DR PRASHANT DUBEY
PG DEPARTMENT OF MEDICINE
SN MEDICAL COLLEGE,AGRA.
• Parkinson’s disease is the second commonest
neurodegenerative disease , exceeded only by
• The mean age of onset is about 60 years , but
cases can be seen in patients in their 20s, and
• Clinically, PD is characterised by rest tremor,
rigidity, bradykinesia and gait impairment
known as cardinal features of the disease
• Pathologically, the hallmark features of PD are
degeneration of dopaminergic neurons in the
substantia nigra pars compacta (SNc),reduced
striatal dopamine, and intracytoplasmic
proteinaceous inclusions known as Lewy
CLINICAL FEATURES OF PARKINSON’S DISEASE
CARDINAL FEATURES OTHER MOTOR FEATURES NON MOTOR FEATURES
Bradykinesia Micrographia Anosmia
Rest tremor Masked facies(hypomimia)
Rigidity Reduced eye blink Mood disorders ( e.g.
Soft voice(hypomimia) Sleep disturbances
Dysphagia Autonomic disturbances
Freezing Cognitive impairment /
BRADYKINESIA – which means slowness rather
than lack of movements . Not only is Parkinson’s
patient slightly slow off the mark , but the
velocity of movement, or the time from onset to
completion of movement is slower than normal.
Akinesia and bradykinesia can be distinguished
by equating akinesia with prolonged reaction
time and bradykinesia with prolonged time of
TREMORS – may be defined as more or less
involuntary and rhythmic oscillatory movement
produced by alternate synchronous contraction
of reciprocally innervated muscle.
Its rhythmic quality distinguishes it from
involuntary movements and involvement of
agonist and antagonist muscle distinguish it
Tremor frequency is 4-6 hz.
RIGIDITY –is increased tone that is present
throughout the range of motion(a lead pipe or
plastic stiffness) and affects flexors and
extensors equally.It sometime has a cogwheel
quality that is enhanced by voluntary movement
of the contralateral limb.
PARKINSONISM AND FESTINATING GAIT
The term festination derives from the latin word ”
to hasten” and appropriately describe the
involuntary activation or hastening that
characterizes the gait of patient with PD.
Diminished or absent arm swing , turning en block,
hesitation in starting to walk, shuffling or freezing
briefly when encountering obstacle. Once the
walking has startedthe upper part of the body
advances ahead of the lower part,and the patient is
impelled totake increasing short stepsas to catch up
with his center of gravity.
• Parkinsonism is a general term that is used to
define a symptom complex manifest by
bradykinesia with rigidity and/or tremor.
• It has a wide differential diagnosis and can reflect
damage to different components of basal ganglia.
• Clinicopathological correlation studies
determined that parkinsonism associated with
rest tremor , asymmetry and a good response to
levodopa was more likely to predict the correct
Genetic Multiple system
Drug induced Wilson,’s disease
Sporadic Cerebellar type Tumor Huntington’s disease
Parkinson type Infection Dystonia parkinsonism
brain iron accumulation
Alzheimer’s ds with
ATYPICAL AND SECONDARY
• Atypical parkinsonism refers to group of
neurodegenerative conditions that usually are
associated with more widespread
neurodegeneration that is found in PD.
• Parkinsonism in these conditions is often
characterised by early speech and gait
impairment, absence of rest tremor, no
asymmetry, poor or no response to levodopa,
and an aggressive clinical course.
• In the early stages, they may show some modest
benefit from levodopa and be difficult to
distinguish from PD.
• Multiple system atrophy(MSA) manifests as a
combination of parkinsonism, cerebellar, and
autonomic features and can be divided into a
predominant parkinsonism(MSA-p) or cerebellar
(MSA- c) form.
• Clinically, MSA is suspected when patient
presents with atypical parkinsonism in
conjunction with cerebellar signs and/or early
and prominent autonomic dysfunction usually
• Progressive supranuclear palsy(PSP) is a form
of atypical parkinsonism that is characterised
by slow ocular saccades, eyelid apraxia, and
restricted eye movements with particular
impairment of downward gaze.
ETIOLOGY AND PATHOGENESIS
• Most PD occurs sporadically(85-90%)
• Twin studies suggest that environmental factors
likely play the more important role in patients
older than 50 years, with genetic factors being
more important in younger patients.
• Epidemiological studies suggest increased risk
with exposure to pesticides, rural living and
drinking well water and reduced risk with
cigarette smoking and caffeine.
• It has been proposed that most cases of PD
are due to “double hit” involving an
interaction between a gene mutation that
induces susceptibility coupled with exposure
to a toxic environmental factor.
FEATURES SUGGESTING ALTERNATE DIAGNOSIS
SYMPTOMS/SIGNS ALTERNATE DIAGNOSIS TO CONSIDER
Early speech and gait impairment Atypical parkinsonism
Exposure to neuroleptics Drug induced parkinsonism
Onset prior to age 40 Genetic form of PD
Liver disease Wilson’s disease, Non Wilson’s hepatolenticular
Early hallucinations Dementia with Lewy Bodies
Poor or no response to levodopa Atypical or secondary parkinsonism
Dementia as first symptom Dementia with Lewy bodies
Prominent orthostatic hypotension MSA -p
Prominent cerebellar signs MSA - c
Impairment of down gaze PSP
High frequency(8-10 Hz) symmetric
postural tremor with a prominent
Since its introduction in late 1960s it is the
mainstay of treatment.
