sensitivity C-reactive protein and fibrinogen and four sonographic indices: intima media thickness (IMT) of the common carotid artery (CCA), IMT from the bulb to the internal carotid artery (ICA), combined IMT measurements from all segments and a plaque score. EDS was assessed by the Epworth Sleepiness Scale (ESS). Pearson correlation analysis, intergroup comparison (ANOVA) and two multiple regression models explored associations between confounders, surrogate markers and EDS. RESULTS Forty-four patients had no OSA (apnea-hypopnea index AHI<5h(-1)), 27 mild (5-15), 25 moderate (15-30) and 51 severe OSA (>30). The ESS significantly distinguished severe OSA from non-OSA patients (p=0.003). It showed significant correlations with the BMI, HbA1c, systolic RR, the AHI, sleep time spent with an oxygen saturation <90%, the respiratory arousal index, IMT of the CCA and combined IMT measurements, but no correlation with serum markers. The ESS was found to be an independent predictor of CCA-IMT in the pre-polysomnographic multiple regression model (p=0.008), but not in the post-polysomnographic model after including respiratory variables. CONCLUSION EDS is associated with obesity, diabetes and all respiratory variables in OSA patients and may serve as an independent predictor of carotid atherosclerosis before polysomnography.

Diagnostik und Therapie des Restless-Legs-Syndroms in der Arztpraxis

SummaryBackgroundRestless legs syndrome (RLS) is a movement and sleep disorder with leg dysesthesias with a high prevalence (9–18% in Austria).Aim of the studyDetermination of frequency, diagnosis and therapy of RLS in general practitioner and specialist offices.MethodsTelephone survey of a random sample of 120 general practitioners, 100 neurologists and 80 specialists in internal medicine.Results69% of the whole sample of doctors reported seeing 1 to 10 RLS patients, but in proportion to the prevalence of these two conditions fewer cases of RLS than of Parkinson’s disease are treated. In all three groups of doctors, 84% consider the 4 key symptoms (urge to move the legs accompanied or caused by dysesthesia; worsening of symptoms at rest or inactivity; relief by activity; worsening of symptoms in the evening/at night) the most important diagnostic criteria for RLS, followed by a complaint of disturbed sleep (75%), daytime tiredness (43%) and dopaminergic responsiveness in a therapeutic trial (29%). 83% of general practitioners and 86% of medical specialists refer their RLS patients to a neurologist, 19% to a polysomnographic examination. 75% of doctors decide for pharmacological treatment of RLS, 18% for psychotherapy, 15% for household remedies. 54% of all doctors (70% of the neurologists, 68% of the GPs, 48% of the medical specialists) prescribe dopamine agonists. L-Dopa is used by 49% (61% of the neurologists, 42% of the GPs, 44% of the medical specialists). 17% prescribe GABAergic drugs, 6% opiates. 51% would be highly interested in obtaining a drug specifically registered for the treatment of RLS.ConclusionRLS is not as well known as Parkinson’s disease. Thus providing doctors with relevant information and further education programs on this subject seems desirable. In Austrian doctors’ offices the diagnosis of RLS is usually obtained clinically on the basis of the 4 key symptoms. Patients suffering from insomnia of multifactorial pathogenesis should be referred to an outpatient clinic for sleep disorders with an associated sleep laboratory. Especially neurologists and GPs consider dopamine agonists the treatment of first choice, closely followed by L-Dopa.ZusammenfassungHintergrundDas Restless-Legs-Syndrom (RLS) ist eine mit Missempfindungen und Schlafstörungen einhergehende Bewegungsstörung mit hoher Prävalenz (in Österreich 9–18%).ZielsetzungErhebung von Häufiqkelt, Diagnose und Therapie des RLS in der Praxis.MethodikÖsterreichweite Befragung mittels eines telefonischen Interviews bei nach dem Zufallsprinzip ausqewählten 120 niedergelassenen Fachärzten für AIIgemeinmedizin, 100 für Neurologie und 80 für Innere Medizin.Resultate69% der Gesamtärztestichprobe betreuen zwischen 1 und 10 RLS-Patienten, doch werden in Relation zur Prävalenz weniger RLS- als M. Parkinson-Patienten behandelt. Für 84% der Ärzte sind die 4 Leitsymptome (Bewegungsdrang der Extremitäten mit Dysästhesien, Auftreten oder Verstärkung der Symptome in Ruhe, Besserung durch Bewegung, abendliche/nächtliche Symptomverschlechterung) das wichtigsten Kriterium für die Diagnose des RLS, gefolgt von der Klage über Schlafstörunqen (75%), Tagesmüdigkeit (43%) und dopaminergem Ansprechen im Therapieversuch (29%). 83% der Allgemeinmediziner und 86% der Internisten überweisen ihre RLS-Patienten zum Neurologen, 23% zur Polysomnographie. 75% der Ärzte setzen Medikamente ein, 18% Psychotherapie, 15% Hausmittel. 54% der Ärzte (70% der Neurologen, 68% der Aligemeinmediziner, 48% der Internisten) verschreiben Dopaminagonisten zur medikarnentösen Therapie des RLS. L-Dopa wird von 49% der Ärzte verwendet (61% der Neurologen, 42% der AlIgemeinmediziner, 44% der Internisten). 17% der Ärzte verordnen GABAerge. Präparate: 6% therapieren RLS mit Opiaten. 51% bekunden großes Interesse an einer spezifischen Zulassung eines Präparates für RLS.KonklusionDas Krankheitsbild RLS verfügt im Vergleich zum M. Parkinson noch über einen geringen Bekanntheitsgrad. Laufende Information der drei Ärztezielgruppen und Fortbildung zu diesem Thema erscheint daher erstrebenswert. Die Diagnose des RLS wird in der österreichischen Praxis anhand der 4 Leitsymptome klinisch gestellt. Bei multifaktorieller Genese einer Insomnie sollte die Überweisung an eine Spezialambulanz für Schlafmedizin mit Schlaflabor erfolgen. Als RLS-Therapie erster Wahl liegen die Dopaminagonisten insbesondere bei Neurologen und Allgemeinmedizinern knapp vor L-Dopa.