Schizophrenia was the working diagnosis. Paraneoplastic limbic encephalitis was the cause.

A two-decade label

A 69-year-old man had lived with a diagnosis of schizophrenia since the age of 47. For over twenty years, he had been institutionalized in a psychiatric hospital. His history included smoking ten cigarettes a day, but he had no prior history of epilepsy or seizures.

The body in crisis

The man was transferred from the psychiatric hospital to an acute care facility after experiencing a five-minute generalized seizure. He presented with a fever and an altered mental status. Initial blood tests showed hyponatremia with a sodium level of 125 mEq/L and a markedly elevated creatine kinase (CK) of 3000 U/L.

A chest CT scan revealed infiltrative opacities in his lungs and enlarged lymph nodes, which were initially treated as pneumonia. While he was seizure-free during his first week of hospitalization, his condition deteriorated sharply on day 8. His consciousness declined, and he began suffering from recurrent, refractory seizures.

Markers of a hidden cause

While an initial brain MRI had been unremarkable, a follow-up scan on day 8 showed bilateral hyperintense lesions in the hippocampi. Cerebrospinal fluid analysis revealed elevated protein and cell counts. These findings shifted the focus toward a paraneoplastic syndrome—a condition where the immune system attacks the brain while trying to fight a hidden cancer.

Testing for paraneoplastic antibodies returned a strongly positive result for anti-SOX1 antibodies. Further investigation into the lung lesions revealed sputum cytology suggestive of small-cell lung carcinoma. The neurological destruction was not a progression of his psychiatric history, but a paraneoplastic limbic encephalitis associated with lung cancer.

Outcome and palliative care

Given the patient’s rapid clinical deterioration and his impaired capacity to make decisions, a palliative approach was chosen. Although his seizures were eventually controlled with levetiracetam and phenobarbital, his consciousness remained poor. He died on day 115 of his hospitalization.

The autopsy findings

A postmortem autopsy confirmed the presence of small-cell lung carcinoma in the right lung. Neuropathological examination of the brain revealed profound neuronal loss and astrogliosis, specifically hippocampal sclerosis. The damage was most severe in the limbic system, including the hippocampus and amygdala.

The autopsy provided direct evidence of an immune-mediated attack. CD8-positive cytotoxic T lymphocytes were found infiltrating the brain tissue, directly attached to shrunken, dying neurons. These immune cells were also found in the sciatic nerve and spinal cord, illustrating a generalized autoimmune process that had spread throughout the nervous system. While the man had a long history of schizophrenia, the findings supported the anti-SOX1 encephalitis as the driver of the severe, acute brain destruction.