Epidermal nerve fibers: confidence intervals and continuous measures with nerve conduction

Area of Science:

• Neurology
• Pathology
• Biostatistics

Background:

• Epidermal nerve fibers (ENFs)/mm are crucial biomarkers for small fiber neuropathy.
• Accurate assessment of ENFs/mm requires determining optimal section numbers for reliable interpretation.
• Current methods may lack a unified approach to assess both small and large fiber integrity.

Purpose of the Study:

• To evaluate the utility of 95% confidence intervals (CIs) for epidermal nerve fiber (ENF)/mm counts in determining the number of sections for confident normality assessment.
• To introduce a novel continuous measure integrating nerve conduction studies and ENF density.

Main Methods:

• Analysis of 95% CIs for ENFs/mm was conducted on serial skip sections (1-10) from biopsies of 67 healthy subjects and 23 diabetic patients.
• Biopsies were taken from leg and thigh.
• A new methodology was developed to combine nerve conduction and ENF data.

Main Results:

• The variability of ENFs/mm counts, assessed via 95% CIs, progressively decreased with an increasing number of evaluated sections.
• 95% CIs aid in determining the adequacy of section evaluation, guiding decisions for borderline cases.
• A combined continuous measure of nerve conduction and ENFs/mm was successfully developed.

Conclusions:

• Estimating 95% CIs for ENFs/mm provides a reliable method to determine the necessary number of sections for confident classification of nerve fiber normality or abnormality.
• A new continuous measure integrates large-fiber (nerve conduction) and small-fiber (ENFs/mm) function, spanning the spectrum of normality and abnormality.
• This combined measure is valuable for therapeutic trials assessing neuropathy.