Changes in quality of life in individuals with narcolepsy type 1 after the H1N1-influenza epidemic and vaccination campaign in Norway: a two-year prospective cohort study

ObjectiveCross-sectional studies show a lower health-related quality of life (HRQoL) in individuals with narcolepsy. We aimed to describe changes in HRQoL after two years of multidisciplinary follow-up in a cohort of mainly post-H1N1 vaccination narcolepsy type-1 (NT1) patients in Norway.MethodsProspective-cohort study. Narcolepsy diagnosis was based on the International Classification of Sleep Disorders (third edition). Psychiatric comorbidity was assessed using the Achenbach System of Empirically Based Assessment (ASEBA). HRQoL was evaluated with the Pediatric Quality of Life Inventory (PedsQL™ Generic Core Scales 4.0) at baseline and follow-up. Mean follow-up time was 20.7 (2.7) months.ResultsThirty one patients (18 females) with NT1, mean age 14.6 (SD = 4.8) years answered questionnaires at baseline and follow-up. On a group level, the PedsQL Total Health Summary score significantly improved by a mean of 5.9 (95%CI = 0.4, 11.9), p = 0.038; this was mainly driven by improvements in the Physical Health Summary score by 9.8 (3.0, 16.5) points, p = 0.006 and the School Functioning Scale score by 7.5 (1.0, 13.9) points p = 0.025. The Total ASEBA score was correlated with PedsQL Total Health Summary score at baseline, but not with changes in HRQoL. Sodium oxybate (Xyrem®) treatment at follow up was positively associated with changes in PedsQL Total Health Summary score, after adjusting for age and gender, p = 0.027.ConclusionHRQoL in NT1 patients improved after two years of follow-up. The use of sodium oxybate (Xyrem®) at follow-up was associated with increases in HRQoL. Psychiatric comorbidity was correlated with HRQoL at baseline but did not predict changes in HRQoL at follow-up.     

High prevalence of ADHD symptoms in unmedicated youths with post-H1N1 narcolepsy type 1

ObjectivesTo characterize attention deficit-hyperactivity disorder (ADHD) symptoms in unmedicated post-H1N1 narcolepsy type 1 (NT1) youths, and explore associations between ADHD symptoms and the narcolepsy phenotype.MethodsA total of 50 consecutively enrolled post-H1N1 NT1 youths (7–20 years, 62% females, 98% HLA-DQB1106:02-positive, 98% CSF hypocretin-1 deficient, 88% vaccinated) were assessed after two weeks off medication for ADHD (ADHD diagnosis pre/post-narcolepsy, parent-rated ADHD symptoms) and narcolepsy-phenotyped (semi-structured interview, Stanford Sleep Questionnaire, Epworth Sleepiness Scale, polysomnography (PSG), Multiple Sleep Latency Test (MSLT)).ResultsIn sum, 26 (52%) and 15 (30%) of participants had ADHD symptoms above and below the clinical significant cut-off, respectively, while 9 (18%) had no ADHD symptoms. High values were found for ADHD total score (mean (SD), 17.9 (9.5)) and ADHD subscores (inattentive score, 11.0 (6.3); hyperactive/impulsivity score, 6.9 (4.7)). These were significantly higher than previously reported in a mainly medicated narcolepsy cohort (p < 0.0001). Age, gender and disease duration did not influence scores. Two participants (4%) had ADHD diagnosis prior to narcolepsy onset. ADHD symptoms were correlated with parent-rated, but not with patient rated ESS scores, objective sleepiness (mean sleep latency), sleep fragmentation (sleep stage shift index, awakening index), or CSF hypocretin-1 level.ConclusionComorbid ADHD symptoms were more prevalent in unmedicated post-H1N1 NT1 youths than previously reported in mainly medicated pediatric narcolepsy cohorts. The high prevalence was not due to pre-existing ADHD and generally not correlated with core narcolepsy sleep/wake phenotype characteristics, indicating that the ADHD symptoms were not a direct consequence of disturbed sleep or daytime sleepiness.     

