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Effect of Il-1 Antagonists (anakinra) On Brain Volume and Cognitive Function In Two Patients With Megalencephalic Leukoencephalopathy With Subcortical Cysts

Introduction: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare leukodystrophy characterized by early-onset macrocephaly and progressive white matter vacuolation that lead to ataxia, spasticity, and cognitive decline. MLC1 protein plays a role in astrocyte activation during neuroinflammation and regulate volume decrease after astrocyte osmotic swelling. Loss of MLC1 function acivates interleukin-1β induced inflammatory signals. Theoretically, IL-1 antagonists (anakinra, canakinumab, etc.) may slow down the progression of MLC.

Material and Methods: Two boys from different families were presented with megalencephaly and psycho-motor retardation. Brain MRI of both patients were compatible with the diagnosis of MLC. The diagnosis was confirmed with Sanger analysis of MLC1. Anakinra was administered to both patients. Volumetric brain studies and psychometric evaluations were made before and after anakinra treatment.

Results: At 6th months of anakinra therapy brain volumes of both patiens decreased significantly and cognitive functions and social interaction improved. No adverse effect was observed during the anakinra therapy. Discussion: Anakinra or other IL-1 antagonists can be used to suppress disease activity in MLC disease. Our results need to be supported by further studies.