Presentasi Kasus

PARKINSON

Pembimbing: dr. Imam Suhada, Sp.S

Nama: Akhmad

NIM: 03011013

Kepaniteraan Klinik Ilmu Penyakit Saraf

RS TNI AL Mintohardjo

Periode 12 Juni 22 Juli 2017

Fakultas Kedokteran Universitas Trisakti

 INTRODUCTION

Parkinsons disease (PD) was first described by Dr. James Parkinson in 1817 as a shaking palsy.
It is a chronic, progressive neurodegenerative disease characterized by both motor and nonmotor
features. The disease has a significant clinical impact on patients, families, and caregivers through its
progressive degenerative effects on mobility and muscle control. The motor symptoms of PD are
attributed to the loss of striatal dopaminergic neurons, although the presence of nonmotor symptoms
supports neuronal loss in nondopaminergic areas as well.1 The term parkinsonism is a symptom
complex used to describe the motor features of PD, which include resting tremor, bradykinesia, and
muscular rigidity. PD is the most common cause of parkinsonism, although a number of secondary
causes also exist, including diseases that mimic PD and drug-induced causes.2

Research suggests that the pathophysiological changes associated with PD may start before the
onset of motor features and may include a number of nonmotor presentations, such as sleep disorders,
depression, and cognitive changes. Evidence for this preclinical phase has driven the enthusiasm for
research that focuses on protective or preventive therapies.3

PD is one of the most common neurodegenerative disorders. The Parkinsons Disease

Foundation reports that approximately 1 million Americans currently have the disease.5 The incidence
of PD in the U.S. is approximately 20 cases per 100,000 people per year (60,000 per year).4

Numerous risk factors and genetic mutations are associated with PD. Risk factors for the disease
include oxidative stress, the formation of free radicals, and a number of environmental toxins.
Interestingly, an inverse relationship exists between cigarette smoking, caffeine intake, and the risk of
developing PD. Inhibition of the enzyme monoamine oxidase (MAO) may explain the protective effects
of tobacco smoking, whereas the benefits of caffeine may be related to its adenosine antagonist
activity.5
 CASE REPORT

PATIENTS IDENTITY

Name : Mr. P

Age : 60 years old

Sex : Male

Marital status : Married

Religion : Islam

Educational background: Middle High School

Occupation : Unemployee

Address : Sumenep, Madura

Admission date : 7 July 2017

Medical record number: 181887

I. Anamnesis
Alloanamnesis with his wife, July 7th, 2017:

1. Chief Complaints :
The whole body was shaking for 3 days

2. Additional Complaints :
Difficult to eat and drink

Whole body stiffness

3. History of present illness

The patient was brought into RSAL DR. Mintohardjo Emergency Room after suffering from the
whole body shake for 3 days. Actually this shaking movement has began from 3 years ago but just
located in the head. In the past 3 days this shaking movement spread to the whole body including his
jaw. Because of that, this patient has difficulities to eat and drink. This shaking movement can be clearly
seen specially when he is at rest and decrease when he start to move. The patient didnt eat and drink
for the past 3 days. He also have difficulities to walk because of the whole body stiffness. When he walk,
he can began to walk just with a small step, hard to stop, also cant to turn right or left. He needs a time
to turn the position to the wanted direction. It is often, when he walked, he just lost his stability and
sometime he just fall to the ground. There is no sign or symptom like hallucination or cognitive
deteoritation.

