Posttraumatic Seizures Research Articles

Abstract 11616: Seizures in Infants with Congenital Heart Disease

Background: Infants with congenital heart disease (CHD) may have an increased risk to develop seizures during hospitalization. Objectives: to examine the association of CHD with non-epileptic, non-traumatic seizures in hospitalized infants up to one year of age. Methods: We conducted a retrospective analysis of the U.S. National Inpatient Sample dataset (2015-2018). We used the international classification of disease-10 th version to identify infants with different types of CHD. We included infants up to one year of age. We excluded infants <35 week gestational age, infants with central nervous system or with major congenital anomalies, common trisomy or genetic disorders. We used chi square testing to examine the association of subtypes of CHD with seizures excluding post traumatic and epileptic seizures. We calculated mortality in infants with CHD who developed seizures versus those who did not have seizures. Results: There was 12,023,781 infants in the weighted sample who met our inclusion criteria. Of them, 48.7% were females, 46.7% were Caucasians, 195,685 (1.63%) were identified with a CHD and 20,565 (0.17%) suffered at least one episode of seizure during hospitalization. Seizures occurred in 4225 (2.2%) of infants with any type of CHD compared to 16,340 (0.14%) in infants with no CHD, odds ratios for seizures is 15.6 (CI: 15.2-16.5, p <0.001). The association of seizures with subtypes of CHD is shown in table-1. Among infants with CHD, 2205 infants expired during hospitalization. Mortality was higher in infants with CHD who suffered seizures (8.5%) vs. those who did not have seizures (1.0%), OR 9.6 (8.5-10.8, p <0.001). Conclusion: Infants with CHD have a higher chance to experience seizure episodes during their hospitalization and those who have seizures have higher chances of mortality during hospitalization. Further analysis is required to understand the pathological correlation between seizures and CHD and its impact on long term developmental outcomes.

Factors Affecting Outcomes in Geriatric Traumatic Subdural Hematoma in a Neurosurgical Intensive Care Unit

Geriatric patients (age ≥65 years) who sustain a traumatic brain injury have an increased risk of poor outcomes and higher mortality compared with younger cohorts. We aimed to evaluate the risk factors for discharge outcomes in a geriatric traumatic subdural hematoma population, stratified by age and pretraumatic medical comorbidities. This was a single-center retrospective cohort study of geriatric patients (N= 207). Patient charts were evaluated for factors including patient characteristics, comorbidities, injury-related and seizure-related factors, neurosurgical intervention, and patient disposition on discharge. Bivariate and multivariate analyses showed that age was nonpredictive of patient outcomes. Underlying vasculopathic comorbidities were the primary determinant of posttraumatic seizure, surgical, and discharge outcomes. Multifactor analysis showed that patients who went on to develop status epilepticus (n= 11) had a higher frequency of vasculopathic comorbidities with strong predictive power in poor patient outcomes. Our findings suggest a need to establish unique prognostic risk factors based on patient outcomes that guide medical and surgical treatment in geriatric patients.

Levetiracetam Prophylaxis for Children Admitted With Traumatic Brain Injury

BackgroundProphylactic antiseizure medications (ASMs) for pediatric traumatic brain injury (TBI) are understudied. We evaluated clinical and radiographic features that inform prescription of ASMs for pediatric TBI. We hypothesized that despite a lack of evidence, levetiracetam is the preferred prophylactic ASM but that prophylaxis is inconsistently prescribed. MethodsThis retrospective study assessed children admitted with TBI from January 1, 2017, to December 31, 2019. TBI severity was defined using Glasgow Coma Scale (GCS) scores. Two independent neuroradiologists reviewed initial head computed tomography and brain magnetic resonance imaging. Fisher exact tests and descriptive and regression analyses were conducted. ResultsAmong 167 children with TBI, 44 (26%) received ASM prophylaxis. All 44 (100%) received levetiracetam. Prophylaxis was more commonly prescribed for younger children, those with neurosurgical intervention, and abnormal neuroimaging (particularly intraparenchymal hematoma) (odds ratio = 10.3, confidence interval 1.8 to 58.9), or GCS ≤12. Six children (13.6%), all on ASM, developed early posttraumatic seizures (EPTSs). Of children with GCS ≤12, four of 17 (23.5%) on levetiracetam prophylaxis developed EPTSs, higher than the reported rate for phenytoin. ConclusionsAlthough some studies suggest it may be inferior to phenytoin, levetiracetam was exclusively used for EPTS prophylaxis. Intraparenchymal hematoma >1 cm was the single neuroimaging feature associated with ASM prophylaxis regardless of the GCS score. Yet these trends are not equivalent to optimal evidence-based management. We still observed important variability in neuroimaging characteristics and TBI severity for children on prophylaxis. Thus, further study of ASM prophylaxis and prevention of pediatric EPTSs is warranted.

