Drug treatments for dystonia and spasticity

1. Drug treatments for dystonia and spasticity Jane Hassell, Paediatric Neurologist Kenya Paediatric Association Annual Scientific Conference 2019 Please do not film or take photos of the children shown in these slides. These images were shared with the Faculty for teaching purposes only. We do not have consent for their wider dissemination.

2. Objectives • To be able to recognise spasticity, dystonia and status dystonicus • To know the principles of management of status dystonicus • To be able to initiate first line medications for the long-term relief of spasticity and dystonia

3. Session outline • Management of acute dystonia • Long term drug management of hypertonia • New non-drug therapies

4. Spasticity, dystonia, or both? Cortex Corticospinal tracts Basal ganglia Cerebellum Brainstem, Cranial nerves Spinal cord Peripheral nerves SEIZURES are a symptom of cortical dysfunction MOTOR FUNCTION

5. Spasticity or dystonia? Spasticity Dystonia Something you see Posturing, co-contraction Involuntary alteration of intended movement • Something you feel • Velocity-dependent • Hyperreflexia, clonus “Scissoring legs” “Striatal toe”

6. Status dystonicus “Frequent/continuous severe episodes of generalised dystonic spasms or choreathetosis” Dev Med 2014, 56: 105-112

7. Status dystonicus • Painful, distressing, exhausting, treatable • Airway and respiratory compromise • High fluid losses (sweating) • Muscle breakdown • Risk of acute renal failure

8. Status dystonicus: Acute management • Identify and treat precipitants • Infection • Gastro-oesophageal reflux, constipation • Pain e.g. pressure sores, orthopaedic, dental • Medication withdrawal • Supportive care – ideally ICU/HDU • (Hyper)hydration • Pain relief, antipyretics • Monitor renal function, CK, urine

9. Status dystonicus meds: Immediate rescue: - Benzodiazepine – diazepam 100-300mcg/kg - Chloral hydrate 30-50mg/kg Maintain (acute illness): - If severe – clonidine infusion or 4-hourly – watch BP • Regular benzodiazepine – infusion or 8-hourly • Chloral hydrate 6 hourly PRN • Melatonin for sleep PLUSstart long-term prophylaxis acutely

10. Long-term anti-dystonia meds: Principles: • Start low, increase slowly (weekly) • Allow 4-8 weeks for effect • Titrate to improved dystonia/side effects • If a drug helps but still symptomatic at max tolerated dose, add another • If not helping, wean off slowly – 4-8 weeks

11. Long-term anti-dystonia meds: GABAPENTIN Mechanism: GABA agonist Good for: Painful dystonia, isolated dystonia, first line choice in status dystonicus. Main side effects: Sedation, gi symptoms Suggested dosing: Start at 5-10mg/kg daily, increase every 5-7 days to BD then TDS. Max 90mg/kg/day in 3 divided doses. Minimum tablet dose in Kenya 100mg. Syrup available.

12. Long-term anti-dystonia meds: BACLOFEN Mechanism: Not clear, ?GABAB agonist Good for: Mixed spasticity and dystonia/ CP Main side effects: Drowsiness, floppiness, drooling Suggested dosing: Start at 2.5mg OD, increase every 5-7 days to BD, TDS, max dose 2mg/kg/day. Minimum ¼ tablet dose in Kenya is 2.5mg.

13. Long-term anti-dystonia meds: TRIHEXYPHENIDYL (BENZHEXOL, ARTANE) Mechanism: M1 muscarinic AChR antagonist Good for: Dystonia Main side effects: Dry eyes, dry mouth, blurred vision, urine retention, constipation Suggested dosing: 1 - 2.5 mg/day, increase every 5-7 days to BD, TDS, then in mg increments up to 2mg/kg/day in 3 doses. Wide dose range. Minimum tablet dose in Kenya is 10mg.

14. Long-term anti-dystonia meds: L-DOPA (in CO-CARELDOPA = L-dopa + carbidopa) Mechanism: Dopamine replacement Specific indication: Dopa-responsive dystonias, worth a try in children with dystonia and normal MRI, OR with dystonic cerebral palsy of known cause Main side effects: Drowisness, sleep disorder, mood disorder/ euphoria, dystonia worse Suggested dosing:Sinemet– see formulary for dosing. Watch out for paradoxical worsening at higher doses. Lowest available in Kenya is 100mg L-dopa/tab. Break + dissolve.

15. Long-term anti-dystonia meds: CARBAMAZEPINE Mechanism: Sodium channel blocker Specific indication: Paroxysmal kinesigenic dyskinesia Main side effects: Drowsiness, dizziness Suggested dosing: Low – 5 – 10mg/kg/day

16. Spasticity or dystonia? Spasticity Dystonia Something you see Posturing, co-contraction Involuntary alteration of intended movement • Something you feel • Velocity-dependent • Hyperreflexia, clonus “Scissoring legs” “Striatal toe”

17. Long-term anti-spasticity meds: BACLOFEN Mechanism: Not clear, ?GABAB agonist Good for: Pure spasticity, mixed signs Main side effects: Drowsiness, floppiness, drooling Suggested dosing: Start at 2.5mg OD, increase every 5-7 days to BD, TDS, max dose 2mg/kg/day. Minimum ¼ tablet dose in Kenya is 2.5mg.

18. Are there any non-medication alternatives? • Specific tight muscle groups –botox (botulinum toxin injections) • Spasticity – selective dorsal rhizotomy • Dystonia – deep brain stimulation

19. Spasticity: Selective Dorsal Rhizotomy Selective cutting of dorsal nerve roots (sensory efferents) to reduce signals to spinal cord

20. Dystonia: Deep brain stimulation For primary and secondary dystonias. Corticospinal tract must be intact.

21. Summary • Differentiate spasticity from dystonia – they have different treatments. • Status dystonicus is a medical emergency, remember to treat exacerbating factors. • Long term medications can help relieve symptoms. Always start at low dose, increase slowly and allow time for them to work.