The sensory neuropathy of Friedreich's ataxia: an autopsy study of a case with prolonged survival

Abstract

Observations have been made on a patient with Friedreich's ataxia who died 52 years after the onset of symptoms. The pathology of the brain and spinal cord was typical of this disorder. Apart from loss of dorsal root ganglion cells, severe loss of secondary sensory neurons was observed, including the nucleus dorsalis in the spinal cord, the spinal and principal trigeminal nuclei and, in particular, the mesencephalic trigeminal nucleus in the brain stem. Morphometric studies on the first sacral nerve root and on the sural nerve at levels from midthigh to ankle revealed a distally accentuated axonal loss that predominantly affected larger myelinated nerve fibres. Regenerative activity was seen, mainly in the spinal root and proximally in the sural nerve. Relative myelin thickness, assessed by a g ratios, tended to be reduced. As teased fibre studies showed only limited evidence of demyelination/remyelination and of axonal regeneration, this therefore suggests the presence of a hypomyelination. The results confirm the presence of a distal axonopathy and provide no evidence that this is preceded by axonal atrophy.

Friedreich’s Ataxia: A New Mutation in Two Compound Heterozygous Siblings with Unusual Clinical Onset

“…They revealed considerable differences in the neuropathological features of the 2 siblings. In fact, patient 1 showed axonal loss and clear signs of de-and remyelination, as already reported in the literature [22,23] , whereas her brother had axonal neuropathy. Demyelination in patient 1 may also have been secondary to axonal atrophy.…”

Peripheral Neuropathy of Machado-Joseph Disease in Taiwan: A Morphometric and Genetic Study

“…Soong and Lin [11, 12]reported that the pathological findings for the peripheral nerves are similar to those seen in Friedreich’s ataxia, suggesting a loss of sensory and motor fibers probably following a lesion of the dorsal root ganglion and the anterior horns in the spinal cord. Jitpimolmard et al [19]reported an autopsy case of Friedreich’s ataxia with sensory neuropathy using morphometric analysis of the g ratio, which showed that the relative myelin thickness tended to be reduced suggesting the presence of a distal axonopathy and hypomyelination without evidence of preceding axonal atrophy. Our findings suggested that the peripheral neuropathy of MJD is a distal axonopathy with relative hypomyelination using the same morphometric analysis of the g ratio.…”

Friedreich ataxia: an overview

“…The corticospinal tract involvement, which is more severe laterally and distally,23 explains the common finding of upgoing plantar responses. A distal axonopathy affecting larger myelinated nerve fibres is also present 24. In the cerebellar cortex, there is only mild neuronal loss 25.…”