Christopher L. Drake

Nocturnal Rapid Eye Movement Sleep Latency for Identifying Patients With Narcolepsy/Hypocretin Deficiency

IMPORTANCEnNarcolepsy, a disorder associated with HLA-DQB1*06:02 and caused by hypocretin (orexin) deficiency, is diagnosed using the Multiple Sleep Latency Test (MSLT) following nocturnal polysomnography (NPSG). In many patients, a short rapid eye movement sleep latency (REML) during the NPSG is also observed but not used diagnostically.nnnOBJECTIVEnTo determine diagnostic accuracy and clinical utility of nocturnal REML measures in narcolepsy/hypocretin deficiency.nnnDESIGN, SETTING, AND PARTICIPANTSnObservational study using receiver operating characteristic curves for NPSG REML and MSLT findings (sleep studies performed between May 1976 and September 2011 at university medical centers in the United States, China, Korea, and Europe) to determine optimal diagnostic cutoffs for narcolepsy/hypocretin deficiency compared with different samples: controls, patients with other sleep disorders, patients with other hypersomnias, and patients with narcolepsy with normal hypocretin levels. Increasingly stringent comparisons were made. In a first comparison, 516 age- and sex-matched patients with narcolepsy/hypocretin deficiency were selected from 1749 patients and compared with 516 controls. In a second comparison, 749 successive patients undergoing sleep evaluation for any sleep disorders (low pretest probability for narcolepsy) were compared within groups by final diagnosis of narcolepsy/hypocretin deficiency. In the third comparison, 254 patients with a high pretest probability of having narcolepsy were compared within group by their final diagnosis. Finally, 118 patients with narcolepsy/hypocretin deficiency were compared with 118 age- and sex-matched patients with a diagnosis of narcolepsy but with normal hypocretin levels.nnnMAIN OUTCOME AND MEASURESnSensitivity and specificity of NPSG REML and MSLT as diagnostic tests for narcolepsy/hypocretin deficiency. This diagnosis was defined as narcolepsy associated with cataplexy plus HLA-DQB1*06:02 positivity (no cerebrospinal fluid hypocretin-1 results available) or narcolepsy with documented low (≤ 110 pg/mL) cerebrospinal fluid hypocretin-1 level.nnnRESULTSnShort REML (≤15 minutes) during NPSG was highly specific (99.2% [95% CI, 98.5%-100.0%] of 516 and 99.6% [95% CI, 99.1%-100.0%] of 735) but not sensitive (50.6% [95% CI, 46.3%-54.9%] of 516 and 35.7% [95% CI, 10.6%-60.8%] of 14) for patients with narcolepsy/hypocretin deficiency vs population-based controls or all patients with sleep disorders undergoing a nocturnal sleep study (area under the curve, 0.799 [95% CI, 0.771-0.826] and 0.704 [95% CI, 0.524-0.907], respectively). In patients with central hypersomnia and thus a high pretest probability for narcolepsy, short REML remained highly specific (95.4% [95% CI, 90.4%-98.3%] of 132) and similarly sensitive (57.4% [95% CI, 48.1%-66.3%] of 122) for narcolepsy/hypocretin deficiency (area under the curve, 0.765 [95% CI, 0.707-0.831]). Positive predictive value in this high pretest probability sample was 92.1% (95% CI, 83.6%-97.0%).nnnCONCLUSIONS AND RELEVANCEnAmong patients being evaluated for possible narcolepsy, short REML (≤15 minutes) at NPSG had high specificity and positive predictive value and may be considered diagnostic without the use of an MSLT; absence of short REML, however, requires a subsequent MSLT.

Habitual short sleep impacts frontal switch mechanism in attention to novelty.

STUDY OBJECTIVESnReduced time in bed relative to biological sleep need is common. The impact of habitual short sleep on auditory attention has not been studied to date. In the current study, we utilized novelty oddball tasks to evaluate the effect of habitual short sleep on brain function underlying attention control processes measured by the mismatch negativity (MMN, index of pre-attentive stage), P3a (attention-dependent), and P3b (memory-dependent) event related brain potentials (ERPs). An extended time in bed in a separate study was used to evaluate the possible reversal of the impairments of these processes in habitual short sleepers.nnnMETHODSnTen self-defined short sleepers (total sleep time [TST] ≤ 6 h) and 9 normal-sleeping subjects with TST 7-8 h, participated. ERPs were recorded via a 64-channel EEG system. Two test conditions: ignore and attend were implemented. The ERPs were analyzed and compared between groups on the 2 task conditions and frontal/central/parietal electrodes by 3-factor ANOVA. Sleep diary data were compared between groups by t-test. Sleep was recorded by the Zeo sleep monitoring system for a week in both habitual and extended sleep conditions at home.nnnRESULTSnThe main findings of the present study show that short sleeping individuals had deficiency in activity of the MMN and P3a brain responses over frontal areas compared to normal-sleeping subjects. The P3b amplitude was increased over frontal areas and decreased over parietal with respect to the control group. Extension of time in bed for one week increased TST (from 5.7 h to 7.4 h), and concomitantly MMN amplitude increased from -0.1 μV up to -1.25 μV over frontal areas.nnnCONCLUSIONSnReduced time in bed is associated with deficiency of the neuronal process associated with change detection, which may recover after one week of sleep extension, whereas attention-dependent neural processes do not normalize after this period of time in habitually short sleeping individuals and may require longer recovery periods.