Diagnostic Criteria for Primary Tic Disorders: Time for Reappraisal

Abstract

The most widely applied diagnostic criteria for Tourette syndrome (TS) and other persistent motor and vocal tic disorders (PMVTD) are those included in the Diagnostic and Statistical Manual (DSM) of Mental Disorders of the American Psychiatric Association.1 These criteria have remained substantially unchanged for the past 30 years since the DSM-IV was published in 1994.2 DSM-IV and DSM-5-text revised (TR) criteria for primary tic disorders (Table 1) have set clear diagnostic standards for tic disorders. However, an increasingly shared view among experienced clinicians is that these criteria neither reflect the critical thinking behind the diagnosis of tic disorders nor the neurobiology of these conditions. Moreover, the current criteria may fail to separate neurobiological different conditions also manifesting with tics and tic-like behaviors. The broad inclusivity of the current criteria has been a longstanding problem that became more pressing with the sharp rise in functional tic-like behaviors (FTLBs) during the coronavirus disease 2019 pandemic.3-5 According to the DSM-5-TR,1 many individuals affected by FTLBs meet the criteria for and can formally be diagnosed with TS. There are serious risks related to this misdiagnosis, including unnecessary investigations, delayed treatment, and unwarranted, possibly harmful interventions. Additionally, some individuals with TS may subsequently develop concurrent FTLBs,6 which complicates management if not accurately recognized. Inaccurate diagnostic criteria can compromise the validity and reproducibility of research findings. Finally, misdiagnosis enhances stigma, leading to social isolation, discrimination, psychological distress, and erosion of trust in healthcare systems.7 In response to the growing number of adolescents and young adults seeking care for disabling FTLBs, an international working group collaborating with the European Society for the Study of Tourette Syndrome (ESSTS) has developed, through Delphi methodology, consensus-based criteria for a clinical diagnosis of FTLBs.8 These constitute a helpful tool for health professionals to diagnose and treat this condition with confidence.9-11 FTLBs display typical features of functional neurological symptoms12, 13 and have been demonstrated not to respond to the typical pharmacological therapy for primary tic disorders.14 Moreover, both conditions may benefit from treatment of psychiatric comorbidities and cognitive behavioral therapy.15 Given the clinical and pathophysiological differences between tics and FTLBs and the potential ambiguity of the current diagnostic criteria for primary tic disorders, we believe it is time to reconsider these criteria. In proposing this revision of diagnostic criteria for primary tic disorders, we have taken into account the key features distinguishing primary tic disorders from a pure FTLB disorder, with the aim of minimizing risk of misdiagnosis and inappropriate management. The DSM criteria for the diagnosis of tic disorders have changed from the different versions of the manual.16 The DSM is a product of the American Psychiatric Association's Committee on Nomenclature on Statistics and, historically, had a role in classifying psychiatric conditions into a clinical and medical framework. Both the original version and subsequent revisions reflected the social understanding of diseases at the time, and the evolving understanding shaped the classification.17 As a result, the modifications of the criteria for tic disorders over time were not informed by new evidence of the biological underpinnings of tic disorders. The most recent DSM-5-TR criteria rest on four pillars: (1) presence of vocal (phonic) and/or motor tics; (2) age at onset; (3) duration of tics; and (4) exclusion of secondary etiologies for tics. The criteria then differentiate TS from other persistent tic disorders based on the co-occurrence of motor and phonic tics. A strength of the DSM-5-TR classification is having included tic disorders in the category of “neurodevelopmental disorders,” also comprising intellectual disability, communication disorders, autism spectrum disorder, and attention-deficit/hyperactivity disorder (ADHD), in line with the current, biology-driven conceptualization of tic disorders. Although specifically referring to tic disorders, the DSM-5-TR criteria do not consider impairment, whereas not all tics are functionally impairing and, therefore, the threshold for tics representing a disorder can be arbitrary. Overall, relevant limitations of the DSM-5-TR criteria should be highlighted, pertaining to four main themes. Because of these limitations, we believe these criteria do not accurately reflect the natural history of primary tic disorders and may fail to differentiate primary tic disorders from FTLBs accurately. The upper age limit of tic disorders onset has been controversial for decades. Although the DSM-III,18 without clear biological justification, first set the upper limit at age 15, the DSM-III-TR19 changed it to age 21. Eventually, again