Our case was analyzed in this series, and em /em -light chains were found in the macrophage intracellular crystals by LC-MS/MS (Rodriguez et al., 2008). criteria, atypical imaging prompted further workup, and advanced proteomic technology helped secured an accurate diagnosis. Crystal-storing histiocytosis should be considered in the differential diagnosis of inflammatory CNS disorders. strong class=”kwd-title” Keywords: Crystal storing histiocytosis, Plasma cell neoplasm, CNS demyelinating disease, Inflammatory CNS disorder, Acute leukoencephalopathy, T2-weight hypointensity 1. Introduction Although the major consideration in the differential diagnosis of an acute leukoencephalopathy is a CNS IIDD, a broad spectrum of demyelinating and non-demyelinating disorders can mimic IIDD (Weinshenker and Lucchinetti, 1998) and may even fulfill established diagnostic criteria for MS. CSH is a rare pathology associated with disorders that express monoclonal immunoglobulins, such as multiple myeloma, monoclonal gammopathy of undetermined significance, and lymphoid disorders such as lymphoplasmacytic lymphoma or extramedullary plasmacytoma (Lebeau et al., 2002). It is presumed to be due to an intralysosomal accumulation of secreted paraproteins or immunoglobulins, which aggregate into crystals. Isolated CNS involvement is extremely uncommon, with only two prior cases reported in the literature. Although CSH shows a variety of appearances sometimes obscuring the underlying disorder, immunoglobulins of light-chain type kappa ( em /em ) have been almost exclusively involved without a consistent association with a particular heavy chain. This suggests that CSH results from the storage of crystals produced by plasma cell tumors that either overproduce em /em -light chain or express a structurally aberrant molecule. We describe a rare case of CNS restricted CSH presenting as a relapsing acute leukoencephalopathy. Atypical clinical and radiographic presentation led to brain biopsy, and diagnosis was confirmed using advanced proteomic technology. 2. Case report A 32-year-old woman initially presented in February 2004 with recurrent headaches in the setting of right eye visual blurring and subtle ONO 4817 incoordination. By April 2004 the headaches intensified, and she had a two-week transient episode of right ONO 4817 sided weakness and aphasia. MRI revealed multiple, predominantly white matter, enhancing and nonenhancing lesions with associated edema and heterogenous T2W signal intensity (Fig. 1(A)C(F)). Visual evoked potentials showed right conduction slowing and optic atrophy on funduscopic exam. CSF was normal. Brain biopsy demonstrated inflammation and crystal deposition (Fig. 2(a)). Clinical and radiographic improvement followed a course of high dose steroids. In August 2005 she had a recurrent two-week Neurod1 episode of aphasia associated with episodic right-sided jerking. Follow-up MRI revealed persistent enhancement of the left hemispheric lesion with development of new brain lesions. Repeat brain biopsy showed crystal deposition (Fig. 2(b)). She again ONO 4817 improved to baseline with steroids and phenytoin. Between November 2005 and May of 2006 she continued to experience recurrent transient episodes of aphasia, confusion, and incoordination lasting days to weeks refractory to 6 months of mycophenolate at a dose of 1000 mg twice a day. MRI of the spine in May 2006 (Fig. 1(G)) revealed several T2W lesions throughout the cord from C2-5; T1-4, and T9CT11, with enhancement at C4-5. Extensive workup for inflammatory and metabolic causes was negative. Bone marrow biopsy/aspirate, fat aspirate and CT chest/abdomen/pelvis were normal. Liquid chromatographyCelectrospray tandem mass spectrometry (LC-MS/MS) performed on the two prior biopsy samples demonstrated em /em -light chain deposition. In situ hybridization labeled monotypic em /em -plasma cells. Her course stabilized with lenalidomide (Revlimid) and dexametasone. However, by April 2007 she developed recurrent seizures and follow-up brain MRI demonstrated increase in size and extent of enhancing lesions, particularly involving the left frontal lobe, with more prominent T2 hypointensity and new linear T2W hypo-intensities along the lateral ventricles (Fig. 1(H)C(K)). Bone marrow biopsy and PET scan were negative. Repeat brain biopsy yielded a more extensive sampling of the tissue, and revealed a marked increase in plasma cells with plasmablastic features, positive for kappa light.