Hereditary spastic paraplegia


Major neuropathologic features of autosomal dominant, uncomplicated HSP are axonal degeneration that is maximal in the terminal portions of the longest descending and ascending tracts (crossed and uncrossed corticospinal tracts to the legs and fasciculus gracilis, respectively). (Behan and Maia, 1974; Harding, 1993; Schwarz and Liu, 1956) Spinocerebellar fibers are involved to a lesser extent. Neuronal cell bodies of degenerating fibers were preserved, and there was no evidence of primary demyelination. Loss of anterior horn cells is observed in some cases. Dorsal root ganglia, posterior roots and peripheral nerves are normal.

The regional pattern of axonal degeneration in uncomplicated HSP is quite different from that seen in "system degeneration" diseases, such as amyotrophic lateral sclerosis (ALS). System degeneration in ALS includes cortical (pyramidal) neurons, corticospinal tracts, anterior horn cells (innervated by corticospinal tracts) and skeletal muscle. Parkinson's disease (with loss of dopaminergic neurons in the substantia nigra pars compacta and secondary changes in brain regions that receive this dopaminergic innervation) may exemplify another system degeneration. Axonal degeneration in uncomplicated, autosomal dominant HSP involves different classes of neurons (corticospinal tract fibers from pyramidal neurons in the motor cortex; fasciculus gracilus [and cuneatus to a lesser extent] from dorsal root ganglia neurons). One obvious feature shared by these degenerating axons is their length. These are the longest fibers in the central nervous system (CNS). Degeneration was maximal in the distal axons of these fibers.

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