Dystonia 101 (& 102)
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Transcript of Dystonia 101 (& 102)
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Dystonia 101 (& 102)
John Fang, M.D.September 19, 2011
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Key Topics
• Types of Dystonia:– Primary vs. Secondary– Dopa-Responsive– Kinesigenic
• Genetic Dystonias• Basic Management Strategies
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Dystonia Vocabulary
• Blepharospasm• Craniocervical (Meige) • Oromandibular
• Focal• Segmental• Hemi-• Generalized
• Geste Antagonist (Sensory Trick)
• Tardive
• ε-Sarcoglycan• TorsinA
• Westphal variant• Wilson’s disease
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Generalized Dystonia
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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
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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
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Wilson’s Disease Treatment• Acute treatments: – Penicillamine– Trientene– TTMB
• Long-term treatments:– Zn– low Cu diet– Liver transplant
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Pseudo-Dystonia• Atlanto-axial subluxation• CN IV palsy
• Camptocormia (Bent spine)• Pleurotonus (Pisa syndrome)
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Degenerative Dystonias• CBD– Alien-limb
• Lubag – aka DYT3 – x-linked– Philippines
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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
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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)
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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
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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
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Botulinum Toxin Formulations
• abobotulinumtoxinA (Dysport)• incobotulinumtoxinA (Xeomin)• onabotulinumtoxinA (Botox)• rimabotulinumtoxinB (Myobloc)
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Quiz: What is the diagnosis?
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Final Points
• There are many types and causes for dystonia
• Do not miss:– DRD– Wilson’s disease– Pseudo-
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The End