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misinterpreted as a new medical condition, leading to another drug being prescribed to treat the adverse effect.3,4 In the current case, the man and his physician misinterpreted the adverse gastrointestinal effects of the cholinesterase inhibitor as a new medical condition, leading to self-medicating with an additional OTC drug at toxic doses. Cholinesterase inhibitors are associated with adverse gastrointestinal events, most commonly abdominal pain, nausea, anorexia, diarrhea, and weight loss.5 Given that many older adults with dementia are malnourished, physicians prescribing cholinesterase inhibitors need to inform them about these potential adverse events and consider the possible contributing role of cholinesterase inhibitors in new-onset gastrointestinal symptoms or weight loss. Furthermore, the possibility of an adverse drug event presenting as a prescribing cascade should always be carefully considered when evaluating an older adult, and any new symptom should be considered to be drug related until proven otherwise.3 The neurotoxicity of bismuth subsalicylate is often underappreciated, despite its long history of use for a variety of gastrointestinal disorders. Two distinct toxicities must be considered: salicylate toxicity and bismuth toxicity. Salicylate toxicity is detailed in the case presentation above. Bismuth neurotoxicity can provoke delirium, psychosis, ataxia, myoclonus, and seizures and is reversible over several weeks, when bismuth intake is stopped.6,7 It is hoped that this case presentation will increase recognition of the adverse effects of cholinesterase inhibitors and salicylate and bismuth neurotoxicity with OTC medications. In addition, this case highlights the potential for prescribing cascades involving OTC preparations that are sometimes missed when taking a medication history. Jarred Rosenberg, MD University of Toronto, Toronto, Ontario, Canada Paula A. Rochon, MD, MPH Women’s College Hospital, University of Toronto, Toronto, Ontario, Canada Sudeep S. Gill, MD, MSc Queen’s University, Kingston, Ontario, Canada
ACKNOWLEDGMENTS This work was supported by Team Grant OTG-88591 from the Canadian Institutes of Health Research (CIHR) Institute of Nutrition, Metabolism, and Diabetes. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: All authors contributed equally. Ethics committee approval and patient consent were obtained. Sponsor’s Role: There was no sponsor involved in the management of the patient or preparation of the paper.
LETTERS TO THE EDITOR
581
REFERENCES 1. Chyka PA, Erdman AR, Christainson G et al. Salicylate poisoning: An evidence-based consensus guideline for out-of-hospital management. Clin Toxicol 2007;45:95–131. 2. Bradberry SM, Beer ST, Vale JA. UKPID Monograph: Bismuth. Birmingham, UK: UK National Poisons Information Service, 1996. 3. Rochon PA, Gurwitz JH. Optimizing drug treatment for elderly people: The prescribing cascade. BMJ 1997;315:1096–1099. 4. Gill SS, Mamdani M, Naglie G et al. A prescribing cascade involving cholinesterase inhibitors and anticholinergic drugs. Arch Intern Med 2005;165:808–813. 5. Birks J. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev 2006;1:CD005593. 6. Gordon MF, Abrams RI, Rubin DB et al. Bismuth subsalicylate toxicity as a case of prolonged encephalopathy with myoclonus. Mov Disord 1995;10:220–222. 7. Molina JA, Jimenez-Jimenez FJ, Calandre L. Bismuth encephalopathy. Neurology 1994;44:582.
NURTURING SYNDROME IN AN ELDERLY WOMAN WITHOUT DEMENTIA To the Editor: Delusions in elderly people result in caregiver burden and institutionalization,1 so careful investigation of delusions is important to increase understanding of underlying neuropsychological and physical abnormalities.2 Delusions of misidentification can give rise to nurturing syndrome (NS) after the death of a loved one.1 NS is rare and has previously only been described in dementia.2–4 Typically, individuals behave appropriately when the death occurs. Weeks later, a delusion emerges that the relative is alive. Nurturing behaviors are exhibited, such as preparing food and even attempting to feed photographs of the deceased.3 NS is associated with right frontal lobe lesions4 and may reflect a deficit in identifying the source of a memory.3 There are no descriptions of NS in which the delusional beliefs resolve.
