Limitations of Skin Biopsy in the Assessment of Isolated Small Fiber Neuropathy (P03.207)

Objective: To correlate intraepidermal nerve fiber density with distal sensory (medial plantar) conduction studies in patients with clinical features of isolated small fiber neuropathy (iSFN). Background Patients with iSFN present with distal paresthesias, pin/thermal hypoesthesia, and pain. Features of large fiber dysfunction are lacking and standard electrodiagnostic testing is normal. Skin biopsy is an established tool to support the diagnosis of iSFN. Many peripheral neuropathies are small fiber predominant by clinical examination, and subtle large fiber involvement may be more frequent than usually appreciated. Design/Methods: We performed a retrospective chart review of patients with a clinical phenotype of iSFN who underwent both skin biopsy and medial plantar conduction studies in addition to standard studies for SFN. Results: Forty four patients were evaluated. Of biopsy negative patients, 85% (23/27) had normal medial plantar responses and 15% (4/27) had abnormal medial plantar responses. In contrast, 18% (2/11) of biopsy positive patients had normal medial plantar responses and 82% (9/11) had abnormal responses. Patients with an equivocal (low-normal density) or non-length dependent pattern on biopsy were less likely to have abnormal medial plantar responses (50%; 3/6). The mean amplitude of the sural sensory response was greater in biopsy negative (18.3 + 7.5uV) than positive (14.1 + 7.0 uV) patients. The mean amplitude of the medial plantar response was greater in biopsy negative (11.2 + 5.4 uV) than positive (5.4 + 3.6 uV) patients. Conclusions: Positive biopsies were usually associated with abnormal medial plantar responses and lower mean distal sensory amplitudes. This finding implies that positive skin biopsy reflects, not isolated SFN, but both small and large fiber involvement. These findings also suggest that medial plantar responses are nearly as sensitive as biopsy for confirming subtle large fiber involvement missed by clinical examination. Thus skin biopsy may be an insensitive tool for detecting isolated or pure SFN. Disclosure: Dr. Lawson has nothing to disclose. Dr. Mongiovi has nothing to disclose. Dr. Arnold has nothing to disclose.