Gardiman et al. first described DLGNT in 2010 in four children who demonstrated thickened and enhancing subarachnoid spaces, more marked in the basal cisterns, and interhemispheric fissures with disseminated cystic lesions throughout the brain [6]. DLGNT usually afflicts children and young adults, and Rodriguez et al. reported the median age at 5 years (range between 5 months and 46 years) [7]. The common manifestations include headache, altered mental status, behavioral abnormalities, paraphasia, and hydrocephalus [4].
Neuroimaging of DLGNT has hitherto been considered characteristic of the entity. Leptomeningeal thickening and enhancement, along with multiple discrete sub-pial cysts involving the cerebrum, brainstem, and spinal cord, have been reported [3]. These cysts or T2-hyperintense foci may result from fibrosis and expansion of the subarachnoid spaces [3, 7]. Nodular enhancement along the brain and spinal cord surface and sugar-coat enhancement of the nerve roots are the other imaging attributes on T1 post-contrast imaging [7]. As in our case, intramedullary lesions are another feature of DLGNT [3, 7]. In the index case, the initial imaging was remarkable for hydrocephalus with diffuse leptomeningeal enhancement, and tubercular etiology was erroneously assigned. Importantly, on follow-up imaging, these changes were more widespread. The perioptic contrast enhancement was observed additionally. However, on a careful re-evaluation of the initial MRI, soft imaging markers emerged, which favored neoplastic etiology, namely, expansion of the basal cisterns and the Meckel’s caves with nonhomogeneous CSF signal on T2-weighted imaging and corresponding enhancement on post-contrast imaging. We intend to highlight the importance of these findings, which may help differentiate DLGNT from infective meningitis. The remarkable discordance between the normal FLAIR imaging (complete inversion) vis-a-vis a brilliant contrast enhancement of the CSF space argues against an exudative infective etiology. In the index case, initial time point MRI showed expanded CSF spaces in the basal cisterns and Meckel’s caves, which were hyperintense on T2W images and inverted on FLAIR. There was contrast enhancement along the expanded CSF spaces. Follow-up MRI did show avid contrast enhancement of the CSF spaces, but the CSF signal were not completely supressed on FLAIR imaging. Progressive accumulation of the neoplastic cells with marked elevation of the CSF proteins may account for the imaging evolution.
The recent WHO update (2016) on CNS tumors classified DLGNT as a distinct entity [3, 7]. On histopathology, these lesions show morphological features resembling oligodendroglioma, often with neurocytic/neuronal differentiation and a low mitotic index [6, 7]. On immunohistochemistry, the tumor cells show positivity for OLIG2, MAP2, S100, and less than 50% are immunopositive for GFAP. Synaptophysin, chromogranin A, and other neuronal markers can be positive in cases with overt neuronal features [7]. IDH1 (R132H) and EMA are negative. The characteristic molecular alteration of this tumor is concurrent KIAA1549-BRAF gene fusions and either solitary 1p deletion or 1p/19q codeletion in the absence of IDH mutation [7]. Recently, DNA methylation profiling has identified two molecular subgroups, MC-1 associated with a better prognosis, and MC-2, associated with a worse prognosis [8].
There is a broad differential diagnosis for diffuse leptomeningeal enhancement. The most common cause of diffuse leptomeningeal enhancement is meningitis, etiologically diverse. Among all the causes, bacterial and viral meningitis are the most common, exhibiting thin-linear meningeal enhancement [1]. Fungal meningitis exhibits thick and nodular enhancement, but the entire neuraxis being plastered with such pathology is unusual, besides the CSF picture is also incongruent. The neoplastic meningeal seeding or “carcinomatous meningitis” often demonstrate thick and nodular enhancement, a highly variable imaging finding [1]. Medulloblastoma and other CNS embryonal tumors, ependymoma, germinoma, pineoblastoma, and high-grade glioma commonly engender carcinomatous meningitis [1]. Involvement of the meninges by secondaries is commonly associated with malignancies originating from the lung and breast, lymphoproliferative disorders, and melanoma [1]. Moyamoya disease seldom show diffuse leptomeningeal enhancement [9]. Other entities exhibiting diffuse leptomeningeal enhancement include primary diffuse leptomeningeal gliomatosis and diffuse leptomeningeal glioneuronal tumor [6, 10]. We underscore the need for suspicion of DLGNT/DLGNT-like neoplasms in such cases demonstrating thick and nodular meningeal enhancement, as it has a bearing on the treatment approaches. While ATT forms the bedrock of TBM management, DLGNT is managed with chemotherapy and/or radiotherapy [4, 7]. Although slow-growing, secondary hydrocephalus leads to considerable morbidity, and the prognosis is hard to ascribe.