4. Past medical history :

No history of hypertension (-) diabetes mellitus (-) head injury (-) psycotic disorder (-)

5. Family medical history :

Older brother died because the lungs problem

II. Physical examination

1. Counciousness :
Glasgow Coma Scale : E4 M6 V5

Vital sign :

Blood pressure : 120/80

Pulse rate : 80 x/min, regular

Respiratory rate : 20 x/min

Temperature : 36,6oC

Oxygen saturation : 99%

2. General examination

Head

Size : Normocephal

Hair : Strong, grey hair and evenly distributed

Eyes

Conjunctiva pallor : -/-

Scleral icterus : : -/-

Pupil : : Isocoria, DLR +/+, NDLR +/+

Mouth
Cyanosis, dryness :-

Tongue (Fasiculation) :-

Deviation: -

Neck

Lymph nodes : Not palpable

Neck stiffness :-

Thorax

Lungs

Vesicular breathing sounds : +/+

Ronchi : -/-

Wheezing : -/-

Pulsasi ictus cordis : Not clearly seen

Heart

S1S2 : Regular

Murmur, gallop :-

Abdomen

Supel :+

Bowel sound : +, normal

Organ enlargement :-

Upper and Lower Extremities

Warm extremities :

Edema :

3. Neurological examination

a. Meningeal Signs
Neck stiffness : (-)
 Brudzinsky I : (-)

Brudzinsky II :-/-

Laseque :-/-

Kernig :-/-

b. Speech
Motor aphasia : (-)

Sensory aphasia : (-)

c. Coordination, gait, & balance

Gait : Not examined

Romberg test : Not examined

Disdiadokinetic : Not examined

Finger to Nose : Not examined

Dix-Hallpike : Not examined

d. Autonomic reflexes
Micturition : Not examined

Defecation : Not examined

Anal Reflex : Not examined

e. Abnormal movements
Tremor : +/+

Athetose : -/-

Myoclonic : -/-

Chorea : -/-

f. Cranial nerve examination

N.I (Olfactory nerve) : Not performed

N. II (Optic nerve) : Not performed

N. III (Oculomotor nerve)

Strabismus : (-)

Nystagmus : (-)

Exophtalmos : (-)
 Pupils : 3 mm / 3 mm isocoria

Direct light reflex : +/+

Indirect light reflex : +/+

N. IV (Throchlear nerve)

Eye movement (downward-inside) : +/+

Diplopia :(-)

N. V (Trigeminal nerve)

Mouth opening : not examined

Chewing : Not examined

Biting : Not examined

Cornea reflex : (+/+)

Face sensibility : Not responding

N. VI (Abducens nerve)

Eye movement (lateral) : (+/+)

Diplopia : (-)

N. VII (Facial nerve)

Furrowing forehead : (+), symmetrical

Closing eyes : Not responding

Puffing cheeks : Not responding

Showing teeth : symmetrical

Taste sensibility : Not examined

N. VIII (Vestibulocochlear nerve)

Swabach : Not examined

Rinne : Not examined

Weber : Not examined

N. IX (Glossopharyngeal nerve)
 Taste sensibility : Not examined

Pharynx sensibility : Not examined

N. X (Vagus nerve)

Pharyngeal arch : cant examined

Speaking : cant examined

Swallowing : cant examined

N. XI (Accessory nerve)

Uplifting shoulders : Not examined

Turning head aside : Not examined

N. XII (Hypoglossal nerve)

Tongue out : cant examined

Tongue movement : tremor

Articulation : cant examined

Upper and Lower extremities

Sensory

Pain : Normal

Temperature : Not examined

Motoric

No lateralization

No mucles atrophy

Physiological reflexes

Biceps : ++ / ++

Triceps : ++ / ++

Patella : ++ / ++

Achilles :++ / ++

Pathological reflexes

Hoffman :-/-

Tromner :-/-
 Babinsky :-/-

Chaddock :-/-

TRAP examination

Resting tremor : +/+

Rigidity : +/+

Monotonus :+

Hypomimic :+

Retropulsion test :+

III. Laboratory examination

Clinical chemistry (6 July 2017)
Triglycerides : 44 mg/dL
Total cholesterol : 186 mg/dL
HDL cholesterol : 52 mg/dL
LDL cholesterol : 130 mg/dL

Renal Function (6 July 2017)

