Adherence to wakefulness promoting medication in patients with narcolepsy

ObjectiveNarcolepsy management usually requires lifelong pharmacotherapy. However, we know little about adherence to prescribed treatment in narcolepsy. We assessed adherence to wakefulness-promoting agents in narcolepsy patients.Patients and methodsWe retrospectively assessed adherence to wakefulness promoting medication in patients with narcolepsy using the Medicines Possession Ratio (MPR). Three levels of adherence were defined: poor (≤50%), intermediate (51–79%), and good (≥80%). Refractory daytime sleepiness was defined as an Epworth sleepiness scale (ESS) score >12 despite trialling at least three wakefulness-promoting agents. We compared demographic and clinical factors, and prescribed medications between patients, stratified by levels of adherence, as well as by presence or not of refractory sleepiness.ResultsWe included 116 patients with narcolepsy (54.3% female, mean age 39.4 (±14) years). In sum, 93 (80.2%) patients had a diagnosis of narcolepsy type 1 (NT1), and 23 (19.8%) of type 2 (NT2). Suboptimal symptom control was common: 39.8% had refractory sleepiness, and 47.3% of NT1 patients had persistent cataplexy. Good adherence was seen in only 55.2% of patients, while 12.9% were intermediately and 31.9% poorly adherent. Patients with poor adherence were more likely to have a diagnosis of NT2, but adherence did not vary according to gender, age, the presence of psychiatric co-morbidity, or the presence of apparent intractable symptoms. Levels of good adherence to therapy were no better in patients with refractory sleepiness than in those with satisfactory symptom control (56.5% vs 54.3%; p = 0.81).ConclusionSuboptimal adherence to prescribed therapy is common in narcolepsy patients, including those with apparent intractable symptoms, and particularly in patients with NT2.     

Parsing the antidepressant effects of non-invasive brain stimulation and pharmacotherapy: A symptom clustering approach on ELECT-TDCS

BackgroundTranscranial direct current stimulation (tDCS) presents small antidepressant efficacy at group level and considerable inter-individual variability of response. Its heterogeneous effects bring the need to investigate whether specific groups of patients submitted to tDCS could present comparable or larger improvement compared to pharmacotherapy. Aggregate measurements might be insufficient to address its effects.Objective/Hypothesis: To determine the efficacy of tDCS, compared to pharmacotherapy and placebo, in depressive symptom clusters.MethodsData from ELECT-TDCS (Escitalopram versus Electrical Direct-Current Therapy for Treating Depression Clinical Study, ClinicalTrials.gov, NCT01894815), in which antidepressant-free, depressed patients were randomized to receive 22 bifrontal tDCS (2 mA, 30 min) sessions (n = 94), escitalopram 20 mg/day (n = 91), or placebo (n = 60) over 10 weeks. Agglomerative hierarchical clustering identified “sleep/insomnia”, “core depressive”, “guilt/anxiety”, and “atypical” clusters that were the dependent measure. Trajectories were estimated using linear mixed regression models. Effect sizes are expressed in raw HAM-D units. P-values were adjusted for multiple comparisons.ResultsFor core depressive symptoms, escitalopram was superior to tDCS (ES = −0.56; CI_95% = -0.94 to −0.17, p = .009), which was superior to placebo (ES = 0.49; CI_95% = 0.06 to 0.92, p = .042). TDCS but not escitalopram was superior to placebo in sleep/insomnia symptoms (ES = 0.87; CI_95% = 0.22 to 1.52, p = .015). Escitalopram but not tDCS was superior to placebo in guilt/anxiety symptoms (ES = 1.66; CI_95% = 0.58 to 2.75, p = .006). No active intervention was superior to placebo for atypical symptoms.ConclusionsPharmacotherapy and non-invasive brain stimulation produce distinct effects in depressive symptoms. TDCS or escitalopram could be chosen according to specific clusters of symptoms for a bigger response.Trial registrationClinicalTrials.gov, NCT01894815     

Association of visceral adiposity and systemic inflammation with sleep disordered breathing in normal weight,never obese adolescents

