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Update on Tourette Disorder

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Update on Tourette Disorder 7/26/2019 Update on Tourette Disorder REBECCA K. LEHMAN, MD, FAAN ASSOCIATE PROFESSOR OF CLINICAL PEDIATRICS (CHILD NEUROLOGY) PALMETTO HEALTH-UNIVERSITY OF SOUTH CAROLINA MEDICAL GROUP PRISMA HEALTH CHILDREN’S HOSPITAL-MIDLANDS AUGUST 9, 2019 1 Disclosures Financial disclosures: Reimbursement from TAA for travel to MAB meeting and lectures. Participating (Sub-I/PI/Rater) in clinical trials for Neurocrine, Teva, and Emalex. Reimbursed for travel to investigator meetings. No other financial conflicts. All of the treatments for Tourette Disorder are off- label, with the following exceptions: Haloperidol (3 years and older) Pimozide (12 years and older) Aripiprazole (6-18 years) Tetrabenazine (orphan drug designation for children 5- 16 years) 2 1 7/26/2019 Objectives By the end of the lecture, attendees should be able to: Describe the clinical characteristics of tics Define Tourette Disorder (Syndrome) Review the symptom criteria for the diagnosis of PANDAS (Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections) Examine the controversies surrounding the diagnosis and treatment of PANDAS List the neuropsychiatric conditions that commonly co-occur with TD Outline the range of management strategies for TD Identify resources that are available for patient education and support 3 What are tics? Movements or vocalizations that are: Sudden Abrupt Transient Repetitive Coordinated (stereotyped) 4 2 7/26/2019 Premonitory Urge Leckman JF, Walker DE, Cohen DJ, 1993. 5 Other Characteristics of Tics • Variable in appearance and frequency over time • Briefly suppressible • Worsened by stress and excitement • Often reduced by focused concentration • May persist in sleep but often abate 6 3 7/26/2019 Classification of Tics Tic Symptom Dimensions Examples Simple motor tics: Sudden, brief, Eye blinking, nose twitching, grimacing, grinning, pouting, meaningless movements mouth opening, head jerking, shoulder shrugging, abdominal or buttock tensing, kicking, finger movements, rapid jerking of any part of the body Complex motor tics: Slower, longer, more Sustained “looks,” facial gestures, biting, touching “purposeful” movements objects/self, thrusting arms, throwing, banging, gestures with hands, gyrating and bending, dystonic postures, copropraxia (obscene gestures) Simple phonic tics: Sudden, meaningless Throat clearing, coughing, sniffing, spitting, screeching, sounds or noises barking, grunting, gurgling, clacking, hissing, sucking, animal noises, and innumerable other sounds Complex phonic tics: Sudden, more Syllables, words or phrases (e.g., “Shut up!,” “Oh, okay.”); “meaningful” utterances speech atypicalities (variations in pitch, volume, etc.); palilalia (repetition of one’s own words) or echolalia (repetition of another’s words or phrases); coprolalia (obscene or inappropriate words or phrases) 7 I Have Tourette’s But Tourette’s Doesn’t Have Me 8 4 7/26/2019 9 Tourette Disorder (Syndrome) A. Both multiple motor and >/= 1 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 >1 year; and during this period, there was never a tic-free period of >3 consecutive months. C. Onset 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. HD or post-viral encephalitis) 10 5 7/26/2019 Other Tic Disorders • Persistent (Chronic) Motor Tic Disorder • Multiple motor tics • Duration >1 year • Persistent (Chronic) Vocal Tic Disorder • Multiple vocal tics • Duration >1 year 11 Other Tic Disorders Provisional Tic Disorder Single or multiple motor and/or vocal tics Duration >4 weeks but <12 consecutive months Other Specified Tic Disorder, Unspecified Tic Disorder Any tic disorder that does not meet criteria for a specific tic disorder (e.g. tics lasting <4 weeks, onset after age 18) 12 6 7/26/2019 Epidemiology • Boys: girls = 3-4: 1 • Affects all ethnic groups • Prevalence among school-age children: Provisional (transient) tic disorders – 20-25% Chronic tic disorders – ~1% Tourette syndrome – 0.3-0.8% 13 Prevalence of TD Community studies* 0.6% Diagnosed + Not Diagnosed Suggests that ~50% of Ages 0-19 years children with TS are undiagnosed National survey data** 0.3% Diagnosed only Ages 6-17 years *Knight et al (2012), Scharf et al., 2014. **Bitsko et al. (2014), CDC (2009) 14 7 7/26/2019 Leckman, J. F. et al. Pediatrics 1998;102:14-19 Copyright ©1998 American Academy of Pediatrics 15 Take Home Point #1 16 8 7/26/2019 Differential Diagnosis Eye rolling -> Absence seizures Blinking -> Allergy, poor