Ureum : 19 mg/dL

Creatinin : 0.9 mg/dL

Uric acid : 4.4 ng/dL

Electrolyte (6 july 2017)

Sodium : 137 mmol/L

Potassium : 3.84 mmol/L

Chloride : 111 mmol/L

IV. Radiology examination

V. Summary

The patient was brought into RSAL DR. Mintohardjo Emergency Room after suffering from the
whole body shake for 3 days. Actually this shaking movement has began from 3 years ago but just
located in the head.this patient has difficulities to eat and drink. This shaking movement can be
clearly seen specially when he is at rest and decrease when he start to move. The patient didnt eat
and drink for the past 3 days. He also has difficulities to walk because of the whole body stiffness.
When he walk, he can began to walk just with a small step, hard to stop, also cant to turn right or
left (like a robot). He needs a time to turn the position to the wanted direction. It is often, when he
walked, he just lost his stability and sometime he just fell to the ground.

TRAP examination :Resting tremor (+/+) Rigidity (+/+) Monotonus (+),Hypomimic

(+),Retropulsion test (+)

VI. Assesment

Working diagnose

Clinical : resting tremor, rigidity, bradykinesia, postural instability

Etiological : parkinson

Topical : substansia nigra

Pathological : degeneration

VII. Treatment
Non-pharmacological : Bedrest, Nasogastric tube insertion, Folley catheter insertion

Pharmacological:

IV line : RL 14 drip/min

Injections : Citicoline injection 2 x 500 mg

Oral : Haloperidol 2 x 1.5 mg

Trihexifenidile 2 x 1

Stalevo 2 x 1
FOLLOW UP: DAY 1 SATURDAY, July 8 , 2017

S Mobilitation (-) eat (-) drink (-)

O Consciousness : GCS E4M6V5

o
BP 110/70 mmHg PR 82x/min T: 36,3 C RR 18x/min SPO2 98%
Pupil isocoria, DRL +/+, NDRL +/+
General examination : Normal
Neurological examination :
- Cranial nerve lesions : (-)
- Meningeal signs: (-)
- Physiological reflexes : upper ++/++ lower ++/++
- Pathological reflexes: upper -/- lower -/-
- Muscle strength: No lateralization
- Tremor (+) rigidity (+) bradykinesia (+) postural instability (+)

A Clinical : resting tremor, rigidity, bradykinesia, postural instability

Etiological : parkinson
Topical: substansia nigra
Pathological : degeneration

P IV line: RL 14 drip/min
NGT (+)
Injections:
Citicoline injection 2 x 500 mg
Oral:
Haloperidol 2 x 1.5 mg
Trihexifenidile 2 x 1
Stalevo 2 x 1 leparson 2 x 1
Diazepam 2 x 2.5 mg
FOLLOW UP: DAY 2 SUNDAY, July 9 , 2017
S mobilitation (-) eat (+) drink (+)

O Consciousness : GCS E4M6V5

o
BP 120/70 mmHg PR 84x/min T: 36,6 C RR 18x/min SPO2 99%
Pupil isocoria, DRL +/+, NDRL +/+
General examination : Normal
Neurological examination :
- Cranial nerve lesions : (-)
- Meningeal signs: (-)
- Physiological reflexes : upper ++/++ lower ++/++
- Pathological reflexes: upper -/- lower -/-
- Muscle strength: No lateralization
- Tremor (-) rigidity (+) bradykinesia (+) postural instability (-)
A Clinical : resting tremor, rigidity, bradykinesia, postural instability
Etiological : parkinson
Topical: substansia nigra
Pathological : degeneration

