DOSE-RESPONSE, COASTING, AND DIFFERENTIAL FIBER VULNERABILITY IN HUMAN TOXIC NEUROPATHY - A PROSPECTIVE-STUDY OF PYRIDOXINE NEUROTOXICITY
DOSE-RESPONSE, COASTING, AND DIFFERENTIAL FIBER VULNERABILITY IN HUMAN TOXIC NEUROPATHY - A PROSPECTIVE-STUDY OF PYRIDOXINE NEUROTOXICITY
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DOI：
10.1212/wnl.42.7.1367
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发表时间：
1992-07-01
期刊：
影响因子：
9.9
通讯作者：
REYNOLDS, R
中科院分区：
文献类型：
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作者：
BERGER, AR;SCHAUMBURG, HH;REYNOLDS, R
我们给5名健康志愿者每天服用1g或3g的吡哆醇(维生素B6)，并反复观察血清吡哆醛磷酸盐水平、临床症状和体征、定量感觉阈值(QST)和腓肠神经电生理。一有临床或实验室异常的迹象，就停用吡哆醇。在所有受试者中，感觉症状和QST异常同时发生。接受高剂量的受试者比接受低剂量受试者更早出现症状。在三个低剂量受试者中，热QST升高先于或超过振动QST；在高剂量受试者中，振动和热QST同时出现异常。在三个受试者中，有两个受试者的腓肠肌感觉电位幅度的降低滞后于QST的变化。尽管停止服用吡哆醇，血清磷酸吡哆醛水平恢复正常，但症状仍持续进展2至3周。这项研究表明：(1)吡哆醇诱导的神经病变存在明显的剂量-百分比关系；(2)QST是检测早期周围神经病变的敏感指标；QST异常可能先于神经传导研究的变化；(3)滑行似乎与持续升高的血液毒素水平无关，以及(4)当暴露于诸如吡哆醇的轴突毒素时，不同口径的神经纤维之间可能存在剂量依赖的脆弱性。
We administered either 1 or 3 g/d of pyridoxine (vitamin B6) to five healthy volunteers and repeatedly followed serum pyridoxal phosphate levels, clinical symptoms and signs, quantitative sensory thresholds (QSTs), and sural nerve electrophysiology. Pyridoxine was discontinued at the first sign of either clinical or laboratory abnormality. In all subjects, sensory symptoms and QST abnormalities occurred concurrently. Subjects receiving higher doses became symptomatic earlier than low-dose subjects. Elevation of thermal QSTs preceded or exceeded that for vibration in the three low-dose subjects; vibration and thermal QST became abnormal simultaneously in the higher-dose subjects. A reduction in the amplitude of the sural sensory potential lagged behind QST changes in two of three subjects. Symptoms continued to progress ("coasting") for 2 to 3 weeks despite stopping pyridoxine administration and the return of serum pyridoxal phosphate levels to normal. This study suggests that (1) there is a clear dose-percent relationship for pyridoxine-induced neuropathy, (2) QST is a sensitive measurement for detecting early peripheral neuropathy; QST abnormalities may precede changes in nerve conduction studies, (3) coasting appears unrelated to persistently elevated blood levels of the toxin, and (4) a dose-dependent vulnerability may exist among nerve fibers of different caliber when exposed to an axonal toxin, such as pyridoxine.