Tourette’s Syndrome: diagnostic and therapeutic algorithms to improve patient's quality of life M. Porta MD - D. Servello MD IRCCS Galeazzi - Milano Tourette Center 20-21/09/2010 Warsaw
Definite Tourette Syndrome (The Tourette Syndrome Classification Study Group) • Both multiple motor and one or more vocal tics have been present at some time during the illness, although not necessarily concurrently • The tics occurs many times a day, nearly every day, or intermittently throughout a period of more than 1 year • Onset before age 21 • Involuntary movements and noises cannot be explained by other medical conditions • Motor and/or vocal tics must be witnessed by a reliable examiner directly at some point in the illness or be recorded by videotape or cinematography (Definite Tourette Syndrome) • Tics must be witnessed by a reliable family member or close friend, and description of tics as demonstrated must be accepted by reliable examiner (Tourette Syndrome by History)
• PHENOMENOLOGY: Jankovic classification of tics and movements • ASSOCIATED/RELATED SYMPTOMS: NOSI, SIB, OCB: have to be included in the syndrome • CLASSIFICATION OF TS: Robertson - Baron Cohen: TS simple TS full blown TS plus CLINICAL EVALUATION • • HEALTH-RELATED QUALITY OF LIFE GTS-QOL inventory
Classification of Movements (Jankovic) VOLUNTARY Intentional (planned, self-initiated) • Responsive (induced by external stimulus) • SEMIVOLUNTARY (UNVOLUNTARY) • Induced by an inner sensory stimulus TIC • Induced by an unwanted feeling/compulsion INVOLUNTARY TIC Non suppressible (reflex, seizures, myoclonus) • • Suppressible (tics, tremor, chorea, dystonia, sterotype… ) AUTOMATIC TIC • Learned, without conscious effort (gait, speech… )
Robertson – Cohen classification of TS • Simple Simple motor/vocal Tics Complex phonic Tics (copro-, eco-, • Full blown pali- lalia/praxia) Hypermotricity/attention deficit, obsessive-compulsive behavior, • Plus psychic disorders, SIB, NOSI, etc..
Classification of Tics (Jankovic) Simple motor tics: Tonic (< 100ms) Distonic (>300 ms) Clonic (>500ms) Complex Motor Tics: Seemingly nonpurposeful Seemingly purposeful Simple Phonic Tics Complex Phonic Tics Ideic Tics
Comorbidity – Morbidity in TS (plus) M M Robertson, 2000; Porta and Servello, 2007 Freeman et al, 2000 OCB 70 – 85% • • OCB 25 – 50% • ANXIETY 40 – 50% • ANXIETY 30 – 40% • ADHD 40 – 60% • ADHD 50 – 60% • MOOD DISORDER 40 – 50% • MOOD DISORDER 50 – 60% • LEARNING DIFFICULTIES LEARNING DIFFICULTIES • • 30 – 40% • 20 – 30% • SIB 40% • SIB ?
Comments • 85 – 90% of TS patients refer premonitory sensations before TICS • Sensory activation facilitates Tics production • Are Tics a sensory - motor disease with involvement of the central integration?
….. AND SO ..… THIS IS TOURETTE SYNDROME (VIDEO)
Conditions not to be confused:
TS Etiology • Genetic influences in the vast majority of cases, but not single gene has been convincingly idientified • Certain infections in a subgroup of patients (PANDAS) • Pregnancy and birth difficulties in some patients • Possibly hormonal influences (androgen exposure)
Genetic Models • Autosomal dominant (with suggestion of incomplete penetrance) • Mixed model • Polygenic model • Bilinear inheritance
Etiological hypotheses Neuroanatomic hypothesis: striatum abnormality (alterated Genetics Environmental synaptogenesis) Neurophysiological hypothesis: Neuro-biology: thalamic afferents disinhibition, GABA, glutammate, 5-HT, blockade of cortical inhibitions dopamine, neuroendocrine factors Neurochemical hypothesis: dopaminergic hypersensitivity, presinaptic abnormality, second Phenotypes of mediator abnormality TS
Comments • TS D 2 (dopamine) disease involving basal ganglia • “ Basal ganglia are usually considered as component of motor system; evidence that basal ganglia interact with all of the frontal cortex and with limbic system …” J.V. Mink • Diseases of the basal ganglia often cause a combination of alterated movements, affective and cognitive disorders ….. • Motion and e-motion!
