PARKINSON’S DISEASE
By Rachel Cheong
WHAT IS PARKINSON’S DISEASE?
REfERS tO IDIOPAthIc/ PRImARy PARKINSON’S DISEASE
Parkinsonism of unknown aetiology
Parkinsinonism= tremor at rest, stiffness,
slowing of movement and postural instability.
Part of the Movement Disorders known as
Akinetic-Rigid syndromes
Akinetic-Rigid Syndromes= slowed movement,
increased tone
Dyskinesias= added, uncontrollable
movements
Definition: Degenerative, progressive disease
Akinetic-Rigid
Syndromes
Dyskinesias
Idiopathic Parkinson’s Disease
Essential tremor
Drug-induced Parkinsonism
Chorea
MPTP-induced Parkinsonism
Hemiballismus
Postencephalitic Parkinsonism
Myoclonus
Parkinsonism-plus
Tics
Wilson’s Disease
Dystonias
Childhood akinetic-rigid
syndromes
Paroxysmal dyskinesias
IDIOPAthIc PARKINSON’S DISEASE
Described in 1817 by James Parkinson- “thE ShAKINg
PAlSy”
Prevalence: 65.6 per 100,000 to 125 per 100,000.
UK Incidence= approx. 128,000 cases
Incidence increases severely with age:
from 17.4 in 100,000 person years between 50 and 59
years of age to 93.1 in 100,000 person years between
70 and 79 years
Slightly more common in men
Insidious onset and progression
Studies suggest patients born in the spring have a
higher incidence of PD
Characterized by accumulation of alpha-
Related factors:
Nicotine: inverse relationship as acts like MAOB inhibitors and stimulates dopamine
Caffeine may be protective
MPTP: methylphenyltetrahydropyridine (illicit
stimulant/herbicides) causes severe
parkinsonism
Encephalitis Lethargica: parkinsonism postencephalitis
Genetics:
(a) Familial clusters of early-onset PD
(b) Mutations on Parkin gene on Chr 6
(under 40s; AR)
(c) α-synuclein gene mutation on Chr 2p13
(d) Ubiquitin carboxyl terminal hydrolase
L1 (UCHL1)
gene on Chr 4p14-16.3
Neuroanatomy
Basal Ganglia
=A large group of nuclei deep
within the brain
that affects
movement.
=Include the caudate nucleus &
putamen (striatum),
globus
pallidus, subthalamic nucleus, and substantia
nigra
Substantia Nigra = Generates dopamine which
regulates reward and
movement.
PATHOPHYSIOLOGY
•The basal ganglia and the cerebellum transmit
information via the thalamus to the cerebral cortex
to regulate movement.
•In a healthy brain, the neurons in the substantia
nigra release dopamine into the striatum modulates
neuronal activity affects movements + behaviours.
• In Parkinson's disease, there is a breakdown in the
connection between the striatum (neuron cells
die/become impaired) decreased dopamine levels
• Symptoms of Parkinson's disease appear after:
•60% - 80% of the neuronal cells become impaired or
die.
•Striatal dopamine levels have decreased by 20% - 50%
of normal levels
SIGNS & SYMPTOMS
1. Tremor- 4-7Hz pill-rolling tremor at rest
(decreases with action)
2. Rigidity- lead-pipe/plastic rigidity, more marked
on one side; Cogwheeling when occurs with
tremor.
3. Akinesia/ Bradykinesia- poverty/slowing of
movement; difficulty initiating movement; loss of
fine-finger movements; micrographia; mask-like
facial expression; serpentine stare (decreased
blinking)
4. Postural/Gait Change- Stooping (Simian);
festinant/shuffling gait with poor arm swing;
balance deterioratesfalls
5. Monotonous, tremulous speech slurring
dysarthria anarthria
6. Cognitive decline
7. Depression, Apathy, Anxiety
DIAGNOSIS
o Clinical diagnosis
o NICE recommends using the UK Parkinson's
Disease Society (PDS) Brain Bank Criteria for
diagnosis:
• Step 1: diagnosis of Parkinsonian syndrome
BRADyKINESIA + ≥ 1 Of :
Muscular rigidity.
4- to 6-Hz resting tremor.
Postural instability not caused by primary
visual,
vestibular, cerebellar or
proprioceptive dysfunction.
• Step 2: exclusion criteria for Parkinson's disease:
History of CVA/ step-wise progression/ head
trauma/ /
autonomic+cerebellar Sx/
Exposure to known drugs/
Negative response
to Dopa trial/ Early severe dementia
Step 3: supportive prospective positive criteria of
Parkinson's disease
Three or more are required for the diagnosis of
definite PD:
Unilateral onset.
Rest tremor present.
Progressive disorder.
Persistent asymmetry affecting the side of onset
most.
Excellent response (70-100%) to L-dopa.
Severe L-dopa-induced chorea.
L-dopa response for five years or more.
Clinical course of ten years or more.
Hyposmia.
Visual hallucinations.
Investigations
To exclude other causes
CT/MRI: Exclude supratentorial tumours, normal
pressure hydrocephalus and extensive
subcortical vascular pathology.
