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Abstract：
OBJECTIVE: To determine the safety and efficacy of orally delivered 4-aminopyridine (4-AP) in persons with Guillain-Barré Syndrome (GBS) >6 months from initial diagnosis.
METHODS: A randomized, double-blind, placebo-controlled, crossover study.
METHODS: Tertiary care clinical outpatient program.
METHODS: Nineteen participants enrolled (14 male, 5 female; N=19), neurologic impairment secondary to GBS and functional loss on the FIM motor score (stable for ≥12mo) and >3.0 but <5.0 on the American Spinal Injury motor scale. Twelve participants (mean age, 59y; range, 23-77y) completed the study.
METHODS: A 4-AP dose-escalation study with 8 weeks in each period with a 3-week washout period, followed by 3 months open-label follow-up.
METHODS: FIM motor score was the primary outcome measure; also evaluated were the American Spinal Injury motor strength score (all limbs), handheld dynamometer, 6-minute walk test, Medical Outcomes Study 12-Item Short Form, Center for Epidemiological Studies Depression scale, Positive and Negative Affect Schedule, pain, GBS disability scale, Jepsen-Taylor Hand Function Test, Minnesota Manual Dexterity Test and Minnesota Rate of Manipulation Test, Get Up and Go Test, McGill Pain Inventory, Craig Handicap Assessment and Reporting Technique, and participant self-evaluation.
RESULTS: Seven participants discontinued the study prematurely: 3 because of adverse events, 3 because of travel difficulties or relocation, and 1 because of pretreatment laboratory abnormalities. After removing 3 participants with maximum FIM scores, 4-AP arm trended superior to placebo (P=.065). Patients subjectively could always tell when they were on the active agent usually by tingling sensations or a sense of wellness. No statistically significant differences were found for other outcome measures although there were strong trends.
CONCLUSIONS: This study demonstrates the safety of 4-AP in the patient population with GBS as the predominate goal of the study. A trend toward improved function after treatment was noted with most patients electing to stay on the medication after the trial.
METHODS: A randomized, double-blind, placebo-controlled, crossover study.
METHODS: Tertiary care clinical outpatient program.
METHODS: Nineteen participants enrolled (14 male, 5 female; N=19), neurologic impairment secondary to GBS and functional loss on the FIM motor score (stable for ≥12mo) and >3.0 but <5.0 on the American Spinal Injury motor scale. Twelve participants (mean age, 59y; range, 23-77y) completed the study.
METHODS: A 4-AP dose-escalation study with 8 weeks in each period with a 3-week washout period, followed by 3 months open-label follow-up.
METHODS: FIM motor score was the primary outcome measure; also evaluated were the American Spinal Injury motor strength score (all limbs), handheld dynamometer, 6-minute walk test, Medical Outcomes Study 12-Item Short Form, Center for Epidemiological Studies Depression scale, Positive and Negative Affect Schedule, pain, GBS disability scale, Jepsen-Taylor Hand Function Test, Minnesota Manual Dexterity Test and Minnesota Rate of Manipulation Test, Get Up and Go Test, McGill Pain Inventory, Craig Handicap Assessment and Reporting Technique, and participant self-evaluation.
RESULTS: Seven participants discontinued the study prematurely: 3 because of adverse events, 3 because of travel difficulties or relocation, and 1 because of pretreatment laboratory abnormalities. After removing 3 participants with maximum FIM scores, 4-AP arm trended superior to placebo (P=.065). Patients subjectively could always tell when they were on the active agent usually by tingling sensations or a sense of wellness. No statistically significant differences were found for other outcome measures although there were strong trends.
CONCLUSIONS: This study demonstrates the safety of 4-AP in the patient population with GBS as the predominate goal of the study. A trend toward improved function after treatment was noted with most patients electing to stay on the medication after the trial.
摘要：
目的：确定口服4-氨基吡啶（4-AP）治疗格林-巴利综合征（GBS）患者的安全性和有效性。
方法：随机，双盲,安慰剂对照,交叉研究。
方法：三级护理临床门诊计划。
方法：19名参与者（14名男性，5名女性；N=19），在FIM运动评分（稳定≥12mo）和>3.0，但在美国脊髓损伤运动量表上<5.0，继发于GBS的神经系统损害和功能丧失。12名参与者(平均年龄，59y；范围，23-77y）完成了研究。
方法：一项4-AP剂量递增研究，每个周期8周，3周洗脱期，随后进行3个月的开放标签随访。
方法：FIM运动评分是主要结果指标；还评估了美国脊柱损伤运动强度评分（所有肢体），手持式测力计,6分钟步行测试，医学成果研究12项简表，流行病学研究中心抑郁量表，正面和负面影响时间表，疼痛,GBS残疾量表，Jepsen-Taylor手函数测试,明尼苏达州手动灵巧测试和明尼苏达州操纵率测试，起床去测试，麦吉尔疼痛清单,克雷格残疾评估和报告技术，和参与者的自我评价。
结果：7名参与者因不良事件而提前中止研究：3名，3因出行困难或搬迁，和1因为预处理实验室异常。移除具有最高FIM分数的3名参与者后,4-AP组的趋势优于安慰剂组（P=0.065）。患者主观上总是可以通过刺痛感或健康感来分辨他们何时在活性剂上。尽管存在强烈的趋势，但其他结果指标未发现统计学上的显着差异。
结论：这项研究证明了4-AP在GBS患者人群中的安全性是该研究的主要目标。注意到治疗后功能改善的趋势，大多数患者选择在试验后继续服药。
方法：随机，双盲,安慰剂对照,交叉研究。
方法：三级护理临床门诊计划。
方法：19名参与者（14名男性，5名女性；N=19），在FIM运动评分（稳定≥12mo）和>3.0，但在美国脊髓损伤运动量表上<5.0，继发于GBS的神经系统损害和功能丧失。12名参与者(平均年龄，59y；范围，23-77y）完成了研究。
方法：一项4-AP剂量递增研究，每个周期8周，3周洗脱期，随后进行3个月的开放标签随访。
方法：FIM运动评分是主要结果指标；还评估了美国脊柱损伤运动强度评分（所有肢体），手持式测力计,6分钟步行测试，医学成果研究12项简表，流行病学研究中心抑郁量表，正面和负面影响时间表，疼痛,GBS残疾量表，Jepsen-Taylor手函数测试,明尼苏达州手动灵巧测试和明尼苏达州操纵率测试，起床去测试，麦吉尔疼痛清单,克雷格残疾评估和报告技术，和参与者的自我评价。
结果：7名参与者因不良事件而提前中止研究：3名，3因出行困难或搬迁，和1因为预处理实验室异常。移除具有最高FIM分数的3名参与者后,4-AP组的趋势优于安慰剂组（P=0.065）。患者主观上总是可以通过刺痛感或健康感来分辨他们何时在活性剂上。尽管存在强烈的趋势，但其他结果指标未发现统计学上的显着差异。
结论：这项研究证明了4-AP在GBS患者人群中的安全性是该研究的主要目标。注意到治疗后功能改善的趋势，大多数患者选择在试验后继续服药。
