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How, When and Why to Do MSLT in 2021

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How, When and Why to Do MSLT in 2021 Madeleine Grigg-Damberger MD Professor of Neurology University of New Mexico ACNS 2021 Annual Meeting Sleep Course Wednesday, February 10, 2021 2:00 to 2:30 PM I Have No Conflicts of Interest to Report Relevant to This Talk Only 0.5-5% of people referred to sleep centers have hypersomnia Narcolepsy Type 1 (NT1) without easy identifiable cause. Narcolepsy Type 2 (NT2) Idiopathic hypersomnia (IH) Central Hypersomnias Central Kleine-Levin syndrome (KLS) Excessive daytime sleepiness (EDS) in people Symptomatic narcolepsies referred to sleep centers is most often due medical/psychiatric disorders, insufficient sleep and/or substances. Multiple Sleep Latency Test (MSLT) • Most widely accepted objective polygraphic test to confirm: a) Pathologic daytime sleepiness; b) Inappropriate early appearance of REM sleep after sleep onset. • Measures of physiological tendency to fall asleep in absence of alerting factors; • Considered a valid, reliable, objective measure of excessive daytime sleepiness (EDS). REFs: 1) Sleep 1986;9:519-524. 2) Sleep 1982;5:S67-S72; 3) Practice parameters for clinical use of MSLT and MWT. SLEEP 2005;28(1):113-21. MSLT Requires Proper Patient Selection, Planning and Preparation to Be Reliable 1) Sleep Medicine Consult before test scheduled: 2) Best to confirm sleep history and sleep/wake schedule (1 to 2-weeks sleep diary and actigraphy) → F/U visit to review before order “MSLT testing”. 3) Standardize sleep/wake schedule > 7 hours bed each night and document by actigraphy and sleep log; 4) Wean off wake-promoting or REM suppressing drugs > 15 days (or > 5 half-lives of drug and its longer acting metabolite) Recent study showed 7 days of actigraphy sufficient vs. 28 days to confirm NT1. MSLT Protocol 1) Level 1 PSG night before (to identify sleep disorders causing/contributing to EDS and confirm slept > 360 min: • Review PSG morning of study, consider cancelling MSLT if patient slept < 6 h on PSG; sleep log + actigraphy shows insufficient sleep (<7 h) or moderate/severe OSA on PSG. 2) Schedule MSLT patient’s customary wake times (challenging for shift workers): 3) 4-5 20-min nap opportunities at 2 h intervals beginning 1.5 to 3 h after awakening from the overnight PSG; 4) 5 naps unless 2 SOREMPs first 4 naps. 5) Urine drug screen morning of MSLT. Important to Standardize the MSLT Naps 1) Sleep rooms dark, quiet; room temperature adjusted for patient’s comfort; no caffeine or bright light exposure day of test; 2) 30 min before each nap stop tobacco; 15 min before stop stimulating activities; 3) Light breakfast 1 h before MSLT start; light lunch after second (noon) trial; 4) Technologist gives same instructions before each nap: “Please lie quietly, assume a comfortable position, and try to fall asleep”. Scoring MSLT Saccades Desynchronized EEG of eyes open High chin EMG tone 30-seconds 1) Each nap opportunity scored in 30-second epochs from LIGHTS OUT to LIGHTS ON. Scoring MSLT 2) Sleep onset in a nap: first 30-second epoch of any stage of sleep (N1, N2, N3, R); if patient falls asleep run for 15 minutes (30 epochs) to see if early onset of REM sleep observed. REM sleep normally appears 70-110 minutes after sleep onset. Scoring MSLT Rapid eye movements EEG = low voltage mixed frequency Can sometimes see RWA 3. If sleep occurs, record 15 min see if REM sleep appears early (SOREMP). Scoring MSLT REMs LVMF Chin EMG - Atonia 4) REM latency in a nap = Time in minutes from first epoch of sleep to first epoch of REM sleep Scoring MSLT 5) Stop nap after 20 min (40 epochs) if no sleep occurs. If no sleep observed in nap, score latency for that nap as 20 min. Reporting and Interpreting Multiple Sleep Latency Test Data Calculated and Tallied for MSLT • Sleep Latency: (Sleep Onset Epoch – 1) For each nap opportunity: Lights Out Epoch) divided by 2 ✓Start and stop times (min) • REM Latency: (REM onset Epoch – Sleep ✓Sleep latency (min) Onset Epoch) divided by 2; ✓REM latency (min) • Mean Sleep Latency (MSL): Sum of sleep ✓Percent REM sleep in nap latency each nap (min)/number of naps. 2) Number of naps; 3) Number of SOREMPs EXAMPLE: Lights Out Epoch 12, Sleep onset Epoch 13 (N1); REM onset Epoch 14 4) Mean sleep latency (MSL). Sleep latency = 13-12/2 =0.5 min; REM latency = 0.5 min after sleep onset). Fundamental MSLT Results Which Support Narcolepsy Diagnosis Mean Sleep Latency MSL <8 • Mean sleep 14 min in latency (MSL) 12 4 or 5 usually 2-3 min in naps patients with NT1. 10 8 6 Control SOREMPs • More often 4 3-5 SOREMPs in > 2 naps patients with NT1. 