Positron emission tomography (PET) scanning:
with fluorodopa to localise dopamine deficiency
in the basal ganglia
Transcranial sonography: differentiate PD from
atypical or secondary Parkinsonian disorders,
for early diagnosis of PD and for detection of
subjects at risk for PD.
Genetic testing- eg, Huntington's gene, singlegene mutations in familial PD
Olfactory testing: differentiate PD from other
Parkinsonian disorders
For young-onset or atypical disease:
measurement of ceruloplasmin levels (Wilson's
Management
NICE suggests specialist review every 6-12 months for
clinical monitoring and medication adjustment
Multidisciplinary management including specialist
nurses, OT, physiotherapy, SALT, psychologists, social
services
Pharmacological Treatment:
Levodopa
Dopamine agonists
MAO-BIs
COMT inhibitors
Amantadine
Apomorphine
Antimuscarinic drugs
Surgical Treatment
Palliative Care
Levodopa
Most effective/ most responsive
Given with a peripheral dopa-decarboxylase
inhibitor, which prevents peripheral conversion to
dopamine
Eg: Sinemet, Madopar
Use lowest effective dose, eg: Sinemet 62.5 mg TDS
increased to 125 mg after two weeks
Adverse effects rare/mild: nausea, dizziness, weight
loss
Dopamine agonists
Treats motor features
Used in early disease, younger patients
Can be adjuvant to Levodopa
More severe/common adverse effects than
Levodopa
Non-ergot derivatives preferred, eg: pramipexole
MAO-B Inhibitors
Eg: Selegiline, Rasagiline
Early treatment with selegiline alone can delay the
need for levodopa therapy
Addition of selegiline to a levodopa/decarboxylase
inhibitor combination is more effective when
introduced at 5 years from onset
COMT Inhibitors
Eg: Entacapone, Tolcapone
Reversibly inhibit the peripheral breakdown of
levodopa by the COMT enzyme
Increases the amount available for conversion to
dopamine in the brain and reducing fluctuations in
plasma levels.
Benefits patients with levodopa motor fluctuations
Antimuscarinic drugs
Eg: orphenadrine, procyclidine and trihexyphenidyl
Improves motor function but common
neuropsychiatric and cognitive S/E
Reduces drug-induced Parkinsonism
Amantadine
monotherapy in early PD (for tremor or bradykinesia)
weak and short-lived benefit; used as adjuvant later
Apomorphine
Given subcutaneously
Used as a rescue agent in advanced disease to provide
rapid but short-lived benefit for sudden, severe 'off'
episodes
use intermittent injections to reduce 'off time' and
continuous infusion to reduce 'off time' and dyskinesias
Surgical Treatment
Developed in the mid-twentieth century before the
advent of effective medical therapy.
Recently enjoyed a resurgence
Pallidotomy
Subthalamic Surgery
Thalamic Surgery
Deep Brain Stimulation
Complications
“WEARINg Off PhENOmENON” OR “ON-Off fluctuAtIONS”
Dyskinesias
Depression & Anxiety
Hallucinations & Psychosis
Dementia
Compulsive Behaviours
Parkinsonian Crisis
-Acute akinesia
-rare but life-threatening complication
-sudden worsening of motor symptoms and severe
akinesia.
-Triggers include infections, surgery,
gastrointestinal disease and
changes in
medication.
-Acute akinesia is difficult to treat and often needs
Parkinson’s Plus Syndrome
Multiple System Atrophy
-Shy-Drager Syndrome
-autonomic dysfunction, parkinsonism, ataxia
Progressive Supranuclear Palsy
-Steele-Richardson-Olszewski syndrome
-Supranuclear ophthalmoplegia, neck dystonia,
Parkinsonism,
Pseudobulbar palsy, behavioral and
cognitive impairment, imbalance and difficulties
walking, frequent falls
Corticobasal Degeneration
-Parkinsonism, Alien Hand Syndrome, Apraxia, Aphasia
Pick’s Disease
-frontotemporal dementia, progressive nonfluent
Case Scenario
A 64 year old man attends his GP after his
wife made him come. For the last 6 months
he has noticed that he is slowing down. It
takes him a long time to do simple tasks like
getting dressed. His hands are shaking all
the time, more so on the right. His wife has
noticed a change in his gait saying he
shuffles when he walks. He has no past
medical history of notes and is on no
regular medication and has no known
allergies. On examination he has a blank
staring expression and marked rigidity of
his limbs, more so on the right. He has
resting pill rolling tremor. His gait is
shuffling and festinant
What is your differential diagnosis?
References
NICE Guidelines
http://www.nice.org.uk/nicemedia/live/10984/30088/
30088.pdf
University of Minnesota- Neurology Teaching
Webpage
Kumar & Clark Pg. 1144-1147
Oxford Handbook Pg. 368-369, 534
Patient Plus Reference
http://www.patient.co.uk/doctor/parkinsonsdisease-management
INtERNAtIONAl PARKINSON’S AND mOvEmENt
Disorders Society
http://www.movementdisorders.org/disorders/par
kinson.php
0
