Friedreich Ataxia: Hypoplasia of Spinal Cord and Dorsal Root Ganglia.

Abstract

After Friedreich's description in 1877, depletion of myelinated fibers in the dorsal columns, dorsal spinocerebellar and lateral corticospinal tracts, and neuronal loss in the dorsal nuclei of Clarke columns were considered unique and essential neuropathological features of Friedreich ataxia (FA). Lack of large neurons in dorsal root ganglia (DRG), thinning of dorsal roots (DR), and poor myelination in sensory nerves are now recognized as key components of FA. Here, we measured cross-sectional areas of the mid-thoracic spinal cord (SC) and neuronal sizes in lumbosacral DRG of 24 genetically confirmed FA cases. Mean thoracic SC areas in FA (24.17 mm2) were significantly smaller than those in 12 normal controls (37.5 mm2); DRG neuron perikarya in FA (1362 µm2) were also significantly smaller than normal (2004 µm2). DRG neuron sizes were not correlated with SC areas. The FA patients included a wide range of disease onset and duration suggesting that the SC undergoes growth arrest early and remains abnormally small throughout life. Immunohistochemistry for phosphorylated neurofilament protein, peripheral myelin protein 22, and myelin proteolipid protein confirmed chaotic transition of axons into the SC in DR entry zones. We conclude that smaller SC areas and lack of large DRG neurons indicate hypoplasia rather than atrophy in FA.