Management of Post-traumatic Seizures and Epilepsy

Post-traumatic seizures and epilepsy are major complication of traumatic brain injury. Early and late and seizures have different implications for prognosis and management. Early seizures, which occur within one week of the trauma, are acute symptomatic events. On the other hand, presence of late seizures indicate epilepsy. Patients with early seizures are treated with anti-epileptic drugs(AEDs)within weeks to avoid status epilepticus, which may increase cerebral blood flow and increase intracranial pressure. Because prophylactic administration of AEDs reduces the incidence of early seizures but not late seizures, it is recommended to limit it to one week. A long-term AED administration is recommended for patients with late seizures, because late seizures represent epilepsy. AED should be selected according to the considerations of age and comorbidity that apply to other individuals with new-onset epilepsy. Since epileptic seizures often cause serious accidents, such as traffic accidents, drowning, burns, falls and others, lifestyle guidance for patients and their families is important.

Thyroid function in the subacute phase of traumatic brain injury: a potential predictor of post-traumatic neurological and functional outcomes

PurposeThat thyroid hormones exert pleiotropic effects and have a contributory role in triggering seizures in patients with traumatic brain injury (TBI) can be hypothesized. We aimed at investigating thyroid function tests as prognostic factors of the development of seizures and of functional outcome in TBI.MethodsThis retrospective study enrolled 243 adult patients with a diagnosis of mild-to-severe TBI, consecutively admitted to our rehabilitation unit for a 6-month neurorehabilitation program. Data on occurrence of seizures, brain imaging, injury characteristics, associated neurosurgical procedures, neurologic and functional assessments, and death during hospitalization were collected at baseline, during the workup and on discharge. Thyroid function tests (serum TSH, fT4, and fT3 levels) were performed upon admission to neurorehabilitation.ResultsSerum fT3 levels were positively associated with an increased risk of late post-traumatic seizures (LPTS) in post-TBI patients independent of age, sex and TBI severity (OR = 1.85, CI 95% 1.22–2.61, p < 0.01). Measured at admission, fT3 values higher than 2.76 pg/mL discriminated patients with late post-traumatic seizures from those without, with a sensitivity of 74.2% and a specificity of 60.9%. Independently from the presence of post-traumatic epilepsy and TBI severity, increasing TSH levels and decreasing fT3 levels were associated with worse neurological and functional outcome, as well as with higher risk of mortality within 6 months from the TBI event.ConclusionsSerum fT3 levels assessed in the subacute phase post-TBI are associated with neurological and functional outcome as well as with the risk of seizure occurrence. Further studies are needed to investigate the mechanisms underlying these associations.

Etiological profile of new-onset seizures among adult Egyptians

BackgroundNew-onset seizure (NOS) is defined as the first seizure within a 24-h period ever experienced by the patient. A first-ever seizure can be the first manifestation of epilepsy. Or it may be a symptom of a brain tumor, a systemic disorder, an infection, or a syndrome that deserves special attention and treatment. This study aims to identify the etiology of NOS among different age and sex groups of adult Egyptian patients. A hundred and twenty adult Egyptian patients (> 18 years) presented with acute NOS were enrolled in a hospital-based cross-sectional observational study from the emergency room and neurology outpatient clinics of our hospitals within a time period of 6 months from March till September 2018. All patients were subjected to neurological examination, laboratory, neuroimaging, and electroencephalogram investigations.ResultsAmong 120 adult patients presented with NOS, males were prevalent (63%). Older adults (age group > 55 years) were the most prevalent cohort (60%). Cerebrovascular diseases (CVDs) were the most common identified etiology of NOS (44.17%), followed by idiopathic epilepsy syndrome (18.33%), symptomatic mainly “metabolic” (11%), brain tumors (9.17%), post-traumatic epilepsy (6.67 %), encephalitis (5.83%), and cryptogenic (5%). Idiopathic epilepsy syndrome was the most common etiology (55.56%) of new-onset seizures among the young adult age group (< 36 years), while CVDs were the most common etiology (65.28%) among older adults (> 55 years). Also, CVDs were the most common etiology among males (43.4%) as well as females (45.4%). However, male predominance was the highest among post-traumatic seizures (87.5%). And female predominance was the highest among brain tumors identified etiology of NOS (54.5%).ConclusionNOS among adults are prevalent in elder males. CVDs are the most commonly identified etiology of adult NOS across males and females. Idiopathic epilepsy syndromes are the predominant etiology among younger adults.

