The MSLT is Repeatable in Narcolepsy Type 1 But Not Narcolepsy Type 2: A Retrospective Patient Study

Abstract

Study objectives: To examine repeatability of Multiple Sleep Latency Test (MSLT) results in narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2) according to the criteria of the International Classification of Sleep Disorders, Third Edition (ICSD-3).

Methods: Repeatability of the MSLT was retrospectively evaluated in NT1 (n = 60) and NT2 (n = 54) cases, and controls (n = 15). All subjects had documented HLA-DQB1*06:02 status and/or hypocretin-1 levels from cerebrospinal fluid. All subjects had undergone 2 MSLTs (≥ 1 meeting ICSD-3 criteria for narcolepsy). Repeatability was explored in children versus adults and in those on versus not on medication(s). Subsample and multivariate analysis were performed.

Results: Both MSLTs in unmedicated patients were positive for narcolepsy in 78%, 18%, and 7% of NT1, NT2, and controls, respectively. NT2 cases changed to idiopathic hypersomnia or to a negative MSLT 26% and 57% of the time, respectively. Although NT1 cases were 10 to 14 times more likely to demonstrate a second positive MSLT compared to NT2 cases (P < 10^-5) and controls (P < 10^-4), respectively, NT2 cases were not significantly different from controls (P = .64). Medication use (P = .009) but not adult versus children status (P = .85) significantly decreased the likelihood of a repeat positive MSLT.

Conclusions: In a clinical setting, a positive MSLT for narcolepsy is a more reproducible and stable feature in NT1 than NT2. The retrospective design of this study hinders interpretation of these data, as there are many different, and possibly opposing, reasons to repeat a MSLT in NT1 versus NT2 (ie, ascertainment bias). Additional systematic MSLT repeatability studies independent of confounds are ideally needed to confirm these findings.

Keywords: HLA-DQB1*06:02; ICSD-3; MSLT; cataplexy; hypocretin-1; idiopathic hypersomnia; narcolepsy type 1; narcolepsy type 2.

Figure 1. MSLT repeatability for NT1, NT2, and controls.

MSLT1 and MSLT2 refer to the first and second MSLT, respectively. Each positive and negative sign denotes whether the MSLT was positive or negative for narcolepsy criteria (MSL ≤ 8 minutes, ≥ 2 SOREMPs based on ICSD-3 criteria), respectively. Data are % (n) (of total population). ICSD-3 = International Classification of Sleep Disorders, Third Edition, MSL = mean sleep latency, MSLT = Multiple Sleep Latency Test, NT1 = narcolepsy type 1, NT2 = narcolepsy type 2, SOREMP = sleep onset rapid eye movement period.

Figure 2. MSLT repeatability for NT1 and NT2 after excluding patients taking medication(s) at time of first and/or second MSLT.

MSLT1 and MSLT2 refer to the first and second MSLT, respectively. Each positive and negative sign denotes whether the MSLT was positive or negative for narcolepsy criteria (MSL ≤ 8 minutes, ≥ 2 SOREMPs based on ICSD-3 criteria), respectively. Data are % (n) (of total population). Medication(s) may include stimulant(s), antidepressant, and/or sodium oxybate at time of second MSLT. ICSD-3 = International Classification of Sleep Disorders, Third Edition, MSL = mean sleep latency, MSLT = Multiple Sleep Latency Test, NT1 = narcolepsy type 1, NT2 = narcolepsy type 2, SOREMP = sleep onset rapid eye movement period.

Figure 3. Bland-Altman plots for NT1 and NT2 after excluding patients taking medication(s) at either MSLT.

Bland Altman Plots for repeatability of MSL and SOREMPs for NT1 and NT2 after excluding patients taking medication(s) at time of first and/or second MSLT. MSL1 and MSL2 represent MSL on first and second MSLT, respectively. SOREMP1 and SOREMP2 represent number of SOREMPs on first and second MSLT, respectively. MSL = mean sleep latency, MSLT = Multiple Sleep Latency Test, NT1 = narcolepsy type 1, NT2 = narcolepsy type 2, SOREMP = sleep onset rapid eye movement period.