Ischemic Injury and Microvasculitis in Treatment Induced Neuropathy of Diabetes
Hebatallah Rashed1, Kamal Shouman1, Catarina Aragon Pinto1, Marcus Vinicius Pinto1, Peter Dyck1, JaNean Engelstad1, Catherine Daley1, Christopher Klein1, P. James B. Dyck1
1Mayo Clinic
Objective:

Because of the similarities in the clinical features of DLRPN and TIND (rapid evolution with pain and often weight loss), we postulate that some cases of TIND may also be due to ischemic injury and microvasculitis

Background:

Treatment induced neuropathy of diabetes (TIND) is a painful, autonomic, subacute neuropathy occurring after rapid hyperglycemia correction, often in type 1 diabetes; the pathophysiology is not understood.  Diabetic lumbosacral radiculoplexus neuropathy (DLRPN) is also a painful, subacute neuropathy mostly of type 2 DM that is due to ischemic injury and microvasculitis.

Design/Methods:

We retrospectively identified TIND patients seen at our institution who had undergone sural nerve biopsy between 1996 - 2022. TIND was defined as acute neuropathic pain and/or autonomic impairment within 8 weeks of marked improvement in glycemic control in DM (decrease in HbA1c of 2% over 3 months).

Results:

Eight TIND patients with nerve biopsies were identified. All were males, and median age was 56.9 years (42-70). Neurological examination showed decreased pinprick and temperature in the feet with normal strength in 4, and mild toe flexion/extension weakness in 4.  All biopsies had abnormal degrees of inflammation with perivascular inflammatory infiltrates (large [3], moderate [3] and small [2]), with 2 diagnostic of microvasculitis, 2 highly suggestive of microvasculitis, and 1 suggestive of microvasculitis. Seven biopsies showed evidence of ischemic injury: multifocal fiber loss (5), neovascularization (5) and perineurial thickening (3). On teased fibers, there was increased axonal degeneration (mean 16.8%; 2.9-60%) and increased rates of segmental demyelination (mean 5.3%; 0-16.2%) which appeared to be secondary.

Conclusions:

We found evidence implicating ischemic injury and microvasculitis as the putative mechanism of TIND. The pathological findings we found are similar to those of  DLRPN. We postulate that the rapid hyperglycemia correction triggers an immune attack on nerves. Larger studies are needed to confirm microvasculitis as the main pathology of TIND.

10.1212/WNL.0000000000206224