without a neurobiological rationale, this was modified to age 18 in the DSM-IV without subsequent modifications. The onset of TS is between age 4 and 8, whereas that of PMVTD is ~2 years later.20-24 Freeman et al.25 reported that 93% of 3500 TS participants exhibited tics before 10 years of age. Unlike previous versions, the 11th revision of the International Classification of Diseases (ICD-11) by the World Health Organisation26 does not include any specific age limit in the “essential” diagnostic criteria. However, among “course features,” age of onset “commonly…between the ages of 4 and 6” is specified. Considering this natural history data, the current upper limit of 18 years for age at onset of primary tic disorders appears not well justified. Keeping this upper limit unchanged or eliminating altogether the age at onset criteria (as implied in the ICD-11 criteria) may dangerously increase the risk of misdiagnosis between primary tic disorders and FTLBs. The latter is typically present after the age of 12, as demonstrated by recent literature9 and stated in the ESSTS 2022 diagnostic criteria.8 To use age at onset as a supportive diagnostic criterion that reflects the actual time course of primary tic disorders, the upper limit of age at onset should be anticipated to be 10 to 12 years of age. Introducing this as a supportive, rather than mandatory, criterion would prevent a potential, and not uncommon, recall bias in self-reporting age at onset from erroneously ruling out the diagnosis of primary tic disorder. In TS and other PMVTD, initial tics are, in the majority of cases, simple tics involving the face, head, and/or neck regions.27, 28 During the following years of the developmental period, more complex tics or tics affecting other body regions may arise.28 Tics typically peak in severity between age 10 and 1420, 21 and decrease in severity over the course of mid-to-late adolescence,21, 29 although tics remit in adulthood in 10% to 20% of individuals.20 An increase in female proportion of the TS population with increasing age has also been observed, and potential differences in clinical course of TS between sexes were reported, which need further investigation.30 Conversely, the natural history of FTLBs differs substantially from that of primary tic disorders. Indeed, FTLBs often emerge abruptly in adolescents or young adults, with maximum disability often reached within the initial weeks, presenting from the outset with vocalizations and complex movements involving multiple body regions, predominantly limbs and torso.8-10 Despite being routinely considered in clinical practice and contributing significantly to the diagnostic process, these basic clinical features of tics are not included in current diagnostic criteria. We propose that early predominance of the cranial and cervical regions and early predominance of simple over complex tics should be included as supportive criteria of primary tic disorders. The current DSM-5-TR criteria specify a minimum 1-year disease duration to define a persistent tic disorder, whereas symptoms of less than 12 months' duration constitute a diagnosis of “Provisional Tic Disorder”. Although the 1-year cut off aligns with the definition of “chronic disease” of the National Center for Chronic Disease Prevention and Health Promotion of the Center for Disease Control and Prevention (https://www.cdc.gov/chronicdisease/about/index.htm) and we consider this criterion acceptable, we acknowledge that it remains arbitrary. In fact, limited evidence suggests that most children with provisional tics may continue to exhibit tics for more than a year.31 However, at the present time, we lack prospective data suggesting the existence of an earlier cut point that would identify persistent tics as efficiently as the 12-months one. It has long been suggested that the differentiation between motor and phonic tics is arbitrary.32-34 Phonic tics are motor tics that involve the oral, nasal, pharyngeal, laryngeal, and respiratory musculature, resulting in the production of an audible sound. Both are often preceded by a premonitory urge, are highly suggestible, are usually suppressible, and may be exacerbated by stress or emotions. Of note, the term vocal tics is used interchangeably with phonic tics, but more accurately conveys tics that make sound because of the involvement of the vocal cords. In most cases, phonic tics do not involve the vocal cords, but the passage of air through the upper respiratory tract eventually produces their sound (ie, throat clearing or sniffing). Although commonalities and differences in the neurobiological basis of motor and phonic tics warrant further investigation, there is no evidence from registry-based and observational studies to support a different prognosis of a tic disorder based on the predominance of motor rather than phonic tics. Overall, although they communicate broad clinical categories of tic presentations, there is insufficient evidence to support a net separation between persistent motor tic disorder and persistent vocal (phonic) tic disorder. In addition, this separation may