vision, blepharospasm Facial grimacing -> Dystonia Sniffing -> Allergy Scratching -> Scabies, lice, skin disorders Tics during sleep -> Hypnic myoclonus, PLMS, epilepsy, parasomnias Extremely exaggerated tics -> Functional movement disorder Other movement disorders (myoclonus, tremor, chorea, dystonia) Compulsions 17 PANDAS Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections (Swedo et al, 1998) OCD and/ or tics Prepubertal onset Episodic (saw-tooth) course Associated with Group A beta-hemolytic Strep infections Association with neurological signs 18 9 7/26/2019 PANS Pediatric Acute-Onset Neuropsychiatric Syndrome (Swedo et al, 2012) Abrupt, dramatic onset OCD or severely restricted food intake Two or more of: Anxiety Emotional lability or depression Irritability, aggression, and/or severely oppositional behavior Behavioral regression Deterioration in school Sensory or motor abnormalities Somatic symptoms, including sleep disturbances, enuresis, and urinary frequency Symptoms not better explained by another neurological or medical disorder 19 Cunningham Panel Antibody Moleculara Upper Hesselmark Upper Limit of Normal Limit of Normal Calcium/ 130 197 Calmodulin Kinase II Anti-Dopamine 8,000 15,200 Receptor 1 Anti-Dopamine 16,000 18,400 Receptor 2 Lysoganglioside 640 1,280 GM01 Antibody Beta-Tubulin 1,000 8,000 Antibody 20 10 7/26/2019 21 Current State of Evidence Guidelines are based on expert consensus Insufficient, high-quality data to support the use of long-term antibiotics, immunomodulation, and/or tonsillectomy Treatment studies have small numbers of subjects Controlled studies have been negative No studies of more specific immunomodulators 22 11 7/26/2019 EMTICS: European Multicentre Tics in Children Studies Longitudinal, observational, prospective study involving 16 sites in Europe Goal: To investigate the association of environmental factors (GAS infection, psychosocial stress) with the onset and course of tics and/or OCD To characterize the immune response to microbial antigens and the hosts immune response regulation in association with onset and exacerbations of tics To increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders To develop prediction models for the risk of onset and exacerbations of tic disorders https://cordis.europa.eu/project/rcn/102102/reporting/en 23 EMTICS Design ONSET cohort At-risk individuals N = 260 children aged 3-10 years who are tic-free at study entry and have a first-degree relative with a chronic tic disorder COURSE cohort Affected individuals N = 715 youth aged 3-16 years with a tic disorder 24 12 7/26/2019 EMTICS Conclusions No indication for a role of new GAS exposures in relation to exacerbations of tic disorders GAS infections are frequent and exposure at some point in childhood is nearly universal Co-occurrence of tic exacerbations and recent new GAS exposures is most likely due to chance Anti-GAS responses in patients with tics did not increase after tic exacerbations Assessing GAS exposure in children with tic disorders is not clinically meaningful Possible altered post-infectious immune response in patients with TD/ OCD 25 26 13 7/26/2019 Take Home Point #2 27 Co-morbid Conditions • ADHD • Anxiety/ OCD • Learning difficulties • Mood disorders • Impulse control disorders • Dysgraphia/ fine motor impairment 28 14 7/26/2019 Treatment of Tics Take Home Point #3: Not all patients require treatment Current treatments do not “cure” tics Think about treating patients whose tics are causing: Pain/injury Social distress Significant disturbance to others in classroom environment No scientific evidence to support the use of dietary interventions Take Home Point #4: Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes. Assess for comorbid disorders and treat most impairing condition first. 29 Take Home Point #5 30 15 7/26/2019 31 Figure 2 . Mean change from Questionnaire-Teacher baseline on the Conners Abbreviated Symptom (ASQ- Teacher) at each evaluation visit for the four treatment groups. Error bars represent 1 SEM. CLON = clonidine; MPH = methylphenidate. Figure 3 . Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups. Error bars represent 1 SEM. CLON = clonidine; MPH = methylphenidate. (Tourette Syndrome Study Group, 2002) 32 16 7/26/2019 Take Home Point #6 Patients with TD/ CTD are at increased risk of suicide Clinicians must inquire about suicidal thoughts and suicide attempts in people with TS and refer to appropriate resources if present Fernandez del la Cruz L., Rydell M, Runeson B, et al. Suicide in Tourette’s and chronic
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