A 23-year-old man with past ethanol abuse and traumatic brain injury 3 years previously was diagnosed with relapsing-remitting MS, after presenting with diplopia, blurred vision, dizziness, and gait ataxia. Imaging showed several enhancing brain lesions and one intramedullary lesion at the C3 level. His CSF examination showed increased cells and proteins, and he had prolonged visual evoked potentials. He was treated with natalizumab monotherapy, which was discontinued after 39 months, because of excessive ethanol consumption. He was subsequently hospitalized with aspiration pneumonia in the setting of ethanol intoxication. Two months after natalizumab interruption, he presented with planning difficulties and ataxia. MRI, 1.5 week after symptom onset (SO), revealed new enhancing lesions in the frontal and left parietal lobes and in the cerebellum. PCR for CSF JC virus (JCV) was positive. He developed a bilateral pyramidal syndrome and aphasia and became bedridden and mute. MRI 2 weeks after SO showed lesion progression in the middle cerebellar peduncles, corticospinal tracts, and left frontal lobe with mass effect (, A–C) and a new enhancing lesion in the right temporal lobe. This was consistent with PML-IRIS. PCR for JCV showed 9,900 copies/mL CSF. He received methylprednisone (1 g/day for 5 days) and started mirtazapine (15 mg qhs).
Overview of MRI evolution
MRI, 3.5 weeks after SO, showed decreased enhancement, but continuous progression of the lesions and mass effect (, D–F). He had one focal motor seizure, treated with levetiracetam, and received mefloquine (250 mg once a day for 3 days), followed by mefloquine (250 mg weekly for 24 weeks). MRI 1 week later showed enhancement, and he was given a prednisone taper, starting at 90 mg/day for 1 month.
Three months after SO, he answered in two-word phrases and could take a few steps. MRI showed a decrease in the size of the PML lesions and absence of mass effect but also atrophy and a faint rim of enhancement in the left frontal lobe.
Three months later, he could walk unassisted and care for most of his daily activities. He still had expressive aphasia, planning difficulties, left-sided neglect, and a bilateral cerebellar syndrome. MRI 6 months after SO showed further atrophy at the site of the PML lesions. There was limited residual contrast enhancement in the left frontal lobe, but new enhancement in the cerebellar lesions, indicating ongoing IRIS (, G–I).
He continued to improve, and MRI performed 3 months later showed resolution of enhancement and marked atrophy (, J–L). One year after onset, he spoke in short sentences and had a residual cerebellar syndrome and a minimal right-sided pyramidal syndrome. No new lesions were seen.
We used proton magnetic resonance spectroscopy (1H -MRS) 3, 6, 9, and 15 months after SO to measure the concentration of N-acetyl-l-aspartate (NAA), a neuronal marker, choline (Cho), a component of cell membranes, myoinositol (mI), a glial marker associated with inflammation, and LIP1 and LIP2, markers of anaerobic metabolism, within PML lesions. Creatine (Cr) is a measure of basal metabolism, and all values are expressed as ratios. There was a decline in the NAA/Cr ratio until 9 months after SO, consistent with neuronal and axonal damage, and an increase at the last time point in the left frontal and cerebellar lesions. The Cho/Cr ratio showed a continuous decline consistent with decreased turnover in cell membranes. mI/Cr, LIP1/Cr, and LIP2/Cr ratios increased in both lesions between 3 and 6 months after SO, concomitant with new enhancement in the cerebellum. When enhancement subsided 9 months after SO, the LIP2/Cr ratio remained elevated in both lesions, whereas the mI/Cr ratio remained elevated in the frontal lesion and the LIP1/Cr ratio continued to rise in the cerebellar lesion. Fifteen months after onset, the mI/Cr ratio decreased in the frontal lesion but increased again in the cerebellar lesion, whereas the lipid/Cr ratios decreased in both.
JCV-specific T-cell responses were detected at the same time points in his blood. Although the CD4+ T-lymphocyte response remained low, the CD8+ T-lymphocyte response became robust over time.