Increased Blood Pressure Dipping in Restless Legs Syndrome With Rotigotine: A Randomized Trial.

OBJECTIVE: The objective of this study was to assess the rotigotine effect on the nocturnal blood pressure (BP) dip by 24-hour ambulatory BP monitoring and on endothelial function in patients with restless legs syndrome (RLS) compared with placebo. METHODS: In this double-blind, placebo-controlled trial, 76 adult patients with moderate to severe RLS and periodic legs movements in sleep index ≥10/hour were randomized to rotigotine at optimal dose of 3 mg per day or placebo for 6 weeks. A total of 6 patients had a major protocol deviation. Polysomnography, ambulatory BP monitoring, and endothelial function were assessed at baseline and end point. The primary outcome was the between-group difference in the percentage of BP nondipper profiles at end point. The main secondary outcomes were the mean BP dip, periodic legs movements in sleep index, and endothelial function. RESULTS: Of the 70 patients (age, 59.4 ± 11.40; 43 women) randomized to rotigotine (n = 34) and placebo (n = 36), 66 (33 rotigotine, 33 placebo) completed the study. The percentage of BP nondippers at end point was higher in the placebo than in the rotigotine group (systolic BP, 72.22% vs 47.06%; diastolic BP, 47.22% vs 20.59%; P < 0.05). Mean BP dip at end point was higher in the rotigotine than in the placebo group (systolic BP, 11.24 ± 6.15 vs 6.12 ± 7.98; diastolic BP, 15.12 ± 7.09 vs 9.36 ± 10.23; P < 0.05). Endothelial function was comparable between the groups. No significant safety concerns were reported with similar incidences of adverse events between groups. CONCLUSION: Rotigotine increased the percentage of BP dipper profiles and the BP dip in patients with RLS. Future studies should assess whether this change is associated with a reduction in the long-term cardiovascular risk in RLS. © 2020 International Parkinson and Movement Disorder Society.

Rhythm disturbances as a potential early marker of Parkinson's disease in idiopathic REM sleep behavior disorder.

OBJECTIVE: We aimed to identify timing distortions in production and perception of rhythmic events in patients with idiopathic REM sleep behavior disorder (iRBD) as early markers of Parkinson's disease (PD). METHODS: Rhythmic skills, clinical characteristics, dysautonomia, depression, and olfaction were compared in 97 participants, including 21 participants with iRBD, 38 patients with PD, and 38 controls, matched for age, gender, and education level. Rhythmic disturbances can be easily detected with dedicated motor tasks via a tablet application. Rhythm production was tested in two conditions: to examine the ability to generate a spontaneous endogenous rhythm, tapping rate and variability in a finger tapping task without external stimulation was measured, while the ability to synchronize to an external rhythm was tested with finger tapping to external auditory cues. Rhythm perception was measured with a task, in which the participants had to detect a deviation from a regular rhythm. Participants with iRBD had dopamine transporter imaging. RESULTS: Participants with iRBD and PD revealed impaired spontaneous rhythm production and poor rhythm perception compared to controls. Impaired rhythm production was correlated with olfaction deficits, dysautonomia, impaired non-motor aspects of daily living, and dopamine uptake measures. CONCLUSIONS: Participants with iRBD show impaired rhythm production and perception; this impairment is correlated with other early markers for PD. Testing rhythmic skills with short and inexpensive tests may be promising for screening for potential future PD in iRBD patients.

Reduced brain amyloid burden in elderly patients with narcolepsy type 1.

