Differential Diagnosis:

  • Primary angiitis of the CNS (PACNS)
  • Secondary CNS vasculitis (infectious, autoimmune, or systemic inflammatory disorders)
  • Chronic small vessel ischemic disease
  • Demyelinating disease (e.g., multiple sclerosis)
  • Vasculopathy related to prior hemorrhage or radiation

Diagnosis and Discussion:

Chronic multifocal vascular and white matter injury in a patient with previously treated granulomatous meningitis clinically suspected to represent CNS vasculitis.

CNS vasculitis represents a heterogeneous group of disorders characterized by inflammation and injury of cerebral blood vessels. It may occur as a primary process confined to the CNS or as a secondary manifestation of systemic inflammatory, infectious, or autoimmune disease. Although this patient had history of testicular inflammation, the great majority of his symptoms were in the CNS. His rapidly progressive interstitial lung disease was concerning as another possible manifestation of vasculitis, but at autopsy the lungs showed non-specific fibrosis, without granulomatous or vasocentric inflammation, or evidence of vessel damage.

Primary angiitis of the CNS (PACNS) can occur over a wide range of ages, with a variety of symptoms, including seizures, headaches, cognitive changes, and focal neurologic deficits. Diagnosis is often a lengthy process. Imaging can be helpful and may show multifocal hemorrhages or abnormalities of vessels on angiography or digital subtraction angiography, though some cases of vasculitis develop more diffuse white matter changes. Biopsy can aid in the diagnosis, but due to the patchy nature of inflammation, a biopsy can be negative even in cases with convincing clinical and radiographic findings.

Histologically, CNS vasculitis shows vascular wall damage and perivascular inflammation, often with thrombosis and secondary injury to adjacent brain tissue. Inflammation can be patchy and discontinuous, and can involve any size of vessel, including venules as well as arterial vessels and capillaries. Common patterns include granulomatous inflammation, lymphocytic inflammation, and necrotizing vasculitis. Vascular β-amyloid may be an instigator of CNS vasculitis (Aβ-related angiitis). In treated cases, active inflammation may be minimal or absent, and the dominant findings may include chronic vascular changes, hemosiderin indicating prior hemorrhage, gliosis, and white matter rarefaction.

In this case, the presence of multifocal white matter lesions in multiple vascular territories, showing axonal loss, gliosis, hemosiderin deposition, and prominent perivascular vascular wall changes is consistent with chronic vascular injury in the setting of previously treated CNS vasculitis. Recognition of the pattern of injury is important because treated vasculitis can lack overt inflammatory infiltrates, making clinicopathologic correlation essential for diagnosis.

References:

Miller DV, Salvarani C, Hunder GG, et al. Biopsy findings in primary angiitis of the central nervous system. Am J Surg Pathol. 2009;33(1):35-43. doi:10.1097/PAS.0b013e318181e097

Agarwal A, Sharma J, Srivastava MVP, et al. Primary CNS vasculitis (PCNSV): a cohort study. Sci Rep. 2022;12(1):13494. Published 2022 Aug 5. doi:10.1038/s41598-022-17869-7

Panda KM, Santosh V, Yasha TC, Das S, Shankar SK. Primary angiitis of CNS : neuropathological study of three autopsied cases with brief review of literature. Neurol India. 2000;48(2):149-154.

Caputi L, Erbetta A, Marucci G, et al. Biopsy-proven primary angiitis of the central nervous system mimicking leukodystrophy: A case report and review of the literature. J Clin Neurosci. 2019;64:42-44. doi:10.1016/j.jocn.2019.03.021