Neuroscientists Create Maps of the Brain After Traumatic Brain Injury

Article found on Science Daily

Every year in the United States, nearly two million Americans sustain a traumatic brain injury (TBI). Survivors can live with lifelong physical, cognitive and emotional disabilities. Currently, there are no treatments.

One of the biggest challenges for neuroscientists has been to fully understand how a TBI alters the cross-talk between different cells and brain regions.

In the new study, researchers improved upon a process called iDISCO, which uses solvents to make biological samples transparent. The process leaves behind a fully intact brain that can be illuminated with lasers and imaged in 3D with specialized microscopes.

The researchers focused on connections to inhibitory neurons, because these neurons are extremely vulnerable to dying after a brain injury. The team first looked at the hippocampus, a brain region responsible for learning and memory. Then, they investigated the prefrontal cortex, a brain region that works together with hippocampus. In both cases, the imaging showed that inhibitory neurons gain many more connections from neighboring nerve cells after TBI, but they become disconnected from the rest of the brain.

To get a closer look at the damaged brain connections, the research team devised a technique for reversing the clearing procedure and probing the brain with traditional anatomical approaches.

The findings surprisingly showed that the long projections of distant nerve cells were still present in the damaged brain, but they no longer formed connections with inhibitory neurons.

The researchers then wanted to determine if it was possible for inhibitory neurons to be reconnected with distant brain regions. To find out, the research team transplanted new interneurons into the damaged hippocampus and mapped their connections, based on the team’s earlier research demonstrating interneuron transplantation can improve memory and stop seizures in mice with TBI.

The new neurons received appropriate connections from all over the brain. While this may mean it could be possible to entice the injured brain to repair these lost connections on its own, the researcher said learning how transplanted interneurons integrate into damaged brain circuits is essential for any future attempt to use these cells for brain repair.

“Our study is a very important addition to our understanding of how inhibitory progenitors can one day be used therapeutically for the treatment of TBI, epilepsy or other brain disorders,” said the researcher.

Hippocampal Position and Orientation as Prognostic Biomarkers for Post-Traumatic Epileptogenesis – an Experimental Study in Rat Lateral Fluid-Percussion Model

Abstract found on Wiley Online Library

Objective: To identify prognostic biomarkers for post-traumatic epileptogenesis derived from parameters related to the hippocampal position and orientation.

Methods: Data was derived from two pre-clinical magnetic resonance imaging (MRI) follow-up studies: EPITARGET (156 rats) and EpiBioS4Rx (UEF Cohort 43 rats). Epileptogenesis was induced with lateral fluid-percussion induced traumatic brain injury (TBI) in adult male Spraque-Dawley rats. In the EPITARGET cohort, ??2T2?-weighted MRI was performed at 2 d, 7 d and 21 d and in the EpiBioS4Rx cohort at 2 d, 9 d, 30 d, and 5 months post-TBI. Both hippocampi were segmented using convolutional neural networks. The extracted segmentation mask was used for a geometric construction, extracting 39 parameters that described the position and orientation of the left and right hippocampus. In each cohort, we assessed the parameters as prognostic biomarkers for post-traumatic epilepsy (PTE) both individually, using repeated measure ANOVA, as well as in combination using random forest classifiers.

Results: The extracted parameters were highly effective in discriminating between sham-operated and TBI rats in both the EPITARGET and EpiBioS4Rx cohorts at all timepoints (t) (balanced accuracy > 0.9). The most discriminating parameter was the inclination of the hippocampus ipsilateral to the lesion at ?=2t=2 d and the volumes at ??7t?7 d after TBI. Furthermore, in the EpiBioS4Rx cohort, we could effectively discriminate epileptogenic vs. non-epileptogenic animals with a longer MRI follow-up, at ?=150t=150 d (AUC 0.78, balanced accuracy 0.80, p=0.0050), based on the orientation of both hippocampi. We found that the ipsilateral hippocampus rotated outward on the horizontal plane, while the contralateral hippocampus rotated away from the vertical direction.

