4-Aminopyridine improves pulmonary function in quadriplegic humans with longstanding spinal cord injury.

STUDY OBJECTIVE

To test the hypothesis that 4-aminopyridine (4-AP) might cause clinically evident improvement in pulmonary function in humans with chronic spinal cord injury (chronic SCI).

DESIGN

Balanced, open-label study with subjects consecutively enrolled.

SETTING

Spinal Cord Injury Service, university-affiliated tertiary level care Department of Veterans Affairs Medical Center.

PATIENTS

Seventeen healthy men and women suffering from traumatic SCI (11 quadriplegic, 6 paraplegic patients) for more than 1 year.

INTERVENTIONS

Each subject was given a single dose of 4-AP 10 mg orally in an immediate-release formulation.

MEASUREMENTS AND MAIN RESULTS

Significant increases in mean values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) that persisted for at least 12 hours were demonstrated in quadriplegic patients beginning 6 hours after 4-AP administration. Tests of pulmonary function that demonstrated statistically significant increases at any time were also numerically, if not statistically, increased at 24 hours compared with pretreatment values obtained in 4-AP-naive subjects.

CONCLUSIONS

The administration of a single dose of an immediate-release formulation of 4-AP to humans with longstanding, traumatic quadriplegia is associated with sustained, clinically meaningful, and statistically significant improvements in pulmonary function. We suggest that the administration of 4-AP may have a salutary effect in patients suffering from SCI and appears to be associated with potentially clinically significant reductions in the pathophysiologic pulmonary sequelae of SCI.