OBJECTIVE: To determine whether brain amyloid burden in elderly patients with narcolepsy type 1 (NT1) is lower than in controls, and to assess in patients with NT1 the relationships between amyloid burden, cerebral spinal fluid (CSF) markers of Alzheimer disease (AD), CSF orexin-A, and cognitive profile. METHODS: Cognitive and 18 F-florbetapir positron emission tomography (PET) data were compared in patients with NT1 aged ≥ 65 years (n = 23) and in age- and sex-matched controls free of clinical dementia selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI; n = 69) and the Multi-Domain Intervention Alzheimer's Prevention Trial (MAPT-18F AV45-PET; n = 23) cohorts. The standardized uptake values (SUVs) of the cortical retention index for 6 regions of interest were computed and averaged to create a mean SUV ratio normalized to 3 subcortical reference regions (cerebellum, pons, and a composite region). A cortical/cerebellum SUV ratio ≥ 1.17 defined positive PET amyloid. RESULTS: Lower cortical amyloid burden was observed in the NT1 than in the ADNI and MAPT-AV45 groups (mean cortical/cerebellum SUV ratios = 0.95 ± 0.15, 1.11 ± 0.18 [p < 0.0001], and 1.14 ± 0.17 [p = 0.0005], respectively). Similar results were obtained with all subcortical reference regions and for all cortical regions of interest, except cingulum. Only 1 patient with NT1 (4.4%) had positive PET amyloid compared with 27.5% in the ADNI and 30.4% in the MAPT-AV45 group. In the NT1 group, cortical or regional amyloid load was not associated with CSF orexin-A, CSF AD biomarkers, or neuropsychological profile. INTERPRETATION: Lower brain amyloid burden, assessed by 18 F-florbetapir PET, in patients with NT1 suggests delayed appearance of amyloid plaques. ANN NEUROL 2019;85:74-83.

Measurement of narcolepsy symptoms: The Narcolepsy Severity Scale.

OBJECTIVE: To validate the Narcolepsy Severity Scale (NSS), a brief clinical instrument to evaluate the severity and consequences of symptoms in patients with narcolepsy type 1 (NT1). METHODS: A 15-item scale to assess the frequency and severity of excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis, and disrupted nighttime sleep was developed and validated by sleep experts with patients' feedback. Seventy untreated and 146 treated adult patients with NT1 were evaluated and completed the NSS in a single reference sleep center. The NSS psychometric properties, score changes with treatment, and convergent validity with other clinical parameters were assessed. RESULTS: The NSS showed good psychometric properties with significant item-total score correlations. The factor analysis indicated a 3-factor solution with good reliability, expressed by satisfactory Cronbach α values. The NSS total score temporal stability was good. Significant NSS score differences were observed between untreated and treated patients (dependent sample, 41 patients before and after sleep therapy; independent sample, 29 drug-free and 105 treated patients). Scores were lower in the treated populations (10-point difference between groups), without ceiling effect. Significant correlations were found among NSS total score and daytime sleepiness (Epworth Sleepiness Scale, Mean Sleep Latency Test), depressive symptoms, and health-related quality of life. CONCLUSIONS: The NSS can be considered a reliable and valid clinical tool for the quantification of narcolepsy symptoms to monitor and optimize narcolepsy management.

Vitamin D deficiency in type 1 narcolepsy: a reappraisal.

OBJECTIVES: Narcolepsy type 1 (NT1) is considered to be an immune-mediated disease in which environmental factors, such as vitamin D, might play a major role. The association between NT1 and vitamin D deficiency has previously been reported. The aim of this case-control study was to reassess vitamin D levels in a large clinic-based adult and paediatric population of patients with NT1 by considering several potential confounding factors. METHODS: The serum level of 25-hydroxyvitamin D (25OHD) was measured in 174 Caucasian patients with NT1 and 174 controls. Demographic and clinical features, body mass index (BMI), Pandemrix® vaccination, age, and season at the time of blood sampling were recorded. Between-group comparisons were made using univariate and multivariate logistic regression analyses. When appropriate, interaction terms were tested using the Wald Chi-squared test. RESULTS: Age, BMI, and season of blood sampling were different between groups. Conversely, the 25OHD level and fraction of subjects with vitamin D deficiency (serum level <75 nmol/L: 46.6% of patients vs 48.3% of controls; <50 nmol/L: 20.7% vs 17.2%) did not differ between patients with NT1 and controls. Overall, vitamin D deficiency was more frequent in men, obese subjects, and in samples collected in winter, without any association with NT1. In the patients group, no significant association was found between vitamin D deficiency, NT1 duration and severity, treatment, and Pandemrix® vaccination. CONCLUSIONS: Vitamin D levels were not associated with NT1 in a large case-control population when potential demographic and clinical confounding factors were taken into account.

Low cancer prevalence in polyglutamine expansion diseases.

