Neuropathology of primary restless leg syndrome: Absence of specific τ- and α-synuclein pathology

The neuroanatomical substrate for restless legs syndrome (RLS) is unknown. We identified 4 patients with idiopathic RLS who came to post-mortem examination, where brain and spinal cord tissue were available for neuropathological assessment. Lewy bodies were not identified and α-synuclein immunohistochemistry was uniformly negative. Neurofibrillary tangle pathology was variable and nonspecific. These findings suggest that τ- or α-synuclein brain pathology is not a component of primary RLS. Although chronic ischemic changes were found in all 4 cases, these were probably incidental. The absence of diagnostic microscopic brain or spinal cord pathology suggests that the pathologic substrate may be neurochemical or receptor based.