Objective/backgroundWhile obesity is a known risk factor for sleep disordered breathing (SDB), a large proportion of children with SDB are not overweight as per body mass index percentile (BMI%) criteria. This study aimed to examine whether premorbid or concurrent adiposity phenotypes and inflammation are associated with SDB in normal weight youth.Patients/methodsA total of 242 persistently non-overweight (BMI%<85) subjects from the Penn State Child Cohort (PSCC, N = 421, 5-12 y at baseline and 12-23 y at follow-up), were studied. The apnea/hypopnea index (AHI) was ascertained via polysomnography (PSG) at both time points. At follow-up, a dual-energy X-ray absorptiometry (DXA) scan assessed android and gynoid distribution and subcutaneous (SAT) and visceral (VAT) adiposity composition, while a fasting blood draw was assayed for C-reactive protein (CRP) and interleukin-6 (IL-6) levels. Multivariable linear regression models with AHI at follow-up as primary outcome were adjusted for sex, race, adenotonsillectomy, age and AHI at baseline.Results and conclusionsIncreased waist circumference (β = 0.227, p = 0.001) at baseline, but not BMI%, neck or hip circumference, was significantly associated with a higher AHI at follow-up. VAT (β = 0.309, p < 0.001), IL-6 (β = 0.243, p < 0.001), SAT (β = 0.235, p = 0.013), CRP (β = 0.221, p = 0.001), and an android distribution (β = 0.196, p = 0.003) at follow-up were significantly associated with a higher AHI at follow-up. Childhood central adiposity predicts SDB in adolescence, even in individuals who have never been overweight since childhood as per BMI criteria. Visceral adiposity and inflammation are concurrent to adolescent SDB, which supports the clinical utility of these biomarkers in predicting its associated cardiometabolic risk.     

Academic and professional paths of narcoleptic patients: the Narcowork study

Objective/BackgroundTo study educational and professional pathways of narcoleptic patients and examine demographic, disease-related and environmental factors associated with a better academic and professional prognosis.Patients/MethodsIn sum, 69 narcoleptic patients (51 narcolepsy type 1 and 18 narcolepsy type 2, age 42.5 ± 18.2 years) were enrolled in this pilot monocentric cross-sectional study with a comparison group (80 age- and sex-matched controls) between October 2017 and July 2018 in Lyon Center for Sleep Medicine. They completed questionnaires about their academic and professional trajectories and specific scales of quality of life (EuroQol quality of life scale EQ-5D-3L), depression (beck depression inventory, BDI), sleepiness (Epworth Sleepiness Scale, ESS) and narcoleptic symptoms severity (narcolepsy severity scale, NSS).ResultsNo difference in grade repetition or final obtained diploma was observed between patients and controls, but patients evaluated their academic curricula as more difficult (45.5% vs 16.9%, p = 0.0007), complained for more attentional deficits (75% vs 22.1%, p < 0.0001), and had needed more educational reorientation (28.6% vs 9.9%, p = 0.01). Even if no difference was observed in occupational category and professional status, patients expressed significantly less satisfaction about their work. Patients had more signs of depression [OR severe depression = 4.4 (1.6–12.6), p = 0.02] and their quality of life was significantly decreased (67.3 ± 18.4 vs 80.6 ± 13.2, p = 0.0007) as compared to controls. Multivariate analysis showed that a more favorable professional career was associated with a better quality of life.ConclusionsEducational and professional pathways do not seem to be significantly impaired in narcoleptic patients, but their experience and quality of life are affected. These findings may allow to reassure patients and should lead to a more comprehensive management of the disease.Clinical trial registrationNarcowork, https://clinicaltrials.gov/ct2/show/NCT03173378, N° NCT03173378.     

Social jetlag is associated with obesity-related outcomes in 9–11-year-old children,independent of other sleep characteristics