Medico-legal study of post-traumatic seizures and epilepsy in patients with traumatic brain injury in El Demerdash and Ain Shams Specialized Hospitals (2017 -2018)

Background: Traumatic brain injury (TBI) is one of the most leading causes of deaths and disability among youth worldwide. Post-traumatic seizures (PTS) and post-traumatic epilepsy (PTE) are important catastrophic complications of TBI. Epilepsy has important medico-legal aspects for both the patient and the physician. Aim of the study: to identify forms of post traumatic seizures (generalized, focal, or focal followed by secondary generalized), site of epileptic focus, nature of brain injury that caused their occurrence, risk factors for epilepsy occurrence and medico-legal importance of PTS. Methods: A prospective cross-sectional study was conducted including patients with PTS and PTE who presented to El Demerdash and Ain shams Specialized Hospitals during the study period. Data were collected from patients by a questionnaire and from clinical sheets. Patients were classified into three groups according to time of occurrence of PTS. Results: A total of 77 patients were included. Cases were mostly in the age group less than 45 years old. Male patients were more represented in the study (64.9%). Transportation injuries were the most prominent pattern of TBI followed by blunt trauma (29.9%), open head injuries (13%), fall from height (13%) and polytrauma (1.3%). The most common affected site was frontal area of the brain (51.9%) followed by temporal region (45.5%). Associated complications included intra-cranial hemorrhage (87%) and skull fracture (35.1%). Immediate seizures were recorded in 9.1 % of the studied patients compared to 26% with early PTS. Patients with late PTS were the majority accounting for 64.9% of study patients of whom 50% with late PTS from the start. Most cases experienced generalized seizures attacks (59.7%) followed by focal with secondary generalization seizures attacks in (27.3%) and the least were with focal seizures attacks (13.0%). EEG showed abnormal activity in (62.3%) of patients and normal activity in (37.7%). Conclusion: Post-traumatic seizures and epilepsy are an important well-known sequel of traumatic brain injury with important medico-legal aspects. Pattern of head injury and site of traumatic area are important risk factors in occurrence of PTS and EEG abnormal activity is an important predictor for occurrence of PTS as well.

Abstract 28: Prognostic value of baseline and early changes of circulating cell-free (cf)DNA in the neoadjuvant setting of early stage colon cancer (CC)

