- The diagnosis of Parkinson's disease is still based on careful history taking and clinical examination, despite ongoing
advances in neuro-imaging and laboratory testing.
- One of the first challenges is to differentiate between Parkinson's disease and Parkinsonism - any group of nervous
system disorders characterised by muscular rigidity, tremor and impaired motor control.
- Management of Parkinson's disease and co-existent health problems is a long journey, requiring a multidisciplinary
- Initiation of drug treatment for early Parkinson's disease is usually delayed until functional problems develop.
- Levodopa is the drug of choice for Parkinson's disease but approximately half of patients will experience fluctuations
in motor control after 5 to 10 years of treatment.
- Long-term management of Parkinson's disease involves careful adjustment of medications and their doses along with
other strategies such as education, exercise, speech therapy and nutrition.
Parkinson's disease is one of the most common neurodegenerative diseases, with prevalence ranging from 100-180
per 100,000 population and an incidence of 4-20 cases per 100,000. There is a male to female predominance of 1.3:1.
It typically presents in those over 60 years and the prevalence will increase with the ageing population.
While most cases of Parkinson's disease are thought to be sporadic in onset, mutations in six nuclear genes have been
associated with autosomal dominant or recessive Parkinson's disease. A number of aetiologic factors have been considered
including infections, toxins, head trauma, coffee and alcohol consumption. The strongest association is that non smokers
are at greater risk of developing Parkinson's disease.
The diagnosis of Parkinson's disease is based upon careful history taking and examination, despite ongoing advances
in neuro-imaging and laboratory testing. Computerised tomography (CT) and Magnetic Resonance Imaging show no specific
changes but may help to exclude other conditions. Positron emission tomography and single photon emission CT may help
in diagnosis but are not routinely available.
Ideally, patients should be managed jointly with GP, specialist and other health professionals including nurse specialist,
physiotherapists, occupational therapists, social workers, speech-language therapists and the Parkinson's Society field
worker. Effective communication and team work are paramount for optimal management.
This is often a long journey which also requires the management of co-existent health problems and may culminate in
end stage Parkinson's disease and palliative care.
Making the Diagnosis
Getting the diagnosis correct underpins the best management of patients and a specialist opinion is usually helpful,
ideally before starting any medications.
Careful history taking is essential and often provides a clear guide to the diagnosis. The duration of symptoms is important,
as is any family history of either Parkinson's disease or tremor.
The error rate in diagnosing idiopathic Parkinson's disease has been reported as around 50% in general practice, 25%
in general specialist clinics and 8% in specialised Parkinson's disease clinics.1
Differentiating Parkinson's disease from Parkinsonism
One of the first challenges is differentiating Parkinson's disease from Parkinsonism as the management is usually quite
Parkinsonism is any of a group of nervous system disorders with symptoms similar to Parkinson's disease, characterised
by muscular rigidity, tremor, and impaired motor control. There is often a specific cause, such as the use of certain
drugs or frequent exposure to toxic chemicals.
It is essential to check for medications which interfere with dopamine release in the brain and hence cause Parkinsonism
(neuroleptics, metoclopramide, prochlorperazine).
Features of Parkinson's disease
Tremor: (Table 1) The most common presenting symptom is tremor, although the majority of those with tremor do not have
Parkinson's disease. Tremor in Parkinson's disease usually presents as a unilateral, pill rolling hand tremor. It may
affect other limbs and the head. Always query the diagnosis if tremor is absent.
The pattern of any tremor should be clarified, for example, whether it is worse on activity or at rest or if there are
any relieving factors. Past medical history may indicate other diseases. A careful medication history is essential to
exclude drug induced tremor.
Essential tremor is relatively common, affecting 0.4 to 4% of the population and approximately 2.5% of those over 60
years. It is often bilateral, progressive and not associated with other extrapyramidal signs.
Cerebellar tremor may be unilateral or bilateral depending upon its aetiology. It is worse on movement, often with a
stuttering or saccadic character and worse at the beginning and end of movement. There may be other cerebellar signs including
nystagmus and ataxia.