P IV line: RL 14 drip/min
Aff NGT (+)
Oral:
Haloperidol 2 x 1.5 mg
Trihexifenidile 2 x 1
Stalevo 2 x 1 leparson 2 x 1
Diazepam 2 x 2.5 mg
Citicolin tab 2 x 500 mg
FOLLOW UP: DAY 3 MONDAY, July 10 , 2017
S mobilitation (-) eat (+) drink (+)
O Consciousness : GCS E4M6V5
o
BP 110/70 mmHg PR 90x/min T: 36,4 C RR 18x/min SPO2 98%
Pupil isocoria, DRL +/+, NDRL +/+
General examination : Normal
Neurological examination :
- Cranial nerve lesions : (-)
- Meningeal signs: (-)
- Physiological reflexes : upper ++/++ lower ++/++
- Pathological reflexes: upper -/- lower -/-
- Muscle strength: No lateralization
- Tremor (-) rigidity (-) bradykinesia (-) postural instability (-)
A Clinical : resting tremor, rigidity, bradykinesia, postural instability (history)
Etiological : parkinson
Topical: substansia nigra
Pathological : degeneration

P IV line: Venflon (+)

Oral:
Haloperidol 2 x 0.5 mg
Trihexifenidile 2 x 1
Stalevo 2 x 1 leparson 2 x 1
Diazepam 2 x 2.5 mg
Citicolin 2 x 500 mg
FOLLOW UP: DAY 4 TUESDAY, July 11 , 2017
S mobilitation (+) eat (+) drink (+)
O Consciousness : GCS E4M6V5
o
BP 120/70 mmHg PR 86x/min T: 36,3 C RR 18x/min SPO2 99%
Pupil isocoria, DRL +/+, NDRL +/+
General examination : Normal
Neurological examination :
- Cranial nerve lesions : (-)
- Meningeal signs: (-)
- Physiological reflexes : upper ++/++ lower ++/++
- Pathological reflexes: upper -/- lower -/-
- Muscle strength: No lateralization
- Tremor (-) rigidity (-) bradykinesia (-) postural instability (-)
A Clinical : resting tremor, rigidity, bradykinesia, postural instability
Etiological : parkinson
Topical: substansia nigra
Pathological : degeneration

P IV line: Venflon (+)

Oral:
Haloperidol 2 x 0.5 mg
Trihexifenidile 2 x 1
Stalevo 2 x 1 leparson 2 x 1
Diazepam 2 x 2.5 mg
Citicolin 2 x 500 mg
 LITERATURE REVIEW

1. Definition
Parkinsons disease (PD) was first described by Dr. James Parkinson in 1817 as a shaking
palsy. It is a chronic, progressive neurodegenerative disease characterized by both motor and
nonmotor features.6

2. Anatomy and Physiology of Basal Ganglia

a. Basal ganglia.
The basal ganglia consist of the caudate nucleus (CN), putamen, globus pallidus (=
pallidum; GPe = external segment, GPi = internal segment; putamen + pallidum = lentiform
nucleus), claustrum, substantia nigra (SN; SNc = pars compacta, SNr = pars reticularis), and the
subthalamic nucleus (STN). CN + putamen = (dorsal) striatum; nucleus accumbens + portions of
olfactory tubercle + anterior portion of putamen + CN = limbic (ventral) striatum. Substantia
nigra (SN): The SNr (ventral portion of SN) contains small amounts of dopamine and iron,
giving it a reddish color, while the SNc (dorsal portion) contains large quantities of dopamine
and melanin, making it black (whence the name, substantia nigra).7

Figure 1. Anatomy of the basal ganglia

b. Connections.
The basal ganglia are part of a number of parallel and largely distinct (segregated) neural
pathways (circuits). Each circuit originates in a cortical area that is specialized for a specific
function (skeletal motor, oculomotor, associative-cognitive, or emotional-motivational control),
passes through several relay stations in the basal ganglia, and travels by way of the thalamus
back to the cerebral cortex. Cortical projection fibers enter the basal ganglia at the striatum (input
station) and exit from the GPi and SNr (output station). 7