OBJECTIVE: Polyglutamine (PolyQ) diseases are dominantly transmitted neurologic disorders, caused by coding and expanded CAG trinucleotide repeats. Cancer was reported retrospectively to be rare in patients with PolyQ diseases and we aimed to investigate its prevalence in France. METHODS: Consecutive patients with Huntington disease (HD) and spinocerebellar ataxia (SCA) were questioned about cancer, cardiovascular diseases, and related risk factors in 4 university hospitals in Paris, Toulouse, Strasbourg, and Montpellier. Standardized incidence ratios (SIR), based on age- and sex-adjusted rate of the French population, were assessed for different types of cancer. RESULTS: We questioned 372 patients with HD and 134 patients with SCA. SIR showed significantly reduced risk of cancer in HD: 23 observed cases vs 111.05 expected ones (SIR 0.21, 95% confidence interval [CI] 0.13-0.31), as well as in SCA: 7 observed cases vs 34.73 expected (SIR 0.23, 95% CI 0.08-0.42). This was surprising since risk behavior for cancer was increased in these patients, with significantly greater tobacco and alcohol consumption in patients with HD vs patients with SCA (p < 0.0056). There was no association between CAG repeat size and cancer or cardiovascular disease. However, in patients with HD, skin cancers were more frequent than expected (5 vs 0.98, SIR 5.11, 95% CI 1.65-11.95). CONCLUSIONS: There was a decreased cancer rate in PolyQ diseases despite high incidence of risk factors. Intriguingly, skin cancer incidence was higher, suggesting a crosstalk between neurodegeneration and skin tumorigenesis.

Mini-Exome Coupled to Read-Depth Based Copy Number Variation Analysis in Patients with Inherited Ataxias.

Next-generation sequencing (NGS) has an established diagnostic value for inherited ataxia. However, the need of a rigorous process of analysis and validation remains challenging. Moreover, copy number variations (CNV) or dynamic expansions of repeated sequence are classically considered not adequately detected by exome sequencing technique. We applied a strategy of mini-exome coupled to read-depth based CNV analysis to a series of 33 patients with probable inherited ataxia and onset <50 years. The mini-exome consisted of the capture of 4,813 genes having associated clinical phenotypes. Pathogenic variants were found in 42% and variants of uncertain significance in 24% of the patients. These results are comparable to those from whole exome sequencing and better than previous targeted NGS studies. CNV and dynamic expansions of repeated CAG sequence were identified in three patients. We identified both atypical presentation of known ataxia genes (ATM, NPC1) and mutations in genes very rarely associated with ataxia (ERCC4, HSD17B4). We show that mini-exome bioinformatics data analysis allows the identification of CNV and dynamic expansions of repeated sequence. Our study confirms the diagnostic value of the proposed genetic analysis strategy. We also provide an algorithm for the multidisciplinary process of analysis, interpretation, and validation of NGS data.

Supine sleep and obstructive sleep apnea syndrome in Parkinson's disease.

OBJECTIVE: Supine sleep is associated with increased obstructive sleep apnea. People with Parkinson's disease (PD) complain about difficulties turning around in bed. The relationship between supine sleep and sleep-disordered breathing has never been explored in people with Parkinson's disease. METHODS: Fifteen consecutive people with PD with severe Obstructive Sleep Apnea Syndrome (OSAS) were compared to: (1) 15 age-matched, gender-matched, body mass index-matched and Unified Parkinson's Disease Rating Scale-III score-matched people with PD without sleep-disordered breathing; (2) 11 age-matched and gender-matched people with severe obstructive sleep apnea syndrome (OSAS) alone; and (3) 11 age-matched and gender-matched healthy controls. Outcomes were: number of position changes during the night and per hour of sleep, and the percentage of sleep time spent in supine. RESULTS: People with PD and severe OSAS spent most of their sleep time in the supine position (93 ± 11%); while people with PD without OSAS (61 ± 24%, p <0.001), people with isolated, severe OSAS (50 ± 28%, p <0.001), and the controls (40 ± 21, p <0.001) spent significantly less time on their back. People with PD and severe OSAS changed their position in bed per hour of sleep (0.4 ± 0.5) less frequently than those with PD without OSAS (1.1 ± 0.8, p = 0.002), those with isolated OSAS (1.2 ± 1.0, p = 0.006) and the controls (1.5 ± 0.5, p <0.001). CONCLUSION: PD and severe OSAS are associated with a major reduction in the number of position changes and an increased supine sleep position during the night. For people with PD, alleviating the difficulties of turning around in bed might reduce the supine sleep position and improve sleep-disordered breathing.

Risk factors for neurodegeneration in idiopathic rapid eye movement sleep behavior disorder: a multicenter study.

