We propose to study the correlation between QSART and pathological confirmation of small fiber neuropathy as determined by punch skin biopsy. We propose to study 10 patients with non diabetic small fiber neuropathy, 10 patients with diabetic neuropathy (with abnormal QSART over the biopsy site), and 10 patients with other, predominantly large fiber neuropathies such as chronic inflammatory dymelinating neuropathy (in whom QSART is likely to be normal) referred for QSART testing as part of an Autonomic Reflex Screen in the Autonomic Reflex Laboratory. We also propose to study 10 normal controls on whom QSART testing will be performed as part of the experimental protocol. Patients and controls will have two 4 mm diameter punch skin biopsies performed at sites of QSART testing (proximal leg 5 cms below the fibular head and distal leg 5 cm above the medial malleolus of the ankle). The procedure will be performed in a sterile fashion. The skin will be closed with a sterile adhesive strip and a dressing applied. The skin biopsy will be placed in fixative and processed for histopathological and immunocytochemical examination. The latter will involve sending biopsy material to the peripheral nerve laboratory at Johns Hopkins Hospital for specialized staining and quantitation of nerve fiber density. Tissue levels of norepinephrine content, using microbore HPLC, will be performed in Dr. Low's laboratory. Biopsy and handling of the specimen will be carried out using universal precautions to minimize any contamination risk.
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