Lazorthes Y, Sallerin-Caute B, Verdie J C, Bastide R, Carillo J P
University Clinic of Neurosurgery, Medical Faculty of Rangueil, University Paul-Sabatier, Toulouse, France.
J Neurosurg. 1990 Mar;72(3):393-402. doi: 10.3171/jns.1990.72.3.0393.
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.
巴氯芬是治疗痉挛最有效的药物，是γ-氨基丁酸-B受体的特异性激动剂，在脊髓浅层中含量非常丰富。口服时，巴氯芬不易穿透血脑屏障，在脑和脊髓中的分布相同。为了通过优先灌注脊髓来改变药物的分布，采用了直接鞘内给药。18例患有严重痉挛综合征的患者接受了腰段脑脊液慢性鞘内输注巴氯芬治疗。经过临床预选，38例患者植入了腰段接入端口以进行长期试验，以确定巴氯芬治疗的疗效和有效的12小时剂量。选择进行慢性给药的18例患者植入了可编程泵。这些病例的病理情况为：多发性硬化症（6例）、创伤后痉挛综合征（8例），以及脑瘫、缺血性脑病变、脊髓缺血和横贯性脊髓炎各1例。平均随访期为18个月（范围4至43个月）。根据Ashworth量表上的肌肉张力亢进情况（因疼痛性痉挛的发生而改变）和功能改善情况对临床结果进行评估。创伤性脊髓损伤继发的痉挛综合征的结果优于脱髓鞘疾病。如霍夫曼（H）反射记录所证实，所有病例的肌张力亢进均得到改善。16例受影响患者中有14例疼痛性肌肉痉挛消失。9例患者有显著的功能改善，3例患者改善明显。过量用药继发副作用（如过度肌张力减退或中枢抑制）的风险以及缺乏特异性巴氯芬拮抗剂强调了准确确定有效剂量的必要性。经过初始滴定期和治疗剂量调整后，个体剂量为21至500微克/24小时（平均160微克/24小时）。这种新的保守方法非常有效、完全可逆，并且在有利于其使用的条件下给药时是安全的。
