History
Ms. Lam was a 40-year-old lady with a history of metastatic adenocarcinoma of the stomach. She has been on treatment with the immune checkpoint inhibitor Nivolumab for 6 months.
She presented with a 1-month history of non-postural headache, left ear hearing impairment, and tinnitus.
She was noted to have a low-grade fever upon admission.
The initial neurological examination was unremarkable.
During her hospitalization, she developed an episode of suspected generalized tonic seizure and a new left abducens nerve palsy.
Physical examination
A repeated neurological examination was pertinent for slow verbal response, neck stiffness, positive Kernig sign, failed left eye abduction, left lower motor neuron type weakness, and no ankle clonus.
Investigation
Baseline blood tests on admission, including inflammatory markers, were normal.
Serial plain CT brain demonstrated progressive ballooning of the frontal and temporal horns of the lateral ventricle and third ventricle. The fourth ventricle remained patent.
Lumbar puncture revealed significantly elevated CSF opening pressure and CSF lymphocytic pleocytosis with markedly lowered glucose level. Preliminary microbiological workup was negative.
An MRI brain did not show parenchymal T2 or contrast-enhanced lesions. There was suspicious leptomeningeal enhancement over the right occipital and midbrain regions.
EEG was suggestive of mild cerebral dysfunction with a generalized mild slowing background.
Though process
The pathology was localized to the brain and the brainstem. Importantly, no features were pointing towards a cord or nerve root involvement.
The symptoms, including the headache, altered mental state, left CN 6/7/8 palsies, and suspected seizure could be attributable to raised intracranial pressure in the context of communicating hydrocephalus and grossly elevated CSF opening pressure.
Given the background of advanced malignancy and markedly lowered CSF glucose, leptomeningeal carcinomatosis remained the most likely etiology. Indolent infections, particularly tuberculosis, would be next on the list because of negative microbiology thus far, bearing in mind that tuberculosis is difficult to completely exclude. (Other causes of markedly lowered CSF glucose include pyogenic meningitis and systemic lupus erythematosus.)
Nivulomab-associated neurological immune-related adverse event, such as aseptic meningitis or encephalitis, was deemed to be a lesser possibility. The progressive communicating hydrocephalus and markedly lowered CSF glucose were atypical for this entity.
Next steps
Cytology came back to show suspicious cells, affirming the clinical impression.
Urine and sputum specimens were sent for tuberculosis. Serum cryptococcal antigen was sent as well.