Significance: We demonstrate that assessment of TBI-induced hippocampal deformation by clinically translatable MRI methodologies detects subjects with prior TBI as well as those at high-risk of PTE, paving the way towards subject stratification for antiepileptogenesis studies.

CURE Epilepsy Discovery: Preventing Post-Traumatic Epilepsy May be Possible by Inhibiting Two Inflammation-Based Signaling Pathways

Key Points:

  • For his CURE Epilepsy “Prevention of Acquired Epilepsies” grant, Dr. Xiaoming Jin and his team sought to understand the role of two related signaling pathways called TLR4 and RAGE, in the development of post-traumatic epilepsy (PTE) following brain injury in mice [1-3].
  • The team found that inhibiting either of these two inflammatory pathways soon after injury decreased seizure susceptibility as well as frequency.
  • In addition, inhibiting these pathways changed the levels of three types of brain cells, improving neuron survival and reducing brain tissue scarring.
  • These results suggest that inhibiting either of these inflammatory pathways may impede the development of PTE. 


Deep Dive:

Post-traumatic epilepsy (PTE) is one of the most devasting consequences of a traumatic brain injury (TBI). Depending on the severity of the injury, anywhere from 5% to 53% of people with TBI may develop PTE [1,4,5], and, unfortunately, PTE is often resistant to currently available antiseizure medications. Importantly, there is often a span of time between the injury and the onset of epilepsy, known as the “latent period,” during which treatments could be initiated to either reduce the chance of or completely prevent PTE [1,6].

One potential cause of PTE is inflammation in the brain. In hopes of preventing PTE or decreasing the  probability of it developing, researchers are working to understand the role of inflammation in the brain as a means to prevent PTE. The inflammatory process is regulated by “parent” proteins that, when activated, bind to target receptors to subsequently activate downstream signaling pathways. One of these “parent” proteins is known as HMGB1, and two of its receptor partner systems are TLR4 and RAGE [7]. All three of these proteins have been implicated in development of seizures, a process called epileptogenesis [8,9]. With funding from CURE Epilepsy, Dr. Jin and his team at the Stark Neurosciences Institute of the Indiana University School of Medicine sought to determine if these proteins also played a role in PTE and whether inhibiting these pathways could represent an approach for reducing the likelihood of epileptogenesis and PTE following TBI [10].

To test their hypothesis, the researchers first confirmed that the expression of HMGB1, RAGE, and TLR4 increased in three types of brain cells (neurons [“regular” nerve cells], astrocytes, and microglia) in their PTE mouse model [3,10] soon after injury. After completing this initial experiment, the team evaluated the ability of inhibitors of TLR4 or RAGE to lower seizure susceptibility and frequency in their PTE mice.  

For TLR4, they used the drug TAK242 (also known as resatorvid), a substance that has previously been employed by other researchers to prevent epileptogenesis in a different rodent model of PTE [11]. For RAGE, the researchers used an antibody (mAb) specifically designed in the laboratory to bind to the RAGE protein (RAGE mAb) and inhibit its signaling pathway. The team found that when either substance (TAK242 or RAGE mAb) was administered to mice one week after injury, the treated PTE mice were less prone to having tonic-clonic seizures and remained seizure-free for a longer period of time [10]. 

To provide additional evidence for the role of RAGE signaling in PTE, the researchers used mice in which RAGE had been genetically deleted (“RAGE knockout mice”). Data revealed that the RAGE knockout mice exhibited a higher threshold of seizure susceptibility and a longer period of seizure freedom after a TBI than their control counterparts.

The fact that similar results were obtained from two different, but complementary, types of experiments (pharmacological and genetic) provide corroboration for the critical roles that RAGE and TLR4 play in the onset of PTE. 

