Images: "Too much heat for my non-24-hour sleep-wake disorder!" A case report.

The non-24-hour sleep-wake disorder (N24SWD) is a rare condition, sometimes associated with blindness or with suprachiasmatic nuclei lesions, resulting in a free-running rhythm or hypernycthemeral syndrome. Synchronizers, such as light, when light perception remains, melatonin, food intakes, physical activity, social interactions, and temperature, play a key role in the treatment of N24SWD. In this report, we describe a case illustrating the impact of outdoor temperature in a 34-year-old man with N24SWD effectively treated through a combination of chronotherapy interventions. During 3 consecutive heat waves, he experienced a recurrence of his natural 25.5-hour free-running rhythm, with a consistent bedtime phase delay caused by temperature, resulting in the discontinuation of chronotherapy. After these heat waves, he was able again to resynchronize his rhythms with the combination of chronotherapeutics. This case report highlights that patients with N24SWD may be particularly at risk of relapse during heat waves, with direct implications for monitoring and reinforcing chronotherapies. CITATION: Garrivet J, d'Ortho M-P, Frija-Masson J, et al. "Too much heat for my non-24-hour sleep-wake disorder!" A case report. J Clin Sleep Med. 2024;20(2):329-333.

Case report: Diagnosis and intervention of a non-24-h sleep-wake disorder in a sighted child with a psychiatric disorder.

Circadian rhythm sleep-wake disorders (CRSWD) are sleep dysfunctions related to circadian functioning. They are characterized by symptoms of insomnia or excessive sleepiness that occur because the intrinsic circadian pacemaker is not entrained to a 24-h light/dark cycle. Affected individuals with a free-running disorder or hypernycthemeral syndrome (N24SWD) have a longer sleep-wake cycle that produces a sleep pattern that typically delays each day. The disorder is seen in 70% of blind people, and among people with healthy vision, it is a rare pathology. Among sighted cases, 80% are young men and 28% have a psychiatric disorder. The patient was a 14-year-old boy with a psychiatric pathology diagnosed with a PANDAS syndrome (pediatric autoimmune neuropsychiatric disorders associated with streptococci), a sudden acute and debilitating onset of intense anxiety and mood lability accompanied by obsessive compulsive-like issues and/or tics, in association with a streptococcal A infection that occurs immediately prior to the symptoms. As a comorbidity, he exhibited severe insomnia due to an irregular sleep pattern that strongly delayed his sleep schedule day to day. It affected his daily routines, as he was not going to school, and aggravated, furthermore, the psychiatric symptoms. He was referred for sleep consultation, where the case was explored by ambulatory circadian monitoring (ACM) using the novel system Kronowise® (Chronolab, University of Murcia) and diagnosed with a non-24-h sleep-wake disorder (N24SWD). The first treatment approach for the patient was focused on improving symptoms during the acute infection and psychiatric symptoms. Additionally, sleep pathology was treated by light therapy and melatonin. After 8 months and different trials, it was possible to establish a treatment to normalize the symptoms and fix his sleep rhythm in a normal schedule as well as to reduce anxious symptoms during the day. The association of PANDAS and N24SWD has not previously been reported in the literature.

Genetics and functional significance of the understudied methamphetamine sensitive circadian oscillator (MASCO).

The last 50 years have witnessed extraordinary discoveries in the field of circadian rhythms. However, there are still several mysteries that remain. One of these chronobiological mysteries is the circadian rhythm that is revealed by administration of stimulant drugs to rodents. Herein we describe the discovery of this circadian rhythm and its underlying oscillator, which is frequently called the methamphetamine-sensitive circadian oscillator, or MASCO. This oscillator is distinct from canonical circadian oscillators because it controls robust activity rhythms independently of the suprachiasmatic nucleus and circadian genes are not essential for its timekeeping. We discuss these fundamental properties of MASCO and integrate studies of strain, sex, and circadian gene mutations on MASCO. The anatomical loci of MASCO are not known, so it has not been possible thus far to discover its novel molecular timekeeping mechanism or its functional significance. However, studies in mutant mice suggest that genetic approaches can be used to identify the neural network involved in the rhythm generation of MASCO. We also discuss parallels between human and rodent studies that support our working hypothesis that a function of MASCO may be to regulate sleep-wake cycles.

Sleep deprivation therapy to reset the circadian pacemaker in a non-24-hour sleep-wake disorder: a case report.

NONE: Non-24-hour sleep-wake disorder is 1 of several chronic circadian rhythm sleep-wake disorders. It is defined as progressive daily shifts in sleep onset and wake times. It mainly affects patients who are sight-impaired, is relatively rare in sighted patients, and is difficult to treat, with no guidelines. This case report discusses non-24-hour sleep-wake disorder in a sighted young man who complained of alternating severe insomnia and excessive sleepiness, with a sleep agenda and actigraphic data showing a daily delay of approximately 2 hours. A novel therapy by total sleep deprivation followed by a combination of morning light therapy and nocturnal melatonin administration was efficient in stopping his free-running sleep-wake pattern both immediately and in the long term. The treatment combination for 6 months resulted in stable circadian entrainment to a 24-hour cycle. Compliance with chronotherapy was maintained over the course of follow-up.

Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders: Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD). An Update for 2015: An American Academy of Sleep Medicine Clinical Practice Guideline.

A systematic literature review and meta-analyses (where appropriate) were performed and the GRADE approach was used to update the previous American Academy of Sleep Medicine Practice Parameters on the treatment of intrinsic circadian rhythm sleep-wake disorders. Available data allowed for positive endorsement (at a second-tier degree of confidence) of strategically timed melatonin (for the treatment of DSWPD, blind adults with N24SWD, and children/ adolescents with ISWRD and comorbid neurological disorders), and light therapy with or without accompanying behavioral interventions (adults with ASWPD, children/adolescents with DSWPD, and elderly with dementia). Recommendations against the use of melatonin and discrete sleep-promoting medications are provided for demented elderly patients, at a second- and first-tier degree of confidence, respectively. No recommendations were provided for remaining treatments/ populations, due to either insufficient or absent data. Areas where further research is needed are discussed.