Description
Parkinson’s Disease (PD) is a progressive neurodegenerative disorder characterised by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc), resulting in a movement disorder with both motor and non-motor symptoms.
Pathogenesis
The exact pathogenesis of PD is not well understood, but it is believed to involve both genetic and environmental factors leading to the degeneration of dopaminergic neurons in the SNc. This degeneration leads to a decrease in striatal dopamine levels, causing an imbalance in the direct and indirect pathways of the basal ganglia, resulting in the characteristic motor symptoms of PD. The accumulation of Lewy bodies, composed of misfolded alpha-synuclein, is a key neuropathologic feature.
Epidemiology, Risk Factors & Associations
PD affects approximately 1-2% of the population over 60 years of age, with a slight male predominance. Risk factors include older age, exposure to certain pesticides, and a family history of PD. Some genes have been associated with familial forms of PD (e.g., SNCA, LRRK2, Parkin).
Clinical Features
The cardinal features of PD are:
- Rest tremor (“pill-rolling” tremor)
- Rigidity (lead-pipe and cogwheel)
- Akinesia/bradykinesia (slowness/absence of movement)
- Postural instability.
Non-motor symptoms include depression, cognitive impairment, autonomic dysfunction, sleep disturbances, and anosmia.
Complications
Common complications include falls, dysphagia with aspiration risk, and neuropsychiatric issues such as depression and dementia.
Pathological Features
Histopathology
Loss of pigmented dopaminergic neurons in the SNc with presence of Lewy bodies and neurites (Lewy pathology) in remaining neurons.
Lewy bodies are cytoplasmic inclusions consisting of aggregated α-synuclein, ubiquitin, tubulin, and neurofi lament proteins. Lewy bodies stain positive for α-synuclein.
Radiological Features
MRI
- T1/T2: Generally normal in early PD.
- SWI: May show hypointensity in the SNc due to iron deposition.
- DTI: May show alterations in white matter tracts.
NM
- PET/SPECT: Demonstrates reduced presynaptic dopamine transporter activity in the striatum.
Diagnosis
PD is primarily a clinical diagnosis based on history and examination findings. There are no definitive diagnostic tests, but functional imaging (SPECT, PET) may support the diagnosis.
Differential Diagnosis
- Multiple system atrophy: Presents with autonomic dysfunction, cerebellar signs, and poor response to levodopa. Cross-shaped T2 hyperintensity within pons (hot cross bun)
- Progressive supranuclear palsy: Characterised by early falls, vertical gaze palsy, and prominent axial rigidity.
- Lewy body dementia: Presents with early cognitive decline, visual hallucinations, and fluctuating consciousness.
Management
Management of PD is typically by a neurologist and includes symptomatic treatment with medication (e.g., levodopa, dopamine agonists), physical therapy, and supportive care. Deep brain stimulation may be considered in refractory cases.