Case Study 22 Craig Horbinski, M.D., Ph.D.

The patient is a 63 year-old woman from an outside hospital with gradual onset of proximal leg pain, weakness, reduced tendon reflexes, and right foot drop. Conduction studies showed peroneal neuropathy in the right leg and decreased motor amplitude to the right leg. A right sural nerve biopsy is performed. Describe the biopsy and stains. Click the following links to view the slides: H&EH&E, Elastic Trichrome, CD3, Toluidine BlueElastic TrichromeCD3Toluidine Blue Question 1

Hematoxylin and eosin stained paraffin nerve sections reveal 9 fascicles with focal necrotizing vasculitis affecting an epineurial arteriole of about 50 microns in diameter. No eosinophils or PMNs are seen. There is also scattered substantial perivascular inflammation. Trichrome reveals no significant endoneurial fibrosis (chronic loss of myelinated axons). CD3 (pan-T-cell antigen) immunohistochemical staining reveals significant reactivity within a vessel wall and scattered perivascular lymphocytes elsewhere. Toluidine blue stained plastic sections show no substantial loss of myelinated axons. There is some crush artifact (dark blue smudgy-looking axons) but there are no obvious myelin ovoids (acutely degenerating axons), regenerative axon clusters, onion bulbs, or thinly myelinated axons. Necrotizing vasculitis is again noted. Answer

Question 2 What is your diagnosis? What is the differential etiology? What should you do next?

Answer Acute necrotizing vasculitis. The differential diagnosis includes polyarteritis nodosa, other primary vasculitides, rheumatoid or other connective tissue disease associated vasculitis, primary PNS vasculitis, cryoglobulinemia, and less likely paraneoplastic vasculitis. In any case of vasculitis the clinician needs to be contacted. This can be difficult, especially when the case is from an outside institution, but it is imperative that such efforts are made and documented in the report.

Question 3 What 2 mistakes did the clinicians make that could have been disastrous?

Answer If the conduction studies are showing abnormalities in the peroneal nerve, then the superficial peroneal nerve is the logical target, not the sural nerve. In addition, a nerve-only biopsy is far less sensitive than a combination muscle (usually peroneus brevis) and nerve biopsy for detecting vasculitis. It was fortunate that the patchy vasculitis was caught on the sural nerve tissue; other deeper H&E levels showed no sign of inflammation at all.

Question 4 How do you reconcile the absence of nerve changes with the obvious vasculitis? What sort of nerve changes would you have expected to see?

Answer Either the onset of leg pain and vasculitis was more recent than suggested in the scant clinical history, or the nerve changes are just as patchy as the inflammation and might have been seen in a different segment of the nerve. Expected nerve changes would have included axonal degeneration, which is always seen in ischemic neuropathies.