Prevalence and neurophysiological correlates of sleep disordered breathing in pediatric type 1 narcolepsy

Study objectivesTo investigate the prevalence and neurophysiological correlates of obstructive sleep disordered breathing (OSA) in type 1 narcolepsy (NT1) children and adolescents.MethodsThirty-eight, drug-naïve, NT1 children and adolescents and 21 age- and sex-balanced clinical controls underwent nocturnal polysomnography (PSG) and multiple sleep latency test (MSLT). According to the rules for pediatric population, an obstructive apnea-hypopnea index (Obstructive AHI) ≥ 1 (comprising obstructive and mixed events), defined comorbid OSA.ResultsNT1 children showed higher prevalence of overweight/obesity and severe nocturnal sleep disruption (lower sleep efficiency, and increased N1 sleep stage percentage) coupled with higher motor activity (periodic limb movement index [PLMi] and REM atonia index) compared to clinical controls. Sleep-related respiratory variables did not differ between NT1 and clinical controls (OSA prevalence of 13.2% and 4.8%, respectively). NT1 children with OSA were younger and showed lower N2 sleep stage percentage and higher PLMi than NT1 children without comorbid OSA. Overweight/obesity was not associated with OSA in NT1.ConclusionsDespite higher body mass index (BMI), OSA prevalence did not differ between children with NT1 and clinical controls. OSA in pediatric NT1 patients is a rare and mild comorbidity, further contributing to nocturnal sleep disruption without effects on daytime sleepiness.     

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.     

Predictors of fatigue severity in early,de novo Parkinson disease patients: A 1-year longitudinal study

IntroductionFatigue is one of the most common and disabling nonmotor symptom in Parkinson's disease (PD). The aim of the present study was to investigate the 1-year course of fatigue in a consecutive sample of de novo drug-naïve patients with PD, and at systematically searching for baseline motor and nonmotor predictors associated with fatigue severity over time.MethodsFifty-five consecutive de novo PD patients (age: 64.71 ± 7.74 years) underwent a comprehensive examination, including Parkinson Fatigue Scale, Epworth Sleepiness Scale, Parkinson's Disease Sleep Scale, Beck Depression Inventory, Parkinson's Anxiety Scale, Apathy Evaluation Scale, and an extensive neuropsychological evaluation. Bivariate and multiple regression analyses were performed to identify baseline predictors independently related to fatigue severity at 1-year follow-up.ResultsPrevalence rate of fatigue (defined by PFS cut-off) increased from 22% at baseline to 38% at 1-year follow-up. A similar increase in prevalence was observed for excessive daytime sleepiness, and apathy. Among patients with fatigue at baseline, 91% had fatigue at follow-up too (i.e., persistent fatigue). Multivariate regression analysis identified fatigue (p < 0.01), daytime sleepiness (p < 0.01), and emotional apathy (p < 0.01) as the main baseline variables significantly predicting fatigue severity at 1-year follow-up.ConclusionIn early PD, fatigue increases and persists over time, and its severity is related to higher baseline levels of fatigue, excessive daytime sleepiness, and emotional apathy. These results warrant to monitor fatigue since the early stage of disease, and suggest that treating excessive daytime sleepiness and emotional apathy might prevent its worsening.     

Using actigraphy to assess sleep and wake rhythms of narcolepsy type 1 patients: a comparison with primary insomniacs and healthy controls

Objective/backgroundIt has been shown that actigraphy may have a discriminant function (DS) for the diagnosis of narcolepsy type 1 patients (NT1), based on a combination of nighttime and daytime parameters. Here, we aimed to test those findings using another actigraph model with a different clinical sample as control (ie, primary insomniacs, PI), carrying out a secondary analysis of previously collected data.Patients/methodsThe study sample consisted of 13 NT1 (nine females; mean age 39.38 ± 11.48), 13 PI (nine females; mean age 38.69 ± 10.72) and 13 Healthy Controls (HC) (nine females; mean age 38 ± 10.77). Participants wore the Actiwatch AW64 (Cambridge Neurotechnology Ltd, Cambridge, UK) around the non-dominant wrist for seven consecutive days.ResultsSignificant differences between groups were observed with a higher number of episodes of wakefulness (wake bouts, WB) in PI than HC, a higher fragmentation index (FI) in NT1 than HC and PI, a higher duration of the longest nap (LNAP) in NT1 than HC and PI and higher DS in PI and NT1 than HC. A new DS (NDS), with LNAP and FI as independent variables, was proposed; which was higher in NT1 than HC and PI.ConclusionsThe present study confirms that actigraphy discriminates NT1 from HC. However, considering PI, a new discriminant function NDS which takes into account LNAP and FI is better for this actigraph model.     

