and therapeutic algorithms to improve patient's quality of life M. - - PowerPoint PPT Presentation

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

VOLUNTARY

• Intentional (planned, self-initiated)
• Responsive (induced by external stimulus)

SEMIVOLUNTARY (UNVOLUNTARY)

• Induced by an inner sensory stimulus
• Induced by an unwanted feeling/compulsion

INVOLUNTARY

• Non suppressible (reflex, seizures, myoclonus)
• Suppressible (tics, tremor, chorea, dystonia, sterotype…)

AUTOMATIC

• Learned, without conscious effort (gait, speech…)

Classification of Movements

(Jankovic)

TIC TIC TIC

Robertson – Cohen classification of TS

• Simple
• Full blown
• Plus

Simple motor/vocal Tics Complex phonic Tics (copro-, eco-, pali- lalia/praxia) Hypermotricity/attention deficit,

• bsessive-compulsive behavior,

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)

Porta and Servello, 2007 M M Robertson, 2000; Freeman et al, 2000

• OCB 70 – 85%
• ANXIETY 40 – 50%
• ADHD 40 – 60%
• MOOD DISORDER 40 – 50%
• LEARNING DIFFICULTIES
• 30 – 40%
• SIB 40%
• OCB 25 – 50%
• ANXIETY 30 – 40%
• ADHD 50 – 60%
• MOOD DISORDER 50 – 60%
• LEARNING DIFFICULTIES
• 20 – 30%
• SIB ?

• 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?

Comments

….. 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 synaptogenesis) Neurophysiological hypothesis: thalamic afferents disinhibition, blockade of cortical inhibitions Neurochemical hypothesis: dopaminergic hypersensitivity, presinaptic abnormality, second mediator abnormality

Genetics Neuro-biology: GABA, glutammate, 5-HT, dopamine, neuroendocrine factors Phenotypes of TS

Environmental

• 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

Comments

Natural history of disease

EXACERBATED POSSIBLE REMISSION

ATTENTION DEFICIT – HYPERACTIVITY DISORDER (ADHD)

MOTOR TICS with rostro – caudal progression PHONIC TICS (simple - complex)

OBSESSIVE – COMPULSIVE DISORDER (OCD)

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

>

• critical measure of clinical outcome (patient's
• wn subjective view)
• used for several movement disorders and

neuropsychiatric conditions (cervical dystonia, hemifacial spasm progressive supranuclear palsy,etc.)

Health-related quality of life Specific for TS

Items of the 5-domain GTS-QOL inventory from Schrag, 2007

PHYSICAL DOMAIN PSYCHOLOGICAL DOMAIN SOCIAL/ FAMILY DOMAIN WORK/ ECONOMIC DOMAIN COGNITIVE DOMAIN

MOVEMENT DISCONTROL ANXIETY DIFFICULTY IN FRIENDSHIPS FINANCIAL PROBLEMS MEMORY DEFICIT PHONIC TICS RESTLESSNESS NO SOCIAL ACTIVITIES NO JOB DIFFICULTY IN FINISHING TASKS PAIN OF INJURES DUE TO TICS MOOD SWITCHES UPSET BY PEOPLE SCHOOL/WORK PROBLEMS LOSING IMPORTANT THINGS EMBARASSING GESTURES LACK OF CONTROL EMBARRASS MENT NO CONCENTRATION INVOLUNTARY SWEARING DEPRESSED MOOD DIFFICULTY IN TALKING ABOUT ILLNESS ECOLALIA ECOPRASSIA SLEEP PROBLEMS LACK OF SELF CONFIDENCE PROBLEMS WITH AUTHORITIES SELF-HARM SEXUAL DIFFICULTIES FAMILIAR 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

• 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)

TS patient evaluation (2)

Refractory patient (RTS): comments

Not completly assested Majority of available drugs without specific claim ! Health Economics problems (cost-utility)

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

Refractory patient (RTS)

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
• Quetiapine
• Aripiprazole
• Nicotine
• Micamilamine
• Cannabis
• Pergolide
• Tetrabenazine

ADHD-oriented medications

• Metilfenidate
• Pemoline
• Clonidine
• Guanfacine
• Atomoxetine

OCB-oriented medications

• SSRI
• Triciclic antidepressant

Psichotherapy

• Cognitive approach
• Self-control methods
• Relaxing methods
• Behavioral techniques

(Habit-Reversal promising)

DBS

(DEEP BRAIN STIMULATION)

• Await
• Possible
• Mandatory

DBS Candidates

Significant social impairment, self-inflicted or TS linked lesions, relevant drug side-effects Mild-to-moderate social impairment, not-satisfying response to drugs (refractory), self-motivation Minimal social impairment, satisfying drug response, not yet attempted, or possible conservative treatment, not defined chronic disease

Malignant Tourette

Significant Tic Related Injuries

CM/pf / VOA Accumbens Pallidum: Anterior, Posterior, External PPN STN

Different and “personalized” targets for DBS

Vo-CM/Pf DBS target

• 5 mm lateral to AC-PC

line

• 2 mm posterior to the

midpoint

• At the AC-PC plane

• “who” (candidate)
• “when” (age)
• “how” (target)
• “why” (social)
• “where” (multidisciplinary team)
• GTS-QOL evaluation

DBS for TS: Hope or Hype?

Social impairment evaluation (GTS-QOL) Therapeutic algorythm Etiology of TS? Clinical fluctuations

Pending questions tree

Evaluation timing Spontaneous remission? Different targets reported Age at DBS? DBS: add-on or “second choice therapy”? Stimulating parameters regulation DBS candidates (refractory)

DBS

• TS fascinating, not rare disorder
• Each patient peculiar phenomenology
• Broad spectrum of the clinic including

behavioral symptoms

• Treatment to improve quality of the life
• Therapeutic algorytms have to be identified and

personalized (also for DBS)

• Point of view of patients/caregivers have to be

evaluated (health-related outcome: GTS-QOL)

• Health economics: cost-utility studies
• Team-work mandatory

Conclusions

THANKS !!