Delirium derived from dementia with Lewy bodies in the cancer perioperative period: a case report

Introduction

In cancer treatment, delirium often occurs during the perioperative or chemotherapy periods. Pharmacotherapy with antipsychotics is a common approach to delirium (1), and high doses of antipsychotics may be used to treat severe psychiatric symptoms.

Notably, dementia with Lewy bodies (DLB) with delirium as a precursor symptom and its risk of drug hypersensitivity is not well recognized in the field of cancer treatment. Our survey of the existing literature showed that no cases of DLB in the perioperative period of cancer or of delirium owing to DLB have been reported. Importantly, the use of antipsychotics for patients suffering from delirium derived from hidden DLB may result in serious side effects such as deep sedation and extrapyramidal symptoms.

Here, we report a case of a patient with esophageal cancer who presented with delirium accompanied by severe psychiatric symptoms and who was subsequently diagnosed with DLB in the cancer perioperative period. In support of safe physical treatment and proper management of psychotropics, we highlight the importance of accumulating clinical knowledge regarding hidden DLB with delirium in the cancer perioperative period. We present this article in accordance with the CARE reporting checklist (available at https://apm.amegroups.com/article/view/10.21037/apm-25-48/rc).

Case presentation

A male in his 80s, who has never been treated by a psychiatrist and with no history of psychiatric hospitalization, presented to our hospital. After graduating from high school, he worked as a truck driver from his 20s to his 60s, and has since been unemployed. He married in his 30s and had 2 daughters.

At Y-2 months, X years, he recognized the difficulty of swallowing and experienced a burning sensation when eating, and was later diagnosed with esophageal cancer by his family physician. He was then hospitalized at our hospital. During the evening of the day of admission, he became disoriented and cried out to the medical staff. “I was brought to a strange place. The devil is here. You are trying to kill me.” His psychomotor agitation was severe to the extent that it made it impossible to safely perform the endoscopy examination. The attending physician diagnosed him with delirium caused by the sudden change in environment, and haloperidol 1A (5 mg, intravenous) was administered to treat his severe psychomotor agitation. He gradually became stable and calm, but the patient and his family desired to discharge him from the hospital. Thereafter, the examination was stopped, and he was discharged on the following day.

The patient visited the first author’s outpatient clinic at Y months. The first author is a psychiatrist trained in the diagnosis and treatment of dementia. The Japanese version of the Mini-Mental State Examination (MMSE-J) (2,3) score was 19/30, and the memory, calculation, and executive function items of the patient indicated impairment. In addition, during this examination, it was discovered for the first time that he had been experiencing visual hallucinations such as peculiar creatures, insects, and strange individuals for approximately 2 years, and at home, he complained of strangers often entering his room. However, he refused to be examined by a psychiatrist because of his anxiety and fear of psychiatric diseases. Rapid Eye Movement (REM)-phase sleep behavior disorder was also admitted based on the information provided by his family. Moreover, he experienced Parkinsonism, such as tremors at rest, slowness of movement, and muscle rigidity. This led to a diagnosis of DLB (4). Clinical symptoms indicating Alzheimer’s disease, vascular dementia, and front-temporal lobe dementia were not admitted. Moreover, his brain computed tomography showed no hydrocephalus or hemorrhage. Based on his overall clinical symptoms, the delirium experienced in the endoscopy room a few months prior was hypothesized to have derived from DLB, instead of a common delirium often observed in the cancer perioperative period. The mental status was stabilized by the initiation of donepezil (3 mg/d, oral), lemborexant (2.5 mg/d, oral), and yokukansan (7.5 g/d, oral). Donepezil was especially effective against visual hallucinations and delusional thoughts, and the patient reportedly complained less of these symptoms after the initiation of treatment. No antipsychotics were necessary to stabilize his mental condition.

Initially, the patient was scheduled for endoscopic treatment, but it was later discovered that the esophageal cancer had progressed, and the operation was rescheduled. He was then admitted to be the hospital again at Y+4 months for the operation. Postoperatively, while oral medication was difficult, donepezil was temporarily changed from oral to a patch formulation (ALLYDONE patch, 27.5 mg/d) with the consent of the patient and family. Mild postoperative delirium occurred, but trazodone (25 mg/d, oral) was administered only when necessary, and regular prescriptions were adjusted simultaneously. Considering the drug sensitivity of DLB, antipsychotics were not added to regular oral medication for psychiatric symptoms of postoperative delirium and were managed with great caution. As a result, mental stability was maintained without oversedation or exacerbation of Parkinsonism by regular oral administration of 5 mg of donepezil, 7.5 g of yokukansan, and 10 mg of lemborexant per day. Postoperative MMSE-J was 20/30, which showed no decline in cognitive function. The absence of serious delirium was presumed to have contributed to the prevention of cognitive decline. The patient was then discharged from the hospital with no side effects. He has since visited the nearby psychiatric clinic, and his mental stability is maintained with no worsening of hallucinations or delusions (Figure 1). After our experience with this case, we continue to regularly educate our medical staff about the presence and risks of delirium associated with DLB. We also inform them of the risks of antipsychotics for delirium associated with DLB from the perspective of drug hypersensitivity.

