Peripheral Neuropathy (PN) in Individuals with Neurofibromatosis Type 1 (NF1) and Plexiform Neurofibromas (PNF) (P6.093)

OBJECTIVE: To describe the incidence of PN associated with NF1 and PNF. BACKGROUND: NF1 is an autosomal dominant disorder associated with the development of tumor and non tumor manifestations including PNF. Neurofibromin, the NF1 gene product, functions as a tumor suppressor and is expressed in neurons, glial-, and Schwann cells. Dysregulation of neurofibromin results in the development of neurofibromas, but its role in the development of PN is unknown. DESIGN/METHODS: Subjects were evaluated under a NCI Natural History and Longitudinal Assessment Study of Children, and Adults with NF1. In addition to detailed clinical evaluation and whole body MRI to determine total PNF tumor burden, subjects underwent neurologic examination and electrodiagnostic studies. Nerve conduction studies (NCS) were performed on a minimum of two sensory nerves (median , sural) and two motor nerves (peroneal, median). Needle EMG was performed if indicated. RESULTS: Twenty seven subjects were evaluated: 11 females, 17 males; mean age 20.3 years, range 7-48 years; median total body PNF burden 897 mL (range, 24.5-6931 mL). Twelve subjects had peripheral nerve abnormalities though there was an overlap of findings in several subjects. Six subjects had PN by NCS; 1 sensory axonopathy, 3 sensorimotor axonopathies, and 2 neuropathies had demyelinative features. Six subjects had isolated neuropathies (median, radial or peroneal) with 3 being related to injury or surgery. Three subjects had radiculopathies with two having prior surgical decompression and one having known cervical tumor bulk. One subject had subacute progressive weakness and NCS showing a demyelinating neuropathy. Symptoms initially responded to corticosteroid therapy. Sural nerve biopsy showed a small PNF without definite evidence of demyelination. CONCLUSIONS: PN was observed in 22% of subjects with NF1 and PNF. In this series, most findings suggested an axonal process though two subjects had demyelinative features. Nerve pathology in one subject with demyelinative findings suggested that the presence of tumor may mimic conduction block and demyelination. Study Supported by: Intramural Research Programs, NINDS & NCI Disclosure: Dr. Lehky has nothing to disclose. Dr. Kwan has nothing to disclose. Dr. Dombi has nothing to disclose. Dr. Baldwin has nothing to disclose. Dr. Akshintala has nothing to disclose. Dr. Gillespie has nothing to disclose. Dr. Widemann has nothing to disclose.