Initial validation of the Mass. General Neuropathy Exam Tool (MAGNET) for evaluation of distal small-fiber neuropathy.

INTRODUCTION/AIMS: Diagnosis of small-fiber neuropathy (SFN) is hampered by its subjective symptoms and signs. Confirmatory testing is insufficiently available and expensive, so predictive examinations have value. However, few support the 2020 SFN consensus-case-definition requirements or were validated for non-diabetes neuropathies. Thus we developed the Massachusetts General Hospital Neuropathy Exam Tool (MAGNET) and measured diagnostic performance in 160 symptomatic patients evaluated for length-dependent SFN from any cause and 37 healthy volunteers. METHODS: We compared prevalences of abnormalities (vital signs, pupil responses, lower-limb appearance, pin, light touch, vibration and position sensitivity, great-toe strength, muscle stretch reflexes), and validated diagnostic performance against objective SFN tests: lower-leg skin-biopsy epidermal neurite densities and autonomic function testing (AFT). Sensitivity/specificity, feasibility, test-retest and inter-rater reliability, and convergence with the Utah Early Neuropathy Scale were calculated. RESULTS: Patients' ages averaged 48.5 ± 14.7 years and 70.6% were female. Causes of neuropathy varied, remaining unknown in 59.5%. Among the 46 with abnormal skin biopsies, the most prevalent abnormality was reduced pin sharpness at the toes (71.7%). Inter-rater reliability, test-retest reliability, and convergent validity excelled (range = 91.3-95.6%). Receiver operating characteristics comparing all symptomatic patients versus healthy controls indicated that a MAGNET threshold score of 14 maximized predictive accuracy for skin biopsies (0.74) and a 30 cut-off maximized accuracy for predicting AFT (0.60). Analyzing patients with any abnormal neuropathy-test results identified areas-under-the-curves of 0.87-0.89 for predicting a diagnostic result, accuracy = 0.80-0.89, and Youden's index = 0.62. Overall, MAGNET was 80%-85% accurate for stratifying patients with abnormal versus normal neuropathy test results. DISCUSSION: MAGNET quickly generates research-quality metrics during clinical examinations.

Ion channels and neuropathic pain.

Pain behaviors in a Fabry mouse model are associated with the accumulation of a fat molecule that disrupts sodium ion channels in small fiber neurons.