A case of sudden psychosis
After her mother dies, Ms. T develops mania and disorganized behavior. She has a seizure and becomes increasingly agitated. Is this grief or something else?
EVALUATION: A medical cause
The psychiatry consultation-liaison service is asked to further evaluate Ms. T for psychiatric contributions to her continued altered mental status. Ms. T remains in restraints and receives fosphenytoin, 200 mg bid; levetiracetam, 1,000 mg bid; and lorazepam as needed for agitation. Following consultation, the team considers a working diagnosis of an autoimmune encephalopathy based on the negative infectious workup, the patient’s demographics, and the clinical picture (psychiatric symptoms, seizure, and encephalopathy). Ms. T undergoes 5 courses of plasma exchange with no effect. Catatonia is considered, but the patient does not demonstrate significant change with numerous doses of lorazepam.
Because Ms. T does not improve, the team starts a more specific paraneoplastic workup. MRI reveals a 9-mm lesion on her right ovary. Corticosteroids, including IV methylprednisolone, 1 g/d, are started. Ms. T’s clinical presentation improves; soon after scheduled corticosteroid dosing, she is taken to the operating room for right salpingo-oophorectomy. Surgical pathology later confirms the lesion as a mature teratoma. A standard paraneoplastic panel is negative; a separate test for anti-NMDA (N-methyl-D-aspartate) receptor antibodies is positive, however, and confirms the diagnosis of ovarian mass-associated anti-NMDA receptor limbic encephalitis.
Paraneoplastic syndromes
This case represents the interface between a complicated medical phenomenon and psychiatric symptomatology. Mood changes (typically depression), memory problems, paranoia, hypersomnolence, aggressive behavior, agitation, and catatonia have been associated with paraneoplastic syndromes.4-6
Common malignant associations include small cell lung carcinoma (most common) and breast, stomach, colon, renal, bladder, ovarian, uterine, testicular, cell line, and thymic cancers. Research strongly suggests an autoimmune mechanism: tumor-related antibodies cross-react with similar antigens in the neurologic system. Paraneoplastic symptoms often precede symptoms of the malignancy, and the diagnosis is suggested by positive imaging and a paraneoplastic panel.
Anti-NMDA receptor limbic encephalitis is a paraneoplastic syndrome associated with ovarian teratomas and antibodies specific to the glutamate receptor. It is thought to be an autoimmune phenomenon whereby tumor-related antibodies elicit an immune response within certain parts of the neurologic system. Ms. T represents a typical clinical presentation of this syndrome—she is a young, otherwise healthy woman with:
- preceding headache
- new-onset psychotic symptoms
- seizure activity (particularly in the temporal lobes)
- central hypoventilation
- hyperthermia and tachycardia
- dyskinesia and catatonia-like symptoms.5
TREATMENT: Rapid improvement
After removal of the dermoid lesion and IV corticosteroids, Ms. T exhibits rapid improvement. She begins acknowledging others in the room, making eye contact for nearly the first time during this hospitalization, and starts recognizing family members. She also begins verbalizing, responding appropriately to questions in 1 or 2 words. After a 34-day hospital stay, Ms. T is transferred to another facility for rehabilitation; her medication list consists of a corticosteroid taper from prednisone, 20 mg/d, over 2 weeks; fosphenytoin, 200 mg bid; and levetiracetam, 1,000 mg bid.
She eventually is discharged from the rehabilitation facility with noted improvement in multiple domains: she demonstrates cognitive improvement and can walk short distances. She continues to require 24-hour care and exhibits intermittent agitation.
The authors’ observations
We present the case of a patient with a specific paraneoplastic disorder—anti-NMDA receptor limbic encephalitis—with symptoms mimicking those seen in psychiatric disorders such as schizophrenia and bipolar disorder. These similarities complicate recognition and treatment of the underlying disorder.
Ms. T had a complicated yet typical presentation of anti-NMDA receptor limbic encephalitis ( Table 2 ) that was initially mistaken for a manic episode with psychotic features. The diagnosis was made more complex by the death of her mother 1 week before presentation, which could have precipitated her symptom onset. Similar case reports have appeared in neurologic and—less frequently—psychiatric literature ( Box ).5,7-10