CASE REPORT Miss S was an 88-year-old single woman who had been diagnosed with mild cognitive impairment at 81. She had never married and had no children. Her siblings had died, including her sister, who also had never married. Miss S was extremely close to her sister, who was diagnosed with a terminal illness and stayed with Miss S until her death. Miss S found this highly stressful, because she could not provide the care her sister required. It became apparent that Miss S did not remember that her sister had died. She left meals for her and cleared room “in case she comes back.” She was treated with antidepressant and antipsychotic medication for possible psychotic depression. She was found wandering, looking for her sister; talked of visiting her; and called the police repeatedly asking them to find her. Feeling distraught, she bought a bottle of vodka, intending to drink herself to death. She was admitted to the hospital, and her insistence on leaving to find her sister resulted in detention under the Mental Health Act.
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Comprehensive hematological and biochemical screening and neurological examination were normal. Cognitive testing revealed deficits on the Mini-Mental State Examination (MMSE)5 in orientation, attention, recall, and construction, with a score of 25 out of 30. Computed tomography (CT) showed generalized cerebral atrophy, with no focal abnormality. Miss S’s presentation was not in keeping with psychotic depression. Her medications were discontinued. There was sustained improvement in her level of functioning with input from the nursing, medical, and occupational therapy teams. After discharge, her delusions regarding her sister resolved, and she coped well with greater home care. One year later, there was no progression of her cognitive impairment. Neuropsychological tests and an 18Ffluorodeoxyglucose positron emission tomography/CT (18FDG PET/CT) brain scan were performed. She scored 30 on the MMSE5 but showed impaired executive functioning, with poor performance on the Trail Making6 and Weigl’s Color-Form Sorting tests.7 This profile was not consistent with Alzheimer’s disease. 18FDG PET/CT brain scan showed moderate atrophy of the right medial temporal lobe (MTL), but glucose metabolism was normal, with no evidence of the Alzheimer pattern of posterior temporoparietal metabolic defects or of any frontal lobe abnormality.
DISCUSSION Miss S’s symptoms were not consistent with a psychotic illness and resolved without medication. Her presentation, neuropsychological tests, and 18FDG PET/CT findings did not suggest dementia. This is the only case we know of in which NS has occurred without dementia and resolved. Grief reactions may include hallucinations and searching for the deceased but do not typically include delusions and nurturing behaviors.8 Miss S’s presentation is perhaps best characterized as an abnormal grief reaction. Studies of NS have shown lesions in the right prefrontal cortex, an area implicated in retrieval of episodic memories and reality monitoring.3,4 Individuals with NS may encode memories of their relatives’ deaths but be unable to retrieve these memories. They also cannot identify the source of their memories, resulting in the delusion that their relative is alive.3 Miss S has focal atrophy of the right MTL, an area essential to the consolidation of autobiographical memories,9 and deficits in executive function, suggestive of frontal lobe impairment. These changes may reflect nonspecific age-related degeneration. Miss S’s presentation may have resulted from impaired consolidation and reality monitoring. She could not distinguish between poorly consolidated memories of her sister’s death and internally generated ideas that she was alive. Further work is needed to clarify the precise mechanisms underlying her presentation.
CONCLUSIONS The case is consistent with work on NS and delusions of misidentification. Evidence suggests that delusions of
MARCH 2014–VOL. 62, NO. 3
JAGS
misidentification are related to right frontotemporal dysfunction.1 Previous studies have been restricted to dementia. This case suggests a common etiology of delusions of misidentification in individuals with and without dementia and shows how evidence from investigating delusions in dementia may generalize to adults without dementia.2
Nina Baruch, BSc, MBBS Catherine M. F. Somerville-Tyler, MSc Oxford Health National Health Service Foundation Trust, Oxford, UK Kevin M. Bradley, MA, BMBCh Oxford University Hospitals National Health Service Trust, Oxford, UK Philip Wilkinson, BMed Sci, BMBS Oxford Health National Health Service Foundation Trust, Oxford, UK University of Oxford, Oxford, UK
ACKNOWLEDGMENTS Written and oral consent was received from Miss S to submit this case report to be considered for publication. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Baruch: literature review, organized investigations, wrote manuscript. SomervilleTyler: neuropsychology testing and findings, reviewed manuscript. Bradley: 18FDG PET/CT scan and findings, reviewed manuscript. Wilkinson: identification of case, reviewed manuscript. Sponsor’s Role: None.
