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