tourette syndrome: the whole tic and kaboodle

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

Case 1

• 10-year-old boy

• “Not himself” past year

• Rubbing eyes and blinking

• Wiping/blowing nose until bleeds

• Allergy medications not helping

Case 3

• 8-year-old boy• Deteriorating school performance• Disruptive in classroom• Recruits kids in noise-making

antics• Moves about classroom

Case 4

• 7-year-old boy with possible otitis media

• Severe lip chapping

• Licking lips

Overview

• Signs and symptoms

• Associated problems

• Management

Take Home Points:

• TS not rare

• Tics usually mild

• Tics usually 1 of many related problems

• Address main problems

Historical timeline of Tourette syndrome events

Charcot&

Tourette

Georges Albert Edouard BrutusGilles de la Tourette

(1857-1904)

Georges Albert Edouard BrutusGilles de la Tourette

(1857-1904)

Childhood onset

Heritable

Coprolalila

Echolalia

Wax & Wane

Motor & Vocal

Premonitory sensation

Eiffel Tower erected in Paris1889

Tic Disorders: Historical context

• Psychological

• Neurological

• Neuropsychiatric–Neurology

–Genetics & Environment

–Behavioral & Functional

Tic Disorders: Characteristics

• Tic Definition

– motor or phonic

– involuntary (unvoluntary?)

– sudden and rapid

– recurrent

– non-rhythmic and stereotyped

Tics: Characteristics

Simple Complex

Motor

Phonic

Tics: Characteristics

Simple Complex

Motor

•“Meaningless”/isolated •Facial and neck•Abdomen•Extremities

Phonic

Tics: Characteristics

Simple Complex

Motor

•“Meaningless”/isolated •Facial and neck•Abdomen•Extremities

•“Purposeful”•Gestures•Dystonic postures•Self-abusive or

vulgar

Phonic

Tics: Characteristics

Simple Complex

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

Tics: Characteristics

Simple Complex

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

. . . . . . . W A X E S

W A N E S . . . . . . .

Tourette’s Disorder

• DSM-IV-TRTM

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

Chronic Tic Disorder (M or V)

• DSM-IV-TRTM

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

Transient Tic Disorder

• DSM-IV-TRTM

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

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

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

PREMONITORY URGE

Tics: Characteristics

Anatomic evolution of tics

top → bottom

midline → peripheral

simple → complex

Anatomic evolution of tics

Anatomic evolution of tics

Anatomic evolution of tics

Anatomic evolution of tics

Anatomic evolution of tics

Anatomic evolution of tics

Anatomic evolution of tics

Epidemiology

• Prevalence – 1% males (or more)

– Male > Female (3-to-10 times)

“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

Tics: Pathophysiology

• Cortical & Subcortical network– Sensory

– Affective

– Motor

Tic Disorders: Characteristics

• Premonitory urge

• Tics can usually be suppressed

Etiology

URGE → TIC → RELIEF

Tics:Tics: PathophysiologyPathophysiology

• Dis-inhibition

– “sensori-motor gating”

– “filtering”

• Motor programs

– “fixed action patterns”

– “muscle memory”

Brain

Regions

in

TS

With permission, NIMH

Striatum

Thalamus

GP / SN

Basal Ganglia

cortex

brainstem

Striatum

PANDAScontroversial

Pediatric

Autoimmune

Neuropsychiatric

Disorders

Associated with

Streptococcal infections

PANDAS5 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

Genetics

• TS is genetic in origin• TS is inherited

– family, twin and adoption studies

• Non-genetic factors also present– Gestational exposure?– Perinatal?– Hormonal?

Genetics

• Major genes are involved– autosomal dominant w/incomplete penetrance?– polygenic?– additive?

• Genomic regions suspected– Seeking susceptibility genes in the regions

• Epigenetic factors

Differential Diagnosis of repetitive behaviors

Neurological Psychiatric

Sydenham chorea Compulsions

Myoclonus Stereotypies

Tremor Perseverations

Dystonia Self-injurious behavior

Athetosis Addictive behaviors

Spasms Habits

Dyskinesias Mannerisms

Differential Diagnosis of repetitive thoughts

PsychiatricObsessions

Ruminations

Delusions

Perseverative thoughts

Cravings

Over-valued ideas

Flash-backs

Identification

• Clinical aspects of tics

• Comorbid conditions

• Emotion and behavior

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

Assessment:co-morbid conditions

• ADHD

• Obsessions/Compulsions

• Learning interferences

• Behavioral disorders

• Developmental disorders

• Mood disorders

• Anxiety

• Social difficulties (including PDDs)

David Sedaris

a plague of tics

from “Naked”Little, Brown and Company, 1997

TOURETTE SYNDROME IN HISTORY

Emperor Claudius

(10 BC - AD 54)

TOURETTE SYNDROME IN HISTORY

Peter the Great

(1672 – 1725)

