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Effect of diet, exercise and sleep on tic severity: a scoping review protocol

Introduction Tourette syndrome is a common childhood-onset neuropsychiatric disorder, with tics that wax and wane in frequency and severity over time. The purpose of the proposed scoping review is to map the types of evidence available pertaining to the effect of diet, sleep and exercise on tic severity and identify key concepts and gaps in research. Methods Our scoping review will use the six-step framework recommended by Arksey and O’Malley, with enhancements from Levac et al and Joanna Briggs Institute. We will attempt to identify all the relevant literature regardless of study design. We will search six electronic databases, the reference lists of all selected studies and the grey literature for studies examining an association between dietary factors, sleep or physical exercise and tics, or studies of interventions targeting diet, sleep or exercise to reduce tics. Our analysis plan includes description of the reported associations among dietary factors, sleep and physical exercise and tics, the effects of interventions, the research methodologies and how outcomes are measured. Ethics and dissemination An approval from a recognised committee is not required to conduct the proposed review, as the study entails secondary analysis of the literature available publicly. For dissemination of the study, the results will be submitted for publication to peer-reviewed scientific journals and presented at relevant public forums and conferences.

Introduction Tourette syndrome is a common childhood onset neuropsychiatric disorder, with tics that wax and wane in frequency and severity over time. The purpose of this scoping review is to map the types of evidence available pertaining to the effect of diet, sleep and exercise on tic severity and identify key concepts and gaps in research.

Methods
Our scoping review will use the 6-step framework recommended by Arksey and O'Malley 1 , with enhancements from Levac et al. 2 and Joanna Briggs Institute 3 . We will attempt to identify all relevant literature regardless of study design. We will search six electronic databases, the reference lists of all selected studies, and grey literature for studies examining an association between dietary factors, sleep or physical exercise and tics, or studies of interventions targeting diet, sleep or exercise to reduce tics. Our analysis plan includes description of the reported associations between dietary factors, sleep and physical exercise and tics, the effects of interventions, the research methodologies, and how outcomes are measured.
Ethics and dissemination An approval from a recognized committee is not required to conduct this review, as this study entails secondary analysis of literature available publicly. For dissemination of the study, the results will be submitted for publication to peer-reviewed scientific journals and presented at relevant public forums and conferences.

Strengths and limitations of this study
-This study will provide a comprehensive synthesis of the effects of diet, sleep and exercise on tic severity. -The search strategy will include six databases, the reference lists of all selected studies, and as well as a wide range of grey literature sources. -This study will be limited to publications in English only. affects approximately 1 in 100 children 5 and 1 in 1000 adults 6 and is three to four times more common in boys than girls. Simple motor tics are sudden, brief, meaningless movements such as blinking, eye movements, grimacing, nose twitching, mouth movements, head jerks and shoulder movements. Simple vocal tics are sudden, meaningless sounds or noise, such as throat clearing, coughing, sniffing, screeching, barking or grunting. The majority of individuals seen in specialized clinics for tic disorders have comorbid neuropsychiatric conditions, of which attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD) are most common, with 50% or more of individuals with TS meeting diagnostic criteria for one of these disorders, and approximately 30% diagnosed with all three disorders 7 . The presence of comorbid disorders has a strong impact on health-related quality of life in children and adults with TS.
Tics characteristically begin in early childhood, peak in severity between 10 and 12 years of age and improve in adolescence. By the age of 16 years, nearly 80% of youth have either mild, minimal or no tics 8 9 . There is understandable reluctance by many parents to treat their children with medication for tics and many seek other options to help alleviate tics and the distress associated with them. There is good evidence to support the use of behavioural interventions including the Comprehensive Behavioural Intervention for Tics (CBIT) 10 . CBIT, a manualized behavioural therapy consisting of eight treatment sessions over ten weeks, has demonstrated efficacy in decreasing tic severity in children ages nine and older as well as adults, with effects sustained for at least six months 10 11 . As treatment must be provided by a trained professional, access to treatment is not universally available.
Tics are known to wax and wane over time-from hour to hour, day to day, week to week and month to month, leading to a great deal of introspection on what factors, if any, influence tic severity. Parents and caregivers often ask about the impact of everyday life factors on tics, including diet, sleep and exercise, and if modification of these factors could bring about an improvement in tics. The purpose of this scoping review was to undertake an examination of lifestyle factors associated with tic severity to provide direction for our own research study in this area, and advise families seeking information on this topic. Our aim is to map the types of evidence available pertaining to the effect of diet, sleep and exercise on tics and identify key concepts and gaps in research in this area.  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  60   F  o  r  p  e  e  r  r  e  v  i  e  w  o  n  l  y   5 The proposed scoping review will use the 6-step framework recommended by Arksey and O'Malley 1 , with enhancements from Levac et al. 2  Consultation. Although, the optional 6 th step of consulting with stakeholders provides important and relevant input to topic at hand, for this scoping review a formal consultation process will not be included, due to time and budget constraints. Even so, insights from patients, their families and healthcare providers have been informally noted through extensive contact with the patient population.