not be helpful in distinguishing between primary tic disorders and pure FTLBs, which too can present with different motor and vocal phenomena that wax and wane over time. Even the complexity of vocalizations is not helpful, as coprolalia is commonly noted among FTLBs.35 Among the important modifications to the DSM, echolalia, suppressibility of tics, fluctuation of symptoms, and impact on daily life activities were all initially proposed as criteria, but subsequently dropped in later editions of the DSM.19 However, the bedrock of the distinction between TS and other PMVTD has always been that motor and phonic tics must co-exist (although not necessarily concurrently or consistently) to diagnose TS. In particular, the DSM-5-TR criteria for TS specify that individuals must experience a combination of a minimum number of tics (ie, at least one phonic and two motor). However, patients with any form of primary persistent tic disorder, including TS, normally experience a much broader and fluid repertoire of tics, which can change widely over time. In keeping with this, the current ICD-11 criteria do not specify the number of required tics. Growing evidence suggests that, rather than distinct clinical entities, TS and PMVTD represent different degrees of severity or impairment of the same underlying condition.36 TS and PMVTD have clinically indistinguishable features, including onset in early childhood, response to the same treatments, waxing and waning clinical course, frequent improvement with age, family history, and comorbidity profile. Although our understanding of the genetic factors contributing to tic disorders is still limited, genome-wide association studies support that TS and PMVTD have a shared genetic profile and represent a continuous spectrum of condition, further reinforcing the diagnostic amalgamation of these two conditions.37 Although patients with TS have greater tic severity and slightly younger age at onset, both TS and PMVTD patients exhibit a high prevalence of psychiatric co-occurring conditions, including obsessive-compulsive disorder (OCD), ADHD, anxiety, and mood disorders.36 As in TS, co-occurring OCD and ADHD in PMVTD predict a higher incidence of maladaptive behaviors.38 This diagnostic differentiation appears, therefore, poorly substantiated. The similarity in comorbidity profile across all primary persistent tic disorders is, on the other hand, in contrast with the difference in frequency of comorbid neurodevelopmental and psychiatric disorders between primary tic disorders and pure FTLBs, with the latter showing greater prevalence of depression, anxiety disorders and, possibly, autism spectrum disorder.9 A unifying corollary to the above considerations is that the categorization of the “primary persistent tic disorder” into different diagnoses or clinical entities is not supported by evidence and has been challenged by the recently increased experience of FTLBs. Keeping the separation among TS, persistent motor tic disorder, and persistent phonic/vocal tic disorder could also perpetuate a stigmatizing divide between TS and non-TS tic disorders that is neither clinically nor neurobiologically justified. We, therefore, propose that the community of clinicians, scientists, and persons with lived experience should join forces to reappraise existing diagnostic criteria and establish a single diagnostic entity identified as primary persistent tic disorder (or other conceptually similar terminology). The key proposed changes are summarized in Table 1. Whether a neutral term will one day be preferred to the use of the TS eponym will require a more detailed risk–benefit analysis, inclusive of impact on stigma and care, patient perspective, as well as research in underdeveloped regions, and is, therefore, beyond the scope of this viewpoint. The lack of in vivo biomarkers and neuropathologic criteria for primary persistent tic disorder currently limit clinicians and scientists to an exclusively clinical definition. Therefore, any proposed revision of clinical criteria will need to be contrasted with newly identified markers when available. We believe that this proposal of revision to the current diagnostic criteria simplifies and provides more clarity to the nosology of primary tic disorders, while offering a diagnostic framework that can limit misdiagnosis and inappropriate management decisions that may occur in routine clinical practice, particularly with respect to pure FTLBs. 1. Research project: A. Conception, B. Organization, C. Execution; 2. Statistical Analysis: A. Design, B. Execution, C. Review and Critique; 3. Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique. M.S.: 1A, 1C, 3A; J.F.: 3B C.G.: 3B D.L.G.: 3B A.H.: 3B T.H.: 3B D.I.: 3B I.M.: 3B J.M.M.: 3B A.M.E.: 3B K.R.M.V.: 3B M.O.: 3B M.P.: 3B H.S.: 3B K.