Once Dr. Jin’s team demonstrated that inhibiting TLR4 or RAGE seemed to have therapeutic value, they sought to understand what would happen at the cellular level when these two pathways were pharmacologically inhibited in their PTE model. Mice that were treated with either TAK242 or RAGE mAb one week after injury lost fewer neurons compared to those that were not treated with one of the two substances. Along with neurons, the team examined astrocytes and microglia. These cells mediate a process known as gliosis, a type of nonspecific scarring of brain tissue generated in response to brain damage that can lead to drug-resistant seizures [12]. Analogous to the results with neurons, there was much less gliosis in treated versus untreated PTE mice.  

Research to assess what happens in the brain after TBI is crucial to discovering possible therapeutic options to prevent epilepsy from developing. Data from Dr. Jin’s lab further validate the roles of HMGB1, its receptors TLR4 and RAGE, and their downstream inflammatory pathways in the PTE process itself, including cellular level changes, and how blocking either of these pathways may one day prevent PTE.


Literature Cited:

  1. Golub, V.M. & Reddy, D.S. Post-traumatic epilepsy and comorbidities: advanced models, molecular mechanisms, biomarkers, and novel therapeutic interventions. Pharmacol. Rev. 2022; 74(2): 387-438.
  2. Pitkänen, A. & McIntosh, T.K. Animal models of post-traumatic epilepsy. J. Neurotrauma 2006; 23(2): 241-261.
  3. Ping, X. & Jin, X. Chronic posttraumatic epilepsy following neocortical undercut lesion in mice. PLoS One 2016; 11(6): e0158231.
  4. Frey, L.C. Epidemiology of posttraumatic epilepsy: a critical review. Epilepsia 2003; 44(s10):11-17.
  5. Lowenstein, D.H. Epilepsy after head injury: an overview. Epilepsia 2009; 50(Suppl. 2): 4-9.
  6. Dulla, C.G. & Pitkänen, A. Novel approaches to prevent epileptogenesis after traumatic brain injury. Neurotherapeutics 2021; 18(3): 1582-1601.
  7. Yang, H. et al. Targeting inflammation driven by HMGB1. Front. Immunol. 2020; 11: 484.
  8. Friedman, A. and Dingledine, R. Molecular cascades that mediate the influence of inflammation on epilepsy. Epilepsia 2011; 52(Suppl 3): 33-39.
  9. Maroso, M. et al. Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures. Nat. Med. 2010; 16(4): 413-419.
  10. Ping, X. et al. Blocking receptor for advanced glycation end products (RAGE) or toll-like receptor 4 (TLR4) prevents posttraumatic epileptogenesis in mice. Epilepsia 2021; 62(12): 3105-3116.
  11. Zhang, D. et al. TLR4 inhibitor resatorvid provides neuroprotection in experimental traumatic brain injury: implication in the treatment of human brain injury. Neurochem. Int. 2014; 75: 11-18.
  12. Losi, G., Cammarota, M. & Carmignoto, G. The role of astroglia in the epileptic brain. Front. Pharmacol. 2012; 3(132): 1-13.

Epilepsy Research News: April 2022

This month in Epilepsy Research News, we highlight an interesting study of 39 products containing cannabidiol (CBD), such as beverages and oils, which found that the majority were inaccurately labeled. Next, we share the announcement of the first FDA-approved drug, Ztalmy®, to treat seizures for CDLK5 deficiency disorder (CDD), a rare epilepsy caused by mutations in the CDKL5 gene, in children two years of age and older.

In pediatrics news, we share a study that found that pediatric patients with drug-resistant epilepsy that received vagus nerve stimulation and antiseizure medications (ASMs), had lower hospital costs compared to those using ASM alone. Additionally, another study found that assessing the number of days that children are minimally impacted by seizures may be a more appropriate method of evaluating severe childhood epilepsies than measuring seizure frequency alone when determining a patient’s quality of life.

