Effectiveness and safety of cervical catheter tip placement in intrathecal baclofen treatment of spasticity: A systematic review

Abstract

Objective To evaluate the effectiveness and safety of intrathecal baclofen treatment of spasticity, administered via a cervical catheter tip. Design A review of PubMed and the Cochrane Library up to September 2020. No restriction in study design. Two reviewers independently evaluated eligibility, extracted data and evaluated risk of bias. Studies were included in which patients were treated with intrathecal baclofen for spasticity, with the catheter tip at or above the first thoracic level, independent of diagnosis and age. Results Thirteen studies were eligible, with a moderate to critical risk of bias. Improvement in spasticity was seen only in the upper extremity in 6% of subjects, only in the lower extremity in 2%, in both upper and lower extremities in 50% and without specification of location in 41%. Upper extremity function improved in 88% of cases. Neither drug-related (1%) nor technical (21%) complications occurred more often than in lower placement of the tip. Effects on respiratory function and sleep apnoea were not investigated. Conclusion Cervically administered intrathecal baclofen seems to improve upper extremity spasticity and function, without causing more complications than thoracolumbar intrathecal baclofen. However, the mainly drug-related complications have not been thoroughly investigated and the available literature is of poor methodological quality. Further research is needed to confirm the efficacy and safety of this procedure. LAY ABSTRACT Spasticity is a common complication in central neurological disorders. It can lead to discomfort and functional limitations. To reduce spasticity, administration of baclofen via a catheter into the spinal canal has been used successfully for several years. However, this treatment often has limited effects on the upper limbs. The catheter tip is often situated in the thoracolumbar region. This review suggests that baclofen treatment via a cervically located catheter tip reduces spasticity of both arms and legs. Also, arm function improved in patients with a cervical catheter tip. Neither drug-related nor technical complications occurred more often than in lower placement of the cervical catheter tip. Few studies were found on this subject, and the available literature is of poor quality. Therefore, more research is needed to confirm the positive effect of this procedure on spasticity of the arms and to monitor for complications.

A Historical Review of Brain Drug Delivery

“…Intrathecal morphine is effective for pain [91], because opioid receptors are expressed on the surface of the spinal cord [92]. Intrathecal baclofen is used to treat spinal spasticity [93], as gamma aminobutyric acid (GABA)-B receptors are expressed on the surface of the spinal cord [94].…”

Spasticity following brain and spinal cord injury: assessment and treatment

“…Baclofen may be continuously administered intrathecally at very low dose by a programmable subcutaneous implanted drug delivery system with reservoir and catheter, which is usually placed at the lumbar, and less often at the cervical level [68]. The most common indication of ITB is severe spastic paraparesis with limited residual function and painful spasms.…”

Cervical catheter placement leads to improved rostral distribution of a radiolabeled 18F-baclofen analog in cynomolgus monkeys

“…Although catheter tips are most commonly placed in the thoracic spine [2], an alternative placement of the tip may be necessary for a variety of reasons, including complicated spinal anatomies that may occur with scoliosis or spinal fusions [3]. Several studies have been performed to understand the clinical implications to treatment efficacy as a result of alternative placement [2,[4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] as well as the effect of cerebrospinal fluid (CSF) concentration of baclofen as a result of varied catheter tip location [19]. However, to date there have been no studies to examine the effect of catheter tip placement on brain distribution of baclofen, which could be an important factor for patients with spasticity of a cerebral origin based on bolus lumbar puncture test observations in patients with spasticity of a cerebral origin performed by Richard et al [16].…”

“…To better understand the effect of catheter tip placement on distribution to the CNS tissues in a larger species, in particular the brain and cervical spine, a therapeutically relevant 18 F-baclofen analog with comparable binding affinity to baclofen was synthesized to facilitate positron emission tomography (PET) imaging in nonhuman primates [34]. Note that the infusion system used for this study is FDA-approved for delivery of intrathecal baclofen but not specifically for the 18 F-Baclofen analog in this study.…”

“…To better understand the effect of catheter tip placement on distribution to the CNS tissues in a larger species, in particular the brain and cervical spine, a therapeutically relevant 18 F-baclofen analog with comparable binding affinity to baclofen was synthesized to facilitate positron emission tomography (PET) imaging in nonhuman primates [34]. Note that the infusion system used for this study is FDA-approved for delivery of intrathecal baclofen but not specifically for the 18 F-Baclofen analog in this study. A flow rate corresponding to a monthly refill interval for a 40-mL implantable pump (55 µL/hr) was selected, and infusate was delivered continuously over a 6-hour interval at two different catheter positions (C1 and T10) with continuous image acquisition.…”