The autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is considered a neurodegenerative disease caused by mutations in the SACS gene, located on chromosome 13q12.12. It is a syndrome that comprises skeletal, retinal and neurological manifestations, among which feature spasticity, cerebellar ataxia and peripheral neuropathy. Five patients with a molecular diagnosis of ARSACS underwent clinical, radiological, and ophthalmologic examinations. Every one of the identified causal mutations was novel. Spastic ataxia, peripheral neuropathy, pes cavus, and hammertoes were found in every case. T2 and T2-fluid attenuation inversion recovery-weighted MRI sequences demonstrated cerebellar atrophy and a hypointense linear striation at the pons. Tensor diffusion sequences revealed that the hypointense striation corresponded with hyperplasia of the pontocerebellar fibres, which gave place to abnormally thick middle cerebellar peduncles. Stereophotographs of the optic discs showed an increased number of retinal fibres, and ocular coherence tomography, increased thickness of the retinal nerve fibre layer. The authors suggest that the hyperplasic pontocerebellar fibres compress the pyramidal tracts at the pons since a very early stage of central nervous system development, causing spasticity, and may also cause cerebellar atrophy by means of glutamate-induced excitotoxicity. The abnormal amount of retinal fibres traversing the optic discs could have caused the detected mild peripheral visual field defects. Taken together, these facts point to a developmental cause in ARSACS, as it does not exhibit the tissue atrophy characteristic of degenerative diseases. Clinical deterioration in ARSACS seems to be mediated by phenomena (compression of the pyramidal tracts and cerebellar glutamate-mediated excitotoxicity) derived from the developmental anomalies referred to, while the neuromuscular symptoms are caused by a peripheral neuropathy with pathologic features suggestive of a similar origin. These observations should be taken into account when research about the origin of ARSACS is undertaken.
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