Most PD cases occur sporadically and are of unknown cause. Degeneration of pigmented pars compacta neurons of the substantia nigra in the midbrain resulting in lack of dopaminergic input to striatum; accumulation of cytoplasmic intraneural inclusion granules (Lewy bodies). Cause of cell death is unknown, but it may result from generation of free radicals and oxidative stress, inflammation, or mitochondrial dysfunction; no environmental factor has yet been conclusively determined to cause typical PD. Rare genetic forms of parkinsonism exist (~5% of cases); most common are mutations in glucocerebrosidase, LRRK2, α-synuclein or parkin genes. Early age of onset suggests a possible genetic cause of PD, although LLRK2 mutations cause PD in the same age range as sporadic.