A Rare Cause of New Onset Psychosis in a Young Male

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1 A Rare Cause of New Onset Psychosis in a Young Male Geoffrey Dang-Vu MD Amanda Wilcox, DO; Jennifer Schmidt, MD Medical College of Wisconsin, Milwaukee, WI

2 ED Case Presentation 23 y/o graduate student with no past medical or psychological history Seen in ED by Psychiatry, discharged on Olanzapine Returned to ED 1 day later with family following suicide attempt

3 Case Continued CC: Agitation, Suicidal Ideation, Euphoria Confusion, bizarre behavior after diarrheal illness 10 days PTA Bizarre sensory hallucinations: Seeing elephants Hearing music he knows is not there Strange smells Pervasive electrical sensation through his body

4 Case Continued Fluctuating mental status Getting lost in familiar places Inability to control thoughts Inappropriate laughing/crying Labile mood Insomnia Depression Short-term memory loss

5 Physical Exam T 98.4F; BP 120/70; HR 80 s; RR 16; SpO2 98% Neurologic Exam: No Meningeal Signs CN: intact Motor: wnl, no pronator drift Sensation: intact to pin-prick + vibration Reflexes: 2/4 throughout

6 Mental Status Exam Awake and oriented x 3 Able to spell World forwards/backwards Could not complete serial 7 s Able to interpret proverb Disorganized thought content Waxing/waning for different interviewers

7 Initial Work-Up Urine Drug Screen: Negative TSH, CBC, CMP, B12: Normal CT Head: Negative Lumbar Puncture: >100 Lymphocytes, glucose + protein wnl

8 EEG Day 1 of admission: Findings: Moderate Diffuse Slowing No epileptiform activity Intermittent rhythmic delta activity in the temporal region Interpretation: mild diffuse cerebral dysfunction, physiologic dysfunction in the temporal regions

9 MRI Day 2 of Admission

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12 MRI Impression Abnormal long TR hyperintensity within the amygdala and right hippocampus, asymmetric when compared to the left. There is also diffuse abnormal leptomeningeal enhancement and nonsuppression of FLAIR throughout the supratentorial brain. Findings are most consistent with meningoencephalitis.

13 Differential Diagnosis: Primary psychiatric disturbance Etiologies of Limbic Encephalitis Viral meningoencephalitis (HSV) Autoimmune or Vasculitic Encephalitis (SLE) Hashimoto s Encephalitis Paraneoplastic encephalitis

14 Further Work-Up Negative: Lyme, West Nile Virus, EBV, HSV, VZV, Bartonella Henslae, anti- TPO, ANA CT C/A/P, PET SCAN, Testicular and Thyroid Ultrasound: negative NMDA-R Ab titer returned 1:40 on Hospital Day 14 Confirming diagnosis of Anti-NMDA Receptor encephalitis

15 Therapeutic Interventions Empiric Acyclovir x 2 courses Treated empirically with high dose corticosteroids and IVIG (Hospital day 12) High suspicion for NMDA-R Encephalitis given psychiatric, behavioral and neurologic disturbance Marginal clinical improvement Second Line Immunotherapy: Rituximab

16 Hospital Course and Outcome Two month hospitalization, treating psychiatric and behavioral disturbance Mentation waxed/waned Kluver-Bucy Syndrome Periodic Catatonia Oral dyskinesia, dystonia, rigidity Patient discharged to Neuro Rehab Returned to school ~ Two months later

17 Anti NMDA-Receptor Encephalitis Anti-NMDAR encephalitis is an autoimmune encephalitis Antibodies attack synaptic NMDA receptors leading to receptor depletion Neurologic syndrome with prominent psychiatric manifestations ie: Limbic encephalitis and frontal lobe dysfunction Usually affects children and young adults

18 Age at Disease Onset

19 Distribution of Cumulative Symptoms during 1 st month of Disease

20 Take Home Points Consider Anti NMDA-Receptor Encephalitis if: Absence of personal history, family history Schizophrenia Presence of neurologic features: i.e. memory, cognition Lack of negative symptoms (social withdrawal, flat affect) Abrupt onset vs. slow progressive decline CSF with lymphocytic pleocytosis or + oligoclonal Bands Treat empirically if strong suspicion for Anti- NMDAR Encephalitis Lengthy time for assay resolution (Two weeks) Search for malignancy if diagnosed

21

22 References Florance NR, Davis RL, Lam C, et al. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Annals Neurology 2009; 66: Titualer MJ, McCracken L, Gabilondo I, Armangue T, Glaser C, Dalmau J. Treatment and prognostic factors for long-term outcome in patients with anti-nmda receptor encephalitis: an observational cohort study. Lancet Neurology 2013; 12: Sabin TD, Jednacz JA, Staats Pn. Case records of the massachusetts general Hospital. Case A 26 year-old woman with headache and behavioral changes. New England Journal of Medicine 2008; 359: Vitaliani R, Mason W, Ances B, Zwerdling T, Jiang Z, Dalmus J. Paraneoplastic encephalitis, psychiatric symptoms and hypoventilation in ovarian teratoma. Annals Neurology 2005; 58:

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