Characterising Sleep Disorders in Children With Tourette Syndrome

Gilles de la Tourette Syndrome (TS) is a neurobehavioural condition characterised by persistent motor and vocal tics, with symptom onset typically around the age of six. Tics are described as sudden, rapid, and repetitive involuntary movements. While the core clinical features of TS are well established, the effects of TS on sleep in children remain poorly understood.

Difficulties with sleep are frequently reported in children, including trouble initiating sleep, frequent night-time awakenings, decreased sleep efficiency, excessive sleep duration, and parasomnias such as night terrors and sleepwalking. Increasing evidence suggests that sleep problems are highly common among children with TS, with reported rates of sleep disorders ranging widely from 9% to 80%. The most frequent sleep disorders reported in this population include insomnia, excessive daytime sleepiness, and disorders of arousal. Beyond the diagnosis of specific sleep disorders, studies have shown that children with TS most commonly exhibit prolonged sleep onset and reduced total sleep efficiency compared to typically developing peers. Considering sleep plays a critical role in daytime functioning and is predictive of neurodevelopment, cognitive performance, and emotional wellbeing, understanding sleep problems in children with TS is of vital importance.

Previous studies of sleep problems in children with TS have primarily used a single objective sleep study. The primary method of sleep assessment is polysomnography (PSG), a sleep study that measures brain activity, heart activity, eye movements, muscle tone, limb movements, and respiratory patterns. One study using PSG found that children with TS had reduced sleep efficiency and increased arousals compared to healthy controls. Similarly, another study that utilised a different sleep study named actigraphy, a watch that tracks movement and light exposure to estimate sleep and wake, also found low sleep efficiency and a higher fragmentation index in children with TS. However, the heightened arousals observed in these studies were scored according to standard criteria for all sleep study analyses. Thus, these arousals cannot be directly attributed to tics, as they represent a general measure of wakefulness during sleep. Moreover, actigraphy has demonstrated low specificity for detecting wakefulness during sleep, although it provides a long-term and naturalistic representation of an individual's sleep. This contrasts with PSG, which may be influenced by the "first night effect", where sleep is altered by the unfamiliar sleep lab environment. Therefore, integrating findings from both PSG and actigraphy will provide a more thorough assessment of sleep in this population.

Furthermore, these objective methods of assessing sleep do not capture how the child or their parents perceive sleep quality and its effect on everyday life. Parent-report studies in TS show high rates of reported sleep disturbance and demonstrate that greater tic severity predicts increased sleep problems and worsening daytime functioning. Moreover, research comparing the concordance of objective and subjective measures of sleep has shown a discrepancy. Subjective reports of sleep in children with TS have consistently underestimated night-time awakenings and overestimated total sleep time compared with actigraphy and PSG results. This discrepancy highlights that subjective measures capture perceptual and experiential aspects of sleep that are not captured in physiological recordings, underscoring the value of including targeted subjective measures when investigating sleep problems in TS.

Previous research investigating sleep problems in children with TS has not examined arousals attributable to tics, has relied on a single objective method to assess sleep patterns, and has not combined objective and subjective measures of sleep to provide a comprehensive characterisation of sleep in this population. This highlights a gap in the research with respect to combining objective data from PSG and actigraphy with subjective reports. To address this, the present study will apply novel Tic indices during PSG analysis of children with TS to quantify tic-related sleep disruption, alongside a newly developed Tic in Sleep questionnaire to provide a holistic evaluation of how TS affects sleep and daytime functioning. The investigators will test the hypothesis that children with TS will exhibit poorer sleep quality, both objectively and subjectively, compared to historical control data from healthy children.

Participants This study involves the retrospective analysis of PSG and actigraphy data from children with TS who are already under investigation for sleep problems by the Evelina London Children's Hospital. All participants will have been referred to the sleep service team, known by the Tics and neuro-developmental movements (TandDEM) team, and will meet the diagnostic criteria for TS according to the International Classification of Diseases (ICD-10; F95.2).

Sample size Power analysis to determine sample size was completed using G*Power 3.1.9.6 software.

