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Parkinson's disease

Parkinson's disease (PD) (also known as idiopathic parkinsonism) is a neurodegenerative disease and movement disorder characterised by a resting tremor, rigidity and hypokinesia. 

Epidemiology

Parkinson's disease is by far the most common cause of the parkinsonian syndrome, accounting for approximately 80% of cases (the remainder being due to other neurodegenerative disease, such as Lewy body dementia) 1

The most common form is encountered in elderly patients and is common, seen in 2-4% of all individuals older than 65 years of age. 

A juvenile form of Parkinson's disease is also recognised, manifesting between 20 - 40 years of age 1

The majority of cases (85 - 90%) are sporadic, however 10 - 15% of patients have a positive family history 1

Clinical presentation

Parkinson's disease is classically characterised by a triad of features: 

  1. resting tremor
  2. rigidity
  3. bradykinesia
  4. postural instability : sometimes added as a cardinal feature 3

Dementia can be a late feature. When present it is known as Parkinson's disease with later developing dementia (PDD). In contrast, Lewy body dementia has cognitive impairment either preceding or at most within 12 months of clinical onset of parkinsonian symptoms 2

Visual hallucinations are also quite common reported to occur in 6-75% of patients (most reports suggest an incidence of 25-50% ), more frequently in patients treated with dopaminergic medication 9-10

Pathology

The dopaminergic tract is predominantly affected in Parkinson's disease, and histologically, it is characterised by nigrostriatal dopaminergic degeneration leading to neuronal loss in the substantia nigra pars compacta, most conspicuous in the ventrolateral tier of neurons 11. A number of other regions including parts of the basal ganglia, brainstem, autonomic nervous system and cerebral cortex 3.  

At least eleven genes have been implicated in various forms of Parkinson's disease 3. Interestingly depending on which genes are involved, various clinical features are more or less prominent (e.g. Kufor-Rakeb syndrome). 

Even more interestingly not all mutations result in Lewy bodies. For example juvenile Parkinson's disease has been linked to mutations in the PARK2 gene, which encodes for the enzyme ubiquitin ligase-L3. In normal individuals, ubiquitin ligase-L3 is involved in ubiquitination of alpha-synuclein (the main component of Lewy bodies) and allows the formation of Lewy bodies. In patients with juvenile Parkinson's disease its function is impaired and the formation of Lewy bodies is impossible. This finding suggests that Lewy bodies cannot be thought of as synonymous  with, and causative of Parkinson's disease. Perhaps even Lewy bodies play a protective role other forms of Parkinson's disease, which manifests 20-40 years later 1

Radiographic features

Initial imaging findings are subtle and only potentially seen on MRI. 

With advanced disease, non-specific generalised minor cerebral volume loss can be demonstrated. 

MRI

MRI is not only able to identify some relatively specific features, but more importantly is often able to identify features which suggest secondary parkinsonism (e.g. extensive small vessel ischaemic change). 

Features of Parkinson's disease include 1:

  • T1
    • mild hyperintensity of reticular parts of the substantia nigra and red nuclei
    • dot-like areas of hyperintensity in the compact part of the substantia nigra
  • T2* (GE / SWI) : loss of normal susceptibility signal drop-out of the substantia nigra and red nuclei 
    • best sign
    • due to loss of melanin containing neurons

Recent studies with high Tesla MRI (7 T) have shown promising results regarding both sensitivity and specificity 4-5.

Nuclear Medicine

holds tracers for both SPECT and PET with high sensitivity for assessment of presynaptic dopaminergic deficits 6,8.

Differentiation between Parkinson's disease and atypic parkinsonism is also possible, with different tracers 7-8.

Treatment and prognosis

The mainstay of treatment is medical. In patients with refractory symptoms, deep brain stimulation may be useful. 

Etymology

Parkinson's disease was first described by a British physician James Parkinson, both in himself and five patients 1. As such it is one case where the apostrophe is recommended. 

Differential diagnosis

There is significant overlap between many neurodegenerative disease, and Parkinson's disease is no exception. Clinically the differential includes 1,3:


Related articles

Neurodegenerative diseases

Neurodegenerative diseases are legion and their classification just as protean. A useful approach is to divide them according to underlying pathological process, although even using this schema, there is much overlap and thus resulting confusion. 

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