IBM is clinically characterized by slowly progressive weakness, often proximal and distal, with muscle atrophy and dysphagia and a lack of improvement with immunosuppressive therapy. While studies performed on muscle reproducibly demonstrate electrophysiologic and histologic evidence of neurogenic changes, minimal information is available concerning spinal cord pathology in sIBM.

A limited autopsy was performed, and the entire spinal cord was submitted for H&E and immunohistochemical assessment. Select sections of the brain were evaluated with immunohistochemistry (IHC). Skeletal muscle was evaluated with IHC, enzyme histochemistry, and electron microscopy. A 31-gene panel (including FUS, SQSTM1, TARDP, and VCP) was performed on skeletal muscle. Additionally, 72 spinal cord levels in 22 non-amyotrophic lateral sclerosis (ALS)/non-IBM adult patients were blindly screened for motor neuron (MN) and glial inclusions using TDP-43 and pTDP-43.

Sampled muscle showed the characteristic features of IBM. The spinal cord demonstrated diffuse ventral nerve root atrophy, and H&E sections revealed mild, patchy MN loss, microglial activation, and chromatolytic neurons at multiple spinal levels. Rare pale or granular cytoplasmic inclusions were seen in MNs, some of which were positive for p62, a-synuclein, N-terminal TDP-43, and phosphorylated TDP-43. No genetic mutations were identified. All non-ALS control spinal cord sections were negative for TDP-43-positive MN inclusions.

These findings suggest that sIBM may be associated with neuronal pathologies at multiple spinal cord levels. In this case, these pathologies are most suggestive of secondary degeneration following injury to the NMJ or distal axon. Further study in additional cases is required to determine whether these alterations are a reproducible part of the pathologic spectrum of sIBM.