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Review the Diagnosis and Pathophysiology of Tic and Tourette's

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Review the Diagnosis and Pathophysiology of Tic and Tourette's 1/14/2016 Matthew Harmelink, MD Associate Program Director, Child Neurology Residency Director, Pediatric Neuromuscular Clinic Assistant Professor of Child Neurology Medical College of Wisconsin Review the diagnosis and pathophysiology of Tic and Tourette’s Syndrome Discuss treatment of Tic Disorders Briefly discuss PANDAs 1 “A rapid, recurrent, nonrhythmic movement (motor tic) or sounds (vocal tic) that are perceeded, in most cases, by a premonitory urge.” Mov Disord. 2015 Aug;30(9):1171-8. doi: 10.1002/mds.26304. Epub 2015 Jul 16. Pathophysiology of tic disorders. Yael D1, Vinner E1, Bar-Gad I1. Simple: ◦ Motor: blinking, grimacing, head jerking, shoulder shrugging ◦ Vocal: grunting or barking, sniffing or snorting, throat clearing Complex: ◦ Motor: combined simple tics, copropraxia, echopraxia ◦ Vocal: coprolalia, echolalia 2 Video of Motor Tic https://www.youtube.com/watch?v=nk7dwexqcdY Video of Motor Tic https://www.youtube.com/watch?v=FAd5lQg9V60 3 Video of Motor Tic https://www.youtube.com/watch?v=2M-dbLvEhiE Transient Tic Disorder: ◦ Motor and/or vocal tics lasting under 1 year Chronic Tic Disorder: ◦ Motor or vocal tics lasting greater than 1 year 4 Tourette Syndrome ◦ Multiple motor and one or more vocal tics for greater than one year before the age of 18 New to DSM-V ◦ Must occur many times a day, nearly every day, or intermittently throughout a period of more than one year ◦ Anatomical location, number, frequency, type, complexity, or severity of tics must change over time Prevalance: ◦ Tourette Syndrome 7.7/1000 children ◦ Transient Tic Disorder 29.9/1000 Children Heavy male preponderance ◦ Tourettes: 1.06% males vs. 0.25% females Meta-regression: prevalence of Tourette syndrome was higher in males than in females (P < 0.0001). Review Article Prevalence of Tic Disorders: A Systematic Review and Meta-Analysis Tristan Knight a, Thomas Steeves MDb, Lundy Day BSc c, Mark Lowerison MSc c, Nathalie Jette MDc,d, Tamara Pringsheim MDc,e,* Pediatric Neurology 47 (2012) 77e90 5 Numbers vary based upon study ◦ All tics disorders combined <1% ◦ Likely between 0.005% for Tourette Syndrome (low end) ◦ To 0.42% for chronic tic Review Article Prevalence of Tic Disorders: A Systematic Review and Meta-Analysis Tristan Knight a, Thomas Steeves MDb, Lundy Day BSc c, Mark Lowerison MSc c, Nathalie Jette MDc,d, Tamara Pringsheim MDc,e,* Pediatric Neurology 47 (2012) 77e90 Retrospective: Columbia Presbyterian Medical Center evaluation or treatment of a tic disorder that had developed after the age of 21 diagnosed or evaluated by a movement disorder specialist 411 patients with tic disorders 22 (5.4%) presented for evaluation after age 21 17 men, 5 women 13 patients- no history of childhood onset 1 Extended cocaine binge 2 TBI 1 Strained neck while weight lifting (Neck Tic) 1 Neuroleptic exposure 1 Severe pharyngitis (throat clearing tic) J Neurol Neurosurg Psychiatry 2000;68:738-743 doi:10.1136/jnnp.68.6.738 Adult onset tic disorders Sylvain Chouinarda, Blair Fordb 6 Pediatric Population ◦ By far and large these are idiopathic ◦ Some genetic factors Autosomal patterns Twin studies: concordance rate: Monozygotic twins is 53% Dizygotic twins is 8% Comella CL. Gilles de la Tourette's syndrome and other tic disorders. CONTINUUM: Lifelong Learning in Neurology. 2004 June. 10 (3):128-41. Premonitory Urge Mov Disord. 2015 Aug;30(9):1171-8. doi: 10.1002/mds.26304. Epub 2015 Jul 16. Pathophysiology of tic disorders. Yael D1, Vinner E1, Bar-Gad I1. 7 Most patients feel a building urge ◦ Continues until the tic is expressed ◦ After the tic there is a feeling of relief Treatment of the urge is the basis for habit reversal therapy Is the urge the true disease process and the tic a symptom? Causal effect is not clear ◦ Mostly reported in patients over 10 years Average age of onset of Tics is 5-7 years ◦ Not all patients report an urge 8 Premonitory Urge Mov Disord. 2015 Aug;30(9):1171-8. doi: 10.1002/mds.26304. Epub 2015 Jul 16. Pathophysiology of tic disorders. Yael D1, Vinner E1, Bar-Gad I1. Two Types of Networks ◦ Expression Networks Neural substrate underlying tic manifestation Network underlying comorbid symptoms ◦ Control Networks Voluntary Tic Suppression States that influence Tic Expression 9 Generation ◦ Cortico-basal ganglia loop Pre and Primary Motor cortex, putamen, limbic and sensory areas are activated pre-tic related activity on fMRI Transient changes in Gpi neuronal activity preceeding tic onset Tic Activity: Thalamus, primary motor cortex, somatosensory cortex Limited time to suppressed based upon ability to tolerate the growing urge Frontal Cortical Activity Related ◦ Modulates basal ganglia activity 10 Mov Disord. 