OBJECTIVE: To assess whether risk factors for Parkinson disease and dementia with Lewy bodies increase rate of defined neurodegenerative disease in idiopathic rapid eye movement (REM) sleep behavior disorder (RBD). METHODS: Twelve centers administered a detailed questionnaire assessing risk factors for neurodegenerative synucleinopathy to patients with idiopathic RBD. Variables included demographics, lifestyle factors, pesticide exposures, occupation, comorbid conditions, medication use, family history, and autonomic/motor symptoms. After 4 years of follow-up, patients were assessed for dementia or parkinsonism. Disease risk was assessed with Kaplan-Meier analysis, and epidemiologic variables were compared between convertors and those still idiopathic using logistic regression. RESULTS: Of 305 patients, follow-up information was available for 279, of whom 93 (33.3%) developed defined neurodegenerative disease. Disease risk was 25% at 3 years and 41% after 5 years. Patients who converted were older (difference = 4.5 years, p < 0.001), with similar sex distribution. Neither caffeine, smoking, nor alcohol exposure predicted conversion. Although occupation was similar between groups, those who converted had a lower likelihood of pesticide exposure (occupational insecticide = 2.3% vs 9.0%). Convertors were more likely to report family history of dementia (odds ratio [OR] = 2.09), without significant differences in Parkinson disease or sleep disorders. Medication exposures and medical history were similar between groups. Autonomic and motor symptoms were more common among those who converted. Risk factors for primary dementia and parkinsonism were generally similar, except for a notably higher clonazepam use in dementia convertors (OR = 2.6). INTERPRETATION: Patients with idiopathic RBD are at very high risk of neurodegenerative synucleinopathy. Risk factor profiles between convertors and nonconvertors have both important commonalities and differences.

Impulse control disorder and rapid eye movement sleep behavior disorder in Parkinson's disease.

INTRODUCTION: The relationship between ICD and RBD is still not yet understood and the results from the current literature are contradictory in PD. We aimed to explore the association between rapid eye movement (REM) sleep behavior disorder (RBD) and impulse control disorder in Parkinson's disease. METHODS: Ninety-eight non-demented patients with Parkinson's disease underwent one night of video-polysomnography recording. The diagnosis of RBD was established according to clinical and polysomnographic criteria. Impulse control disorders were determined by a gold standard, semi-structured diagnostic interview. RESULTS: Half of the patients (n = 49) reported clinical history of RBD while polysomnographic diagnosis of RBD was confirmed in 31.6% of the patients (n = 31). At least one impulse control disorder was identified in 21.4% of patients, 22.6% with RBD and 20.9% without. Logistic regression controlling for potential confounders indicated that both clinical RBD (OR = 0.34, 95% CI = 0.07-1.48, P = 0.15) and polysomnographic confirmed RBD diagnoses (OR = 0.1.28, 95% CI = 0.31-5.33, P = 0.34) were not associated with impulse control disorder. CONCLUSION: In Parkinson's disease, REM Sleep Behavior Disorder is not associated with impulse control disorder. The results of our study do not support the notion that PSG-confirmed RBD and ICD share a common pathophysiology.

Daytime sleepiness in Parkinson's disease: a reappraisal.

BACKGROUND: Excessive daytime sleepiness is a frequent complaint in Parkinson's disease (PD); however the frequency and risk factors for objective sleepiness remain mostly unknown. We investigated both the frequency and determinants of self-reported and objective daytime sleepiness in patients with Parkinson's disease (PD) using a wide range of potential predictors. METHODS: One hundred and thirty four consecutive patients with PD, without selection bias for sleep complaint, underwent a semi-structured clinical interview and a one night polysomnography followed by a multiple sleep latency test (MSLT). Demographic characteristics, medical history, PD course and severity, daytime sleepiness, depressive and insomnia symptoms, treatment intake, pain, restless legs syndrome, REM sleep behaviour disorder, and nighttime sleep measures were collected. Self-reported daytime sleepiness was defined by an Epworth Sleepiness Scale (ESS) score above 10. A mean sleep latency on MSLT below 8 minutes defined objective daytime sleepiness. RESULTS: Of 134 patients with PD, 46.3% had subjective and only 13.4% had objective sleepiness with a weak negative correlation between ESS and MSLT latency. A high body mass index (BMI) was associated with both ESS and MSLT, a pain complaint with ESS, and a higher apnea/hypopnea index with MSLT. However, no associations were found between both objective and subjective sleepiness, and measures of motor disability, disease onset, medication (type and dose), depression, insomnia, restless legs syndrome, REM sleep behaviour disorder and nighttime sleep evaluation. CONCLUSION: We found a high frequency of self-reported EDS in PD, a finding which is however not confirmed by the gold standard neurophysiological evaluation. Current treatment options for EDS in PD are very limited; it thus remains to be determined whether decreasing pain and BMI in association with the treatment of sleep apnea syndrome would decrease significantly daytime sleepiness in PD.

