Which histologic findings are characteristic of spinal muscular atrophy (SMA)?

Updated: Dec 22, 2019
  • Author: Hidehiro Takei, MD; Chief Editor: Adekunle M Adesina, MD, PhD  more...
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Autopsy findings of spinal muscular atrophy (SMA) have mostly been reported from patients with SMA type I. The cardinal histologic feature of SMA type I is the paucity of motor neurons in the spinal cord and brainstem, with the few surviving motor neurons characterized by ballooning and chromatolysis. [59] In SMA type I, chromatolytic neurons tend to be markedly ballooned and spheroidal and to contain as yet ill-defined material inside them, in contrast to the neurons seen in other motor neuron disorders (MNDs), such as ALS. [60]

Chou and Wang described the following histopathologic tetrad of SMA type I [60] :

  • Central chromatolysis

  • Empty cell beds – These are empty (glial) shells or spaces that are still enclosed by the usual fiber network left by the previous occupants, motor neurons; they are easily visible with special stains (Bodian and others)

  • Migratory (heterotopic) motor neurons – These are seen along the distal pathways of their axons in the anterior spinal roots

  • Glial bundles of spinal roots – Outgrowth of birefringent glial bundles parallel to the spinal root axons is frequently seen in the anterior spinal nerve roots (proximal portion), which is apparent with polarizing microscopy

Other reported findings, especially in individuals with longer survival periods, include involvement of the dorsal root ganglia (with nodules of Nageotte), Clarke column, and lateral thalamic nucleus, with neuronal chromatolysis and ballooning. [59, 61]

An autopsy report on 2 patients with clinicogenetically confirmed SMA type II described severe reduction of motor neurons and gliosis in the spinal cord and brainstem. [61] However, in contrast to SMA type I, the Clark and lateral thalamic nuclei were spared, and ballooned and chromatolytic neurons were rarely seen. Additional findings were reduced Betz cells and large myelinated fibers in the lateral funiculus. [61]

The main histologic finding with SMA type III is a marked neuronal loss in the anterior horns throughout the spinal cord. The only autopsy report of a patient with clinicogenetically confirmed SMA type III noted inconspicuous empty cell bed formation, a small number of migratory (heterotopic) motor neurons, and prominent glial bundles in spinal roots in addition to the typical changes in the spinal anterior horns. [62]

Chromatolytic motor neurons were not as enlarged, were small in number, and were observed only in the anterior horn. [62] Changes other than those in motor neurons included moderate loss of myelinated fibers in the fasciculus gracilis and marked loss of neurons with severe gliosis in the dentate nucleus.

Because histopathologic features of muscle biopsies in SMA types I and II are essentially identical, the 2 types cannot be distinguished on the basis of muscle pathology alone. Characteristic features include atrophy affecting both type 1 and type 2 fibers, with type I fiber hypertrophy, and (in non–early onset cases) fiber type grouping (see the images below). The atrophic fibers are usually round in shape, in contrast to other forms of neurogenic atrophy, such as ALS. Excess endomysial connective tissue is not seen.

Pathology of motor neuron disorders. Spinal muscul Pathology of motor neuron disorders. Spinal muscular atrophy type I (Werdnig-Hoffmann disease). This muscle biopsy histologic slide shows large group atrophy with fiber hypertrophy. (Hematoxylin and eosin stain, ×40)
Pathology of motor neuron disorders. Spinal muscul Pathology of motor neuron disorders. Spinal muscular atrophy type I (Werdnig-Hoffmann disease). This muscle biopsy histologic slide shows large group atrophy with hypertrophic fibers identifiable as type I fibers. (ATPase pH 4.3, ×40)

The muscle pathology in SMA type III is variable, ranging from minimal changes to small or large group atrophy with fiber type grouping. Fatty infiltration of variable degree is noted. Hypertrophic type I fibers can be seen. A concomitant myopathic pattern can also be present.

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