Management of parkinson’s disease.

1. Management of parkinson’s disease. Dr. Sanjiv Chandratre. Consultant in med. for elderly 2010

2. What you should expect from this teaching session. • How to diagnose PD. • What is the D/D of PD • How to treat PD ( Medical treatment.) • When to refer pts to secondary care. • Tricks of the trade in managing special problems related to PD. • What services are available in our area for PD patients. • Nice guidelines on PD and results of our audit.

3. James parkinson 1817 • Involuntary tremulous motion, with lessened muscular power, in part not in action and even when supported;with a propensity to bend the trunk forward, and to pass from a walking to a running pace: the senses and intellect being uninjured.

4. Terminology in P. D. • Parkinson’s disease or Idiopathic P. D. • Parkinsonism / Parkinsonian syndrome. • Drug induced Parkinsonism. • Post encephalitic parkinsonism. • Vascular pseudo Parkinsonism. • Lower body parkinsonism.

5. Terminology in P. D. • Parkinsonism plus syndrome. • PSP • MSA • CBD

6. Parkinson’s disease • Progressive, disabling and distressing • Appropriate management and planning right from the start can prevent some of the most distressing features • Team work can solve most of the problems and can help deliver better care cost effectively • The 4 stages….

7. 4 stage clinical management scale • Diagnosis • Maintenance therapy • Complex • Palliative care

8. Incidence Number of new cases in a population, usually /100,000 Around 11 per 100,000 Prevalence Total number of people in a population with the condition, I.e.cumulative incidence per annum minus deaths. Around 100- 200 per 100,000 Incidence and Prevalence

9. Per GP. Say 2500 Per district / pct. Say 200,000 Prevalence

10. Brain Bank Criteria • Step 1 • Diagnosis of parkinsonian syndrome • Step2 • Exclusion criteria for IPD • Step3 • Supportive criteria for IPD

11. Step1- Diagnosis of parkinsonian Syndrome. • Bradykinesia +at least one of the following • Muscular rigidity • 4 –6 Hz resting tremor • Postural instability

12. Brady / Hypokinesia • Hypokinesia –poverty of movement • Loss of facial expression, arm swing, gesture etc. • Bradykinesia -Slowness of movement • ‘Decay’ – finger/ heel tap

13. Rigidity • Resistance to passive movement • Reinforcement – ‘froment’s manoeuvre’ • Constant [ c. f. ‘clasp-knife’] • ‘Lead pipe’ • ‘cogwheel’ • Gagenhalten

14. Tremor • Involuntary rhythmical alternating movement • Begins unilaterally – upper limb • 4 – 6 hertz, ‘pill rolling’ • First symptom in 75% • - 20 % never develop it • Postural tremor can also occur

15. Postural instability. • Last cardinal feature to appear • Limited diagnostic specificity in the elderly. • Pull test • Early falls – ‘red flag’

16. Step 2 – exclusion criteria • History of repeated strokes. • History of repeated head injury. • History of definite encephalitis. • Cerebellar signs. • Early severe autonomic involvement • Supranuclear gaze palsy • Neuroleptic drugs • Negative response to large doses of levodopa

17. Step3- positive supportive criteria • [>3 for ‘definite’ PD ] • Unilateral onset. • Rest tremor • Progressive • Persistent asymmetry • Excellent levodopa response • Severe levodopa induced chorea • Levodopa response>=5years • Clinical course>=10 years

18. Diagnosis- Accuracy • Meara 1999 Age and ageing • Community study- 402 cases • 73 % Parkinsonism • 53% ‘probable’ IPD • Essential tremor • Alzheimer’s disease • vascular

19. Accuracy of diagnosis • Brain bank post mortem series • 24 % error rate. • 10 % latest studies. • 2% MD specialists. • Community series • >50 % error rate

20. Is the diagnosis correct? • Diagnosis of P. D. can be very difficult. • There is no diagnostic test. • Diagnosis is made clinically. • DAT scan of limited value. • Error rate is high. 25 % in the hands of neurologist. Upto 50 % in the community. • F.U. and review of diagnosis is important.

21. Parkinson’s disease Progressive Supranuclear Palsy Multiple System Atrophy Essential Tremor Neuroleptic-induced Parkinsonism Vascular disease Dopamine Transporter Imaging agent

22. Differential diagnosis of parkinsonian syndrome • Idiopathic Parkinson’s disease • Drug induced – phenothiazines • Multiple cerebral infarct state. • Trauma – pugilistic encephalopathy • Toxin induced- MPTP, CO, Mn, Cu, • Parkinson’s plus syndromes

23. Essential tremor • Most common diagnostic error. • 10 times more common than PD. • Postural or action tremor. • Titubation. • Family history. • B – Blockers help.

24. Drug induced parkinsonism. • Causes • Predictable Neuroleptic drugs (both typical and atypical) Hidden neuroleptics- metoclopromide, prochlorperazine Combination with antidepressants( fluphenazine ) Calcium antagonist --Idiosyncratic Lithium, sodium valproate, amiodarone mainly tremor but parkinsonism reported.

