Paranoia and Slowed Cognition Ijeoma Ijeaku, MD, MPH, and Melissa Pereau, MD

Cases That Test Your Skills

Paranoia and slowed cognition Ijeoma Ijeaku, MD, MPH, and Melissa Pereau, MD

Mr. K, age 45, is paranoid, combative, and agitated. Two weeks How would you ago he sustained chemical abrasions at home. What could be handle this case? Visit CurrentPsychiatry.com causing his altered mental status? to input your answers and see how your colleagues responded

CASE Behavioral changes aggressive and combative. He throws chairs at Mr. K, age 45, is brought to the emergency de- his peers and staff on the unit and is placed in partment (ED) by his wife for severe paranoia, physical restraints. He requires several doses combative behavior, confusion, and slowed of IM haloperidol, 5 mg, lorazepam, 2 mg, and cognition. Mr. K tells the ED staff that a chemi- diphenhydramine, 50 mg, for severe agitation. cal abrasion he sustained a few weeks earlier Mr. K is guarded, perseverative, and selectively has spread to his penis, and insists that his mute. He avoids eye contact and has poor penis is retracting into his body. He has tied grooming. He has slow thought processing and a string around his penis to keep it from dis- displays concrete thought process. Prednisone appearing into his body. According to Mr. K’s is discontinued and olanzapine, titrated to 30 wife, he went to an urgent care clinic 2 weeks mg/d, and mirtazapine, titrated to 30 mg/d, are ago after he sustained chemical abrasions started for psychosis and depression. from exposure to cleaning solution at home. Mr. K’s mood and behavior eventually re- The provider at the urgent care clinic started turn to baseline but slowed cognition persists. Mr. K on an unknown dose of oral prednisone. He is discharged from our facility. Mr. K’s wife reports that her husband had a dysphoric episode approximately 6 months What is the most likely diagnosis for Mr. K? ago when his business was struggling but his a) major depressive disorder with psychotic mood improved without psychiatric care. Mr. features K’s medical history includes episodic sarcoid- b) delusional disorder osis of the eyes, skin, and lungs. In the past c) substance-induced psychotic disorder these symptoms remitted after he received d) substance-induced mood disorder oral prednisone. e) substance-induced delirium ED clinicians consider neurosarcoidosis and substance-induced delirium in the differential The authors’ observations diagnosis (Table, page 44).1 A CT scan of the Cortisone was first used to treat rheuma- head fails to show lesions suggestive of neuro- toid arthritis in 1948 and corticosteroids sarcoidosis. Chest radiography does not reveal Dr. Ijeaku is a Child and Adolescent Psychiatry Fellow, University lesions suggestive of lung sarcoids and Mr. K of Southern California, Los Angeles, CA. She was a resident at has no skin lesions. Loma Linda University Behavioral Medical Center, Redlands, Mr. K is admitted to the psychiatric inpatient CA at the time of this case. Dr. Pereau is Attending Psychiatrist and Medical Director on the Adult Inpatient Unit, Loma Linda Current Psychiatry unit for acute stabilization, where he remains University Behavioral Medical Center, Redlands, CA. Vol. 11, No. 12 43 Cases That Test Your Skills

