We searched PubMed for English language articles on Parkinson's disease from 1998 to 2004, with the key phrase “Parkinson disease” and other keywords or phrases including: “treatment”, “therapy”, “epidemiology”, “diagnosis”, “etiology”, “pathogenesis”, “imaging”, “positron emission tomography”, “single photon emission computed tomography”, “genetic”, “environment”, “neuroprotection”, “deep brain stimulation”, “transplantation”, and many other keywords relevant to every section. We also reviewed
SeminarParkinson's disease
Section snippets
Terminology
Parkinsonism describes a syndrome characterised by rigidity, tremor, and bradykinesia, of which Parkinson's disease is the main cause. Parkinson's disease is usually asymmetric and responsive to dopaminergic treatment, with no historical or examination clues to suggest a cause for symptoms. Pathological findings show that nigral dopamine neurons are greatly diminished and Lewy bodies are present in the remaining neurons. Thus, to obtain a definite diagnosis of idiopathic Parkinson's disease,
Epidemiology
The prevalence of Parkinson's disease in industrialised countries is estimated at 0·3% of the general population and about 1% of the population older than age 60 years.3, 4 People of all ethnic origins can be affected, and men are slightly more prone to the disorder.5, 6 In one study, the annual incidence of Parkinson's disease was about 13 cases per 100 000.7 Mean age of onset of this disorder was estimated to be in the late 50s,8 but is now thought to be in the early-to-mid 60s.9 In people
Clinical features
The three cardinal features of Parkinson's disease are rest tremor, rigidity, and bradykinesia. Postural instability—sometimes judged a cardinal feature—is non-specific and is usually absent in early disease, especially in the younger patient. Although motor features define the disorder, various non-motor features typically are seen, including autonomic dysfunction, cognitive and psychiatric changes, sensory symptoms, and sleep disturbances.
A resting tremor with a frequency of 3–5 Hz
Diagnostic criteria
A definite diagnosis of Parkinson's disease needs autopsy. However, clinical diagnosis of this disorder has become more rigorous, with gradations of diagnostic certainty, including clinically possible, clinically probable, and clinically definite Parkinson's disease (panel 1).19 Sustained improvement of motor symptoms with levodopa is generally a feature of clinically definite disease.20 Panel 1 shows exclusion criteria for idiopathic Parkinson's disease, which suggest an alternative diagnosis.
Differential diagnosis of Parkinson's disease
The clinical diagnosis of Parkinson's disease relies heavily on history, physical examination, and improvement of symptoms and signs with dopaminergic treatment. The differential diagnosis of this disorder includes normal ageing, essential tremor, drug-induced parkinsonism, the Parkinson-plus syndromes, vascular parkinsonism, and normal pressure hydrocephalus.22 Less common entities with parkinsonism include dopa-responsive dystonia,23 juvenile-onset Huntington's disease,24 and
Neuroimaging
Parkinson's disease is mainly diagnosed clinically, and in typical cases no laboratory test or neuroimaging is necessary. However, when the patient's history or clinical findings are atypical, MRI can be helpful in detection of other causes such as vascular parkinsonism.38
Functional neuroimaging of the nigrostriatal dopaminergic pathway has become an important method for quantification of functional dopaminergic terminals in the striatum.41 Parkinson's disease is characterised by decreased
Cause and pathogenesis
The underlying pathological finding in Parkinson's disease is injury to the dopaminergic projections from the substantia nigra pars compacta to the caudate nucleus and putamen (striatum). Intraneuronal Lewy bodies and Lewy neurites are the pathological hallmarks of the disease. Clinical signs of Parkinson's disease are evident when about 80% of striatal dopamine and 50% of nigral neurons are lost.50 Lewy bodies are not confined to the substantia nigra and can be seen in cortex, amygdala, locus
Mechanisms of neurodegeneration
Neurodegeneration could be related to mitochondrial dysfunction, oxidative stress, excitotoxicity, apoptosis, and inflammation.83 The discovery of mutations in the genes coding for α synuclein, parkin, and ubiquitin C-terminal hydrolase L1 in familial Parkinson's disease suggests that the failure of the ubiquitin-proteasome system is the common final pathway of neurodegeneration.64 Ubiquitin molecules are normally attached to damaged proteins as a signal for degradation (figure).
Medical treatment
In an evidence-based review of treatment options for Parkinson's disease, data were surveyed for slowing disease progression, providing symptomatic relief of motor and non-motor symptoms, and preventing motor fluctuations and dyskinesia.97 Here, we discuss salient features of the above-mentioned topics.
Surgical options for treatment
Surgical ablation of deep brain structures to treat Parkinson's disease goes back six decades.136 Before levodopa, thalamotomy was successful at reduction of contralateral tremor,137 and pallidotomy variably improved motor symptoms in Parkinson's disease.136 Functional neurosurgery was virtually abandoned with the introduction of levodopa in the late 1960s. However, complications of motor fluctuations and dyskinesia with long-term drug treatment led to a resurgence of surgical treatment.138
Restorative (transplantation) treatment
The goal of transplantation is to restore neuronal tissue lost to neurodegeneration. Fetal mesencephalic tissue transplantation has shown successful graft survival on PET scanning and on autopsy.152, 153 In a randomised sham surgery controlled study, some improvement was noted in the drug-off state in young patients but disabling dyskinesia arose in many patients.154 In a further randomised controlled study, no relevant motor improvement was recorded despite robust survival of dopamine neurons.
Search strategy and selection criteria
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Early onset Parkinson's disease: are juvenile- and young-onset different?
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Autonomic dysfunctions in idiopathic Parkinson's disease
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Sixteen-year follow-up of 100 patients begun on levodopa in 1968: emerging problems
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Sleep disorders in Parkinson's disease: epidemiology and management
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Criteria for diagnosing Parkinson's disease
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Research diagnostic criteria for Parkinson's disease
Adv Neurol
Diagnostic criteria for Parkinson disease
Arch Neurol
Differential diagnosis of parkinsonism
Can J Neurol Sci
Dopa-responsive dystonia: recent advances and remaining issues to be addressed
Mov Disord
Huntington disease in children: genotype-phenotype correlation
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Localization of the gene for rapidly progressive autosomal dominant parkinsonism and dementia with pallido-ponto-nigral degeneration to chromosome 17q21
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Normal aging of the nervous system
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Prevalence of parkinsonian signs and associated mortality in a community population of older people
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Aging and extrapyramidal function
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Aging produces a specific pattern of striatal dopamine loss: implications for the etiology of idiopathic Parkinson's disease
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Essential tremor: clinical characteristics
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Essential tremor and Parkinson's disease
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Drug-induced movement disorders
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Progressive supranuclear palsy: clinical features, pathophysiology and management
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Corticobasal degeneration: a clinical study of 36 cases
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Clinical Lewy body syndromes
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Vascular parkinsonism: a distinct, heterogeneous clinical entity
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Vascular parkinsonism: a review of the precision and frequency of the diagnosis
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Effectiveness and safety of different catechol-o-methyl transferase inhibitors for patients with parkinson's disease: Systematic review and network meta-analysis
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