2 Narcolepsy 0 Nap 1 Nap 2 Nap 3 Nap 4 Nap 5 Richardson GS et al. Electroencephalogr Clin Neurophysiol 1978;45:621–7. MSLT Findings in Narcolepsy Types 1 & 2, Idiopathic Hypersomnia and Insufficient Sleep Sleep disorder N Mean sleep Naps with SOREMP latency (MSL) SOREMP after N1 Narcolepsy type 1 25 2.6 ± 1.6 63% 75% Narcolepsy type 2 41 4.0 ± 2.1 60% 52% Idiopathic 21 5.4 ± 1.8 1% 0% hypersomnia Insufficient sleep 20 7.6 ± 3.9 7% 0% syndrome • Diagnosing idiopathic hypersomnia may require 48 h of extended sleep monitoring or 7-days of wrist actigraphy. • REFs: 1) Drakatos P et al. Sleep stage sequence of SOREMPs in hypersomnia. J Neurol Neurosurg Psychiatry 2013;84:223-7; Other Findings on MSLT Which Increase Sensitivity the Patient Has Narcolepsy 1) 3-5 SOREMPs on MSLT 2) N1-REM SOREMPs on MLST and PSG; 3) Mean REM sleep percent in naps > 40-50% of total sleep time (TST); 4) REM sleep without atonia and RBD behaviors on MSLT • If 4 SOREMPs on MSLT test-reliability was 0.97 (3 naps 0.85, 2 naps 0.65) Findings on Overnight PSG in Narcolepsy • SOREMP REM latency < 15 min; • Red flag for narcolepsy; 33-55% of Narcolepsy Type 1 and 2; • High specificity (95-99%), but low sensitivity (7%); Positive Predictive Value 89%. • Marked fragmentation of nocturnal sleep, decreased sleep efficiency, increased wake and arousals; REM sleep instability; N1-REM transitions. • PLMS in NREM and REM sleep, RWA, RBD behavior events REFs: 1) Leschiziner G. Practical Neurology 2014;5:323-31’ 2) Andlauer O JAMA Neurol 2013;70(7):891-902; 3) Cairns A Sleep 2015;38(10):1575-81; 4) Reiter J Sleep 2015;38 (5): 859-65 Validity and Reliability of MSLT Validity of MSLT Lessened By • Deviations from standard protocol (room noisy MSLT Interpretation Pitfalls or too hot); • Medications affect sleep and/or REM latencies; • Patient slept < 360 min overnight PSG; • Severity of sleep disorder(s) or sleep fragmentation on PSG; • Insufficient time after discontinuing drugs which affect results; • Drugs on urine toxic screen. Test-Retest Reliability of MSLT • Studies have found the MSLT test-retest reliability is good for narcolepsy type 1 (NT1), poor for NT2 or Idiopathic hypersomnia (IH): • One large study found both MSLTs were positive for narcolepsy in 78% N1, but only 18% NT2 and 7% controls. • NT1 10-14 times more likely have 2nd positive MSLT vs. NT2. False Negative MSLT in Patients with NT1 and False Positive MSLT in Controls MSLT False-Negative MSLT False-Positive ▪ 7-16% NT1 patients due to ▪ 16% of controls had MSL < 5 environmental factors, anxiety, min; older (or younger) age; ▪ False-positive MSL <5 min medications that interfere with in 10-25% in patients with sleep sleep. deprivation, sleep apnea, adolescents with early school times, drug effects. 1-2 SOREMPs on MSLT Common in General Adult Population • Study 1: Population-based • Study 2: 556 community dwelling sample of 539 adults: 4% > 2 adults:2 SOREMPs:1 • 13% M and 6% F > 2 SOREMPs; • 2.5% met narcolepsy criteria (MSL • 4% M and 0.4% F met narcolepsy < 8 min + > 2 SOREMPs). criteria (MSL < 8 min + > 2 SOREMPs + ESS >10). • Majority false positive MSLT due to shift work, insufficient sleep, • Particularly common shift workers. sleep apnea, or medications. REFs: 1) Singh M et al. Prevalence of SOREMPs in population –based sample Brain 2006;29:890-5; 2) Mignot E et al. Correlates of SOREMPS in community adults. Brain 2006;129:1609-23. Positive Urine Toxic Screen in MSLT • 33% of 186 consecutive patients who underwent MSLT:1 • Most often opioids, cannabis or amphetamines; • 16% patients MSL < 8 min tested positive; • 52% of 23 NT2; 20% 53 IH patients.2 • 16% of 69 MSLT/MWT patients: • Amphetamines, THC, opiates or BZPs; none reported self-use before discovery);3 • 10% of 383 pediatric patients; 43% had MSL < 8 min and >2 SOREMPs.4 REFs: 1) Kosky CA. JCSM 2016;12(11):1499-1505; 2) Anniss AM JCMS 2016;12(12:1633-40; 3) Drodzomenyo S. JCMS 2015;11(2):93-9; 4) Katz ES. JCSM 2014;10(8):897-901. Drugs That Decrease REM Sleep Can Cause REM Sleep Rebound When Discontinued Drugs Half-Life (hours) Fluoxetine 48-72 Mirtazapine 20-40 Citalopram 35 Sertraline 26 Paroxetine 21 ▪ TCAs, MOAIs, SSRIs; Venlafaxine; Lithium; Venlafaxine 3-7 ▪ Amphetamine, methylphenidate, cocaine; Amitriptyline 9-46 ▪ Barbiturates; Clonidine; Clomipramine; Longest half life: fluoxetine (2- ▪ Scopolamine; alcohol; trazodone; CBD/THC. 4 d) and its active metabolite norfluoxetine (7-15 d) ➔ 5-week washout period. Cannabis Need 4-Weeks Abstinence • THC detectable in urine 3-10 days; heavy users positive 1-3 months after ceasing cannabis use.2 • Cannabis withdrawal associated with SOREMPs and REM rebound; need 4 weeks of abstinence to return to baseline. ▪ CBD/THC withdrawal can cause SOREMPs and REM rebound, need 4- 6 weeks of abstinence if chronic use to return to baseline.
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