Unmyelinated nerve fiber degeneration in chronic inflammatory demyelinating polyneuropathy

Abstract

To determine whether unmyelinated nerve fibers escape degeneration as one might expect in an immune response exclusively directed at myelin, we performed a morphometric examination of unmyelinated axons and myelinated nerve fibers in sural nerve biopsy specimens of 14 patients with a chronic inflammatory demyelinating polyneuropathy (CIDP) and of 12 age-matched normal controls. The numbers of unmyelinated axons, myelinated nerve fibers, denervated Schwann cell units and collagen pockets were quantified and related to the clinical and electrophysiological data of the patients with CIDP. In 4 patients with a rapid onset of the neuropathy and a highly elevated CSF protein, the numbers of both unmyelinated axons and myelinated nerve fibers were decreased equally. In 8 patients we found that the unmyelinated axons were relatively spared compared with the loss of myelinated nerve fibers. In these patients, however, the presence of denervated Schwann cell units and of collagen pockets was increased. We conclude that unmyelinated nerve fibers are affected in patients with CIDP.

Disease activity in chronic inflammatory demyelinating polyneuropathy: A comparative study of clinical and skin biopsy markers

“…The results of this exploratory study confirm that small fibers are also affected in CIDP 13,14,16 . Unmyelinated nerve fiber involvement in sural nerve biopsy 26,27 and a reduction in corneal nerve fiber parameters have already been shown in CIDP 14,28,29 …”

“…The results of this exploratory study confirm that small fibers are also affected in CIDP. 13,14,16 Unmyelinated nerve fiber involvement in sural nerve biopsy 26,27 and a reduction in corneal nerve fiber parameters have already been shown in CIDP. 14,28,29 The first study evaluating skin biopsy in CIDP showed that IENFD in the distal legs of 18 CIDP patients was significantly reduced compared with healthy controls, and the decline was significantly associated with autonomic symptoms.…”

“…Another explanation is the possibility of an immune response directed to a common antigen shared by unmyelinated and myelinated nerve fibers, leading to the loss of both nerve fiber types in a subgroup of CIDP patients. 27 The limitations of our study include the small number of CIDP patients who gave consent for skin biopsy, causing a sampling bias, heterogeneity of patient characteristics such as disease subtypes, disease and treatment durations and treatment modalities, lack of agematched disease controls and follow-up, and lack of other biomarkers of disease activity such as imaging and electrophysiological (eg, MUNIX and CMAP) measures. Although there was no statistically significant difference in demographics between patients and healthy subjects, the healthy control group was younger than the patient group, which may also have impacted our results.…”

“…In a sural nerve biopsy study, reduction of unmyelinated axons was more prominent in large-diameter axons, possibly indicating that larger unmyelinated axons are more susceptible to nerve damage than smaller fibers. 27 Reduced IENFD may be a reflection of secondary axonal degeneration related to inflammatory demyelination of large myelinated sensory nerves in CIDP. Another explanation is the possibility of an immune response directed to a common antigen shared by unmyelinated and myelinated nerve fibers, leading to the loss of both nerve fiber types in a subgroup of CIDP patients.…”

Chronic Inflammatory or Chronic Inflammatory Demyelinating Polyradiculoneuropathy?

“…Axonal loss is usually considered as a secondary event in demyelinating disorders and its severity has implications for the diagnosis and prognosis; nevertheless recent studies indicate that axonal damage might also occur early in the disease ( 8 ). CIDP involves mainly myelinated fibers, but unmyelinated nerve fibers are also involved, probably due to a heterogeneous immunological pathogenesis and the severity of the inflammatory process ( 9 ).…”