ImmunoChip study implicates antigen presentation to T cells in narcolepsy.

Recent advances in the identification of susceptibility genes and environmental exposures provide broad support for a post-infectious autoimmune basis for narcolepsy/hypocretin (orexin) deficiency. We genotyped loci associated with other autoimmune and inflammatory diseases in 1,886 individuals with hypocretin-deficient narcolepsy and 10,421 controls, all of European ancestry, using a custom genotyping array (ImmunoChip). Three loci located outside the Human Leukocyte Antigen (HLA) region on chromosome 6 were significantly associated with disease risk. In addition to a strong signal in the T cell receptor alpha (TRA@), variants in two additional narcolepsy loci, Cathepsin H (CTSH) and Tumor necrosis factor (ligand) superfamily member 4 (TNFSF4, also called OX40L), attained genome-wide significance. These findings underline the importance of antigen presentation by HLA Class II to T cells in the pathophysiology of this autoimmune disease.

Narcolepsy and pregnancy: a retrospective European evaluation of 249 pregnancies.

In a retrospective cohort study undertaken in 12 European countries, 249 female narcoleptic patients with cataplexy (n = 216) and without cataplexy (n = 33) completed a self-administrated questionnaire regarding pregnancy and childbirth. The cohort was divided further into patients whose symptoms of narcolepsy started before or during pregnancy (308 pregnancies) and those in whom the first symptoms of narcolepsy appeared after delivery (106 pregnancies). Patients with narcolepsy during pregnancy were older during their first pregnancy (P < 0.001) and had a higher body mass index (BMI) prior to pregnancy (P < 0.01). Weight gain during pregnancy was higher in narcoleptic patients with cataplexy (P < 0.01). More patients with narcolepsy-cataplexy during pregnancy had impaired glucose metabolism and anaemia. Three patients experienced cataplexy during delivery. The rate of caesarean sections was higher in the narcolepsy-cataplexy group compared to the narcolepsy group (P < 0.05). The mean birth weight and gestational age of neonates were within the normal range and did not differ across groups. Neonatal care was affected adversely by symptoms of narcolepsy in 60.1% of those with narcolepsy during pregnancy. This study reports more obstetric complications in patients with narcolepsy-cataplexy during pregnancy; however, these were not severe. This group also had a higher BMI and higher incidence of impaired glucose metabolism during pregnancy. Caesarian section was conducted more frequently in narcolepsy-cataplexy patients, despite cataplexy being a rare event during delivery. Furthermore, symptoms of narcolepsy may render care of the infant more difficult.

Validation of the Innsbruck REM sleep behavior disorder inventory.

A diagnosis of definite REM sleep behavior disorder requires both a positive history for REM sleep behavior disorder and polysomnographic demonstration of REM sleep without atonia. To improve and facilitate screening for REM sleep behavior disorder, there is a need for simple clinical tools with sufficient sensitivity and specificity for the identification of subjects with probable REM sleep behavior disorder. We developed a short REM sleep behavior disorder screening questionnaire with 7 REM sleep behavior disorder- and 2 non-REM sleep behavior disorder-specific control items and performed a validation study in 70 REM sleep behavior disorder subjects and 140 sleep disorder controls. Response patterns to all 7 REM sleep behavior disorder-specific items differed between REM sleep behavior disorder and non-REM sleep behavior disorder patients (all P < 0.05), whereas the 2 non-REM sleep behavior disorder-specific control items did not differentiate between REM sleep behavior disorder and non-REM sleep behavior disorder (all P > .05). In 5 of the 7 REM sleep behavior disorder-specific items, AUC was greater than 0.700. These 5 items were included in the Innsbruck REM sleep behavior disorder inventory. In this questionnaire, a cutoff of 0.25 (number of positive symptoms divided by number of answered questions) had a sensitivity of 0.914 and a specificity of 0.857 for both idiopathic and Parkinson's-related REM sleep behavior disorder (AUC, 0.886). The Innsbruck REM sleep behavior disorder inventory is a promising, easy-to-use, short screening tool for REM sleep behavior disorder with excellent sensitivity and specificity for both idiopathic and Parkinson's-related REM sleep behavior disorder.

