Dose-response relationship between the H-reflex and continuous intrathecal baclofen administration for management of spasticity

Abstract

Objective: To determine the relationship between the H-reflex (H/M ratio) and continuous intrathecal baclofen (CITB) dose after pump implantation for control of spastic hypertonia. Methods: Soleus H-reflexes were serially recorded in 34 subjects (19 men, mean age 32 years, mean follow-up 1.7 years) during simple continuous mode of CITB delivery. Different fitting methods were explored to determine which function best described changes in H/M ratio with increasing CITB dose. We then calculated effective CITB doses yielding H/M ratios equal to 75, 50, and 25% (ED 75 , ED 50 , ED 25 ) of the baseline recorded before the implant in 22 subjects. Results: We found a significant dose-response relationship between the soleus H/M ratio and CITB dose. A two-decay exponential function was the best fit on each side for pooled data, but a general linear model when controlling for subject. The mean ED 75 , ED 50 , ED 25 were 30, 70, and 110 mcg/day. Logistical regression predicted with high probability that the H/M ratio should be less than 30% at CITB doses above 150 mcg/day. Conclusions: H/M ratio is strongly dependent on CITB dose. It sharply decreases up to 150 mcg/day of CITB followed by a plateau. Significance: Establishing the relationship between the H/M ratio and CITB dose may be useful for dose titration and early identification of an ITB system malfunction. © 2006 International Federation of Clinical Neurophysiology. AuthorsConclusions:Thus, the knowledge of the dose response relationship between the H/M ratio and CITB [continuous intrathecal baclofen] dose has potential clinical applications, including dose titration and identification and characterization of ITB [intrathecal baclofen] system malfunction, that warrant [sic] further investigation. AdverseEffects:No adverse events were mentioned. Patients:34 outpatients, 15 women and 19 men, mean age of 32 years, age range 15-58 years. Mean follow-up time 1.7 years, range 22 days to 6.5 years. TypeofStudy:A study investigating the relationship between the H-reflex (H/M ratio) and continuous intrathecal Lioresal dose after pump implantation in patients with spastic hypertonia. Single-blind , comparative clinical study. FreeText:Spasticity was due to brain injury in 28 subjects (14 trauma, 5 intraparenchymal hemorrhage, 4 cerebral palsy, 3 aneurysmal subarachnoid hemorrhage, 2 hypoxic ischemic encephalopathy), 5 spinal cord disorder subjects (2 trauma, 3 neurodegenerative disease), and 1 multiple sclerosis. The H-reflex was recorded prior to any dose manipulation. In 22 of 34 subjects, H-reflex was also recorded during the screening bolus trial thereby permitting an inclusion of the baseline H/M ratio (no Lioresal) into the analyses. H-reflex was evoked using 1-ms pulses repeated every 10 s, with the subject resting comfortably in the supine position. Auditory feedback was provided to ensure the absence of soleus muscle activation during the recording. The stimulus intensity was increased in small increments (0.8 mA), from threshold for H-reflex to supramaximal for M wave, and 20-30 traces were recorded (one at each intensity). Thereby, a bell-shaped H-reflex curve and a sigmoid M-wave curve were mapped with special attention to the H-reflex ascending limb and the peak. Effective doses (ED) yielding H/M ratios equal to 75, 50, and 25% (ED75, ED50, ED25) of the baseline recorded before the implant in 22 subjects were calculated. Results:The lowest dose for 12 subjects studied only after the pump implantation was 262 mcg daily (50-660) and the highest 523 mcg daily (100-1200). The highest tested continuous intrathecal Lioresal dose for 22 subjects with baseline H/M ratio was 188 mcg daily (range 50-80). 76% of all responses yielded H/M ratios <10% and only a few were larger than 10% above 150 mcg daily. H/M ratios above 40% mainly represent the baseline data bilaterally acquired among the patients evaluated before pump implantation. For these 22 subjects, the baseline H/M ratio for the two sides combined was 67%. The H/M ratio was, however, above the limits in 17 muscles (87G8%), within the limits in 12 (68%), and below the limits in 15 (43%). The size of H/M ratio sharply decreased up to 200 mcg daily, and at the similar rate on both sides, followed by a steady plateau thereafter. Increasing intrathecal Lioresal dose significantly decreased H/M ratio, although each subject, had a unique intercept or ‘starting point’. The origin of spasticity (spinal vs. supraspinal) did not have a significant effect. The overall results were significant for all H/M and continues intrathecal Lioresal combinations (P < 0.001). The results indicate that if an intrathecal Lioresal dose is above 150 mcg daily, H/M ratio is about 13 times more likely to be below 10%, 36 times more likely to be below 20%, and 86 times more likely to be below 40%. The odds are increasingly higher using higher H/M cutoff points. This analysis confirmed that the H/M ratio should remain low across the higher intrathecal Lioresal doses. The mean intrathecal Lioresal doses with the corresponding 99% confidence interval limits were 28 mcg daily (20-36 mcg daily) for ED75, 70 mcg daily (59-81 mcg daily) for ED50, and 112 mcg daily (94-129 mcg daily) for ED25. The calculated mean intercept was 63%, which was on average 4% smaller than the actual baseline H/M ratios, indicating fairly good fit overall. DosageDuration:The mean lowest dose was 92 mcg daily (range 0-660 mcg daily) and the mean highest dose was 307 mcg daily (range 50-1200 mcg daily) infused continuously via intrathecal pump. Duration not stated. Indications:34 patients with spasticity.

Publication
Clinical Neurophysiology