We describe three cases of isolated parenchymal sarcoidosis with vascular involvement mimicking granulomatous primary central nervous system (CNS) vasculitis.

Sarcoidosis is an idiopathic granulomatous inflammatory disorder with neurological involvement in up to 25% of patients in autopsy studies, occasionally without systemic disease.  CNS sarcoid granulomas classically involve brain and spinal cord surfaces, particularly basilar meninges, whereas parenchymal disease is less common and often perivascular, extending through Virchow-Robin spaces into adjacent parenchyma with rare vessel wall infiltration. Vascular involvement is uncommon but diagnostically consequential, as granulomatous vessel wall infiltration can produce luminal narrowing or injury, mimicking granulomatous primary CNS vasculitis (PCNSV). This distinction is critical because PCNSV is typically treated with cyclophosphamide-based regimens, whereas neurosarcoidosis often responds to anti-granulomatous therapy, including tumor necrosis factor-α inhibition.

Patients presented with headache, acute/subacute encephalopathy, seizures, and/or focal deficits. MRI demonstrated miliary enhancement pattern with diffuse regional white matter T2-hyperintensities; two cases showed deep medullary vein engorgement and enhancement. CSF showed lymphocytic pleocytosis (2/3), elevated protein (2/3), and absent oligoclonal bands (3/3). Brain biopsies revealed perivascular non-necrotizing granulomas with heterogeneous parenchymal involvement and transmural vessel wall infiltration without fibrinoid necrosis, infection, malignancy, or systemic disease on whole-body 18F-FDG-PET/CT. Pathologic morphology favored neurosarcoidosis spreading through Virchow-Robin spaces with secondary vascular involvement rather than primary angiodestructive vasculitis, although granulomatous vasculitis could not be fully excluded as vessel damage can occur at later stages or have patchy distribution. Two patients relapsed on rituximab but achieved sustained steroid-free remission with infliximab after prednisone taper. The third improved clinically with cyclophosphamide and glucocorticoids but had persistent perivascular enhancement and an asymptomatic infarct at last follow-up.

These cases highlight the challenge of distinguishing early isolated parenchymal neurosarcoidosis with vascular involvement from granulomatous PCNSV. Integrated clinicoradiologic-pathologic assessment, disease-specific biomarkers, and pathology-informed diagnostic frameworks are needed to guide diagnosis and treatment.