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Case Reports
. 2018 Apr 15;14(4):603-613.
doi: 10.5664/jcsm.7054.

Diagnostic and Treatment Challenges of Sighted Non-24-Hour Sleep-Wake Disorder

Roneil G Malkani  1 , Sabra M Abbott  1 , Kathryn J Reid  1 , Phyllis C Zee  1
Affiliations
Case Reports

Diagnostic and Treatment Challenges of Sighted Non-24-Hour Sleep-Wake Disorder

Roneil G Malkani et al. J Clin Sleep Med. .

Abstract

Study objectives: To report the diagnostic and treatment challenges of sighted non-24-hour sleep-wake disorder (N24SWD).

Methods: We report a series of seven sighted patients with N24SWD clinically evaluated by history and sleep diaries, and when available wrist actigraphy and salivary melatonin levels, and treated with timed melatonin and bright light therapy.

Results: Most patients had a history of a delayed sleep-wake pattern prior to developing N24SWD. The typical sleep-wake pattern of N24SWD was seen in the sleep diaries (and in actigraphy when available) in all patients with a daily delay in midpoint of sleep ranging 0.8 to 1.8 hours. Salivary dim light melatonin onset (DLMO) was evaluated in four patients but was missed in one. The estimated phase angle from DLMO to sleep onset ranged from 5.25 to 9 hours. All six patients who attempted timed melatonin and bright light therapy were able to entrain their sleep-wake schedules. Entrainment occurred at a late circadian phase, possibly related to the late timing of melatonin administration, though the patients often preferred late sleep times. Most did not continue treatment and continued to have a non-24-hour sleep-wake pattern.

Conclusions: N24SWD is a chronic debilitating disorder that is often overlooked in sighted people and can be challenging to diagnose and treat. Tools to assess circadian pattern and timing can be effectively applied to aid the diagnosis. The progressive delay of the circadian rhythm poses a challenge for determining the most effective timing for melatonin and bright light therapies. Furthermore, once the circadian sleep-wake rhythm is entrained, long-term effectiveness is limited because of the behavioral and environmental structure that is required to maintain stable entrainment.

Keywords: bright light; circadian rhythm; delayed sleep-wake phase disorder; melatonin; non–24-hour sleep-wake disorder.

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Figures

Figure 1
Figure 1. Circadian phase marker assessment of N24SWD.
Sleep log (A) and salivary melatonin profile (B) in case 1. (A) Double-plotted sleep diaries from case 1 show daily delays of the sleep-wake schedule typical of N24SWD. (B) Salivary melatonin profile under dim light conditions performed on day 6 of the sleep log (between brackets) revealed a DLMO (defined as exceeding 2 standard deviations from baseline) at 4:00 PM (arrow). The time from DLMO at 4:00 PM to sleep onset at 1:00 AM was 9 hours. DLMO = dim light melatonin onset, N24SWD = non–24-hour sleep-wake disorder.
Figure 2
Figure 2. Actigraphic assessment of N24SWD.
Double-plotted rest-activity rhythms in case 3 (A), case 5 (B), case 6 (C), and case 7 (D). Rates of delay can be variable among patients with N24SWD. As seen in (A) and (B), rates of daily delays are slower than in (C) and (D). In those who delay more slowly, the N24SWD pattern may not be apparent in monitoring for 7 days. Therefore, monitoring for at least 14 days is recommended. In addition, the rate of delay can change within an individual (C), with greater delays when the sleep onset time occurs during the day. N24SWD = non–24-hour sleep-wake disorder.
Figure 3
Figure 3. Timed melatonin and bright light therapy for N24SWD.
Double-plotted sleep diaries and wrist actigraphy in case 4 (A,B) and case 5 (C,D) are shown. The days on the actigraphy overlap with those on the sleep log. Prior to treatment, both cases had daily delays of the sleep-wake schedule. Treatment was initiated when the predicted sleep time was at the patient's desired time. In case 4, melatonin 1 mg (closed circles) 3 to 4 hours before the desired sleep time and bright light therapy for 60 minutes (open circles) after waking led to successful entrainment to a 24-hour schedule. In case 5, melatonin (closed circles) 2 to 3 hours before the desired sleep time and bright light therapy for usually 45 minutes (open circles) on awakening initially led to successful entrainment as seen in the first 8 days of treatment. In (D), the arrow indicates the day treatment was initiated. However, the patient gradually delayed the timing of melatonin and light, leading to delays in the sleep-wake schedule. After discontinuing treatment, he continued to delay in a N24SWD pattern. These cases highlight the ability of timed melatonin and bright light therapy to successfully entrain the sleep-wake schedule in patients with N24SWD, but consistent timing and dose is required to maintain the effect. N24SWD = non–24-hour sleep-wake disorder.
Figure 4
Figure 4. Salivary melatonin profile in case 6.
Sampling began at 5:00 PM and continued every 30 minutes until midnight. The DLMO occurred at approximately 5:15 PM, when the melatonin concentration exceeded the 25% of maximum melatonin threshold. DLMO = dim light melatonin onset.
Figure 5
Figure 5. Effect of high dose melatonin versus low dose melatonin with bright light on N24SWD.
Double-plotted sleep diaries in case 7 are shown before taking melatonin, (top) while taking melatonin 10 or 20 mg (closed circles), and (bottom) while taking melatonin 0.5 mg (closed circles) and using bright light therapy (open circles) for 60 minutes. (Top) This patient had daily delaying of the sleep-wake schedule, which was slower when the sleep onset time occurred during the night. With addition of melatonin 10 to 20 mg, the patient continued to delay each day. Furthermore, the rate of daily delaying increased when the melatonin was taken after or near the end of the primary sleep episode, and it was slower when melatonin was taken within several hours before sleep onset. (Bottom) Combination of low dose melatonin and bright light therapy led to entrainment of the sleep-wake cycle, though sleep remained fragmented. After treatment was discontinued, the sleep-wake scheduled resumed delaying. Low dose melatonin may be more effective than high dose melatonin but the combination with timed bright light therapy may also be necessary for successful entrainment in patients with N24SWD. N24SWD = non–24-hour sleep-wake disorder.
Figure 6
Figure 6. An algorithm for the evaluation and management of N24SWD.
N24SWD = non–24-hour sleep-wake disorder.
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