Giant axonal neuropathy: Correlation of clinical findings with postmortem neuropathology

Abstract

We report the clinical and postmortem neuropathological findings in a case of long-standing giant axonal neuropathy. The patient, a caucasian male with kinky hair, was first seen at 4 years of age because of increasing unsteadiness of gait. Clinical examination showed nystagmus, cerebellar ataxia, distal sensory loss, and weakness. A sural nerve biopsy at 8 years of age revealed giant axonal neuropathy. The patient became increasingly demented and was incapacitated by weakness and ataxia; he died at 18 years of age. Histological examination of the brain and spinal cord showed numerous Rosenthal fibers, a distal axonopathy that most severely affected the corticospinal tracts, middle cerebellar peduncles, and posterior columns, and olivocerebellar degeneration.

Giant axonal neuropathy: clinical and genetic study in six cases

“…33 37 Demyelination with gliotic changes, few giant axons, and numerous astrocytic processes and Rosenthal fibres were reported microscopically in the white matter lesions of patients with GAN. 28 In accordance with the histopathological features, recently, cerebral proton magnetic resonance spectroscopy of a patient with GAN showed findings of demyelination in the white matter, and increased amounts of choline containing compounds and myoinositol. 17 The cavum septi pellucidi and vergae abnormalities were detected in the MRI of all patients, and have also been noted in other patients with GAN.…”

Neuroaxonal Leukoencephalopathy with Axonal Spheroids

“…Recently, enlarged axons have been found accompanying numerous spheroids in the sural nerve in several cases of infantile NAD [25, 26]. On the other hand, degenerative changes of the CNS have been occasionally reported in giant axonal neuropathy [27, 28, 29, 30]. In the cases of giant axonal neuropathy with CNS involvement, giant axons were noted together with spheroids throughout the CNS, especially in the long tracts, including the corticospinal and spinocerebellar tracts and posterior columns.…”

Giant axonal neuropathy–like disease in an Alexandrine parrot (Psittacula eupatria)

“…However, the absence of neurofilament positivity with immunohistochemistry, together with the negative Bodian staining, suggests that the material does not contain any of the normal major subunits associated with neurofilament triplet proteins in 2 This is distinct from the human form of giant axonal neuropathy, in which the axonal aggregates are both argyrophilic and neurofilament positive. 1,20 The lack of staining with Gallyas stain further indicates that the aggregates do not contain tau protein, 13 a microtubule-associated protein. Although formalin fixation precluded further identification of the material, it is possible that the bodies may represent an accumulation of other structural elements of neurons, such as internexin, nestin, peripherin, or β-tubulin III.…”