The patient was a 57-year-old man with no psychiatric history, no major medical problems, and a recent diagnosis of major depressive disorder (MDD). At initial psychiatric evaluation, the patient had severe anxiety, intrusive thoughts, odd behavior, poor concentration, sleep disturbance, and impairments in activities of daily living, family relationships, and leisure activities. He was not engaged in alcohol or illicit drug use and did not have a family history of dementia.
Per the family report, the patient's symptoms began in May 2015 when he became obsessed with a minor routine financial matter involving a family member. He vaguely described his thoughts to be intrusive and unusual. Since then, he experienced difficulty in concentration, as well as insomnia and anhedonia. Zolpidem was administered by the first primary care provider (PCP). Alprazolam and clonazepam were also prescribed for muscle tightness and headache. Subsequent PCPs attempted to reduce his medications, but he presented with recurrent tinnitus, headache, and unusual bodily sensations.
In November 2017, the patient stated that he was at the gym and felt that he was having a heart attack; he was transferred to the emergency department (ED) owing to auditory hallucinations. He initially thought that someone was talking to him, but shortly realized that he could hear his own thoughts, which could not be controlled. To reduce his anxiety, hallucinations, and intrusive thoughts, the patient began compulsively counting up to the number 14, believing that this number was the “lucky one.” A few days after his discharge from the hospital, he typed a message (“I love you”) at the computer screen to his wife while gathering four knives in a box. He also, out of the context, showed her a video of a gun previously purchased by the family for protection. Thus, due to safety concerns, he was hospitalized. He was diagnosed with MDD without psychotic symptoms and was prescribed zolpidem, clonazepam, and quetiapine on discharge.
According to his family, the patient has always been social; however, he now preferred to stay at home and watch television. He tried to lead a normal life but faced difficulty in coping with changing patterns and compulsive behavior. The family reported that he started misusing his medications and making impulsive decisions; however, no negative feedback was received from his workplace.
Treatment and Management
Upon initial evaluation at our clinic in 2018, the patient described the timeline of his symptoms in detail, but got irritated when interrupted. He was awake, alert, and did not seem to have any depressive or psychotic symptoms. Our initial strategy was to obtain and review his past medical records and also perform brain magnetic resonance imaging (MRI).
Within days after the clinic appointment, he dialed 911 to be taken to the Health Facility ED and handed a message to be delivered to the new treating psychiatrist stating that he had spoken with God last night and did not need to go to the emergency department. He asked to be seen next and stated that he was a risk to himself and his family. He also stated that if he was not seen soon then there was a chance that he would harm himself or his family. He was then directly admitted to the psychiatric inpatient unit from the ED for safety and stabilization.
On admission, his doses of clonazepam and zolpidem were tapered. The patient showed significant deficits on the Montreal Cognitive Assessment test (score, 18 of 30), which prompted further investigation, including MRI, laboratory assessment for dementia (cerebrospinal fluid [CSF] analysis), encephalitis-associated antibody evaluation, and electroencephalography (EEG), given his subacute behavioral presentation. Brain MRI findings were normal. However, his inflammatory marker levels (C-reactive protein, erythrocyte sedimentation rate) were found to be elevated, and antinuclear antibody titer was positive at 1:80, with a nucleolar pattern. CSF examination showed elevated protein levels; 24-hour video-EEG findings were unremarkable. Tumor screening was negative. Because he showed disorganized behavior in the psychiatric inpatient unit, he was administered quetiapine for the management of psychosis; this was switched to olanzapine for sedating purposes (titrated to 20 mg at bedtime).
Given the progression of his symptoms, elevated inflammatory marker, and CSF protein levels, he was diagnosed with autoimmune encephalitis. Steroid pulse therapy was started, which resulted in rapid improvement of his symptoms.
On neuropsychological testing, primary impairments were observed in executive functions and memory, as well as aspects of processing speed, language, and visuospatial abilities; attention was variable. A relative weakness in his dominant hand's fine motor speed was noted, although his performance was average.
Psychiatric symptoms can be experienced in the early stages of limbic encephalitis. Moreover, some patients may present with progressive dementia and behavioral symptoms mimicking neurological/psychiatric diagnosis, such as cognitive disorders, sleep disorders, obsession, disinhibition, apathy, delusion, and hallucination.1–3
According to Macher et al.,4 CSF findings can be normal in such cases, but mild to moderately elevated cell counts can be seen in some patients, as observed in this case. Similarly, EEG findings may be helpful, although nonspecific abnormalities are occasionally seen in infectious and immune-mediated encephalitis. Literature reviews suggest that appropriate tentative diagnosis should also consider the findings obtained from CSF analyses in addition to the medical history, anamnesis status, EEG findings, and MRI findings.5 Based on these findings, the suspected syndrome should subsequently be confirmed using immunological evaluation for autoimmune encephalitis-associated auto-antibodies. Some patients, like in this case, do not show immune-mediated antibodies but still meet the criteria for probable autoimmune encephalitis.3,4
This case study prompted us to review the importance of performing encephalitis-associated antibody evaluation screening tests for patients with cognitive impairment or behavioral changes suggestive of dementia. We also aim to increase awareness among mental health providers about differential diagnoses in similar cases. This case study contributes essential information on psychiatric symptoms in patients with encephalitis. Early immunotherapy can result in improved symptoms and quality of life.1,5 Furthermore, we found that routine screening for encephalitis-associated antibody evaluation in classical primary dementia cases may not be warranted, but it may be required in cases with subacute-onset progressive dementia.6,7
- Pittock SJ, Palace J. Paraneoplastic and idiopathic autoimmune neurologic disorders: approach to diagnosis and treatment. Handb Clin Neurol. 2016;133(10):165–183. doi:10.1016/B978-0-444-63432-0.00010-4 [CrossRef] PMID:27112677
- Barry H, Byrne S, Barrett E, Murphy KC, Cotter DR. Anti-N-methyl-D-aspartate receptor encephalitis: review of clinical presentation, diagnosis and treatment. BJPsych Bull. 2015;39(1):19–23. doi:10.1192/pb.bp.113.045518 [CrossRef] PMID:26191419
- Herken J. Red flags: clinical signs for identifying autoimmune encephalitis in psychiatric patients. Front Psychiatry. 2017;8:25. doi:10.3389/fpsyt.2017.00025 [CrossRef]. PMID:28261116
- Macher S, Zimprich F, De Simoni D, Höftberger R, Rommer PS. Management of autoimmune encephalitis: an observational monocentric study of 38 patients. Front Immunol. 2018;9:2708. doi:10.3389/fimmu.2018.02708 [CrossRef] PMID:30524441
- Bost C, Pascual O, Honnorat J. Autoimmune encephalitis in psychiatric institutions: current perspectives. Neuropsychiatr Dis Treat. 2016;12:2775–2787. doi:10.2147/NDT.S82380 [CrossRef] PMID:27822050
- Ganesh A, Wesley SF. Practice current: when do you suspect autoimmune encephalitis and what is the role of antibody testing?Neurol Clin Pract. 2018;8(1):67–73. doi:10.1212/CPJ.0000000000000423 [CrossRef] PMID:29517071
- Çoban A, Ismail Küçükali C, Bilgiç B, et al. Evaluation of incidence and clinical features of antibody-associated autoimmune encephalitis mimicking dementia. Behav Neurol. 2014;2014:935379. doi:10.1155/2014/935379 [CrossRef] PMID:24825964