Chronic intrathecal baclofen administration for control of severe spasticity

Abstract

Baclofen, the most effective drug for treating spasticity, is a specific agonist of gamma-aminobutyric acid-B receptors, and is very abundant in the superficial layers of the spinal cord. Given orally, baclofen does not easily penetrate the blood-brain barrier, and is distributed equally to the brain and spinal cord. Direct intrathecal administration was given in order to change the distribution of the drug by preferentially perfusing the spinal cord. Eighteen patients presenting a severe spastic syndrome were treated with chronic intrathecal infusion of baclofen in the lumbar cerebrospinal fluid. After clinical preselection, 38 patients were implanted with a lumbar access port allowing long-term trials in order to determine the efficacy of baclofen therapy and the effective 12-hour dose. The 18 patients selected for chronic administration were implanted with a programmable pump. The pathology in these cases was: multiple sclerosis (6 cases), posttrauma spastic syndrome (eight cases), and (one case each) cerebral palsy, ischemic cerebral lesion, spinal ischemia, and transverse myelitis. The mean follow-up period was 18 months (range 4 to 43 months). The clinical results were evaluated according to muscular hypertony on Ashworth's scale (changed for occurrence of painful spasms) and functional improvement. Results were better for spastic syndrome secondary to traumatic medullary lesion than for demyelinating disease. Hypertonia was improved in all cases as confirmed by the registration of the Hoffman (H) reflex. Painful muscular spasms disappeared in 14 of the 16 affected patients. Significant functional improvement was noted in nine patients and was considerable in three. The risk of side effects secondary to overdose (such as excessive hypotonia or central depression) and the absence of a specific baclofen antagonist stresses the necessity for accurate determination of the efficient dose. After an initial titration period and adjustment of the therapeutic dose, the individual doses were from 21 to 500 micrograms/24 hrs (mean 160 micrograms/24 hrs). This new conservative method is very effective, perfectly reversible, and safe when administered in conditions favorable to its use.

Treatments for spasticity and pain in multiple sclerosis: a systematic review

“…The non-ambulatory patients gained only in terms of QoL and comfort. Lazorthes and colleagues 70 reported similar findings. On the other hand, Patterson and colleagues 71 found no change in the Barthel index, despite substantial improvements in the Ashworth and spasm scores.…”

Regeneration of Lesioned Corticospinal Tract Fibers in the Adult Rat Induced by a Recombinant, Humanized IN-1 Antibody Fragment

“…This represents an important step toward a potential treatment because the rIN-1 Fab could be applied in a way that is routinely used for application of substances like baclofen to the spinal cord in human patients (Penn et al, 1989;Lazorthes et al, 1990). …”

New surgical interventions for cerebral palsy and the place of gait analysis

“…Penn et al 27 reduced tone in the lower limbs from around 4 to 1.2 points on the Ashworth Scale and this continued for several years without drug resistance 28 , findings which have been duplicated by others [29][30][31] . Similar results, although generally less dramatic, have been obtained in adults with supraspinal spasticity due to trauma or hypoxia, benefiting tone, spasms and improving nursing care 32,33 .…”