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.

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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

  • 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 SyndromeJankovic J. N Engl J Med 2001;345:1184-1192Tics:

    MotorPhonicSensoryTOURETTE SYNDROME

  • Temporal course of symptoms in TS Natural history of Tourette SyndromeJankovic J. N Engl J Med 2001;345:1184-1192

  • Tourettes SyndromePremonitory Urge Discomfort Tic

    RepetitiveUndesired/unwilledCompelled

  • Like a sneeze that keeps building or an itch that wont 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 it5. Questions

  • The Big Picture

  • How the brain works

  • Some disorders characterized clinically by deficient inhibition (gating) of motor, sensory or cognitive information:Huntingtons Disease Tourette SyndromeObsessive Compulsive DisorderSchizophrenia

  • 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 it5. Questions

  • Albin et al. 2003CTL

    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

  • Copyright 2005 by the National Academy of SciencesKalanithi, Paul S. A. et al. (2005) Proc. Natl. Acad. Sci. USA 102, 13307-13312Increase in the number of PV-containing neurons in the GPi (and reduced numbers in striatum) of TS patients

  • TS: Postmortem FindingsTwo 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).

    StriatumGPiNeuronal Migration Bottleneck?

  • Summary of main findings in brain studies of TS:

    Within different parts of the basal ganglia:

    Excesses of chemicals related to the neurotransmitter, dopamineReduced size of specific areasSmaller size predicts symptom persistenceWrong 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. 1993Kataoka et al. 2010Albin et al. 2003Abelson 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:

    Change thoughts (psychoeducation, cognitive / psychotherapy, etc.)

    Change behaviors (behavioral therapy (CBIT))

    Change chemicals (medication, nutrition, sleep, etc.)

    Change electrical activity (neuromodulation)

  • Schwartz et al. 1996

  • Efficacy of Habit Reversal Therapy (HRT) in Adults with TS

  • TS Medication: General Classes

    Anti-dopaminergic therapiesExamples: haloperidol, pimozide, risperidone, tetrabenazine2. 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)

  • http://www.youtube.com/watch?v=TyW6yJTBhlgAckermans L et al. Brain 2011;134:832-844Individual 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?

    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 it5. Questions

    *Figure 1. Clinical Hallmarks of Tourette's Syndrome.The diagnosis is based on the occurrence of tics along with behavioral disorders, including attention-deficithyperactivity disorder (ADHD) and obsessivecompulsive disorder (OCD). Other behavioral disorders include anxiety and mood disorders, learning disorders, sleep disorders, conduct and oppositional behavior, and self-injurious behavior.*********************