Fluphenazine-Induced Neurotoxicity with Acute Almost Transient Parkinsonism and Permanent Memory Loss: Lessons from a Case Report

Abstract

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.

Keywords: Fluphenazine; extrapyramidal syndrome; memory loss; neuroleptics; neurotoxicity; parkinsonism.

Figure 1

DaTScan assessment. No abnormalities of the nigro-striatal pathway were found bilaterally. Cau-R/L, Caudatum Right/Left; Put-R/L, Putamen Right/Left.

Figure 2

MRI post-analysis. (A) T1-weighted axial images of the brain as segmentation output obtained using the Sienax tool. From this comparison of the 2007 and 2019 MRIs, note the structures that most contribute to brain atrophy are the periencephalic liquoral spaces (with a reduction of grey matter and its peripheral fraction). (B) Siena color-coded image output of the brain. Blue indicates atrophy; red indicates growth. Note the prevalence of blue in the grey matter, mainly in the peripheral grey matter as well as the ventricular system.