Lauren Schrock, M.D Assistant Professor of Neurology University of Utah Co-Director, Movement Disorders Program

Transcription

1 Lauren Schrock, M.D Assistant Professor of Neurology University of Utah Co-Director, Movement Disorders Program

2 Brief clinical overview What are tics? Definition of TS and related tic disorders What we know: Inheritance and Epidemiology Natural History Comorbidities ( the TS Triad ) Etiology (causes) Management Education of Patient, Family, and School Behavioral and Medical treatment approach

3 Georges Gilles de la Tourette French neurologist 1885, described 9 pts with motor and phonic tics Attributed to psychogenic causes for many years 1960s with advent of neuroleptics, finally thought to have organic underpinnings

4 Involuntary, purposeless, repetitive muscle contractions that produce stereotyped movements (motor tics) or sounds (vocal tics) What kind of movements are tics? Semivoluntary (unvoluntary) Induced by inner sensory stimulus/unwanted feeling No Bereitschaftpotential Involuntary Suppressible May occur during all stages of sleep

5 Mimic normal coordinated movement Occur out of a background of normal motor activity Not constantly present Vary in intensity Lack rhythmicity Voluntarily suppressible Usually characterized by a premonitory sensation

6 Motor or vocal/phonic tics Simple tics involves individual muscles or small groups of muscles Eye blinking, nose twitching, head jerking, eye deviation, mouth opening, sniffing, throat clearing Complex tics muscles acting in a coordinated pattern (may resemble purposeful voluntary movements) Head shaking, scratching, touching, throwing, hitting, gestures, uttering phrases Compulsive, Impulsive, Dystonic, and Myoclonic tics

7 Simple Tics

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9 She feels compelled to repeat the tics 6 times when she feels the urge.

10 DSM-IV-TR (2000) CRITERIA Tourette Syndrome A. Both multiple motor and one or more vocal tics have been present at some time during the illness, although not necessarily concurrently. B. The tics occur many times a day (usually in bouts) nearly every day or intermittently throughout a period of more than 1 year, and during this period there was never a tic-free period of more than 3 consecutive months. C. The onset is before age 18 years. D. The disturbance is not due to the direct physiological effects of a substance (e.g., stimulants) or a general medical condition (e.g., Huntington s disease or postviral encephalitis).

11 Transient tic disorder (10-24% of school children) Chronic multiple motor or phonic tic disorder Tourette syndrome

12 Polygenic Frequently Bilineal TS triad : tics, OCD, ADHD In 84%, at least one parent has history 25%: both parents More tics in fathers (31 vs 16%) More OCS in mothers (33 vs 16%) 70% concordance in monozygotic twins Hanna et al. Bilineal Transmission in Tourette Syndrome. Neurology, 1999

13 Not a rare disorder Accurate prevalence rate not established Transient tic disorder (10-24% of school children) Chronic tic disorders (1-4%) Tourette syndrome (1%) Males > females 4:1 Rarely a disorder identical to TS will arise de novo in adults poorer prognosis

14 DSM-IV DSM-IV-TR Tics- all forms Regular School Aged Kids 0.8% 3.8% 18.5% Special Education Children 1.5% 7% 23.4% Kurlan et al. Neurology 2001; 57:

15 Onset by age 11 years in 96% Mean age of onset 5-7 years Peak severity: ~10 years Remission (0-50%), lessening of tic severity/disability: late adolescence/early adulthood Long-term prognosis favorable for most patients Robertson, 1989;Leckman et al., 1998; Goetz et al., 1992; Pappert et al., 2003; Bloch et al., 2006; Eapen et al., 2002.

