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

• Published in: International journal of molecular sciences Vol. 24; no. 3; p. 2968
• Main Authors: De Masi, Roberto, Orlando, Stefania, Toni, Vincenzo, Costa, Maria Carmela
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03.02.2023; MDPI
• Subjects: Adult; Amnesia; Antipsychotic Agents - adverse effects; Antipsychotics; Apathy; Brain diseases; Case Report; Case reports; Cerebrospinal fluid; Dopamine; Drug dosages; Female; Fluphenazine - adverse effects; Humans; Magnetic resonance imaging; Memory Disorders - chemically induced; Neurotoxicity; Parkinson Disease, Secondary - chemically induced; Parkinson's disease; Parkinsonian Disorders; Patients; Psychotropic drugs; Tremor (Muscular contraction); United Kingdom > UK; extrapyramidal syndrome; Fluphenazine; neurotoxicity; parkinsonism; neuroleptics; memory loss
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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.