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Case Study of a 25-Year-Old Female with Complaints of a Severe Headache and Agitation
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Case Study of a 25-Year-Old Female with Complaints of a Severe Headache and Agitation
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1Case Study of a 25-Year-Old Female with Complaints of a
Severe Headache and Agitation
Immunopathology
Contributed by Jessica Dwyer, MD and Bruce Rabin, MD, PhD
Clinical History
A 25-year-old African American female with no significant past medical history presented to the
hospital with complaints of a severe headache and agitation for approximately one week. While
in the emergency department, she became extremely agitated and violent, requiring physical
restraints and benzodiazepine sedation. Her initial workup was unremarkable with the exception
of a qualitative urine toxicology screen that was positive for cannabinoids. The patient was
admitted to the inpatient psychiatry service for presumed acute psychosis. Within a few hours,
she developed generalized seizures and required intubation for airway protection. A CT scan of
her head, a brain MRI, and an EEG were negative for any acute intracranial pathology. Despite
sedation and anti-epileptic medication, the patient continued to have persistent seizures and
agitation. She was immediately transferred to the ICU where her sedation was increased and she
was maintained on mechanical ventilation. She remained afebrile, had stable vital signs, and had
an unremarkable physical exam. However, any time sedation was held she developed generalized
tonic clonic seizure activity and had to be re-sedated. A work-up for acute status epilepticus was
initiated, and the results of relevant laboratory tests are provided in Table 1.
Table 1. The results of relevant laboratory tests are as follows:
1
,2
In addition to the listed results, a CT angiogram of the head was negative for acute intracranial
abnormalities, including venous thrombosis. A pan-CT scan of the chest, abdomen, and pelvis
was negative. A repeat EEG demonstrated findings consistent with a marked post-ictal or
encephalopathic state, but with some additional possible ictal activity. Based on these results, it
was thought that the seizures and altered mental status were likely due to encephalitis of either an
infectious or autoimmune etiology. She was started on empiric anti-viral and antibiotic therapies,
but did not demonstrate clinical improvement. In addition, the results of all the tests for bacterial,
fungal, and viral organisms were negative. Due to the suspicion of an autoimmune etiology, she
2
, 3
was started on an empiric regimen of intravenous methylprednisolone for five days with five
rounds of plasmapheresis, but again she did not demonstrate clinical improvement. She was
screened for multiple autoantibodies including anti-nuclear antibodies (ANA), anti-double
stranded DNA (anti-dsDNA), anti-Ro, anti-La, anti-neutrophil cytoplasmic antibodies (ANCA),
anti-thyroglobulin antibodies, and anti-thyroid peroxidase antibodies. These were all negative.
The clinicians then requested a panel of autoantibodies associated with various neurologic
syndromes and paraneoplastic diseases to be performed. This panel was performed at an outside
reference laboratory, and included assays to detect anti-neuronal nuclear antibodies, anti-glial
nuclear antibodies, anti-Purkinje cell antibodies, amphiphysin antibodies, CRMP-5 IgG
antibodies, anti-glutamate decarboxylase antibodies, anti-voltage gated calcium channel
antibodies, anti-voltage gated potassium channel antibodies, and anti-NMDA receptor
antibodies. Eventually, the final diagnosis was made when the patient's CSF returned POSITIVE
for anti-NMDA receptor antibodies.
Once the diagnosis was made, she was started on more aggressive immunotherapy with
cyclophosphamide and rituximab since she did not demonstrate initial improvement with steroids
and plasmapheresis. Given the high association of this disease with ovarian malignancies, the
patient was evaluated by Gynecology-Oncology. A CA-125 level was noted to be mildly
elevated at 36.9 U/mL (normal <35 U/mL). All other ovarian tumor markers, including β-HCG,
testosterone, and α-fetoprotein, were negative. A pelvis MRI did not demonstrate any evidence
of an ovarian neoplasm, but there were multiple bilateral peripherally located ovarian follicles
which were thought to be consistent with the diagnosis of polycystic ovarian syndrome. It was
eventually decided that since the patient did not demonstrate any clinical improvement with
medical therapy, a prophylactic bilateral salpingo-oophorectomy should be performed. On gross
3
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