Dystonia 101 (& 102)

John Fang, M.D.September 19, 2011

Key Topics

• Types of Dystonia:– Primary vs. Secondary– Dopa-Responsive– Kinesigenic

• Genetic Dystonias• Basic Management Strategies

Dystonia Vocabulary

• Blepharospasm• Craniocervical (Meige) • Oromandibular

• Focal• Segmental• Hemi-• Generalized

• Geste Antagonist (Sensory Trick)

• Tardive

• ε-Sarcoglycan• TorsinA

• Westphal variant• Wilson’s disease

Generalized Dystonia

Secondary Dystonia• Drug-induced (D2 blockers, flecainide)• Structural• Psychogenic• Toxic (Mn, CO, CS2, Hymenoptera)• Metabolic • DRD - TH deficiency, sepiapterin, GCH-deficiency• Lesch-Nyhan• PKAN• NBIA

Wilson’s Disease• Excessive copper accumulation due to

mutation of the ATP7B gene• Low ceruloplasmin • High urine copper, sometimes requiring

penicillamine challenge• Kayser-Fleischer Rings• May affect liver, bone, behavior

Wilson’s Disease Treatment• Acute treatments: – Penicillamine– Trientene– TTMB

• Long-term treatments:– Zn– low Cu diet– Liver transplant

Pseudo-Dystonia• Atlanto-axial subluxation• CN IV palsy

• Camptocormia (Bent spine)• Pleurotonus (Pisa syndrome)

Degenerative Dystonias• CBD– Alien-limb

• Lubag – aka DYT3 – x-linked– Philippines

Tyrosine Hydroxylase Deficiency

• TH converts Tyr to DOPA• Tetrahydrobiopterin is cofactor– GTP cyclohydrolase (GCH)– 6-pyruvoyltetrahydropterin synthase (PTPS)– Sepiapterin reductase (SR)

• Tetrahydrobiopterin also affects metabolism of nitric oxide, serotonin, and phenylalanine

• Sapropterin is FDA approved for PKU

Treatment Options

• Anticholinergics• Dopamine agonists or levodopa• GABA agonists (A and B, also intrathecal)• Other anticonvulsants• VMAT inhibitor• Botulinum toxins• Surgical (Myectomy, SDR, DBS, thalamotomy)

Tetrabenazine

• Inhibits Vesicular Monoamine Transporter 2• Typical starting dose = 6.25mg bid• Typical effective dose = 25mg bid• Metabolism affected by CYP2D6• FDA approved for Huntington’s Chorea• Also effective for tardive dyskinesia and some

dystonias• Sleepiness and depression are major SE’s

Botulinum Toxin

• Inhibits presynaptic Ach release by destroying SNARE proteins

• Dosing can be tricky• FDA approved for cervical dystonia,

blepharospasm, and a few other disorders• Typical duration of action = 90-120 days• Weakness is the major SE• Four current formulations: 3 A and 1 B

Botulinum Toxin Formulations

• abobotulinumtoxinA (Dysport)• incobotulinumtoxinA (Xeomin)• onabotulinumtoxinA (Botox)• rimabotulinumtoxinB (Myobloc)

Quiz: What is the diagnosis?

Final Points

• There are many types and causes for dystonia

• Do not miss:– DRD– Wilson’s disease– Pseudo-

The End