2. Tourette Syndrome: The Whole Tic & Kaboodle Tourette Syndrome Association, Inc. & CDC Samuel H. Zinner, M.D. Associate Professor of Pediatrics & Developmental-Behavioral Pediatrician University of Washington, Seattle depts.washington.edu/dbpeds Wayne State University February 13, 2013

3. Tourette Syndrome: The Whole Tic & Kaboodle This presentation will reference unlabeled/unapproved uses of medications and products, and will be identified as such.

4. Evaluation Form TSA Referral List

5. Objectives Dis-inhibition Discuss neurological dis-inhibition in Tourette syndrome as a basis for tics & epiphenomena Whole-child Describe the whole-child approach to caring for children with Tourette syndrome & their families

6. Overview Tics & associated problems Assessment Tic management (non-Rx) – Conventional – Experimental

7. Take Home Points: TS is not rare Tics are usually mild, not catastrophic In most people with TS, tics are one of many related complications Address main problems, often not tics

8. Charcot & Tourette

9. Tic Disorders: Characteristics Tic Definition – motor or phonic – involuntary (unvoluntary?) – sudden and rapid – recurrent – non-rhythmic and stereotyped

10. Tics: Characteristics SimpleComplex Motor Phonic

11. Tics: Characteristics SimpleComplex Motor “Meaningless”/isolated Facial and neck Abdomen Extremities Phonic

12. Tics: Characteristics SimpleComplex Motor “Meaningless”/isolated Facial and neck Abdomen Extremities “Purposeful” Gestures Dystonic postures Self-abusive or vulgar Phonic

13. Tics: Characteristics SimpleComplex Motor “Meaningless”/isolated Facial and neck Abdomen Extremities “Purposeful” Gestures Dystonic postures Self-abusive or vulgar Phonic “Meaningless” “Allergy”-like Grunting Tongue-clicking Animal noises

14. Tics: Characteristics SimpleComplex Motor “Meaningless”/isolated Facial and neck Abdomen Extremities “Purposeful” Gestures Dystonic postures Self-abusive or vulgar Phonic “Meaningless” “Allergy”-like Grunting Tongue-clicking Animal noises “Linguistic” Syllables Words, obscenities Imitative (“echoic”) Speech atypicalities

16. Anatomic evolution of tics

22. With permission – Leonardo “Leo” da Vinci

23. Tic Disorders: Characteristics Premonitory urge Tics can usually be suppressed

24. ....... W A X E S W A N E S.......

27. Transient Tic Disorder DSM-IV-TR TM Criteria –Multiple ( &/or single ) motor &/or vocal –Many times/day ( 4 weeks – 1 year ) –Onset before 18 years –Not due to substance or medical condition

28. Chronic Tic Disorder (Motor or Vocal) DSM-IV-TR TM Criteria –Multiple (or single) motor or vocal –Many times/day and at least 1 year –Onset before 18 years –Not due to substance or medical condition

29. Tourette’s Disorder DSM-IV-TR TM Criteria –Multiple motor plus 1 or more vocal –Many times/day and at least 1 year –Onset before 18 years –Not due to substance or medical condition

30. Epidemiology Prevalence – 1% males (or more) – Male > Female (3-to-10 times)

31. Etiology URGE → TIC → RELIEF

32. Tics: Pathophysiology Dis-inhibition – “sensori-motor gating” – “filtering” Fixed action patterns / Motor pgms

33. Brain Regions in TS With permission, NIMH

34. Striatum Thalamus GP / SN Basal Ganglia cortex brainstem Striatum

35. Genetics Genetic Inherited Epigenetics Non-genetic factors

36. Genetics barriers to identifying genes Diagnosis based on behaviors Defining the TS phenotypic spectrum –“endophenotypes” Family pedigree problems Environmental influences Combinations of genes may be involved Symptoms decrease with age Transient tics

37. Differential Diagnosis of tics Compulsions Habits Stereotypies Allergies Sydenham chorea Various involuntary neuromuscular

38. Diagnostic Pitfalls 101 Unaware Waxing / waning Suppression Rare Catastrophic Coprolalia

39. With Permission: Jankovic J. Tourette’s Syndrome. NEJM. 2001. 345:1184 Copyright © 2001 Massachusetts Medical Society. All rights reserved.

