Insomnia in neurological diseases.

Insomnia is defined as difficulties of initiating and maintaining sleep, early awakening and poor subjective sleep quality despite adequate opportunity and circumstances for sleep with impairment of daytime performance. These components of insomnia - namely persistent sleep difficulties despite of adequate sleep opportunity resulting in daytime dysfunction - appear secondary or co-morbid to neurological diseases. Comorbid insomnia originates from neurodegenerative, inflammatory, traumatic or ischemic changes in sleep regulating brainstem and hypothalamic nuclei with consecutive changes of neurotransmitters. Symptoms of neurological disorders (i.e motor deficits), co-morbidities (i.e. pain, depression, anxiety) and some disease-specific pharmaceuticals may cause insomnia and/or other sleep problems.This guideline focuses on insomnias in headaches, neurodegenerative movement disorders, multiple sclerosis, traumatic brain injury, epilepsies, stroke, neuromuscular disease and dementia.The most important new recommendations are: Cognitive behavioral therapy (CBTi) is recommended to treat acute and chronic insomnia in headache patients. Insomnia is one of the most frequent sleep complaints in neurodegenerative movement disorders. Patients may benefit from CBTi, antidepressants (trazodone, doxepin), melatonin and gaba-agonists. Insomnia is a frequent precursor of MS symptoms by up to 10 years. CBTi is recommended in patients with MS, traumatic brain injury and. Melatonin may improve insomnia symptoms in children with epilepsies. Patients with insomnia after stroke can be treated with benzodiazepine receptor agonists and sedating antidepressants. For patients with dementia suffering from insomnia trazodone, light therapy and physical exercise are recommended.

Proactive telemedicine monitoring of sleep apnea treatment improves adherence in people with stroke- a randomized controlled trial (HOPES study).

OBJECTIVE: Obstructive sleep apnea (OSA) impacts stroke recovery and outcome negatively. Although its identification and treatment are part of the current stroke guidelines, standard management with positive airway pressure (PAP) therapy is not routinely performed and adherence rates are very low. The purpose of this study was to determine whether PAP adherence can be improved by a PAP training strategy during in-hospital rehabilitation combined with a telemedicine monitoring system after discharge. METHODS: In this study, we performed a controlled trial (RCT) on standard PAP treatment (SG) as compared with proactive telemonitored PAP treatment (TG). After three months and one year, PAP adherence (min of use per day) and clinical outcome variables were compared. RESULTS: In 33 (47.1%) out of 70 patients diagnosed with therapy-relevant OSA [70% male, 62 (5) years, body mass index (BMI) 30 (4) kg/m2, Barthel Index 90 (20), NIHSS 3 (3)] in-hospital PAP titration was performed. Subsequently, they were randomized to SG or TG. Drop-out rates after three months and after one year were 12% and 30%, respectively, with no differences between the groups. After three months, telemonitored patients used the PAP device 76 min longer per night (SG: 299 (76), TG: 375 (86) minutes per night; p = 0.017), after one year there was no significant difference. CONCLUSION: People with stroke and therapy-relevant OSA who accept PAP therapy should receive additional telemedicine monitoring at least for three months. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov; Unique identifier: NCT02748681.

[Strangulation as scenic behavior. A case report of a pseudosuicide in the course of a NREM-parasomnia]. / Strangulation als szenische Handlung. Ein Fallbericht über einen Pseudosuizidversuch im Verlauf einer NREM-Parasomnie.

It is generally accepted, that sleepwalkers show complex behaviors leading to non-intended consequences. It is not unusual that these persons are thereby injured. However, sporadically a bizarre endangering of themselves or others is reported also, which ranges from homicide of the life partner to accidental (pseudo-)suicide.In this article, we report on a 28year-old man who unexpectedly attempted to hang himself by a whip at night. We discuss the reasons, why this bizarre act should actually be taken as a scenic behavior in the course of a NREM-parasomnia, and the difficulty to proof this claim.

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.

Subjective evaluation of sleep apnea is not sufficient in stroke rehabilitation.

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.

Comparative placebo-controlled polysomnographic and psychometric studies on the acute effects of gabapentin versus ropinirole in restless legs syndrome.

