Progressive narcolepsy: how to deal with intermediate hypocretin-1 values?

According to the International Classification of Sleep Disorders, third edition guidelines, the diagnosis of narcolepsy type 1 is based on the association of excessive daytime sleepiness plus either cataplexy and electrophysiological criteria, or a cerebrospinal fluid hypocretin-1 concentration below 110 pg/mL. This threshold remains debated, and recent works have proposed alternative values in the intermediate (110 to 200 pg/mL) zone. We report the case of a patient who presented with typical clinical symptoms of narcolepsy type 1 developing over six years but in whom initial polysomnography and multiple sleep latency test were negative and cerebrospinal fluid hypocretin-1 was intermediate (132 pg/mL). Cerebrospinal fluid hypocretin-1 reassessment four years later found a dramatic decrease, < 50 pg/mL, and the multiple sleep latency test proved to be abnormal, eventually allowing to confirm the diagnosis. This case highlights the importance of reassessing patients with intermediate hypocretin-1 values and contributes to the debate on the determination of alternative cerebrospinal fluid hypocretin1 thresholds for narcolepsy type 1 diagnosis. CITATION: Ricordeau F, Bridoux A, Raverot V, Peter-Derex L. Progressive narcolepsy: how to deal with intermediate hypocretin-1 values? J Clin Sleep Med. 2023;19(7):1375-1378.

Observation and Interview-based Diurnal Sleepiness Inventory for measurement of sleepiness in patients referred for narcolepsy or idiopathic hypersomnia.

STUDY OBJECTIVES: First, to determine whether the 3-item Observation and Interview-based Diurnal Sleepiness Inventory (ODSI) measures the degree of excessive daytime sleepiness in patients with suspected narcolepsy or idiopathic hypersomnia (IH). Second, to assess the correlation between the ODSI and the Epworth Sleepiness Scale (ESS) as well as objective polysomnographic measurements. Third, to test the accuracy of the ODSI to detect narcolepsy or IH (narcolepsy/IH) compared with the ESS. METHODS: A total of 181 patients complaining of excessive daytime sleepiness filled in the ESS and the ODSI and underwent measurements including actigraphy, full-night polysomnography, Multiple Sleep Latency Test, and 24-hour bedrest sleep recording. RESULTS: Narcolepsy or IH was diagnosed in 76 patients. The ODSI found excessive daytime sleepiness in 92.3% of all patients and in 98.7% of those diagnosed with narcolepsy/IH. In the whole population, the ODSI was significantly positively correlated with the ESS (R = .547; 95% confidence interval: .436, .642; P < .001) and weakly with 24-hour total sleep time on bedrest recording (R = .208; 95% confidence interval: .056, .350; P = .047) but not with the Multiple Sleep Latency Test. The ODSI offered a higher negative (92.9%) and positive (44.9%) predictive value to detect narcolepsy/IH than did the ESS (66.7% and 43.3%, respectively). In the IH group, the ODSI's third-item score (daily sleepiness duration) was significantly higher in patients with than without increased 24-hour total sleep time (P = .023). CONCLUSIONS: The ODSI is a brief, simple first-line questionnaire that explores both intensity and duration of daytime sleepiness and offers a high sensitivity to detect narcolepsy and IH.

Impaired sleep-associated modulation of post-exercise corticomotor depression in multiple sclerosis.

OBJECTIVE: To compare the beneficial effect of nap versus rest on the recovery of motor evoked potentials (MEPs) after a fatiguing exercise performed in patients with multiple sclerosis (MS) and healthy controls. METHODS: In 12 MS patients and 12 healthy controls, MEPs were recorded from the adductor pollicis muscle before, 10 and 60 min (T0, T10, and T60) after an effort of thumb adduction at 25% of maximal voluntary contraction force for 24 min. After the effort, the subject was maintained at rest or invited to have a nap while monitored with polysomnography. The two sessions (nap and rest) were randomly performed in each subject during the same day. The impact of nap and rest on post-exercise changes in MEP amplitude were studied in each group (patients and controls) and then compared between the two groups. RESULTS: Although MEP amplitude at baseline was lower in MS patients than in controls, post-exercise corticomotor depression (PECD), expressed as T10/T0 MEP amplitude ratio, was similar in both groups. Regarding MEP amplitude recovery at T60, nap was significantly more beneficial than rest in healthy subjects, but not in MS patients. CONCLUSION: Motor recovery from PECD following a fatiguing exercise can be enhanced by sleep (at least a short nap) in healthy subjects. In MS patients, sleep restorative effect is reduced or lost, maybe contributing to the excessive fatigue or fatigability characterized in these patients.