Input from the thalamus and brain stem also arrives at the striatum. Within the basal
ganglia, there are two circuits subserving motor function, the so-called direct and indirect
pathways. The direct pathway runs from the putamen to the GPi and SNr, while the indirect
pathway takes the following trajectory: putamen , GPe , STN , GPi , SNr. The GPi and SNr
project to the thalamus and brain stem. 7

c. Neurotransmitters.
Glutamate mediates excitatory impulses from the cortex, amygdala, and hippocampus to
the striatum. Synapses from STN fibers onto cells of the GPi and SNr are also glutamatergic.
Both the excitatory and the inhibitory projections of the SNc to the basal ganglia are
dopaminergic. In the striatum, dopamine acts on neurons bearing D1 andD2 receptors, of which
there are various subtypes (D1 group: d1, d5; D2 group: d2 ,d3 ,d4).D1 receptors predominate in
the direct pathway, D2 receptors in the indirect pathway. Cholinergic interneurons in the
striatum form a relay station within the basal ganglia (transmitter: acetylcholine). Medium spiny-
type neurons (MSN) in the striatum have inhibitory projections to the GPe, GPi, and SNr
(transmitters: GABA, substance P/SP, enkephalin/Enk). Other inhibitory GABAergic projections
run from the GPi to the STN, from the GPi to the thalamus (ventrolateral and ventroanterior
nucleus), and from the SNto the thalamus. The thalamocortical projections are excitatory. 7

d. Motor function.
The direct pathway is activated by cortical and dopaminergic projections to the striatum.
The projection from the striatum in turn inhibits the GPi, diminishing its inhibitory output to the
thalamic nuclei (i.e., causing net thalamic activation). Thalamocortical drive thus facilitates
movement initiated in the cerebral cortex (voluntary movement). In the indirect pathway, the
striatum, under the influence of afferent cortical and dopaminergic projections, exerts an
inhibitory effect on the GPe and STN. The result is a diminished excitatory influence of the STN
on the GPi and SNr, ultimately leading to facilitation of cortically initiated voluntary movement
and inhibition of involuntary movement. 7

Besides having nonmotor functions that are not clearly understood, the basal nuclei play a
complex role in controlling movement. In particular, they are important in (1) inhibiting muscle
tone throughout the body (proper muscle tone is normally maintained by a balance of excitatory
and inhibitory inputs to the neurons that innervate skeletal muscles); (2) selecting and
maintaining purposeful motor activity while suppressing useless or unwanted patterns of
movement; and (3) helping monitor and coordinate slow, sustained contractions, especially those
related to posture and support. Th e basal nuclei do not directly influence the eff erent motor
neurons that bring about muscle contraction but act instead by modifying ongoing activity in
motor pathways. 7

3. Epidemiology
PD is one of the most common neurodegenerative disorders. The Parkinsons Disease
Foundation reports that approximately 1 million Americans currently have the disease.5 The
incidence of PD in the U.S. is approximately 20 cases per 100,000 people per year (60,000 per
year), with the mean age of onset close to 60 years. The prevalence of PD is reported to be
approximately 1% in people 60 years of age and older and increases to 1% to 3% in the 80-plus
age group 3

4. Pathogenesis
This condition is associated with a gradual destruction of neurons that release the
neurotransmitter dopamine in the basal nuclei. Because the basal nuclei lack enough dopamine to
exert their normal roles, three types of motor disturbances characterize PD: (1) increased muscle
tone, or rigidity; (2) involuntary, useless, or unwanted movements, such as resting tremors (for
example, hands rhythmically shaking, making it difficult or impossible to hold a cup of coff ee);
and (3) slowness in initiating and carrying out diff erent motor behaviors. People with PD find it
difficult to stop ongoing activities. If sitting down, they tend to remain seated, and if they get up,
they do so very slowly. 7
5. Pathophysiology
The cause of Parkinson disease is unknown. Its structural pathological correlate is a loss
of neurons in the caudal and anterolateral parts of the SNc, with reactive gliosis and formation
of Lewy bodies (eosinophilic intracytoplasmic inclusions in neurons) and Lewy neurites
(abnormally phosphorylated neurofilaments) containing synuclein. Loss of pigment in the
substantia nigra can be seen macroscopically. The most prominent neurochemical abnormality is
a deficiency of dopamine in the striatum, whose extent is directly correlated with the severity of
PD. The physiological effect of the lack of (mostly inhibitory) dopamine neurotransmission in
the striatum is a relative increase in striatal activity, in turn causing functional disinhibition of the
subthalamic nucleus via the indirect pathway.