Switching gears, we report on the development of a system that uses specialized sound waves to release medication into specific areas of the brain to stop seizure activity. Finally, a group of researchers reports the development of an animal model of post-traumatic epilepsy (PTE) that has spontaneous seizures after traumatic brain injury as well as behavioral disturbances which can occur in people with PTE.

Summaries of the above mentioned information follow below.

Inaccuracy of Non-Prescription Cannabidiol (CBD) Product Labeling: An analysis of 39 products containing CBD (a non-intoxicating substance found in the cannabis sativa plant) finds that most of these products were inaccurately labeled, and in fact, may contain measurable amounts of THC (an intoxicating substance found in cannabis sativa). The study analyzed the contents of CBD-infused beverages, oils, and other products, including chocolate bars, honey, coconut oil, transdermal patches, and more. Of these products, only 15.4 percent were accurately labeled. Unreliable labeling raises concerns about potential exposure to unwanted substances like THC and inconsistent exposure to CBD if used for medicinal purposes. Learn more

FDA Approves Ztalmy® (Ganaxolone) for CDLK5 Deficiency Disorder (CDD): The FDA has approved a new therapy to treat seizures for CDD, a rare epilepsy caused by mutations in the CDKL5 gene. The drug, Ztalmy (ganaxolone), manufactured by Marinus Pharmaceuticals, is now approved to treat seizures associated with CDD in patients 2 years of age and older. This medication is the first FDA-approved treatment specifically for CDD. It is expected to be available for patients in July 2022. Learn more

Vagus Nerve Stimulation (VNS) Lowers Costs of Care for Children with Uncontrolled Epilepsy: A new study examined a population of pediatric patients with drug-resistant epilepsy and found that the patients who received VNS, when used with antiseizure medications (ASM), had lower hospital costs compared to the use of ASMs alone. Vagus nerve stimulators are implantable devices that send mild electrical pulses to the brain by stimulating the vagus nerve.  The researchers note that these results are important because they show lower costs to the health care system following VNS surgery. Learn more

Measuring Quality of Life in Children with Epilepsy: Researchers have found that assessing the days children are minimally impacted by seizures may be a more appropriate method of evaluating severe childhood epilepsies than measuring seizure frequency alone when determining quality of life. The researchers worked with patient advocacy organizations and developed a questionnaire that was distributed to primary caregivers of children with developmental and epileptic encephalopathies (DEEs), a group of severe epilepsies that often have a genetic basis. The researchers found that quality of life scores were strongly associated with the number of days minimally disrupted by seizures rather than seizure frequency alone, an often-used measure of quality of life. These results suggest the need to re-evaluate how disease severity is measured in DEEs. Learn more

Development of Drug Delivery System to Control Seizures: Researchers have developed a system that uses specialized sound waves to release medication into specific areas of the brain to stop seizure activity. So far, the researchers have tested the system in a laboratory setting but envision creating a device that could be triggered by a person when they have an aura before the onset of a seizure, or automatically by a system that detects seizure activity beginning in the brain, activating the release of the drug to stop the seizure from developing. Though the researchers note that further studies are necessary to determine the utility and safety of the technology in humans, they state that this novel new way of delivering drugs could be an effective solution, and a life-changer for some patients with epilepsy. Learn more

Development of an Animal Model of Post-Traumatic Epilepsy (PTE): A team of researchers have created a novel animal model that has spontaneous recurrent seizures after brain injury, similar to the spontaneous recurrent seizures that occur in humans who develop epilepsy following a traumatic brain injury, a type of epilepsy called PTE. In addition to changes in brain activity, the team also found changes in the animals’ behavior and degeneration of neurons in the brain. The team states that this model provides a vital tool to further understand PTE and can be used to test medical treatments to prevent seizures and other neuropsychiatric conditions in military personnel. Learn more

Susceptibility to Epilepsy After Traumatic Brain Injury is Associated with Preexistent Gut Microbiome Profile

Abstract found in Wiley Online Library


Objective: We examined whether post-traumatic epilepsy (PTE) is associated with measurable perturbations in gut microbiome.

