ETIOLOGY

The etiology of Parkinson disease is still unclear, most cases are

hypothesized

to

be

due

to

combination

of

genetic

and

environmental factors.
Enviroment causes : use of pesticides, living in a rural
environment, consumption of well water, exposure to herbicides,
and proximity to industrial plants or quarries. 5
MPTPinterference with mitochondrial function
self injection of 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP) MPTP crosses the blood-brain barrier oxidized by
monoamine oxidase (MAO)-B 1-methyl-4-phenylpyridinium
(MPP+) MPP+ accumulates in mitochondria and interferes with
the function of complex I of the respiratory chain. A chemical
resemblance between MPTP and some herbicides and pesticides
suggested that an MPTP-like environmental toxin might be a
cause of Parkinson disease developed bradykinesia, rigidity,
and tremor, which progressed over several weeks.

ETIOLOGY
Oxydation hypothesis
free radical damage, resulting from dopamine's oxidative metabolism,
plays a role in the development or progression of Parkinson disease.
Genetic Factors
The identification of a few families with familial Parkinson disease
sparked further interest in the genetics of the disease. In one large
family in Salerno, Italy, 50 of 592 members had Parkinson disease;
linkage analysis incriminated a region in bands 4q21-23, and
sequencing revealed an A-for-G substitution at base 209 of the alphasynuclein gene.
Alpha-sysnuclein comformational changes and aggregation
Abnormally aggregated alpha-synuclein is the major component of
Lewy bodies and Lewy neurites, which are characteristic pathologic

PATOPHYSIOLOGY

The

term

Parkinsons

disease

refers

to

group

of

neurodegenerative conditions that affect several regions of the

brain (the pigmented nuclei in midbrain and brainstem, the
olfactory tubercle, the cerebral cortex, and elements of the
peripheral nervous) paucity and slowness of movement
(akinesia, bradykinesia), muscle stiffness (rigidity), and tremor
at rest.

In large part, these problems result from the prominent

degeneration of dopaminergic neurons in the midbrain, and the
consequent deficiency of dopamine in brain areas that receive
dopaminergic inputs from those neurons, specifically the post-

Motor sign:

HISTORY

typically asymmetric, with the most common initial

finding being an asymmetric resting tremor in an upper
extremity.
patients notice symptoms related to progressive
bradykinesia, rigidity, and gait difficulty

Nonmotor sign:
patients have a substantial reduction in olfactory
function (smell) by the time motor signs emerge.
constipation and excessive daytime sleepiness,
excessive saliva, forgetfulness, urinary urgency,

HISTORY
Common early motor signs of Parkinson disease
include tremor, bradykinesia, rigidity, and dystonia.
1. Tremor
shakiness or nervousness and usually begins
in one upper extremity and initially may be
intermittent
Classically, the tremor of Parkinson disease is
a resting tremor (occurring with the limb in a
resting position) and disappears with action or
use of the limb
Tremor can vary considerably, emerging only
with stress, anxiety, or fatigue.

Features
differentiating
Parkinsons
disease from
essential
tremor

History
2. Bradykinesia
refers to slowness of movement.
subjective sense of weakness, without true weakness on
physical examination; loss of dexterity, sometimes described
by patients as the "message not getting to the limb";
fatigability; or achiness when performing repeated actions.
Facial bradykinesia : decreased blink rate and facial expression.
Speech may become softer, less distinct, or more monotonal,
speech is become slurred, poorly articulated, and difficult to
understand.
Truncal bradykinesia : slowness or difficulty in rising from a
chair, turning in bed, or walking. If walking is affected, patients
may take smaller steps and gait cadence is reduced. Some
patients experience a transient inability to walk, as though
their feet are frozen to the floor.
In upper extremities : small, effortful handwriting (ie,
micrographia) and difficulty using the hand for fine dexterous
activities such as using a key or kitchen utensils.
In the lower extremities, unilateral bradykinesia commonly
causes scuffing of that foot on the ground, as it is not picked up

History
3. Dystonia
Defined as symptom onset before age 40 years.
Commonly consists of a foot involuntary turning in
(inversion) or down (plantar flexion)
Often associated with cramping or aching in the
leg.
Dorsiflexion of the big toe may also occur.
Adduction of the arm and elbow, causing the hand
to rest in front of the abdomen or chest. Dystonic
postures can wax and wane, occurring with
fatigue or exertion.

History
4. Rigidity
individuals may describe a feeling of
ratchety stiffness when moving a
limb, which may be a manifestation
of cogwheel rigidity.

HISTORY
Initial clinical symptoms in Parkinson disease include the following:
Tremor
A subtle decrease in dexterity; for example, a lack of coordination with activities such
as playing golf or dressing (about 20% of patients first experience clumsiness in one
hand)
Decreased arm swing on the first-involved side
Soft voice
Decreased facial expression
Sleep disturbances
RBD, in which there is a loss of normal atonia during REM sleep: In one study, 38% of
50-year-old men with RBD and no neurologic signs went on to develop parkinsonism;
patients act out their dreams and may kick, hit, talk, or cry out in their sleep
Decreased sense of smell
Symptoms of autonomic dysfunction, including constipation, sweating abnormalities,
sexual dysfunction, and seborrheic dermatitis
A general feeling of weakness, malaise, or lassitude
Depression or anhedonia
Slowness in thinking8