REFERENCES 1. Holt AE, Albert ML. Cognitive neuroscience of delusions in aging. Neuropsychiatr Dis Treat 2006;2:181–189. 2. Shanks MF, Venneri A. Thinking through delusions in Alzheimer’s disease. Br J Psychiatry 2004;184:193–194. 3. Venneri A, Shanks MF, Staff RT et al. Nurturing syndrome: A form of pathological bereavement with delusions in Alzheimer’s disease. Neuropsychologia 2000;38:213–224. 4. Staff RT, Venneri A, Gemmell HG et al. HMPAO SPECT imaging of Alzheimer’s disease patients with similar content-specific autobiographic delusion: Comparison using statistical parametric mapping. J Nucl Med 2000;41:1451–1455. 5. 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;12:189–198. 6. Reitan RM. The relation of the Trail Making Test to organic brain damage. J Consult Psychol 1955;19:393–394. 7. Byrne LM, Bucks RS, Cuerden JM. Validation of a new scoring system for the Weigl Color Form Sorting Test in a memory disorders clinic sample. J Clin Exp Neuropsychol 1998;20:286–292. 8. Gelder M, Harrison P, Cowen P. Shorter Oxford Textbook of Psychiatry, 5th Ed. Oxford: Oxford University Press, 2006. 9. Squire LR, Stark CE, Clark RE. The medial temporal lobe. Annu Rev Neurosci 2004;27:279–306.
MARCH 2014–VOL. 62, NO. 3
misinterpreted as a new medical condition, leading to another drug being prescribed to treat the adverse effect.3,4 In the current case, the man and his physician misinterpreted the adverse gastrointestinal effects of the cholinesterase inhibitor as a new medical condition, leading to self-medicating with an additional OTC drug at toxic doses. Cholinesterase inhibitors are associated with adverse gastrointestinal events, most commonly abdominal pain, nausea, anorexia, diarrhea, and weight loss.5 Given that many older adults with dementia are malnourished, physicians prescribing cholinesterase inhibitors need to inform them about these potential adverse events and consider the possible contributing role of cholinesterase inhibitors in new-onset gastrointestinal symptoms or weight loss. Furthermore, the possibility of an adverse drug event presenting as a prescribing cascade should always be carefully considered when evaluating an older adult, and any new symptom should be considered to be drug related until proven otherwise.3 The neurotoxicity of bismuth subsalicylate is often underappreciated, despite its long history of use for a variety of gastrointestinal disorders. Two distinct toxicities must be considered: salicylate toxicity and bismuth toxicity. Salicylate toxicity is detailed in the case presentation above. Bismuth neurotoxicity can provoke delirium, psychosis, ataxia, myoclonus, and seizures and is reversible over several weeks, when bismuth intake is stopped.6,7 It is hoped that this case presentation will increase recognition of the adverse effects of cholinesterase inhibitors and salicylate and bismuth neurotoxicity with OTC medications. In addition, this case highlights the potential for prescribing cascades involving OTC preparations that are sometimes missed when taking a medication history. Jarred Rosenberg, MD University of Toronto, Toronto, Ontario, Canada Paula A. Rochon, MD, MPH Women’s College Hospital, University of Toronto, Toronto, Ontario, Canada Sudeep S. Gill, MD, MSc Queen’s University, Kingston, Ontario, Canada
ACKNOWLEDGMENTS This work was supported by Team Grant OTG-88591 from the Canadian Institutes of Health Research (CIHR) Institute of Nutrition, Metabolism, and Diabetes. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: All authors contributed equally. Ethics committee approval and patient consent were obtained. Sponsor’s Role: There was no sponsor involved in the management of the patient or preparation of the paper.
