Baclofen intrathecal injection (ITB?) therapy is used for the treatment of severe myasthenia gravis. ITB? therapy is based on the use of an implantable perfusion system from Medtronic and the drug baclofen injection, which is injected directly into the intrathecal and cerebrospinal fluid (CSF). 1. Background material on the clinical application and developmental experience of ITB. In the United States, ITB?therapy (intrathecal baclofen injection) was approved for the treatment of severe myospasm of spinal origin in 1992 and for severe myospasm of cerebral origin in 1996 (see Figure 1). Patients considered for ITB?therapy are those who have failed with other less invasive therapies, including oral medications, local injections (e.g., Botulinum toxin Botox®), and irreversible injurious neurosurgery. High doses of oral medications often produce side effects that are difficult for patients to tolerate. A large number of clinical studies on ITB have provided clinically relevant data as well as useful individual case data. 2. Overview of the screening test The screening test procedure uses a concentration of 50 μg/ mL of baclofen injection. The patient’s initial response will determine whether additional injections are necessary on subsequent days. An initial screening dose of 1 mL containing 50 μg of drug is recommended. For very young patients, some clinicians are using a dose of 25 μg. The screening trial was administered by aspirate plus drug injection, administered intrathecally over a period of greater than one minute. Patients are observed over the next 4 to 8 hours. If the initial response does not achieve the desired effect, a second one-time injection may be administered at least 24 hours after the initial injection. The recommended screening dose for the second one-time injection is 1.5 mL, containing 75 μg of drug. The patient is then observed every 4 to 8 hours. If the patient still does not respond satisfactorily, a final one-time screening injection may be administered 24 hours later at the maximum recommended dose of 2 mL containing 100 μg of drug. Patients who do not respond well to the 100 μg one-time intrathecal injection should be considered unfit to receive ITB?long-term therapy using an implantable perfusion system. 3. Efficacy evaluation Various evaluation methods can be used to evaluate the degree of improvement of spasticity. Myospasm of spinal cord origin: A randomized controlled study was conducted on 576 patients with severe myospasm due to spinal cord injury or multiple sclerosis. The efficacy of placebo was compared with that of a single intrathecal dose of baclofen or with a three-day screening injection of baclofen. The results obtained confirmed the efficacy of Lioresal® intrathecal injection (baclofen injection) (Medtronic (Medtronic) archived data). Baclofen was superior to placebo on two primary measures used in the trial: change in frequency and/or severity of spasticity compared to baseline Ashworth spasticity score cerebral myoclonus: three controlled clinical trials investigated the efficacy of Lioresal® intrathecal injection in cerebral myoclonus: two studies enrolled patients with cerebral palsy and one two of them enrolled patients with cerebral palsy and the other enrolled patients with myasthenia gravis due to previous brain injury (Medtronic archive). One of the randomized, controlled crossover studies enrolling 51 patients with cerebral palsy produced robust and statistically significant results: baclofen injection was superior to placebo in relieving myospasm as evaluated by the Ashworth Scale1. A second randomized, double-blind, placebo-controlled, crossover, screening trial was conducted in 11 patients with myasthenia gravis due to brain injury. Despite the small sample size, this study yielded an almost significant test statistic (p=0.066) and provided results in favor of baclofen injection [1],[2],[3]. Another pre-marketing study with a total of 211 patients also provided original information on the safety and efficacy of baclofen injection (Medtronic archives). Two controlled clinical studies (one single-center and one multicenter) confirmed the efficacy and safety of ITB?therapy in the treatment of myospasm of spinal origin (Medtronic data on file). In these monitored trials conducted in the United States, the clinical results for efficacy suggested a 97% response rate. 225 of 231 subjects had the expected response to the screening dose. The first controlled clinical trial, initiated in 1984, demonstrated the efficacy of baclofen injection in reducing the degree and incidence of muscle spasticity and correlated the results of the screening trial with those obtained with continuous infusion. 20 patients with refractory myasthenia gravis secondary to multiple sclerosis (MS) or spinal cord injury (SCI) were enrolled in the study.4 For each of the two etiologies, 10 subjects were recruited. Ten subjects were recruited for each of the two etiologies. In this open screening trial, each patient received up to three single doses of baclofen (50, 75, and 100 μg) to significantly reduce the degree and incidence of muscle spasticity. All patients showed a positive response and entered a long-term follow-up study. The efficacy was evaluated using the Ashworth scale (to evaluate the muscle tone level) and the spasticity scale (to evaluate the frequency of spasticity). Baclofen injection vs. placebo analysis suggested a statistically significant difference between the two treatment groups. In patients treated with baclofen injection, there was a mean reduction of 2.8 points in Ashworth score and a mean reduction of 2.1 points in spasticity score. There were no significant differences between the two groups in terms of age, gender, or duration of spasticity. Baclofen injection was effective regardless of which disease the patients had (MS or SCI) and regardless of how long they had been taking baclofen tablets orally. The efficacy of baclofen injection was reconfirmed in a second clinical multicenter study that began in 1988. The trial was conducted at 12 centers in the United States, and 45 patients were randomized to receive either a single injection of 50 μg of baclofen injection or a placebo in random order. Patients who did not respond to the drug received a second randomization to either 75 μg of baclofen injection as a single injection or placebo in random order, and those who still did not respond to that dose continued to receive 100 μg of baclofen injection (in random order? or placebo). The study showed a clinically and statistically significant reduction in spasticity (mean reduction in Ashworth score of 2.0) and spasticity frequency (mean reduction in spasticity score of 2.6) in patients treated with baclofen injection. Based on more than two decades of documented safety and efficacy, ITB? has been widely used around the world as a safe and effective treatment for refractory severe myasthenia gravis. There is a good correlation between the results of positive screening tests and successful long-term treatment outcomes, as evidenced by a large number of clinical studies and extensive clinical experience.