Bilateral thalamic stimulation induces insomnia in patients treated for intractable tremor.

STUDY OBJECTIVES: To explore the influence of acute bilateral ventral intermediate thalamic nucleus (VIM) stimulation on sleep. DESIGN: Three consecutive full-night polysomnography recordings were made in the laboratory. After the habituation night, a random order for night ON-stim and OFF-stim was applied for the second and third nights. SETTING: Sleep disorders unit of a university hospital. PATIENTS: Eleven patients with bilateral stimulation of the ventral intermediate nucleus of the thalamus (VIM) for drug-resistant tremor. MEASUREMENTS: Sleep measures on polysomnography. RESULTS: Total sleep time was reduced during night ON-stim compared to OFF- stim, as well as rapid eye movement sleep percentage while the percentage of N2 increased. Wakefulness after sleep onset time was increased. CONCLUSION: Our results show that bilateral stimulation of the VIM nuclei reduces sleep and could be associated with insomnia.

Sleep continuity: a new metric to quantify disrupted hypnograms in non-sedated intensive care unit patients.

INTRODUCTION: Sleep in intensive care unit (ICU) patients is severely altered. In a large proportion of critically ill patients, conventional sleep electroencephalogram (EEG) patterns are replaced by atypical sleep. On the other hand, some non-sedated patients can display usual sleep EEG patterns. In the latter, sleep is highly fragmented and disrupted and conventional rules may not be optimal. We sought to determine whether sleep continuity could be a useful metric to quantify the amount of sleep with recuperative function in critically ill patients with usual sleep EEG features. METHODS: We retrospectively reanalyzed polysomnographies recorded in non-sedated critically ill patients requiring non-invasive ventilation (NIV) for acute hypercapnic respiratory failure. Using conventional rules, we built two-state hypnograms (sleep and wake) and identified all sleep episodes. The percentage of time spent in sleep bouts (<10 minutes), short naps (>10 and <30 minutes) and long naps (>30 minutes) was used to describe sleep continuity. In a first study, we compared these measures regarding good (NIV success) or poor outcome (NIV failure). In a second study performed on a different patient group, we compared these measurements during NIV and during spontaneous breathing. RESULTS: While fragmentation indices were similar in the two groups, the percentage of total sleep time spent in short naps was higher and the percentage of sleep time spent in sleep bouts was lower in patients with successful NIV. The percentage of total sleep time spent in long naps was higher and the percentage of sleep time spent in sleep bouts was lower during NIV than during spontaneous breathing; the level of reproducibility of sleep continuity measures between scorers was high. CONCLUSIONS: Sleep continuity measurements could constitute a clinically relevant and reproducible assessment of sleep disruption in non-sedated ICU patients with usual sleep EEG.

Ventricular orexin-A (hypocretin-1) levels correlate with rapid-eye-movement sleep without atonia in Parkinson's disease.

OBJECTIVE: Patients with Parkinson's disease frequently complain of sleep disturbances and loss of muscle atonia during rapid-eye-movement (REM) sleep is not rare. The orexin-A (hypocretin-1) hypothalamic system plays a central role in controlling REM sleep. Loss of orexin neurons results in narcolepsy-cataplexy, a condition characterized by diurnal sleepiness and REM sleep without atonia. Alterations in the orexin-A system have been also documented in Parkinson's disease, but whether these alterations have clinical consequences remains unknown. METHODS: Here, we measured orexin-A levels in ventricular cerebrospinal fluid from eight patients with Parkinson's disease (four males and four females) who underwent ventriculography during deep brain-stimulation surgery and performed full-night polysomnography before surgery. RESULTS: Our results showed a positive correlation between orexin-A levels and REM sleep without muscle atonia. CONCLUSION: Our results suggest that high levels of orexin-A in Parkinson's disease may be associated with loss of REM muscle atonia.