Abstract Introduction Circulating tumour (ct)DNA is an indicator of minimal residual disease and negative prognostic factor in stage II-III CC treated with surgery +/- adjuvant chemotherapy. No study, however, has ever analysed the prognostic value of this biomarker in CC patients (pts) treated with neoadjuvant chemotherapy. We sought to evaluate the prognostic value of baseline and early, on-treatment changes of cfDNA and ctDNA in stage II-III CC pts who were treated with one cycle of neoadjuvant FOLFOX chemotherapy followed by surgery +/- adjuvant FOLFOX chemotherapy in the PePiTA trial. Methods PePITA was a multicentre, single-arm, prospective phase II trial aiming to test in vivo tumour chemosensitivity as assessd by metabolic response using 18F-FDG PET/CT scan of early stage CC and to evaluate its association with survival outcome (NCT00994864). Plasma samples were prospectively collected at baseline and 2 weeks (ie, after one cycle of neoadjuvant FOLFOX chemotherapy). cfDNA was isolated with the QIAmp circulating nucleic acid kit (Qiagen), and quantified with the Qubit fluorometer (Life-Technologies). cfDNA samples were bisulfite converted using the EZ DNA Methylation-Gold™ Kit (Zymo Research), with NPY and WIF1 being selected as universal methylation markers for ctDNA and analysed with digital droplet (dd)PCR technology. Data from ddPCR were processed with the QuantaSoft V1.6 software (BioRad). The primary outcome measure was 3-year disease-free survival (DFS). Receiver operating characteristics curve analyses, Kaplan-Meier method, cox proportional hazards models and log-rank tests were used. Statistical analyses were carried out with the SPSS for MacOS version 25.0 (SPSS Inc). Results 80 pts were included (ypStage I-II 56%, ypStage III 44%). After a median follow-up of 52.5 months, 3-year DFS was 80% (95%CI 71.2-90.8) and 5-year OS 84% (95%CI 75.2-94.9). Pts with high (≥1.2 ng/µl) baseline cfDNA level had worse 3-year DFS (48% vs 80%; HR 2.72, 95%CI 1.02-7.25; p=0.036) and 5-year OS (71% vs 90%; HR 5.36, 95%CI 1.14-25.28; p=0.017) than those with low baseline cfDNA level. In a multivariable analysis (including sex, ypStage and CEA), baseline cfDNA was the only factor showing a trend towards statistical significance (HR DFS 2.6, 95%CI 0.96-7.01; p=0.059; HR OS 4.65, 95%CI 0.97-22.32; p=0.055). Early changes of cfDNA (Δ ≥11%) after one cycle of neoadjuvant FOLFOX chemotherapy failed to predict survival (HR DFS 1.08, 95%CI 0.42-2.81; p=0.873; HR OS 0.68, 95%CI 0.19-2.39; p=0.543). ctDNA analyses are ongoing and will be presented at the meeting. Conclusions For the first time, we have shown that baseline cfDNA may predict survival outcome in early stage CC pts treated with neoadjuvant chemotherapy. Pending confirmation in larger series, testing for cfDNA at baseline could help select high-risk pts who may benefit from neoadjuvant, FOXTROT-like, treatment strategies. Citation Format: Giacomo Bregni, Elena Trevisi, Chiara Senti, Andrea Pretta, Caroline Vandeputte, Pashalina Kehagias, Elena Acedo Reina, Amélie Deleporte, Paraskevas Gkolfakis, Jean-Luc Van Laethem, Philippe Vergauwe, Marc Van den Eynde, Guido Deboever, Jos Janssens, Gauthier Demolin, Stephane Holbrechts, Marylene Clausse, Thierry De Grez, Marc Peeters, Lionel D'Hondt, Karen Geboes, Tatiana Besse-Hammer, Alexis Buggenhout, Françoise Rothé, Patrick Flamen, Alain Hendlisz, Francesco Sclafani. Prognostic value of baseline and early changes of circulating cell-free (cf)DNA in the neoadjuvant setting of early stage colon cancer (CC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 28.

Incidence of Epilepsy and Drug Dependence after Post Traumatic Contusions Managed Conservatively

contusions managed conservatively.&#x0D; Material and Methods: A prospective observational study was carried out in, Punjab Institute of Neurosciences, Lahore. A total of 97 patients, from 15-65 years, who were diagnosed with cerebral contusions and being managed conservatively were enrolled from July 2019 to December 2019. They were followed-up for 12 – 18 months.&#x0D; Results: A total of 23% patients developed early post-traumatic seizures (PTS) and 11% of patients developed late post-traumatic seizures with mild to moderate brain injury.6% of patients with early PTS used antiepileptic drugs (AED) for at least three months during follow up and 7% with late PTS used AED. 8% of patients developed late PTS without any early PTS. The results of our study show that among 23% early PTS and 11% late PTS only 3 % actually required to use AED for at least 6months. To prevent this, 3% of the population 44% were using AED supplementary.&#x0D; Conclusion: In our study, the incidence of early and late PTS is comparable to the other studies. The non-judicious use of the anti-epileptic drug is common in our country which leads to an increase in the risk of drug resistance and cost-intensive for poor patients in developing countries as prophylactic and excessive use of anti-epileptics does not affect the PTE.

A Scalable Model to Study the Effects of Blunt-Force Injury in Adult Zebrafish.