Childhood narcolepsy with cataplexy: comparison between post-H1N1 vaccination and sporadic cases

ObjectivesWe aimed to compare post-Pandemrix® vaccination (postvaccine) childhood narcolepsy with cataplexy (NC) vs sporadic pre-H1N1 pandemic (pre-H1N1) cases.MethodsClinical, anthropometric, polysomnographic, and cerebrospinal hypocretin 1 (hcrt-1) measurements were collected together with the video recordings of cataplexy in 27 Finnish patients with NC onset after H1N1 Pandemrix® vaccination (mean age, 12 ± 4 years; 52% boys) and 42 Italian NC patients with NC onset before the H1N1 pandemic (mean age, 11 ± 3 years; 48% boys). All subjects carried the HLA-DQB1*0602 allele.ResultsPostvaccine subjects were older at NC onset (12 ± 3 vs 9 ± 3 years; P = .008) and displayed a shorter mean sleep latency in multiple sleep latency tests (MSLT) (2.3 ± 2.2 vs 3.7 ± 2.9 min; P = .026) compared to pre-H1N1 cases. Anthropometric, clinical (core NC symptoms), hcrt-1 deficiency, and polysomnographic data did not differ among groups, but higher disrupted nocturnal sleep was observed in postvaccine subjects. Comparison of cataplexy features at video assessment showed an overlapping picture with the exception for hyperkinetic movements which appeared to be more evident in pre-H1N1 subjects.ConclusionsThe clinical picture of childhood NC was similar in postvaccine and pre-H1N1 children.     

Psychiatric disturbances in radiologically isolated syndrome

BackgroundRadiologically isolated syndrome (RIS) is characterized by incidental lesions suggestive of multiple sclerosis (MS) on MRI without typical symptoms of MS. Clinically isolated syndrome (CIS) is characterized by a first episode of neurologic symptoms caused by demyelination in the central nervous system. To date, psychiatric disorders have not been systematically addressed in RIS subjects. We assessed emotional disturbances, personality features and health-related quality of life (HRQoL) in a cohort of RIS patients as compared with clinically isolated syndrome (CIS).MethodsTwenty-eight RIS patients, 25 clinically isolated syndrome (CIS) patients, and 22 healthy subjects were enrolled in the study. Participants were administered a mood scale (Hamilton Depression Rating Scale), behavioural measures (Personality Assessment Inventory), and fatigue measures (Fatigue Impact Scale for Daily Use). HRQoL was quantified using the EuroQol-5.Results14 (50%) of RIS patients had clinically significant depression, with over one-third of these having moderate depression, scores virtually identical to those observed in CIS patients. 11 of 28 (39.3%) subjects with RIS had anxious depression, a figure three times higher than that found in CIS patients. RIS patients' HAMD-17 total score showed a very strong correlation with severity of fatigue. In addition, RIS patients reported lower HRQoL (p = 0.036) and a significantly higher symptoms load for somatisation compared to both CIS and control groups (p < 0.002).ConclusionRIS patients had high rates of depression, particularly anxious depression and somatization. Future studies are warranted to clarify whether these psychiatric disturbances are causally associated with a distinct white matter psychopathologic process.     

