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

Clinical Hallmarks of Tourette's Syndrome Jankovic J. N Engl J Med 2001;345: Tics: Motor Phonic Sensory TOURETTE SYNDROME

Temporal course of symptoms in TS Natural history of Tourette Syndrome Jankovic J. N Engl J Med 2001;345:

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 ……

HD Frey et al. Albin et al. TS Schwartz et al. OCD Csernansky et al. Lewis et al. Narr et al. SZ C S P T 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

Albin et al 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, 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) % 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, 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 Kataoka et al Albin et al 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 P T

Ackermans L et al. Brain 2011;134: 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 ( ! 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 it 5. Questions