2. Tourette Syndrome: The Whole Tic and Kaboodle Tourette Syndrome Association, Inc. & CDC Samuel H. Zinner, M.D. Associate Professor of Pediatrics University of Washington, Seattle depts.washington.edu/dbpeds December 15, 2012

3. Case 1 10-year-old boy “Not himself” past year Rubbing eyes and blinking Wiping/blowing nose until bleeds Allergy medications not helping

4. Case 3 8-year-old boy Deteriorating school performance Disruptive in classroom Recruits kids in noise-making antics Moves about classroom

5. Case 4 7-year-old boy with possible otitis media Severe lip chapping Licking lips

6. Overview Signs and symptoms Associated problems Management

7. Take Home Points: TS not rare Tics usually mild Tics usually 1 of many related problems Address main problems

8. Historical timeline of Tourette syndrome events

9. Charcot & Tourette

10. Georges Albert Edouard Brutus Gilles de la Tourette (1857-1904)

11. Childhood onset Heritable Coprolalila Echolalia Wax & Wane Motor & Vocal Premonitory sensation

12. Eiffel Tower erected in Paris 1889

13. Tic Disorders: Historical context Psychological Neurological Neuropsychiatric –Neurology –Genetics & Environment –Behavioral & Functional

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

15. Tics: Characteristics SimpleComplex Motor Phonic

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

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

18. 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

19. 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

20. ....... W A X E S W A N E S.......

22. 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

23. Chronic Tic Disorder (M or V) 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

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

25. Tourette’s Disorder DSM-V –Duration criterion for chronic tics Tics persist for > 1 yr since first tic onset Changes from DSM-IV-TR. Removed: –More than 9/12 months of any year –Tic-free period of no more than 3 months –Transient Tic Disorder –Provisional tic disorder

26. Tourette’s Disorder DSM-V –Duration criterion for chronic tics Tics persist for > 1 yr since first tic onset Changes from DSM-IV-TR. Removed: –More than 9/12 months of any year –Tic-free period of no more than 3 months –Transient Tic Disorder –Provisional tic disorder

27. PREMONITORY URGE

28. Tics: Characteristics Anatomic evolution of tics top →bottom midline→peripheral simple→complex

29. Anatomic evolution of tics

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

42. “If the brain were simple enough that we could understand it, we’d be so simple that we couldn’t” Paul Greengard, Ph.D. Nobel Prize in Physiology or Medicine 2000

43. Tics: Pathophysiology Cortical & Subcortical network – Sensory – Affective – Motor

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

45. Etiology URGE → TIC → RELIEF

46. Tics: Pathophysiology Dis-inhibition – “sensori-motor gating” – “filtering” Motor programs – “fixed action patterns” – “muscle memory”

47. Brain Regions in TS With permission, NIMH

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

49. PANDAS controversial Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections

50. PANDAS 5 identifying criteria developed for research by clinical observation 1.Dramatic emergence or exacerbation of OCD and/or tics 2.Pre-pubertal symptom onset 3.Other neurological signs 4.Association with GABHS 5.Episodic or sawtooth symptom course

51. Genetics TS is genetic in origin TS is inherited –family, twin and adoption studies Non-genetic factors also present –Gestational exposure? –Perinatal? –Hormonal?

52. Genetics Major genes are involved –autosomal dominant w/incomplete penetrance? –polygenic? –additive? Genomic regions suspected –Seeking susceptibility genes in the regions Epigenetic factors

53. Differential Diagnosis of repetitive behaviors NeurologicalPsychiatric Sydenham choreaCompulsions MyoclonusStereotypies TremorPerseverations DystoniaSelf-injurious behavior AthetosisAddictive behaviors SpasmsHabits DyskinesiasMannerisms

54. Differential Diagnosis of repetitive thoughts Psychiatric Obsessions Ruminations Delusions Perseverative thoughts Cravings Over-valued ideas Flash-backs

56. Identification Clinical aspects of tics Comorbid conditions Emotion and behavior

57. Identification – comorbid conditions KEY POINT! Always assess for non-tic comorbidity * 90% occurrence if tics mild * 100% occurrence if tics severe *in clinically-referred samples