Clinical significance of periodic limb movements during sleep: the HypnoLaus study

ObjectivePeriodic limb movements during sleep (PLMS) are prevalent in the general population, but their impact on sleep and association with cardiometabolic disorders are a matter of debate.MethodsData from 2162 participants (51.2% women, mean age 58.4 ± 11.1 years) of the population-based HypnoLaus study (Lausanne, Switzerland) were collected. Subjective sleep complaints and habits were assessed using the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale (ESS). Participants underwent a full polysomnography (PSG) at home and were evaluated for the presence of hypertension, diabetes, and metabolic syndrome.ResultsParticipants with a PLMS index (PLMSI) > 15/h (28.6% of the sample) had longer subjective sleep latency (18.6 ± 17.2 vs. 16.1 ± 14.3 min, p = 0.014) and duration (7.1 ± 1.2 vs. 6.9 ± 1.1 h, p < 0.001) than participants with PLMSI ≤ 15/h. At the PSG, they spent more time in stage N2 sleep (49.0 ± 11.2 vs. 45.5 ± 9.8%, p < 0.001), less in stage N3 (17.6 ± 8.2 vs. 20.6 ± 8.4%, p < 0.001) and in REM sleep (20.3 ± 6.4 vs. 22.4 ± 6.0%, p < 0.001), and exhibited longer REM latency (104.2 ± 70.2 vs. 91.7 ± 58.6 min, p < 0.001) and higher arousal index (26.5 ± 12.3 vs. 19.2 ± 9.7 n/h, p < 0.001). Participants with a PLMSI > 15/h had a lower ESS scores and higher prevalence of hypertension, diabetes, and metabolic syndrome. Multivariate analysis adjusting for confounding factors confirmed the independent association of PLMSI > 15/h with subjective sleep latency and duration, and with objective sleep structure disturbances. However, the associations with sleepiness and cardiovascular risk factors disappeared.ConclusionsIn our large middle-age European population-based sample, PLMSI > 15/h was associated with subjective and objective sleep disturbances but not with sleepiness, hypertension, diabetes, or metabolic syndrome.     

Fatigue, reduced sleep quality and restless legs syndrome in Charcot-Marie-Tooth disease: a web-based survey

To investigate the prevalence of fatigue, daytime sleepiness, reduced sleep quality, and restless legs syndrome (RLS) in a large cohort of patients with Charcot-Marie-Tooth disease (CMT) and their impact on health-related quality of life (HRQoL). Participants of a web-based survey answered the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index, the Multidimensional Fatigue Inventory, and, if the diagnostic criteria of RLS were met, the International RLS Severity Scale. Diagnosis of RLS was affirmed in screen-positive patients by means of a standardized telephone interview. HRQoL was assessed by using the SF-36 questionnaire. Age- and sex-matched control subjects were recruited from waiting relatives of surgical outpatients. 227 adult self-reported CMT patients answered the above questionnaires, 42.9% were male, and 57.1% were female. Age ranged from 18 to 78 years. Compared to controls (n = 234), CMT patients reported significantly higher fatigue, a higher extent and prevalence of daytime sleepiness and worse sleep quality. Prevalence of RLS was 18.1% in CMT patients and 5.6% in controls (p = 0.001). RLS severity was correlated with worse sleep quality and reduced HRQoL. Women with CMT were affected more often and more severely by RLS than male patients. With regard to fatigue, sleep quality, daytime sleepiness, RLS prevalence, RLS severity, and HRQoL, we did not find significant differences between genetically distinct subtypes of CMT. HRQoL is reduced in CMT patients which may be due to fatigue, sleep-related symptoms, and RLS in particular. Since causative treatment for CMT is not available, sleep-related symptoms should be recognized and treated in order to improve quality of life.     