Meanwhile, in the direct pathway, decreased striatal inhibition of the GPi enhances the
inhibitory influence of the GPi on the thalamus, leading to reduced activity in the thalamocortical
projection. These changes in neural activity manifest themselves in the clinically observable
akinesia, rigidity, and postural instability. 7

Figure 2. Functional anatomi of motor cortex basal ganglia and thalamus in normal compare to
person who suffer PD
6. Clinical Manifestations
I. Cardinal Manifestations 7
a. Bradykinesia, hypokinesia, and akinesia.
Motor disturbances include slow initiation of movement (akinesia), sluggishness of
movement (bradykinesia) and diminished spontaneous movement (hypokinesia); these terms are
often used nearly interchangeably, as these disturbances all tend to occur together. Spontaneous
fluctuations of mobility are not uncommon. The motor disturbances are often more pronounced
on one side of the body, especially in the early stages of disease. They affect the craniofacial
musculature to produce a masklike facies (hypomimia), defective mouth closure, reduced
blinking, dysphagia, salivation (drooling), and speech that is diminished in volume
(hypophonia), hoarse, poorly enunciated, and monotonous in pitch (dysarthrophonia). The
patient may find it hard to initiate speech, or may repeat syllables; there may be an involuntary
acceleration of speech toward the end of a sentence (festination). Postural changes include
stooped posture, a mildly flexed and adducted posture of the arms, and postural instability. Gait
disturbances appear in the early stages of disease and typically consist of a small-stepped gait,
shuffling, and limping, with reduced arm swing. Difficulty initiating gait comes about in the later
stages of disease, along with episodes of freezing complete arrest of gait when the patient is
confronted by doorway or a narrow path between pieces of furniture. It becomes difficult for the
patient to stand up from a seated position, or to turn over in bed. Impairment of fine motor
control impairs activities of daily living such as fastening buttons, writing (micrographia), eating
with knife and fork, shaving, and hair-combing. It becomes difficult to perform two activities
simultaneously, such as walking and talking.

b. Tremor.
Only about half of all PD patients have tremor early in the course of the disease; the rest
usually develop it as the disease progresses. It is typically most pronounced in the hands (pill-
rolling tremor) and is seen mainly when the affected limbs are at rest, improving or disappearing
with voluntary movement. Its frequency is ca. 5 Hz, it is often asymmetrical, and it can be
exacerbated by even mild stress (mental calculations, etc.).
c. Rigidity.
Elevated muscle tone is felt by the patient as muscle tension or spasm and by the
examiner as increased resistance to passive movement across the joints. Examination may reveal
cogwheel rigidity, i.e., repeated, ratchetlike oscillations of resistance to passive movement across
the wrist, elbow, or other joints, which may be brought out by alternating passive flexion and
extension.

d. Postural instability (loss of balance).

Propulsion and retropulsion arise in the early stages of Parkinson disease because of
generalized impairment of the postural reflexes that maintain the bipedal stance. Related
phenomena include involuntary acceleration of the gait (festination), difficulty in stopping
walking, gait instability, and frequent falls.

Figure 3. Clinical feature of parkinsons disease

II. Accompanying Manifestations
a. Behavioral Changes 8
Depression.
The range of depressive manifestations includes worry, anxiety, avoidance of social
contact, general unhappiness, listlessness, querulousness, brooding, somatoform disturbances,
and (rarely) suicidal ideation.