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

60. David Sedaris a plague of tics from “Naked” Little, Brown and Company, 1997

61. TOURETTE SYNDROME IN HISTORY Emperor Claudius (10 BC - AD 54)

62. TOURETTE SYNDROME IN HISTORY Peter the Great (1672 – 1725)

63. TOURETTE SYNDROME IN HISTORY Samuel Johnson (1709 – 1784)

64. TOURETTE SYNDROME IN HISTORY Wolfgang Amadeus Mozart (1756-1791)

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

66. Time course of symptom dev’t Autism, Abuse/Neglect ADHD, Anxiety Depression, ODD Bipolar, Conduct Personality Disorder, Conduct Disorder Adapted from presentation by John Walkup, MD

67. Clinical Assessment: complex presentations Tics plus: – separation (or other) anxiety – autism – disruptive behavior disorders – depression (or bipolar) – substance abuse – personality disorders

68. Quality of Life? “Tourette differs from other neuropsychiatric disorders in one simple way: It is largely the disease of the onlooker. When I tic, I am usually not the problem. You are.” Peter Hollenbeck, Ph.D. (a neuroscientist with TS) -Cerebrum (2003)

69. Diagnostic Pitfalls 101 Subject or clinician unaware of tics Waxing and waning nature of tics Tics are suppressible

70. Diagnostic Pitfalls 102 T.S. is not rare T.S. is usually not catastrophic Few have coprolalia You may not see the tics

71. Management General Guidelines –Education –Monitoring –Containment

72. Management Containment - overcome assumptions –“He can’t control it” –“I can’t set limits on him” –“He has a tough life. I want it easier” – “He needs special accommodations” –“Medication is the answer” –“It’s all related to the Tourette” Adapted from a presentation by John Walkup, MD

73. Management Anger: An easily conditioned behavior –Effective in interactions –Associations: Mood & Anxiety Cognitive / Brain –Culture Adapted from a presentation by John Walkup, MD

74. Management General Guidelines - Education –Clarify neurological basis –Reassurance and support –Emphasize strengths –Whole child –Whole family

75. Management Outcome is associated with: Severity of co-occurring conditions & self-control + The courage to overcome adversity Adapted from presentation by John Walkup, MD

76. Management Is further treatment necessary: –For tics? –For comorbid conditions? Caution: There is often > 1 condition

77. Management Lumpers vs. Splitters – Tic suppression – Co-occurring conditions – Children: Raising kids w/ TS – Adults: Building on strengths Adapted from presentation by John Walkup, MD

78. Management Splitters – Make problem list – Rank & treat by impairment – Treat each problem/diagnosis – Consider consult – Goal: “Fix” other diagnoses Adapted from presentation by John Walkup, MD

79. Management Splitter – OCD: CBT & / or Rx – Behavior: Parent training – Tics: Education, Advocacy, Monitor, Consider Rx (esp. α2 agonist) Adapted from presentation by John Walkup, MD

80. Management Lumpers problem problem problem problem problem Adapted from presentation by John Walkup, MD Tourette

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

82. Management parent perspective Most Important –Episodic rage –Attention deficit –Learning difficulties Least Important –Motor tics –Vocal tics

83. FOCUS ON TARGET SYMPTOMS

84. Types of Reinforcement Adapted from presentation by John Walkup, MD +- Internal Gratification Relieves distress External Attention & Support Avoidance

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

86. Management - tics Non-pharmacological –Dynamic psychotherapy Supportive Cognitive-Behavioral Parenting education

87. Management – tics: environment Things that worsen tics –Excitement & stress –Fatigue –Attending to tics / Accepting of tics Things that improve tics –Calm, focused activities –Deep relaxation –Inhibiting environments Adults’ experience w/behavior strategies Adapted from presentation by John Walkup, MD

88. Management - tics Non-pharmacological –Behavioral approaches CBIT (Comprehensive Behavioral Intervention for Tics) –HRT (Habit Reversal Therapy) »Awareness Training »Competing Response »Relaxation »Social Support –FA (Functional Analysis) »Social situations that influence behaviors

89. Management - tics Non-pharmacological –Behavioral approaches CBIT –Behavioral Antecedent - Behavior - Consequence –Functional + & - reinforcing functions