Ś.: 3B N.S.: 3B K.T.: 3B Y.W.: 3B T.P.: 1B, 3B D.M.: 1A, 1C, 3B M.S. is employed by King's College Hospital National Health Service (NHS) Trust. J.F. received honoraria from The New England Journal of Medicine: Clinical Neurology Update and American Academy of Neurology Course Presenter; and received grants from TAA Young Investigator Award. C.G. is employed by the University of Toronto; has received honoraria from the Movement Disorders Society; and has received grants from VolkswagenStiftung. D.G. provided consultancies to PTC Therapeutics and Emalex Biosciences; is employed by the Cincinnati Children's Hospital Medical Center; received honoraria from Illumina, PTC Therapeutics; received royalties from Elsevier, Wolters Kluwer; and received grants to the Institution of the United States (US) National Institute of Mental Health, US Department of Defense, Clinical Trials site investigator PTC Therapeutics, and Emalex Biosciences. A.H. provided consultancies to Noema Pharma; belongs to the advisory board of Association Française pour le syndrome Gilles de la Tourette; and is employed by Assistance Publique des Hôpitaux de Paris. T.H. is employed by GSTT and Kings College London, Faculty of Life Sciences and Medicine, Department of Women and Children's Health, London United Kingdom. D.I. belongs to the advisory board of Tourette Association of America; is employed by Vanderbilt University Medical Center; received honoraria from Tourette Association of America; received grants from National Institute of Neurological Disorders and Stroke (NINDS) (K23NS131592), Teva Branded Pharmaceutical Products, and R&D. I.M. provided consultancies to AbbVie; is employed by the University of Florida; received honoraria from the Tourette Association of America, Parkinson Foundation, Medscape, Efficient CME, and Cleveland Clinic; received royalties from Robert Rose publishers; received grants from the Parkinson Foundation, Tourette Association, Dystonia Coalition, AbbVie, Boston Scientific, Eli Lilly, Neuroderm, and Revance. J.M.M. is employed by Wake Forest University Health Sciences; received honoraria from the Movement Disorders Society, American Academy of Neurology; received grants from the Tourette Association of America, American Board of Psychiatry and Neurology, and NINDS NeuroNEXT. A.M.E. is employed by Horizon Health Network, New Brunswick, Canada. K.M.V. provided consultancies to Abide Therapeutics, adjupharm, Alexion, AMP Alternative Medical Products, Becanex, Boehringer Ingelheim International, Bionorica Ethics, CannaMedical Pharma, Canopy Grouth, Columbia Care, CTC Communications, Demecan, Enua pharma, DHMS Direct Health Medical Services, Ethypharm, Eurox Group, Global Praxis Group, Hormosan Pharma, Lundbeck, Marry Jane, MCI Germany, Neuraxpharm, Noema Pharma, Sanity Group, Stadapharm, Synendos Therapeutics AG, Syqe, Tilray, and Zambon; belongs to the advisory boards of Alexion, Branchenverband Cannabiswirtschaft e.V., CannaMedical Pharma, Bionorica Ethics, Canopy Growth, Columbia Care, Ethypharm, Hormosan Pharma, IMC Germany, Leafly Deutschland, Neuraxpharm, Sanity Group, Stadapharm, Synendos Therapeutics AG, Syqe Medical, Therapix Biosciences, and Tilray; received honoraria from Agaplesion Frankfurter Diakonie Kliniken gemeinnützige, Almirall, Aphria Deutschland, Arbeitsgemeinschaft Cannabis als Medizin, Astra Zeneca, Bedrocan, Bundesverband pharmazeutischer Cannabinoidunternehmen, Camurus, canymed, CEREBRO SPAIN BIDCO S.L, Cogitando, Deutsche Gesellschaft für Psychiatrie und Psychotherapie, Psychosomatik und Nervenheilkunde, Diplomado Internacional de de International Eurox Deutschland, pharma, Pharma, Medical Cannabis für e.V., Therapeutics, Tilray, e.V., Group, and received royalties from und Elsevier, and and received grants from Research Foundation, of and Tourette Gesellschaft e.V., and is employed by Medical received honoraria from The Movement Disorders Society, American Academy of Neurology, Vanderbilt received royalties from received grants from National of Health The Foundation, and Tourette Association of provided consultancies to Global and to the advisory board of employed by College of received honoraria from The Movement Disorders Society; and received grants from Clinical support from PTC Therapeutics, Alexion, and Biosciences. provided consultancies to received honoraria from The Movement Society and American Academy of Neurology; and received grants from Clinical support from Neuroderm, Pharma, and is employed by the received honoraria from and and received grants supported by the Disease is employed by the University of and received grants supported by an American Academy of Neurology American Foundation, and Tourette Association as well as of Health, and from the International Movement Disorders is employed by King's College Hospital Trust. provided consultancies to is employed by Boston Children's and received grants from is employed by the University of and received grants from The of Health Research and the provided consultancies to to the advisory board of is employed by the University of received honoraria from Dystonia Medical Research Movement Disorders Society, Movement Disorders Society; received royalties from University and received grants from and Clinical of the Health Services, Foundation, Dystonia Medical Research and National Association in of Parkinson The of Health and The data that support the of this are from the