Table 1: Characteristics of Tremor
||Action, Past pointing
Rigidity and Bradykinesia: Bradykinesia and rigidity, micrographia, stiffness and slowness, may be
features of other conditions including ageing, depression, dementia, arthropathies, polymayalgia rheumatica, and hypothyroidism,
as well as Parkinson's disease. At first presentation of Parkinson's disease, patients may complain of a general slowing
up and stiffness which can be attributed to ageing or osteoarthritis. There may be difficulties in turning over in bed,
which may contribute to sleep disturbance. Speech may be slower, quieter and more monotonous. Patients may have expressionless
faces and be less spontaneous.
The increased tone is classically present throughout movement (lead pipe) or has a cog-wheeling component to it. This
can be thought of as the additive effects of tremor upon the lead pipe rigidity.
Gait disorder, postural changes and falls: These occur later in the disease course and if present early,
should alert the clinician to an alternative diagnosis.
In Parkinson's disease, the characteristic features usually begin with unilateral loss of arm swing and it is often
helpful to watch the patient walk along a corridor. The gait is typically small-stepped and shuffling, described as festinating.
The posture becomes stooped, and arms flexed. Patients turn en bloc, shuffling around on the spot. Postural stability
becomes impaired and the risk of falling increases. Postural hypotension as a result of autonomic dysfunction and/or medication
can contribute to falls.
Assessment should include:
- Cognitive function
- Lying and standing blood pressure
- Musculoskeletal conditions
- Thyroid disease
Neurological assessment should include checking for red flags for alternative diagnoses.
There are some "red flags" (Table 2) which should always alert the clinician to an alternative diagnosis (Table 3).
Table 2: Red Flag alerting clinicians to an alternative diagnosis
|No tremor at time of diagnosis
|Bilateral signs at onset
|Dementia or hallucinations early in the disease course
|Early onset of postural hypotension and autonomic failure
|Reduced range of eye movements at diagnosis
|Falls or drop attacks early in history
|Up-going plantar reflex
|No response to levodopa
Table 3: Parkinsonian Syndromes
|Drug Induced Parkinsonism
|Alzheimer's Disease or Vascular Dementia
|Dementia with Lewy Bodies
|Multiple Systems Atrophy/ Shy Drager Syndrome
|Progressive Supra-nuclear Palsy
|Normal Pressure Hydrocephalus
|See panel for more details
By the time symptoms of Parkinson's disease appear, approximately 70-80% of the dopamine is lost from the substantia
nigra indicating a substantial sub-clinical period. While dopamine is the primary neuro-transmitter involved in the pathology
of Parkinson's disease it is clear that others are involved including acetylcholine, noradrenaline, adenosine, glutamate
The factors which determine prognosis and disease progression in Parkinson's disease are not clearly established.
Initially, patients experience a prompt and even response to medication. Usually within two years, medication doses
need to be increased and patients often take a combination of medications.
|"One of the first challenges is differentiating
Parkinson's disease from Parkinsonism"
The lowest dose of medication needed should always be used. The progressive degeneration of dopamine terminals means
the concentration of dopamine in the basal ganglia becomes more dependent upon plasma levels. These can fluctuate because
of the 90 minute half life of levodopa and its unpredictable absorption. At this time, the consensus is that chronic administration
of levodopa does not exacerbate the disease process.
Motor fluctuations occur in approximately half of patients after 5 to 10 years of treatment. These often are more severe
in younger patients and are associated with the use of levodopa containing preparations. These include wearing off, dyskinesias
and dystonias, and on-off episodes.
When the effect of levodopa wears off in less than four hours, this can initially be managed by increasing the dose
of medication and/or shortening the dosing interval.
|"Fluctuations in motor control occur in approximately
half of patients after 5 to 10 years of treatment with levodopa"
This can progress to on-off episodes (fluctuations between control and no control). Initially the pattern may be predictable
with timing of medication and its effectiveness but it may become unpredictable. Patients may find themselves suddenly
freezing, often when moving through doorways. Dyskinetic movements may occur typically when patients are in an "on" period.
Dystonia, often painful, including dystonic inversion of the foot, may occur when the patient is either "on" or "off"
The treatment of such complications can be difficult and specialist help is usually required.