Utility of measuring CSF hypocretin-1 level in patients with suspected narcolepsy

ObjectivesThe patho-aetiology of narcolepsy Type I (NT1) is the loss of hypocretin-1 secreting neurons in the hypothalamus. Diagnostic criteria for NT1 include excessive daytime sleepiness (EDS) for at least three months not explained by any other condition, cataplexy and cerebrospinal fluid (CSF) hypocretin-1 concentrations lower than 110 pg/ml. In this study we evaluated the utility of measuring CSF hypocretin-1 levels in patients with suspected narcolepsy (N).MethodsThe study included 29 consecutively recruited patients at a tertiary sleep centre presenting with EDS for exclusion of N. All patients were examined using an extensive clinical interview followed by two weeks of actigraphy and sleep diary recordings, polysomnography (PSG) and multiple sleep latency testing (MSLT). Additionally, HLA-typing, urinary screening for substances of abuse and a lumbar puncture to measure CSF hypocretin-1 expression using radioimmunoassay were carried out.ResultsIn sum, 19 patients (66%) had a CSF hypocretin-1 level <110 pg/ml, of whom two had current severe depression without any features of narcolepsy except EDS. The predictive potential of hypocretin-1 measurement in diagnosing narcolepsy revealed a positive predictive value (PPV) of 89%, a specificity of 83%, with both negative predictive value (NPV) and sensitivity equal to 100%.ConclusionsDespite a high sensitivity and specificity, the MSLT is not always a reliable diagnostic test for narcolepsy and where this uncertainty exits, CSF hypocretin-1 concentrations <110 pg/ml can be useful. However, due to a lower PPV and specificity at this cut-off, it may also not be entirely reliable as a stand-alone diagnostic test, particularly in the context of severe depression.     

Predictors of onset of psychosis in patients with Parkinson's disease: Who gets it early?

IntroductionPsychosis is one of the common non-motor symptoms of PD, which substantially worsens the quality of life. Hence, it is important to identify factors that are associated with early onset of psychosis in PD. In order to identify those factors, the current study aims to compare various demographic and clinical features of PD patients with early and late onset psychosis.MethodologyIn this prospective case-control study, 51 consecutive patients with PD having psychosis (PDP) were recruited. Median of the latency of onset of psychotic symptoms from the onset of motor symptoms was calculated (5.5 years) and after doing a median split, the cohort of PDP was divided into early onset PDP (EOP, n = 25) and late onset PDP (LOP, n = 26). Both the groups were compared for several demographic and clinical characteristics.ResultsCompared to those with LOP, patients with EOP had poor scores on frontal assessment battery (13.8 ± 2.0 vs 15.3 ± 1.8, p = 0.007), more frequently had Rapid Eye movement sleep Behavior Disorder (RBD) (80% vs 46.2%, p = 0.02), Postural Instability with Gait Difficulty (PIGD) phenotype (72% vs 26.9%, p = 0.002), and excessive daytime sleepiness (Epworth Sleepiness Scale: 8.04 ± 3.7 vs 3.9 ± 3.1). Patients with LOP were older (63.4 ± 7.0 years vs 56.5 ± 8.1 years, p = 0.002) and had higher Levodopa equivalent dose/day (LEDD: 819.1 ± 365.8 vs 608.5 ± 356.3, p = 0.04) compared to those with EOP.ConclusionPresence of RBD, excessive daytime sleepiness, frontal lobe dysfunction, and PIGD phenotype of PD may be associated with early onset of psychosis in PD. Higher LEDD may not trigger early occurrence of psychosis in PD.     

Association between loneliness,sleep behavior and quality: a propensity-score-matched case–control study

ObjectiveTo explore the influence of loneliness on sleep behavior and sleep quality based on propensity score-matched samples in Southwest China.MethodsIndividual-level data were obtained from a Southwest China cohort study. Participants who felt lonely were matched with those who did not with propensity scores on the basis of age, gender, socioeconomic factors, physical exercise and social connection level. Sleep behavior (onset and offset timing), sleep quality (sleep latency, nocturnal awakenings and subjective sleep quality), and daytime function (daytime sleepiness and fatigue) were assessed with the Pittsburgh Sleep Index Scale (PSQI) and compared between the two groups. The data were collected between May 2019 and December 2019, and data analyses were completed in April 2021.ResultsA total of 11,696 participants were included, and 824 out of 839 participants who felt loneliness were statistically matched with 824 participants who did not. Analyses of the matched samples showed that sleep onset and offset timing were similar between those who felt lonely and those who did not (p = 0.110 and p = 0.751, respectively). Sleep latency was longer in those who felt lonely (26.84 [0.9] vs. 35.52 [1.2] min, p < 0.001) than in those who did not. Furthermore, participants who felt lonely tended to have poor subjective sleep, a higher frequency of nocturnal awakenings, daytime sleepiness and fatigue (all p < 0.001).ConclusionsLoneliness was associated with extended sleep latency, increased nocturnal awakenings, and reduced subjective sleep quality and daytime function but was not associated with sleep behavior, including sleep onset and offset timings.     