The Tic in Sleep questionnaire will be completed by TS children only. As no control group will be included, sample size calculation is based on detecting a correlation between questionnaire responses and objective measures (PSG and actigraphy). An a priori power calculation indicated that 29 participants are required to detect a medium effect (ρ = 0.5) with α = 0.05 and 80% power. To allow for incomplete data, 34 children with TS will be recruited for completion of the Tic in Sleep questionnaire.

A sample size of 12-15 participants for retrospective analysis of PSG and actigraphy data is suitable for this part of the study. This will provide sufficient data to examine whether the Tic indices can reliably assess the impact, severity, and frequency of tics on sleep. In the future, this data can be used to calculate proper effect sizes for a larger study employing the Tic indices.

Tic indices PSG and actigraphy studies will be scored using the latest AASM guidelines (Version 3.0). Within the PSG analysis framework, two novel Tic indices will be introduced: one scores tics during sleep (Ts); the other scores tics during sleep that cause arousal (Tsa). The indices will be broken down for each sleep stage (wake, NREM1, NREM2, NREM3, REM). A feature will be added within Embla® RemLogic™ to enable scoring of the Tic indices directly within the software.

Tic in Sleep Questionnaire A purpose-designed Tic in Sleep questionnaire will be created to provide a subjective assessment of sleep in TS children. This will be completed by the participants, with support from parents/guardians to capture both child and parental observations of tic-related influences on sleep quality, dreams, and daytime functioning. Additionally, the questionnaire will collect information on participant comorbidities and medications.

Study Design Assessment of sleep in TS children typically involves a two week actigraphy and an inpatient PSG. As this is a retrospective study, these investigations will have been completed as part of their routine care. Eligible participants will be identified through sleep clinics, and inclusion and exclusion criteria will be reviewed by the research team.

Once consent and assent have been obtained, participants will be invited to complete the Tic in Sleep questionnaire via a Jisc link. PSG and actigraphy data of the selected participants will then be scored using the Tic indices by an AASM certified sleep physiologist

Statistical Analysis Statistical analysis will be performed in SPSS 30.0 (SPSS Inc., Chicago, IL).

An independent samples t-test will be applied to compare TS children's sleep parameters to historical control data from healthy children, as published in the AASM Scoring Manual, Version 3.0 (2023). This test will identify if the difference in their sleep parameters (sleep efficiency, total sleep time, arousal index, etc.) is a real, statistically significant difference or due to random chance.

Tic indices will be calculated as the number of tics per hour, reported as a mean ± standard deviation (SD). A repeated-measures ANOVA will be used to compare the Tic indices between sleep stages and wake within the same participant to identify if, overall, sleep stage makes a difference to the Tic index. If it does, post-hoc tests can be employed, such as a Bonferroni correction.

To directly compare Ts and Tsa within each participant, a paired samples t-test can be used. This will explore if a child generally arouses from tics during sleep, or if they continue to sleep during their tics.

Finally, Cronbach's alpha will determine the internal consistency of responses received from the questionnaire, thus testing the validity of this new Tic in Sleep questionnaire. Descriptive statistics, including means, standard deviations, medians, and percentages, will be used to evaluate specific questionnaire responses.

Research Ethics and Clinical Governance Ethical approval is currently being obtained from the Health Research Authority (HRA) [IRAS:362134, pending], alongside governance approval from GSTT Research and Development (R\&D). Before data collection, approval from the University Ethics Committeettee (EthOS) at Manchester Metropolitan University will be acquired.

Key outcomes and impacts This study aims to validate the newly defined Tic index as an objective measure of sleep disruption in children with TS. Analysis of actigraphy and PSG data will characterise how tics affect sleep architecture, sleep-stage patterns, and overall sleep quality relative to historical control data from healthy children. By combining objective results from actigraphy and PSG with subjective reports from the Tic in Sleep questionnaire, this study will describe the impact, severity, and frequency of tics in sleep and how this relates to the perceived quality of sleep and daytime functioning.

The impact of this research lies in providing the first systematic evidence supporting the Tic index as a direct tool for evaluating tic-related sleep disruption. It will also assess the feasibility of applying the Tic index in future larger-scale studies. Furthermore, this study will enhance our understanding of how tics affect sleep physiology, and how sleep is experienced by children with TS and their parents. Ultimately, this work will contribute to the development of standardised assessment tools that can be used to evaluate sleep disruption and support improved management and treatment of sleep problems in children with TS.