Methods: Adult Sprague-Dawley rats were subjected to Lateral Fluid Percussion Injury (LFPI). PTE was examined 7 months after LFPI, during a 4-week continuous video-EEG monitoring. 16S ribosomal ribonucleic acid gene sequencing was performed in fecal samples collected before LFPI/sham-LFPI and 1 week, 1 and 7 months thereafter. Longitudinal analyses of alpha diversity, beta diversity, and differential microbial abundance were performed. Short-chain fatty acids (SCFA) were measured in fecal samples collected before LFPI by Liquid Chromatography with Tandem Mass Spectrometry.

Results: Alpha diversity changed over time in both LFPI and sham-LFPI subjects; no association was observed between alpha diversity and LFPI, the severity of post-LFPI neuromotor impairments, and PTE. LFPI produced significant changes in beta diversity and selective changes in microbial abundances associated with the severity of neuromotor impairments. No association between LFPI-dependent microbial perturbations and PTE was detected. PTE was associated with beta diversity irrespective of timepoint vis-à-vis LFPI, including at baseline. Preexistent fecal microbial abundances of four amplicon sequence variants belonging to the Lachnospiraceae family (three enriched and one depleted) predicted the risk of PTE with area under the curve (AUC) of 0.73. Global SCFA content was associated with the increased risk of PTE with AUC of 0.722, and with 2-Methylbutyric (depleted), valeric (depleted), isobutyric (enriched) and isovaleric (enriched) acids being most important factors (AUC of 0.717). When the analyses of baseline microbial and SCFA compositions were combined, AUC to predict PTE increased to 0.78.

Significance: While lateral fluid percussion injury produces no perturbations in the gut microbiome that are associated with PTE, the risk of PTE can be stratified based on preexistent microbial abundances and short-chain fatty acid content.

Researchers Create Breakthrough Model For Helping Patients With Post-Traumatic Epilepsy

Article published in Texas A&M Today

TBI is among the leading causes of injury-related death and disability in the United States, with an estimated 5 million people living with the challenges of a long-term TBI-related disability. With symptoms ranging from “mild” to “severe,” individuals who suffer from TBIs can develop a wide range of long-term consequences such as poor motor balance, depression, post-traumatic stress disorder (PTSD), dementia, epilepsy and premature death.

Spontaneous recurrent seizures (SRS) may occur in the months or years following the injury, which is commonly referred to as post-traumatic epilepsy (PTE). Currently, there is no effective treatment or cure for PTE; therefore, there is a critical need to develop animal models to help further understand and assess the mechanisms and interventions related to TBI-induced epilepsy.

  1. Samba Reddy, a professor in the Department of Neuroscience and Experimental Therapeutics at the Texas A&M University College of Medicine, and his team have created a novel experimental model that is able to successfully replicate the same spontaneous recurrent seizures that occur in humans who develop TBI-induced epilepsy. Their findings were recently published in the journal Experimental Neurology. This research, funded by grants from the Department of Defense, can be used to test medical treatments to prevent seizures and other neuropsychiatric conditions in military personnel.

This is a game-changing model on many fronts, Reddy said.

In addition to long-term EEG analysis, Reddy’s team profiled a longitudinal change in the brain in two other major areas: brain tissue histology and behavioral patterns. Behaviorally, the test subjects showed sensory and behavioral functional deficits as well as long-term memory dysfunction — too often overlooked facets of the condition in humans that can negatively affect the quality of life and independent functioning.

In neuropathology analysis, the researchers’ findings showed degeneration of principal neurons and a loss of inhibitory interneurons in the brain. Interneurons normally function as a brake to slow electrical activity, so loss of these special neurons causes excess electrical activity in the brain. There was also an increased incidence of mossy fiber sprouting, which is a hallmark cellular change found in temporal lobe epilepsy.