The aim of the present placebo-controlled sleep laboratory study was to compare the acute effects of gabapentin (GBT) and ropinirole (ROP) in restless legs syndrome (RLS). In a parallel-group design, 40 RLS patients received 300 mg GBT and another 40 patients 0.5 mg ROP as compared with placebo. Polysomnographic and psychometric measures were obtained in three sleep laboratory nights (screening/placebo/drug). Statistics included a Wilcoxon test for differences between drug and placebo and a U test for inter-group differences. Sleep efficiency and latency were found significantly improved after GBT, while they remained unchanged after ROP, with significant inter-drug differences. Sleep architecture showed oppositional changes after the two drugs: While GBT decreased S1, increased slow-wave sleep and SREM and shortened REM latency, ROP increased S2, decreased slow-wave sleep and SREM and increased REM latency. Periodic leg movements (PLM) showed a significantly greater decrease after ROP (-73%) than after GBT (-35%). Subjective sleep quality improved significantly only after GBT; mental performance improved after both drugs with no inter-drug differences. In conclusion, the dopamine agonist ROP showed acute therapeutic efficacy with regard to PLM measures only, whereas GBT had a less pronounced effect on these measures, but improved objective and subjective sleep and awakening quality as compared with both placebo and ROP. Differential acute drug effects may serve as prognostic indicators of therapeutic response of individual patients.

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.

Event-related-potential low-resolution brain electromagnetic tomography (ERP-LORETA) suggests decreased energetic resources for cognitive processing in narcolepsy.

OBJECTIVE: Event-related potentials (ERPs) are sensitive measures of both perceptual and cognitive processes. The aim of the present study was to identify brain regions involved in the processes of cognitive dysfunction in narcolepsy by means of ERP tomography. METHODS: In 17 drug-free patients with narcolepsy and 17 controls, ERPs were recorded (auditory odd-ball paradigm). Latencies, amplitudes and LORETA sources were determined for standard (N1 and P2) and target (N2 and P300) ERP components. Psychometry included measures of mental performance, affect and critical flicker fusion frequency (CFF). RESULTS: In the ERPs patients demonstrated delayed cognitive N2 and P300 components and reduced amplitudes in midline regions, while N1 and P2 components did not differ from controls. LORETA suggested reduced P300 sources bilaterally in the precuneus, the anterior and posterior cingulate gyri, the ventrolateral prefrontal cortex and the parahippocampal gyrus. In psychometry, patients demonstrated deteriorated mood, increased trait anxiety, decreased CFF and a trend toward reduced general verbal memory and psychomotor activity. CONCLUSIONS: Narcoleptic patients showed prolonged information processing, as indexed by N2 and P300 latencies and decreased energetic resources for cognitive processing. SIGNIFICANCE: Electrophysiological aberrations in brain areas related to the 'executive attention network' and the 'limbic system' may contribute to a deterioration in mental performance and mood at the behavioral level.

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.

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.

Prevalence of movement disorders in men and women aged 50-89 years (Bruneck Study cohort): a population-based study.

BACKGROUND: There is emerging awareness that movement disorders rank among the most common neurological diseases. However, the overall burden of these disorders in the general community is not well defined. We sought to assess the prevalence of all common categories of movement disorders in a population, accounting for sex differences and age trends. METHODS: As part of an ongoing prospective population-based study of carotid atherosclerosis and stroke risk (the Bruneck Study), a total of 706 men and women aged 50-89 years underwent a thorough neurological assessment. The diagnosis of movement disorders and ratings for disease severity were based on standard criteria and scales. Prevalences were estimated from logistic regression models (regression-smoothed rates) and standardised to the age and sex structure of the general community. FINDINGS: The prevalence of all common categories of movement disorders was 28.0% (95% CI 25.9-30.1). Proportions in men (27.6% [95% CI 24.5-30.7]) and women (28.3% [25.5-31.2]) were closely similar and sharply increased with age (from 18.5% [15.0-22.0] in 50-59-year olds to 51.3% [44.9-57.7] in 80-89-year olds). Almost half of all patients (90/214) had moderate-to-severe disease expression, but only 7.0% (15/214) received standard drug treatment. Prevalence of tremor was 14.5%, followed by restless legs syndrome (10.8%), parkinsonism (7%), primary dystonia and secondary dystonia (1.8%), and chorea and tics (<1% each). A fifth of all movement disorders were diagnosed to be probably drug-induced. INTERPRETATION: There is a high prevalence of and substantial under-recognition and under-treatment of movement disorders in the general community.

