Dear Editor:

Although poststroke psychosis is a reasonably well-established clinical phenomenon,¹ few articles describing the development of psychotic symptoms on the background of a perinatal stroke history or other anoxic brain injury have been published to date,^2–7 despite the well-known association between obstetrical complications, including hypoxic events, and schizophrenia.⁸ The case presented here represents the earliest reported onset of psychosis in this context not thought to be seizure-related.

This case concerned a 37-year-old male patient with a history of focal structural epilepsy stemming from a neonatal intracranial hemorrhage in the context of Escherichia coli (E. coli) meningitis, and resultant developmental delay, moderate intellectual disability, and right-sided hemiplegia. As brain imaging studies were last completed when he was young, the results were no longer accessible. While his seizures were historically left frontocentral in origin, he has been seizure-free since 2013.

In 2023, the patient was referred to a developmental disabilities mental health clinic for the management of longstanding intermittent agitation/aggression, typically triggered by misinterpreting others’ statements, as well as in response to referential ideas related to television/movies. Since early childhood, he had also often been observed muttering to himself incoherently, seemingly in response to internal stimuli. At the time of the initial assessment, his presentation was thought to represent a combination of dysphasia and retreat into fantasy in the broader context of his neurodevelopmental history, given that such symptoms had been occurring on a daily basis for decades (absent any sustained periods of quiescence) without having meaningfully evolved. Importantly, his clinical presentation did not materially change after the abatement of his seizures in 2013, making a direct association between the two unlikely (eg, in the context of postictal psychosis, interictal psychosis, or forced normalization).

His medications included carbamazepine controlled-release (CR) 600mg twice daily, clobazam 25mg twice daily, quetiapine extended-release (XR) 150mg nightly, and rosuvastatin 5mg daily. Although a quetiapine serum level was not obtained, it was presumed to be subtherapeutic given his concurrent use of carbamazepine (in light of its cytochrome P450 3A4-inducing effects), and as such he was transitioned to risperidone to target his agitation/aggression. Not only did his behavioral issues quickly resolve during titration up to 2mg daily, but his longstanding self-talk and perseveration on various ideas of reference surprisingly also significantly improved over the course of a few months, despite persisting to some degree. He additionally appeared far less internally preoccupied and presented as much more organized, coherent, and communicative. Remarkably, his ability to perform complex behaviors (primarily related to activities of daily living) also improved after his dose was further increased to 3mg daily. No side effects have been identified or endorsed.

Although his aforementioned presentation was initially not thought to be a manifestation of psychosis, in retrospect, this seems probable given the breadth of positive changes observed after the initiation of antipsychotic therapy. In particular, while perceived disturbances of thought form in relation to a left hemisphere stroke could conceivably be attributed to delirium and/or an aphasic syndrome, his dramatic improvement in this respect make these explanations less likely.

The development of psychosis in the context of a perinatal stroke/anoxic brain injury history has only been reported a few times previously,^2–7 and two of these presentations were thought to be seizure-related.^3,7 The other four individuals had an onset of psychosis in their early-to-mid teenage years,^2,4–6 making it difficult to draw conclusions about causality, whereas the individual described here reportedly began exhibiting his presumed psychotic symptoms early in life, making an association with his perinatal stroke history more plausible. All four also experienced auditory hallucinations and disorganization,^2,4–6 while a select few additionally exhibited paranoia,^5,6 erotomanic delusions,² and somatic hallucinations.⁵ Response to antipsychotic therapy was reportedly good in two cases,^2,6 partially good in one,⁵ and seemingly poor in another.⁴ Interestingly, although two of these individuals were explicitly noted to have a diagnosis of cerebral palsy, none were clearly intellectually disabled; however, one had a full-scale intelligence quotient (IQ) of 70.²

The paucity of published reports on this topic is likely in part artifactual. That is, although cerebral palsy is known to be associated with psychosis/schizophrenia,⁹ details regarding a given individual’s diagnosis of cerebral palsy are often not specified, despite presumably resulting from an anoxic brain injury in some cases.

Given the location of this patient’s historical seizure focus, this case implicates aberrant frontal lobe functioning during early development in psychosis pathogenesis. This is perhaps not surprising given that frontal lobe development is necessary for a diverse array of functions and considering that frontal lobe abnormalities are known to occur in schizophrenia populations.¹⁰

This case also illustrates the need for clinicians to be vigilant with respect to screening for psychosis in individuals with a perinatal stroke history, particularly given the inherent communication difficulties and intellectual impairment that can confound the assessment.

With regards,

Mark A. Colijn, MD, MSc, FRCPC, UCNS

Dr. Colijn is with the Department of Psychiatry, Mathison Centre for Mental Health Research and Education, and Hotchkiss Brain Institute at the University of Calgary in Calgary, Canada.

Funding/financial disclosures. The author is a co-investigator for a RCT in generalized anxiety disorder sponsored by Sunovion and Sumitomo, and a study physician for a RCT in major depressive disorder partially funded by Otsuka (part of CAN-BIND). He also provides psychiatric consultation for the ATLAS study (Biogen). The author has no conflicts of interest relevant to the content of this letter. This manuscript did not receive any specific grant funding. MC’s salary is supported by the AMHSP (Alberta Health Services and the University of Calgary).

Statement of ethical considerations. Ethics approval was not required for this case report in accordance with local/national guidelines. However, written informed consent for the publication of this case report was obtained from the patient’s legal guardian. The patient himself also provided assent.

References:

1. Stangeland H, Orgeta V, Bell V. Poststroke psychosis: a systematic review. J Neurol Neurosurg Psychiatry. 2018;89(8):879–885.
2. Mann J, Foreman DM. Homo-erotomania for a delusional parent: erotomania with Capgras and Fregoli syndromes in a young male with learning difficulties. J Intellect Disabil Res. 1996;40(Pt 3):275–278.
3. Nissenkorn A, Moldavsky M, Lorberboym M., et al. Postictal psychosis in a child. J Child Neurol. 1999;14(12):818–819.
4. Gilmore JH, Castillo M, Rojas M. Early onset schizophrenia in a patient with premature birth, germinal matrix hemorrhage and periventricular leukomalacia. Schizophr Res. 2000;44(2):158–160.
5. Kunugi H, Urushibara T, Murray RM, et al. Prenatal underdevelopment and schizophrenia: a case report of monozygotic twins. Psychiatry Clin Neurosci. 2003;57(3):271–274.
6. Grody MB, Coffey BJ. Presentation and treatment of acute psychosis in an adolescent girl with cerebral palsy. J Child Adolesc Psychopharmacol. 2012;22(2):175–178.
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8. Davies C, Segre G, Estrade A, et al. Prenatal and perinatal risk and protective factors for psychosis: a systematic review and meta-analysis. Lancet Psychiatry. 2020;7(5):399–410.
9. Ryan JM, Albairami F, Hamilton T, et al. Prevalence and incidence of chronic conditions among adults with cerebral palsy: a systematic review and meta-analysis. Dev Med Child Neurol. 2023;65(9):1174–1189.
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