Title: Adult male with progressive neurologic decline and multifocal white matter lesions

Author(s): Hannah E. Xavier, Kathryn P. Scherpelz

Institution: University of Washington

Clinical History:

A 30 year-old male with history of diabetes mellitus type 2 and non-infectious granulomatous inflammation of the testis developed central nervous system (CNS) symptoms including episodes of aphasia, headache, vertigo, and localized numbness or weakness. Biopsy found granulomatous meningitis, clinically suspected to represent CNS vasculitis. ANCA testing was negative. He was treated with multiple immunosuppressive therapies, but developed progressive neurologic deficits and seizure disorder. He died at age 40 due to interstitial lung disease.

Radiology:

MRI at age 39 demonstrated, per report, foci of perivascular enhancement, left frontal encephalomalacia/gliosis, right frontal gliosis, and blood products in bilateral frontal lobes and cerebellum.

Representative Photograph:

Biopsy showed non-necrotizing granulomatous inflammation in the meninges and extending along Virchow-Robin spaces.

After autopsy, the fixed brain weighed 1340 g and had no external lesions. On cut surfaces, multifocal areas of discoloration and softening were present in the cerebral white matter, mostly within the frontal white matter and periventricular regions, and focally present in pons.

Postmortem white matter lesions were characterized by rarefaction, astrogliosis, and hemosiderin deposition. Inflammatory infiltrates were minimal or absent. Many small- and medium-sized parenchymal vessels demonstrated hyalinized walls and expanded perivascular spaces

Questions for Viewers:

1)      What entities should be considered in the differential diagnosis of multifocal white matter injury (rarefaction, prior hemorrhage)?

2)      What findings would favor CNS vasculitis over other causes of chronic ischemic or hemorrhagic injury?

3)      How might prior immunosuppressive therapy influence the histologic appearance of vasculitis?