Case Presentation: A 61-year-old female with history of alcoholism presented with confusion and hallucinations. Three days prior to admission, the patient fell while intoxicated. She typically drank 1-2 bottles of wine daily. She endorsed dizziness and blurry vision since the fall as well as visual hallucinations and paranoid delusions. On examination, she was unable to appropriately answer questions and had fluctuating level of consciousness. Initial head CT was concerning for temporal lobe encephalitis. MRI demonstrated right temporal and frontal T2 hyperintensities concerning for limbic encephalitis. An EEG showed focal slowing and lateralized periodic discharges (LPDs) over the right hemisphere. The patient was treated with IV Acyclovir for presumed HSV encephalitis but did not improve. Lumbar puncture and CSF PCR infectious panel showed no evidence of infection including HSV. She then developed left upper extremity myoclonic jerks concerning for epilepsia partialis continua and was started on levetiracetam and clonazepam. Autoimmune and paraneoplastic encephalitis remained on the differential. Several autoimmune/paraneoplastic panels were sent, and a search for malignancy began. CT of the chest, abdomen and pelvis revealed right upper lobe lung and right adrenal lesions. She was then treated empirically for paraneoplastic encephalitis with IVIG for 3 days with drastic improvement in symptoms. Biopsies showed adenocarcinoma of the lung, confirming the diagnosis of paraneoplastic encephalitis.
Discussion: Paraneoplastic encephalitis is an immune-mediated process whereby, in the setting of malignancy, auto-antibodies are produced which attack the central nervous system. This form of encephalitis often affects the limbic system, though it can also involve the brainstem or cause widespread inflammation of the CNS. In paraneoplastic limbic encephalitis (PLE), the affected structures include the amygdala, hippocampus, cingulate gyrus, and limbic cortex. PLE can manifest as acute or sub-acute behavioral changes, short-term memory problems, seizures, and cognitive dysfunction. As seen in this case, MRI often shows T2 hyperintensities localizing to the medial temporal lobes. EEGs can demonstrate focal or generalized slowing with epileptiform activity in the temporal lobes. While numerous malignancies are associated with PLE, the most common is small cell lung cancer, although non-SCLC is a frequent cause as well. As we experienced, in a significant portion of PLE, a specific auto-antibody is never detected. The best treatment for PLE is typically identification and treatment of the primary tumor with initiation of immunotherapy (IVIG, PLEX, rituximab, cyclophosphamide).
Conclusions: It is prudent to consider a paraneoplastic syndrome as a potential cause of encephalitis once more common etiologies have been ruled out. In many cases of PLE, a specific antibody is never detected. Early treatment of the neoplasm with joint immunotherapy is crucial to slowing the progression of PLE.