Narcolepsy-cataplexy: deficient prepulse inhibition of blink reflex suggests pedunculopontine involvement.

Hypocretin (orexin) deficiency plays a major role in the pathophysiology of narcolepsy-cataplexy. In animal models, hypocretinergic projections to the pedunculopontine nucleus are directly involved in muscle tone regulation mediating muscle atonia - a hallmark of cataplexy. We hypothesized that pedunculopontine nucleus function, tested with prepulse inhibition of the blink reflex, is altered in human narcolepsy-cataplexy. Twenty patients with narcolepsy-cataplexy and 20 healthy controls underwent a neurophysiological study of pedunculopontine nucleus function. Blink reflex, prepulse inhibition of the blink reflex and blink reflex excitability recovery were measured. Blink reflex characteristics (R1 latency and amplitude, and R2 and R2c latency and area under the curve) did not differ between patients and controls (P > 0.05). Prepulse stimulation significantly increased R2 and R2c latencies and reduced R2 and R2c areas in patients and controls. However, the R2 and R2c area suppression was significantly less in patients than in controls (to 69.8 ± 14.4 and 74.9 ± 12.6%, respectively, versus 34.5 ± 28.6 and 43.3 ± 29.5%, respectively; each P < 0.001). Blink reflex excitability recovery, as measured by paired-pulse stimulation, which is not mediated via the pedunculopontine nucleus, did not differ between patients and controls (P > 0.05). Our data showed that prepulse inhibition is reduced in narcolepsy-cataplexy, whereas unconditioned blink reflex and its excitability recovery are normal. Because the pedunculopontine nucleus is important for prepulse inhibition, these results suggest its functional involvement in narcolepsy-cataplexy.

Can observers link dream content to behaviours in rapid eye movement sleep behaviour disorder? A cross-sectional experimental pilot study.

Motor activity in rapid eye movement (REM) sleep behaviour disorder (RBD) has been linked to dream content. Systematic and controlled sleep laboratory studies directly assessing the relation between RBD behaviours and experienced dream content are, however, largely lacking. We aimed to investigate whether a link can be established between RBD behaviours and dream content when both are systematically sampled in a controlled setting. We investigated six patients with Parkinson syndrome and RBD who underwent 2-3 nights of video-polysomnographic recording during which they were awakened from REM sleep (10 min after the onset of the second and successive REM periods). Spontaneous free-worded dream reports and a structured dream questionnaire were obtained. Video recordings of motor manifestations were each combined with four dream reports, and seven judges had to match the video clip with the correctly reported dream content from a choice of four possibilities. Of the 35 REM sleep awakenings performed, a total of 17 (48.6%) motor-behavioural episodes with recalled dream content were obtained. The mean of correctly identified video-dream pairs was 39.5% (range 0-100%). Our data showed that reported dream content can be linked to motor behaviours above chance level. Matching accuracy was affected mainly by the clarity of dream reports and the specific nature of movements manifest in video recordings.

Motor disturbances during non-REM and REM sleep in narcolepsy-cataplexy: a video-polysomnographic analysis.

Motor events during sleep can be frequently observed in patients with narcolepsy-cataplexy. We hypothesized that increased motor events and related arousals contribute to sleep fragmentation in this disease. We aimed to perform a detailed whole-night video-polysomnographic analysis of all motor events during non-rapid eye movement and rapid eye movement sleep in a group of narcolepsy-cataplexy patients and matched controls, and to assess the association with arousals. Video-polysomnographic registrations of six narcolepsy-cataplexy patients and six sex- and age-matched controls were analysed. Each motor event in the video was classified according to topography, number of involved body parts, duration and its association with arousals. The mean motor activity index was 59.9 ± 23.0 h(-1) in patients with narcolepsy-cataplexy compared with 15.4 ± 9.2 h(-1) in controls (P = 0.004). Distribution of motor events was similar in non-rapid eye movement and rapid eye movement sleep in the patient group (P = 0.219). In narcolepsy-cataplexy, motor events involved significantly more body parts (≥ 2 body regions: 38.2 ± 15.6 versus 14.9 ± 10.0; P = 0.011). In addition, the proportion of motor events lasting longer than 1 s was higher in patients than controls (88% versus 44.4%; P < 0.001). Both total and motor activity-related arousal indices were increased in narcolepsy-cataplexy (total arousal index: 21.6 ± 9.0 versus 8.7 ± 3.5; P = 0.004; motor activity-related arousal index: 17.6 ± 9.8 versus 5.9 ± 2.3; P = 0.002). Motor activity and motor activity-related arousal indices are increased in both non-rapid eye movement and rapid eye movement sleep in narcolepsy-cataplexy compared with controls. This supports the concept of a general sleep motor dysregulation in narcolepsy-cataplexy, which potentially contributes to or even underlies sleep fragmentation in this disease.

