Complex Operative Unit of Neurology, "F. Ferrari" Hospital, Casarano, 73042 Lecce, Italy.
Laboratory of Neuroproteomics, Multiple Sclerosis Centre, "F. Ferrari" Hospital, Casarano, 73042 Lecce, Italy.
Int J Mol Sci. 2023 Feb 3;24(3):2968. doi: 10.3390/ijms24032968.
We report the singular case of a 31-year-old woman who developed very serious Fluphenazine-induced parkinsonism over a few days due to a doubly incongruent drug prescription by indication and dosage having been applied to a healthy subject over one week instead of seven months. Unlike gradual drug-induced parkinsonism, our patient experienced acute extrapyramidal syndrome (EPS), reaching significant motor and sphincter disability in just a few days, followed by a gradual incomplete recovery over more than six months. In fact, after drug discontinuation, hypomimia and slight left hemi-somatic rigidity with bradykinesia remained, as well as stable non-progressive memory disturbances. Despite bio-humoral and instrumental investigations and DaTScan were negative, MRI post-analysis evidenced a 6.5% loss in brain volume. Specifically, irreversible cortical and sub-cortical grey matter reduction and cerebrospinal fluid space enlargement with spared white matter were found. Our observations suggest that the sudden availability of Fluphenazine results in a kind of plateau effect of parkinsonism presentation, partially reversible due to the neurotoxic drug effect on the cortical and sub-cortical grey matter, resulting in asymmetric EPS and stable memory loss, respectively. Our report confirms the debated neurotoxicity of first-generation neuroleptics and the postulated theory of differential susceptibility to the cytotoxic stressors on the central nervous system.
我们报告了一个特殊的病例,一名 31 岁女性在几天内因指示和剂量双重不相符的药物处方而患上了非常严重的氟奋乃静诱导的帕金森病,这种情况原本应在七个月内而非一周内应用于一个健康受试者。与逐渐出现的药物诱导的帕金森病不同,我们的患者经历了急性锥体外系综合征(EPS),仅在几天内就出现了显著的运动和括约肌功能障碍,随后在六个月以上的时间里逐渐不完全恢复。事实上,停药后,仍然存在运动不能和轻微的左侧半身躯体僵硬伴运动迟缓,以及稳定的非进行性记忆障碍。尽管进行了生物-体液和仪器检查以及 DaTScan 检查,但均为阴性,MRI 后分析显示大脑体积损失了 6.5%。具体来说,发现皮质和皮质下灰质不可逆性减少,脑脊液空间扩大,而白质未受影响。我们的观察结果表明,氟奋乃静的突然出现导致帕金森病表现出现一种类似平台效应,部分可逆,这是由于神经毒性药物对皮质和皮质下灰质的作用所致,分别导致了不对称的 EPS 和稳定的记忆丧失。我们的报告证实了第一代神经安定药的神经毒性以及关于对中枢神经系统细胞毒性应激源的易感性差异的假设理论。