Early Seizures Research Articles

Prophylactic Levetiracetam for the Prevention of Seizures in Acute Nontraumatic Intracerebral Hemorrhage: A Retrospective Propensity-matched Patient Outcome Analysis (P7-5.030)

<h3>Objective:</h3> This study aims to determine if prophylactic levetiracetam in nontraumatic intracerebral hemorrhage (nt-ICH) decreases seizure risk and improves mortality. <h3>Background:</h3> Early seizures is a common morbidity in nt-ICH, often associated with worsening neurological outcome. There are conflicting data on the use of prophylactic antiepileptic drugs (AEDs) in the form of levetiracetam in this population. Current guidelines do not endorse prophylactic AED use due to limited evidence for clinical benefit; however, they are routinely prescribed in the acute setting. <h3>Design/Methods:</h3> This was a retrospective cohort study using data collected from TriNetX, a deidentified patient database collated from 71 healthcare organizations. Using ICD-10 codes, we identified nt-ICH patients excluding those with a history of seizure disorders. Patients were dichotomized based on prophylactic levetiracetam use or not. Propensity score adjustment matched cohorts on age, sex, race, significant comorbidities, complications of nt-ICH, location of nt-ICH, and NIHSS score. Associations with mortality; occurrence of seizure, acute kidney injury (AKI), transient ischemic attack (TIA), stroke, myocardial infarction; percutaneous endoscopic gastrostomy and tracheostomy placement at day 30 were measured between groups using unadjusted odds ratios (OR) with 95% confidence intervals (CI). <h3>Results:</h3> This study identified 1,571 patients with nt-ICH who received prophylactic levetiracetam and 9,570 patients who did not. After matching, 1,492 patients remained in each cohort. Our analysis showed that prophylactic levetiracetam in patients with nt-ICH was not associated with decreased seizure occurrence (OR, 1.21 [95% CI, 0.88, 1.68]) or mortality benefit (OR, 1.06 [95% CI, 0.90, 1.25]); was associated with decreased incidence of AKI (OR 0.552 [95% CI 0.344, 0.884]) and TIA [OR 0.496 (95% CI 0.304, 0.807)]. <h3>Conclusions:</h3> This data suggests that prophylactic levetiracetam does not provide a mortality benefit or decrease the occurrence of seizures in the acute setting of nt-ICH. Prospective studies are necessary to confirm these findings and assess the impact on longitudinal functional outcomes. <b>Disclosure:</b> Miss Nguyen has nothing to disclose. Ms. Bhanja has nothing to disclose. Dr. Hallan has nothing to disclose. Kevin Cockroft has received personal compensation in the range of $5,000-$9,999 for serving as an officer or member of the Board of Directors for Intersocietal Accreditation Commission. The institution of Kevin Cockroft has received research support from Intersocietal Accreditation Commission. The institution of Kevin Cockroft has received research support from Nico Corporation. The institution of Kevin Cockroft has received research support from Idorsia Pharmaceuticals . The institution of Kevin Cockroft has received research support from AstraZeneca . Dr. Rizk has nothing to disclose.

Fragile-X-associated Tremor/Ataxia Syndrome in a Woman with Full Mutation: A Case Report (P5-11.009)

