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.
Parkinson's disease is classically characterised by a triad of features:
- resting tremor
- 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.
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.
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 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:
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.
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.
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.
There is significant overlap between many neurodegenerative disease, and Parkinson's disease is no exception. Clinically the differential includes 1,3:
dementia with Lewy bodies
- dementia is clinically evident before, concurrently or at most within 12 months of onset of parkinsonian symptoms 2
- multiple system atrophy (MSA)
- progressive supranuclear palsy (PSP)
- cerebrovascular disease
metabolic diseases with parkinsonian signs and symptoms : basal ganglia signal abnormalities are usually more pronounced 1.
- Wilson disease
- manganese toxicity
- chronic hepatitis
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.
neurodegenerative MRI brain (an approach)
- measurements and ratios
- midbrain to pons area ratio (for PSP)
- Magnetic Resonance Parkinsonism Index (MRPI) (for PSP)
- frontal horn width to intercaudate distance ratio (FH/CC) (for Huntington's disease)
- intercaudate distance to inner table width ratio (CC/IT) (for Huntington's disease)
- scoring systems
- measurements and ratios
- progressive supranuclear palsy (PSP)
fronto-temporal lobar degeneration (FTLD)
- behavioural variant fronto-temporal dementia (bvFTLD)
- language variant fronto-temporal dementia (lvFTLD), (aka primary progressive aphasia (PPA)
- corticobasal degeneration
- typical / classical Alzheimer's disease
- variant (e.g. posterior cortical atrophy)
- cerebral amyloid angiopathy (CAA)
- transthyretine-associated cerebral amyloidoses
- human prion diseases (not always included as neurodegenerative)
- neuronal intranuclear hyaline inclusion disease (NIHID)
- Alzheimer disease
- spinocerebellar ataxias
- Huntington disease
- hereditary spastic paraplegia
- amyotrophic lateral sclerosis (ALS)
- clinically unclassifiable parkinsonism (CUP)
- 1. Kornienko VN, Pronin IN. Diagnostic Neuroradiology. Springer Verlag. (2008) ISBN:3540756523. Read it at Google Books - Find it at Amazon
- 2. Harding AJ, Broe GA, Halliday GM. Visual hallucinations in Lewy body disease relate to Lewy bodies in the temporal lobe. Brain. 2002;125 (Pt): 391-403. doi:10.1093/brain/awf033 - Pubmed citation
- 3. Dekker MC, Bonifati V, Van duijn CM. Parkinson's disease: piecing together a genetic jigsaw. Brain. 2003;126 (Pt): 1722-33. doi:10.1093/brain/awg172 - Pubmed citation
- 4. Cosottini M, Frosini D, Pesaresi I et-al. MR Imaging of the Substantia Nigra at 7 T Enables Diagnosis of Parkinson Disease. Radiology. 2014; 131448. doi:10.1148/radiol.14131448 - Pubmed citation
- 5. Kwon DH, Kim JM, Oh SH et-al. Seven-Tesla magnetic resonance images of the substantia nigra in Parkinson disease. Ann. Neurol. 2012;71 (2): 267-77. doi:10.1002/ana.22592 - Pubmed citation
- 6. Darcourt J, Booij J, Tatsch K et-al. EANM procedure guidelines for brain neurotransmission SPECT using (123)I-labelled dopamine transporter ligands, version 2. Eur. J. Nucl. Med. Mol. Imaging. 2010;37 (2): 443-50. doi:10.1007/s00259-009-1267-x - Pubmed citation
- 7. Van Laere K, Varrone A, Booij J et-al. EANM procedure guidelines for brain neurotransmission SPECT/PET using dopamine D2 receptor ligands, version 2. Eur. J. Nucl. Med. Mol. Imaging. 2010;37 (2): 434-42. doi:10.1007/s00259-009-1265-z - Pubmed citation
- 8. Brooks DJ. Imaging approaches to Parkinson disease. J. Nucl. Med. 2010;51 (4): 596-609. doi:10.2967/jnumed.108.059998 - Pubmed citation
- 9. Williams DR, Warren JD, Lees AJ. Using the presence of visual hallucinations to differentiate Parkinson's disease from atypical parkinsonism. J. Neurol. Neurosurg. Psychiatr. 2007;79 (6): 652-5. doi:10.1136/jnnp.2007.124677 - Pubmed citation
- 10. Bertram K, Williams DR. Visual hallucinations in the differential diagnosis of parkinsonism. J. Neurol. Neurosurg. Psychiatr. 2012;83 (4): 448-52. doi:10.1136/jnnp-2011-300980 - Free text at pubmed - Pubmed citation
- 11. Fearnley JM, Lees AJ. Ageing and Parkinson's disease: substantia nigra regional selectivity. Brain. 1991;114 ( Pt 5): 2283-301. Pubmed citation
Synonyms & Alternative Spellings
|Synonyms or Alternative Spelling||Include in Listings?|
|Parkinson disease (PD)||✗|
|Parkinson's disease (PD)||✗|