SummaryThe effects of intrathecal baeZofen infusion were studied in 9 spinal cord injury patients whose spasticity had been refractory to oral medications. In a two stage, placebo controlled trial, baeZofen was administered into the lumbar intrathecal space and subsequent eZinical and neurophysiologic changes were assessed.In stage 1, 9 patients underwent a 5 day percutaneous infusion of baeZofen and placebo via an external pump. Ashworth and reflex scores were assessed at time of enrollment, after infusion of that amount of baeZofen which provided optimal spasticity control and after intrathecal infusion of placebo. The mean Ashworth grade decreased from 3·78 ± 1·34 to 1·16 ± 0·48 (p < 0·001) while mean reflex score decreased from 3·57 ± 1·05 to 0·64 ± 0·87 (p < 0·001). These values differed significantly from those associated with placebo therapy (Ashworth grade-2·54 ± 1·04, P < 0·001; reflex score-2·56 ± 1·04, P < 0·01). Objective improvements in functional abilities and independence were noted in 8 patients, while somatosensory and brainstem auditory evoked potentials were unchanged in all patients. Urodynamic evaluation revealed increased bladder capacity in 3 patients, while in 4 no change was observed.In Stage 2, permanent programmable infusion pumps were implanted in 7 patients who demonstrated a good response during Stage 1. In this group, mean Ashworth score decreased from 3·79 ± 0·69 to 2 ± 0·96 (p < 0·001) and mean reflex score decreased from 3·85 ± 0·62 to 2·18 ± 0·43 (p < 0·001). BaeZofen dosage increased from 182 ± 135 to 528 ± 266 mcg/day over the 3-22 month follow-up period. Most of the dosage increase occurred within the initial 12 months following infusion pump implantation and tended to plateau thereafter.Minor complications such as catheter dislodgement/kinking and nausea occurred infrequently while no device related infections were observed. There was no eZinical evidence of any significant baeZofen neurotoxicity either in Stage 1 or 2. The only ambulatory patient developed marked lower extremity weakness during Stage 1 intrathecal baeZofen infusio� and was temporarily unable to walk.We coneZude that continuous administration of intrathecal baeZofen is an effective and safe modality for spasticity control in patients who are refractory to oral medications.

Study design: Intrathecal administration of 4-aminopyridine (4-AP) in chronic spinal cord injured (SCI) patients. Objective: To determine the safety and e ects of intrathecal administration of 4-AP in a small population of chronic SCI patients. Setting: The post anesthesia care unit of a tertiary care hospital. Methods: Following animal mode studies to establish dosing safety, six subjects with chronic SCI were examined. In each subject, an intrathecal catheter was placed with the tip as close to the lesion level as possible. 4-AP was infused at 5 mg/h for a period of 4 ± 5 h. Vital signs were recorded and sensory-motor physical examinations and pain questionnaires were administered for 24 h. In two patients, samples of cerebrospinal¯uid for analysis were drawn from a second intrathecal catheter. Results: No adverse systemic side e ects were noted. One patient showed transient improvement in sensory function; two showed transient increases in spasticity; three showed transient increases in cutaneomuscular re¯exes and two showed an apparent small increase in volitional motor control. The concentration of 4-aminopyridine in the cerebrospinal¯uid reached a peak of 163 ng/ml at 4 h in one subject and 122 ng/ml at 5 h in the other subject examined. Conclusion: Intrathecal administration of 4-aminopyridine at a rate of 5 mg/h does not appear to cause adverse e ects and may modify spinal cord function. This route of administration allows local cerebrospinal¯uid concentrations equivalent to those produced by maximum tolerable systemic doses, which require 1000 times more drug substance to be delivered to the subject as a whole. Intrathecal administration o ers the potential to focus therapeutic e ects to the lesion site while minimizing systemic side e ects. Spinal Cord (2000) 12, 728 ± 732

Concern over the development of tolerance in patients on continuous intrathecal baclofen therapy has arisen as this new form of treatment for spasticity has gained wider use. We have studied time-dose relationships in 18 spinal cord injured patients who have undergone intrathecal baclofen infusion pump implantation since February 1988 in our facility. Our data show that there was a significant increase in baclofen dosage needed to control spasticity during the first 12 months post implantation. After 12 months, however, no significant changes in dosage requirement was detected. In addition, there was no significant difference between completely and incompletely spinal cord injured patients with regard to both the initial dose and the tolerance trend.