16 Tourette International Consortium Database (Freeman et al.,2000) 12% Tics 60% 59% anger control problems - 37% ADHD OCD sleep disorder - 25% learning disability -23% mood disorders - 20% anxiety disorders - 18% self-injurious behavior - 14%

17 16 to 68% of child and adolescent cases of TS have experienced school-related problems Children with TS are 5x more likely to require special education (SpEd) services Causes of impairment: tics themselves, associated disorders (ADHD, OCD, etc.), medication side effects May have deficits in fine motor control, motor inhibition, visual motor integration, procedural memory Comings DE. Am J Hum Genet 1987;41:

18 Tics are reliably suppressed by dopamine antagonists OCBs are improved by SSRIs Implicates the dopaminergic and serotonergic pathways and suggest that regions where dopaminergic and serotonergic neurons interact are candidate loci of abnormalities in TS: Striatum Substantia nigra Prefrontal cortices Increasing evidence suggests TS is a disorder involving frontalsubcortical circuits

19 Recent post-mortem data: the density of the nigrostriatal (dopaminergic) projection changes during normal development, reaching a peak during the pre-adolescent period and then declining (Haycock JW et al. J Neurochem 2003) Correlates approximately with the natural history of tics Functional connectivity MRI: early and mid-adolescent subjects with TS appear to have immature functional connections compared to an age-matched unaffected group. (Church JA et al., Brain 2008) Hypothesis: changes in the extent or timing of development of the nigrostriatal dopaminergic projection might underlie tics and TS

20 The Life Cycle of Dopamine Age (years) Clinical Correlate Mean age of tic onset = 5.6 (SD 2.3) Mean age of peak tic severity = 10.6 (SD 2.6) Tic remission Reappearance of tics Neurobiologic al Events Basal ganglia dopamine levels plateau (age 2-9) Gray matter synaptic density peaks (age 11 to 13) Prefrontal cortical pruning begins, peak cortical D1 receptor density Decline in striatal D1/D2 receptor ratios

21 Education of parents, teachers, and peers is a critical initial intervention Many tics do not require treatment Decision to intervene is based on a relative evaluation of tic severity vs. consequences of potential side effects on school and work Tics can rarely be eradicated entirely: goal is maximum control with minimum side effects Choose medications based on target symptoms: tics, OCB, ADHD

22 Empower patient and family to educate teachers, peers Emphasize current information about causes of tics (genetic factors, brain neurochemical imbalances); not signs of psychological or emotional illness Explain process of voluntary suppression; there is no value for anyone to point out tics to the child or tell them to stop their tics Encourage open, supportive family environment Focus on building self-confidence, self-esteem

23 Highlight fact that most TS pts have improvement of tics in late adolescence/early adulthood Educate family about clinical triad (tics, ADHD, OCD) of TS Emphasize key decision-making element in whether to treat tics or related symptoms: is the symptom is causing significant problems in daily functioning? Emphasize focus on patient s disability; we don t want to treat simply because parents find child s tics annoying or embarrassing

24 Education of school personnel is critical for child Misperceptions of tics as being voluntary, attentionseeking, or purposely disruptive behaviors Education of classmates bullying prevention Trained professionals in many areas Educational videos, etc. available from the Tourette Syndrome Association ( Consider special accommodations Allow child to sit in back of classroom Excuse child (at his/her request) to nurse s office to release tics Provide additional time in separate room for tests

25 Kurlan, R. N Engl J Med 2010;363:

26 Comprehensive Behavioral Intervention for Tics (CBIT) Habit reversal training Tic-awareness Competing-response training Relaxation training Functional intervention Randomized controlled trial of CBIT vs. supportive therapy and education in children with TS or chronic tic disorder CBIT: greater improvement in symptom severity Similar improvements as dopamine-blocking meds 87% with continued benefit at 6 months Piacentini J et al. JAMA.2010; 303(19):

27 Tic disorders are relatively common and complex neurobehavioral disorders with solid biological underpinnings Tics are involuntary or unvoluntary ; if a child could stop them, he/she would Tics disorders are usually inherited, and are commonly associated with ADHD, OCD, and other neurobehavioral disorders Learning disabilities are common in children with tics Most children with tic disorders have a good long-term prognosis Children with tic disorders are at high risk of bullying: Education of family, school, and peers is a critical initial intervention

28 Tourette Syndrome Association