Motor events during healthy sleep: a quantitative polysomnographic study.

STUDY OBJECTIVES: Many sleep disorders are characterized by increased motor activity during sleep. In contrast, studies on motor activity during physiological sleep are largely lacking. We quantitatively investigated a large range of motor phenomena during polysomnography in physiological sleep. DESIGN: Prospective polysomnographic investigation. SETTING: Academic referral sleep laboratory. PARTICIPANTS: One hundred healthy sleepers age 19-77 y were strictly selected from a representative population sample by a two-step screening procedure. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Polysomnography according to American Academy of Sleep Medicine (AASM) standards was performed, and quantitative normative values were established for periodic limb movements in sleep (PLMS), high frequency leg movements (HFLM), fragmentary myoclonus (FM), neck myoclonus (NM), and rapid eye movement (REM)-related electromyographic (EMG) activity. Thirty-six subjects had a PLMS index > 5/h, 18 had a PLMS index > 15/h (90th percentile: 24.8/h). Thirty-three subjects had HFLM (90th percentile: four sequences/night). All subjects had FM (90th percentile 143.7/h sleep). Nine subjects fulfilled AASM criteria for excessive FM. Thirty-five subjects had NM (90th percentile: 8.8/h REM sleep). For REM sleep, different EMG activity measures for the mentalis and flexor digitorum superficialis muscles were calculated: the 90th percentile for phasic mentalis EMG activity for 30-sec epochs according to AASM recommendation was 15.6%, and for tonic mentalis EMG activity 2.6%. Twenty-five subjects exceeded the recently proposed phasic mentalis cutoff of 11%. None of the subjects exceeded the tonic mentalis cutoff of 9.6%. CONCLUSION: Quantification of motor phenomena is a basic prerequisite to develop normative values, and is a first step toward a more precise description of the various motor phenomena present during sleep. Because rates of motor events were unexpectedly high even in physiological sleep, the future use of normative values for both research and clinical routine is essential.

Is there a polysomnographic signature of augmentation in restless legs syndrome?

OBJECTIVE: Augmentation of restless legs syndrome (RLS) is a potentially severe side-effect of dopaminergic treatment. Data on objective motor characteristics in augmentation are scarce. The aim of this study was to investigate in detail different variables of leg movements (LM) in untreated, treated, and augmented RLS patients. METHODS: Forty-five patients with idiopathic RLS [15 untreated, 15 treated (non-augmented), 15 augmented] underwent RLS severity assessment, one night of video-polysomnography with extended electromyographic montage, and a suggested immobilization test (SIT). RESULTS: Standard LM parameters as well as periodicity index (PI) and muscle recruitment pattern did not differ between the three groups. The ultradian distribution of periodic leg movements (PLM) in sleep during the night revealed significant differences only during the second hour of sleep (P <0.05). However, augmented patients scored highest on RLS severity scales (P <0.05) and were the only group with a substantial number of PLM during the SIT. CONCLUSION: This study demonstrates that polysomnography is of limited usefulness for the diagnosis and evaluation of RLS augmentation. In contrast, the SIT showed borderline differences in PLM, and differences on subjective scales were marked. According to these results, augmentation of RLS is a phenomenon that predominantly manifests in wakefulness.

Quantitative assessment of isolated rapid eye movement (REM) sleep without atonia without clinical REM sleep behavior disorder: clinical and research implications.