Figure 1 Clinical course of the patient.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Delirium is often experienced in patients undergoing cancer treatment, both perioperatively and during anticancer therapy. Antipsychotics are empirically used to treat delirium (1), and severe psychiatric symptoms such as psychomotor agitation and delusion often require relatively high doses of these medications.

Notably, mixed cases of delirium associated with DLB (5) possess a high risk of drug hypersensitivity against antipsychotics and possible exacerbation of Parkinsonian symptoms. However, based on a literature review, no reported cases of DLB in cancer treatment currently exist, and no prior reports regarding delirium derived from DLB in the cancer perioperative period are known either. Although the risk of delirium in cancer surgery is well known, the existence of hidden DLB with delirium has not been fully recognized among healthcare professionals. Therefore, an update of knowledge regarding this topic is required.

Several problems have been identified regarding the psychiatric manifestations of DLB. The clinical findings of delirium and DLB are noted to have much in common and are often difficult to differentiate (6). A misdiagnosis of the appropriate diagnosis is also noted as potentially compromising patient care and safety (6). For the future diagnosis of DLB, the importance of establishing a direct biomarker to detect pathological α-synuclein has been suggested (7). However, currently, there is very little evidence-based management for delirium in patients diagnosed with DLB (6). While there is a problem of drug hypersensitivity, psychiatric symptoms attributed to DLB are severe, and as much as 45.9% of primary caregivers are reported to have experienced violent behavior from DLB patients (8).

McKeith et al. recently showed that multiple types of DLB exist, with delirium as the initial symptom in addition to mild cognitive impairment or psychotic symptoms (9). Some types of DLB first present as delirium, and a significant correlation between delirium and DLB has been reported (1). In addition, delirium and dementia share a common genetic basis (10,11), indicating that precursor delirium and hidden DLB are hypothesized to have the same origin.

Regarding the rate of delirium, it is present in 19.4% of all patients with dementia, but in 31.8% of patients with DLB, which is higher compared to that of other types of dementia (12). Notably, the Neuro-Psychiatric Inventory score for the behavioral and psychological symptoms of dementia is exacerbated in the presence of delirium (12). This means that the management of delirium is even more crucial in DLB than in other dementias. Especially, patients with DLB are at risk for drug hypersensitivity, and the use of antipsychotics without careful consideration can lead to the exacerbation of Parkinsonism. In addition, delirium in patients with DLB has been reported to be exacerbated by risperidone (13); therefore, careful attention should be given when selecting psychotropics. However, in cancer treatment, this has not been fully considered, and as the present case showed, the risk of being diagnosed with sole delirium and overusing large doses of antipsychotic drugs exists.

To distinguish the delirium owing to hidden DLB from cancer perioperative delirium, patients and their families should be asked beforehand whether or not psychiatric symptoms such as visual hallucinations, delusions, and fluctuation of symptoms, all of which are common with delirium, are present at home. If these symptoms are derived solely from perioperative delirium, it can be deduced that the constellation of these clinical symptoms has not been previously admitted before hospitalization.

For specific delirium, the first author formerly reported benzodiazepine withdrawal delirium owing to the accidental discontinuation of benzodiazepines in the cancer perioperative period (14). In the treatment of benzodiazepine withdrawal, the proper approach is restarting benzodiazepine, which differs entirely from the approach of managing ordinary perioperative delirium (14,15). Similar to benzodiazepine withdrawal delirium, delirium derived from DLB should be assessed and treated differently from ordinary delirium, considering drug hypersensitivity.

In delirium derived from DLB, the use of antipsychotics is not suitable in all cases and may cause severe side effects, leading to a poor prognosis. In cases of delirium due to DLB, basically, treating the DLB itself using donepezil and medications such as lemborexant and yokukansan that do not aggravate Parkinsonism, instead of high-dose antipsychotics may be effective. Lemborexant is effective in the treatment of sleep disorders, an exacerbating factor for delirium (16-18). It has also been shown to be effective in the treatment of sleep disorders and delirium in cancer patients (19). Yokukansan has been reported to reduce perioperative anxiety in cancer patients (20), which is an aggravating factor for delirium, and to be also effective for agitated delirium in cancer patients (21).

Conclusions

These findings highlight that the re-education regarding specific, hidden, and high-impact types of delirium is required for medical staff in the field of oncology. Further case reports and knowledge accumulation on specific types of delirium are required for safe and effective cancer treatment.

