BCRP Expression with Lipofuscin Accumulation in Abnormal Neurons from a Child with Transmantle Cortical Dysplasia (TMCD) and Refractory Epilepsy

Abstract

Cerebral cortical development’s malformations, including the transmantel cortical dysplasia (TMCD), have been associated with refractory epilepsy (RE). Several ABC-transporters as “P-glycoprotein (P-gp), Multidrug resistance proteins (MRP-1) and breast Cancer Resistant Protein (BCRP)” are up-regulated in human epileptogenic brain lesions of RE, however they have not been explored in Transmantle cortical dysplasia (TMCD). We describe a 13 years old boy with Refractory Epilepsy (RE) and abnormal Magneic Resonance Image (MRI) (T1, FLAIR and T2) compatible with TMCD. Clinical follow-up, images and pathologic studies were developed by routinely methods. Epilepsy surgical treatment included total lesion resection with complete seizures remission at date. Deeper brain areas related with images findings, showed features of TMCD with abnormal ballooned neurons with high accumulation of PAS+, sudanophilic and autoflourescent lipopigment (LP). Immunohistochemistry, using primary monoclonal antibodies for P-gp, MVP and BCRP proteins, showed high expression of BCRP in several ballooned-LP+ cells. In contrast, P-gp and MVP were negative and MRP-1 has not been investigated. The links of BCRP with LP and AEDs are not known, however, the expression of BCRP in these LP+ ballooned neurons from the epileptogenic brain area, with P-gp/MVP negative results, suggest that BCRP could be associated to refractory epileptic phenotype.