WASHINGTON — Sural nerve biopsy may be indicated in patients with refractory diabetic neuropathy, because they may have neural inflammation that responds to intravenous immunoglobulin, Dr. David S. Younger reported in a poster at the annual meeting of the American Association of Neuromuscular and Electrodiagnostic Medicine.
“Diabetes itself is a partially autoimmune process, or leads to the development of immunological changes,” Dr. Younger said in an interview. “Diabetic neuropathy is emerging as a disease mediated by autoimmunity and, therefore, it appears to respond to immunomodulating treatment—especially the neuropathic pain.”
In 1996, Dr. Younger, of New York University Medical Center, and his colleagues at Columbia University in New York, reported CD8-positive T cell infiltration in and around the walls of peripheral nerve microvessels in patients with diabetic neuropathy. They also noted inflammatory intermediate cytokines and activated C5b-9 membrane attack complex (MAC) in the endoneurium in the majority of the patients they studied. The researchers concluded that cell and humoral mediated immunologic mechanisms might be contributing to the pathogenesis of diabetic neuropathy (Muscle Nerve 1996;19:722–7).
At the meeting, Dr. Younger presented a 10-year review of 111 diabetic patients (aged 31–95 years) with neuropathic pain, progressive motor weakness, and disability characterized by distal symmetric polyneuropathy or proximal neuropathy, and 3 patients with mononeuritis multiplex. All underwent sural nerve biopsies to assist in management.
Axonopathy was present in 45 nerves, and myelinopathy in 23; 16 nerves met clinical and pathologic criteria for chronic inflammatory demyelinating polyneuropathy. Twenty-nine nerves showed inflammation in the microvasculature, including perivasculitis (26), microvasculitis (3), and necrotizing arteritis (3).
Twenty-nine patients with microvascular inflammation and/or chronic demyelinating polyneuropathy received immunotherapy with intravenous immunoglobulin in a regimen of 2 g/kg per month for 3–6 months. During follow-up phone interviews, all reported significant improvement in neuropathic pain.
There's little to lose by performing a nerve biopsy on patients whose diabetic neuropathy pain is poorly controlled on medication, Dr. Younger said. “Sural nerve biopsy is relatively safe, and it assists in the selection of patients who might benefit from immunotherapy.”
In this specimen, microvasculitis with lymphocytic T-cell infiltration of peripheral nerve neuropathy is visible.
This photo shows lymphocytic T-cell infiltration in perivasculitis of peripheral nerve microvessels. Photos courtesy Dr. David S. Younger