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stimulating hormone level of < 0.01, free thyroid recommended. Prior to initiation of Rituximab, a urine
hormone level (T4) of 3.53 positive anti-TPO and pregnancy test (UPT) was repeated on day 36 and found
thyroid stimulating immunoglobulin, suggesting to be positive (admission UPT had been negative).
hyperthyroidism-induced psychosis. Methimazole Subsequent plasma human chorionic gonadotropin test
treatment resulted in a euthyroid state, but no was positive and transvaginal ultrasound confirmed a
symptomatic improvement. On day 4, brain magnetic viable fetus.
resonance image (MRI) showed no acute intracranial
process. Due to concerns that the MRI was performed On discovery of a viable fetus, all teratogenic medications
too early to detect changes, it was repeated 1-month after were discontinued, folate supplements were started,
presentation. This second scan was also unremarkable. and the plan for rituximab therapy was abandoned.
The patient’s electroencephalogram showed no At this time, the patient’s psychosis and agitation were
epileptiform activity during sleep or wakefulness. more controlled. She seemed to exhibit more restraint
due to knowledge of her pregnancy and her care for
Cerebrospinal fluid (CSF) analysis on day 8 yielded the child’s health. Thus, she tolerated the central line
lymphocytic pleocytosis (white blood cell (WBC) well. After extensive discussions with the patient,
count of 44 with 95% lymphocytes) with negative family, and consulting services, the patient underwent
bacterial cultures, fungal cultures, and viral polymerase seven cycles of PLEX over 2 weeks (days: 44-58), with
chain reactions. A 3 days course of IV steroids for a resolution of psychosis and bizarre behavior. During
inflammatory encephalitis yielded no symptomatic this time, additional CSF and serum analyses came back
improvement. On day 17, repeat CSF studies showed positive for anti-GAD antibody (titers unavailable), and
persistent pleocytosis (WBC count of 44 with 3% a yet unidentified neuronal autoantibody found in CSF
lymphocytes). A second trial of IV steroids for 7 days only; no other antibodies were identified (e.g. AMPAR,
followed by oral steroid taper again failed to achieve GABA-BR). Clinically, the patient did not demonstrate
symptomatic improvement. CSF and serum samples sequelae of Stiff-Person syndrome. The patient was
were sent to two laboratories for further testing, largely asymptomatic by day 58 and discharged home
specifically for neuronal cell surface antigens and on prenatal vitamins, folate, and levothyroxine. At
synaptic proteins such as NMDAR, AMPAR, GABA-BR, 4-month follow-up, the patient was symptom-free and
and autoantigens. One laboratory, the Josep Dalmau found to have subclinical hyperthyroidism.
laboratory, uses recombinant technology, while the
other, the ARUP laboratory at the University of Utah, DISCUSSION
uses immunofluorescence to identify antibodies. On
day 24, the initial CSF samples returned positive for Three cases of anti-NMDAR encephalitis in pregnant
[7]
anti-NMDAR antibody (titer 1:5). The patient was women have been described in the literature, but
thus diagnosed with anti-NMDAR encephalitis; no to the best of our knowledge, this is the first with
anti-NMDAR antibodies were detected in the serum. multiple autoimmune antibodies present. Our patient
Scans for malignancy with whole body computed demonstrated two distinct antibodies, anti-NMDAR and
tomography images uncovered a thickened uterine anti-GAD, as well as another neuronal autoantibody that
endometrium but no evidence of ovarian masses; this has not yet been characterized. Both the anti-NMDAR
finding was confirmed by transvaginal ultrasound. The and anti-GAD antibodies have been described in
patient repeatedly refused a pelvic MRI. association with autoimmune limbic encephalitis,
though our patient’s titer of anti-NMDAR antibody (1:5)
For the management of her neuropsychiatric was significantly lower than previously described
[7]
symptoms, the patient received olanzapine, valproate, cases (> 1:80). It is unclear whether one of the
and haloperidol for psychosis control and mood antibodies was the dominant cause of encephalitis
stabilization. However, as she developed significant or if the three worked synergistically. Our patient
Parkinsonian features (hypertonicity, mask-like facies, was atypical for anti-NMDAR encephalitis in that
tremor), haloperidol was discontinued, and benztropine she had less severe symptoms and never progressed
and diphenhydramine were added with subsequent to autonomic instability or central hypoventilation.
resolution of Parkinsonism. Although she likely experienced a few seizures, she
never experienced the typical movement disorders of
As the patient failed repeated steroid treatments, anti-NMDAR encephalitis. Her disease also manifested
alternate treatments were considered. While IVIG or much earlier in the pregnancy (5 weeks of gestation)
PLEX would be first-line treatments for anti-NMDAR compared with previous gravid patients who presented
encephalitis, there was concern that the patient would at 8, 14, or 17 weeks of gestation. She responded well
[7]
not tolerate an indwelling central line given her agitation, to PLEX, with significant symptomatic improvement
mania, and psychosis. Thus, Rituximab therapy was by the fifth cycle. She was also atypical for anti-GAD

Neuroimmunol Neuroinflammation | Volume 2 | Issue 1 | January 15, 2015 47