DIAGNOSIS & TREATMENT

OF PARKINSONS DISEASE
May 7, 2008
Sadhana Prasad

Symposium on Changes and
Challenges in Geriatric Care
Disclosures
Work with various pharmaceutical
companies intermittently
Honorarium will be donated

OBJECTIVES

1. Illustrate medications and
conditions that may mimic PD
2. Describe the early symptoms of Parkinsons
Disease (PD)
3. Discuss initiating and stopping medications
Parkinsons Disease
Characterized by: (Slow,Stiff,Shaky)
Bradykinesia *
Rigidity *
Rest tremor--3-6Hz pill-rolling (absent 1/3)
Postural instability

Parkinsons 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
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
Parkinsons Syndromes
Metabolic causes--
Hypothyroidism
Hypoparathyroidism
Alcohol withdrawl (pseudoparkinsonism)
Chronic liver failure
Wilsons disease


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




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

P. Syndromes
CBD (cortico basal degeneration)---
---Asymmetric parkinsonism
---postural instability
---ideomotor apraxia
---aphasia
---alien limb phenomenon
---impaired cortical sensations
P. Syndromes
Multi System Atrophy-- (alpha-synuclein +
glial cytoplasmic inclusions, autonomic
dysfunction, pyramidal signs)
Shy Drager Syndrome,
Olivopontocerebellar atrophy,
Striatonigral degeneration


P. Syndromes
Other Neurodegenerative Disorders
Alzheimers Disease, later stages**
Huntingtons Disease (rigid form)
Frontotemporal Dementia with
Parkinsonism, Chromosome-17 linked
(FTDP-17)
Spinocerebellar ataxias
P. Syndromes
Infections---
encephalitis
HIV/AIDS
Neurosyphilis
Toxoplasmosis
CJD (Creuzfeld Jakob)--prion disease
Progressive multifocal
leukoencephalopathy
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

P. Disease

??DIAGNOSIS??
P. Dis -- Diagnosis


A clinical diagnosis
Cardinal features: Bradykinesia, rigidity
Trial of sinemet (Levodopa/carbidopa)
Confirmatory test: neuropathologic
(autopsy)
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
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
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)
P. Disease-Diagnosis
Alternative Diagnosis contd
Cerebellar signs
Positive Babinski
Apraxia
Gaze abnormailities
Dementia concurrently with Parkinsonism
Strokes
P. Disease

INVESTIGATIONS:
TSH
Calcium, albumin
CT head

OBJECTIVES

1. Illustrate medications and conditions that may
mimic PD
2. Describe the early
symptoms of Parkinsons
Disease (PD)
3. Discuss initiating and stopping medications
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)


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


PD-case



I dont have Parkinsons Disease!!
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


IADL
Instrumental Activities of Daily Living
S shopping
H housework
A accounting
F food preparation
T transportation
ADL
Activities of Daily Living
D dressing
E eating
A ambulation
T toiletting
H hygiene
PD- case 1
PD-case 1
clock
PD Case 1

Diagnosis:

Parkinsons disease ---Hoehn & Yahrs**
stage 2
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.
PD- case 1
MTO notified, not to cancel license
Paxil *
Sinemet regular 100/25 mg tid, increase
by weekly till 1 tid
Calcium and vitamin D3

2 months later, smiling, clock better,
moving better, still flexed, no falls
PD-case 1
clock
PDother issues
Depression
Dementia
Driving
Falls
Neuropsychiatric features
slowing down of thought processes (the
clock in Mr AB)
Constipation


PD-Treatment



????
OBJECTIVES

1. Illustrate medications and conditions that
may mimic PD
2. Describe the early symptoms of
Parkinsons Disease (PD)
3. Discuss initiating and
stopping medications
PD--Treatment
Geared towards mobilitylevodopa, dopamine
agonists, MAO B inhibitors
Rest tremor, cosmeticanticholinergics (may
worsen cognition)
Postural imbalanceno 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
PD--Which pharmaceutical?
In Elderly--
Levodopa/ carbidopa (sinemet) regular
vs CR (controlled release)
or
Levodopa/ benserazide (prolopa) regular
vs HBS

COMT- inhibitor entacapone (comtan)


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
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

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

PD- medications
L-dopa contd

Motor fluctuations (in 50%, after 5-10yrs)
-wearing-off Rx COMT inhibitor*, ?CR
-dyskinesias (??Rx amantadine??)
-dystonias
-variety of complex fluctuations in motor
function

PD- medications
L-dopa contd
Discontinuation
- gradually over weeks,
- to prevent malignant neuroleptic like
syndrome or akinetic crisis

PD-medications
L-dopa contd
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 dysregulationJ. Neurol Neurosurg Psychiatry
2000; 68:243

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


PD-medications
Dopamine Agonists: adjunct Rx to L-dopa.
-Ergotaminesbromocriptine, ((pergolide)),
((cabergoline))
SE-same as L-dopa, uncommon Raynauds,
erythromelalgia, retroperitoneal/pulmonary
fibrosis
-Non-Ergotpramipexole, ropinirole, ((transdermal
rotigotine))
SEsame as L-dopa, Sudden somnolence
caution with driving
PD-medications
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

PD-medications
Anticholinergicsadjunct 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


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

1. Illustrate medications and conditions that
may mimic PD
2. Describe the early symptoms of
Parkinsons Disease (PD)
3. Discuss initiating and stopping
medications