Blunt-force traumatic brain injuries (TBI) are the most common form of head trauma, which spans a range of severities and results in complex and heterogenous secondary effects. While there is no mechanism to replace or regenerate the lost neurons following a TBI in humans, zebrafish possess the ability to regenerate neurons throughout their body, including the brain. To examine the breadth of pathologies exhibited in zebrafish following a blunt-force TBI and to study the mechanisms underlying the subsequent neuronal regenerative response, we modified the commonly used rodent Marmarou weight drop for the use in adult zebrafish. Our simple blunt-force TBI model is scalable, inducing a mild, moderate, or severe TBI, and recapitulates many of the phenotypes observed following human TBI, such as contact- and post-traumatic seizures, edema, subdural and intracerebral hematomas, and cognitive impairments, each displayed in an injury severity-dependent manner. TBI sequelae, which begin to appear within minutes of the injury, subside and return to near undamaged control levels within 7 days post-injury. The regenerative process begins as early as 48 hours post-injury (hpi), with the peak cell proliferation observed by 60 hpi. Thus, our zebrafish blunt-force TBI model produces characteristic primary and secondary injury TBI pathologies similar to human TBI, which allows for investigating disease onset and progression, along with the mechanisms of neuronal regeneration that is unique to zebrafish.

Neuroinflammation and Neuronal Loss in the Hippocampus Are Associated with Immediate Posttraumatic Seizures and Corticosterone Elevation in Rats.

Hippocampal damage after traumatic brain injury (TBI) is associated with late posttraumatic conditions, such as depression, cognitive decline and epilepsy. Mechanisms of selective hippocampal damage after TBI are not well understood. In this study, using rat TBI model (lateral fluid percussion cortical injury), we assessed potential association of immediate posttraumatic seizures and changes in corticosterone (CS) levels with neuroinflammation and neuronal cell loss in the hippocampus. Indices of distant hippocampal damage (neurodegeneration and neuroinflammation) were assessed using histological analysis (Nissl staining, Iba-1 immunohistochemical staining) and ELISA (IL-1β and CS) 1, 3, 7 and 14 days after TBI or sham operation in male Wistar rats (n = 146). IL-1β was elevated only in the ipsilateral hippocampus on day 1 after trauma. CS peak was detected on day 3 in blood, the ipsilateral and contralateral hippocampus. Neuronal cell loss in the hippocampus was demonstrated bilaterally; in the ipsilateral hippocampus it started earlier than in the contralateral. Microglial activation was evident in the hippocampus bilaterally on day 7 after TBI. The duration of immediate seizures correlated with CS elevation, levels of IL-1β and neuronal loss in the hippocampus. The data suggest potential association of immediate post-traumatic seizures with CS-dependent neuroinflammation-mediated distant hippocampal damage.

Early discharge after cryoablation procedure: is it safe?

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Discharge after overnight hospital stay is standard procedure in patients submitted to elective atrial fibrillation (AF) ablation. Taking into consideration the low rate of cryoablation procedure complications could the same day discharge be an option? Purpose To access the safety of same day discharge of patients submitted to AF cryoablation. Methods Single-center retrospective study of consecutive pts admitted to elective AF cryoablation in a tertiary center between February 2017 and November 2020. Patients were divided into two groups: same day discharge and next day discharge. Only patients submitted to ablation until 4 p.m. were included. Complication rates were obtained up to six months after the procedure. Complications were defined as death, pericardial tamponade, hematoma requiring evaluation and/or intervention, major bleeding requiring transfusion, hospital admission related to the procedure. Results One hundred fifty-four pts were included, with a mean age of 61 ± 10.9 years, 66.2% were males, 18.2% with diabetes, 65.6% with dyslipidemia, 77.9% with hypertension, 10.4% with chronic kidney disease KDIGO stage 3 or more. Median follow-up of 436 (IQ 178 – 729) days. Most of the pts had paroxysmal (73.4%) and persistent short duration AF (23.4%). Sixty-two pts (40.3%) were early discharged and there were no differences between the two groups regarding epidemiological and clinical characteristics (p = NS). A very low rate of complications in both groups was observed, occurring in 6.5% of pts with early discharge and in 8.7% of pts in overnight stay, without statistical significance between the two groups (p = 0.61). The most frequent complications were local hematoma (5 pts, 2 in early discharged group), pericardial effusion (3 pts, all in overnight stay), femoral pseudo-aneurism (2 pts, 1 in each group) and arteriovenous fistula (1 pt in overnight stay group). The type of complications did not differ between the two groups (p = 0.51). Two pts died during the follow up, unrelated with the procedure. In addition, no difference in success rate and arrhythmic recurrence was observed between the two groups. (p = NS) Conclusion Our study suggests that is safe to early discharge pts submitted to AF ablation, reducing the hospital stay length in selected pts. Larger studies are needed to confirm this data before routine implementation of this strategy.