IntroductionSocial jetlag has been reported to predict obesity-related indices, independent of sleep duration, with associations in female adolescents but not males. However, such sex-specific relationships have not been investigated in pre-adolescents.ObjectivesTo examine: (i) the relationships between sleep characteristics, including social jetlag, and obesity-related outcomes during childhood, and (ii) whether these relationships are moderated by sex.MethodsThis cross-sectional study included 381 children aged 9–11 years (49.6% female). Average sleep duration, social jetlag, and physical activity were assessed via wrist-worn accelerometry. Sleep disturbances were quantified from the Children's Sleep Habits Questionnaire. Obesity-related outcomes included age-specific body mass index Z-scores (zBMI) and waist-to-height ratio. Additionally % fat, total fat mass, and fat mass index were assessed via bioelectrical impedance analysis. Linear mixed models that nested children within schools were used to identify relationships among sleep characteristics and obesity-related outcomes.ResultsPositive associations between social jetlag with zBMI, % fat, and fat mass index were seen in univariable and unadjusted multivariable analyses. Following adjustments for known confounders, social jetlag remained significantly associated with zBMI (β = 0.12, p = 0.013). Simple slopes suggested a positive association in girls (β = 0.19, p = 0.006) but not in boys (β = 0.03, p = 0.703).ConclusionsObesity prevention efforts, particularly in girls, may benefit from targeted approaches to improving the consistency of sleep timing in youth.     

The relationship between gross motor function impairment in cerebral palsy and sleeping issues of children and caregivers

AimTo investigate, among children and adolescents with cerebral palsy (CP), the relationship between impairment of the gross motor function and: (i) child sleep disorders; (ii) the need for nocturnal support; and (iii) the quality of sleep of their caregivers.MethodsFor children, we considered their scores on the gross motor function measure (GMFM-88) and on the sleep disturbance scale for children (SDSC), besides analyzing qualitative features about their sleep. For caregivers, we considered their scores in the Pittsburgh sleep quality index (PSQI).ResultsOur sample was comprised of 87 participants with mean age of 11.4 years old (±3.4). We observed correlations between GMFM-88 and disorders of initiating and maintaining sleep (DIMS) (r = −0.22; p = 0.039), sleep–wake transition disorders (SWTD) (r = 0.26; p = 0.017) and disorders of arousal (DA) (r = 0.23; p = 0.033). Children receiving nocturnal support presented lower scores in the GMFM-88 (p = 0.001) and higher scores in the SDSC (p = 0.029). For the caregivers, we found no correlation between GMFM-88 and PSQI. Nonetheless, their PSQI scores correlated with the SDSC scores (r = 0.24; p = 0.027).ConclusionImpairment of the gross motor function correlated with DIMS and the need for nocturnal support but might not have an impact on the caregivers’ sleep, which in turn correlated with child sleep disorders.     

Narcolepsy in Slovakia – Epidemiology,clinical and polysomnographic features,comorbid diagnoses: a case-control study

ObjectiveAn increase in the incidence of narcolepsy after the pandemic influenza with the H1N1 vaccination in 2009 resulted in an interest in narcolepsy epidemiology. The aim of the study was to examine the incidence and prevalence rates of narcolepsy and to describe the associated characteristics in Slovakia.MethodsEpidemiology data were calculated for each year from 2000 to 2017 based on records found in specialized centres. In sum, 61 narcoleptic patients were diagnosed, of which 51 (84%) had narcolepsy type 1 (NT1). Clinical data and results of polysomnography (PSG), Human Leukocyte Antigen (HLA)-typing, hypocretin (HCRT)-1 levels and body mass index (BMI) were summarised and evaluated for NT1 and narcolepsy type2 (NT2). Later, 244 sex and age matched controls were chosen to evaluate the comorbid diagnoses.ResultsThe prevalence of narcolepsy in 2017 in Slovakia was 10.47 (CI 95% 8.26–14) cases/million inhabitants, and the mean incidence rate (2000–2017) was 0.57 (CI 95% 0.4–0.74) cases/million inhabitants.Narcoleptic patients were comorbid with arterial hypertension (17%), ischemic heart disease (8%), dyslipidaemia (18%), diabetes mellitus type 2 (10%), cardiac arrhythmia/atrial fibrillation (5%), autoimmune disorders (20%), allergy (11%), malignancy (3%), headache (15%) and mental disorders (20%). Patients with narcolepsy showed double the excess prevalence in mental disorders (OR 2.15, p < 0.05), and dyslipidaemia (OR 2.22, p < 0.05). The presence of autoimmune disorders and allergy showed a mild increase in the narcolepsy group (OR 1.46, resp. 1.63). Hashimoto thyroiditis (HT) was the most frequent autoimmune disorder.ConclusionsNarcolepsy is a rare disorder in Slovakia. From the phenotype, genetic characteristics and comorbidities the disorder does not vary from other European countries.     

