Sural nerve biopsy utility by masked assessment of individual histologic preparations

Pannathat Soontrapa, Peter J. Dyck, P. James B. Dyck, Caroline M. Klein, Ja Nean Engelstad, Jenny Davies, Shelly Shahar, W. Scott Harmsen, Jay Mandrekar, Robert J. Spinner, Cristiane M. Ida, Christopher J. Klein

Research output: Contribution to journalArticlepeer-review


Background and Aims: Comprehensive study of sural nerve biopsy utility based on individual histopathologic preparations is lacking. We aimed to quantify the value of different histologic preparations in diagnosis. Methods: One hundred consecutive sural nerves were studied by standard histological preparations plus graded teased nerve fibers (GTNF), immunohistochemistry, and epoxy-semithin morphometry. Three examiners scored the individual preparations separately by a questionnaire of neuropathic and interstitial abnormalities, masked to the biopsy number, versus a gold-standard of all preparations. Multivariate modeling was utilized to determine best approach versus the gold-standard. Results: Highest confidence (range 8–9 of 10) and inter-rater reliability (99%) for fiber abnormalities came from GTNF, and interstitial abnormalities from paraffin stains (range 7–8, 99%). Vasculitic neuropathy associated with GTNF axonal degeneration (moderate to severe 79%) with OR 3.8, 95% CI (1.001–14.7), p =.04, but not significantly with the other preparations. Clinicopathologic diagnoses associated with teased fiber abnormalities in chronic inflammatory demyelinating polyradiculoneuropathy, 80% (8/10); amyloidosis, 50% (1/2); adult-onset polyglucosan disease 100% (1/1). GTNF and paraffin stains significantly correlated with fiber density determined by morphometric analysis (GTNF: OR 9.9, p <.0001, paraffin: OR 3.8, p =.03). GTNF combined with paraffin sections had highest accuracy for clinicopathologic diagnoses and fiber density with 0.86 C-stat prediction versus morphometric analysis. Pathological results lead to initiation or changes of immunotherapy in 70% (35/50; initiation n = 22, reduction n = 9, escalation n = 4) with the remaining having alternative intervention or no change. Interpretation: Nerve biopsy paraffin stains combined with GTNF have highest diagnostic utility, confidence, inter-rater reliability, improving accuracy for a pathologic diagnosis aiding treatment recommendations. Immunostains and epoxy preparations are also demonstrated useful supporting consensus guidelines. This study provides class II evidence for individual nerve preparation utility.

Original languageEnglish (US)
Pages (from-to)191-201
Number of pages11
JournalJournal of the Peripheral Nervous System
Issue number2
StatePublished - Jun 2023


  • biopsy
  • histopathology
  • immunostains
  • neuropathy
  • teased fibers

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology


Dive into the research topics of 'Sural nerve biopsy utility by masked assessment of individual histologic preparations'. Together they form a unique fingerprint.

Cite this