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)
The quality of life in Parkinson's disease
Mov Disord
Health related quality of life in Parkinson's disease: a prospective longitudinal study
J Neurol Neurosurg Psychiatry
Quality of life and care in Parkinson's disease
Br J Clin Pract
Resource use and costs in a Swedish cohort of patients with Parkinson's disease
Mov Disord
Cost-effectiveness analysis in Parkinson's disease: determining the value of interventions
Mov Disord
Parkinson's disease in practice
Diagnosis and differential diagnosis
Parkinson's disease: clinical features
Accuracy of diagnosis in patients with presumed Parkinson's disease
Age Ageing
Accuracy of clinical diagnosis in parkinsonism — a prospective study
Can J Neurol Sci
Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases
J Neurol Neurosurg Psychiatry
Improved accuracy of clinical diagnosis of Lewy body Parkinson's disease
Neurology
Slower progression of Parkinson's disease with ropinirole versus levodopa: the REAL-PET study
Ann Neurol
Beta-CIT scans without evidence of dopaminergic deficit (SWEDD) in the ELLDOPA-CIT and CALM-CIT studies: long-term imaging assessment
Neurology
Prospective study of presynaptic dopaminergic imaging in patients with mild parkinsonism and tremor disorders; part 1: baseline and 3 month observations
Mov Disord
Parkinson's disease
EMJ
Neuroprotective agents for clinical trials in Parkinson's disease
Neurology
Mortality from Parkinson's disease
J Neurol Neurosurg Psychiatry
Mortality from Parkinson's disease in England and Wales 1921–89
J Neurol Neurosurg Psychiatry
Does levodopa therapy delay death in Parkinson's disease? A review of the evidence
Mov Disord
A ‘cure’ for Parkinson's disease: can neuroprotection be proven with current trial designs?
Mov Disord
Increased life expectancy resulting from addition of L-deprenyl to madopar treatment in Parkinson's disease: a long-term study
J Neurol Transm
Protection against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by monoamine oxidase inhibitors
Nature
Effect of deprenyl on the progression of disability in early Parkinson's disease
N Engl J Med
Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease
N Engl J Med
Living with a person who has Parkinson's disease: the spouse's perspective by stage of disease. Parkinson's Study Group
Mov Disord
Comparison of the therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in patients with early, mild Parkinson's disease
BMJ
Investigation by Parkinson's Disease Research Group of United Kingdom into excess mortality seen with combined levodopa and selegiline treatment in patients with early, mild Parkinson's disease: further results of randomised trial and confidential inquiry
BMJ
A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study
Arch Neurol
Effect of lazabemide on the progression of disability in early Parkinson's disease
Ann Neurol
A controlled trial of lazabemide (Ro 19–6327) in levodopa treated Parkinson's disease. Parkinson Study Group
Arch Neurol
Dopamine agonists and neuroprotection in Parkinson's disease
Attenuation of levodopa-induced toxicity in mesencephalic cultures by pramipexole
J Neurol Transm
Chronic levodopa is not toxic for remaining dopamine neurons, but instead promotes their recovery, in rats with moderate nigrostriatal lesions
Ann Neurol
Dopamine transporter brain imaging to assess the effects of pramipexole versus levodopa on Parkinson disease progression
JAMA
Initial agonist treatment of Parkinson's disease
Neurology
Slowing Parkinson's disease progression
Neurology
Agonists versus levodopa in Parkinson's disease
Neurology
Anatomic and disease specificity of NADH CoQl reductase (complex 1) deficiency in Parkinson's disease
J Neurochem
Cited by (59)
Fluoxetine tunes the abnormal hippocampal oscillations in association with cognitive impairments in 6-OHDA lesioned rats
2021, Behavioural Brain ResearchEmerging neuroprotective effect of metformin in Parkinson's disease: A molecular crosstalk
2020, Pharmacological ResearchCitation Excerpt :Despite the promising results of pre-clinical studies investigating various neuroprotective agents in PD, all current clinical trials testing potential disease-modifying therapies against PD have failed. The gold standard therapy for PD is based on levodopa, one of the intermediate molecules in dopamine formation [9]. Levodopa and dopaminergic agonists are initially effective at improving PD symptoms for most patients.
Biomarkers of Parkinson's Disease
2019, Biomarkers in ToxicologyProtective and therapeutic activity of honokiol in reversing motor deficits and neuronal degeneration in the mouse model of Parkinson's disease
2018, Pharmacological ReportsCitation Excerpt :Multiple epidemiological and experimental studies have demonstrated that environmental toxicants such as herbicides, pesticides, solvents, metals, and neurotoxicants may elicit the progressive loss of specific neuronal cells, thereby leading to neurodegeneration and PD [1,2]. Current PD medications rely heavily on dopamine (DA) replacement agents [3]. Although such therapies are efficacious in improving the motor symptoms and quality of life for patients during the early stages of PD, long-term use of these agents cannot halt disease progression and often causes side effects, including unwanted dyskinesia, psychotic symptoms, and mood disturbances [4].
Moutan Cortex Radicis inhibits the nigrostriatal damage in a 6-OHDA-induced Parkinson's disease model
2018, Chinese Journal of Natural MedicinesUrate and the risk of Parkinson's disease in men and women
2018, Parkinsonism and Related DisordersCitation Excerpt :Although there is no clear consensus, treatment is typically initiated at diagnosis in patients with functional disability, which is based on clinical judgment of motor symptoms. Treatment is delayed for some months in patients with mild early disease [30]. However, PD incidence in our study was comparable with that reported for Norway [24].