The diagnosis of Parkinson’s Disease (PD) is made clinically. The diagnostic features include the presence of resting tremor, bradykinesia, rigidity, unilateral onset, and a good response to levodopa treatment.

Atypical features which suggest a Parkinson-plus syndrome include the presence of cerebellar signs, significant autonomic dysfunction, impaired eye movements, early dementia, and hallucinations unrelated to medications.

In the past, all patients with PD were treated with levodopa. However, over the years it has been found that up to 50% of patients on this medication would develop motor complications after 5 years. These include levodopa-induced dyskinesias (a difficulty to manage abnormal involuntary movements) and a "wearing-off" effect (a situation when levodopa is effective for only 2-3 hours at a time).

It was thought that dopamine agonists are less likely to result in these motor complications because of their longer half-lives and more continuous stimulation of the dopamine receptors. This has indeed been proven in clinical trials conducted on the newer dopamine agonists which showed that patients treated with these agents were less likely to develop these complications compared to patients treated on levodopa. For this reason, the latest guidelines issued by the American Academy of Neurology recommended the institution of a dopamine agonist to treat patients with PD who are functionally impaired (see algorithm). We have adopted this recommendation to use dopamine agonist and/or other levodopa-sparing medications (see table) as first-line treatment of patients with PD. This is particularly so for patients who are 65 years and younger as the risk of levopa-related complications are higher in these patients. Levodopa therapy could then be delayed till later when a patient’s condition is no longer well-controlled on dopamine agonist and other drugs.

In summary, there has been a paradigm shift in the treatment of PD. Dopamine agonists are now considered to be first-line therapy for symptoms of PD whenever possible instead of levodopa. This, together with the development of newer therapies, will ensure that PD patients will be able to maximise their current physical and mental function while maintaining options for a healthy future.

Treatment Strategies	Use in Parkinson’s disease
Neuro-protection
1. Selegiline	Has mild symptomatic benefit hence neuroprotection difficult to prove clinically, laboratory evidence support neuroprotection.
2. Coenzyme Q10	Small study showed that 1,200mg dose associated with significant slowing of PD but more evidence required.
3. Dopamine agonists	Preliminary results in functional imaging suggest slower rate of cell loss in patients treated on the newer dopamine agonists compared with levodopa.
Symptomatic Treatment
1. Anti-cholinergics (eg. benzhexol)	Mild symptomatic effect, useful for tremors, use with caution in elderly because of CNS side effects.
2. Amantadine	Effective in 2/3 of patients, effects wear out after several months.
3. Dopamine Agonists (eg bromocriptine, pergolide, piribedil, ropinirole)	Effective as monotherapy for early PD, needs gradual titration of dose to minimise side effects, reduce incidence of dyskinesias compared with levodopa.
4. Levodopa	Most potent drug to control symptoms. Significant risk of dyskinesias and "wearing-off" of medications over time.
Treatment of Complications
1. Amantadine	Effective in reducing levodopa-induced dyskinesias.
2. Catechol-O-methyltransferase (COMT) inhibitors (eg entacapone)	Increases bioavailability of levodopa and half-life of levodopa, only works in combination with levodopa. Smoothens out motor fluctuations eg "wearing-off".
3. PD Surgery	Deep brain stimulation or lesioning for advanced cases.
Neuro-restoration
1. Foetal transplants	2 double-blind placebo trials on embryonic tissue transplants did not find beneficial results overall.
2. Stem cells	Intensive research being done on dopaminergic stem cells in animal models.