Hypothalamic immunopathology in anti-Ma-associated diencephalitis with narcolepsy-cataplexy.

IMPORTANCE: Idiopathic narcolepsy with cataplexy is thought to be an autoimmune disorder targeting hypothalamic hypocretin neurons. Symptomatic narcolepsy with low hypocretin level has been described in Ma antibody­associated encephalitis; however, the mechanisms underlying such an association remain unknown. OBSERVATIONS: We described a 63-year-old man with clinical criteria for diencephalic encephalitis with sleepiness, cataplexy, hypocretin deficiency, and central hypothyroidism, together with brainstem encephalitis reflected by supranuclear ophtalmoparesis and rapid eye movement sleep behavior disorder with underlying abnormalities on brain magnetic resonance imaging. An autoimmune process was demonstrated by the detection of antibodies against Ma protein. Death occurred 4 months after disease onset without any tumor detected. Neuropathology, immunohistochemistry, and immunoreactivity results were compared with those obtained in idiopathic narcolepsy-cataplexy and with normal control brains. The principal findings revealed almost exclusive inflammation and tissue injury in the hypothalamus. The type of inflammatory reaction suggests cytotoxic CD8+ T lymphocytes being responsible for the induction of tissue injury. Inflammation was associated with complete loss of hypocretinergic neurons. Autoantibodies of the patient predominantly stained neurons in the hypothalamus and could be absorbed with Ma2. CONCLUSIONS AND RELEVANCE: The encephalitic process, responsible for narcolepsy-cataplexy and hypocretin deficiency, reflects a CD8+ inflammatory-mediated response against hypocretin neurons.

Ipsilateral uveitis and optic neuritis in multiple sclerosis.

Background. Uveitis is 20 times more frequent in multiple sclerosis (MS) patients than in the general population. Methods. A retrospective study of local multiple sclerosis (n = 700) and uveitis cohorts (n = 450) described the ophthalmological and neurological characteristics of patients with multiple sclerosis and uveitis. Results. Uveitis and multiple sclerosis were associated in seven patients. The time intervals between diagnoses of MS and uveitis ranged from 6 months to 15 years. Analysis of the patients' characteristics revealed that multiple sclerosis was associated with an older age of onset than usually expected, that is, 39 years. Uveitis was bilateral in three cases and mainly posterior (5/10). Five patients presented with acute optic neuritis (two in one eye and three in both eyes). All eyes presenting with acute optic neuritis were also affected by uveitis (P = 0.02), though not simultaneously. Conclusion. The ipsilateral association between optic neuritis and uveitis in this series of patients with multiple sclerosis may suggest a reciprocal potentiation between optic neuritis and uveitis in multiple sclerosis.

Subcutaneous IFN-ß1a to treat relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is the main nontraumatic cause of handicap in young adults. Immunomodulators and treatments limiting lymphocyte migration have been proven efficient to treat relapsing-remitting MS. Subcutaneous IFN-ß1a improve relapse rate and MRI parameters in a series of double-blind, placebo-controlled trials in relapsing-remitting MS patients. Similar results, and with a greater extent, were obtained when treating patients with a first demyelinating event suggestive of MS. Except for the rare liver toxicity, the drug is well tolerated and has no severe adverse reaction. When compared with intramuscular IFN-ß1a, both relapse rate and MRI parameters were modulated in favor of the subcutaneous administration. Although the effect of subcutaneous IFN-ß1a on disability progression is limited, the good tolerance profile together with the efficiency of the drug explain why this treatment, as well as the other interferons and glatiramer acetate, is a first-line therapy for relapsing-remitting MS.

Suggested immobilization test for diagnosis of restless legs syndrome in Parkinson's disease.

