Outline: 1. What is TS? 2. How does the brain work? 3. What does the brain do differently in TS? 4....
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Transcript of Outline: 1. What is TS? 2. How does the brain work? 3. What does the brain do differently in TS? 4....
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 it5. 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 it5. Questions
Clinical Hallmarks of Tourette's Syndrome
Jankovic J. N Engl J Med 2001;345:1184-1192
Tics:
MotorPhonicSensory
TOURETTE SYNDROME
Temporal course of symptoms in TS
Natural history of Tourette Syndrome
Jankovic J. N Engl J Med 2001;345:1184-1192
Tourette’s Syndrome
Premonitory Urge Discomfort Tic
RepetitiveUndesired/unwilled
“Compelled”
Like a sneeze that keeps building or an itch Like a sneeze that keeps building or an itch that wonthat won’’t go away… the tag on the back of t go away… the tag on the back of your shirt collar...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 it5. Questions
The Big PictureThe Big Picture
How the brain worksHow the brain works
Some disorders Some disorders characterized clinically characterized clinically by deficient inhibition by deficient inhibition
(gating) of motor, sensory (gating) of motor, sensory or cognitive information:or cognitive information:
• Huntington’s Disease • Tourette Syndrome• Obsessive Compulsive Disorder
• Schizophrenia• ……
HD
Frey et al.
Albin et al.
TS
TS
Schwartz et al.
OCD
Csernansky et al.
Lewis et al.
Narr et al.
SZ
SZ
SZ
C
S
P
T
Mink 2006
Spiny I GABAergic neuronSpiny 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 it5. Questions
Albin et al. 2003
CTL
TS
∆
Elevated striatal levels of VMAT in TS
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
Bloch et al., 2005
Copyright ©2005 by the National Academy of Sciences
Kalanithi, Paul S. A. et al. (2005) Proc. Natl. Acad. Sci. USA 102, 13307-13312
Increase in the number of PV-containing neurons in the GPi (and reduced numbers in striatum) of TS patients
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).
Striatum
GPi
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, dopamine2.Reduced size of specific areas3.Smaller size predicts symptom persistence4.Wrong proportions of certain neurons suggesting an interruption of cell migration early in development
TSTS runs in runs in familiesfamilies
Leckman et al. Familial developmental pattern of Leckman et al. Familial developmental pattern of
tic severity tic severity
Leckman et al. 1993
Kataoka et al. 2010Albin et al. 2003
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 it5. 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 therapiesExamples: haloperidol, pimozide, risperidone, tetrabenazine
2. Alpha-noradrenergic agonistsExamples: clonidine, guanfacine
3. Medications used primarily for OCD symptomsExamples: fluoxetine, citalopram, sertraline
4. Medications used primarily for ADHD:Examples: amphetamine, methylphenidate, atomoxetine
5. Botulinum toxin
Deep Brain Stimulation
(DBS)
C
S
P
T
http://www.youtube.com/watch?v=TyW6yJTBhlg
Ackermans L et al. Brain 2011;134:832-844
Individual changes in total YGTSS scores in six patients with Tourette syndrome with thalamic DBS
The role of advocacy organizations in the application of new therapeutic technologies
What can I do?
1. Learn about TS!2. Get active in the community (like this group)!3. Stay connected to the TAA (www.tsa-usa.org) !4. 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 it5. Questions