TOURETTE SYNDROME IN HISTORY

Samuel Johnson

(1709 – 1784)

TOURETTE SYNDROME IN HISTORY

Wolfgang Amadeus Mozart

(1756-1791)

Clinical Course

• < 7 ADHD

• 7 Simple motor tic (head)

• 8 Vocal tic

• 11 OCS + peak tic severity

• > 11 tics ↓ (but lifelong in 50-90%)

Time course of symptom dev’t

Autism, Abuse/Neglect

ADHD, Anxiety

Depression, ODD

Bipolar, Conduct

PersonalityDisorder, Conduct Disorder

Adapted from presentation by John Walkup, MD

Clinical Assessment: complex presentations

• Tics plus:– separation (or other) anxiety

– autism

– disruptive behavior disorders

– depression (or bipolar)

– substance abuse

– personality disorders

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)

Diagnostic Pitfalls 101

• Subject or clinician unaware of tics

• Waxing and waning nature of tics

• Tics are suppressible

Diagnostic Pitfalls 102

• T.S. is not rare

• T.S. is usually not catastrophic

• Few have coprolalia

• You may not see the tics

Management

• General Guidelines

–Education

–Monitoring

–Containment

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

Management

• Anger: An easily conditioned behavior–Effective in interactions–Associations:

• Mood & Anxiety• Cognitive / Brain

–CultureAdapted from a presentation by John Walkup, MD

Management

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

Management

Outcome is associated with:

Severity of co-occurring conditions & self-control

+

The courage to overcome adversity

Adapted from presentation by John Walkup, MD

Management

• Is further treatment necessary:

–For tics?

–For comorbid conditions?

Caution: There is often > 1 condition

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

Management

• Splitters– Make problem list

– Rank & treat by impairment

– Treat each problem/diagnosis

– Consider consult

– Goal: “Fix” other diagnosesAdapted from presentation by John Walkup, MD

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

Management

• Lumpers

problem problem

problem problem

problem problem

problem problem

Adapted from presentation by John Walkup, MD

Tourette

Management

• Perspectives:

– The child

– The parent

– The school

– You

Managementparent perspective

• Most Important– Episodic rage– Attention deficit– Learning difficulties

• Least Important– Motor tics– Vocal tics

FOCUS ON TARGET

SYMPTOMS

Types of ReinforcementAdapted from presentation by John Walkup, MD

+ -

Internal GratificationRelieves

distress

External

Attention

&

Support

Avoidance

Management: tics

• Education & Accommodation

• Medications

• Experimental– Behavioral

– Integrative

– Surgical

Management - tics

• Non-pharmacological

–Dynamic psychotherapy

•Supportive

•Cognitive-Behavioral

•Parenting education

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

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

Management - tics

• Non-pharmacological–Behavioral approaches

• CBIT–Behavioral

Antecedent - Behavior - Consequence

–Functional

+ & - reinforcing functions

Change in Advice Adapted from presentation by John Walkup, MD

OLD (intuitive) NEW (counterintuitive)

Ignore tics Become more aware

Can’t be controlled Learn to manage

Don’t punish Reward successful mgt

Behavior tx won’t work Use beh. strategies

Don’t try to suppress Beh. tx. doesn’t ↑ tics

Suppression ↑ tics Urges will fade away

Suppression ↑ urges Beh. tx. doesn’t create new tics

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)

Management:“co-morbid” conditions

– Family dysfunction– OCD & other anxiety disorders– ADHD – Learning difficulties– Behavioral Disorders– Sleep disturbances– Other self-injurious behaviors

Management – bullying

• Stop Bullying Now - HRSA

www.stopbullyingnow.hrsa.gov

Pharmacotherapy

KEY POINTS!•Do not assume medication is necessary

•Address comorbid condition(s)

•Complete tic remission is rare

•Stimulants are generally safe

Pretty much everything known to humankind tried Pretty much everything known to humankind tried for ticsfor tics

• Alkaloidnicotine reserpine

• Alpha adrenergic agonistclonidine lofexidineguanfacine

• Anti-androgenfinasteride flutamide

• Anti-cholinesterasedonepezil

• Anti-convulsantlevetiracetam topiramate

• Anti-depressant (tricyclic)desipramine

• Anti-hypertensive (misc.)mecamylamine

• Anti-Parkinsonpergolide

• Anti-psychotic (other)tetrabenazine

• Atypical neurolepticaripiprazole risperidoneolanzapine ziprasidonequetiapine

• Atypical neuroleptic (N/A in US & Canada)sulpiride tiapride

• Benzodiazepineclonazepam

• Cannabinoid delta-9-tetrahydrocannibinol (THC)

