American Society for Peripheral Nerve

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Heterotopic ossification of a peripheral nerve following blast injury: A report of two cases
Patrick E. Jones, MD1; Kevin o'Malley, MD2; Youngmi Ji, PhD3; Leon J. Nesti, MD, PhD1
1Orthopaedic Surgery, Walter Reed National Military Medical Center, Bethesda, MD; 2Orthopaedic Surgery, Georgetown University, Washington, DC; 3Nesti Orthopaedic Research Group, National Institutes of Arthritis, Musculoskeletal and Skin diseases, Bethesda, MD

Introduction: We report on two cases of patients, who had high energy penetrating injuries resulting in transection of their sciatic nerves. At the time of surgical exploration and nerve reconstruction, fibrotic tissue consistent with early heterotopic ossification was encountered. This tissue was not limited to the surrounding muscle, when the residual nerve was opened to identify the fascicles fibrotic tissue and osteoid was also encountered. To our knowledge this is the first instance of combat related heterotopic ossification of a peripheral nerve.

Methods: Resected nerve tissue from sciatic nerve exploration and grafting was determined intraoperativley to have ectopic bone in it. Nerve tissue was taken to the National Institutes of Health Orthopedic Basic Science lab and analyzed for osteogenic and fibrotic markers in addition to markers of mesenchymal progenitor cells (MPCs).

Results: Two patients sustained sciatic nerve transections as a result of gunshot wounds were taken to the OR for exploration and grafting. The nerves were identified as completely transected and the proximal and distal neuromas removed. The defects were reconstructed with cadaveric allograft and the resected nerve ends were analyzed histologically. H and E staining demonstrated osteoid in the nerve sheath while picosirus red staining displayed high levels of collagen 1 in the nerve consistent with a fibrotic environment. Immunofluroesence demonstrated high levels of BMP2 in the neuron with CD44 (a marker for MPCs) in the surrounding tissue and invading the nerve.

Discussion: Heterotopic ossification has been well described in traumatic wounds particularly those relating to combat trauma however this is the first description of it occurring in a peripheral nerve following trauma. The early cases of neuritis ossificans occurred in the absence of trauma without surrounding tissue involvement. When analyzed the nerve stained positive for BMP2 and substance P both proteins that have been associated with heterotopic ossification. Substance P is known to be increased at sites of bone regeneration and BMP2 is known to sensitize tissue to trauma-induced HO. Additionally there was staining for CD44 in the surrounding tissue of the nerve. Previous studies have identified CD44 as a marker of MPCs and demonstrated the capability of MPCs to undergo osteogenesis. These findings would suggest that high levels of BMP2 in the nerve and surrounding MPCs make the peripheral nerve primed for HO development. The intact nerve sheath likely plays a prominent role in prevention of HO formation in peripheral nerves following trauma.

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