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Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) was first described in the French-Canadian founder population of Quebec in 1978, but genetically confirmed patients have now been reported in individuals from Europe and Japan. Ataxia, dysarthria, spasticity with extensor plantar reflexes, distal muscle wasting, sensorimotor neuropathy and horizontal gaze-evoked nystagmus constitute the most frequent progressive neurological signs. Neuroimaging reveals atrophy of the superior vermis, cervical spinal cord, and cerebral cortex.1 SACS is the most frequent gene associated with ARSACS.2
Previous authors reported that retinal hypermyelinated fibres observed in funduscopy are a minor diagnostic criterion for ARSACS that may identify patients with early-onset cerebellar ataxia and characteristic pontine abnormalities.2 ,3 We found patients with full ophthalmological examination and retinal nerve-fibre layer (RNFL) photographs showing significant increases in RNFL thickness compared to healthy subjects, but not the myelinated fibres radiating from the optic disk described by previous authors. In addition, digital imaging technologies such as optical coherence tomography to measure peripapillary RNFL thickness and provide retinal images show an increase in the RNFL density in these patients.
These findings suggest that RNFL hypertrophy in ARSACS patients was interpreted as hypermyelinated retinal fibres in previous reports, and thus the ARSACS diagnostic criteria, particularly with regard to retinal alterations, should be revised. Increases in RNFL density cause retinal streaks observed in the funduscopy exam that may be confused with hypermyelinated fibres, but the physiopathology, clinical manifestations and optical coherence tomography images and measurements are different (figure 1).4–6
The SACS gene is involved in nerve fibre development, so ARSACS patients may tend to have hypermyelinated retinal fibres, but re-evaluation of the published articles that some of the images that were considered to show myelinated fibres radiating from the optic disk by previous authors actually shown an increase in the number of retinal nerve fibres (figure 1).
In addition, our hypothesis of RNFL hypertrophy is strengthened by the following findings: tensor diffusion sequences indicate that the hypointense striation corresponds with hyperplasia of the pontocerebellar fibres, which leads to abnormally thick middle cerebellar peduncles;5 ,6 T2 and T2-fluid attenuation inversion recovery-weighted MRI sequences reveal cerebellar atrophy and a hypointense linear striation at the pons;5 ,6 ultrastructural observations do not corroborate the notion that hypermyelinated fibres constitute the basic pathophysiology of the retinal abnormities in ARSACS patients;4 genetic studies indicate that SACS functions in nerve fibre development; and nerve biopsies in patients published to date reveal only a depletion of myelinated fibres, and not hypermyelinated fibres (figure 2).4
Our results suggest that the retinal streaks are caused by increases in RNFL density, but diagnostic histology of pathological specimens from deceased patients are needed to confirm it. The most recent studies in ARSACS patients suggest a role for the SACS gene in nerve fibre development, causing RNFL hypertrophy and alterations in the central nervous system.
In our opinion, some of the fundus images described as showing hypermyelinated retinal fibres are actually showing increased thickness of the RNFL as in our patients2 ,3 (figure 1). Therefore, we recommend that experts review these published photographs and perform a complete ophthalmological examination based on stereophotographs, RNFL photographs and analysis with digital image analysis devices.
Contributors EG-M, LEP, JG, VP, AF, JML have made a substantive intellectual contribution to the submitted manuscript (design and conceptualisation of the study and manuscript, analysis and interpretation of the data and revising the manuscript). These authors have given final approval of the version to be published.
Competing interests None.
Ethics approval Comité ético de Investigación clínica de Aragón (CEICA).
Provenance and peer review Not commissioned; externally peer reviewed.
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