EEG-mapping differences between narcolepsy patients and controls and subsequent double-blind, placebo-controlled studies with modafinil.

The aim of the present study was to investigate the role of EEG mapping as an objective and quantitative measure of vigilance in untreated and modafinil-treated narcoleptics, and compare it with the conventional neurophysiological method of the Multiple Sleep Latency Test (MSLT) and the subjective Epworth Sleepiness Scale (ESS). In 16 drug-free narcoleptics and 16 normal controls a baseline 3-min vigilance-controlled EEG (V-EEG) and a 4-min resting EEG (R-EEG) were recorded during midmorning hours. Thereafter, in a double-blind, placebo-controlled crossover design, patients were treated with a 3-week fixed titration of modafinil (200, 300, 400 mg) and placebo. EEG-mapping, MSLT and ESS measures were obtained before and at the end of the third week of therapy. Statistical overall analysis by means of the omnibus significance test demonstrated significant EEG differences between untreated patients and controls in the resting condition only (R-EEG). Subsequent univariate analysis revealed an increase in absolute and relative theta power, a decrease in alpha-2 and beta power as well as a slowing of the dominant frequency and the centroids of the alpha, beta and total power spectrum and thus objectified a vigilance decrement in narcolepsy. Modafinil 400 mg/d significantly improved vigilance as compared with placebo (p < or = 0.01), inducing changes opposite to the aforementioned baseline differences (key-lock principle). The MSLT and the ESS also improved under modafinil as compared with placebo, but changes were less consistent. Spearman rank correlations revealed the highest correlations between EEG mapping and the ESS, followed by those between EEG mapping and the MSLT, while the lowest correlation was found between the MSLT and the ESS. In conclusion, EEG mapping is a valuable instrument for measuring vigilance decrements in narcolepsy and their improvement under psychostimulant treatment.

[Diagnosis and therapy of restless legs syndrome in the doctor's office]. / Diagnostik und Therapie des Restless-Legs-Syndroms in der Arztpraxis.

BACKGROUND: Restless legs syndrome (RLS) is a movement and sleep disorder with leg dysesthesias with a high prevalence (9-18% in Austria). AIM OF THE STUDY: Determination of frequency, diagnosis and therapy of RLS in general practitioner and specialist offices. METHODS: Telephone survey of a random sample of 120 general practitioners, 100 neurologists and 80 specialists in internal medicine. RESULTS: 69% 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. CONCLUSION: RLS 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.

EEG mapping in patients with restless legs syndrome as compared with normal controls.

Restless legs syndrome (RLS) is a sensorimotor movement and sleep disorder with a high prevalence. While the sleep disturbance due to RLS has been studied quite well polysomnographically, little is known about the electrophysiological function during daytime. The aim of the present study was to investigate the diurnal quantitative EEG and clinical symptomatology in 33 drug-free RLS patients as compared with age- and sex-matched normal controls. Investigations comprised brain mapping of the vigilance-controlled EEG as well as completion of the Zung Self-Rating Depression Scale, the Zung Self-Rating Anxiety Scale, the Quality of Life Index, the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale for evaluation of clinical symptomatology. Statistical analysis demonstrated an increase in absolute delta and absolute and relative alpha-2 power, a decrease in absolute and relative alpha-1 power, an acceleration of the dominant frequency and the alpha centroid, and a slowing of the delta/theta centroid, as well as a non-significant attenuation in total power. These findings are characteristic of dissociated vigilance changes described in depression. Indeed, RLS patients demonstrated significantly higher depression and anxiety scores, lower quality of life and deteriorated sleep quality. The score of the Epworth Sleepiness Scale was not elevated, in contrast to the increased daytime sleepiness observed in other highly prevalent organic sleep disorders (e.g. sleep apnea). In conclusion, daytime EEG mapping revealed neurophysiological correlates of depression in RLS, which was confirmed by self-ratings at the symptomatological level.