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DIAGNOSIS & TREATMENT OF PARKINSON’S DISEASE May 7, 2008 Sadhana Prasad Symposium on Changes and Challenges in Geriatric Care.

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Presentation on theme: "DIAGNOSIS & TREATMENT OF PARKINSON’S DISEASE May 7, 2008 Sadhana Prasad Symposium on Changes and Challenges in Geriatric Care."— Presentation transcript:

1 DIAGNOSIS & TREATMENT OF PARKINSON’S DISEASE May 7, 2008 Sadhana Prasad Symposium on Changes and Challenges in Geriatric Care

2 Disclosures Work with various pharmaceutical companies intermittently Honorarium will be donated

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5 OBJECTIVES 1. Illustrate medications and conditions that may mimic PD 2. Describe the early symptoms of Parkinson’s Disease (PD) 3. Discuss initiating and stopping medications

6 Parkinson’s Disease Characterized by: (Slow,Stiff,Shaky) Bradykinesia * Rigidity * Rest tremor--3-6Hz pill-rolling (absent 1/3) Postural instability

7 Parkinson’s Disease (PD) First description 1817 Parkinson, James An Essay on the Shaking Palsy, Sherwood, Neely, and Jones, London Progressive neurodegenerative disease Affects ages 40 onwards, mean age at diagnosis 70.5 Complex disorder with motor, non-motor, neuropsychiatric features

8 Disease vs Syndrome Disease = a morbid process having characteristic symptoms; pathology, etiology, and prognosis may be known Syndrome = a set of symptoms occurring together; different etiologies but similar presentation

9 Parkinson’s Syndromes Metabolic causes-- Hypothyroidism Hypoparathyroidism Alcohol withdrawl (pseudoparkinsonism) Chronic liver failure Wilson’s disease

10 P. Syndromes Medications**/chemicals— neuroleptics (typicals more than the atypicals), SSRI (selective serotonin reuptake inhibitors), metoclopromide/maxeran, Reserpine, MPTP, in Methcathinone (ephedrone) users – high plasma Manganese levels (NEJM Mar 6, 2008) CO, cyanide, organic solvents, carbon disulfide

11 P. Syndromes Structural Causes— Strokes Tumors Chronic subdurals NPH (Normal Pressure Hydrocephalus)

12 P.Syndromes Lewy Body spectrum of Diseases (DLB=Dementia with LB)--- ---early onset visual (or other) hallucinations ---fluctuating cognitive abilities ---sleep disorders ---neuroleptic sensitivity, even to atypicals

13 P. Syndromes PSP (progressive supranuclear palsy)—or Steeles Richardson Olszewski Syndrome ---gaze abnormalities ---postural instability, early unexplained falls ---bulbar features—dysphonia, dysarthria, dysphagia ---rapidly progressive---median 6 yrs.

14 P. Syndromes CBD (cortico basal degeneration)--- ---Asymmetric parkinsonism ---postural instability ---ideomotor apraxia ---aphasia ---alien limb phenomenon ---impaired cortical sensations

15 P. Syndromes Multi System Atrophy-- (alpha-synuclein + glial cytoplasmic inclusions, autonomic dysfunction, pyramidal signs) Shy Drager Syndrome, Olivopontocerebellar atrophy, Striatonigral degeneration

16 P. Syndromes Other Neurodegenerative Disorders— Alzheimer’s Disease, later stages** Huntington’s Disease (rigid form) Frontotemporal Dementia with Parkinsonism, Chromosome-17 linked (FTDP-17) Spinocerebellar ataxias

17 P. Syndromes Infections--- encephalitis HIV/AIDS Neurosyphilis Toxoplasmosis CJD (Creuzfeld Jakob)--prion disease Progressive multifocal leukoencephalopathy

18 P. Syndrome Essential Tremor--- ---action tremor (not rest tremor) ---more rapid (greater than 3-6 Hz) ---usually hands, but can also affect legs, head/chin, voice, trunk ---can present with falls if legs and trunk involved

19 P. Disease ??DIAGNOSIS??

20 P. Dis -- Diagnosis A clinical diagnosis Cardinal features: Bradykinesia, rigidity Trial of sinemet (Levodopa/carbidopa) Confirmatory test: neuropathologic (autopsy)

