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 Brutus
Gilles de la Tourette
(1857-1904)
Georges Albert Edouard Brutus
Gilles de la Tourette
(1857-1904)
Childhood onset
Heritable
Premonitory
sensation
Motor & Vocal
Coprolalila
Echolalia
Wax & Wane
Eiffel Tower erected in Paris
1889
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
Motor
Phonic
Complex
Tics: Characteristics
Simple
Motor
Phonic
•“Meaningless”/isolated
•Facial and neck
•Abdomen
•Extremities
Complex
Tics: Characteristics
Simple
Motor
Phonic
•“Meaningless”/isolated
•Facial and neck
•Abdomen
•Extremities
Complex
•“Purposeful”
•Gestures
•Dystonic postures
•Self-abusive or
vulgar
Tics: Characteristics
Simple
Motor
Phonic
•“Meaningless”/isolated
•Facial and neck
•Abdomen
•Extremities
•“Meaningless”
•“Allergy”-like
•Grunting
•Tongue-clicking
•Animal noises
Complex
•“Purposeful”
•Gestures
•Dystonic postures
•Self-abusive or
vulgar
Tics: Characteristics
Simple
Motor
Phonic
•“Meaningless”/isolated
•Facial and neck
•Abdomen
•Extremities
•“Meaningless”
•“Allergy”-like
•Grunting
•Tongue-clicking
•Animal noises
Complex
•“Purposeful”
•Gestures
•Dystonic postures
•Self-abusive or
vulgar
•“Linguistic”
•Syllables
•Words, obscenities
•Imitative (“echoic”)
•Speech atypicalities
.......W
W
A
A
X
E
S
N
E
S .......
Tourette’s Disorder
TM
• DSM-IV-TR 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)
TM
• DSM-IV-TR 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
TM
• DSM-IV-TR 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
midline
simple
→
→
→
bottom
peripheral
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: Pathophysiology
• Dis-inhibition
– “sensori-motor gating”
– “filtering”
• Motor programs
– “fixed action patterns”
– “muscle memory”
Brain
Regions
in
TS
With permission, NIMH
Basal Ganglia
cortex
Striatum
GP / SN
brainstem
Thalamus
PANDAS
controversial
Pediatric
Autoimmune
Neuropsychiatric
Disorders
Associated with
Streptococcal infections
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
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
Sydenham chorea
Myoclonus
Tremor
Dystonia
Athetosis
Spasms
Dyskinesias
Psychiatric
Compulsions
Stereotypies
Perseverations
Self-injurious behavior
Addictive behaviors
Habits
Mannerisms
Differential Diagnosis of
repetitive thoughts
Psychiatric
Obsessions
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
7
8
11
> 11
ADHD
Simple motor tic (head)
Vocal tic
OCS + peak tic severity
tics ↓ (but lifelong in 50-90%)
Time course of symptom dev’t
Adapted from
presentation by John
Walkup, MD
Personality
Disorder,
Bipolar, Conduct Disorder
Conduct
Depression,
ODD
ADHD, Anxiety
Autism,
Abuse/Neglect
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
–Culture
Adapted 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 diagnoses
Adapted 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
Tourette
problem
problem
problem
problem
Adapted from presentation by John Walkup, MD
Management
• Perspectives:
– The child
– The parent
– The school
– You
Management
parent perspective
• Most Important
– Episodic rage
– Attention deficit
– Learning difficulties
• Least Important
– Motor tics
– Vocal tics
FOCUS ON TARGET
SYMPTOMS
Types of Reinforcement
Adapted from presentation by John Walkup, MD
+
-
Internal
Gratification
Relieves
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
Can’t be controlled
Don’t punish
Behavior tx won’t work
Don’t try to suppress
Suppression ↑ tics
Suppression ↑ urges
Become more aware
Learn to manage
Reward successful mgt
Use beh. strategies
Beh. tx. doesn’t ↑ tics
Urges will fade away
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
for tics
•
Alkaloid
nicotine
•
Alpha adrenergic agonist
clonidine
guanfacine
•
lofexidine
flutamide
Anti-cholinesterase
donepezil
•
•
topiramate
Anti-depressant (tricyclic)
desipramine
•
Anti-hypertensive (misc.)