Early Posttraumatic Seizures Linked to Poor Outcomes in Moderate to Severe TBI Patients

Article published in Healio

Early posttraumatic seizures following moderate to severe TBI were linked to poorer in-hospital and long-term outcomes, including posttraumatic epilepsy, according to an Australian registry-based cohort study published in JAMA Neurology.

“The role of [early posttraumatic seizures (EPS)] in the subsequent development of recurrent unprovoked seizures, or posttraumatic epilepsy (PTE), is not well understood,” Joshua Laing, BBiomedSc, MBBS, of the department of neurosciences at Monash University, and colleagues wrote. “Early posttraumatic seizures may increase the risk of PTE. Whether treatment of EPS exerts an antiepileptogenic effect on developing PTE is largely unknown.”

Researchers evaluated risk factors for EPS and contribution to PTE, as well as associated morbidity and mortality, by collecting data from an Australian-based cohort of 15,152 adults (69% male, median age 60 years) diagnosed with moderate to severe TBI between January 2005 and December 2019, along with a 2-year follow-up.

After adjusting for confounders, researchers associated EPS with increased ICU admission and length of stay, ventilation and duration, length of hospital stay and discharge to rehabilitation facilities instead of home, but not in-hospital mortality. Outcomes in TBI admission survivors at the 2-year follow-up included mortality (RR=2.14; 95% CI, 1.32-3.46), development of PTE (RR=2.91; 95% CI, 2.22-3.81) and use of antiseizure medications (RR=2.44; 95% CI, 1.98-3.02), which were poorer for cases with EPS after adjustment for confounders.

“In this study of moderate to severe TBI inclusive of all seizures during the acute admission, just 11% of patients with EPS developed PTE, although this was significantly greater that the 3% incidence in those without EPS,” Laing and colleagues wrote.

In a related editorial, CURE Epilepsy Grantee James J. Gugger, MD, PharmD, and Ramon Diaz-Arrastia, MD, PhD, from the department of neurology at University of Pennsylvania Perelman School of Medicine, noted that while Laing and colleagues’ findings were significant, statistics may be even more alarming for PTE development following EPS.

Brivaracetam (Briviact®) Prevents the Development of Epileptiform Activity When Administered Early After Cortical Neurotrauma in Rats

Abstract, originally published in Epilepsia

Objectives: There is no effective therapy to prevent the development of posttraumatic epilepsy (PTE). Recently, we reported that administration of the antiseizure medication (ASM) levetiracetam (LEV) shortly after trauma prevented the development of epileptiform activity in two experimental models of neurotrauma. However, the time window for effective intervention with LEV may be too narrow for most clinical settings. Using the controlled cortical impact (CCI) injury model, the current study tested whether early administration of brivaracetam (BRV), an ASM with 20 times the affinity of LEV for the SV2A synaptic vesicle protein, could improve upon the antiepileptogenic action observed with LEV.

Methods: Rats (postnatal day [P] 24–32) subjected to CCI injury were given a single dose of BRV (21 or 100 mg/kg, i.p.) at one of three post-injury time points: immediately (0–2 minutes), 30 minutes, or 60 minutes. Control animals received only vehicle (0.9% saline). Posttraumatic electrographic epileptiform activity was assayed ex vivo from coronal neocortical slices collected proximal to the injury (four per rat) 3–4 weeks after injury. In this model, ictal-like burst discharges occur spontaneously or can be evoked in an “all or none” manner with applied electrical stimulation within the first 2 weeks after injury.

Results: A single dose of BRV administered to rats up to 60 minutes after traumatic brain injury (TBI) significantly reduced the development of posttraumatic epileptiform activity by (1) inhibiting the development of both evoked and spontaneous epileptiform activity, (2) raising the threshold for stimulus-evoked epileptiform discharges, and (3) reducing the intensity of epileptiform bursts that arise after cortical neurotrauma.

