Abstract Background Cases of atraumatic, rapidly progressive, neurologic decline in the pediatric population are uncommon and challenging, as the etiology often remains undiagnosed. We present an unusual presentation of a teenager with a fulminant leptomeningeal Diffuse Midline Glioma, H3K27-altered (DMG), which developed refractory intracranial hypertension and progressive neurological decline without diagnosis and aimed therapy. Case Report A previously healthy fourteen-year-old female presented with somnolence and paraplegia preceded by subacute neck and back pain. Neurologic examination revealed depressed consciousness and flaccid paralysis with absent deep tendon reflexes. MRI of the brain and spine demonstrated hydrocephalus, multifocal areas of diffusion restriction throughout the brain, abnormal T2 hyperintensity along the spinal cord, and an exophytic non-enhancing mass of the conus medullaris. The patient developed sudden pupillary dilation and underwent emergent external ventricular drain placement within 48 hours of admission. Refractory to maximal medical and surgical management, the patient progressed to brain death on hospital day 4 without a diagnosis. Cerebrospinal fluid studies revealed markedly elevated cytokines without evidence of infection or malignancy. Autopsy revealed a predominant diffuse leptomeningeal gliomatosis of the entire spinal cord with scant hypothalamic parenchymal involvement. The glioma was H3K27M immunopositively and methylation profiling further confirmed the diagnosis of DMG. Conclusions This case illustrates a treatment dilemma without tissue diagnosis due to her rapid deterioration and the unusual presentation. This case represents the youngest reported case of fulminant DMG in the literature. DMG with metastasis is observed in only 3% of previously published cohorts and disseminated DMG is even rarer. Although the differentials included primary leptomeningeal disease, the rapid neurological decline made it difficult to obtain the tissue diagnosis. The future of liquid biopsy may hold potential for early detection and tailored treatment planning.
Gomes et al. (Tue,) studied this question.