A hypothesis for the role of axon demyelination in seizure generation

Abstract

Loss of myelin and altered oligodendrocyte distribution in the cerebral cortex are commonly observed both in postsurgical tissue derived from different focal epilepsies (such as focal cortical dysplasias and tuberous sclerosis) and in animal models of focal epilepsy. Moreover, seizures are a frequent symptom in demyelinating diseases, such as multiple sclerosis, and in animal models of demyelination and oligodendrocyte dysfunction. Finally, the excessive activity reported in demyelinated axons may promote hyperexcitability. We hypothesize that the extracellular potassium rise generated during epileptiform activity may be amplified by the presence of axons without appropriate myelin coating and by alterations in oligodendrocyte function. This process could facilitate the triggering of recurrent spontaneous seizures in areas of altered myelination and could result in further demyelination, thus promoting epileptogenesis.

Periods of synchronized myelin changes shape brain function and plasticity

“…-have been reported in autism spectrum disorders, epilepsy, schizophrenia, depression and Alzheimer's disease 25,26,138 . These observations are consistent with recent genome-wide association studies and transcriptome analyses that have linked mutations in myelin-specific genes or dysregulation of oligodendrocyte gene expression to diseases thought to be primarily of neuronal aetiology [27][28][29][30][31][32] .…”

“…4A). Whether deficits in myelin formation and maintenance contribute to the changes underlying some of these disorders is receiving increasing consideration 138,139 .…”

A Whole-Brain 3D Myeloarchitectonic Atlas: Mapping the Vogt-Vogt Legacy to the Cortical Surface

“…Thus, classification of cortical myeloarchitectonic areas and patterns through parcellation and MGL mapping has significant translational potential in both health and disease. Future neuroimaging studies may leverage this information to elucidate pathological whole-brain myeloarchitectural patterns, for instance in multiple sclerosis (Rahmanzadeh et al, 2021) and epilepsy (de Curtis et al, 2021; Drenthen et al, 2019).…”

Infantile status epilepticus disrupts myelin development

“…Well-developed white matter serves a crucial role in signal conduction and timing of the neuronal firing, while myelin loss may change excitability and induce axonal vulnerability (reviewed in ( Bercury and Macklin, 2015 ; de Curtis et al, 2021 ; Seidl, 2014 )). In this study, we addressed myelin integrity in the animal model of early-onset TLE and its potential impact on functional connectivity.…”