Cochrane systematic reviews of PD therapy and reviews by a Movement Disorder, Society task force, published in Movement Disorders, formed the basis of this review. References were also obtained by searches of electronic databases, including MEDLINE and EMBASE, with the search terms “Parkinson's disease” and “Parkinson”. In most cases, only papers published in English since 1990 were reviewed.
ReviewNeuroprotection and pharmacotherapy for motor symptoms in Parkinson's disease
Section snippets
Differential diagnosis
Before treatment is started, it is of crucial importance to accurately differentiate idiopathic PD from disorders such as essential tremor, multiple cerebral infarct state, and drug-induced parkinsonism. Idiopathic PD must also be differentiated from Parkinson-plus syndromes such as progressive supranuclear palsy and multiple system atrophy;7, 8, 9 failure to do so can lead to a poor response to antiparkinsonian medication and inaccurate prognoses.
Poor differential diagnosis is a major problem
Definitions
The degeneration of dopaminergic neurons in PD leads to loss of the pathway from the substantia nigra to the corpus striatum. It is the deficiency of dopamine in the striatum that leads to most of the motor features of PD such as bradykinesia, hypokinesia, and rigidity. The aim of neuroprotective therapy is to prevent further dopaminergic cell death, thereby slowing or halting disease progression.18 “Neurorescue” is the salvage of dying neurons and may be part of the process of neuroprotection.
Symptomatic therapy
In the absence of neuroprotective therapy for PD, clinicians treat the motor and psychiatric symptoms of the disorder. At presentation, these symptoms are typically mild and include bradykinesia, rigidity, and unilateral rest tremor. In many patients disability does not significantly affect function, so symptomatic therapy can be avoided for 6–18 months.
Management algorithm
Providing a high quality evidence base for prescription in PD is a laudable goal but, in many cases, it has not helped the clinician. Many guidelines for PD management have been developed, few have used rigorous methodologies and many have been funded by the pharmaceutical industry.97, 98, 99, 100, 101, 102 The National Institute for Clinical Excellence is developing guidelines for the investigation and management of PD in England and Wales; these will be ready for consultation in July 2005 and
Future developments
The triple combination of levodopa, carbidopa and entacapone has recently been launched and rasagiline will probably be licensed for use in later PD in 2005. The non-ergot dopamine agonist rotigotine is highly lipophilic and has been formulated into a transdermal patch. This is the subject of phase III clinical trials after positive results in phase II studies.104, 105 By providing continuous 24 h dopaminergic stimulation, the rotigotine patch may be able to reduce motor complications but
Search strategy and selection criteria
References (106)
- et al.
Functional brain imaging in the differential diagnosis of Parkinson's disease
Lancet Neurol
(2004) - et al.
Dopamine D2 receptor-mediated antioxidant and neuroprotective effects of ropinirole, a dopamine agonist
Brain Res
(1999) - et al.
Dopa and dopamine cause cultured neuronal death in the presence of iron
J Neurosci
(1991) - et al.
Dopamine agonist monotherapy in Parkinson's disease
Lancet
(2002) - et al.
Coenzyme Q10 attenuates the MPTP induced loss of striatal dopamine and dopaminergic axons in aged mice
Brain Res
(1998) - et al.
When should levodopa be started?
Lancet
(1986) - et al.
Levodopa: why the controversy?
Lancet
(2002) - et al.
Treatment of Parkinson's disease with pergolide and relation to restrictive valvular heart disease
Lancet
(2004) Monoamine oxidase inhibitors—is it time to up the TEMPO
Lancet Neural
(2003)- et al.
Direct economic impact of Parkinson's disease: a research survey in the United Kingdom
Mov Disord
(2003)