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Epilepsy As A Brain Network Disease: Implications For The Clinician

Administrator: Sanem Yilmaz

Epilepsy as a network disease
Lieven Lagae

The concept of the human brain as a network has resulted in a paradigm shift in the recognition of epilepsy as an archetypical network disease. A network representation of epilepsy offers an effective basis for understanding how seizures begin, propagate, terminate, and even have long-term neuropsychological effects. Epilepsy is considered, with seizures and interictal activity originating and propagating in networks involving neocortical, thalamo-cortical, limbic, and brainstem structures. Histopathological and neuroimaging studies including both focal and generalized epilepsies have revealed structural and functional compromise across widespread brain networks. Epileptic children frequently exhibit cognitive comorbidity and may have extensive network abnormalities beyond the epileptic zone, which may impact a variety of cognitive functions and global intelligence. Understanding the network mechanisms of epilepsy and its comorbidities allows us to identify the primary source of epilepsy in the network and predict the clinical course and long-term outcome, which aids in the selection of appropriate therapies to counteract the effect of abnormal network.

 

Neuronal connectivity in self-limited epilepsy with centrotemporal spikes
Sanem Yılmaz

The most common type of focal epilepsy in children is self-limited epilepsy with centro-temporal spikes (SeLECTS). Because of its brief, infrequent nighttime seizures, it was initially classified as benign. However, the term "benign" is no longer used because 15-30% of affected children develop neuropsychological impairment, particularly in the domains of language, cognitive, memory, and attention, the pathophysiological mechanisms of which remain unknown. In SeLECTS, diffusion tensor imaging (DTI) studies suggests the presence of subtle neurodevelopmental changes in the epileptogenic zone and distant regions. This structural reorganization most likely occurs prior to diagnosis and evolves over time, particularly in patients with cognitive impairment, implying that epileptogenic processes may interfere with brain dynamics during a critical period of development and/or normal maturation processes. Functional brain imaging reveals profound disorganization in the epileptogenic zone.   The network disorganizations may play a central and causal role in the neuropsychological impairment described in SeLECTS.

 

Neuronal connectivity in Tuberous Sclerosis Complex and related mTORopathies.
Darcy Krueger

 

In tuberous sclerosis complex (TSC), disrupted early brain development at the cellular level leads to aberrant neural connections and neurologic disorders such as epilepsy, autism spectrum disorder, and intellectual disabilities. Overactivation of the mechanistic target of rapamycin pathway causes abnormalities in cell growth, differentiation, and migration, which result in the formation of macroscopic lesions in the brain, such as tubers, radial migration lines, and subependymal nodules. Tubers are potentially epileptogenic, and approximately 50% of children with TSC develop infantile spasms. The pathophysiology of focal lesions leading to epileptic spasms is currently unknown. It is possible, however, that infantile spasms are the result of injury to a particular network, as opposed to dysfunction of a single region. Lesion network mapping identifies the network of brain regions connected to each lesion location using a normative map of functional connectivity.  Connectivity between tuber locations and the bilateral globi pallidi may be associated with the development of infantile spasms in TSC patients.

 

Brain connectivity with EEG and neuroradiologic modalities in developmental epileptic encephalopathy with spike-and-wave activation in sleep
Hasan Tekgul

Developmental epileptic encephalopathy with spike-and-wave activation in sleep (DEE-SWAS) is a spectrum of conditions characterized by various phenotypes of cognitive, linguistic, and behavioral regression associated with spike-and-wave activation in sleep (Tekgul et al. 2016). The first EEG-fMRI study on DEE-SWAS was published by De Tiege et al. (2007). DTI and EEG-fMRI studies in DEE-SWAS patients demonstrate a specific neuronal network of propagation, regardless of etiology or individual area of initial epileptic activity (Siniatchkin et al.,2013). The perisylvian/prefrontal network activation is linked to both activation of thalamocortical network and deactivation of default mode network. Since these networks appear to be important in neuropsychological processes and memory formation during sleep, a possible influence of epileptic spikes on these networks could explain neuropsychological deficits and developmental abnormalities in DEE-SWAS. The models of effective connectivity can be used to study the causal relationships at the neural level from fMRI data such as Dynamic Causal Modelling (Friston et al., 2003). Independent of aetiology and individual area of initial epileptic activity, patients with CSWS were characterized by a consistent specific neuronal network of propagation.