LETTERS TO THE EDITOR
581
REFERENCES 1. Chyka PA, Erdman AR, Christainson G et al. Salicylate poisoning: An evidence-based consensus guideline for out-of-hospital management. Clin Toxicol 2007;45:95–131. 2. Bradberry SM, Beer ST, Vale JA. UKPID Monograph: Bismuth. Birmingham, UK: UK National Poisons Information Service, 1996. 3. Rochon PA, Gurwitz JH. Optimizing drug treatment for elderly people: The prescribing cascade. BMJ 1997;315:1096–1099. 4. Gill SS, Mamdani M, Naglie G et al. A prescribing cascade involving cholinesterase inhibitors and anticholinergic drugs. Arch Intern Med 2005;165:808–813. 5. Birks J. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev 2006;1:CD005593. 6. Gordon MF, Abrams RI, Rubin DB et al. Bismuth subsalicylate toxicity as a case of prolonged encephalopathy with myoclonus. Mov Disord 1995;10:220–222. 7. Molina JA, Jimenez-Jimenez FJ, Calandre L. Bismuth encephalopathy. Neurology 1994;44:582.
NURTURING SYNDROME IN AN ELDERLY WOMAN WITHOUT DEMENTIA To the Editor: Delusions in elderly people result in caregiver burden and institutionalization,1 so careful investigation of delusions is important to increase understanding of underlying neuropsychological and physical abnormalities.2 Delusions of misidentification can give rise to nurturing syndrome (NS) after the death of a loved one.1 NS is rare and has previously only been described in dementia.2–4 Typically, individuals behave appropriately when the death occurs. Weeks later, a delusion emerges that the relative is alive. Nurturing behaviors are exhibited, such as preparing food and even attempting to feed photographs of the deceased.3 NS is associated with right frontal lobe lesions4 and may reflect a deficit in identifying the source of a memory.3 There are no descriptions of NS in which the delusional beliefs resolve.
CASE REPORT Miss S was an 88-year-old single woman who had been diagnosed with mild cognitive impairment at 81. She had never married and had no children. Her siblings had died, including her sister, who also had never married. Miss S was extremely close to her sister, who was diagnosed with a terminal illness and stayed with Miss S until her death. Miss S found this highly stressful, because she could not provide the care her sister required. It became apparent that Miss S did not remember that her sister had died. She left meals for her and cleared room “in case she comes back.” She was treated with antidepressant and antipsychotic medication for possible psychotic depression. She was found wandering, looking for her sister; talked of visiting her; and called the police repeatedly asking them to find her. Feeling distraught, she bought a bottle of vodka, intending to drink herself to death. She was admitted to the hospital, and her insistence on leaving to find her sister resulted in detention under the Mental Health Act.
582
LETTERS TO THE EDITOR
Comprehensive hematological and biochemical screening and neurological examination were normal. Cognitive testing revealed deficits on the Mini-Mental State Examination (MMSE)5 in orientation, attention, recall, and construction, with a score of 25 out of 30. Computed tomography (CT) showed generalized cerebral atrophy, with no focal abnormality. Miss S’s presentation was not in keeping with psychotic depression. Her medications were discontinued. There was sustained improvement in her level of functioning with input from the nursing, medical, and occupational therapy teams. After discharge, her delusions regarding her sister resolved, and she coped well with greater home care. One year later, there was no progression of her cognitive impairment. Neuropsychological tests and an 18Ffluorodeoxyglucose positron emission tomography/CT (18FDG PET/CT) brain scan were performed. She scored 30 on the MMSE5 but showed impaired executive functioning, with poor performance on the Trail Making6 and Weigl’s Color-Form Sorting tests.7 This profile was not consistent with Alzheimer’s disease. 18FDG PET/CT brain scan showed moderate atrophy of the right medial temporal lobe (MTL), but glucose metabolism was normal, with no evidence of the Alzheimer pattern of posterior temporoparietal metabolic defects or of any frontal lobe abnormality.