25. Multiple infarct state • Synonymous with leucoariosis, Binswanger’s encephalopathy • Related to hypertension and other risk factors • Common misdiagnosis. • Poor prognosis • Aspirin and dipyridamole retard may be effective and safe

26. Vascular parkinsonism • PM studies 2-3 %incidence of ‘pure’ vascular causes -no lewy bodies or nigral degeneration Acute or abrupt onset basal ganglia infarct Insidious progression Diffuse sub cortical white matter ischaemia.

27. Fluctuating alertness Hallucinations Mild parkinsonism Neuroleptic sensitivity Tremor less common More symmetrical Myoclonus more common More rigid, less bradykinetic Dementia with Lewy bodies

28. Medical treatment of P. D. Only 18 drugs for PD in BNF 2008 14 Dopaminergic 4 Anticholinergic.

29. Drugs to avoid 1 • Antiemetics • Metoclopromide (Maxalon) • Prochlorperazine (Stemetil) • The only recommended antiemetics are • Domperidone • 5ht3 antagonists eg. Ondensetron.

30. Drugs to avoid 2 • Antipychotics • Chlorpromazine • Sulpride • Haloperidol • Thioridazine. • Newer antipsychotic can be used with caution

31. When to start treatment ? • Controversial • Is the diagnosis certain. • Age of patient. • Effect on ADL. • Patient Choice.

32. Drugs in PD • Levodopa preparations. • Dopamine receptor agonists. • Monoamine oxidase-B inhibitors. • Catechol-o-methyltransferase inhibitors. • Anticholinergics. • Amantadine

33. Levodopa • Used since the 1960’s • Remains the ‘gold standard’ • Always used with dopa decarboxylase inhibitor.( either carbidopa or benserazide.) • Side effects are common.

34. Levo dopa preparations. • Madopar or co beneldopa—Levodopa with benserazide • Sinemet or co careldopa—Levodopa with carbidopa

35. Levodopa formulations • Effervescent or dispersible eg. Madopar dispersible. • Conventional release.eg. Madopar • Controlled release.eg. Madopar CR orSinemet CR • Duodopa– As a gel.

36. Levodopa preparations • Dispersible preparations—Use for morning kick start or for on off fluctuations. Also in patients with swallowing difficulties. • CR preparations– unpredictable absorption. Use now mostly at night for nocturnal symptoms like difficulty turning in bed or AM dystonias

37. Side effects of levodopa • Very common • Nausea, vomiting • Excessive drowsiness • Insomnia • End of dose fluctuations. • Nocturnal immobility. • Motor fluctuations and dyskinesias.

38. Dopamine agonists • First available since 1970’s • Six DA’s available for oral use. • Apomorphine administered parenteraly • Act directly on post synaptic receptors. • Two types • Ergot derived. • Non ergot derived.

39. ERGOT Bromocriptin Lisuride Pergolide Cabergoline Non ERGOT Ropinirole Pramipexol Apomorphine. Dopamine agonists

40. Rotigotine • DA • Mono therapy or adjunct. • Patches.

41. Side effects of DA’s • Similar to levodopa • Nausea. • Vomiting. • Postural hypotension. • Confusion. • Hallucinations. • Somnolence.

42. Side effects of ERGOT DA’s • Fibrotic reactions. • Pulmonary, retroperitoneal and pericardial fibrosis. • Cardiac valvulopathy. • In most cases non ergot DA’s preferred. • CXR, PFT’s, ESR,and S. creatinine before starting treatment.

43. Unusual side effects of DA’s • Complex group of impulse control disorders • Pathological gambling. • Hypersexuality. • Compulsive eating or shopping. . Repetitive perseverative behavior. -- Punding -- Excessive hobbyism.

44. Unusual side effects of DA’s 2 • ‘Dopamine dysregulation syndrome’ • Compulsive use of increasing doses of levodopa • ‘hedonistic homeostatic dysregulation syndrome’. • 14% prevalence of ICD. • Eight fold increase in those taking DA’s • Young pts. are particularly prone.

45. SOOS • Excessive day time sleepiness and soos can occur with levodopa preparations and with DA’s • Warn patients about driving.

46. Amantidine • Antiviral properties. • Weak DA • Only for moderate to severe dyskinesia. • Glutamate antagonist. • 100 mg. BD or TDS

47. COMT inhibitors • Entacapone • Talcapone • In combination with levo dopa • ( STALEVO)

48. Stalevo • Combination of Levodopa, carbidopa and Entacapone. • 50 mg./12.5 mg./200 mg. • 100 mg./25mg./200mg. • 150 mg./37.5mg./200 mg. • 200 mg./50 mg./ 200 mg.

49. MAO -B inhibitors • Selegiline • 10 mg. Od or 5 mg. Bd • 2.5 mg in elderly. • Zelapar( oral lyophilisate ) 1.25 mg. Before breakfast. Place on tongue and allow to dissolve • Neuroprotective?? • Rasagiline • 1 mg. Expensive.

50. Antimuscarinic drugs. - Benzatropine, Procyclidine,Orphenadrine - Limited use. - Cognitive impairment in elderly. - Useful in drug induced Parkinsonism. - can be used for excessive salivation.