Beck Marcus, Flachenecker Peter, Magnus Tim, Giess Ralf, Reiners Karlheinz, Toyka Klaus V, Naumann Markus
Department of Neurology, ALS Study Group, Julius-Maximilians-University Wuerzburg, Germany.
Amyotroph Lateral Scler Other Motor Neuron Disord. 2005 Jun;6(2):100-3. doi: 10.1080/14660820510028412.
This pilot study aimed at exploring the effects of intrathecally administered brain derived neurotrophic factor (BDNF) on autonomic functions in patients with ALS. A battery of autonomic sympathetic and parasympathetic tests was performed at baseline and after nine months of treatment in 10 ALS patients participating in a double-blind placebo-controlled phase II/III study of intrathecally administered BDNF. Results of patients treated with BDNF (25 or 150 microg/day) were compared to those receiving placebo. Sudomotor function and blood pressure response to handgrip significantly worsened during the treatment period (55.4+/-26.1 vs. 38.9+/-23.9 g/m(2)h, p<0.05; 20+/-6 vs. 13+/-4 microHg, p<0.05) whereas other sympathetic and all parasympathetic function tests only tended to be more abnormal at follow-up. Serum norepinephrine levels increased significantly during the nine-months observation period. The results of autonomic function tests were not different between patients treated with BDNF and placebo, but norepinephrine levels were higher in the BDNF group. We conclude that autonomic nervous system function deteriorates along with poorer motor performance independently from treatment with BDNF. The elevation of norepinephrine levels might reflect a non-specific up-regulation, and its association with BDNF an autocrine effect.
这项初步研究旨在探讨鞘内注射脑源性神经营养因子（BDNF）对肌萎缩侧索硬化症（ALS）患者自主神经功能的影响。在一项鞘内注射BDNF的双盲安慰剂对照II/III期研究中，对10例ALS患者在基线时和治疗9个月后进行了一系列自主神经交感和副交感神经测试。将接受BDNF治疗（25或150微克/天）的患者结果与接受安慰剂的患者结果进行比较。在治疗期间，发汗功能和对握力的血压反应显著恶化（55.4±26.1对38.9±23.9克/平方米小时，p<0.05；20±6对13±4微汞柱，p<0.05），而其他交感神经和所有副交感神经功能测试在随访时仅倾向于更异常。在9个月的观察期内，血清去甲肾上腺素水平显著升高。接受BDNF治疗的患者和接受安慰剂治疗的患者自主神经功能测试结果没有差异，但BDNF组的去甲肾上腺素水平更高。我们得出结论，自主神经系统功能随着运动表现变差而恶化，与BDNF治疗无关。去甲肾上腺素水平的升高可能反映了一种非特异性上调，其与BDNF的关联是一种自分泌效应。