Table DSM-IV-TR criteria for substance-induced delirium A. Disturbance of consciousness (ie, reduced clarity of awareness of the environment) with reduced ability to focus, sustain, or shift attention B. A change in cognition (such as memory deficit, disorientation, language disturbance) or the development of a perceptual disturbance that is not better accounted for by a pre-existing, established, or evolving dementia C. The disturbance develops over a short period of time (usually hours to days) and tends to fluctuate during the course of the day D. There is evidence from the history, physical examination, or laboratory findings of either 1) or 2) 1) The symptoms in criteria A and B developed during substance intoxication 2) Medication use is etiologically related to the disturbance Clinical Point Source: Reference 1 Symptoms of steroid dementia include have been linked to multiple neuropsy- showed a predominance of verbal declara- impaired verbal chiatric complications that have been tive memory deficits out of proportion to memory and spatial broadly defined as steroid psychosis. This other cognitive symptoms. These symp- thinking but normal syndrome includes reversible behavioral toms and recent corticosteroid exposure manifestations such as hypomania, irrita- differentiated steroid dementia from other procedural memory bility, mood reactivity, anxiety, and insom- forms of dementia. nia in addition to more severe symptoms In a later article, Varney reviewed elec- such as depression, mania, and psycho- troencephalography (EEG) and CT findings sis.2 Although mild cognitive deficits have associated with steroid dementia, noting bi- been noted in patients taking corticoste- lateral EEG abnormalities and acute cortical roids, most published cases have focused atrophy on CT.4 Steroid dementia largely on steroid-induced psychosis. was reversible, resolving 3 to 11 months In 1984, Varney et al3 noted a phenome- after corticosteroid discontinuation. non they called “steroid dementia” in 6 pa- Additionally, Varney noted that patients tients treated with corticosteroids. On first who had psychosis and dementia had more evaluation, these patients presented with severe and longer-lasting dementia. symptoms similar to early Alzheimer’s dementia—impaired memory, attention, and concentration. Three patients initially were TREATMENT Progressive decline diagnosed first with Alzheimer’s demen- Mr. K is college educated, has been married tia until their symptoms spontaneously for 15 years, has 2 children, age 9 and 11, and improved when steroids were reduced or owns a successful basketball coaching busi- discontinued. Although their presentation ness. He has no history of substance abuse, resembled Alzheimer’s dementia, patients legal issues, or violence. He reports a good with steroid dementia had a specific cogni- childhood with normal developmental mile- Discuss this article at tive presentation associated with cortico- stones and no history of trauma. www.facebook.com/ steroid use. Symptoms included impaired In the 6 months after his initial psychiatric CurrentPsychiatry verbal memory and spatial thinking but admission, Mr. K sees various outpatient pro- normal procedural memory. These pa- viders, who change his psychotropics multiple tients showed intact immediate recall but times. He also receives 4 courses of prednisone impaired delayed recall with difficulty for ocular sarcoidosis. He is admitted twice to tracking conversations and word finding. other psychiatric facilities. After he has para- Current Psychiatry 44 December 2012 Overall, patients with steroid dementia noid interactions with colleagues and families Cases That Test Your Skills

of the youth he coaches, his business fails. mood improve dramatically once he reaches a After his third psychiatric inpatient hospi- therapeutic lithium level; however, his cogni- talization, Mr. K becomes severely paranoid, tion remains slowed and he is unable to care for believing his wife is having an affair. He be- his basic needs. comes physically abusive to his wife, who obtains a restraining order and leaves with The authors’ observations their children. Mr. K barely leaves his house Steroid dementia may be the result of ef- and stops grooming. A friend notes that Mr. fects in the medial temporal lobe, specifi- K’s home has become uninhabitable, and it cally dorsolateral prefrontal cortex, which goes into foreclosure. After Mr. K’s neighbors impairs working memory, and the para- report combative behavior and paranoia, po- hippocampal gyrus.6,7 The cognitive pre- lice bring him in on an involuntary hold for a sentation of steroid dementia Varney et al3 fourth psychiatric hospitalization (the second described has been replicated in healthy Clinical Point in our facility). volunteers who received corticosteroids.3 During this hospitalization—6 months Patients with Cushing’s syndrome also Steroid-induced after the initial ED presentation—the neurol- have been noted to have diminished hippo- cognitive ogy team conducts a repeat medical workup. campal volume and similar cognitive defi- impairment may be EEG shows generalized slowing. Head CT and cits. Cognitive impairment experienced by due to cell death in MRI show diffuse cortical atrophy that was patients treated with corticosteroids may the hippocampus not seen in previous imaging. Mr. K has ocu- be caused by neuronal death in the hip- and dorsolateral lar lesions characteristic of ocular sarcoidosis. pocampus and dorsolateral prefrontal His mental status examination is similar to his cortex. The etiology of cell death is multi- prefrontal cortex first presentation except that the psychosis factorial and includes glutamate-mediated and thought disorganization are considerably excitotoxicity, activation of proinflamma- worse. His cognitive functioning also shows tory pathways, inhibited utilization of significant decline. Cognitive screening re- glucose in the hippocampus, telomere veals intact remote memory with impaired shortening, and diminished cell repair by recent memory. His thinking is concrete and brain-derived neurotrophic factor. The net his verbal memory is markedly impaired. His result is significant, widespread damage Mini-Mental State Examination score is 27/30, that in some cases is irreversible.8 indicating functional capacity that is better Because of the severity of Mr. K’s psy- than his clinical presentation. Because of dif- chosis and personality change from base- ficulty with concentration and verbal process- line, his cognitive symptoms were largely ing, Mr. K is unable to complete the Minnesota overlooked during his first psychiatric Multiphasic Personality Inventory despite sub- hospitalization. The affective flattening, stantial assistance. On most days he cannot delayed verbal response, and markedly recall recent conversations with his wife, staff, concrete thought process were considered or physicians. He is taking no medications at within the spectrum of resolving psycho- this time. sis. After further hospitalizations and ab- Mr. K is restarted on olanzapine, titrated to normal results on cognitive testing, Mr. 30 mg/d, to control his psychosis; this medi- K’s cognitive impairment was fully noted. cation was effective during his last stay in our His symptoms match those of previously facility. Oral prednisone is discontinued and documented cases of steroid dementia, in- methotrexate, 10 mg/week, is initiated for cluding verbal deficits out of proportion to ocular sarcoidosis. Based on recommendations other impairment, acute cerebral atrophy from a case series report,5 we start Mr. K on lith- on CT after corticosteroid treatment, and ium, titrated to 600 mg twice a day, for steroid- gradual improvement of symptoms when Current Psychiatry induced mood symptoms, Mr. K’s psychosis and corticosteroids were discontinued. Vol. 11, No. 12 45 continued Cases That Test Your Skills

