Parkinson’s Disease and Related Alpha-Synucleinopathies

Sporadic Parkinson's disease: mean age of onset around 61 years

No gender predominance

Prevalence: markedly increases with age

• Whites: 150 to 400 per 100,000 individuals

• Asians: 100 to 130 per 100,000 individuals

• African Americans: 105 per 100,000 individuals

Overall incidence: 15 to 20 per 100,000/year

Symptoms caused by dopamine deficiency from substantia nigra degeneration

Half of patients initially present with resting tremor in unilateral hand or leg with progressive involvement of other extremities

Other features include the following:

• Cogwheel rigidity

• Bradykinesia and akinesia (slowness and absent movement)

• Righting reflex loss and gait abnormalities

• Loss of automatic movements of skeletal muscle (eye blinking, masked facies)

• Autonomic dysfunction (bowel and bladder dysfunction)

• Cognitive decline and depression

Disease progression to death within 8 to 15 years after symptom onset

Symptomatic treatment with l -DOPA, dopamine agonists, monoamine oxidase B inhibitors

Deep brain stimulation may improve symptoms

No specific radiographic findings

Mild cortical atrophy may be present

Depigmentation/pallor of substantia nigra and locus coeruleus

Pigmented neuron loss within the substantia nigra and locus coeruleus

Lewy bodies: single to multiple intracytoplasmic inclusions composed of round, eosinophilic central material surrounded by prominent pale haloes; found within brain stem neurons

Cortical Lewy bodies (usually not the dominant feature): intraneuronal, eosinophilic, rounded to reniform inclusions without prominent haloes

• Prominent within cerebral cortical neurons of layers V and VI of temporal lobe, cingulated gyrus, insula

“Pale bodies”: intracytoplasmic, amorphous, pale, eosinophilic material present within pigment neurons which displaces neuromelanin to cell periphery; may be precursors to classic Lewy bodies

Lewy neurites: dystrophic/degenerated neurites; most commonly found in the hippocampus (CA2-3 region) and amygdala (accessory cortical nuclei)

Current consensus guidelines score Lewy body pathology based on regional involvement:

• None : no Lewy bodies or related changes in α-synuclein immunohistochemistry

• Brain stem predominant : Lewy bodies in medulla, pons, or midbrain

• Limbic (transitional) : Lewy bodies in cingulate or entorhinal cortices, usually with brain stem involvement

• Neocortical (diffuse) : Lewy bodies in frontal, temporal, or parietal cortices, usually with involvement of brain stem and limbic sites, which may include amygdala

• Amygdala predominant : Lewy bodies in amygdala with paucity of Lewy bodies in the preceding regions

Lewy bodies and Lewy neurites: positive for α-synuclein (most specific antigen), ubiquitin, neurofilament, amyloid β peptide, amyloid precursor protein