Time course of the effect of a bolus dose of intrathecal baclofen on severe cerebral spasticity

Abstract

Continuous intrathecal administration of baclofen with implanted programmable pump systems is recommended in the treatment of severe spasticity of cerebral origin. Prior to pump implantation, a baclofen bolus test (BBT) is used to assess the effectiveness of intrathecal baclofen using clinical scales such as the Modified Ashworth Scale (MAS). In the literature, the time and period of maximum effect of a bolus dose of intrathecally administered baclofen in patients with cerebral spasticity is variously reported. The aim of the study was, therefore, to reveal the time course of the effect of a BBT on severe cerebral spasticity by the use of a recently described spasticity measurement method. Spasticity in knee joints of 13 patients with severe cerebral spasticity was repeatedly assessed using the MAS and also continuously recorded by the measurement of force under circular fibreglass casts. Force was recorded as nettorque by multiplying the force by the distance between sensor and joint axis, thus allowing inter-individual comparison. Half-hour time integrals (TI) of net-torque were determined 9 hours before and 22 hours after intrathecal baclofen administration. Post-BBT half-hour time integrals (TI(+0), TI(+0.5), to TI(+22)) were compared with the mean of 17 pre-BBT half-hour time integrals. Significantly lower post-BBT half-hour time integrals compared with were found between TI(+2) and TI(+8) (Dunnett adjusted p < 0.05). The median lowest TI after BBT of the 13 patients was TI(+4). The lowest mean MAS scores were found 4 hours after BBT. The findings suggest that the greatest effect of BBT on cerebral spasticity occurs between 2 and 8.5 hours, with a maximal effect at 4 hours after intrathecal baclofen injection. Clinical scales used to determine the effect of BBT should thus be carried out during this period-ideally at 4 hours after baclofen injection.

Tolerance to continuous intrathecal baclofen infusion can be reversed by pulsatile bolus infusion

“…The total continuous daily dose was decreased by 10%, to be cautious, avoiding high peak concentrations from the bolus infusion. The remaining daily dose was divided over six identical boluses, with a bolus interval of 4 h. This was based on the half-life of baclofen (4-5 h) and on own clinical experience, showing a mean duration of effect after an optimal ITB bolus of about 4 h. 15,16 The fixed bolus injection speed of the pump (Synchromed II; Medtronic) resulted in bolus durations between 3 and 5 min, depending on the magnitude of the bolus dose.…”

Contractures and involuntary muscle overactivity in severe brain injury

“…Spontaneous involuntary muscle activity in plegic legs in patients and unintentional muscle activity in normal controls were assessed by isometric measurement of knee joint flexion torque under circular fibreglass casts. The measurement principle has been described in part in previous publications by the authors [16,26].…”

“…To this end we developed a non-spastic muscle overactivity measurement method using involuntary isometric torque at 'rest' [16,26]. This method directly measures the common final product muscle torque which correlates closely to 'muscle work' of the relevant limb, resulting from 'background contraction', associated reactions (synkinesias), hyperexcitability, (hypertonia), spastic dystonia, flexor and extensor spasms, cocontraction, and other phenomena [3,16,26,37].…”

“…This method directly measures the common final product muscle torque which correlates closely to 'muscle work' of the relevant limb, resulting from 'background contraction', associated reactions (synkinesias), hyperexcitability, (hypertonia), spastic dystonia, flexor and extensor spasms, cocontraction, and other phenomena [3,16,26,37]. and c) and the ongoing increased 'background contraction' [37] in these patients (Figure 3a and b).…”

“…Previous studies by the authors have shown that muscle overactivity in terms of 'intermittent or sustained involuntary activation of muscles' [1] can be continuously and quantitatively measured by the measurement of force under fibreglass casts in patients with severe brain damage and associated spasticity and contractures [16,26]. The goals of this study were, first, to measure involuntary non-spastic knee joint flexion muscle overactivity of patients with severe brain injury using a continuous 12-hour measurement technique developed by the authors.…”