Significance: Clinically there has been little success preventing the development of posttraumatic epilepsy. The results of this study support the hypothesis that early intervention with briveracetam has the potential to prevent or reduce posttraumatic epileptogenesis, and that there may be a limited time window for successful prophylactic intervention.

Blocking Receptor for Advanced Glycation End Products (RAGE) or Toll-Like Receptor 4 (TLR4) Prevents Post-Traumatic Epileptogenesis in Mice

Featuring the work of CURE Epilepsy grantee Dr. Xiaoming Jin

Abstract, originally published in Epilepsia

Objective: Effective treatment for the prevention of posttraumatic epilepsy is still not available. Here, we sought to determine whether blocking receptor for advanced glycation end products (RAGE) or toll-like receptor 4 (TLR4) signaling pathways would prevent posttraumatic epileptogenesis.

Methods: In a mouse undercut model of posttraumatic epilepsy, daily injections of saline, RAGE monoclonal antibody (mAb), or TAK242, a TLR4 inhibitor, were made for 1 week. Their effects on seizure susceptibility and spontaneous epileptic seizures were evaluated with a pentylenetetrazol (PTZ) test in 2 weeks and with continuous video and wireless electroencephalography (EEG) monitoring between 2 and 6 weeks after injury, respectively. Seizure susceptibility after undercut in RAGE knockout mice was also evaluated with the PTZ test. The lesioned cortex was analyzed with immunohistology.

Results: Undercut animals treated with RAGE mAb or TAK242 showed significantly higher seizure threshold than saline-treated undercut mice. Consistently, undercut injury in RAGE knockout mice did not cause a reduction in seizure threshold in the PTZ test. EEG and video recordings revealed a significant decrease in the cumulative spontaneous seizure events in the RAGE mAb- or TAK242-treated group (p < 0.001, when the RAGE mAb or TAK242 group is compared with the saline group). The lesioned cortical tissues of RAGE mAb- or TAK242-treated undercut group showed higher neuronal densities of Nissl staining and higher densities of glutamic acid decarboxylase 67-immunoreactive interneurons than the saline-treated undercut group. Immunostaining to GFAP and Iba-1 revealed lower densities of astrocytes and microglia in the cortex of the treatment groups, suggesting reduced glia activation.

Significance: RAGE and TLR4 signaling are critically involved in posttraumatic epileptogenesis. Blocking these pathways early after traumatic brain injury is a promising strategy for preventing posttraumatic epilepsy.

Is Severe Head Injury Associated with Functional (Psychogenic) Seizures?

Abstract, published in Seizure

Objectives: The aim of the current study was to compare the frequency of significant head injuries in three groups of people with seizures [idiopathic generalized epilepsies (IGE) vs. temporal lobe epilepsy (TLE) vs. functional seizures (FS)].

Methods: This was a retrospective study. All patients with a diagnosis of IGE, TLE, or FS were recruited at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2020.

Results: One thousand and four hundred ninety-two patients were studied (559 patients with IGE, 646 people with TLE, and 287 persons with FS). Overall, 77 (5.2%) individuals of the studied people reported experiencing severe head injuries before the onset of their seizures [9 patients (1.6%) with IGE, 56 people (8.7%) with TLE, and 12 persons (4.2%) with FS; p = 0.0001]. Compared to people with IGE, the odds ratio of having a premorbid history of severe head injury in the FS group was 2.67 [95% Confidence Interval (CI): 1.11-6.40; p = 0.0280]. Compared to people with TLE, the odds ratio of having a premorbid history of severe head injury in the FS group was 0.46 (95% CI: 0.24-0.87; p = 0.0170).

Conclusion: Severe head injury is significantly associated with functional (psychogenic) seizures. However, since head injury is also a significant risk factor for focal epilepsies, it may be necessary to ascertain the diagnosis of post-traumatic seizures by obtaining a detailed clinical history and also by performing video-EEG monitoring in order to adopt an appropriate treatment strategy in these patients.