Case Report Shows Neuropathological, Molecular Findings of SMA Type 3 With Superficial Siderosis

Researchers have published their postmortem report on a case of spinal muscular atrophy type 3 complicated by spinal superficial siderosis, offering details on their neuropathological and molecular findings.

The subject of the case report, a 55-year-old woman, had SMA type 3 and presented with lower extremity sensory symptoms characterized by pain and consistent with a myelo-radiculo-neuropathy. The woman, who began experiencing these symptoms at age 35, was diagnosed with SMA type 3—also known as the Kugelberg-Welander form of SMA—at 5 or 6 years. She was never fully ambulatory and had a surgical rod inserted at the age of 19 years for her severe scoliosis.

Prior to this case report, there was just 1 autopsy report of a patient with SMA type 3 genetically documented. According to the researchers, the neuropathological findings of the current case are in line with that first report, with classic changes of lower motor neuron neurodegeneration. Although, they noted the significant finding of a severe superficial siderosis involving predominantly the lower thoracic and lumbar-sacral spinal cord and nerve roots.

According to the researchers, the pathology of superficial siderosis in the central nervous system has previously been analyzed in an analysis of tissue from 9 patients, which found extensive deposits of iron and ferritin in siderotic tissues, severe loss of axons but better preservation of axons where the accumulation of iron is less severe, and anuclear foamy structures that were through to be to be axonal swellings. The researchers of the analysis concluded that the iron-induced neuronal injury was likely nor reversible.

In the current case study, the researchers saw similar findings, observing that axonal damage resulting from the superficial siderosis was present and severe. They also documented some axonal swellings in the affected tissue.

“In the sensory pathways specifically, the unbalanced demyelination of the gracile fasciculi (superficial regions as opposed to the inner regions) empasises the loss of axons within the siderotic regions. In the sensory nerve roots, the axonal loss was subtle, but the deposition of hemosiderin was significant,” noted the researchers. “We propose that the nerve root involvement, that is axonal loss or chemical irritation, best explain the sensory symptoms our patient presented in the evolution of her SMA type III with the understanding that mechanical factors cannot be totally excluded.”

Other neuropathologic observations included:

• The anterior gray horns in the spinal cord were significantly decreased in volume
• Severe loss of motor neurons
• A severe circumferential hemosiderosis as shown by spinal lower thoracic and lumbo-sacral levels
• Very thin anterior nerve roots with severe loss of myelinated axons and fibrosis
• A very mild subacute leptomeningitis with Gram positive cocci

Reference

Pringle C, Nelson R, Miller W, Kothary, Michaud J. Spinal muscular atrophy type III complicated by spinal superficial siderosis: a case report with molecular and neuropathological findings. Acta Neuropathol Commun. Published online November 9, 2020. doi:10.1186/s40478-020-01063-9