Influence of post-stroke fatigue on reaction times and corticospinal excitability during movement preparation

ObjectivesReduced corticospinal excitability at rest is associated with post-stroke fatigue (PSF). However, it is not known if corticospinal excitability prior to a movement is also altered in fatigue which may then influence subsequent behaviour. We hypothesized that the levels of PSF can be explained by differences in modulation of corticospinal excitability during movement preparation.Methods73 stroke survivors performed an auditory reaction time task. Corticospinal excitability was measured using transcranial magnetic stimulation. Fatigue was quantified using the fatigue severity scale. The effect of time and fatigue on corticospinal excitability and reaction time was analysed using a mixed effects model.ResultsThose with greater levels of PSF showed reduced suppression of corticospinal excitability during movement preparation and increased facilitation immediately prior to movement onset (β = −0.0066, t = −2.22, p = 0.0263). Greater the fatigue, slower the reaction times the closer the stimulation time to movement onset (β = 0.0024, t = 2.47, p = 0.0159).ConclusionsLack of pre-movement modulation of corticospinal excitability in high fatigue may indicate poor sensory processing supporting the sensory attenuation model of fatigue.SignificanceWe take a systems-based approach and investigate the motor system and its role in pathological fatigue allowing us to move towards gaining a mechanistic understanding of chronic pathological fatigue.     

Inflammation in children with neuromuscular disorders and sleep disordered breathing

IntroductionPaediatric obstructive sleep apnoea is associated with systemic inflammation and co-morbidities. We assessed whether sleep disordered breathing (SDB) due to neuromuscular weakness was associated with elevated airway and systemic pro-inflammatory cytokines.MethodsConsecutive neuromuscular children (age 5–18years) underwent overnight full polysomnography and morning collection of serum and breath condensate, analysed for cytokines (Interleukin-10, Interleukin-6, Interleukin-1β, Tumour Necrosis Factorα, high-sensitivity C-Reactive Protein, Intercellular and Vascular Adhesion Molecules ICAM-1, VCAM-1). Cytokine levels were related to Oxygen desaturation index (ODI), desaturation>4%/h, and levels of transcutaneous carbon dioxide overnight (tcCO2≥6.7 kPa > 2% sleep).ResultsA total of 23 patients were included, median age 12.6 years (IQR 8.7–14.6). ODI>3/h was associated with higher breath and serum IL-6 (p = 0.02). Children with elevated CO₂ overnight had higher ICAM-1 and VCAM-1. CO₂ levels correlated with serum ICAM-1 (rs0.570, p = 0.026) and VCAM-1 (rs0.76, p = 0.001).DiscussionSDB in neuromuscular children is associated with raised serum IL-6, VCAM-1, ICAM-1. This may predispose these children to future cardiovascular and other co-morbidities.     

Comparison of clinical outcomes with two Transcranial Magnetic Stimulation treatment protocols for major depressive disorder

BackgroundTranscranial magnetic stimulation (TMS) is an effective treatment for major depressive disorder (MDD). The rest time between pulse trains is the inter-train interval (ITI). Since 2016, some TMS clinicians have adopted a stimulation protocol with shorter ITIs than were used in regulatory clinical trials.ObjectiveTo contrast treatment outcomes with the Standard TMS protocol (38.5 min per session) and the “Dash” protocol, which, at the shortest ITI, has a session duration of 18.75 min.MethodsRegistry data were collected at 103 practice sites. Of 7759 participants, 5010 were included in an intent-to-treat (ITT) sample, defined as a primary MDD diagnosis, age ≥ 18, and completion of the PHQ-9 before TMS and with at least one PHQ-9 assessment after baseline. Completers (N = 3814) were responders or had received ≥ 20 sessions and had an end of acute treatment PHQ-9 assessment. Within the ITT sample, 613 patients were treated with the Standard NeuroStar 38-min protocol and 1493 patients with the new Dash protocol. CGI-S ratings were obtained in smaller samples. Treatment outcomes were also examined in subgroups considered Completers, as well as the subgroups who met criteria for Full Adherence to the Standard or Dash protocol parameters.ResultsIn the ITT, Completer, and Fully Adherent samples, response (58–72%) and remission (28–53%) rates were notably high across PHQ-9 and CGI-S ratings. The Standard and Dash protocols did not differ in number of treatment sessions, and both manifested strong antidepressant effects.ConclusionsThe Standard and Dash protocols did not meaningfully differ in efficacy.     

