Transcript Tic/Tourette Support Group Presentation: Sept. 29, 2015

Outline:
1. What is TS?
2. How does the brain work?
3. What does the brain do
differently in TS?
4. Things we can do about it
5. Questions
Outline:
1. What is TS?
2. How does the brain work?
3. What does the brain do
differently in TS?
4. Things we can do about it
5. Questions
TOURETTE SYNDROME
Clinical Hallmarks of Tourette's Syndrome
Tics:
Motor
Phonic
Sensory
Jankovic J. N Engl J Med 2001;345:1184-1192
Natural history of Tourette Syndrome
Temporal course of symptoms in TS
Jankovic J. N Engl J Med 2001;345:1184-1192
Tourette’s Syndrome
Premonitory Urge  Discomfort  Tic
Repetitive
Undesired/unwilled
“Compelled”
Like a sneeze that keeps building or an itch that won’t
go away… the tag on the back of your shirt collar...
Leckman et al. 1993
Outline:
1. What is TS?
2. How does the brain work?
3. What does the brain do
differently in TS?
4. Things we can do about it
5. Questions
The Big Picture
How the brain works
Some disorders characterized
clinically by deficient inhibition
(gating) of motor, sensory or
cognitive information:
•
•
•
•
•
Huntington’s Disease
Tourette Syndrome
Obsessive Compulsive Disorder
Schizophrenia
……
Abnormalities in limbic cortico-striato-pallido-thalamic circuitry in
disorders of deficient motor, sensory and cognitive “gating
TS
OCD
SZ
TS
Albin et al.
Schwartz et al.
Lewis et al.
SZ
C
Frey et al.
S
HD
T
Narr et al.
SZ
P
Csernansky et al.
Mink 2006
Spiny I GABAergic neuron
Outline:
1. What is TS?
2. How does the brain work?
3. What does the brain do
differently in TS?
4. Things we can do about it
5. Questions
Elevated striatal levels of VMAT in TS
CTL
TS
∆
Albin et al. 2003
Nucleus Accumbens Volume, mm3
Findings from the TSA Neuroimaging Consortium shows that the
ventral striatum are called the nucleus accumbens is significantly
smaller in TS children than in age-matched control children
600
500
P = 1.1 x 10-3
P = 4.8 x 10-3
400
300
P = 0.41
200
TS
TS -Rx
CTR
Bloch et al., 2005
Increase in the number of PV-containing neurons in the GPi
(and reduced numbers in striatum) of TS patients
Kalanithi, Paul S. A. et al. (2005) Proc. Natl. Acad. Sci. USA 102, 13307-13312
Copyright ©2005 by the National Academy of Sciences
TS: Postmortem Findings
Two classes of interneurons are reduced in
striatum (caudate and putamen), and perhaps
increased in GPi:
• Reduced number of PV+ fast-spiking striatal
GABAergic interneurons in the striatum (51%
and 37% reductions in the caudate and
putamen, respectively, and a 122% increase in
the GPi (Kalanithi et al. 2005).
• 50-60% reduction in “tonically active”
cholinergic interneurons in associative and
sensorimotor (but not limbic) striatum
(Kataoka et al. 2010).
Neuronal Migration
“Bottleneck”?
Summary of main findings in brain studies of TS:
Within different parts of the basal ganglia:
1. Excesses of chemicals related to the
neurotransmitter, dopamine
2. Reduced size of specific areas
3. Smaller size predicts symptom persistence
4. Wrong proportions of certain neurons suggesting an
interruption of cell migration early in development
TS runs in families
Leckman et al. Familial developmental pattern of tic severity
Leckman et al. 1993
Albin et al. 2003
Kataoka et al. 2010
Abelson et al. 2005
Outline:
1. What is TS?
2. How does the brain work?
3. What does the brain do
differently in TS?
4. Things we can do about it
5. Questions
TREATMENT
Easiest ways to correct abnormal neural circuit activity in
brain disorders:
1. Change thoughts (psychoeducation, cognitive /
psychotherapy, etc.)
2. Change behaviors (behavioral therapy (CBIT))
3. Change chemicals (medication, nutrition, sleep, etc.)
4. Change electrical activity (neuromodulation)
Schwartz et al. 1996
Efficacy of Habit Reversal Therapy (HRT) in Adults with TS
TS Medication: General Classes
1.Anti-dopaminergic therapies
Examples: haloperidol, pimozide, risperidone, tetrabenazine
2. Alpha-noradrenergic agonists
Examples: clonidine, guanfacine
3. Medications used primarily for OCD symptoms
Examples: fluoxetine, citalopram, sertraline
4. Medications used primarily for ADHD:
Examples: amphetamine, methylphenidate, atomoxetine
5. Botulinum toxin
Deep Brain Stimulation
(DBS)
C
S
T
P
http://www.youtube.com/watch?v=TyW6yJTBhlg
Individual changes in total YGTSS scores in six patients
with Tourette syndrome with thalamic DBS
Ackermans L et al. Brain 2011;134:832-844
The role of advocacy
organizations in the
application of new
therapeutic
technologies
What can I do?
1.
2.
3.
4.
Learn about TS!
Get active in the community (like this group)!
Stay connected to the TAA (www.tsa-usa.org) !
Participate in TS research studies !
Outline:
1. What is TS?
2. How does the brain work?
3. What does the brain do
differently in TS?
4. Things we can do about it
5. Questions