Protocol Design
Step 1: Identifying the research questions This scoping review aims to explore a population with tic disorders and Tourette's syndrome and the concept will be the role of diet, exercise and sleep patterns on tic severity in any setting or age (context). As scoping reviews are explorative in nature, the research question will be refined throughout the review to map all the current literature and identify knowledge gaps. Nonetheless, the objective is to identify factors and interventions associated with positive and negative impacts on tic severity in various settings. The contributing factors and interventions will be analyzed for advantages/disadvantages, limitations, facilitators and effectiveness with regards to tic severity.
Step 2: Identifying relevant studies The literature search will be conducted to include the time frame from inception to June 2018.
The key terms used to search the database will be a variation of 'tics disorder', 'Tourette's syndrome', 'diet', 'exercise' and 'sleep' (see Table 1). The search will be performed in June 2018 and the online databases that will be used include MEDLINE ( Preliminary study selection criteria include articles published in English language with any type of study methodology or study design, regardless of healthcare setting. The participants included are of any age, gender, and geographical location. All non-human subjects based studies and articles in languages other than English will be excluded from the literature search.
Step 3: Study selection The combined search through all the databases will be imported to a citation software and duplicate search results will be eliminated. Two reviewers will independently screen titles and abstracts from the search results according the criteria set for inclusion and exclusion. To resolve uncertainties, a discussion among the authors will be conducted until a consensus is reached.
Step 4: Charting the data For the selected titles and abstracts, full articles will be obtained and reviewed by 2 authors. The charting of data will be divided amongst two authors, with verification of extracted information performed by a third author. A data extraction form (Tables 2-a and 2-b) will be used to tabulate pertinent information. In order to validate the form, a pilot test will be conducted after revision and charting of 5 to 10 studies. The data extraction form will be modified to include and exclude variables during the charting process.
Step 5: Collating, summarizing and reporting the results Using the data extraction form (see Tables 2-a and 2-b), analysis of the selected studies will be presented through descriptive methods (quantitative and qualitative) of the information relating to diet, exercise and sleep patterns on tic severity. Study characteristics (eg, type of study, location of study, year of publication), population characteristics (eg, sample size, mean age, sex, comorbidities) and intervention characteristics (eg, types, providers, dose, duration, frequency, intensity) will be documented. Where applicable, data will be organized visually into charts and tables to relay an overview of the study findings. An approval from a recognized committee is not required to conduct this review, as this study entails secondary analysis of literature available publicly. As for dissemination of the study, the results will be submitted for publication to peer-reviewed scientific journals and presented at relevant public forums and conferences. The findings of the review are predicted to organize literature available and enlighten on knowledge gaps pertaining to the research topic.

ETHICS AND DISSEMINATION
Furthermore, the results of this scoping review will determine the benefits of conducting a systematic review. Additionally, the results will be available to policy makers, healthcare providers and patients to effectively modify lifestyle patterns and tic severity.

CONCLUSION
This review will map the types of evidence available pertaining to the effect of diet, sleep and exercise on tics. The standardized language framework will tie together the sparse and varied literature and help identify the scope, depth, key themes and gaps that exist. The results from this scoping review will inform and guide our next research study in this area, and advise families seeking information on this topic.

ABSTRACT
Introduction Tourette syndrome is a common childhood onset neuropsychiatric disorder, with tics that wax and wane in frequency and severity over time. The purpose of the proposed scoping review is to map the types of evidence available pertaining to the effect of diet, sleep and exercise on tic severity and identify key concepts and gaps in research.

Methods
Our scoping review will use the 6-step framework recommended by Arksey and O'Malley, with enhancements from Levac et al. and Joanna Briggs Institute. We will attempt to identify all relevant literature regardless of study design. We will search six electronic databases, the reference lists of all selected studies, and grey literature for studies examining an association between dietary factors, sleep or physical exercise and tics, or studies of interventions targeting diet, sleep or exercise to reduce tics. Our analysis plan includes description of the reported associations between dietary factors, sleep and physical exercise and tics, the effects of interventions, the research methodologies, and how outcomes are measured.

Ethics and dissemination
An approval from a recognized committee is not required to conduct the proposed review, as the study entails secondary analysis of literature available publicly. For dissemination of the study, the results will be submitted for publication to peer-reviewed scientific journals and presented at relevant public forums and conferences.