Comparison of clinical outcomes with left unilateral and sequential bilateral Transcranial Magnetic Stimulation (TMS) treatment of major depressive disorder in a large patient registry

BackgroundIt has been suggested that sequential bilateral (SBL) TMS, combining high frequency, left dorsolateral prefrontal cortex (DLPFC) stimulation and low frequency, right DLPFC stimulation, is more effective than unilateral TMS.ObjectiveTo contrast treatment outcomes of left unilateral (LUL) and SBL protocols.MethodsRegistry data were collected at 111 practice sites. Of 10,099 patients, 3,871 comprised a modified intent-to-treat (mITT) sample, defined as a primary MDD diagnosis, age ≥18, and PHQ-9 completion before TMS and at least one PHQ-9 assessment after baseline. The mITT sample received high frequency (10 Hz) LUL TMS exclusively (N = 3,327) or SBL TMS in at least 90% of sessions (N = 544). Completers (N = 3,049) were responders or had received ≥20 sessions and had an end of acute treatment PHQ-9 assessment. To control for site effects, a Matched sample (N = 653) included Completers at sites that used both protocols. To control for selection bias, the SBL group was also compared to a Restricted LUL group, drawn from sites where no patient switched to SBL after substantial exposure to LUL TMS. Secondary analyses were conducted on CGI-S ratings.ResultsThe LUL group had superior outcomes compared to the SBL group for multiple PHQ-9 and CGI-S continuous and categorical measures in the mITT, Completer and Matched samples, including in the specified primary analyses. However, outcome differences were not observed when comparing the Restricted LUL and SBL groups. Within SBL protocols, the LUL-RUL order had superior outcomes compared to the RUL-LUL order in all CGI-S, but not PHQ-9, measures.ConclusionsWhile limited by the naturalistic design, there was no evidence that SBL TMS was superior to LUL TMS. The sequential order of RUL TMS followed by LUL TMS may have reduced efficacy compared to LUL TMS followed by RUL TMS.     

Objective measurement of limb bradykinesia using a marker-less tracking algorithm with 2D-video in PD patients

BackgroundQuantitative measurement of parkinsonian motor symptoms is crucial in clinical practice and in research. However, the widely used Unified PD Rating Scale (UPDRS) part III is based on a semi-quantitative evaluation with high inter- and intra-rater variability. Sensor-based measurements have been widely studied but are limited for their accessibility.MethodsWe analyzed 2D-RGB videos recording finger tapping and leg agility tests in 29 PD patients with a marker-less deep-learning based tracking algorithm. The tracking performance was validated with an accelerometer. Four parameters (mean amplitude, mean interpeak interval, amplitude variability and interpeak interval variability) were calculated from the position tracking.ResultsThe performance of the video-tracking was in good agreement with the accelerometer-based tracking (Intra-class correlation coefficient > 0.9 for the peak amplitude, and >0.6 for the interpeak interval). The video-tracking successfully captured variable aspects of limb bradykinesia that have a distinct correlation with the general parkinsonian motor symptoms and gait. In the finger-tapping task, the mean amplitude (R = −0.6, p = 2.4 × 10⁻⁶), amplitude variability (R = 0.36, p = 0.0092), mean interpeak interval (R = 0.34, p = 0.014), and interpeak interval variability (R = 0.66, p = 1.4 × 10⁻⁷) was significantly correlated with the UPDRS scores. In leg agility test, the mean amplitude (R = −0.58, p = 1.7 × 10⁻⁵), mean interpeak interval (R = 0.37, p = 0.0088) and interpeak interval variability (R = 0.7, p = 6.2 × 10⁻⁸) were significantly correlated with the UPDRS scores, but not with amplitude variability (R = 0.17, p = 0.26). Limb rigidity was significantly correlated with the interpeak interval (R = 0.40, p = 0.0036) and its variability (R = 0.59, p = 4.2 × 10⁻⁶) in the leg agility test.ConclusionThe video-based tracking could objectively measure limb bradykinesia in PD patients.     