Anxiety.
Tension, worry, mental agitation, lack of concentration, and dizziness are relatively
common complaints.

Dementia.
Impairment of memory and concentration in early PD-associated dementia may be
difficult to distinguish from depressive manifestations. The side effects of pharmacotherapy (p.
212) must be kept in mind before treatment is initiated for patients suffering from disorientation,
confusion, suspiciousness, and other emotional changes.

Hallucinations.
A state of excessive suspiciousness, vivid dreams, and increasing anxiety may evolve into
one of severe confusion with visual hallucinations. Frank psychosis (e. g., paranoid delusions,
ideas of reference, or delusional jealousy) may be due to other causes than PD, particularly an
adverse effect of antiparkinsonian medication.

b. Autonomic Dysfunction 7,8

Blood pressure changes.
Hypotension is a common side effect of antiparkinsonian medications (levodopa,
dopamine agonists). Marked orthostatic hypotension, if present, suggests the possible diagnosis
of multisystem atrophy.

Constipation
This may be caused by autonomic dysfunction, as a manifestation of the disease, or as a
side effect of medication (anticholinergic agents).
 Bladder disorders.
Polyuria, urinary urgency, and urinary incontinence occur mainly at night and in patients
with severe akinesia (who have difficulty getting to the toilet). PD only rarely causes severe
bladder dysfunction.

Sleep disorders.
PD commonly causes disturbances of the sleepwake cycle, including difficulty falling
asleep, nocturnal breathing problems similar to sleep apnea syndrome, and shortening of the
sleep cycle. Sleep may also be interrupted by nocturnal akinesia, which makes it difficult for the
patient to turn over in bed.

Sexual dysfunction.
Spontaneous complaints of diminished libido or impotence are rare. Increased libido is a
known side effect of levodopa and dopamine agonists.

Leg edema
This is often as the result of physical inactivity.

c. Sensory Manifestations
Pain
Pain in the arm or shoulder, sometimes accompanied by fatigue and weakness, may be
present for years before the cardinal manifestations arise and enable a diagnosis of PD. Back
pain and nuchal cramps are frequent secondary effects of parkinsonian rigidity and abnormal
posture. Dystonia may also come to attention because of the pain it produces.

The symptoms and signs of Parkinsons disease reflect a highly selective pattern of
degeneration in the brain. The worst damage occurs in the dopamine-producing neurones of the
substantia nigra, and this accounts for many of the abnormalities of movement, referred to as
parkinsonism. These neurons project to the corpus striatum via the nigrostriatal pathway. The
consequence of loss of neurones in the substantia nigra is dopamine deficiency in the corpus
striatum. This may be unilateral, asymmetrical or symmetrical.7
 The noradrenaline- and 5HT-producing neurones in the brainstem are also affected, and
this may explain the high incidence of depression in Parkinsons disease. The neurones that
deliver acetylcholine to the cerebral cortex are affected as well; this, together with involvement
of the cortial neurones themselves, contributes to cognitive symptoms. In all these locations the
neurones degenerate in a characteristic way, forming clumps of protein called Lewy bodies.

7. Diagnosis
The diagnosis of Parkinson disease (PD; sometimes termed idiopathic Parkinson disease,
to distinguish it from symptomatic forms of parkinsonism, and from other primary forms) is
mainly based on the typical neurological findings, their evolution over the course of the disease,
and their responsiveness to levodopa (Ldopa). Longitudinal observation may be necessary before
a definitive diagnosis of PD can be given. PD is characterized by a number of disturbances of
motor function (cardinal manifestations) and by other accompanying manifestations of different
kinds and variable severity. 7

