Treatment of parkinson’s disease

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

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
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6. Parkinson’s Disease
Characterized by: (Slow,Stiff,Shaky)
• Bradykinesia *
• Rigidity *
• Rest tremor--3-6Hz pill-rolling (absent 1/3)
• Postural instability
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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
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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
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9. Parkinson’s Syndromes
Metabolic causes--
• Hypothyroidism
• Hypoparathyroidism
• Alcohol withdrawl (pseudoparkinsonism)
• Chronic liver failure
• Wilson’s disease
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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
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11. P. Syndromes
Structural Causes—
• Strokes
• Tumors
• Chronic subdurals
• NPH (Normal Pressure Hydrocephalus)
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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
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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.
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14. P. Syndromes
CBD (cortico basal degeneration)---
---Asymmetric parkinsonism
---postural instability
---ideomotor apraxia
---aphasia
---alien limb phenomenon
---impaired cortical sensations
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15. P. Syndromes
Multi System Atrophy-- (alpha-synuclein +
glial cytoplasmic inclusions, autonomic
dysfunction, pyramidal signs)
• Shy Drager Syndrome,
• Olivopontocerebellar atrophy,
• Striatonigral degeneration
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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
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17. P. Syndromes
Infections---
• encephalitis
• HIV/AIDS
• Neurosyphilis
• Toxoplasmosis
• CJD (Creuzfeld Jakob)--prion disease
• Progressive multifocal
leukoencephalopathy
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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
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19. P. Disease
??DIAGNOSIS??
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20. P. Dis -- Diagnosis
• A clinical diagnosis
• Cardinal features: Bradykinesia, rigidity
• Trial of sinemet (Levodopa/carbidopa)
• Confirmatory test: neuropathologic
(autopsy)
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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
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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
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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)
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24. P. Disease-Diagnosis
Alternative Diagnosis cont’d…
• Cerebellar signs
• Positive Babinski
• Apraxia
• Gaze abnormailities
• Dementia concurrently with Parkinsonism
• Strokes
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25. P. Disease
INVESTIGATIONS:
• TSH
• Calcium, albumin
• CT head
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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
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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)
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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
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29. PD-case
“I don’t have Parkinson’s Disease!!”
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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
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31. IADL
Instrumental Activities of Daily Living
• S shopping
• H housework
• A accounting
• F food preparation
• T transportation
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32. ADL
Activities of Daily Living
• D dressing
• E eating
• A ambulation
• T toiletting
• H hygiene
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33. PD- case 1
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34. PD-case 1
clock
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35. PD –Case 1
Diagnosis:
Parkinson’s disease ---Hoehn & Yahr’s**
stage 2
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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.
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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 fallsBrought to you by

38. PD-case 1
clock
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39. PD—other issues
• Depression
• Dementia
• Driving
• Falls
• Neuropsychiatric features
• “slowing down of thought processes” (the
clock in Mr AB)
• Constipation
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40. PD-Treatment
????
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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
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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
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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)Brought to you by

44. PD- medications
LevodopaLevodopa
• 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
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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
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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
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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
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48. PD- medications
L-dopa cont’d
• Discontinuation—
- gradually –over weeks,
- to prevent malignant neuroleptic like
syndrome or akinetic crisis
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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
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50. PD- medications
COMT – inhibitorCOMT – 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
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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
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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
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53. PD-medications
AnticholinergicsAnticholinergics—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
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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
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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”
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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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