BACKGROUND: Rapid eye movement (REM) sleep without atonia (RWA) is observed in some patients without a clinical history of REM sleep behavior disorder (RBD). It remains unknown whether these patients meet the refined quantitative electromyographic (EMG) criteria supporting a clinical RBD diagnosis. We quantitatively evaluated EMG activity and investigated its overnight distribution in patients with isolated qualitative RWA. METHODS: Fifty participants with an incidental polysomnographic finding of RWA (isolated qualitative RWA) were included. Tonic, phasic, and 'any' EMG activity during REM sleep on PSG were quantified retrospectively. RESULTS: Referring to the quantitative cut-off values for a polysomnographic diagnosis of RBD, 7/50 (14%) and 6/50 (12%) of the patients showed phasic and 'any' EMG activity in the mentalis muscle above the respective cut-off values. No patient was above the cut-off value for tonic EMG activity or phasic EMG activity in the anterior tibialis muscles. Patients with RWA above the cut-off value showed higher amounts of RWA during later REM sleep periods. CONCLUSIONS: This is the first study showing that some subjects with incidental RWA meet the refined quantitative EMG criteria for a diagnosis of RBD. Future longitudinal studies must investigate whether this subgroup with isolated qualitative RWA is at an increased risk of developing fully expressed RBD and/or neurodegenerative disease.

A prospective questionnaire study in 100 healthy sleepers: non-bothersome forms of recognizable sleep disorders are still present.

STUDY OBJECTIVES: Despite several polysomnographic normative studies and multiple surveys of sleep disorders in the general population, few data have been collected on healthy sleepers. We aimed to survey the characteristics of healthy sleep. METHODS: We prospectively investigated the sleep history of 100 subjects of a representative population sample who reported undisturbed sleep and in whom relevant sleep disorders were ruled out by a two-step screening procedure. Approximately four subjects had to be contacted for identifying 1 eligible subject who participated. RESULTS: The median reported time in bed was from 23:00 (21:30-02:00) to 07:00 (05:30-11:00). The total sleep duration was 7.3 h (5-10 h), varying from 7.5 h in the age group ≤ 30 years to 7 h in subjects aged 40-60 years and to 8 h in subjects > 60 years (p = 0.002). The median sleep efficiency was high (93.3%, range: 55.6% to 100%). Fifty-one subjects reported occasional snoring. Forty-five subjects reported sporadic non-bothersome sleep-related movement disorders (25 sleep-related leg cramps, 22 lifetime bruxism, 5 restless legs syndrome), and 36 had a history of sporadic non-bothersome parasomnias (27 nightmares, 12 sleepwalking, 1 sleep paralysis). CONCLUSION: In this population of healthy sleepers, snoring is the most common finding. Moreover, non-bothersome forms of recognizable sleep-related movement disorders and parasomnias are surprisingly common. These findings may suggest that diagnostic criteria of sleep disorders should not only be based on the presence of symptoms but also account for a minimum frequency or discomfort.

Defining muscle activities for assessment of rapid eye movement sleep behavior disorder: from a qualitative to a quantitative diagnostic level.

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by dream enacting behavior. Its polysomnographic hallmark is loss of physiological REM muscle atonia. Current diagnostic criteria require both a typical history of RBD or videographic documentation of abnormal REM-sleep related behaviors and the polysomnographic demonstration of REM sleep without atonia with "the electromyographic (EMG) finding of excessive amounts of sustained or intermittent elevation of submental EMG tone or excessive phasic submental or limb EMG twitching". Until now, there has not been a generally accepted consensus on how muscle activity during REM sleep should be scored. Moreover, current diagnostic criteria do not specify which muscle or muscle combinations are the most suitable for differentiating between RBD and non-RBD. The term "excessive" refers to the scorer's subjective impression and not to objective quantitative cutoff values. This article reviews published manual and computer-assisted scoring methods of EMG activity that are applied in RBD research. It includes the existing studies on EMG activity assessment in different muscles, available data on night-to-night variability, as well as recently established quantitative EMG cutoff values. The research that has been undertaken in the last years has greatly improved RBD diagnosis, taking it from a qualitative to a quantitative level. This development is of upmost importance, since RBD is often the first non-motor symptom of a neurodegenerative disease.

Is a diagnosis of ancillary restless legs syndrome reproducible over time? Experience with the Wayne Hening telephone diagnostic interview.

