A 54-year-old Caucasian male who smoked 20 cigarettes per day and had an otherwise unremarkable medical history was admitted to our hospital due to subacute neurologic symptoms. He presented with nocturnal myoclonus, sexual dysfunction, mood swings, insomnia, daytime sleepiness, and occasional disorientation. His vital signs were normal at the time of admission, and a physical examination did not detect any abnormality. A neurologic examination revealed anterograde amnesia, apathy, and a disorder index in the Mini-Mental State Examination of 24/30.
All blood test findings were within normal limits, and serology was negative for hepatitis B virus, hepatitis C virus, human immunodeficiency virus, leishmaniasis, histoplasmosis, syphilis, and borreliosis. The findings of immunological studies were normal for antinuclear antibodies, anti-DNA antibody, angiotensin-converting enzyme, complement, IgA, antineutrophil cytoplasmic autoantibodies, anti-Ro/La antibody, and anticardiolipin antibody; a proteinogram also yielded normal findings. A polymerase chain reaction performed using the cerebrospinal fluid (CSF) yielded negative findings for herpes simplex and varicella zoster virus. A cytologic analysis of the CSF did not reveal any malignant cells.
The CSF was also negative for paraneoplastic antibodies with specificity for recombinant Hu, Yo, Ri, Ta, amphiphysin, and Ma2 antigens. The electroencephalogram (EEG) was normal. Cerebral CT demonstrated hypodense lesions in the medial bitemporal region and in the right caudate nucleus, with pseudonodular uptake in both unci. MRI demonstrated diffuse hyperintensities in the parenchyma, with predominantly medial bitemporal involvement extending into the basal ganglia, frontal lobes, and leptomeninges on FLAIR images, which is the most characteristic sequence, suggesting a PLE (Fig. 1).
An extension study was conducted to locate a tumor. Testicular and prostate ultrasonography revealed slight changes suggestive of chronic prostatitis and normal gonads. CT of the abdomen and chest revealed a 33-mm nodule in the right inferior lobe (RIL), suggestive of hamartoma, and lymph nodes of significant size at stations 7 and 2R. Ultrasound endoscopy confirmed the presence of paraesophageal right hilar adenopathy, which was suggestive of malignancy. Histopathology of the lymph node was positive for squamous cell carcinoma. Fibrobronchoscopy demonstrated erythematous mucosa in the right superior lobe. Bronchoalveolar aspiration and bronchoalveolar lavage produced negative findings. Positron-emission tomography and CT (PET/CT) demonstrated a hypermetabolic lesion in the azygos-esophageal recess that have could represented a lymph-node conglomerate. Outbreaks of high metabolic activity in both hippocampal regions that were suggestive of limbic encephalitis were observed, but with no evidence of metastatic lesions.
The patient was diagnosed with squamous cell carcinoma of the lung TxN2M0 (stage IIIA). He was treated with three cycles of 75 mg/m2 cisplatin and 75 mg/m2 docetaxel every 3 weeks. A postreatment evaluation by PET/CT demonstrated a slight reduction of the mediastinal lesions. A right inferior lobectomy and a mediastinal lymphadenectomy were performed 3 months after completing the last cycle of chemotherapy. A pathologic examination demonstrated that the peribronchial, interlobar, and subcarinal lymph nodes contained squamous cell carcinoma with extension into the soft tissues and capsular rupture. The nodule in the RIL was confirmed as a pulmonary chondroid hamartoma. The surgical margins were free of disease. Brain FLAIR imaging after the surgery revealed remarkable decreases in both the extension and signal intensity within the medial region of both temporal lobes. Secondary mesial atrophy with temporal horns dilatation was observed (Fig. 2). The patient's neurologic symptoms improved after surgery. The postoperative therapy included 4 cicles of carboplatin (area under the curve 5) and 500 mg/m2 pemetrexed administered every 3 weeks with concomitant mediastinal radiotherapy.
After postoperative treatment, PET/CT revealed two hypermetabolic lesions in the right pleuroesophageal recess, and MRI revealed persistence of the T2-signal intensity and mesial bitemporal lobe atrophy. After 8 months of follow-up the patient presented with acute neurologic symptoms that required admission to an intensive care unit (ICU) due to fever, upper-extremity myoclonus, and somnolence. Brain MRI and CT demonstrated a persistent T2-elongation of the mesial regions and no definitive gadolinium enhancement. The CSF was positive for Escherichia coli and Staphylococcus aureus. An EEG revealed diffuse neuronal dysfunction with no focal or diffuse paroxysms suggestive of seizures. Despite treatment with broad-spectrum antibiotics, the patient had a low level of consciousness with persistent neurologic deterioration, and died 1 month after ICU admission. The autopsy revealed persistent squamous cell carcinoma in the tracheal and mediastinal lymph nodes with extensive infiltration of the esophagus wall and a tracheoesophageal fistula. Infiltration of the right atrium, right ventricle, and renal capsule was also observed. In the brain, the autopsy confirmed advanced bilateral T-cell-mediated limbic encephalitis with persistent inflammatory activity (Fig. 3) extending to the midbrain tectum.