Atypical dementia and spastic paraplegia in a patient with primary lateralsclerosis and numerous neocortical beta amyloid plaques: New disorder or Alzheimer's disease variant?

Primary lateral sclerosis (PLS) and hereditary spastic paraplegia (HSP) are clinically similar disorders in which progressive lower limb spasticity an d corticospinal tract degeneration are characteristic. We report the occurr ence of progressive spastic paraplegia and frontal systems dementia in a pa tient with postmortem features of PLS combined with moderate Alzheimer-like changes in neocortex and hippocampus. This combination of clinical and neu ropathologic findings has not been described in PLS or HSP and varies from other cases in which spastic paraplegia, dementia, and Alzheimer neuropatho logy occurred concurrently. This 69-year-old woman developed spastic quadri plegia and dementia over 12 years. Left leg weakness progressed over 7 year s to paraplegia, then quadriplegia by age 68. Sensory and cerebellar functi on were preserved and fasciculations were absent. Dementia characterized by concrete thinking, perseveration, and impaired executive function appeared in the seventh year and remained relatively stable until 6 months before d eath at age 69. Degeneration of the lateral corticospinal and dorsal spinoc erebellar tracts confined to the spinal cord was evident at postmortem exam ination. Brain stem, midbrain, and cerebellum were normal. Numerous beta/A4 amyloid positive diffuse plaques (10-15/200 x field) were apparent in neoc ortex, and neurofibrillary tangles immunopositive for paired helical filame nt were detected in hippocampus. This case broadens the spectrum of disorde rs associated with Alzheimer neuropathologic changes. The relationship betw een PLS, HSP, and Alzheimer's disease requires further study.