40. Assessment: co-morbid conditions ADHD Obsessions/Compulsions Learning interferences Behavioral disorders Developmental disorders Mood disorders Anxiety Social difficulties (including PDDs)

41. Clinical Course < 7ADHD 7Simple motor tic (head) 8Vocal tic 11OCS + peak tic severity > 11 tics ↓ (but lifelong in 50-90%)

42. Management General Guidelines – Education – Monitoring (tics and non-tics) – Containment

43. Management Is additional treatment needed: – for tics? – for co-morbid conditions?

44. Management Perspectives: – The child – The parent – The school – You

45. Management: “co-morbid” conditions – Family dysfunction – OCD & other anxiety disorders – ADHD – Learning difficulties – Behavioral Disorders – Sleep disturbances – Other self-injurious behaviors

46. Management: tics Education & Accommodation Medications Experimental – Behavioral – Integrative – Surgical

47. Management: tics Education & Accommodation Tourette Syndrome Ass’n Teacher in-service Classroom education Teacher as role model Tic breaks/sanctuaries

48. Management: tics Experimental: Behavioral CBIT ( Comprehensive Behavioral Intervention - Tics ) HRT (Habit Reversal Training) Awareness Training Competing Response Relaxation & Social Support FA (Functional Analysis) Social situations

49. Management: tics Experimental: Integrative – Complementary – Alternative – Holistic

50. A common sense guide to complementary/alternative medicine Safe? YES NO YES RecommendTolerate NO Monitor closely or discourage Discourage Effective? Source: Cohen MH & Eisenberg DM, Ann Intern Med (2002)

51. Deep Brain Stimulation Printed with permission, Medtronic DBS lead Extension adjust settings Neuro- stimulator

52. Pharmacotherapy KEY POINTS! Do not assume medication is necessary Address comorbid condition(s) Complete tic remission is rare Stimulants are generally safe

53. Pharmacotherapy Internat’l Psychopharmacology Algorithm Project Supportive evidence ( short - term safety/efficacy )  Category A:Good  Category B:Fair  Category C:Minimal

54. Pretty much everything known to humankind tried for tics Alkaloid nicotine reserpine Alpha adrenergic agonist clonidine lofexidine guanfacine Anti-cholinesterase donepezil Anti-convulsant levetiracetam topiramate Anti-depressant (tricyclic) desipramine Anti-hypertensive (misc.) mecamylamine Anti-Parkinson pergolide Anti-psychotic (other) tetrabenazine Atypical neuroleptic aripiprazole risperidone olanzapine ziprasidone quetiapine Atypical neuroleptic ( N/A in US & Canada ) sulpiride tiapride Benzodiazepine clonazepam Cannabinoid delta-9-tetrahydrocannibinol (THC) Dopamine agonist ropinirole Dopamine antagonist metoclopramide MAO inhibitor selegiline Muscle relaxant baclofen Neurotoxin botulinum toxin A Selective NE reuptake inhibitor atomoxetine Typical neuroleptic fluphenazine pimozide haloperidol

55. Pharmacotherapy for tics: American opinions 1 st tier2 nd tier3 rd tier Clonidine Guanfacine Baclofen Topiramate Levetiracetam Clonazepam Pimozide Fluphenazine Risperidone Aripiprazole Olanzepine Haloperidol Ziprasidone Quetiapine Sulpiride Tiapride Dopamine agonists Tetrabenazine BoTox Singer et al. In Movement Disorders in Children, 2010

56. Pharmacotherapy for tics  Mild tics  No medication treatment

57. Pharmacotherapy for tics  Mild tics w/ or w/o comorbid ADHD  Monotherapy – α-adrenergic agonists – Stimulants – Atomoxetine

58. Pharmacotherapy for tics Moderate tics – α -adrenergic agonists and/or: – Atypical neuroleptics Severe tics – Atypical neuroleptics – Typical neuroleptics

59. Take Home Points: Clarifying Common Misconceptions TS is not rare Tics are usually mild, not catastrophic In most people with TS, tics are one of many related complications Address main problems, often not tics

60. For further information, including Rx discussion: Tourette Syndrome Association, Inc. www.tsa-usa.org NEWLY DIAGNOSED Video Webstream with Dr. John Walkup

61. Extensive Resources in Medical Home partnership: Developmental-Behavioral Pediatrics Depts.washington.edu/dbpeds

62. Tourette Syndrome Association, Inc. www.tsa-usa.org