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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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
![Page 2: 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](https://reader036.vdocuments.mx/reader036/viewer/2022062518/56649f2f5503460f94c49f11/html5/thumbnails/2.jpg)
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
![Page 3: 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](https://reader036.vdocuments.mx/reader036/viewer/2022062518/56649f2f5503460f94c49f11/html5/thumbnails/3.jpg)
Clinical Hallmarks of Tourette's Syndrome
Jankovic J. N Engl J Med 2001;345:1184-1192
Tics:
MotorPhonicSensory
TOURETTE SYNDROME
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Temporal course of symptoms in TS
Natural history of Tourette Syndrome
Jankovic J. N Engl J Med 2001;345:1184-1192
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Tourette’s Syndrome
Premonitory Urge Discomfort Tic
RepetitiveUndesired/unwilled
“Compelled”
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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
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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
![Page 8: 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](https://reader036.vdocuments.mx/reader036/viewer/2022062518/56649f2f5503460f94c49f11/html5/thumbnails/8.jpg)
The Big PictureThe Big Picture
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How the brain worksHow the brain works
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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• ……
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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
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Spiny I GABAergic neuronSpiny I GABAergic neuron
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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
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Albin et al. 2003
CTL
TS
∆
Elevated striatal levels of VMAT in TS
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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
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Bloch et al., 2005
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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
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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”?
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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
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TSTS runs in runs in familiesfamilies
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Leckman et al. Familial developmental pattern of Leckman et al. Familial developmental pattern of
tic severity tic severity
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Leckman et al. 1993
Kataoka et al. 2010Albin et al. 2003
Abelson et al. 2005
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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
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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)
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Schwartz et al. 1996
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Efficacy of Habit Reversal Therapy (HRT) in Adults with TS
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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
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Deep Brain Stimulation
(DBS)
C
S
P
T
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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
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The role of advocacy organizations in the application of new therapeutic technologies
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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 !
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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