Seizures
Alexander R. Toftness in Incredible Consequences of Brain Injury, 2023
Genetics play a role in epilepsy, but it can sometimes be an acquired disorder. That is, if the brain changes in particular ways, someone who has never had a seizure before may begin having seizures. This process where the brain becomes capable of generating seizures is called epileptogenesis (Thijs et al., 2019). One common event that can lead to epileptogenesis is traumatic brain injury (Ding et al., 2016). This is referred to as post-traumatic epilepsy and, curiously, it often has a “silent period” of months or years between the injury and the onset of the seizures—perhaps up to 20 years in extreme cases (Piccenna et al., 2017, p. 123). More work is needed to understand it, but post-traumatic epilepsy seems to be a relatively common type of epilepsy (Semple et al., 2019). Other types of acquired epilepsy may come from tumors, strokes, parasites, and infections (Thijs et al., 2019). Epilepsy is not just a neurological disorder in which people have seizures however, as it is also affiliated with other less visible changes that may put a person at risk for heart disease, hypertension, migraine, and more (Yuen et al., 2018). But putting those complexities aside, let's focus on the major symptom which is not coincidentally the title of this chapter: seizures.
Prophylactic and Preventive Use of Antiepileptic Drugs
Stanley R. Resor, Henn Kutt in The Medical Treatment of Epilepsy, 2020
Physicians occasionally administer antiepileptic drugs (AEDs) to patients liable to have generalized tonic-clonic seizures (GTCSs), but not known to have epilepsy, with the intent to prevent a convulsive seizure. Examples of such preemptive treatment include administration of AEDs to patients with head trauma of such severity that the physiologic changes associated with an acute convulsive seizure would complicate management. Further, some patients with absences may be treated with AEDs prior to occurrence of a GTCS. Preventive treatment in these narrow contexts may be successful. However, some patients are given AEDs in an apparent attempt to interfere with the process of epileptogenesis. Examples of this prophylactic use include the routine administration of AEDs to patients with head trauma or to patients undergoing neurosurgical procedures requiring incision of the neocortex. Although prevention of seizures is a worthy goal and may be effective, prophylaxis of epilepsy is problematic and may not be effective, since no data are available to suggest that AED administration has any impact on the process of epileptogenesis.
Control of neuronal activity by electrical fields: in vitro models of epilepsy
Hans O Lüders in Deep Brain Stimulation and Epilepsy, 2020
Several of these models rely on drugs that produce imbalance between excitation and inhibition by either blocking inhibitory synaptic pathways (e.g. penicillin, picrotoxin and bicuculline, all GABA blockers) or enhancing excitatory synaptic function (e.g. kainic acid and NMDA). Other convulsive drugs increase neuronal excitability by directly effecting intrinsic membrane properties (e.g. veratridine, 4–aminopyridine). Manipulation of extracellular ionic activities (e.g. high potassium and low calcium) can also lead to spontaneous epileptiform activity in vitro, by increasing neuronal excitability and/or synchronization mechanisms. The mechanisms of in-vitro epileptogenesis have been studied extensively and are reviewed elsewhere.4,5
In vivo KPT-350 treatment decreases cortical hyperexcitability following traumatic brain injury
Published in Brain Injury, 2020
David Cantu, Danielle Croker, Sharon Shacham, Sharon Tamir, Chris Dulla
Each year in the United States, an estimated 1.7 million people sustain a traumatic brain injury (TBI). According to the Centers for Disease Control and Prevention, in 2013 there were approximately 2.5 million TBI-related emergency department visits, 282,000 TBI-related hospitalizations, and 56,000 TBI-related deaths (1). Apart from these devastating outcomes, TBI can also lead to post-traumatic epilepsy in approximately 8–33% of all civilian head injuries and up to 50% in military populations (234–5). The precise mechanisms by which TBI leads to post-traumatic epilepsy are not fully understood, yet various cellular and molecular processes have been identified as potential contributors, including inflammation, cell death, excessive glutamate release, oxidative stress, metabolic dysfunction, synaptic changes, and network reorganization (6789–10). These potentially epileptogenic events occur frequently during the latent period, which is defined as the time between an initial injury and onset of the first unprovoked seizure. In many patients, the latent period can last months or even years; however, animal models of TBI have much shorter latent periods lasting between weeks to months. Identifying the key molecular, cellular, and circuit-level changes that contribute to epileptogenesis during the latent period is of particular clinical interest since it may allow for novel therapeutic strategies.
Is there a role for microRNAs in epilepsy diagnostics?
Published in Expert Review of Molecular Diagnostics, 2020
Sebastian Bauer, Vanessa Schütz, Adam Strzelczyk, Felix Rosenow
The biological and biochemical properties of miRNAs make them promising biomarker candidates, especially regarding elucidating the risk of developing epilepsy after a brain insult. Current medical treatment of epilepsies is, with few exceptions, purely symptomatic. Anticonvulsant drugs suppress seizures but do not affect the brain pathology underlying epilepsy. Thus, an important goal of epilepsy research is the development of a causal therapy. It can be reasonably assumed that the prevention of epileptogenesis has greater prospects for success than reverting structural and functional brain alterations in established epilepsy. Therefore, biomarkers of epileptogenesis are urgently needed. Many candidates have been identified to date in experimental epilepsy models in animals [14,57,89]. In contrast, studying epileptogenesis in humans is cumbersome because the development of epilepsy after an initial precipitating injury frequently lasts for years [90] and the percentage of patients who develop epilepsy after a brain insult is relatively low [91]. However, once biomarkers of epileptogenesis are established in humans, research in this important field will be exceptionally facilitated.
Avoiding complacency when treating uncontrolled seizures: why and how?
Published in Expert Review of Neurotherapeutics, 2020
Ushtar Amin, Selim R. Benbadis
Another current focus in the mechanisms underlying epileptogenesis involves inflammation. Specifically, changes that involve alterations in gene expression, inflammation, proteins, and connectivity. A prime example of which is the mammalian target of rapamycin (mTOR) pathway (Figure 3) [36]. mTOR is a kinase that plays a role in protein synthesis. Inhibition of mTOR, cell growth, and replication, by the rapamycin analogue everolimus reduce overgrowth of malignantly transformed tubers, which can be epileptogenic [36]. A 40% dose-related seizure reduction was reported in patients with tuberous sclerosis when treated with everolimus, indicating that inhibition of mTOR results in anti-epileptogenic effects via alteration of signaling pathways and protein expression involved in causing epilepsy [37].
Related Knowledge Centers
- Brain Tumor
- Central Nervous System
- Traumatic Brain Injury
- Stroke
- Brain
- Epilepsy
- Status Epilepticus
- Seizure
- Neuron
- Neurodegenerative Disease