In 1817 the British physician Dr. James Parkinson published An Essay on the Shaking Palsy, describing a 50 year old gardener who he described as suffering:
“Involuntary tremulous motion, with lessened muscular power, in parts not in action and even when supported with a propensity to bend the trunk forwards and to pass from a walking to a running pace: the senses and intellects being uninjured.”
Parkinson’s Disease is the second most frequently occurring neurodegenerative disorder after Alzheimer’s disease, affecting some 2% of the population over the age of 60 (Gasser 2005).
The disease is more common in males than females (~67% vs. 33%), with onset in late adulthood (60-80 years of age) (Baba et al. 2005, Kang et al. 2005). Males may present with greater rigidity whilst females present with greater instability and a tendency towards increased levodopa induced dyskinesias (Baba et al. 2005).
Approximately 15% of patients have a family history of Parkinson’s Disease, and there may also be a family history of Alzheimer’s Disease (Baba et al. 2005, Kang et al. 2005). First degree family members have a modestly higher risk of developing PD compared to controls (RR, 1.71, 95% CI, 1.11-2.64), although this is higher in relatives of younger onset PD patients (<66 years old, RR 2.62, 95% CI, 1.66-4.15) (Gasser 2005). There is low concordance rates between twins, with a recent Swedish study finding only two concordant pairs from a sample of 257 twins (Wirdefeldt et al. 2004).
Diagnosis is performed clinically on the basis of at least two of the following three signs: bradykinesia (slow movement), resting tremor, rigidity.
At presentation, rigidity, gait problems and bradykinesia are present in approximately 90-95% of patients, with tremor found in 43% (Kang et al. 2005).
Measurement and Staging
In the absence of a surrogate marker for PD, disease severity is most commonly described on a clinical basis using either the Hoehn and Yahr (H&Y) staging system (see Table 1.1), or the Unified Parkinson’s Disease Rating Scales (UPDRS). It is worth noting that PD does not inevitably progress to stages 4 and 5 on the H&Y scale.
Table 1.1: Hoehn and Yahr Staging of Parkinson's Disease
Based on an 8-year longitudinal study of 89 PD patients, deterioration is thought to occur at a rate of ~3% (mean = 1.9 points) of UPDRS score per year. Age, age at onset, disease duration, and excessive daytime somnolence are all strong predictors of greater impairment, with younger age at onset associated with a slower progression (Alves et al. 2005). Similarly, longitudinal PET using 18F fluorodopa reveals a 4-6% annual decline in loss of striatal dopaminergic neurones (Hilker et al. 2005). However, this latter study suggested a more rapid progression in earlier stages of the disease, slowing down in later years.
Parkinson's Plus Syndromes
The term “Parkinson’s Plus” refer to a number of syndromes with initial presentations that may resemble idiopathic PD, but differ in several key respects. The most significant clinical difference between these syndromes is that progression through H&Y staging categories (see Table 1.1) appears to be more rapid in these syndromes, suggesting a poorer prognosis. For example, a pathological study found that whilst no patients with idiopathic PD developed HY-III symptoms within the first year, this was the case for 72% of patients with PD+ syndromes.
The key to understanding this disease, as with the other neurodegenerative diseases, is to discover why and how specific populations of nerve cells in the brain or other parts of the nervous system die. Clues to what to investigate come from the known abnormalities in the brain in these diseases. For example, different proteins aggregate inside nerve cells and this results in the death of the affected cells. In Alzheimer’s disease, the characteristic neurofibrillary tangles are made of a protein called tau. In Parkinson’s disease the hallmark of the pathology is the presence of Lewy bodies made of the protein alpha-synuclein, while in motor neurone disease (MND) neurofilaments aggregate in the motor neurones. We have been studying all three of these proteins along with a number of other proteins implicated in other neurodegenerative diseases, and have made a number of significant discoveries that may help us understand how these proteins become involved in pathogenesis.
Alves G, Wentzel-Larsen T, Aarsland D, Larsen JP. Progression of motor impairment and disability in Parkinson disease: a population-based study. Neurology 2005; 65: 1436-1441.
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6/6/2012 2:43:17 PM - 18.104.22.168