Idiopathic hypersomnia: a homogeneous or heterogeneous disease?

IntroductionIdiopathic hypersomnia (IH) is a rare orphan disease characterized by excessive daytime sleepiness, frequently accompanied by prolonged nocturnal sleep and difficulties awakening, termed sleep inertia or sleep drunkenness. Severe sleepiness usually causes a greater handicap than manifestations of narcolepsy.MethodsForty-three IH patients (17 male, mean age 42.8 ± SD 12.2 years, range 20–67), diagnosed in the past 20 years according to ICSD-2 or ICSD-3 criteria were invited for clinical examination to evaluate the course, manifestations and severity of the disease, as well as clinical comorbidities. The patients completed a set of questionnaires scoring sleepiness, sleep inertia, fatigue, depression, anxiety, circadian preference, and quality of life.ResultsIH patients were divided according to the duration of nocturnal sleep at the time of their diagnosis into two cohorts: (1) with normal sleep duration (n = 25, 58.1%) and (2) with long sleep duration (n = 18, 41.9%). The mean duration of ad libitum sleep per 22 h in the second cohort was 732.0 ± 115.4 min (range 603–1100), and women markedly prevailed (n = 14, 77.8%). Age at disease onset was younger in the group with long sleep duration (21.2 ± 11.4 years versus 28.1 ± 13.6 years, p = 0.028), their MSLT latency was longer (7.2 ± 3.7 min versus 5.1 ± 1.7 min, p = 0.005), a history of sleep inertia prevailed (p = 0.005), and daily naps were mostly non-refreshing (p = 0.014). Additionally, questionnaires in the group with long sleep duration showed more severe sleep inertia (p = 0.007), fatigue (p = 0.004), and a tendency towards evening chronotype (p = 0.001).ConclusionsIH patients with long sleep duration differ clinically as well as by objective measures at the time of diagnosis and in long-term follow up from IH patients without long 24-h sleep time. In our opinion they represent an independent clinical entity to be considered in the revised ICSD-3 criteria.     

Subjective sleep quality in adult patients affected by Duchenne muscular dystrophy. Beyond nocturnal hypoventilation

ObjectiveIn stable neuromuscular patients under long-term non-invasive ventilation (NIV), subjective sleep quality may be predicted by chronic hypoventilation, as assessed by base excess (BE), and %N3 sleep stage duration. In this study, we explored how other variables, closely associated with self-reported health complaints, contributed to subjective sleep quality in adult patients with Duchenne muscular dystrophy (DMD).MethodsThis is a secondary analysis of a quality of life study in 48 adult DMD patients under NIV therapy, with little evidence of residual hypoventilation. Subjective sleep quality was evaluated by the Pittsburgh Sleep Quality Index (PSQI). A PSQI score >5 was considered indicative of poor sleep quality. Several other symptoms were evaluated: sleepiness, by the Epworth Sleepiness Scale (ESS); depression and anxiety, by the anxiety and depression subscales of the Hospital Anxiety and Depression Scale (HADS-A and HADS-D); autonomic symptoms, by the Composite Autonomic Symptom Score 31; pain, by the Numeric Pain Rating Scale (NPRS); and fatigue, by the Fatigue Severity Scale (FSS).ResultsMean PSQI was 6.1 ± 2.9. Abnormal scores were found for NPRS in 40, for HADS-A in 10 and for FSS in 24 subjects. The NPRS, HADS-A and FSS scores and the N3 sleep stage, independently predicted PSQI (R² = 0.47, p < 0.0001).ConclusionsIn adult DMD patients, pain, fatigue and anxiety may have a prominent influence on subjective sleep quality. Improvement of sleep quality may be of utmost importance in DMD, as it may ameliorate quality of life and extend its benefits to cardiovascular morbidity and life expectancy.     