21 P. Disease-Diagnosis 1/3 will not respond to levodopa therapy 1/5 with P. Syndrome will respond to levodopa ---Follow- up with time needed to clarify diagnosis

22 P. Disease---Diagnosis Minimum therapeutic dose: ---300mg levodopa per day in divided doses ---can be lower in biologically old old ---vast majority will need 400-600mg levodopa daily to achieve significant benefit

23 P. Disease- Diagnosis Consider alternative diagnosis if: Early falls (postural instability) Poor response to levodopa Dysautonomia (urinary retention/atonic bladder, incontinence, orthostatic hypotension, impotence) No rest tremor (in 1/3)

24 P. Disease-Diagnosis Alternative Diagnosis cont’d… Cerebellar signs Positive Babinski Apraxia Gaze abnormailities Dementia concurrently with Parkinsonism Strokes

25 P. Disease INVESTIGATIONS: TSH Calcium, albumin CT head

26 OBJECTIVES 1. Illustrate medications and conditions that may mimic PD 2. Describe the early symptoms of Parkinson’s Disease (PD) 3. Discuss initiating and stopping medications

27 PD- CASE Mr AB, married, active farmer, stressed care-giver Drove his wife to the clinic, wife to see me re agitated dementia One son also attended Mr AB –stressed care-giver, on paxil (SSRI)

28 PD- case Mr. AB--- stressed caregiver Slightly flexed posture Slightly bradykinetic Slightly diminished facial expression No difficulty turning, getting in/out of armless chair

29 PD-case “I don’t have Parkinson’s Disease!!”

30 PD- case Mr. AB--- 1 month later, referred re ? PD?? CT head, TSH, Ca normal Slowing down x 1 yr, hypophonia, denied trouble turning in bed but took 5 tries in clinic, trouble getting out of soft chair, stopped taking baths x 3 years, mild rest tremor R hand, trouble doing up buttons and laces

31 IADL Instrumental Activities of Daily Living S shopping H housework A accounting F food preparation T transportation

32 ADL Activities of Daily Living D dressing E eating A ambulation T toiletting H hygiene

33 PD- case 1

34 clock

35 PD –Case 1 Diagnosis: Parkinson’s disease ---Hoehn & Yahr’s** stage 2

36 Hoehn and Yahr scale 1. Unilateral involvement only, usually with minimal or no functional disability 2. Bilateral or midline involvement without impairment of balance 3. Bilateral disease; mild to moderate disability with impaired postural reflexes; physically independent 4. Severely disabling disease; still able to walk or stand unassisted 5. Confinement to bed or wheelchair unless aided Hoehn, MM, Yahr, MD. Parkinsonism: onset, progression and mortality. Neurology 1967; 17:427.

37 PD- case 1 MTO notified, “not to cancel license” Paxil * Sinemet regular 100/25 mg ½ tid, increase by ½ weekly till 1 tid Calcium and vitamin D3 2 months later, smiling, clock better, moving better, still flexed, no falls

38 PD-case 1 clock

39 PD—other issues Depression Dementia Driving Falls Neuropsychiatric features “slowing down of thought processes” (the clock in Mr AB) Constipation

40 PD-Treatment ????

41 OBJECTIVES 1. Illustrate medications and conditions that may mimic PD 2. Describe the early symptoms of Parkinson’s Disease (PD) 3. Discuss initiating and stopping medications

42 PD--Treatment Geared towards mobility—levodopa, dopamine agonists, MAO B inhibitors Rest tremor, cosmetic—anticholinergics (may worsen cognition) Postural imbalance—no pharmacological treatment; exercise, gait aids, prevent fractures (Ca, Vit D3, +/- bisphosphonates) Dyskinesias-- ?amantadine (no clear evidence) Almeida,QJ, Recent Patents on CNS Drug Discovery, 2008:3, 5--54

43 PD--Which pharmaceutical? In Elderly-- Levodopa/ carbidopa (sinemet) – regular vs CR (controlled release) or Levodopa/ benserazide (prolopa) – regular vs HBS COMT- inhibitor– entacapone (comtan)

