Update on TOURETTE SYNDROME Paediatric Society of Queensland ASM 2012 Dr Jim Pelekanos Paediatric Neurologist RBWH UQCCR

Movement disorders chapter in any neurology book: - Bradykinesias ... - Hyperkinetic movement disorders: Athetosis Ballismus Chorea Dystonia Myoclonus Tics Tremor

TICS- definition involuntary or semivoluntary contractions of functionally related groups of muscles resulting in: sudden brief intermittent nonrhythmic repetitive movements or sounds

MOTOR TICS - examples blinking, eye deviation eye closure, eyebrow raising grimacing, mouth opening head shaking shoulder shrugging torticollis (head turning) tensing limb or abdominal muscles skipping imitating others (echopraxia) obscene gestures (copropraxia) “blocking” tics

SENSORY ASPECTS of TICS very common patients has an unpleasant sensation in the affected body part which is “relieved” when a certain action is performed - premonitory urge sensory aspects can occur without motor component overlap with compulsions

VOCAL TICS simple or complex sniffing, snorting throat clearing, coughing grunting barking, roaring, shouting echolalia (repeating someone else’s words) palilalia (repeating one’s own words) coprolalia (obscene words – quite uncommon)

TICS- characteristics common- ? up to 10% of 5-10 year old boys have transient tics fluctuate over time many times per day can be voluntarily suppressed for a short period (then “pressure”) worse when nervous, excited, tired; better or worse when relaxed, often better when concentrating, absorbed (“hyperfocus”) often (not always) disappear during sleep sometimes triggered by specific external cues (“suggestibility”) rostro-caudal progression

How do we diagnose tics ? visual confirmation (direct observation in the clinic or by video clip) differentiate tics from other movement disorders / seizures / stereotypies etc exclude other rare neurological disorders which can mimic tics

PRACTICAL CLASSIFICATION OF TIC DISORDERS transient tic disorder (TTD) < 12 months chronic motor or vocal tics (CTD) > 12 months Tourette Syndrome (TS) “NOS” / “provisional TD”

TOURETTE SYNDROME (TS) Described in 1885 by Georges Gilles de la Tourette (1857-1904) defined by: 1) multifocal motor tics 2) one or more vocal tics 3) present for more than one year 4) age of onset prior to 21 years

Tics – natural history often begin at 3 to 8 years peak onset at 6 to 7 years fluctuate +++ maximum tic severity at 8 to 12 years then many improve, though most adults still have some tics adult onset is possible

Prevalence of Tourette Syndrome meta-analysis of 13 studies in children: 0.77% of children (95% confidence interval, 0.39 - 1.51%) M > F (1.06 % of boys v 0.25% of girls) Transient tic disorder: 2.99% meta-analysis of 2 studies in adults: prevalence of TS = 0.05% Knight, T. et al. (2012) Pediatr Neurol 47(2): 77-90

TS – associated features / comorbidities ADHD ( ? 50% - 70% of boys with TS) obsessive-compulsive behaviours / disorder (OCD- ?30 - 50%) learning difficulties (up to 50%) speech dysfluency (like stuttering) co-ordination problems conduct disorder / ODD / “explosiveness” autism / Asperger syndrome / personality disorders low self esteem / poor social adaptation depression (20-50%), anxiety disorders, substance abuse self injury sleep disorders, migraine inappropriate sexual behaviour / gestures (copropraxia)

Prevalence of Tourette Syndrome co-mordidities OCD and ADHD prevalence in TS may be lower than previously thought from clinic-based studies a population based study: 69% did not have ADHD or OCD 8.2 had both ADHD and OCD Scharf J. et al. (2012) J. Am. Acad. Child Adolesc. Psychiatry, 51(2):192–201

if a person with TS does develop co-morbidities, they don’t usually all begin at the same age – different aspects can emerge over the first few years tics and comorbid features usually (but not always) fluctuate in severity at the same time as each some comorbidities (eg ADHD, OCD) might be slightly different clinically and biologically to these conditions in the non-TS population

Quality of life outcomes are more related to comorbidities than to the tics medications for comorbid features generally have fewer side effects than the “tic medications” therefore, identification and management of comorbid features of TS is often the most helpful and rewarding thing we can do for our TS patients

What are TICS ? Theory: "some tics are inappropriately expressed (normally inhibited) fragments of primitive motor and vocal programs ….."

BIOLOGICAL BASIS OF TS - SUMMARY exact mechanism unknown strong genetic + environmental factors affect brain development (BG + cortical structures) TS is thought to be a disorder of : cortical – striatal – thalamic – cortical circuits: decreased inhibitory output from basal ganglia resulting in increased activity in frontocortical areas

PANDAS Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection “In summary, this author believes that the proposed poststreptococcal autoimmune disorder PANDAS deserves careful study, but that, to date, its validity remains unproven”. Singer 2011

TS- AN APPROACH TO TREATMENT -philosophy "It is not the disorder itself but the reaction to it that affects the lives of those with TS most." Andrew Rosen Tourette's Syndrome: The School Experience Clinical Pediatrics Sept 1996:467-469