90. Change in Advice Adapted from presentation by John Walkup, MD OLD (intuitive)NEW (counterintuitive) Ignore ticsBecome more aware Can’t be controlledLearn to manage Don’t punishReward successful mgt Behavior tx won’t workUse beh. strategies Don’t try to suppressBeh. tx. doesn’t ↑ tics Suppression ↑ ticsUrges will fade away Suppression ↑ urgesBeh. tx. doesn’t create new tics

91. Management - tics Teacher in-service on T.S. Classroom education on T.S. Teacher as role model Tic breaks/sanctuaries Testing accommodations Opportunities for movement Scribes Tic suppression (behavioral and/or medical)

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

93. Management – bullying Stop Bullying Now - HRSA www.stopbullyingnow.hrsa.gov

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

97. Pretty much everything known to humankind tried for tics Alkaloid nicotine reserpine Alpha adrenergic agonist clonidine lofexidine guanfacine Anti-androgen finasteride flutamide 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

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

99. Pharmacotherapy for tics  Mild tics  Monotherapy – α-adrenergic agonists – Clonidine (shorter-acting) – Guanfacine (longer-acting) “Small”

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

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

102. Pharmacotherapy for tics Category A –Typical Neuroleptics Haloperidol (Haldol) Pimozide –Atypical Neuroleptics Risperidone

103. Pharmacotherapy for tics Category B –Typical Neuroleptics Fluphenazine (Prolixin) –Atypical Neuroleptics Aripiprazole (Abilify) –Other Clonidine (Catapres) Guanfacine (Tenex) Botulinum toxin (Botox)

104. Pharmacotherapy for tics Category C –Atypical Neuroleptics Olanzapine (Zyprexa) Quetiapine (Seroquel) Ziprasidone (Geodon) –Other Baclofen Nicotine patch or chewing gum

105. Pharmacotherapy for tics Other options that may be effective –Benzodiazepines Clonazepam (Klonopin) –Anticonvulsants Topiramate (Topamax) growing interest –Tricyclic antidepressants

106. Newer Antipsychotics  Lots of aripiprazole studies  Few olanzapine, ziprasidone studies  Expect lots of tetrabenazine studies  Ecopipam (First orphan drug)

107. Pharmacotherapy for tics: European experts ratings Roessner et al. Eur Child Adolesc Psychiatry, 2011

108. 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

109. T I C S OCD more impairing than tics ADHD more impairing than tics Tics cause interference, impairment or pain Treat OCD, then reassess tic severity Treat ADHD (stimulants may be OK), then reassess tic severity Clonidine or guanfacine Effective Intolerable side effects or inadeq. benefit Monitor 2 nd -line Non-DA receptor blocking meds Effective 3 rd -line DA receptor blocking meds Monitor Monitor closely for weight ↑, extra- pyramidal side effects, etc. Treatment Algorithm Gilbert. J Child Neurology 2006

110. Pharmacotherapy for Comorbid Conditions KEY POINT! Target the most troubling symptoms

111. Treatment Integrative Medicine “Complementary” “Alternative”

112. Treatment Integrative Medicine Why the interest? –Medication problems –Autonomy –Readily available information and “information” –Personal values –Liabilities in conventional medicine

113. Integrative Medicine Tourette syndrome Fish Oil / Omega 3 Double-blind trial 2012 33 youth O3FA v. PBO (20 weeks) No difference on tics Improvement on tic-impairment No change OC, anxiety, depression

115. 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)

116. Pharmacotherapy - Experimental Naloxone Anti-androgen Cannabinoids N-Acetylcysteine Other agents now less experimental –Botulinum toxin –Nicotine patch

117. Surgical Treatment - Experimental Deep Brain Stimulation (DBT)

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

119. Surgical Treatment - Experimental DBS Inclusion Criteria –25 years old –Severe tics –Failed Rx –Failed behavioral tx –Stable co-morbidities –Active psychological interventions

120. Advocacy and Legal Rights

121. Tourette Syndrome Association Protection and Advocacy Office Local Bar Association IDEA (now IDEIA) Section 504

122. Case 1 10-year-old boy Mother states “not himself” past year Rubbing eyes and blinking Wiping/blowing nose until nose bleeds Allergy medications not helping

123. Case 3 8-year-old boy Deteriorating in school performance Disruptive in the classroom Recruits kids in noise-making antics Moves about the classroom

124. Case 4 7-year-old boy with possible otitis media Severe circumoral chapping Licking lips

125. 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

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

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

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