Parkinson disease

Parkinson disease (PD), also known as idiopathic parkinsonism, is a neurodegenerative disease and movement disorder characterised by a resting tremor, rigidity and hypokinesia due to progressive degeneration of dopaminergic neurons in the substancia nigra. 

Epidemiology

Parkinson 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 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 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 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 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 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 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 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 disease. Perhaps even Lewy bodies play a protective role other forms of Parkinson 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

Loss of the normal swallow tail appearance of susceptibility signal pattern in the substantia nigra on axial imaging is perhaps the most promising diagnostic sign ¹². Apart from these changes, the signal intensity in substantia nigra depends on loss of neuromelanin and iron accumulation. In addition to aiding diagnosis, MRI is also used to identify features which may indicate secondary parkinsonism rather than primary disease, such as extensive small vessel ischaemic change.  

Features of Parkinson disease include ¹:

• T1
  • may show mild hyperintensity of compact and reticular parts of the substantia nigra and red nuclei (due to iron accumulation) ¹
  • may show loss of normal slight hyperintentisty in substantia nigra due to loss of neuromelanin ¹³

• T2* (GE/SWI)
  • absent swallow tail sign
    • nigrosome-1 is usually SWI hyperintense but this is lost in Parkinson disease
    • reported diagnostic accuracy of over 90%, with a 100% sensitivity and negative predictive value, 95% specificity, and 69% positive predictive value being reported in one study ¹²
  • may show loss of normal susceptibility signal drop-out of the substantia nigra and red nuclei (due to loss of melanin containing neurons)
    • dot-like areas of hyperintensity in the compact part of the substantia nigra ¹
  • may show confluence of the normal hypointense regions of substantia nigra (due to iron accumulation) ¹

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

Nuclear Medicine

Both SPECT and PET tracers can be used with high sensitivity for assessment of presynaptic dopaminergic deficits ^6,8.

Using I-123 FP CIT there is loss of the normal comma-shaped tracer uptake in the basal ganglia. Instead a period shape of uptake is seen within the caudate nucleus head without tracer uptake in the putamen.

Differentiation between Parkinson 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. 

History and etymology

Parkinson disease was first described by a British physician Dr James Parkinson, both in himself and five patients ¹.  

Differential diagnosis

There is significant overlap between many neurodegenerative disease, and Parkinson 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)
• corticobasal degeneration
• cerebrovascular disease
• metabolic diseases with parkinsonian signs and symptoms: basal ganglia signal abnormalities are usually more pronounced ¹
  • Wilson disease
  • manganese toxicity
  • chronic hepatitis