OBJECTIVE: The Hening telephone diagnostic interview (HTDI) is a validated structured diagnostic instrument for restless legs syndrome (RLS). A diagnosis of ancillary RLS is defined as RLS with non bothering or only sporadic occurrence of RLS symptoms. The aim of our study was to test the reproducibility of a previously received diagnosis of ancillary RLS with the HTDI in a telephone follow-up examination. METHODS: Patients with a diagnosis of ancillary RLS underwent a telephone follow-up after an interval of 6 or more months from their entry into the RLS database. The interview included the HTDI, the International RLS Study Group severity rating scale (IRLS) and questions on current RLS medication. RESULTS: Sixty patients with ancillary RLS were eligible for this study, 50 participated. Thirty-six patients were assigned to definite RLS, 11 to probable RLS, one to possible RLS, and two patients were rated as not RLS. Median IRLS score of those with RLS was 10 (0-30). CONCLUSIONS: This is the first study to report results of the German version of the HTDI. We demonstrate a high reproducibility of a diagnosis of ancillary RLS over time and that the HTDI is an excellent diagnostic tool for RLS even in ancillary cases.

Night-to-night variability of periodic leg movements during sleep in restless legs syndrome and periodic limb movement disorder: comparison between the periodicity index and the PLMS index.

BACKGROUND: The number of periodic leg movements during sleep (PLMS index) shows high night-to-night variability, requiring multiple nights for its reliable estimation. It is currently not known if this is also the case for the degree of periodicity of leg movements, quantified by the Periodicity index. OBJECTIVE: To compare night-to-night variability of PLMS and Periodicity indices in patients with restless legs syndrome (RLS) or periodic limb movement disorder (PLMD). METHODS: Eighteen idiopathic RLS patients and 9 PLMD patients were recruited. Subjects underwent two consecutive full night polysomnographic studies. Polysomnographic recordings were scored and leg movement activity analyzed during sleep for the computation of the PLMS and Periodicity indices. RESULTS: In both patient groups, the Periodicity index showed a significantly lower degree of variability than that of PLMS index, being >6.5 times lower in RLS patients and 2 times lower in PLMD patients. CONCLUSIONS: These data support the use of the Periodicity index in the evaluation of PLMS in RLS and PLMD and indicate that this parameter seems to be more stable than the widely used PLMS index which has higher night-to-night variability.

Delayed diagnosis, range of severity, and multiple sleep comorbidities: a clinical and polysomnographic analysis of 100 patients of the innsbruck narcolepsy cohort.

STUDY OBJECTIVES: Narcolepsy is reported to affect 26-56/100,000 in the general population. We aimed to describe clinical and polysomnographic features of a large narcolepsy cohort in order to comprehensively characterize the narcoleptic spectrum. METHODS: We performed a chart- and polysomnographybased review of all narcolepsy patients of the Innsbruck narcolepsy cohort. RESULTS: A total of 100 consecutive narcolepsy patients (87 with cataplexy [NC], 13 without cataplexy [N]) were included in the analysis. All subjects had either excessive daytime sleepiness or cataplexy as their initial presenting clinical feature. Age at symptom onset was 20 (6-69) years. Diagnostic delay was 6.5 (0-39) years. The complete narcolepsy tetrad was present in 36/100 patients; 28/100 patients had three cardinal symptoms; 29/100 had two; and 7/100 had only excessive daytime sleepiness. Severity varied broadly with respect to excessive daytime sleepiness (median Epworth Sleepiness Scale score: 18, range 10-24), cataplexy (8-point Likert scale: median 4.5, range 1-8), hypnagogic hallucinations (median 4.5, range 1-7), and sleep paralysis (median 3, range 1-7). Sleep comorbidity was highly prevalent and ranged from sleeprelated movement disorders (n = 55/100), parasomnias (n = 34/100), and sleeprelated breathing disorders (n = 24/100), to insomnia (n = 28/100). REM sleep without atonia or a periodic limb movement in sleep index > 5/h were present in most patients (90/100 and 75/100). A high percentage of narcoleptic patients in the present study had high frequency leg movements (35%) and excessive fragmentary myoclonus (22%). Of the narcolepsy patients with clinical features of REM sleep behavior disorder (RBD), 76.5% had EMG evidence for RBD on the multiple sleep latency test (MSLT), based on a standard cutoff of a minimum of 18% of 3-sec miniepochs. CONCLUSION: This study is one of the largest monocentric polysomnographic studies to date of patients with narcolepsy and confirms the frequent comorbidity of narcolepsy with many other sleep disorders. Our study is the first to evaluate the percentage of patients with high frequency leg movements and excessive fragmentary myoclonus in narcolepsy and is the first to demonstrate EMG evidence of RBD in the MSLT. These findings add to the growing body of literature suggesting that motor instability is a key feature of narcolepsy.

