Central Nervous System Crystal-Storing Histiocytosis: Neuroimaging, Neuropathology, and Literature Review

Discussion

CSH is a very uncommon lesion and is distinctly unusual in the brain. This case illustrates advanced imaging findings of this rare process. We believe that the slightly increased regional cerebral blood volume and increased regional cerebral blood flow are related to hyperemia from the underlying reactive/inflammatory process. Additionally, we postulate that the flow-void-like areas on FLAIR imaging represent prominent veins, which result from the partial perivascular nature of the inflammation. Mild postcontrast enhancement likely relates to an element of breakdown at the blood-brain barrier from the same process. NAA is a marker of neuronal cell health. Decreased NAA peak is commonly seen in nonspecific neuronal loss, including ischemia, trauma, inflammation, infection, tumors, dementia, and gliosis. Choline is a marker of membrane turnover and is present to a greater degree in white matter than in gray matter. Choline is increased in tumors, inflammation, and chronic hypoxia. Lactate is not seen in the normal brain. It is the end product of anaerobic respiration and is elevated in foamy macrophages. The presence of lactate can be seen in patients with ischemia, inborn errors of metabolism, tumors, abscess, and inflammation. In our case, the constellation of MR spectroscopy findings could be related to inflammation.

In previous case reports, morphologically similar crystalline material was most often comprised of immunoglobulin in the setting of monoclonal gammopathy.¹ However, cases associated with Charcot-Leyden crystals related to eosinophilic inflammation, resulting from treatment with the drug clofazimine, have also been reported.^2,3 Our pathologist raised the latter possibility because the patient's tissue sample had a somewhat orange discoloration, which can be seen after treatment with clofazimine. However, research indicates that this antimycobacterial medication does not cross the blood-brain barrier. An extensive Web-based literature search for other etiologies failed to yield prior reports of CSH associated with Pentasa-type (mesalamine) medications (the patient had a history of noncompliant treatment with Pentasa). However, the search did yield 1 prior case report in 1984 of a 38-year-old woman with “crystalline encephalopathy.” ⁴

Our patient's brain biopsy did demonstrate the focal presence of perivascular lymphocytes and lymphocytes focally within the vessel wall. The previously described features may suggest angiitis,⁵ but the possibility that the inflammatory cells merely represent an inflammatory response to tissue injury from whatever is causing the crystalline material to accumulate cannot be excluded. Previous cases with accompanying advanced radiologic imaging of such a disease process within the brain parenchyma have not been identified during our extensive Web-based literature search.