Acknowledgments

The authors thank the patient and his family for their participation in this study.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://apm.amegroups.com/article/view/10.21037/apm-25-48/rc

Peer Review File: Available at https://apm.amegroups.com/article/view/10.21037/apm-25-48/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://apm.amegroups.com/article/view/10.21037/apm-25-48/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Neufeld KJ, Yue J, Robinson TN, et al. Antipsychotic Medication for Prevention and Treatment of Delirium in Hospitalized Adults: A Systematic Review and Meta-Analysis. J Am Geriatr Soc 2016;64:705-14. [Crossref] [PubMed]
2. Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-98. [Crossref] [PubMed]
3. Sugishita M, Koshizuka Y, Sudou S, et al. The validity and reliability of the Japanese version of the Mini-Mental State Examination (MMSE-J) with the original procedure of the attention and calculation task (2001). Jpn J Cogn Neurosci 2018;20:91-110.
4. McKeith IG, Boeve BF, Dickson DW, et al. Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology 2017;89:88-100. [Crossref] [PubMed]
5. Fujishiro H, Kawakami I, Oshima K, et al. Delirium prior to dementia as a clinical phenotype of Lewy body disease: an autopsied case report. Int Psychogeriatr 2017;29:687-9. [Crossref] [PubMed]
6. Richardson S, Lawson RA, Price A, et al. Challenges in diagnosis and management of delirium in Lewy body disease. Acta Psychiatr Scand 2023;147:475-80. [Crossref] [PubMed]
7. Kobayashi R, Iwata-Endo K, Fujishiro H. Clinical presentations and diagnostic application of proposed biomarkers in psychiatric-onset prodromal dementia with Lewy bodies. Psychogeriatrics 2024;24:1004-22. [Crossref] [PubMed]
8. Morain E, Fayel A, De Linares P, et al. Domestic violence in Lewy body dementia: A national study. J Alzheimers Dis 2025;105:44-8. [Crossref] [PubMed]
9. McKeith IG, Ferman TJ, Thomas AJ, et al. Research criteria for the diagnosis of prodromal dementia with Lewy bodies. Neurology 2020;94:743-55. [Crossref] [PubMed]
10. Petersen Hella MN, Bergland AK, Soennesyn H, et al. What we know about the possible link between delirium and dementia with Lewy bodies, and why we need to learn more. Acta Psychiatr Scand 2023;147:401-2. [Crossref] [PubMed]
11. Cai Y, Wang J, Wang X, et al. Causal relationship between dementia and delirium: Insights from a bidirectional two-sample Mendelian randomization analysis. J Affect Disord 2024;349:69-76. [Crossref] [PubMed]
12. Hasegawa N, Hashimoto M, Yuuki S, et al. Prevalence of delirium among outpatients with dementia. Int Psychogeriatr 2013;25:1877-83. [Crossref] [PubMed]
13. Morikawa M, Kishimoto T. Probable dementia with Lewy bodies and risperidone-induced delirium. Can J Psychiatry 2002;47:976. [Crossref] [PubMed]
14. Yamaguchi J, Sadahiro R, Wada S, et al. A case report of benzodiazepine withdrawal delirium due to accidental discontinuation of benzodiazepines in cancer perioperative period. PCN Rep 2024;3:e70026. [Crossref] [PubMed]
15. Omichi C, Ayani N, Oya N, et al. Association between discontinuation of benzodiazepine receptor agonists and post-operative delirium among inpatients with liaison intervention: A retrospective cohort study. Compr Psychiatry 2021;104:152216. [Crossref] [PubMed]
16. De Crescenzo F, D'Alò GL, Ostinelli EG, et al. Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis. Lancet 2022;400:170-84. [Crossref] [PubMed]
17. McElroy H, O'Leary B, Adena M, et al. Comparative efficacy of lemborexant and other insomnia treatments: a network meta-analysis. J Manag Care Spec Pharm 2021;27:1296-308. [Crossref] [PubMed]
18. Takaesu Y, Sakurai H, Aoki Y, et al. Treatment strategy for insomnia disorder: Japanese expert consensus. Front Psychiatry 2023;14:1168100. [Crossref] [PubMed]
19. Terada T, Hirayama T, Sadahiro R, et al. Pilot Study of Lemborexant for Insomnia in Cancer Patients with Delirium. J Palliat Med 2022;25:797-801. [Crossref] [PubMed]
20. Tanaka M, Tanaka T, Takamatsu M, et al. Effects of the Kampo medicine Yokukansan for perioperative anxiety and postoperative pain in women undergoing breast surgery: A randomized, controlled trial. PLoS One 2021;16:e0260524. [Crossref] [PubMed]
21. Sadahiro R, Wada S, Matsuoka YJ, et al. Prevention of delirium with agitation by yokukansan in older adults after cancer surgery. Jpn J Clin Oncol 2022;52:1276-81. [Crossref] [PubMed]