Dysregulation of soluble immune checkpoint proteins in newly-diagnosed early breast cancer patients.

556 Background: Checkpoint proteins regulate the immune system. Breast cancer (BC) cells exploit the up-regulation or down-regulation of these proteins to evade anti-tumor immune responses. Soluble forms of immune checkpoint molecules (ICM) can be measured in human plasma, however their biological and clinical significance remains essentially unknown. The aim of the present analysis was to measure the pre-treatment ICM in newly- diagnosed BC patients (pts) and compare them to healthy controls. Methods: Soluble forms of ICM, as well as cytokines and chemokines, were measured using Multiplex bead array and ELISA technologies. Plasma samples from 98 BC pts and 45 healthy controls were analyzed for each protein. Data was prospectively obtained. Measured levels were compared between BC pts and healthy controls using a non-parametric test (Mann-Whitney). P-values below 0.05 were considered statistically significant. Results: Soluble stimulatory molecules GITR (p &lt; 0,000002), GITRL (p &lt; 0,007), CD27 (p &lt; 0,002), CD28 (p &lt; 0,003), CD40 (p &lt; 0,003), CD80 (p &lt; 0,009), ICOS (p &lt; 0,0006), as well as inhibitory molecules PD-L1 (p &lt; 0.0000001), CTLA-4 (p &lt; 0,005), TIM-3 (p &lt; 0,00006), HVEM (p &lt; 0,00002) TLR-2 (p &lt; 0,05), levels were significantly lower in early BC pts compared to healthy controls. When analyzed according to BC characteristics (TNBC vs. non-TNBC, tumor size, stage, nodal status and age) no significant difference was detected between the soluble levels of these ICM between the different subsets. Additionally, serum CXCL5 (p &lt; 0,000001), CCL23 (p &lt; 0,04), IL-16 (p &lt; 0,00005), interferon-α (p &lt; 0,03) and IL1-RA (p &lt; 0,03) were significantly lower compared to healthy controls. Serum CX3CL1 or fractalkine (p &lt; 0,024465) was significantly higher compared with healthy controls. Serum interferon-γ (p &lt; 0,2), IL-6 (p &lt; 0.6) and IL-2 (p &lt; 0.6) levels were not significantly different between the BC pts and the healthy controls. Conclusions: We identified low levels of both the stimulatory and inhibitory immune checkpoint molecules, in newly-diagnosed, non-metastatic BC pts compared to healthy controls. These results indicate that early BC is associated with a down-regulation of both soluble stimulatory and inhibitory immune-checkpoint pathways. Newly-diagnosed early BC pts have a generalized immune-suppression independent of subtype (TNBC vs non-TNBC) and stage, which, to our knowledge, is the first study to describe soluble immune checkpoints in early BC pts.

Prognostic value of baseline and early changes of circulating-free (cf) and circulating tumor (ct) DNA in the neoadjuvant (NA) setting of early stage colon cancer (CC).