2015 Aug;30(9):1171-8. doi: 10.1002/mds.26304. Epub 2015 Jul 16. Pathophysiology of tic disorders. Yael D1, Vinner E1, Bar-Gad I1. Common (up to 90% in some studies) ◦ Chronic tic disorder and Tourette’s syndrome ADHD Obsessive-Compulsive Disorder/Behavior Learning Disorder Conduct Disorder 11 All associated with cortico-basal ganglia pathways ADHD ◦ MRI showed smaller globus pallidus, caudate, putamen volumes in patients Mild, non-disabling Not socially affecting the patient ◦ Counseling and Education More severe tics may require pharmacomanagement 12 Antidopaminergic drugs Alpha adrenergic agonists Topiramate Botulinum toxin injection Habit reversal training Deep brain stimulation Meta-analysis: ◦ Significant benefit of antipsychotics compared to placebo ◦ Stratified subgroup analysis No significant difference in the efficacy of the 4 antipsychotic agents tested (risperidone, pimozide, haloperidol and ziprasidone). Hannah Weisman, Imraan A. Qureshi, James F. Leckman, Lawrence Scahill, Michael H. Bloch, Systematic review: Pharmacological treatment of tic disorders – Efficacy of antipsychotic and alpha-2 adrenergic agonist agents, Neuroscience & Biobehavioral Reviews, Volume 37, Issue 6, July 2013, Pages 1162-1171 13 Hannah Weisman, Imraan A. Qureshi, James F. Leckman, Lawrence Scahill, Michael H. Bloch, Systematic review: Pharmacological treatment of tic disorders – Efficacy of antipsychotic and alpha-2 adrenergic agonist agents, Neuroscience & Biobehavioral Reviews, Volume 37, Issue 6, July 2013, Pages 1162- 1171, ISSN 0149-7634, Hannah Weisman, Imraan A. Qureshi, James F. Leckman, Lawrence Scahill, Michael H. Bloch, Systematic review: Pharmacological treatment of tic disorders – Efficacy of antipsychotic and alpha-2 adrenergic agonist agents, Neuroscience & Biobehavioral Reviews, Volume 37, Issue 6, July 2013, Pages 1162- 1171, ISSN 0149-7634, 14 Meta-analysis also demonstrated a benefit of alpha-2 agonists compared to placebo (SMD = 0.31 (95% confidence interval CI: 0.15– 0.48). Stratified subgroup analysis and meta- regression: ◦ Significant moderating effect of co-occurring ADHD ◦ Tics and ADHD: Medium to large effect ◦ Tics without ADHD Small, non-significant benefit Hannah Weisman, Imraan A. Qureshi, James F. Leckman, Lawrence Scahill, Michael H. Bloch, Systematic review: Pharmacological treatment of tic disorders – Efficacy of antipsychotic and alpha-2 adrenergic agonist agents, Neuroscience & Biobehavioral Reviews, Volume 37, Issue 6, July 2013, Pages 1162-1171, ISSN 0149-7634, http://dx.doi.org/10.1016/j.neu biorev.2012.09.008. (http://www.sciencedirect.com/s cience/article/pii/S01497634120 01613) 15 Small trials indicate a short-term benefit No long-term or comparative data 16 “Conclusions. ◦ BoNT is possibly effective for the treatment of motor tics (one Class II study). There are insufficient data to determine the effectiveness of BoNT in phonic tics (one Class IV study). Recommendation. ◦ BoNT may be considered as a treatment option for motor tics (Level C). Clinical context. ◦ There are no data to compare the efficacy of BoNT and neuroleptics in the treatment of tic disorders.” 17 Preliminary evidence for DBS ◦ I have not had experience for this Two main components: ◦ Tic-awareness training, which teaches patients to recognize early signs that precede the onset of a tic ◦ Competing-response training, which teaches patients to perform a voluntary movement that is incompatible with the particular type of tic 18 A systematic review and meta-analysis of eight trials: ◦ 438 subjects with TS who were treated with behavioral therapy (either HRT or Comprehensive Behavioral Intervention for Tics [CBIT], which is based primarily on HRT) Produced moderate treatment effects McGuire JF, Piacentini J, Brennan EA, et al. A meta-analysis of behavior therapy for Tourette Syndrome. J Psychiatr Res 2014; 50:106. Ideal for patients/families who are: ◦ Medication adverse ◦ Mild to moderate symptoms 19 Do CNS stimulants precipitate or exacerbate tics? ◦ Study of 246 children Randomly assigned clonidine, methylphenidate, clonidine plus methylphenidate or placebo ◦ Significant improvement of ADHD in all treatment groups compared with placebo ◦ Tic severity lessened in all treatment groups compared with placebo ◦ A similar proportion of patients with worsening tics with methylphenidate, clonidine, and placebo (20, 26, and 22 percent, respectively) ◦ The combination of clonidine and methylphenidate was most effective in improving ADHD and lessening tic severity ◦ Drugs were well tolerated, although clonidine was associated with moderate to severe sedation in 28 percent of patients Tourette's Syndrome Study Group. Treatment of ADHD in children with tics: a randomized controlled trial. Neurology 2002; 58:527. Do CNS stimulants precipitate
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