Efficacy of pitolisant in patients with high burden of narcolepsy symptoms: pooled analysis of short-term,placebo-controlled studies

Study objectiveTo evaluate the efficacy of pitolisant, a histamine 3 (H₃)-receptor antagonist/inverse agonist, in adult patients with high burden of narcolepsy symptoms.MethodsData were pooled from two randomized, placebo-controlled, 7- or 8-week studies of pitolisant (titrated to a potential maximum dose of 35.6 mg/day) in adults with narcolepsy. Analyses included three independent patient subgroups: Epworth Sleepiness Scale (ESS) baseline score ≥16, Maintenance of Wakefulness Test (MWT) sleep latency ≤8 min, and ≥15 cataplexy attacks per week.ResultsThe analysis populations included 118 patients for ESS (pitolisant, n = 60; placebo, n = 58), 105 for MWT (pitolisant, n = 59; placebo, n = 46), and 31 for cataplexy (pitolisant, n = 20; placebo, n = 11). On the ESS, least-squares mean change from baseline was significantly greater for pitolisant (−6.1) compared with placebo (−2.3; P < 0.001). Significantly more pitolisant-treated patients were classified as treatment responders: ESS score reduction ≥3, 69.0% in the pitolisant group versus 35.1% in the placebo group (P = 0.001); final ESS score ≤10, 36.2% versus 10.5%, respectively (P = 0.005). On the MWT, mean sleep latency increased from 3.5 min to 10.4 min with pitolisant and from 3.4 min to 6.8 min with placebo (P = 0.017). Least-squares mean change in the weekly rate of cataplexy was significantly greater for pitolisant (−14.5; baseline, 23.9; final, 9.4) compared with placebo (−0.1; baseline, 23.1; final, 23.0; P = 0.004). Headache was the most common adverse event with pitolisant.ConclusionsPitolisant, at once-daily doses up to 35.6 mg, was efficacious for reducing excessive daytime sleepiness and cataplexy in patients with severe narcolepsy symptom burden.     

A multimodal approach using TMS and EEG reveals neurophysiological changes in Parkinson's disease

IntroductionAlterations in large scale neural networks leading to neurophysiological changes have been described in Parkinson's disease (PD). The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has been suggested as a promising tool to identify and quantify neurophysiological mechanisms. The aim of this study was to investigate specific changes in electrical brain activity in response to stimulation of four brain areas in patients with PD.Methods21 healthy controls and 32 patients with PD underwent a combined TMS-EEG assessment that included stimulation of four brain areas: left M1, right M1, left dorso-lateral prefrontal cortex (DLPFC), and right DLPFC. Six measures were calculated to characterize the TMS evoked potentials (TEP) using EEG: (1) wave form adherence (WFA), (2) late phase deflection (LPD), (3) early phase deflection (EPD), (4) short-term plasticity (STP), (5) inter-trial adherence, and (6) connectivity between right and left M1 and DLPFC. A Linear mixed-model was used to compare these measures between groups and areas stimulated.ResultsPatients with PD showed lower WFA (p = 0.052), lower EPD (p = 0.009), lower inter-trial adherence (p < 0.001), and lower connectivity between homologs areas (p = 0.050), compared to healthy controls. LPD and STP measures were not different between the groups. In addition, lower inter-trial adherence correlated with longer disease duration (r = −0.355, p = 0.050).ConclusionsOur findings provide evidence to various alterations in neurophysiological measures in patients with PD. The higher cortical excitability along with increased variability and lower widespread of the evoked potentials in PD can elucidate different aspects related to the pathophysiology of the disease.     

