Dr Barry Snow. Neurologist Auckland District Health Board

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1 Dr Barry Snow Neurologist Auckland District Health Board

2 Dystonia and Parkinson s disease Barry Snow

3 Gowers 1888: Tetanoid chorea

4 Dystonia a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Dystonia is a: Clinical description Diagnosis

5

6 Involuntary Sustained Patterned Often repetitive Twisting movements Abnormal postures Rapid movements Tremor Head tremor Postural tremor of hands 25% of cervical dystonia Overflow Phenomenology

7

8

9 Pathophysiology Sensory disturbance Abnormal spatial discrimination Abnormal cortical representation of dystonic structure fusion of representational zones Aberrant or maladaptive brain plasticity

10 Classification of Dystonia Distribution Focal cervical dystonia, blepharospasm, spasmodic dysphonia, oromandibular dystonia, brachial dystonia Segmental For example, Meige syndrome, craniocervical dystonia, bibrachial dystonia Multifocal Hemidystonia Generalised Age of onset Early-onset ( 26 years) Late-onset (>26 years)

11 Focal dystonia: age of onset O Riordan S, Raymond D, Lynch T et al. Neurology 2004;63: WC 38.4 CD 40.8 SD 43.0 Bleph-oromand 55.7 DYT yrs

12 Cause Classification of Dystonia Primary (idiopathic) dystonia Secondary dystonia Associated with inherited neurological disorders Dystonia-plus syndromes Degenerative diseases Symptomatic of an exogenous or environmental cause Associated with Parkinson's disease and other parkinsonian disorders Dystonic phenomenology in another movement disorder

13

14

15 Dystonia Abnormal posturing Often with extra movements Responds to treatment Sometimes medications Botulinum toxin DBS Needs a neurologist!

16

17 Parkinsonism Tremor resting Slowness bradykinesia Stiffness rigidity Loss of balance

18

19 Olanow. Neurology 2009

20

21 Dopa Dopa Dopamine

22 Cause Dopamine deficit Tremor, rigidity, bradykinesia, postural impairment Dopamine replacement

23 Golbe 1990

24

25 Parkinson s divergent causes, convergent mechanisms (Science 21 May 04)

26

27 Braak 2005

28 Cause Dopamine deficit Tremor, rigidity, bradykinesia, postural impairment Dopamine replacement

29 Cause Cause Cause Cause Cause Mechanism Dopamine deficit Cortical Lewy bodies Other neurotransmitters Parkinsonism Dementia Sleep disturbance Pain Levodopa complications Depression Autonomic dysfunction Falls

30 Dopaminergic Parkinsonism Motor fluctuations and dyskinesia 5 years 10 years

31 5 years 10 years anosmia RBD anxiety depression pain Falls autonomic failure dementia Non-Dopaminergic

32 Dopaminergic Parkinsonism Motor fluctuations and dyskinesia Diagnosis and early treatment Motor complications General neurodegeneration 5 years 10 years anosmia RBD anxiety depression pain Falls autonomic failure dementia Non-Dopaminergic

33 Hely 2008

34 Kempster Brain 2010

35 Does early treatment lead to better later PD status?

36 % dyskinesia <70 > Levodopa Ropinirole Adapted from Rascol 054 Study

37 Initial treatment Young patients: dyskinesia Dopamine agonists (ropinirole 3 mg tds) Old patients: dementia Levodopa (100 mg tds)

38 Ropinirole Adverse Events (compared to levodopa) Ropinirole Levodopa Nausea 48.6% 36.7% Somnolence Hallucination Edema

39 Agonists and disinhibition Gambling Impulsive sexual behaviour Shopping Eating Punding

40

41 Levodopa Levodopa Dopamine

42

43 Nyholm. Clinical Neuropharmacology 2002;25:89

44 Levodopa Enzyme Inhibition entacapone carbidopa tolcapone selegiline rasagiline modified from Olanow et al. Neurology 2001;56(11 Suppl 5) S1-88)

45 COMT inhibition: Entacapone 200mg with each dose of levodopa Easy to use Minimal diarrhoea 2.5% Not as powerful as tolcapone

46

47 COMT inhibition: Tolcapone mg tds do not adjust the dose Powerful More levodopa side effects More diarrhoea - 12% Need to monitor liver function

48 Fraction 1.2 Blood dopa fraction Tol Time (minutes)

49 Fraction Time (minutes)

50 Apomorphine Morphine decomposition product by boiling with concentrated acid Occasionally used to enhance erectile function Non-selective dopamine agonist Suitable for parenteral use

51 Apomorphine

52

53

54 Deep Brain Stimulation

55

56 3387S-4X Electrodes 1.5mm apart; over 10.5mm 3389S-4X Electrodes 0.5mm apart; over 7.5mm Body of Leads are 1.27mm diam.

57 Deuschl NEJM 2006

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