Inactive by itself, but immediate precursor of
On oral administration >90% is decarboxylated
in peripheral tissues
1-2%crosses brain and convertad to DA.
• Routinely administered with decarboxylase
inhibitor (Carbidopa , Benserazide) to prevent
peripheral metabolism to DA and
development of nausea vomiting due to
stimulation of DA receptors in area posterna
not protected by BBB.
• Benefits classic motor features of PD, prolongs
independence and employability, improves
quality of life and increases life span.
AT INITATION OF THERAPY-
1. Nausea and vomiting –In almost every
patient . Tolerance develops gradually.
2. Postural hypotension
3. Cardiac arrhythmias due to B adrenergic
4. Exacerbation of angina axn of DA
5. Alteration in taste sensation
AFTER PROLONGED THERAPY –
1.Fluctuation in motor performance – After 2-5
years control of symptomatology shows
”END OF DOSE” detoriation (wearing off)which
is intially gradual, develops into rapid
“SWITCHES” or “ON-OFF EFFECT”.
With time “ALL OR NONE RESPONSE” develops.
2.Abnormal movements – Facial tics, grimacing ,
choreoathetosis of limbs etc. Starts appearing
after few months and progress with time. No
3. Behavioural effects-Range from mild anxiety,
nightmares to severe depression , mania,
hallucinations, mental confusion or frank
CAUSE – Excessive DA action in limbic system.
CAUTIONS – Ischemic heart disease, CVA,
hepatic and renal disease, peptic ulcer ,
DOPAMINE AGONIST –
Act directly on DA receptors.
Do not require metabolism to active product like
Initial DA agonists were ergot derivatives
(eg bromocriptine, pergolide, cabergoline)
which were associated with ergot related side
Replaced by second generation non ergot DA
agonists(eg pramipexole , ropinirole, rotigotine)
Do not have comparable efficacy to levodopa.
Initially introduced as adjunct to levodopa to
enhance motor function and reduce “off” time
in fluctuating patients.
Long acting, less prone than levodopa to induce
Pramipexole,ropinirole administered orally.
Rotigotine as transdermal patch.
APOMORPHINE –Very short half life and
duration of activity.
Side effects –
Nausea, vomiting, orthostatic hypotension,
hallucinations, cognitive impairment . Sedation
and unintended episodes of falling asleep.
Impulse control disorders, hypersexuality,
compulsive eating and shopping.
Most alarming side effect is valvular heart
MAO – B INIBITORS -
Block central DA metabolism and increase
sympathatic concentration of DA.
Selegiline and Rasagiline.
Provide modest benefit when used as
monotherapy, and reduced off time when used
as adjunct to levodopa in patients with motor
Safe and well tolerated.
Increases dyskinesia in levodopa treated
CHEESE REACTION – Inhibition of MAO-A
isoform prevents metabolism of tyramine in gut
leading to fatal hypertensive reaction.
Precipitated by, food rich in tyramine eg- cheese,
aged meats , red wine.
MPTP toxicity can be prevented by
coadministration of MAO – B inhibitors that
blocks its conversion to toxic pyridinium ion
COMT INHIBITORS –
Increases elimination half life of levodopa and
increases brain availability.
Combining levodopa with COMT inhibitor
reduces “OFF” time and prolongs “ON” time in
Tolcapone and entacapone.
Side effects – Nausea, vomiting increased
dyskinesia, discoloration of urine.
Tolcapone – Severe diarrhoea
CENTRAL ACTING ANTI CHOLINERGICS –
Major clinical effect on tremor.
Use is limited particularly in elderly.
Side effects – urinary dysfunction, glaucoma,
AMANTADINE – Historical importance.
Introduced as antiviral agent.
Anti parkinsons effect due to NMDA receptor
Antidyskinesia agent in advanced PD.
Side effects – Livido reticularis,weight gain,
Should be discontinued slowly as patients
experience withdrawl symptoms.
NEUROPROTECTION – Trials of promising agents
as rasagiline, selegiline, coenzyme Q
10,pramipexole and ropinirole have positive
results in clinical trials consistent with disease
AGENT AVAILABLE DOSE TYPICAL DOSE
Entacapone 200mg 200mg with each
Tolcapone 100,200mg 100-200mg
Selegiline 5mg 5mg bid
Rasagiline 0.5,1.0mg 1.0mg /d
SURGICAL TREATMENT- Most surgical
procedures utilize deep brain stimulation.
Primarily targets STN or GPI.
1.Requires a dose of levodopa which produces
3.Patient who is constantly cycling between on
and off period.
Q 1.Which of the following is not a risk factor for
c)Drinking well water
Q 2.Which of the following drug is not used in
c)MAO – A inhibitors
d)MAO – B inhibitors
Q 3. Which of the following is not a feature of
• Q4 What is the characterstic inclusion body
found in PD?
• A) lewy body
• B) lofora body
• C)nicolous body
• D)ashcoff body
• Q4.Most comman age of presentation of PD?
• A)In childhood
• Q5. A patient present with features eyelid
apraxia ,restricted eye movement&history of
repeated fall what is probable diagionsis?
• a)multiple system atrophy
• B)cortico basal ganglion degeneration
• C)progressive supranuclear palsy
• D)frontotemporal dementia