Comprehensive autoimmune/paraneoplastic evaluations are critical in identifying coexisting antibodies
Clinical cases: Neurology
Background
A 42-year-old woman with a 20-pack-per-year history of smoking presented with suspiciousness, altered mental status, that progressed to an obtunded state, necessitating emergency room evaluation. An MRI of brain was unremarkable, but a CSF demonstrated an elevated white cell count of 40, lymphocyte predominant.
She had a seizure in the emergency room and was admitted to the intensive care unit. She was started on intravenous antiseizure medications, levetiracetam, followed by lacosamide for seizure control. Her seizures stopped, but she had persistent coma. She also developed abnormal mouth movements. An NMDA receptor antibody stand-alone test in the spinal fluid was sent to ARUP and was positive.
Consistent with her clinical course and autoantibody positivity, she was diagnosed with anti-NMDA receptor encephalitis. She had a pelvic ultrasound at the bedside which did not reveal ovarian teratoma. She was treated with corticosteroids and plasma exchange without improvement. She subsequently had a follow-up MRI of her brain under general anesthesia, which demonstrated some hazy T2 signal abnormality throughout the cerebral hemispheric white matter. A MOG antibody stand-alone test in serum was ordered and was negative.
Autoimmune encephalopathy evaluations, serum and CSF (ENS2, ENC2) were sent to Mayo Clinic and confirmed NMDA receptor antibody positivity in the CSF and disclosed coexisting neuronal intermediate filament antibody by tissue-based indirect immunofluorescence assay in the CSF only, confirmed as being high titer 1:256. Reflexes to three neuronal intermediate filament antibody subtype cell-based assays revealed positivity for alpha internexin, neurofilament light chain, and neurofilament heavy chain.
Because of the association of this finding with neuroendocrine neoplasm, the patient underwent a PET-CT of trunk. This disclosed a left-sided perihilar lung mass. The patient underwent bronchoscopy with biopsy, which disclosed small-cell carcinoma. After several weeks of IVIG therapy, the patient gradually improved and was discharged to the floor. She started small-cell carcinoma specific chemotherapy, with good radiologic response, and after two months in hospital was discharged to a step-down nursing facility.
Teaching points
- Coexisting autoantibodies provide a differentiated profile that may be informative of cancer types in a paraneoplastic autoimmune context.
- NMDA receptor antibody, though commonly associated with gonadal teratoma, should prompt a more general search for cancer in patients over 40 years of age.
- Neuronal intermediate filament antibody profile, with positivity for light chain autoantibody, should prompt search for neuroendocrine lineage carcinoma such as Merkel cell carcinoma, pancreatic neuroendocrine carcinoma or small-cell carcinoma.
- Phenotype-specific, profile-based testing is more efficient than stand-alone antibody testing.
- Companion serum and CSF neuronal IgG testing in the setting of autoimmune encephalitis is appropriate to sensitively confirm a diagnosis of definite autoimmune encephalitis, and direct cancer search in a paraneoplastic context.
Find out how our autoimmune/paraneoplastic encephalopathy evaluations can identify multiple antibodies and guide the search for occult cancer.
