A Leland Albright1. 1. Department of Neurosurgery, University of Wisconsin Medical Center, Madison, Wisconsin 53792, USA. l.albright@neurosurg.wisc.edu
Abstract
OBJECT: This study was designed to evaluate the clinical and histopathological effects of long-term (3-month) intraventricular baclofen (IVB) infusion in beagle dogs. METHODS: Catheters were inserted stereotactically into the lateral ventricles of nine dogs and were connected to implanted Synchromed II pumps. Saline solution (control animals) and IVB (experimental animals) were infused continuously. The IVB dosages ranged from 100 to 1000 microg/day. RESULTS: An IVB infusion of 135 microg/day or less throughout a 3-month period was associated with no adverse side effects in any animal. Infusion of 150 microg/day produced overt seizures in one dog and produced adverse side effects in another; a reduction in the dosage given to these animals to 135 microg/day was tolerated with no adverse effects. Infusion of IVB at a dosage of 250, 500, or 1000 microg/day caused lethal toxicity within the first 4 days of infusion. Histopathological specimens obtained at necropsy revealed no ventricular or subependymal changes in animals receiving an IVB dosage of 135 microg/day or less. CONCLUSIONS: Intraventricular baclofen infusion in beagles has dose-related toxicity; however, no clinical or neurological toxicity was evidenced at clinically tolerated dosages (< or =135 microg/day) throughout 3 months of infusion.
OBJECT: This study was designed to evaluate the clinical and histopathological effects of long-term (3-month) intraventricular baclofen (IVB) infusion in beagle dogs. METHODS: Catheters were inserted stereotactically into the lateral ventricles of nine dogs and were connected to implanted Synchromed II pumps. Saline solution (control animals) and IVB (experimental animals) were infused continuously. The IVB dosages ranged from 100 to 1000 microg/day. RESULTS: An IVB infusion of 135 microg/day or less throughout a 3-month period was associated with no adverse side effects in any animal. Infusion of 150 microg/day produced overt seizures in one dog and produced adverse side effects in another; a reduction in the dosage given to these animals to 135 microg/day was tolerated with no adverse effects. Infusion of IVB at a dosage of 250, 500, or 1000 microg/day caused lethal toxicity within the first 4 days of infusion. Histopathological specimens obtained at necropsy revealed no ventricular or subependymal changes in animals receiving an IVB dosage of 135 microg/day or less. CONCLUSIONS: Intraventricular baclofen infusion in beagles has dose-related toxicity; however, no clinical or neurological toxicity was evidenced at clinically tolerated dosages (< or =135 microg/day) throughout 3 months of infusion.
Authors: Barbara King; Neil R Marshall; Sofia Hassiotis; Paul J Trim; Justin Tucker; Kathryn Hattersley; Marten F Snel; Robert D Jolly; John J Hopwood; Kim M Hemsley Journal: J Inherit Metab Dis Date: 2016-11-10 Impact factor: 4.982