Diagnosis of restless leg syndrome (RLS) in Parkinson's disease (PD) is difficult because of clinical confounds. The suggested immobilization test (SIT) is validated for diagnosis of primary RLS. This study evaluated the usefulness of the SIT for diagnosis of RLS in PD. We compared SIT scores, as well as polysomnography measures in 50 patients with PD (25 with RLS, 25 without), 25 patients with primary RLS, and 25 age/sex matched controls. Mean leg discomfort score was increased in patients with PD and RLS compared to PD without RLS, and also in patients with primary RLS compared to controls. Leg discomfort was significantly higher at the end of the test in patients with RLS compared to patients without RLS. Intensity of leg discomfort was similar between patients with RLS, with or without PD. Using a mean leg discomfort cutoff of 11, we showed sensitivity of 91% and specificity of 72% for RLS diagnosis in PD during symptomatic time intervals. Periodic leg movements index during the SIT did not differ between groups. Periodic leg movements index during sleep and wakefulness was increased in patients with primary RLS compared to controls, but did not differ between patients with PD, with and without RLS. The sensory SIT is a simple test that may help diagnose RLS in patients with PD.

Low vitamin D in narcolepsy with cataplexy.

BACKGROUND: Narcolepsy with cataplexy (NC) is currently thought to be an autoimmune-mediated disorder in which environmental risk factors make a significant contribution to its development. It was proposed that vitamin D deficiency plays a role in autoimmune diseases. Here we investigated whether NC can be associated with 25-hydroxyvitamin D (25(OH)D) level deficiency in patients with NC compared with gender- and age-matched normal controls. METHODOLOGY: Serum level of 25 (OH)D was determined in 51 European patients with typical NC compared to 55 age-, gender-, and ethnicity-matched healthy controls. Demographic and clinical data (age at onset, duration and severity of disease at baseline, and treatment intake at time of study) and season of blood sampling were collected to control for confounding variables. PRINCIPAL FINDINGS: Serum 25(OH)D concentration was lower in NC compared to controls (median, 59.45 nmol/l [extreme values 24.05-124.03] vs. 74.73 nmol/l [26.88-167.48] p = 0.0039). Patients with NC had significantly greater vitamin D deficiency (<75 nmol/l) than controls (72.5% vs 50.9%, p = 0.0238). Division into quartiles of the whole sample revealed that the risk of being affected with NC increased with lower 25(OH)D level, with a 5.34 OR [1.65-17.27] for the lowest quartile (p = 0.0051). Further adjustment for BMI did not modify the strength of the association (OR: 3.63, 95% CI = 1.06-12.46, p = 0.0191). No between BMI and 25(OH)D interaction, and no correlation between 25(OH)D level and disease duration or severity or treatment intake were found in NC. CONCLUSION: We found a higher frequency of vitamin D deficiency in NC. Further studies are needed to assess the contribution of hypovitaminosis D to the risk of developing narcolepsy, and to focus on the utility of assessing vitamin D status to correct potential deficiency.

Decision making in narcolepsy with cataplexy.

OBJECTIVES: To investigate decision-making and addictive behaviors in narcolepsy-cataplexy (NC). NC is caused by the loss of hypothalamic neurons that produce hypocretins. The hypocretin system plays a crucial role in sleep, wakefulness, and energy homeostasis, and is also involved in emotion regulation, reward processing, and addiction. SETTING: Academic sleep center. PATIENTS: 23 subject with NC and 23 matched healthy controls. DESIGN: We used the Iowa Gambling Task (IGT) to assess decision making under ambiguity condition based on emotional feedback processing and the Game of Dice Task (GDT) to assess decision making under risk condition. All participants underwent a semi-structured psychiatric interview and completed the Beck Depression Inventory-II and the UPPS Impulsive Behavior Scale. Patients underwent one night of polysomnography followed by an MSLT, with neuropsychological evaluation performed between MSLT sessions. MEASUREMENTS AND RESULTS: NC patients had higher depressive symptoms and showed a significant lack of perseverance. One NC patient had a past history of drug dependence. NC patients also exhibited selective reduced IGT performance and normal performance on the GDT. No clinical or polysomnographic characteristics were associated with increased sensitivity to reward and/or decreased sensitivity to punishment. However, lack of perseverance in NC patients was associated with disadvantageous decision making on the IGT. CONCLUSION: We demonstrated a lack of perseverance and a selective reduced performance on decision making under ambiguity in NC in contrast to normal decision making under explicit conditions. Patients with narcolepsy-cataplexy may opt for choices with higher immediate emotional valence, regardless of higher future punishment, to compensate for their reduced reactivity to emotional stimuli.