Acta Neurochir Suppl (2006) 99: 61–63
# Springer-Verlag 2006 Printed in Austria
Fifteen year experience of intrathecal baclofen treatment in Japan
T. Taira, T. Ochiai, S. Goto,and T. Hori
Department of Neurosurgery, Neurological Institute, Tokyo Women’s Medical University, Tokyo, Japan
Summary
Intrathecal baclofen administration is a fully established treatment for severe spasticity. However, it is scarcely known that Baclofen, an agonist of GABA-B receptor, has other potential effects on pain, restoration coma, dystonia, tetanus, and hypothalamic storm. Sporadic episodes of dramatic recovery from persistent vegetative state are reported after intrathecal administration of baclofen. There are also reports on the use of baclofen for neuropathic pain including poststroke central pain syn- drome. Baclofen is also used for control of dystonia due to cerebral palsy or reflex sympathetic dystrophy. On the other hand, epidural spinal cord stimulation has been used for pain, spasticity, dystonia, or attempt to improve deteriorated consciousness, though the effects seem variable and modest. Similarity between baclofen and spinal cord stimulation is interesting in that both involve the spinal GABAergic system. Based on the 15-year personal experience of intrathecal baclofen, I would stress importance of this treatment not only for spasticity but also for other difficult neurological disorders.
Keywords: Intrathecal baclofen; pain; dystonia.
It was more than 15 years ago that the first author be- came interested in neurosurgical management of spasti- city, when almost no neurosurgeons in Japan knew about neurosurgical management of spasticity. During my fel- lowship study in Birmingham U.K. from 1988, my great mentor, Professor Hitchcock used to perform stereotac- tic dentatotomy for various kinds of spasticity. Although the effect of dentatotomy was transient, I observed many instances of dramatic immediate changes after relief of severe spasticity. This was the main reason I realized the importance of neurosurgical management of spasticity.
After coming back to Japan, because baclofen for intra- thecal use was not available, I personally imported the medication from Basel, Switzerland, and started trial bo- lus injection mainly to patients with post cerebrovasular accidents. Implantable pumps for chronic treatment were not available, but even with bolus injections. I noticed a variety of neurological changes from careful clinical observation.
One day, in the early 90s, I injected baclofen to a patient with foot spasticity after a stroke. The patient also had poststroke dysesthetic pain, and to my big sur- prise, the patient reported not only relief of spasticity but also the pain, which I could not believe in the beginning.
In the same room of the ward, there was another patient with poststroke central pain who had undergone thala- mic deep brain stimulation and motor cortex stimulation without remarkable benefit. This patient eagerly asked me to inject baclofen as a trial case. I hesitated and explained the difference of indication, but the patient insisted on trying, and finally I did. Again, it worked as shown in Fig. 1. I did not tell the patient the possible time course of drug effect, but the time curve of pain relief was compatible with bolus intrathecal baclofen for spasticity. Since then, I investigated the effect of bolus baclofen injection on various kinds of neuropathic pain.
Analgesic effect of baclofen is not widely known, though baclofen is the second choice drug for idiopath- ic trigeminal neuralgia. In clinical studies, intrathecal baclofen, of course, relieves muscle spasm pain, which is generally believed secondary to relief of spasticity.
However, there have been some clinical reports concern- ing pain relief with intrathecal baclofen. Herman et al. [3]
reported that central pain caused by spinal lesions is successfully controlled with lumbar intrathecal baclofen and obviously this is not the secondary effect. In their report, a patient even with a C3 lesion experienced relief of pain in the leg. I also reported that intrathecal baclo- fen effectively suppresses even poststroke central pain [5]. Such baclofen analgesia as in patients with central pain of spinal origin can be explained by suppression of the abnormal neuronal activities in the spinal posterior horn. Baclofen analgesia is not mediated through the en- dogenous opiate system. The neural structures rostral to
the medulla and caudal to the midbrain are necessary for the analgesic effect of baclofen. These findings suggest that there is an ascending pain control system from the spinal cord to the pons that is not mediated by the opiate system. Because baclofen acts on GABA-B receptor sites that are present in high concentration in the spinal dorsal horn, GABA may be the mediator of this pain control system. It has been reported that GABA is re- leased by electrical spinal cord stimulation [2, 4], which technique has been widely used for pain relief. This further supports the importance of the GABAergic sys- tem in pain mechanism [8].
In 1995, I was asked to accept a patient from Kyushu area (900 km from Tokyo). The patient was a young boy who had become bed-ridden after severe traumatic brain injury. I had no idea what to do. When I first saw him, he
was severely tetra-spastic, unconscious, and in so-called vegetative state. I desperately asked my residents to inject baclofen through a lumbar tap every day for at least one month. Then, to everyone’s big surprise, the boy woke up after 25 injections, started talking, and eating by himself. Six months later, he returned home on foot (Fig. 2). Ten years from then, he is now a high school student. The recovery from vegetative state was dramatic [7].
There are some communications [Becker 1996, Meythaler 1996 and others] that they also experienced dramatic recovery of consciousness after intrathecal ad- ministration of baclofen. It is known that, in cerebral palsy children, selective dorsal rhizotomy and resultant relief of leg spasticity, it may show subsequent positive effects on higher brain functions. The effect of baclofen on persistent vegetative state may thus be secondary, but the effects in some limited cases are so dramatic that we have to consider the primary role of baclofen on dis- turbed consciousness. It is known that baclofen im- proves conduction in demyelinated axons and therefore intrathecal baclofen may accelerate the repair of diffuse axonal injury. Spinal cord stimulation has been used in the hope of recovery from persistent vegetative state, and in some cases, it is really effective. Thus, spinal cord stimulation and baclofen are also similar in terms of re- covery from persistent vegetative state.
Spinal cord stimulation used to be reported as effec- tive treatment of dystonia, though the results were not always uniform [10]. Intrathecal baclofen has been in- troduced for the treatment of generalized dystonia due to cerebral palsy or of unknown etiology, and the results seem promising [1]. It also opened a new therapeutic option for dystonia and pain in reflex sympathetic dys- trophy that is refractory to most treatment [9]. Spinal cord stimulation is regarded as a choice of surgical treat- ment of reflex sympathetic dystrophy. Cerebral blood flow Spinal cord stimulation increases cerebral blood flow through unknown mechanisms not related with in- creased sensory input. The stimulation has been tried in ischemic stroke or vasospasm after subarachnoid hemor- rhage. To our knowledge, there is no report on cerebral blood flow and baclofen in clinical setting, while we have experimental data on cerebral blood flow that in- creased following intrathecal administration of baclofen.
This year, the Government of Japan finally approved intrathecal baclofen and implantable pumps after 29 cases of clinical trial. They had requested us to perform high-cost domestic clinical trials despite the fact that several thousand patients have been benefiting every
Fig. 1. Pain relief after intrathecal injection of baclofen. Baclofen was injected at 10:55 am and pain in the leg became 2=10 after 4 hours, and the effect on arm pain was still present on the following morning. Pain score was assessed by the patient
62 T. Taira et al.
year from this treatment in many other countries. Be- cause of such political delay, I learnt a lot more on the action of baclofen and various aspects of intrathecal medical treatment.
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Correspondence: Takaomi Taira, TWMU Neurosurgery, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. e-mail: ttaira@
nij.twmu.ac.jp
Fig. 2. Tetraspastic unconscious boy after traumatic brain injury. Intrathecal baclofen was used to relieve spasticity, and consciousness dramatically improved
Fifteen year experience of intrathecal baclofen treatment in Japan 63
