Cortical and Subcortical Network Dysfunction in a Female Patient With NEXMIF Encephalopathy

Maria Cristina Cioclu,Manuela Tondelli,Sanjay M Sisodiya,Giada Giovannini,Anna Elisabetta Vaudano,Stefano Meletti,S Krithika,Antonietta Coppola,Federico Zara,Michele Iacomino

doi:10.3389/fneur.2021.722664

Abstract

The developmental and epileptic encephalopathies (DEE) are the most severe group of epilepsies. Recently, NEXMIF mutations have been shown to cause a DEE in females, characterized by myoclonic–atonic epilepsy and recurrent nonconvulsive status. Here we used advanced neuroimaging techniques in a patient with a novel NEXMIF de novo mutation presenting with recurrent absence status with eyelid myoclonia, to reveal brain structural and functional changes that can bring the clinical phenotype to alteration within specific brain networks. Indeed, the alterations found in the patient involved the visual pericalcarine cortex and the middle frontal gyrus, regions that have been demonstrated to be a core feature in epilepsy phenotypes with visual sensitivity and eyelid myoclonia with absences.

Highlights

The developmental and epileptic encephalopathies (DEEs) are the most severe group of epilepsies in which frequent epileptic activity, in addition to the underlying etiology, contributes to developmental impairment, with onset typically in infancy or childhood [1]
Affected females have been described [10,11,12,13,14] and recently a large multicentric study outlined the epilepsy phenotype of affected females [15] which is consistent with a generalized DEE characterized by myoclonic–atonic epilepsy overlapping with eyelid myoclonia with absence
We report a female patient with a de novo Neurite EXtension and MIgration Factor gene (NEXMIF) pathogenic variant and recurrent prolonged episodes of absence status with eyelid myoclonia

Summary

Introduction

The developmental and epileptic encephalopathies (DEEs) are the most severe group of epilepsies in which frequent epileptic activity, in addition to the underlying etiology, contributes to developmental impairment, with onset typically in infancy or childhood [1]. We report a female patient with a de novo NEXMIF pathogenic variant and recurrent prolonged episodes of absence status with eyelid myoclonia.

Results

Conclusion