3600 Background: ctDNA is an indicator of minimal residual disease and negative prognostic factor in stage II-III CC treated with surgery +/- adjuvant chemotherapy (CT). No study, however, has ever analysed the prognostic value of this biomarker in CC patients (pts) treated with NACT. We sought to evaluate the prognostic value of baseline and early changes of cf/ctDNA in stage II-III CC pts who were treated with one cycle of NA FOLFOX CT followed by surgery +/- adjuvant FOLFOX CT in the PePiTA trial. Methods: PePiTA was a multicentre, single-arm, prospective phase II trial testing in vivo tumour chemosensitivity of early stage CC (as assessed by 18F-FDG PET/CT-based metabolic response to one cycle of NA FOLFOX) and its association with long-term outcome (NCT00994864). Plasma samples were prospectively collected at baseline, 2 weeks after one cycle of NA FOLFOX CT, and before surgery. NPY and WIF1 were selected as universal methylation markers for ctDNA and analysed with digital droplet (dd)PCR technology. Data from ddPCR were processed with the QuantaSoft v1.6 software (Bio-Rad). Survival outcome measures were 5-year disease-free survival (DFS) and 6-year overall survival (OS). ROC curve analyses, Kaplan-Meier method, cox proportional hazards models and log-rank tests were used. Statistical analyses were carried out with SPSS v25.0 (SPSS Inc.). Results: 80 pts were included (44 ypStage I-II and 36 ypStage III). After a median follow-up of 52.5 months, 5-year DFS and 6-year OS were 68% (95%CI 52-84) and 84% (95%CI 74-94), respectively. Pts with high (≥1600 ng/ml) baseline cfDNA had worse 6-year OS (HR 6.45, 95%CI 1.61-25.84; p = 0.008). Early changes of cfDNA after one cycle of NA FOLFOX CT failed to predict survival (HR DFS 0.96, 95%CI 0.38-2.43; p = 0.92; HR OS 0.62, 95%CI 0.16-2.50; p = 0.50). At baseline, 25 out of 60 (42%) ctDNA-assessable patients were positive. Detectable ctDNA at baseline (HR DFS 2.06, 95%CI 0.65-6.49; p = 0.22; HR OS 3.11, 95%CI 0.57-16.99; p = 0.19) or at any timepoint before surgery (HR DFS 1.65, 95%CI 0.54-5.04; p = 0.38; HR OS 2.80, 95%CI 0.54-14.44; p = 0.22) was not significantly associated with survival. A trend toward a significant association between ctDNA increase at surgery and 5-year DFS was found (HR 3.66, 95%CI 0.81-16.44; p = 0.09). Data on the correlation between early changes of cf/ctDNA and 18F-FDG PET/CT-based metabolic response will be presented at the meeting. Conclusions: For the first time, we have shown that baseline cfDNA may predict survival outcome in early stage CC pts treated with NACT. Pending confirmation in larger series, testing for cfDNA at baseline could help select high-risk pts who may benefit from FOxTROT-like, NACT treatment strategies. While analysis of ctDNA in this setting did not appear useful to predict prognosis, these results might be secondary to the small sample size.

Risk factors for post-traumatic epilepsy

PurposeThe aim of the current study was to investigate the risk factors for post-traumatic epilepsy (PTE) in a large cohort of patients after severe non-penetrating civilian traumatic brain injury (TBI). MethodsThis was a longitudinal study. All patients with a severe non-penetrating TBI, who were admitted at the neuro-intensive care unit of Shahid Rajaee Trauma Hospital, affiliated with Shiraz University of Medical Sciences, Shiraz, Iran, from 2015 until 2019, were studied. Severe TBI was defined as a Glasgow Coma Scale-Motor score below six. Post-traumatic epilepsy was defined as any seizures that occurred after being discharged from the hospital. ResultsIn total, 803 patients with severe non-penetrating TBI were studied; 82 patients (10.2%) reported any late post-traumatic seizures (PTSs). A higher Glasgow outcome scale (extended) at discharge was significantly inversely associated with PTE [Odds Ratio (OR)= 0.76, 95% Confidence Interval (CI): 0.65–0.87; p = 0.0001]. Depressed skull fracture (OR= 1.88, 95% CI: 0.92–3.80; p = 0.081), epi‑dural hematoma (OR= 1.67, 95% CI: 0.93–2.97; p = 0.083), and sub-dural hematoma (OR= 1.64, 95% CI: 0.96–2.78; p = 0.068) were associated with PTE as trends. ConclusionOur study adds to the literature on the risk of PTE after severe non-penetrating civilian TBI. Our large sample size and also the application of a logistic regression analysis model may suggest that other variables (e.g., depressed skull fracture and intracranial hematoma) are indeed associated with the Glasgow outcome scale (extended) at discharge and that is why they lost their significance in the model.

Is severe head injury associated with functional (psychogenic) seizures?

ObjectivesThe 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)]. MethodsThis 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. ResultsOne 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). ConclusionSevere head injury is significantly associated with FS. 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 obtaing a detailed clinical history and also by performing video-EEG monitoring in order to adopt an appropriate treatment strategy in these patients.