• Dopamine agonistropinirole

• Dopamine antagonistmetoclopramide

• MAO inhibitorselegiline

• Muscle relaxantbaclofen

• Neurotoxinbotulinum toxin A

• Selective NE reuptake inhibitoratomoxetine

• Typical neurolepticfluphenazine pimozidehaloperidol

Pharmacotherapy for tics

Mild ticsNo medication treatment

Pharmacotherapy for tics

Mild ticsMonotherapy

– α-adrenergic agonists

– Clonidine (shorter-acting)

– Guanfacine (longer-acting)

“Small”

Pharmacotherapy for tics

Mild tics w/ or w/o comorbid ADHDMonotherapy

– α-adrenergic agonists

– Stimulants

– Atomoxetine

Pharmacotherapy for tics

•Moderate tics– α-adrenergic agonists and/or:

– Atypical neuroleptics

• Severe tics– Atypical neuroleptics

– Typical neuroleptics

Pharmacotherapy for tics

•Category A

–Typical Neuroleptics•Haloperidol (Haldol)•Pimozide

–Atypical Neuroleptics•Risperidone

Pharmacotherapy for tics•Category B

–Typical Neuroleptics•Fluphenazine (Prolixin)

–Atypical Neuroleptics•Aripiprazole (Abilify)

–Other•Clonidine (Catapres)•Guanfacine (Tenex)•Botulinum toxin (Botox)

Pharmacotherapy for tics•Category C

–Atypical Neuroleptics•Olanzapine (Zyprexa) •Quetiapine (Seroquel)•Ziprasidone (Geodon)

–Other•Baclofen•Nicotine patch or chewing gum

Pharmacotherapy for tics

•Other options that may be effective–Benzodiazepines

•Clonazepam (Klonopin)–Anticonvulsants

•Topiramate (Topamax) growing interest–Tricyclic antidepressants

Newer Antipsychotics

Lots of aripiprazole studiesFew olanzapine, ziprasidone studiesExpect lots of tetrabenazine studiesEcopipam (First orphan drug)

Pharmacotherapy for tics:European experts ratings

0

10

20

30

40

50

60

Drug

Risperidone

Clonidine

Aripiprazole

Pimozide

Sulpiride

Tiapride

Haloperidol

Tetrabenazine

Ziprasidone

Quetiapine

THC

Desipramine

BoTox

Thioridzine

Guanfacine

Oxcarbazepine

Atomoxetine

Roessner et al. Eur Child Adolesc Psychiatry, 2011

Pharmacotherapy for tics:American opinions

1st tier 2nd tier 3rd 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

T I C S

OCD more impairing than tics

ADHDmore 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

2nd-lineNon-DA receptor blocking

meds

Effective

3rd-lineDA

receptor blocking

meds

Monitor

Monitor closely for weight ↑,

extra-pyramidal

side effects,

etc.

Treatment Algorithm

Gilbert. J Child Neurology 2006

Pharmacotherapy for Comorbid Conditions

KEY POINT!

Target the most troubling symptoms

TreatmentIntegrative Medicine

• “Complementary”

• “Alternative”

TreatmentIntegrative Medicine

• Why the interest?–Medication problems–Autonomy–Readily available information and “information”–Personal values–Liabilities in conventional medicine

Integrative MedicineTourette 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

A common sense guide to complementary/alternative medicine

Safe?

YES NO

YES Recommend Tolerate

NOMonitor closely or discourage

Discourage

Effective?

Source: Cohen MH & Eisenberg DM, Ann Intern Med (2002)

Pharmacotherapy - Experimental

• Naloxone• Anti-androgen• Cannabinoids• N-Acetylcysteine• Other agents now less experimental

– Botulinum toxin– Nicotine patch

Surgical Treatment - Experimental

• Deep Brain Stimulation (DBT)

Deep

Brain

Stimulation

Printed with permission, Medtronic

DBS leadExtension

adjustsettings

Neuro-stimulator

Surgical Treatment - Experimental

• DBS Inclusion Criteria– 25 years old– Severe tics– Failed Rx– Failed behavioral tx– Stable co-morbidities– Active psychological interventions

Advocacy and Legal Rights

Advocacy and Legal Rights

• Tourette Syndrome Association

• Protection and Advocacy Office

• Local Bar Association

• IDEA (now IDEIA)

• Section 504

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

Case 3

• 8-year-old boy

• Deteriorating in school performance

• Disruptive in the classroom

• Recruits kids in noise-making antics

• Moves about the classroom

Case 4

• 7-year-old boy with possible otitis media

• Severe circumoral chapping

• Licking lips

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

For further information, including Rx discussion:

Tourette Syndrome Association, Inc.

www.tsa-usa.org

NEWLY DIAGNOSED Video Webstreamwith Dr. John Walkup

Extensive Resources in Medical Home partnership:

Developmental-Behavioral Pediatrics

Depts.washington.edu/dbpeds

Tourette Syndrome Association, Inc.

www.tsa-usa.org