A generally healthy sixty-five-year-old Caucasian man with a medical history of mild hypertension developed new onset of headaches 3 months prior to his diagnosis of AT-RT, without a prior history of such headaches. The patient's headaches were described as throbbing, occipital, and retro-orbital, with occasional neck pain without associated phonophobia or photophobia with the headaches.
On initial presentation at another institution, the patient had normal vital signs and a normal neurological examination. He was initially thought to have a primary headache disorder and was treated conservatively with over-the-counter medications. This provided little to no symptomatic relief. In the following month, the patient's symptoms progressed to a persistent severe headache with mild intermittent confusion. As his headaches and cognitive status worsened, he presented to a local emergency department (ER), where a lumbar puncture revealed elevated protein of 58 mg/dL with 38 nucleated cells, 206 RBC, but otherwise normal studies (cytology, viral, and bacterial studies were negative). Opening pressure was within normal range. Computed tomography (CT) of the head without contrast was normal. CT angiography of the head and neck with iodine contrast was however noted for question of diminutive appearance of the distal MCA (middle cerebral artery) and ACA (anterior cerebral artery) bilaterally, although the clinical significance of this was initially uncertain (Figure 1). Subsequently, initial magnetic resonance imaging of the brain, with and without contrast was reported as unremarkable. An MR venogram, without contrast, of the brain was obtained and was normal. Conventional catheter-based cerebral angiography of the brain (digital subtraction angiography) was performed and revealed segmental narrowing of the most distal MCA branches.
Given the above initial evaluation, a working diagnosis of possible vasculitic meningitis was rendered. The patient was treated with high-dose steroids (prednisone 100 mg) and discharged on a gradual prednisone taper. The patient, however, had no relief and his symptoms continued to worsen, including progressive encephalopathy and new gait instability, prompting a second opinion at a large tertiary academic medical center.
Repeat magnetic resonance imaging (MRI) brain with and without gadolinium revealed a new 12 mm focus of mass-like enhancement in the pineal region with adjacent right midbrain T2 signal abnormality and prominent adjacent leptomeningeal enhancement involving parieto-occipital sulci and superior cerebellum (Figure 2). A lumbar spine MRI with and without contrast was obtained and revealed small foci of enhancement around the cauda equina (Figure 3). A lumbar puncture was performed and was significant for RBC 4000, 126 nucleated (lymphocytic predominance), protein 144 mg/dL, and glucose 23 mg/dL. Opening pressure was within normal range. Cerebrospinal fluid (CSF) cultures (bacterial, TB, and fungal) and viral polymerase chain reactions (PCRs) were all negative. CSF cytology, however, was notable for abnormal cells, described as large plasmacytoid cells with frequent cytoplasmic vacuoles. Flow cytometry showed no monoclonal B-cell population.
An EVD (external ventricular drain) was placed due to concern of developing communicating hydrocephalus, which was confirmed by this intervention. Brain biopsy of the right pineal gland confirmed the diagnosis of AT-RT (World Health Organization (WHO) grade IV). Fluorescence in situ hybridization (FISH) testing did not show rearrangement of the EWSR1 (22q12) gene region. Patient continued to clinically decline due to encephalopathy and stupor leading to poor functional status and family elected to rescind any further therapies given his rapidly worsening quality of life and the confirmed diagnosis of a terminal disease. The patient expired after 2 weeks of his hospitalization. The prospect of autopsy was not desired by the family.