Investigation of autonomic function in idiopathic REM sleep behavior disorder.

Idiopathic REM sleep behavior disorder (iRBD) has been suggested as an early "pre-motor" stage of Parkinson's disease (PD) in a significant proportion of cases. We investigated autonomic function in 15 consecutive iRBD patients and compared these findings to PD patients and healthy controls. All participants underwent cardiovascular autonomic function testing, and were rated on the COMPASS scale. Symptomatic orthostatic hypotension was present in two iRBD patients, two PD patients and none of the healthy controls. In the tilt table examination, blood pressure changes were similar between iRBD patients and healthy controls. In the PD group, blood pressure drops were more pronounced. In the orthostatic standing test, iRBD patients had higher blood pressure changes than healthy controls. Highest drops were found in PD. Valsalva ratio was lower in iRBD and PD compared to healthy controls. Total COMPASS score was higher in iRBD compared to healthy controls. Highest scores were found in PD. These results support the presence of autonomic dysfunction in iRBD. On several measures, dysfunction was intermediate between healthy controls and PD consistent with the concept that iRBD can be manifestation of synuclein-associated neurodegenerative disorders. Follow-up studies are needed to determine whether iRBD patients with dysfunction on several autonomic domains are at particular risk for developing one of these diseases.

Decision making and executive functions in REM sleep behavior disorder.

STUDY OBJECTIVES: This study was designed to assess decision making and executive functions in patients with idiopathic REM sleep behavior disorder (iRBD). IRBD is often seen as an early sign of later evolving neurodegenerative disease, most importantly Parkinson disease (PD) and Lewy body dementia (DLB). It has been proposed that iRBD patients show a cognitive profile similar to patients with PD. DESIGN: All participants performed an extensive test battery tapping executive functions as well as the IOWA gambling task, which measures decision making under ambiguity. SETTING: University hospital sleep disorders center. PARTICIPANTS: 16 iRBD patients and 45 age- and education-matched controls. INTERVENTION: N.A. MEASUREMENTS AND RESULTS: Compared with controls, iRBD patients showed disadvantageous decision making under ambiguity and did not learn by feedback over the task. IRBD patients' decision pattern was characterized by the lack of a consistent strategy, as indicated by frequent shifts between the single choices. A high proportion of iRBD patients (75%) showed random performance or worse even at the end of the task. No group differences were found in tasks assessing information sampling, flexibility and categorization, problem solving, and impulsivity. CONCLUSIONS: As suggested by the present investigation, iRBD patients may show difficulties in decision making under ambiguity in a stage when other cognitive functions are relatively well preserved. Whether this is driven by subgroups of patients prone to develop PD or DLB has to be assessed by follow-up investigations.

White and gray matter abnormalities in narcolepsy with cataplexy.