DISCUSSION Miss S’s symptoms were not consistent with a psychotic illness and resolved without medication. Her presentation, neuropsychological tests, and 18FDG PET/CT findings did not suggest dementia. This is the only case we know of in which NS has occurred without dementia and resolved. Grief reactions may include hallucinations and searching for the deceased but do not typically include delusions and nurturing behaviors.8 Miss S’s presentation is perhaps best characterized as an abnormal grief reaction. Studies of NS have shown lesions in the right prefrontal cortex, an area implicated in retrieval of episodic memories and reality monitoring.3,4 Individuals with NS may encode memories of their relatives’ deaths but be unable to retrieve these memories. They also cannot identify the source of their memories, resulting in the delusion that their relative is alive.3 Miss S has focal atrophy of the right MTL, an area essential to the consolidation of autobiographical memories,9 and deficits in executive function, suggestive of frontal lobe impairment. These changes may reflect nonspecific age-related degeneration. Miss S’s presentation may have resulted from impaired consolidation and reality monitoring. She could not distinguish between poorly consolidated memories of her sister’s death and internally generated ideas that she was alive. Further work is needed to clarify the precise mechanisms underlying her presentation.
CONCLUSIONS The case is consistent with work on NS and delusions of misidentification. Evidence suggests that delusions of
MARCH 2014–VOL. 62, NO. 3
JAGS
misidentification are related to right frontotemporal dysfunction.1 Previous studies have been restricted to dementia. This case suggests a common etiology of delusions of misidentification in individuals with and without dementia and shows how evidence from investigating delusions in dementia may generalize to adults without dementia.2
Nina Baruch, BSc, MBBS Catherine M. F. Somerville-Tyler, MSc Oxford Health National Health Service Foundation Trust, Oxford, UK Kevin M. Bradley, MA, BMBCh Oxford University Hospitals National Health Service Trust, Oxford, UK Philip Wilkinson, BMed Sci, BMBS Oxford Health National Health Service Foundation Trust, Oxford, UK University of Oxford, Oxford, UK
ACKNOWLEDGMENTS Written and oral consent was received from Miss S to submit this case report to be considered for publication. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Baruch: literature review, organized investigations, wrote manuscript. SomervilleTyler: neuropsychology testing and findings, reviewed manuscript. Bradley: 18FDG PET/CT scan and findings, reviewed manuscript. Wilkinson: identification of case, reviewed manuscript. Sponsor’s Role: None.
REFERENCES 1. Holt AE, Albert ML. Cognitive neuroscience of delusions in aging. Neuropsychiatr Dis Treat 2006;2:181–189. 2. Shanks MF, Venneri A. Thinking through delusions in Alzheimer’s disease. Br J Psychiatry 2004;184:193–194. 3. Venneri A, Shanks MF, Staff RT et al. Nurturing syndrome: A form of pathological bereavement with delusions in Alzheimer’s disease. Neuropsychologia 2000;38:213–224. 4. Staff RT, Venneri A, Gemmell HG et al. HMPAO SPECT imaging of Alzheimer’s disease patients with similar content-specific autobiographic delusion: Comparison using statistical parametric mapping. J Nucl Med 2000;41:1451–1455. 5. 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;12:189–198. 6. Reitan RM. The relation of the Trail Making Test to organic brain damage. J Consult Psychol 1955;19:393–394. 7. Byrne LM, Bucks RS, Cuerden JM. Validation of a new scoring system for the Weigl Color Form Sorting Test in a memory disorders clinic sample. J Clin Exp Neuropsychol 1998;20:286–292. 8. Gelder M, Harrison P, Cowen P. Shorter Oxford Textbook of Psychiatry, 5th Ed. Oxford: Oxford University Press, 2006. 9. Squire LR, Stark CE, Clark RE. The medial temporal lobe. Annu Rev Neurosci 2004;27:279–306.
