127 - Management of Spasticity by Central Nervous System Infusion Techniques

Abstract

Chronic intrathecal delivery of baclofen via an implanted drug pump is an extremely successful treatment for severe spasticity due to spinal cord injury, multiple sclerosis, traumatic brain injury, stroke, and cerebral palsy. It is also been helpful in decreasing dystonic muscle tone. Specificity is caused by an overactivity of spinal circuits due to brain or spinal cord injury that decreases inhibitory signals modulating those circuits. This results in uncoordinated movements, hyperreflexia, mass withdrawal, and postural abnormalities. Baclofen's major mode of action is to increase presynaptic inhibition by activating B receptors. The receptors reduce the amount of calcium influx and thus decrease synaptic release of neural excitatory substances. Intrathecal baclofen, by reducing the drive of these overactive circuits, can result in normal underlying movement patterns being expressed. Also, reduction of spasticity can reduce pain and spasms and facilitate rehabilitation efforts. It also can improve sleep that has been disrupted by spasms. Using a catheter and an implanted drug pump that supplies a steady infusion, intrathecal baclofen can be concentrated in the spinal cord tissue. This avoids the central side effects of drowsiness and confusion. An average of only 25% of the intrathecal baclofen reaches the brain and brainstem. The kinetics of intrathecal drug distribution are slow. The brain and spinal cord tissue act as a reservoir for the drug, and movement of the drug into and out of the tissue is limited by diffusion. A bolus dose can cause baclofen to distribute to the brain and result in drowsiness and respiratory depression. Sudden interruption of the infusion sometimes results in marked increases in muscle tone, seizures, and hallucinations.