STUDY OBJECTIVES: The authors applied diffusion-tensor imaging including measurements of mean diffusivity (MD), which is a parameter of brain tissue integrity, fractional anisotropy (FA), which is a parameter of neuronal fiber integrity, and voxel-based morphometry, which is a measure of gray and white matter volume, to detect brain tissue changes in patients with narcolepsy-cataplexy. DESIGN: N/A. PATIENTS: Patients with narcolepsy-cataplexy (n = 16) and age-matched healthy control subjects (n = 12) were studied. INTERVENTIONS: Whole cerebral MD, FA measures, and the volumes of the gray and white matter compartments were analyzed using statistical parametric mapping. MEASUREMENT AND RESULTS: Significant MD increases and concomitant FA decreases were localized in the fronto-orbital cortex (P < 0.001) and the anterior cingulate (FA, P < 0.001; MD, P = 0.03) in narcolepsy-cataplexy. Additional MD increases without FA changes were detected in the ventral tegmental area, the dorsal raphe nuclei (P < 0.001), and the hypothalamus (P < 0.01). FA signal decreases were observed in the white matter tracts of the inferior frontal and inferior temporal cortices of narcolepsy-cataplexy patients (P < 0.001). Brain volume loss was evident in focal areas of the inferior and superior temporal cortices (P < 0.001) and the cingulate (P = 0.038). CONCLUSIONS: Areas of increased diffusivity in the hypothalamus appear consistent with hypocretinergic cell loss reported in narcolepsy-cataplexy. Signal abnormalities in the ventral tegmental area and the dorsal raphe nuclei correspond to major synaptic targets of hypocretin neurons that were associated with the regulation of the sleep-wake cycle. Brain tissue alterations identified in the frontal cortex and cingulate are crucial in the maintenance of attention and reward-dependent decision making, both known to be impaired in narcolepsy-cataplexy.

Normative EMG values during REM sleep for the diagnosis of REM sleep behavior disorder.

BACKGROUND: Correct diagnosis of rapid eye movement sleep behavior disorder (RBD) is important because it can be the first manifestation of a neurodegenerative disease, it may lead to serious injury, and it is a well-treatable disorder. We evaluated the electromyographic (EMG) activity in the Sleep Innsbruck Barcelona (SINBAR) montage (mentalis, flexor digitorum superficialis, extensor digitorum brevis) and other muscles to obtain normative values for the correct diagnosis of RBD for clinical practice. SETTING: Two university hospital sleep disorder centers. PARTICIPANTS: Thirty RBD patients (15 idiopathic [iRBD], 15 with Parkinson disease [PD]) and 30 matched controls recruited from patients with effectively treated sleep related breathing disorders. INTERVENTIONS: Not applicable. METHODS AND RESULTS: Participants underwent video-polysomnography, including registration of 11 body muscles. Tonic, phasic, and "any" (any type of EMG activity, irrespective of whether it consisted of tonic, phasic or a combination of both) EMG activity was blindly quantified for each muscle. When choosing a specificity of 100%, the 3-sec miniepoch cutoff for a diagnosis of RBD was 18% for "any" EMG activity in the mentalis muscle (area under the curve [AUC] 0.990). Discriminative power was higher in upper limb (100% specificity, AUC 0.987-9.997) than in lower limb muscles (100% specificity, AUC 0.813-0.852). The combination of "any" EMG activity in the mentalis muscle with both phasic flexor digitorum superficialis muscles yielded a cutoff of 32% (AUC 0.998) for patients with iRBD and with PD-RBD. CONCLUSION: For the diagnosis of iRBD and RBD associated with PD, we recommend a polysomnographic montage quantifying "any" (any type of EMG activity, irrespective of whether it consisted of tonic, phasic or a combination of both) EMG activity in the mentalis muscle and phasic EMG activity in the right and left flexor digitorum superficialis muscles in the upper limbs with a cutoff of 32%, when using 3-sec miniepochs.

Executive functions, information sampling, and decision making in narcolepsy with cataplexy.

OBJECTIVE: Narcolepsy with cataplexy (NC) affects neurotransmitter systems regulating emotions and cognitive functions. This study aimed to assess executive functions, information sampling, reward processing, and decision making in NC. METHOD: Twenty-one NC patients and 58 healthy participants performed an extensive neuropsychological test battery. RESULTS: NC patients scored as controls in executive function tasks assessing set shifting, reversal learning, working memory, and planning. Group differences appeared in a task measuring information sampling and reward sensitivity. NC patients gathered less information, tolerated a higher level of uncertainty, and were less influenced by reward contingencies than controls. NC patients also showed reduced learning in decision making and had significantly lower scores than controls in the fifth block of the IOWA gambling task. No correlations were found with measures of sleepiness. CONCLUSIONS: NC patients may achieve high performance in several neuropsychological domains, including executive functions. Specific differences between NC patients and controls highlight the importance of the hypocretin system in reward processing and decision making and are in line with previous neuroimaging and neurophysiological studies.