Treating Post-Traumatic Seizures to Limit Tau Accumulation in Larval Zebrafish.

Seizures Are a Druggable Mechanistic Link Between TBI and Subsequent Tauopathy Alyenbaawi H, Kanyo R, Locskai LF, et al. Elife. 2021;10:e58744. doi:10.7554/eLife.58744Traumatic brain injury (TBI) is a prominent risk factor for dementias including tauopathies such as chronic traumatic encephalopathy. The mechanisms that promote prion-like spreading of Tau aggregates after TBI are not fully understood, in part due to lack of tractable animal models. Here, we test the putative role of seizures in promoting the spread of tauopathy. We introduce “tauopathy reporter” zebrafish expressing a genetically encoded fluorescent Tau biosensor that reliably reports accumulation of human Tau species when seeded via intraventricular brain injections. Subjecting zebrafish larvae to a novel TBI paradigm produced various TBI features including cell death, post-traumatic seizures, and Tau inclusions. Bath application of dynamin inhibitors or anticonvulsant drugs rescued TBI-induced tauopathy and cell death. These data suggest a role for seizure activity in the prion-like seeding and spreading of tauopathy following TBI. Further work is warranted regarding anticonvulsants that dampen post-traumatic seizures as a route to moderating subsequent tauopathy.

Post Traumatic Seizures (PTS) in Geriatric Traumatic Brain Injury (TBI): A Retrospective Analysis of Incidence, Risk Factors, and Outcomes (4210)

Post Traumatic Seizures (PTS) in Geriatric Traumatic Brain Injury (TBI): A Retrospective Analysis of Incidence, Risk Factors, and Outcomes (4210)

Post-Traumatic Seizures: A Deep-Dive Into Pathogenesis.

Post-traumatic seizures (PTS) have become an emerging challenge for neurologists worldwide with the rise of brain injuries. Trauma can lead to various outcomes, ranging from naive spasms to debilitating post-traumatic epilepsy (PTE). In this article, we will explore the pathogenesis of convulsions following a concussion. We will look at multiple studies to explain the various structural, metabolic, and inflammatory changes leading to seizures. Additionally, we will explore the association between severity and location of injury and PTE. PTE's pathophysiology is not entirely implicit, and we are still in the dark as to which anti-epileptic drugs will be useful in circumventing these attacks. The purpose of this narrative review is to explain the post-traumatic brain changes in detail so that such attacks can be either thwarted or treated more resourcefully in the future.

Development and external validation of a predictive nomogram model of posttraumatic epilepsy: A retrospective analysis

ObjectiveWe aimed to develop and validate a predictive model of posttraumatic epilepsy (PTE). MethodsThe training cohort was patients registered at West China Hospital and diagnosed as traumatic brain injury (TBI) between January 1, 2011, and December 31, 2017. On the basis of multivariable cox proportional hazards model using a forward stepwise method, the nomogram was generated. We externally validated this instrument in 834 participants from two independent cohorts to assess its performance. ResultsThe nomogram was built based on the results of multivariable cox proportional hazards regression analysis of 1301patients from West China Hospital. The prevalence of PTE was 12.8% (95% confidence interval [CI], 10.9–14.6%) in training cohort, 10.5% (95% CI, 7.5–13.4%) in the testing 1 cohort, and 6.1% (95% CI, 3.7–8.4%) in the testing 2 cohort. 7 independent predictors of PTE composed the nomogram (sex, time of loss of consciousness, subdural hemorrhage, contusion sites, early posttraumatic seizures, TBI severity, and treatment). The C-index was 0.846 (95% CI, 0.817–0.876), and the corresponding sensitivity and specificity were 0.867 and 0.738. External validations showed good discrimination in overall testing cohorts with a C-index of 0.895 (95% CI, 0.859–0.930), in the testing 1 cohort (C-index 0.897, 95% CI, 0.855–0.938) and testing 2 cohort (C-index, 0.883, 95% CI, 0.814–0.952). Calibration of this model was also good since the calibration plots were close to the ideal line. ConclusionsThis nomogram was developed and validated in a large cohort for individualized prediction of PTE, which can identify individuals at high risk of epilepsy and help us find preventive drugs based on these targeted population.