Sleep positions in children with Down syndrome and obstructive sleep apnea

ObjectivesTo assess sleep positions in children with both Down syndrome (DS) and obstructive sleep apnea (OSA) and determine if there is a preferred sleep position by severity of apnea.MethodsA single-center retrospective review of patients with both DS and OSA was performed. Caregivers reported sleep position utilized greater than 50% of observed sleep time. Accuracy of this report was confirmed through review of hypnograms from polysomnography studies.ResultsEighty-two patients met inclusion criteria. Median body mass index (BMI) was 26.6 and 56% of patients had a prior tonsillectomy and/or adenoidectomy. The mean obstructive AHI (OAHI) was 25.33 with 90.4% having severe OSA, 9.6% having moderate OSA, and no patients having mild OSA. Reported sleep positions were skewed towards lateral/decubitus (82.9%) compared to prone (11.0%) and supine (6.1%). This was consistent with hypnogram data where 71% of total sleep time in lateral/decubitus positions compared to prone (13%) and supine (6%). The median changes in sleep position per patient was 5 (IQR: 3–6). Lower BMI (p < 0.001, 95% CI: 0.32–1.13) and tonsillectomy (p < 0.001, 95% CI: 7.7–18.19) were associated with lower OAHI. Sleep position was not associated with age (p = 0.19), sex (p = 0.66), race (p = 0.10), ethnicity (p = 0.68) nor history of tonsillectomy (p = 0.34). Preferred sleep position was not correlated with OAHI (p = 0.78, r = 0.03) or OSA severity (p = 0.72, r = 0.03).ConclusionsThis study highlights the possibility that children with DS may have preferential sleep positions that cater to optimized airflow in the context of OSA although further prospective study is needed.     

Sleep-disordered breathing in cystic fibrosis

IntroductionCystic fibrosis (CF) is a life-shortening, genetic disease that affects approximately 30,000 Americans. Although patients frequently report snoring, mouth breathing, and insomnia, the extent to which sleep-disordered breathing (SDB) may underlie these complaints remains unknown.MethodsSingle-center retrospective review of polysomnography results from referred patients with and without CF individually-matched (1:2) for age, gender, race, and body mass index (BMI).ResultsMean ages were 8.0 ± 5.2 (sd) and 35.9 ± 12.9 years, among 29 children and 23 adults with CF respectively. The CF and non-CF groups were well-matched in age and BMI. Subjects with vs. without CF had three times greater odds of moderate-severe SDB (apnea-hypopnea index (AHI) ≥ 5 in children, ≥ 15 in adults) (p = 0.01). Nocturnal oxygen saturation nadir (Minimum SpO₂) was lower among CF vs. non-CF groups (p = 0.002). For every 1-unit increase in AHI, the decline in Minimum SpO₂ was larger for subjects with vs. without CF (p = 0.05). In subjects with CF, forced expiratory volume in 1 s percent predicted (FEV1 PPD) was associated with Minimum SpO₂ (Pearson r = 0.68, p < 0.0001) but not AHI (r = −0.19, p = 0.27). For every 1-unit increase in AHI, magnitude of decline in Minimum SpO₂ was larger for those with low vs. normal FEV1 PPD (p = 0.01).ConclusionSeverity of SDB may be worse among referred patients with vs. without CF. The SDB may modify the relationship between CF lung disease and nocturnal hypoxemia. Markers of lung disease severity including lung function do not predict SDB severity, suggesting the need for routine polysomnography to screen for this sleep disorder.     

Theta-burst versus 20 Hz repetitive transcranial magnetic stimulation in neuropathic pain: A head-to-head comparison

ObjectiveHigh-frequency repetitive transcranial magnetic stimulation (rTMS) has been shown to reduce neuropathic pain, but intermittent “theta-burst” stimulation (iTBS) could be a better alternative because of shorter duration and greater ability to induce cortical plasticity. Here we compared head-to-head the pain-relieving efficacy of the two modalities when applied daily for 5 days to patients with neuropathic pain.MethodsForty-six patients received 20 Hz-rTMS and/or iTBS protocols and 39 of them underwent the full two procedures in a random cross-over design. They rated pain intensity, sleep quality, fatigue and general health status daily during 5 consecutive weeks.ResultsPain relief during the month following stimulation was superior after 20 Hz-rTMS relative to iTBS (F(1,38) = 4.645; p = 0.037). Correlation between respective levels of maximal relief showed a significant deviation toward the 20 Hz-rTMS effect. A greater proportion of individuals responded to 20 Hz-rTMS (52% vs 32%, 95 %CI[0.095–3.27]; p = 0.06), and reports of fatigue significantly improved after 20 Hz-rTMS relative to iTBS (p = 0.01). General health and sleep quality scores did not differentiate both techniques.ConclusionsHigh-frequency rTMS appeared superior to iTBS for neuropathic pain relief.SignificanceAdequate matching between the oscillatory activity of motor cortex and that of rTMS may increase synaptic efficacy, thus enhancing functional connectivity of motor cortex with distant structures involved in pain regulation.     