OUTCOME Long-term deficits Related Resources After a 33-day stay in our adult inpatient psy- • Sacks O, Shulman M. Steroid dementia: an overlooked diagnosis? Neurology. 2005;64(4):707-709. chiatric facility, the county places Mr. K in a • Cipriani G, Picchi L, Vedovello M, et al. Reversible dementia from permanent conservatorship for severe grave corticosteroid therapy. Clinical Geriatrics. 2012;20(7):38-41. disability. He is discharged to a long-term Drug Brand Names psychiatric care locked facility for ongoing Diphenhydramine • Benadryl Methotrexate • Rheumatrex, management. Mr. K spends 20 months in the Divalproex • Depakote Trexall Haloperidol • Haldol Mirtazapine • Remeron long-term care facility while his family remains Lamotrigine • Lamictal Olanzapine • Zyprexa hopeful for his recovery and return home. He is Lithium • Eskalith, Lithobid Prednisone • Deltasone, Lorazepam • Ativan Meticorten, others admitted to our facility for acute stabilization of Memantine • Namenda psychotic symptoms after he is released from Disclosure the locked facility. Although no imaging studies Clinical Point The authors report no financial relationship with any company are conducted, he remains significantly forget- whose products are mentioned in this article or with manufactur- ful. Additionally, his paranoia persists. ers of competing products. Lamotrigine and Mr. K is poorly compliant with his psycho- memantine may tropics, which include divalproex, 1,000 mg/d, be cognitively and olanzapine, 30 mg/d. Although he is dis- protective for How would you manage Mr. K? charged home with his family, his functional patients taking a) continue olanzapine and lithium and capacity is less than expected and he requires monitor him closely for changes in continuous support. Insisting that Mr. K abstain prednisone mood or cognition from steroids after the first psychiatric hospital- b) continue olanzapine and lithium and add ization might have prevented this seemingly a cognitive enhancer, such as memantine irreversible dementia. c) recommend transfer to a long-term care facility References 1. Diagnostic and statistical manual of mental disorders, 4th ed, text rev. Arlington, VA: American Psychiatric Association; 2000. 2. Warrington TP, Bostwick JM. Psychiatric adverse effects of Management recommendations corticosteroids. Mayo Clin Proc. 2006;81(10):1361-1367. 3. Varney NR, Alexander B, MacIndoe JH. Reversible steroid Educate patients taking steroids about dementia in patients without steroid psychosis. Am J possible side effects of mood changes, Psychiatry. 1984;141(3):369-372. 4. Varney NR. A case of reversible steroid dementia. Arch Clin psychosis, and cognitive deficits. Close Neuropsychol. 1997;12(2):167-171. monitoring of patients on corticosteroids 5. Sirois F. Steroid psychosis: a review. Gen Hosp Psychiatry. 2003;25(1):27-33. is paramount. If psychiatric or cognitive 6. Wolkowitz OM, Burke H, Epel ES, et al. Glucocorticoids: mood, memory, and mechanisms. Ann N Y Acad Sci. 2009; symptoms develop, gradually discon- 1179:19-40. tinue the corticosteroid and seek other 7. Lupien SJ, McEwen BS. The acute effects of corticosteroids on cognition: integration of animal and human model treatments. studies. Brain Res Brain Res Rev. 1997;24(1):1-27. Randomized, placebo-controlled trials 8. Sapolsky RM. The physiological relevance of glucocorticoid endangerment of the hippocampus. Ann NY Acad Sci. 1994; of lamotrigine and memantine have shown 746:294-304. these medications are cognitively protective 9. Brown ES. Effects of glucocorticoids on mood, memory and the hippocampus. Treatment and preventative therapy. Ann for patients taking prednisone.9 N Y Acad Sci. 2009;1179:41-55. Bottom Line Quick identification of steroid-induced mood or cognitive changes is vital for symptom recovery. The primary interventions are to reduce or discontinue corticosteroids, provide supportive care as needed, and monitor for further Current Psychiatry 46 December 2012 cognitive changes.