Fatigue,sleepiness, and physical activity in patients with multiple sclerosis

Fatigue is a frequent and disabling symptom in patients with multiple sclerosis (MS). The objective of the study was to compare fatigue and sleepiness in MS, and their relationship to physical activity. Eighty patients with MS rated the extent of experienced fatigue (Fatigue Severity Scale, FSS) and sleepiness (Epworth Sleepiness Scale, ESS). The relationship between the scales was analysed for the scales as a whole and for single items. The clinical status of the patients was measured with the Extended Disability Status Scale (EDSS). In addition, physical activity was recorded continuously for 1 week by wrist actigraphy. The mean scores of fatigue and sleepiness were significantly correlated (FSS vs. ESS r = 0.42). Single item analysis suggests that fatigue and sleepiness converge for situations that demand self-paced activation, while they differ for situations in which external cues contribute to the level of activation. While fatigue correlated significantly with age (r = 0.40), disease severity (EDSS, r = 0.38), and disease duration (r = 0.25), this was not the case for sleepiness. Single patient analysis showed a larger scatter of sleepiness scores in fatigued patients (FSS > 4) than in non-fatigued patients. Probably, there is a subgroup of MS patients with sleep disturbances that rate high on ESS and FSS. The amount of physical activity, which was measured actigraphically, decreased with disease severity (EDSS) while it did not correlate with fatigue or sleepiness.     

Impact of acute administration of sodium oxybate on heart rate variability in children with type 1 narcolepsy

BackgroundCurrently, cardiovascular measurements in children affected with type 1 narcolepsy (NT1) have never been investigated, and neither have their modulation by the administration of sodium oxybate (SO).MethodsTwelve drug-naïve NT1 children (four males, eight females) with a mean age of 11 ± 3.16 years underwent a nocturnal polysomnography, at baseline and during the first night of SO administration. Data were contrasted with those recorded in 23 age-matched healthy controls. Heart rate variability (HRV) analysis was performed by analyzing the electrocardiogram signal for automatic detection of R waves with a computer program calculating a series of standard time-domain measures and obtaining spectral parameters, by means of a Fast-Fourier Transform.ResultsIn sleep stages N2 and N3, NT1 children showed increased power in the low-frequency (LF) and very-LF (VLF) ranges, when compared to controls. In addition, HRV (as measured by time domain parameters) during all sleep stages tended to be slightly higher in patients when compared to controls. Treatment with SO did not change significantly any parameter, but an overall trend to mildly decreased HRV that reached a significant value only during R sleep.ConclusionsHRV during all sleep stages tended to be slightly higher in young patients when compared to controls, confirming the presence of a slight sympathovagal system imbalance even in NT1 children. SO tends to decrease these values especially during REM sleep and in that regard, further studies supporting these preliminary findings and considering the long-term effects of SO on heart rate parameters are warranted.     

Night-shift work increases cold pain perception

BackgroundAlthough night-shift work (NSW) is associated with a higher risk for several physical and mental disorders, the impact of NSW on pain perception is still unclear. This study investigates the impact of NSW on cold pain perception considering the impact of mood and sleepiness.MethodQuantitative sensory testing (QST) was performed in healthy night-shift workers. Cold pain threshold as well as tonic cold pain was assessed after one habitual night (T1), after a 12-hour NSW (T2) and after one recovery night (T3). Sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI) before T1, sleepiness with the Stanford Sleepiness Scale (SSS) and mood with a German short-version of the Profile of Mood States (ASTS) at T1, T2 and T3. Depending on the distribution of the data, ANOVAs or Friedman tests as well as t- or Wilcoxon tests were performed.ResultsNineteen healthy shift-workers (13 females; 29.7 ± 7.5 years old; 8.1 ± 6.6 years in shift work, PSQI: 4.7 ± 2.2) were included. Tonic cold pain showed a significant difference between T1 (48.2 ± 27.5 mm), T2 (61.7 ± 26.6 mm; effect size: Cohen's d=.49; percent change 28%), and T3 (52.1 ± 28.7 mm) on a 0–100 mm Visual Analog Scale (p = 0.007). Cold pain threshold changed from 11.0 ± 7.9 °C (T1) to 14.5 ± 8.8 °C (T2) (p = 0.04), however, an ANOVA comparing T1, T2, and T3 was not significant (p = 0.095). Sleepiness (SSS) and mood (ASTS) changed significantly between T1, T2 and T3 (p-values < 0.01). The change of mood but not of sleepiness correlated with the difference in tonic cold pain from T1 to T2 (R: 0.53; R²: 0.29; p = 0.022).DiscussionNSW increases cold pain perception. The same tonic cold pain stimulus is rated 28% more painful after NSW and normalizes after a recovery night. Increases in cold pain perception due to NSW appear to be more strongly related to changes in mood as compared to changes in sleepiness.     