44 PD- medications Levodopa Well-established, for bradykinesia and rigidity SE: nausea, orthostatic hypotension Combined with peripheral decarboxylase inhibitor (carbidopa, benserazide) to prevent conversion to dopamine in the periphery before it crosses blood brain barrier

45 PD- medications Levodopa (l-dopa) -- l-dopa / carbidopa = sinemet reg. or CR -- l-dopa / benserazide = prolopa, medopar or medopar HBS Competes with amino acids from protein for GI absorption Regular-- before meals, quick in quick out, T1/2 = 90 min CR--- With meals,Controlled Release, slow in slow out, need 30% more to achieve same effect as reg. dose, erratic absorption in elderly

46 PD-medications L-dopa cont’d SE- Nausea (Rx Domperidone) -Hallucinations (Rx lower dose, atypical n neuroleptics) -somnolence, confusion, agitation -motor fluctuations- after sev yrs of Rx

47 PD- medications L-dopa cont’d Motor fluctuations (in 50%, after 5-10yrs) -wearing-off– Rx COMT – inhibitor*, ?CR -dyskinesias –(??Rx amantadine??) -dystonias -variety of complex fluctuations in motor function

48 PD- medications L-dopa cont’d Discontinuation— -gradually –over weeks, -to prevent malignant neuroleptic like syndrome or akinetic crisis

49 PD-medications L-dopa cont’d Dopaminergic dysregulation syndrome (DDS)— tolerance to mood elevating effects -Compulsive use of dopaminergic drugs -Early onset males -Cyclical mood disorder -Impulse control disorder (hypersexuality, pathologic gambling) Giovannoni, G, Hedonistic homeostatic dysregulation…J. Neurol Neurosurg Psychiatry 2000; 68:243

50 PD- medications COMT – inhibitor -Catechol-O-Methyl Transferase Inhibitor -((eg Tolcapone (Tasmar)---off market due to fulminant hepatitis causing 3 deaths)) -eg Entacapone (Comtan) -for wearing-off at end-of-dose of L-dopa -dose 200mg-1600mg, divided, daily, with L-dopa -SE-diarrhea in 5%, due to increased dopaminergic stimulation from L-dopa availability

51 PD-medications Dopamine Agonists: adjunct Rx to L-dopa. -Ergotamines—bromocriptine, ((pergolide)), ((cabergoline)) SE-same as L-dopa, uncommon Raynaud’s, erythromelalgia, retroperitoneal/pulmonary fibrosis -Non-Ergot—pramipexole, ropinirole, ((transdermal rotigotine)) SE—same as L-dopa, Sudden somnolence – caution with driving

52 PD-medications MAO-B inhibitors- MAO-B inhibitors--adjunct Rx to L-dopa -eg selegiline (eldepryl), rasagiline -somewhat helpful in young, early in disease -neuroprotective properties in animal models only Arch Neurology. 2002; 59:1937

53 PD-medications Anticholinergics Anticholinergics—adjunct Rx to L-dopa, best avoided in elderly -acetylcholine (ACh) and dopamine in balance in basal ganglia -decrease Ach to balance decrease in L-dopa -eg trihexyphenidyl (artane), benztropine (cogentin), orphenadrine, procyclidine (kemadrin) -SE-confusion, hallucinations, dry mouth, blurred vision, constipation, nausea, u. retention, glaucoma

54 PD-medications Amantadine-adjunct to L-dopa, best avoided in elderly -for dyskinesias -Antiviral agent—mechanism unknown -NMDA-receptor antagonist properties- interferes with excessive glutamate -SE-livedo reticularis, ankle edema, hallucinations

55 PD- Medications When do you stop the medications? --ALWAYS taper gradually over days to weeks to avoid NM-like syndrome --unable to take meds (dysphagia) --significant, intolerable SE impairing QOL --end-stage--- “infection comes as a friend”

56 OBJECTIVES 1. Illustrate medications and conditions that may mimic PD 2. Describe the early symptoms of Parkinson’s Disease (PD) 3. Discuss initiating and stopping medications


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