A dose-response study of dexamethasone in a model of spinal cord compression caused by epidural tumor.
In order to assess the clinical and biological effects of glucocorticoids in the therapy of epidural spinal cord compression, the T8-10 epidural space of 50 rats was implanted with Walker 256 tumor. The rats were studied 10 to 20 days later when they became paraparetic. The regional blood-spinal cord transport constant (K, a function of the blood-spinal cord barrier) of 14Carbon-labeled aminoisobutyric acid was measured with quantitative autoradiography 6 hours after intravenous injection of low-dose (0.1 mg/kg), intermediate dose (1 mg/kg), and high-dose (10 mg/kg) dexamethasone. The effects of dexamethasone in these doses on the clinical signs and water content of the compressed cord were also evaluated 40 hours after treatment began. The K factor increased 730% in compressed compared with noncompressed spinal cords (p less than 0.001). Dexamethasone induced a dose-related reduction of both K (p = 0.007) and water content of the compressed cord (p less than 0.0001). Stabilization or, more rarely, improvement of weakness at 24 and 40 hours posttreatment correlated with the dose of dexamethasone (r = 0.88, p less than 0.001). This study demonstrates that dexamethasone has a dose-related beneficial clinical effect associated with an improvement of blood-spinal cord barrier breakdown and a reduction of the water content of the compressed cord. This study supports the use of highdose dexamethasone for the initial treatment of epidural spinal cord compression.
Delattre
J Y
JY
Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York.
Arbit
E
E
Thaler
H T
HT
Rosenblum
M K
MK
Posner
J B
JB
D000818:Animals; D002279:Carcinoma 256, Walker / Q000150:complications; D003907:Dexamethasone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004824:Epidural Space; D051381:Rats; D011919:Rats, Inbred Strains; D013117:Spinal Cord Compression / Q000188:drug therapy* / Q000209:etiology; D013120:Spinal Cord Neoplasms / Q000150:complications
D003907:Dexamethasone