TS- AN APPROACH TO TREATMENT (I) make correct diagnosis investigations- rarely needed explanation / reassurance / support emphasize that the problem is not primarily psychological counsel family- pay less attention to the tics counsel child- how to deal with the questions / teasing; teach "tricks” counsel teachers (TSAA podcast at www.tourette.org,au) explain likely long term outcome – probable improvement

www.tourette.org.au TSAA TSAA PURPOSE—The purpose of the Association is to support people with Tourette Syndrome and increase awareness of the disability among medical practitioners, public utilities and the general public. ACTIVITIES—Support those with TS and their families. Gather and circulate to members information regarding Tourette Syndrome and available forms of treatment. Circulate information regarding Tourette Syndrome to doctors, schools and other interested parties. Gain publicity through the media and other outlets about TS. Raise funds for research into the causes and cure of Tourette Syndrome and to assist in the achievement of the above activities. www.tourette.org.au The national office of the Tourette Syndrome Association of Australia (TSAA) is located in Sudney. It was founded in 1989 and is the only national, voluntary, non-profit memebrship organisation dedicted to identifying the cause, finding the cure and controlling the effects of TS.

TS- AN APPROACH TO TREATMENT (II) define which aspects are causing the disabilities and treat each appropriately (the profile) formal therapy if necessary (CBT, educational assessments etc) decide if medications are needed for tics painful tics significant secondary emotional, social or academic problems (interfering with quality of life or functioning) decide if medications are needed for other aspects trial medications (“ n=1 study” approach)

first visit never start medications explanation diary review in 4 – 8 weeks

examples of some real patients on a hypothetical “profile” scale

TS – nonpharmacologic treatments for tics Contingency management Relaxation training Cognitive behavioural therapy Habit reversal training (HRT) misc others this area has been a little disappointing – these treatments are either unavailable, expensive, ineffective (or effective for only a short period) or the effort of training can make some other aspects of TS worse

CBIT - Comprehensive behavioural intervention for tics combination of techniques – predominantly habit reversal training currently being researched but some are cautiously optimistic that it might reduce tic severity without medications currently an 8 week program, research only

Medications used in Tic Disorders Singer 2011 Tier 1 Tier 2 Tier 3 Drug Category Clonidine B Pimozide A Dopamine agonists   Guanfacine Fluphenazine Pergolide (B) Baclofen C Risperidone Pramipexole ? Topiramate Aripiprazole Tetrabenazine Levetiracetam Olanzapine Delta-9-THC Clonazepam Haloperidol Donepezil Ziprasidone Botulinum toxin Quetiapine Sulpiride and tiapride – A - Good supportive (two randomized, placebo-controlled studies). B - Fair (one positive placebo-controlled study). C - Minimal (open-labeled, case reports). Italicized drugs are FDA-approved for the treatment of tics.

Medications for Tics - summary Due to significant side effects, I consider medications for tics are a last resort clonidine, risperidone start low, go slow monitor for the inevitable side-effects consider trial off after a few months – their role is really only to get the patient through a bad patch

Attention Deficit Disorder medication use must be part of overall program (eg educational testing, behavioural strategies) tricks and tips: check hearing look for “fixed” specific learning difficulties OCD sedation from medications sleep disorders

Medications for ADHD in TS Meta-analysis: treatment of ADHD in children with comorbid tic disorders “CONCLUSIONS: Methylphenidate seems to offer the greatest and most immediate improvement of ADHD symptoms and does not seem to worsen tic symptoms. Alpha-2 agonists offer the best combined improvement in both tic and ADHD symptoms. Atomoxetine and desipramine offer additional evidence-based treatments of ADHD in children with comorbid tics. Supratherapeutic doses of dextroamphetamine should be avoided” J Am Acad Child Adolesc Psychiatry. 2009 Sep;48(9):884-93

Medications for ADHD in TS methylphenidate + clonidine may be better than either alone may treat different aspects of the disorder Neurology 2002;58:527-536

Medications for ADHD in TS - summary stimulants are well studied, very effective and not contraindicated. if they aren’t working, go through the checklist again long acting preparations are sometimes not well tolerated atomoxetine ? not effective in the ADHD of TS

Obsessive-compulsive disorder Obsessions – the part of the iceberg invisible under the water ! how do we know if a young child is having obsessions? ask them !! look for compulsions (eg distal “tics” in hands) look for anxiety – often the “flip side of the coin” of OCD in TS

Medications FOR OCD in TS - there are no major studies of OCD Rx in TS SSRIs SNRIs clomipramine buspirine, clonazepam, lithium, neuroleptics

Medications FOR OCD SSRIs on PBS for OCD: fluoxetine (this is commonly prescribed but in my experience, it doesn’t seem to work well for the OCD of TS) fluvoxamine (may work) paroxetine (may work) sertraline (in my experience, it is effective more often than other SSRI’s for the OCD of TS) citalopram (in my experience, it is probably the second most effective SSRI for the OCD of TS – but not on PBS for OCD)

more anecdotal tips: oppositional / explosive behaviour seems to improve with SSRIs

more anecdotal tips: ADHD + ODD sertraline plus methylphenidate

more anecdotal tips: consider SSRIs (sertraline) “distal tics” not responding to other Rx compulsions obsessions anxiety ODD / explosiveness start low, go slow, build to high doses they do not take 6 weeks to start working – they often start to work within a few days ! if effective, prob treat for 1-2 years before trial off

TS- SUMMARY common presents in many ways most people with TS only require explanation and support (no meds) a small group have a complex interaction of problems, requiring an individualized, multimodal therapy program some benefit from sequential polytherapy increased services are greatly needed !!

Ideal service delivery model Multidisciplinary research clinic www.tourette.org.au