8. Treatment
The goal of treatment is improvement of the motor, autonomic, and cognitive symptoms
of the disease. The treatment generally consists of medication along with physical, occupational,
and speech therapy. Neurosurgical procedures are mostly reserved for intractable cases (see
below). Pharmacotherapy is palliative, not curative. It is begun when the patient has trouble
carrying out the activities of daily living and is prescribed, not according to a uniform pattern,
but in relation to the needs of the individual patient. 8

Dopaminergic agents.
Levodopa is actively absorbed in the small intestine and rapidly distributed throughout
the body (especially to skeletal muscle). Amino acids compete with the levodopa transport
system at the bloodbrain barrier. A decarboxylase inhibitor that does not penetrate the blood
brain barrier (benserazide or carbidopa) is administered together with levodopa to prevent its
rapid breakdown in the peripheral circulation. Once it reaches the brain, levodopa is
decarboxylated to dopamine, which is used for neurotransmission in the striatum. After it has
been released from the presynaptic terminals of dopaminergic neurons in the striatum and
exerted its effect on the postsynaptic terminals, it is broken down by two separate enzyme
systems (deamination by monoamine oxidase type B, MAO-B; methylation by catechol- O-
methyltransferase, COMT). Levodopa effectively reduces akinesia and rigidity, but has only a
mild effect against tremor. Its long-term use is often complicated by motor fluctuations,
dyskinesia, and psychiatric disturbances. 8

Dopamine agonists (DAs) mimic the function of dopamine, binding to dopamine

receptors. Their interaction with D1 and D2 receptors is thought to improve motor function,
while their interaction with D3 receptors is thought to improve cognition, motivation, and
emotion. Long-term use of DAs is less likely to cause unwanted motor side effects than long-
term use of levodopa. Commonly used DAs include bromocriptine (mainly a D2 agonist),
lisuride (mainly a D2 agonist), and pergolide (a D1, D2, and D3 agonist). Apomorphine, an
effective D1 and D2 agonist, can be given by subcutaneous injection, but its effect lasts only
about 1 hour. Other, recently introduced dopamine agonists are ropinirol and pramipexol (D2
and D3), cabergoline (D2), and dihydroergocryptine (mainly D2). Selegiline inhibits MAO-B
selectively and irreversibly ( reduced dopamine catabolism increase in striatal dopamine
concentration). Entacapone increases the bioavailability of levodopa via peripheral inhibition of
COMT. 9

Figure 4. Diagram to show the substantia nigra in the midbrain, and the nigrostriatal pathway.
 Figure 5. Pharmacological treatment of Parkinson disease 10

Nondopaminergic agents.
Anticholinergic agents

(biperidene, bornaprine, metixene, trihexyphenidyl) act on striatal cholinergic

interneurons. Budipine can relieve tremor (risk of ventricular tachycardia ECG monitoring).
Glutamate antagonists (amantadine, memantine) counteract increased glutamatergic activity at
the N-methyl-D-aspartate (NMDA) glutamate receptor in the indirect pathway. 10

Transplant Surgery
Current research on intrastriatal transplantation of stem cells (derived from fetal tissue,
from umbilical cord blood, or from bone marrow) seems promising.

Stereotactic Neurosurgical Procedures, Deep Brain Stimulation

These procedures can be used when PD becomes refractory to medical treatment.
Pallidotomy (placement of a destructive lesion in the GPi) derives its rationale from the observed
hyperactivity of this structure in PD. Deep brain stimulation requires bilateral placement of
stimulating electrodes in the GPi or STN. Highfrequency stimulation by means of a
subcutaneously implanted impulse generator can improve rigor, tremor, akinesia, and dyskinesia.

Genetics of PD
A genetic predisposition for the development of PD has been postulated. Mutations in the
genes for synuclein (AD), parkin (AR), and ubiquitin C-terminal hydrolase L1 (UCHL1; AD)
have been found in pedigrees affected by the rare autosomal dominant (AD) and autosomal
recessive (AR) familial forms of PD. 7
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