mecamylamine
•
Anti-psychotic (other)
tetrabenazine
•
Atypical neuroleptic
aripiprazole
olanzapine
quetiapine
tiapride
Benzodiazepine
clonazepam
Cannabinoid
delta-9-tetrahydrocannibinol (THC)
•
Dopamine agonist
ropinirole
Dopamine antagonist
metoclopramide
•
MAO inhibitor
selegiline
•
Muscle relaxant
baclofen
Neurotoxin
botulinum toxin A
pergolide
•
•
•
Anti-Parkinson
Atypical neuroleptic (N/A in US & Canada)
sulpiride
•
Anti-convulsant
levetiracetam
•
•
Anti-androgen
finasteride
•
reserpine
risperidone
ziprasidone
•
Selective NE reuptake inhibitor
atomoxetine
•
Typical neuroleptic
fluphenazine
haloperidol
pimozide
Pharmacotherapy for tics
Mild tics
No medication treatment
Pharmacotherapy for tics
Mild tics
Monotherapy
– α-adrenergic agonists
– Clonidine (shorter-acting)
– Guanfacine (longer-acting)
“Small”
Pharmacotherapy for tics
Mild tics w/ or w/o comorbid ADHD
Monotherapy
– 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 studies
Few olanzapine, ziprasidone studies
Expect lots of tetrabenazine studies
Ecopipam (First orphan drug)
Pharmacotherapy for tics:
European experts ratings
60
50
40
30
20
10
0
Drug
Roessner et al. Eur Child Adolesc Psychiatry, 2011
Risperidone
Clonidine
Aripiprazole
Pimozide
Sulpiride
Tiapride
Haloperidol
Tetrabenazine
Ziprasidone
Quetiapine
THC
Desipramine
BoTox
Thioridzine
Guanfacine
Oxcarbazepine
Atomoxetine
Pharmacotherapy for tics:
American opinions
1st tier
Clonidine
Guanfacine
Baclofen
Topiramate
Levetiracetam
Clonazepam
2nd tier
Pimozide
Fluphenazine
Risperidone
Aripiprazole
Olanzepine
Haloperidol
Ziprasidone
Quetiapine
Sulpiride
Tiapride
3rd tier
Dopamine agonists
Tetrabenazine
BoTox
Singer et al. In Movement Disorders in Children, 2010
OCD
more
impairing
than tics
Treat OCD,
then
reassess tic
severity
Effective
3rd-line
DA
receptor
blocking
meds
Treatment Algorithm
2 -line
nd
T
I
C
S
Monitor
ADHD
more
impairing
than tics
Treat
ADHD
(stimulants
may be
OK), then
reassess tic
severity
Tics cause
Clonidine
Gilbert.
interference,
or J Child
impairment
guanfacine
or pain
Non-DA
receptor
blocking
meds
Intolerable
side effects
or inadeq.
benefit
Monitor
closely for
weight ↑,
extrapyramidal
side
effects,
etc.
Effective
Monitor
Neurology 2006
Pharmacotherapy for
Comorbid Conditions
KEY POINT!
Target the most troubling symptoms
Treatment
Integrative Medicine
• “Complementary”
• “Alternative”
Treatment
Integrative Medicine
• Why the interest?
–Medication problems
–Autonomy
–Readily available information and “information”
–Personal values
–Liabilities in conventional medicine
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
A common sense guide to
complementary/alternative medicine
Effective?
YES
YES
NO
Recommend
Tolerate
Safe?
NO
Monitor closely
Discourage
or discourage
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)
DBS lead
Deep
Brain
Stimulation
Printed with permission, Medtronic
Extension
adjust
settings
Neurostimulator
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 Webstream
with Dr. John Walkup
Extensive Resources
in Medical Home partnership:
Developmental-Behavioral Pediatrics
Depts.washington.edu/dbpeds
Tourette Syndrome Association, Inc.
www.tsa-usa.org