Comments • TS difficult to be investigated • No “gold standard” • No hall mark imaging abnormalities • No neuropathological post-mortem lesions • No genetic tests
Comments • But always, even if variable, presence of Social Impairment with personal distress, and comprimised quality of life of the family involving often colleagues, caregivers etc. (GTS-QOL inventory) • Bad compliance (active and passive) • High social costs (no utility-cost data) • Significant misdiagnosis • Not easily identifiable natural hystory of disease
Natural history of disease EXACERBATED POSSIBLE REMISSION OBSESSIVE – COMPULSIVE DISORDER (OCD) PHONIC TICS (simple - complex) MOTOR TICS with rostro – caudal progression ATTENTION DEFICIT – HYPERACTIVITY DISORDER (ADHD) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 AGE (YEARS)
Social impairment due to: • psychopathology and associated > abnormal behaviour (part of TS) • sound tics (not only vocal) > • motor tics
Health-related quality of life Specific for TS • critical measure of clinical outcome (patient's own subjective view) • used for several movement disorders and neuropsychiatric conditions (cervical dystonia, hemifacial spasm progressive supranuclear palsy,etc.)
Items of the 5-domain GTS-QOL inventory from Schrag, 2007 SOCIAL/ WORK/ PHYSICAL PSYCHOLOGICAL COGNITIVE FAMILY ECONOMIC DOMAIN DOMAIN DOMAIN DOMAIN DOMAIN DIFFICULTY FINANCIAL MOVEMENT ANXIETY IN MEMORY DEFICIT DISCONTROL PROBLEMS FRIENDSHIPS NO SOCIAL DIFFICULTY IN PHONIC TICS RESTLESSNESS NO JOB ACTIVITIES FINISHING TASKS UPSET BY SCHOOL/WORK LOSING IMPORTANT PAIN OF INJURES MOOD SWITCHES DUE TO TICS PEOPLE PROBLEMS THINGS EMBARRASS EMBARASSING LACK OF CONTROL NO CONCENTRATION GESTURES MENT DIFFICULTY INVOLUNTARY IN TALKING ECOLALIA DEPRESSED MOOD SWEARING ABOUT ECOPRASSIA ILLNESS PROBLEMS LACK OF SELF SLEEP WITH PROBLEMS CONFIDENCE AUTHORITIES SEXUAL FAMILIAR SELF-HARM DIFFICULTIES MATTERS
Comments • GTS-QOL instrument for validation of self-rating measure in TS • GTS-QOL inventory validated (London) using two generic HR-QOL (QOLAS and SF.36)
TS patient evaluation (1) • Definite TS (DSM IV tr, ICD-10) • Refractory patients • Tic analysis according to Jankovic • TS phenotype (Robertson-Cohen) • Significant social impairment • SIB or tic-related injuries • Psychological and behavioral assesment
TS patient evaluation (2) • Videotaping: Modified RushVideo-Based Tic Rating Scale (VTRS) • Yale Global Tic Severity Scale ( YGTSS) • Diagnostic Confidence Index (DCI) • Premonitory Urge for Tic Scale ( PUTS) • Yale Brown Obsessive Compulsive Scale (YBOCS) • State Trait Anxiety Inventory (STAI) • Visual Analogic Scale (VAS) • Social impairment assesment (GTS-QOL)
Refractory patient (RTS): comments Not completly assested Majority of available drugs without specific claim ! Health Economics problems (cost-utility)
Refractory patient (RTS) At least 2 years of psychological therapy At least 2 of the following drugs: Traditional and/or innovative antipsychotics Cathecolamines depletors SSRI Inadequate clinical response and/or side effects
Treatment justified to improve social impairment (algorytm) Observation Conservative treatment Mini invasive therapy (Btx – DBS – etc.)
TS conservative therapy Tic-oriented medications • Aloperidol • Pimozide • Sulpiride • Ziprasidone Psichotherapy • Quetiapine • Cognitive approach • Aripiprazole • Nicotine • Self-control methods • Micamilamine • Relaxing methods • Cannabis • Behavioral techniques • Pergolide • Tetrabenazine (Habit-Reversal promising) ADHD-oriented medications • Metilfenidate • Pemoline • Clonidine • Guanfacine • Atomoxetine OCB-oriented medications • SSRI • Triciclic antidepressant
DBS (DEEP BRAIN STIMULATION)
Minimal social impairment, satisfying drug response, not yet attempted, or possible conservative treatment, not • Await defined chronic disease DBS Mild-to-moderate social impairment, not-satisfying • Possible response to drugs (refractory), Candidates self-motivation • Mandatory Significant social impairment, self-inflicted or TS linked lesions, relevant drug side-effects
Malignant Tourette Significant Tic Related Injuries
Different and “ personalized ” targets for DBS CM/pf / VOA Accumbens Pallidum: Anterior, Posterior, External PPN STN
Vo-CM/Pf DBS target • 5 mm lateral to AC-PC line • 2 mm posterior to the midpoint • At the AC-PC plane
DBS for TS: Hope or Hype? • “who” (candidate) • “when” (age) • “how” (target) • “why” (social) • “where” (multidisciplinary team) • GTS-QOL evaluation
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