The purpose of this study is to evaluate the role of single dose 4-aminopyridine (4-AP) on the diagnosis of severing vs non-severing nerve injury after peripheral nerve traction and/or crush injury. The investigational treatment will be used to test the hypothesis that 4-aminopyridine can speed the determination of nerve continuity after peripheral nerve traction and/or crush injuries allowing the identification of incomplete injuries earlier than standard electrodiagnostic (EDX) and clinical assessment.

Participants will be randomized to one of two groups to determine the order of treatment they receive (drug and placebo vs placebo and drug). Participants will undergo baseline testing for nerve assessment, receive either drug or placebo based on randomization and undergo hourly sensory and motor evaluation, EDX testing and serum 4AP levels for three hours after dosing. Participants will then repeat this with the crossover arm.

This is a single-center study that will be conducted at the University of Arizona College of Medicine, Tucson. It is a double-blind, randomized, crossover trial design. Group A will receive the study drug followed by the placebo on the main trial day, and Group B will receive placebo first followed by the study drug. These groups will exist for both aims (both types of included patients).

Patients are randomized for the order (drug and placebo vs placebo and drug) of treatment they receive. Eligible, consented patients will present for testing from one of three locations (emergency department, inpatient ward, or home). Patients will undergo testing under the direction of trial personnel. Patients will undergo a thorough baseline sensory and motor evaluation and establish an intravenous line for blood sampling. A baseline blood sample (prior to drug and placebo) will be performed. These tests comprise part of a standardized array of tests performed hourly. This array of tests (serum 4AP level and sensorimotor examination) will be repeated every hour after treatment for three hours during which the drug will have decreased to a level low enough to have no expected effect. The final hourly test is the return to baseline test. It is likely going to occur at the third hourly post-test, but is depicted separately for clarity. Only three tests after dosing will be necessary, based on our expectations from known pharmacokinetic data. Patients will then repeat this with the crossover arm (drug vs placebo). Testing is concluded at the end of this period.

Following the initial testing, subjects will be seen for a period of 20 weeks after injury to monitor recovery and progress. Subjects will return for follow-up visits at 2, 6, 12, 18, and 20 weeks post injury. Subjects will receive a physical exam at all follow-up visit. Subjects will complete a telephone interview at 9 and 15 weeks post injury at which time subjective motor and sensory function will be assessed by asking 1) Can you move your (affected extremity)? Yes or No 2) Can you feel your (affected extremity)? Yes or No. Review of the subject diary will also be completed. The 9, 15, and 20 week visits are not part of standard of care and are being done for research purposes only. Each visit or phone interview will last approximately 30 minutes.

Inclusion Criteria:

• Patients with trauma involving two or less limbs where the continuity of a given peripheral nerve or nerves is unclear on presenting physical examination.
• Closed soft tissue envelope obscuring direct observation of the continuity of the affected nerve.
• Cognitive ability to report sensory and motor deficit during examination.
• Eligible for standard of care plan of monitoring vs surgical exploration of the nerve.
• Adults subject aged 18-90
• Known limb trauma which resulted in nerve injury (aim 1) or post-operative/post intervention nerve injury (aim 2).
• Ability to give written informed consent.
• Availability for all testing days and main trial day.

Exclusion Criteria:

• Distracting injury which prevents adequate examination.
• Plan for surgical exploration of the nerve during the ensuing 48 hours.
• Plan for surgical exploration of the nerve as part of another surgical procedure within 48 hours of evaluation.
• Intoxication during examination or evidence of cognitive deficit that emerges during examination.
• History of multiple sclerosis, stroke or any other diagnosed neurological disorder
• History of hypersensitivity to AMPYRA® or 4-aminopyridine
• Current use of aminopyridine medications, including other compounded 4-AP
• Renal impairment based on calculated GFR (GFR<80 mL/min). This laboratory value is measured in all inpatient trauma patients as part of the standard of care.
• History of difficult compliance with timely follow up or plan to seek care at another institution closer to home.
• Patients outside the age range or unable to consent.
• Patients with a known history of a seizure disorder (4AP overdose can, in selected cases, result in limited seizure activity).
• Patients with a concomitant traumatic brain injury.
• Patients unable to communicate return or loss of sensation.
• Patients unable to exhibit motor control on the affected limb at baseline.
• Patients unwilling to complete the study requirements.
• Patients with injuries too extensive to isolate a single nerve(s) for testing.
• Patients currently taking organic cat-ion transporter 2 (OCT2) inhibitors, e.g. Cimetidine.
• Pregnancy, breastfeeding or incarcerated individuals.