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Advanced Neurology Epilepsy after traumatic brain injuries

Table 1. Emerging assessment of TBI with their limitations
Emerging assessment Description Current limitations
Wearable sensor Real-time monitoring using wearable devices to track Limited validation studies for TBI-specific impairments 28
technologies movement, balance, and gait patterns
AI models Use of AI and machine learning to analyze complex datasets Lack of TBI-specific algorithms and insufficient
for diagnosis and prognosis peer-reviewed evidence 29
Cognitive digital tools Digital and gamified platforms for assessing cognitive Limited comparisons with traditional neuropsychological
functions like memory and attention tests 30
Advanced biomarker Exploration of microRNAs, extracellular vesicles, and Early-stage research; minimal clinical validation in TBI 31
analyses inflammatory markers for objective injury measures
VR-based assessments Simulated environments for testing motor, cognitive, and Insufficient studies on reliability and sensitivity for TBI
psychosocial functions populations 32
Mobile health (mHealth) Smartphone-based tools for remote symptom tracking, Limited accuracy and reproducibility studies in TBI
applications cognitive tests, and behavioral data collection contexts 33
Advanced neuroimaging Use of fMRI, DTI, and MEG to assess structural and High cost, limited accessibility, and lack of standardization
techniques functional brain changes for TBI findings 34
Abbreviations: AI: Artificial intelligence; DTI: Diffusion tensor imaging; fMRI: Functional magnetic resonance imaging;
MEG: Magnetoencephalography; TBI: Traumatic brain injury; VR: Virtual reality.

4. Deep mechanism of epilepsy during TBI role in maintaining homeostasis. Their dysfunction leads
to impaired glutamate clearance and potassium buffering,
Epilepsy resulting from TBI, also known as PTE, is a fostering a hyperexcitable environment. 37-39
significant neurological complication characterized by
recurrent, unprovoked seizures. The development of 4.3. Chronic phase: Network reorganization and
epilepsy following TBI involves complex cellular, molecular, epileptogenesis
and network-level changes in the brain. These mechanisms The chronic phase spans months to years after TBI, during
can be divided into acute, subacute, and chronic phases. which structural and functional brain remodeling occurs
4.1. Acute phase: Initial injury with abnormal synaptic plasticity, including the sprouting of
excitatory mossy fibers in the hippocampus, which creates
The acute phase involves the immediate effects of the aberrant excitatory networks. Dysregulated neurogenesis in
40
traumatic insult, which may set the stage for epileptogenesis. regions such as the dentate gyrus and apoptosis of inhibitory
Mechanical damage to brain tissue causes neuronal and glial interneurons disrupt the balance between excitation and
cell damage, axonal shearing, and BBB disruption. These inhibition, leading to heightened neuronal excitability. Changes
changes can lead to an environment prone to hyperexcitability. in voltage-gated ion channels and receptor expression (e.g.,
Massive ionic shifts, including elevated intracellular calcium GABAergic and glutamatergic receptors) shift the excitation-
and sodium and extracellular potassium, disrupt membrane inhibition balance toward hyperexcitability. The epileptiform
41
potential, leading to hyperexcitability. Excessive release of activity and seizure threshold reduction in persistent neuronal
glutamate activates NMDA and AMPA receptors, resulting hyperexcitability and lowered seizure thresholds result from
in sustained depolarization and excitotoxicity, contributing these cumulative changes, leading to recurrent seizures. In
42
to neuronal damage. 36 addition, other contributing factors such as oxidative stress,
that is, increased production of reactive oxygen species,
4.2. Subacute phase: Inflammatory and cellular contribute to neuronal damage and inflammation. Epigenetic
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responses modifications, such as DNA methylation and histone
During the subacute phase, days to weeks after injury, acetylation, may alter gene expression involved in synaptic
secondary mechanisms contribute to epileptogenesis. function and excitability. This damage to thalamocortical and
Activation of microglia and astrocytes leads to the release hippocampal networks can disrupt normal brain oscillations,
of inflammatory mediators such as cytokines (e.g., IL-1β, promoting epileptiform activity. 44
TNF-α) and chemokines. These factors modulate neuronal 5. Impact of TBI on behavior and cognitive
excitability and synaptic transmission. Persistent BBB
dysfunction allows infiltration of serum proteins and function
immune cells into the brain, exacerbating inflammation TBI has wide-ranging effects on an individual’s cognitive,
and increasing seizure susceptibility. Astrocytes play a behavioral, and physical health. Cognitive effects commonly

Volume 4 Issue 4 (2025) 5 doi: 10.36922/an.8356