Sayama S, Fujimoto K, Nakano I
Department of Neurology, National Sanatorium Ashikaga Hospital.
Rinsho Shinkeigaku. 1998 Jun;38(6):495-8.
We applied valproic acid (VPA) on the rigidity of three parkinsonian patients, two with Parkinson disease and one with striatonigral degeneration. They were all at Hoehn and Yahr's stage V and showed marked rigidity. In these patients, effect of L-DOPA had become limited or increasing the dosage of L-DOPA was difficult because of its side effects. Parkinsonian symptoms were assessed by using motor score of Unified Parkinson's Disease Rating Scale. The degree of rigidity in these three patients was markedly decreased with 300-600 mg/day of VPA. The blood level of VPA ranged from 24.8 to 66.5 micrograms/ml, which was relatively low compared with the effective blood level as an anti-epileptic agent. Parkinsonian symptoms other than rigidity, and the increased deep tendon reflexes which were present in the patient with striatonigral degeneration were not affected by VPA. Reduction of L-DOPA intensified rigidity again which had been under control. Trials of VPA on parkinsonism have been reported from two groups (Price PA, et al. 1978; Nutt J, et al. 1979), neither of which has observed any benefit of VPA. The difference of their results and ours seems to depend on the stage of patients; their patients had mild to moderate symptoms, whereas ours were in the end stage with marked rigidity. Since the effect of VPA upon parkinsonism is limited to rigidity, the end-stage patients whose care is difficult due to severe rigidity may obtain the best benefit of VPA. VPA is considered to take effect by activating gamma-aminobutyric acid (GABA) system. Because GABA is a common inhibitory neurotransmitter distributed in the wide areas of the central nervous system, it is difficult to locate the action site of VPA with regard to the amelioration of rigidity. The stretch reflex loop in the spinal cord does not seem to be the action site because no change was noted in deep tendon reflex. GABAergic striatal efferent neurons do not seem to be the sole action site either, because parkinsonian symptoms were not affected except for rigidity. The vestibular nucleus which receives strong GABAergic afferents from cerebellar Purkinje cells is an efficient tonus regulator. Since suppression of the function of the nucleus is known to reduce rigidity, it is at least a candidate for the action site of VPA. But there is no direct evidence for this matter. The exact action site of VPA remains to be elucidated.
我们对三名帕金森病患者（其中两名患帕金森病，一名患纹状体黑质变性）的强直症状应用了丙戊酸（VPA）。他们均处于霍恩和雅尔分级的V期，表现出明显的强直。在这些患者中，左旋多巴（L-DOPA）的效果变得有限，或者由于其副作用而难以增加L-DOPA的剂量。通过使用统一帕金森病评定量表的运动评分来评估帕金森病症状。这三名患者服用300 - 600毫克/天的VPA后，强直程度明显降低。VPA的血药浓度范围为24.8至66.5微克/毫升，与作为抗癫痫药物的有效血药浓度相比相对较低。除强直外的帕金森病症状，以及纹状体黑质变性患者中出现的深腱反射增强，均未受VPA影响。L-DOPA剂量减少后，原本得到控制的强直症状再次加重。已有两组报道了VPA治疗帕金森病的试验（Price PA等人，1978年；Nutt J等人，1979年），但均未观察到VPA有任何益处。他们的结果与我们的结果不同似乎取决于患者的病情阶段；他们的患者症状为轻度至中度，而我们的患者处于末期且有明显的强直。由于VPA对帕金森病的作用仅限于强直，因此因严重强直而护理困难的末期患者可能从VPA中获得最大益处。VPA被认为是通过激活γ-氨基丁酸（GABA）系统起作用。由于GABA是一种广泛分布于中枢神经系统的常见抑制性神经递质，因此就强直改善而言，很难确定VPA的作用位点。脊髓中的牵张反射环路似乎不是作用位点，因为深腱反射未发现变化。GABA能纹状体传出神经元似乎也不是唯一的作用位点，因为除了强直外，帕金森病症状未受影响。前庭核从小脑浦肯野细胞接收强烈的GABA能传入纤维，是一个有效的紧张性调节中枢。由于已知抑制该核的功能可减轻强直，因此它至少是VPA作用位点的一个候选者。但此事尚无直接证据。VPA的确切作用位点仍有待阐明。