Depressive feelings in children with narcolepsy

ObjectivesWe aimed to evaluate depressive feelings and their correlations in children and adolescents with narcolepsy collected in national reference centers for narcolepsy.MethodsWe compared clinical and sleep characteristics of patients with and without depressive symptoms evaluated on the Children’s Depression Inventory (CDI).ResultsOur study sample included 88 children (44 boys; 44 de novo patients) with a mean age of 11.9 ± 3.1 years at diagnosis (37.5% were aged ⩽10 years). Obesity was found in 59% of the sample and cataplexy was present in 80.7%. The DQB1*0602 allele was positive in 93.5% of our sample. There were 25% of children who had clinically depressive feelings (CDI > 16), especially girls older than the age of 10 years. Bivariate associations indicated that depressive feelings were associated with fatigue (48%), hyperactivity (31%), insomnia (16%), and excessive daytime sleepiness (EDS) (14–24%). In the multivariate model adjusted for gender and age, only fatigue explained the variability of the depression score.ConclusionIn our large cohort, high levels of depressive symptoms essentially expressed by fatigue affected 25% of children with narcolepsy. The girls older than 10 years of age were especially vulnerable. The similar prevalence of depressive feelings in treated vs never-treated patients suggests a specific need for diagnosing and managing this symptom in young patients with narcolepsy.     

Motor,behavioural, and cognitive correlates of fatigue in early,de novo Parkinson disease patients

IntroductionFatigue is one of the most common and disabling non-motor symptoms in Parkinson's disease (PD). The objective of this study was to determine prevalence and motor, behavioural, and cognitive correlates of distressing fatigue in early, de novo PD patients.MethodsEighty-one consecutive de novo PD patients (64% men; mean age 65.73 ± 8.26 years) underwent a comprehensive examination, including Parkinson's disease Fatigue Scale (PFS), Epworth Sleepiness Scale (ESS), Parkinson's Disease Sleep Scale (PDSS), Beck Depression Inventory (BDI), Parkinson's Anxiety Scale (PAS), and Apathy Evaluation Scale (AES). Moreover, all patients underwent a detailed neuropsychological evaluation exploring attention and working memory, executive functions, memory, visuospatial abilities and language. Score of patients with or without distressing fatigue (defined as a PFS score ≥ 8) were compared by Student's t-test or Pearson's chi-square test. Logistic regression analyses were performed to search for motor and non-motor features independently associated with presence of distressing fatigue.ResultsTwelve (15%) patients presented distressing fatigue. Logistic regression identified sleepiness (p = 0.04), “episodic anxiety” subscale of PAS (p = 0.005), and “cognitive apathy” subscale of AES (p = 0.017) as the main factors associated with distressing fatigue. No significant association was found between diagnosis of Mild Cognitive Impairment and distressing fatigue (p = 0.745).ConclusionIn a sample of consecutive de novo PD patients, distressing fatigue is associated with episodic anxiety, cognitive apathy and sleepiness, but not with cognitive impairment. Our findings suggest possible shared pathogenic mechanisms underlying these non-motor symptoms and foster development of early combined therapeutic approaches.