Study design: A prospective double blind cross over trial of intravenous 4-Aminopyridine (4-AP). Objective: To determine the ecacy of this drug in the treatment of spinal cord injured (SCI) patients for neurologic impairment, pain and spasticity. Setting: The post anesthesia care unit (PACU) of a tertiary care acute hospital. Methods: Twelve paraplegic patients were enrolled in a double blind cross over intravenous trial of 4-Aminopyridine (4-AP). Thirty milligrams of 4-AP or placebo were administered over a 2 h period. Patients were serially examined during and after the infusion clinically for pain, sensorimotor function, hypertonicity and motor control using electromyography (EMG). Samples of blood and cerebrospinal¯uid (CSF) were also analyzed at similar intervals. Results: Despite penetration of 4-AP into the CSF, no signi®cant dierences were noted in the clinical and EMG parameters at the times measured. Individual changes in sensory function were reported by some patients in both the placebo and 4-AP trials, however mean values were not robust. Frequently, patients complained of unpleasant symptoms during the 4-AP infusion. Conclusion: The intravenous route may not be the best way to administer this drug as no short term bene®ts were observed. Spinal Cord (2000) 38, 7 ± 15

The results of omental transposition in chronic spinal cord injury have been reported in 160 patients operated upon in the United States, Great Britain, China, Japan, India and Mexico, with detailed outcomes reported in few studies. Recovery of function to a greater degree than expected by natural history has been reported. In this series, 15 patients with chronic traumatic spinal cord injury (> 1.5 years from injury) underwent transposition of pedicled omentum to the area of spinal cord injury. Of the first series of four patients who were operated upon in 1988, one died, one was lost to follow-up and two were followed with sequential neurological examinations and Magnetic Resonance Imaging (MRI) scans preoperatively, at 1 year post injury and 4 V2 years post injury. Another 11 patients were operated in 1992 and underwent detailed neurological and neurophysiological examinations and had MRI scans preoperatively and every 4 months for at least 1 year after surgery. All patients completed a detailed self-report form. Of the total of 13 operated patients in both series followed for 1-4 V2 years, six reported some enhanced function at 1 year and five of these felt the changes justified surgery primarily because of improved truncal control and decreased spasticity. MRI scans showed enlargement of the spinal cord as compared to preoperative scans in seven patients. Increased T2 signal intensity of the spinal cord was found by 1 year after surgery in eight of 13 operated patients. Neurophysiological examinations of 11 patients in the second series agreed with self-reports of increases or decreases in spasticity (r = 0.65, P < 0.03). Somatosensory evoked potentials and motor evoked potentials at 4 month intervals up to 1 year in these patients showed no change after surgery. Neurological testing, using the American Spinal Injury Association (ASIA) and International Medical Society of Paraplegia (IMSOP) international scoring standards, failed to show any significant changes when the I-year post operative examination was compared to the first preoperative examination except for decreased sensory function after surgery which approached statistical significance. When the 11 patients in the second series were compared to eight non-operated matched patients, followed for a similar length of time, no significant differences were found. Complic,!tions encountered in the operated patients from both series included one postoperative death from a pulmonary embolus, one postoperative pneumonia, three chronic subcutaneous cerebrospinal fluid (CSF) fistulae requiring wound revision, and one patient who developed biceps and wrist extensor weakness bilaterally requiring graft removal. We conclude that the omental graft remains viable over time and this operation can induce anatomical changes in the spinal cord as judged by MRI. Some patients reported subjective improvement but this was not supported by objective testing. We, therefore, find no justification for further clinical trials of this procedure in patients who have complete or...