Abnormal patterns of corticomuscular and intermuscular coherence in childhood dystonia

ObjectiveSensorimotor processing is abnormal in Idiopathic/Genetic dystonias, but poorly studied in Acquired dystonias. Beta-Corticomuscular coherence (CMC) quantifies coupling between oscillatory electroencephalogram (EEG) and electromyogram (EMG) activity and is modulated by sensory stimuli. We test the hypothesis that sensory modulation of CMC and intermuscular coherence (IMC) is abnormal in Idiopathic/Genetic and Acquired dystonias.MethodsParticipants: 11 children with Acquired dystonia, 5 with Idiopathic/Genetic dystonia, 13 controls (12–18 years). CMC and IMC were recorded during a grasp task, with mechanical perturbations provided by an electromechanical tapper. Coherence patterns pre- and post-stimulus were compared across groups.ResultsBeta-CMC increased post-stimulus in Controls and Acquired dystonia (p = 0.001 and p = 0.010, respectively), but not in Idiopathic/Genetic dystonia (p = 0.799). The modulation differed between groups, being larger in both Controls and Acquired dystonia compared with Idiopathic/Genetic dystonia (p = 0.003 and p = 0.022). Beta-IMC increased significantly post-stimulus in Controls (p = 0.004), but not in dystonia. Prominent 4–12 Hz IMC was seen in all dystonia patients and correlated with severity (rho = 0.618).ConclusionIdiopathic/Genetic and Acquired dystonia share an abnormal low-frequency IMC. In contrast, sensory modulation of beta-CMC differed between the two groups.SignificanceThe findings suggest that sensorimotor processing is abnormal in Acquired as well as Idiopathic/Genetic dystonia, but that the nature of the abnormality differs.     

Could non-HDL-cholesterol be a better marker of atherogenic dyslipidemia in obstructive sleep apnea?

Background/objectiveObstructive sleep apnea (OSA) is independently associated with dyslipidemia, a surrogate marker of atherosclerosis. Low-density lipoprotein (LDL)-cholesterol is accepted as a major independent risk factor for cardiovascular disease. However, non-high-density lipoprotein (HDL)-cholesterol is a better marker of atherogenic dyslipidemia and recommended as a target of lipid lowering therapy. We aimed to assess the prevalence of atherogenic dyslipidemia, and relationship between OSA severity and serum LDL-cholesterol and non-HDL cholesterol levels in OSA patients.MethodsWe retrospectively evaluated treatment naïve 2361 subjects admitted to the sleep laboratory of a university hospital for polysomnography. All subjects’ lipid profile including total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and non-HDL-cholesterol were measured.ResultsOut of 2361 patients (mean age 49.6 ± 11.9 years; 68.9% male, apnea-hypopnea index 36.6 ± 28.4/h), 185 (7.8%) had no OSA and 2176 (92.2%) had OSA. Atherogenic dyslipidemia prevalence was high (57–66%) in OSA patients, and especially increased in severe OSA compared to other groups (p < 0.05). Though total and LDL-cholesterol did not differ between those with and without OSA, non-HDL-cholesterol (p = 0.020), and triglycerides (p = 0.001) were higher and HDL-cholesterol levels (p = 0.018) were lower in OSA patients than non-OSA. Non-HDL-cholesterol was significantly correlated with OSA severity (p < 0.001) and hypoxia parameters (p < 0.01), whereas LDL-cholesterol showed no correlation.ConclusionsAtherogenic dyslipidemia is highly prevalent and non-HDL-cholesterol levels are significantly increased, predominantly in severe OSA patients. Non-HDL-cholesterol but not LDL-cholesterol, is significantly correlated with OSA severity and hypoxia parameters. Therefore, it could be better to use non-HDL-cholesterol, which is a guideline recommended target of lipid therapy, as a marker of atherosclerotic cardiovascular risk in OSA patients.