Strengths and limitations of this study
-The proposed study will summarize the types of evidence available on the effects of diet, sleep and exercise on tic severity. -The search strategy will include six databases, the reference lists of all selected studies, and as well as a wide range of grey literature sources. -The proposed study will be limited to publications in English only.  Tics characteristically begin in early childhood, peak in severity between 10 and 12 years of age and improve in adolescence. By the age of 16 years, nearly 80% of youth have either mild, minimal or no tics 5 . While children and their parents are often reassured by the favourable prognosis for tics in the long-run, tics can be impairing when frequent, if they are the cause of unwanted attention, or are a source of emotional distress. Currently available medical interventions for tics can be helpful and have good evidence to support their use, but long-term treatment can be limited by adverse effects 6 . There is understandable reluctance by many parents to treat their children with  7 . CBIT, a manualized behavioural therapy consisting of eight treatment sessions over ten weeks, has demonstrated efficacy in decreasing tic severity in children ages nine and older as well as adults, with effects sustained for at least six months 7 8 . As treatment must be provided by a trained professional, access to treatment is not universally available.
Tics are known to wax and wane over time-from hour to hour, day to day, week to week and   Consultation. Although, the optional 6 th step of consulting with stakeholders provides important and relevant input to topic at hand, for this scoping review a formal consultation process will not be included, due to time and budget constraints. Even so, insights from patients, their families and healthcare providers have been informally noted through extensive contact with the patient population.
Step 1: Identifying the research questions The scoping review aims to explore a population with tic disorders and Tourette's syndrome and the concept will be the role of diet, exercise and sleep patterns on tic severity in any setting or age (context). As scoping reviews are explorative in nature, the research question will be refined throughout the review to map all the current literature and identify knowledge gaps. Nonetheless, the objective is to identify factors and interventions associated with positive and negative impacts on tic severity in various settings. The contributing factors and interventions will be  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  60   F  o  r  p  e  e  r  r  e  v  i  e  w  o  n  l  y   6 analyzed for advantages/disadvantages, limitations, facilitators and effectiveness with regards to tic severity.
Step 2: Identifying relevant studies The literature search will be conducted to include the time frame from inception to June 2018.
The key terms used to search the database will be a variation of 'tics disorder', 'Tourette's syndrome', 'diet', 'exercise' and 'sleep' (see Table 1). The search will be performed in June 2018 and the online databases that will be used include MEDLINE (OVID), EMBASE,

PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL Plus and Cochrane
Database of Systematic Reviews for published studies. A general search of organization websites such as Tourette Canada and Tourette Association of America will also be conducted to retrieve relevant articles and information pertaining to the study goal. Additionally, grey literature and reference lists from relevant articles (including systematic reviews) will also be searched. For grey literature, a search will be conducted on CADTH Grey Matters, SIGLE, greyNET, TRIP and AHRQ. Also, a google scholar search will be performed utilizing the time frame and key terms used with the scientific database. The first 200 results of this search will be analyzed.
Lastly, Web of Science, Movement Disorder Society and the American Academy of Neurology will be searched for the most updated abstracts and conference meetings summaries and Clinicaltrials.gov for intervention studies with results not yet published.
Preliminary study selection criteria include articles published in English language with any type of study methodology or study design, regardless of healthcare setting. We will include participants of any age, gender, or geographical location, who have been diagnosed with TS by a co-morbid neurodevelopmental or psychiatric disorders, we will include data from individuals regardless of the presence of comorbid disorders. All non-human subjects based studies and articles in languages other than English will be excluded from the literature search.
Step 3: Study selection The combined search through all the databases will be imported to a citation software and duplicate search results will be eliminated. Two reviewers will independently screen titles and abstracts from the search results according the criteria set for inclusion and exclusion. To resolve uncertainties, a discussion among the authors will be conducted until a consensus is reached.
Step 4: Charting the data For the selected titles and abstracts, full articles will be obtained and reviewed by 2 authors. The charting of data will be divided amongst two authors, with verification of extracted information performed by a third author. A data extraction form (Tables 2-a and 2-b) will be used to tabulate pertinent information. In order to validate the form, a pilot test will be conducted after revision and charting of 5 to 10 studies. The data extraction form will be modified to include and exclude variables during the charting process.
Step 5: Collating, summarizing and reporting the results Using the data extraction form (see Tables 2-a   location of study, year of publication), population characteristics (eg, sample size, mean age, sex, comorbidities) and intervention characteristics (eg, context, types, providers, dose, duration, frequency, intensity) will be documented. Where applicable, data will be organized visually into charts and tables to relay an overview of the study findings.

Patient and Public Involvement
Patients and the public were not formally involved in the development of this protocol, however the development of the research question was informed by decades of clinical experience working with patients and families affected by tic disorders, in acknowledgement of their interest in non-pharmacological therapies.

ETHICS AND DISSEMINATION
An approval from a recognized committee is not required to conduct the proposed review, as the study entails secondary analysis of literature available publicly. As for dissemination of the study, the results will be submitted for publication to peer-reviewed scientific journals and presented at relevant public forums and conferences. The findings of the review are predicted to organize literature available and enlighten on knowledge gaps pertaining to the research topic.

CONCLUSION
The proposed review will map the types of evidence available pertaining to the effect of diet, sleep and exercise on tics. The standardized language framework will tie together the sparse and varied literature and help identify the scope, depth, key themes and gaps that exist. The results from the scoping review will inform and guide our next research study in this area, and advise families seeking information on this topic.
Contributors EN and SSH drafted the manuscript. TP, ZG and DM designed the study and read and revised the manuscript. All authors approved the final manuscript submitted.
Funding This work was supported by the Owerko Centre at the Alberta Children's Hospital Research Institute.