VEXAS syndrome-associated tumefactive demyelination

Abstract

Introduction: Vacuoles, E1 enzyme, X-linked (Xp11.3), autoinflammatory, somatic (VEXAS) syndrome is a novel acquired disorder of adulthood, discovered in 2020. Neurological symptoms and sequelae of this new disease are underreported and rarer than their systemic counterparts. We aim to shed light upon the neurological manifestations of this disease by reporting a complex case of a 58-year-old male with a biopsy supporting tumefactive demyelination in the setting of VEXAS syndrome.

Case report: A 58-year-old male with a history of VEXAS syndrome (diagnosed in 2020 as only myelodysplastic syndrome (MDS)), diabetes mellitus, and relapsing polychondritis presented to our institution's emergency department with an acute onset of right lower extremity weakness and headache in April 2022. His weakness progressed to right lower extremity hemiparesis with extinction in sensory modality. He was evaluated for acute stroke, with initial differential diagnosis favoring acute venous infarct from cerebral venous thrombosis (CVT) secondary to MDS. However, brain magnetic resonance imaging (MRI) suggested tumefactive demyelination or acute disseminated encephalomyelitis (ADEM) with a left parietal focus, and diagnostic catheter cerebral angiogram found no evidence of CVT. The patient then developed partial status epilepticus without a history of seizures and later became obtunded with global aphasia upon eventual awakening. Subsequent MRI substantiated tumefactive demyelination or glioma. The lesion was biopsied, displaying no neoplastic cells, supporting diagnosis of tumefactive demyelination. The patient received 1 g of daily solumedrol for 5 days and a few months of prednisone taper, with resolution of mental status despite persistence of right-sided hemiplegia and global aphasia. In March 2023, the patient's genetic testing revealed a UBA1 gene mutation, solidifying a diagnosis of VEXAS syndrome. At this time, the patient exhibited Broca's aphasia with intact comprehension. He was neurologically stable in a wheelchair.

Conclusion: To our knowledge, this case is the first reported in the literature of a VEXAS syndrome-associated central demyelination. Further research into the molecular mimicry and pathogenesis of VEXAS syndrome and its neurobiological involvement is strongly encouraged. A growing body of literature will increase comprehension of this novel disease and its role in cerebral pathology.

Keywords: Differential; Epilepsy; New; Novel; Seizures; Syndrome; Tumefactive demyelination; VEXAS.

Fig. 1

Day 2 brain imaging. A Axial CT brain without contrast demonstrating interval worsening of the left paramedian parieto-occipital hypoattenuation with more severe mass effect and rightward midline shift. B Axial DWI MRI with plus without contrast demonstrating left parietal lobe lesion with involvement of the splenium of the corpus callosum with a leading edge of diffusion restriction. C Coronal MRI post-gadolinium contrast T1-weighted image depicting patchy enhancement involving the left parietal lobe and midline shift

Fig. 2

Mid-hospitalization axial MRI brain with plus without contrast displaying evolving hemorrhage within the FLAIR hyperintense enhancing mass-like lesion in the left parietal lobe crossing over the splenium of the corpus callosum with mass effect and midline rightward shift of almost 7 mm

Fig. 3

Day 11 brain imaging. A Axial T1 MRI with contrast depicting 60.9 × 38.3 mm mass-like lesion, favoring glioma or glioblastoma. B Sagittal T1 MP-RAGE with contrast redemonstrating mass-like lesion, favoring glioma or glioblastoma

Fig. 4

Histopathology. A High-power H&E view of the lesion where macrophages (green arrow) become discernible. There are also perivascular lymphocytes on the right (blue arrow). B Neurofilament immunostain shows evidence for axonal destruction. The blue central area (circled) is devoid of axons as opposed to the peripheral brown areas (arrow) where axons are preserved

Fig. 5

September 2022 sagittal T1 MP-RAGE with contrast demonstrating a healed, treated process of the left parietal lesion with a central area of encephalomalacia and mild enhancement