<h3>Objective:</h3> To describe the first case of FXTAS in a full mutation woman without Fragile X syndrome. <h3>Background:</h3> Fragile-X-associated tremor/ataxia syndrome (FXTAS) is caused by expanded trinucleotide (CGG) repeats between 55–199 (premutation) in the <i>Fragile X Mental Retardation 1 (FMR1) gene</i>. Core clinical features of FXTAS include cerebellar ataxia, intention tremor and Parkinsonism. In contrast, a full mutation of CGG repeats&gt;200 repeats with methylation of the gene leads to fragile X syndrome, which is characterized by early intellectual disability, autistic features, and seizures. <i>FMR1</i> premutation carrier women presenting as FXTAS have been reported. This is the first report of a woman with a full mutation presenting with FXTAS. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 65-year-old woman presented with problems with dexterity and shuffling gait. The patient also complained of urinary urgency, constipation, anxiety, depression, and mild cognitive complaints. The patient’s son was diagnosed with fragile X syndrome at 14 months. Neurological exam of the patient showed parkinsonism, action tremor and limb ataxia. MRI brain demonstrated chronic ischemic small vessel disease and mildly reduced brain volume. <i>FMR1 CGG</i> repeat sizes were 20 and &gt;200. The 20 repeat allele was seen on the active X chromosome (representing non-random X-inactivation), while the &gt;200 repeat allele was fully methylated on Southern blot. Testing for Parkinson’s disease-associated genes were negative. <h3>Conclusions:</h3> This is the first report of a woman with a <i>FMR1</i> full mutation presenting with signs and symptoms of FXTAS. Several cases of FXTAS have been reported in <i>FMR1</i> full mutation men with fragile X syndrome due to mosaicism of repeat sizes and the presence of a premutation allele. Full mutation adults with complete methylation have not been reported to have FXTAS. The clinical presentation of this case might be due to size or methylation mosaicism in brain. Alternatively, one could also consider a different disease mimicking FXTAS. <b>Disclosure:</b> Dr. Kazanci has nothing to disclose. The institution of Dr. Berry-Kravis has received research support from NIH. The institution of Dr. Berry-Kravis has received research support from Ovid. The institution of Dr. Berry-Kravis has received research support from Zynerba. The institution of Dr. Berry-Kravis has received research support from Roche. The institution of Dr. Berry-Kravis has received research support from CDC. The institution of Dr. Berry-Kravis has received research support from FRAXA Research Foundation. The institution of Dr. Berry-Kravis has received research support from GeneTx. The institution of Dr. Berry-Kravis has received research support from Angelman Syndrome Foundation. The institution of Dr. Berry-Kravis has received research support from Acadia. The institution of Dr. Berry-Kravis has received research support from GW. The institution of Dr. Berry-Kravis has received research support from Anavex. The institution of Dr. Berry-Kravis has received research support from Rett Syndrome Research Trust. The institution of Dr. Berry-Kravis has received research support from Ultragenyx. The institution of Dr. Berry-Kravis has received research support from Mallinckrodt. The institution of Dr. Berry-Kravis has received research support from Together Strong Foundation. The institution of Dr. Berry-Kravis has received research support from Orphazyme. The institution of Dr. Berry-Kravis has received research support from Ionis. The institution of Dr. Berry-Kravis has received research support from Taysha. The institution of Dr. Berry-Kravis has received research support from Erydel. The institution of Dr. Berry-Kravis has received research support from Tetra. The institution of Dr. Berry-Kravis has received research support from Neuren. The institution of Dr. Berry-Kravis has received research support from FRAXA Research Foundation. Dr. Hall has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Academy of Neurology. Dr. Hall has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier - Parkinsonism and Related Disorders. Dr. Hall has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Annals of Neurology. The institution of Dr. Hall has received research support from Parkinson’s Foundation. The institution of Dr. Hall has received research support from CHDI. The institution of Dr. Hall has received research support from Biohaven. The institution of Dr. Hall has received research support from Neurocrine. The institution of Dr. Hall has received research support from Uniqure. Dr. Hall has received personal compensation in the range of $500-$4,999 for serving as a Study section with NIH.

A Novel Approach to Assess the Impact of Disease in Patients with SCN8A-Related Developmental and Epileptic Encephalopathy (P3-9.008)

<h3>Objective:</h3> Clinical data generated using Invitae’s Ciitizen patient-consented, real-world data platform were used to explore disease burden in <i>SCN8A</i>-DEE. <h3>Background:</h3> <i>SCN8A</i>-related DEE is a rare disease associated with pathogenic variants in the <i>SCN8A</i> gene encoding the voltage-gated sodium channel alpha subunit Na_v1.6. Due to significant phenotypic heterogeneity, comprehensive understanding of disease impact and progression is limited. <h3>Design/Methods:</h3> Real-world clinical data were extracted from patients with an <i>SCN8A</i> variant using the Ciitizen platform, which employs a proprietary approach combining machine learning and expert human review to streamline generation of research-grade data from unstructured health records spanning ~10 years. Extracted data including seizure history, comorbidities, and therapeutic interventions were analyzed. <h3>Results:</h3> 79 patients were enrolled and contributed data for analyses. Mean patient age was 8.2 years (1–23), with similar percentages of males and females. Patients were categorized based on age at seizure onset; ≤6 months (75.6%) or &gt;6 months (34.2%). A further group included patients without seizures (5%). Mean age at seizure onset was 70.4 days (1–175) for patients with early (≤6 months) seizures and 749.3 days (224–4409) for those with later (&gt;6 months) seizures. While seizure frequency was variable, most patients continued to experience seizures over time. Procedural interventions and hospitalizations were high across the lifespan; nearly a third occurring in the first year of life. Mean number of medications prescribed over a patient’s lifetime was 17.6 (3–44). Patients experienced multiple comorbidities; global developmental delay was the most common (81%), with sleep disorders, hypotonia, feeding difficulties and GERD reported in &gt;50%. <h3>Conclusions:</h3> This work represents a new generation of natural history study providing the most robust real-world dataset to date on disease burden and progression in <i>SCN8A</i>-DEE. Knowledge from this study is anticipated to accelerate drug development efforts by providing new insights into the broad, longitudinal impact of disease, therefore informing trial endpoints beyond seizure symptomatology. <b>Disclosure:</b> Kelley Dalby has received personal compensation for serving as an employee of Praxis Precision Medicines. Kelley Dalby has stock in Praxis Precision Medicines. Kelley Dalby has stock in RogCon. Mr. Snyder has received personal compensation for serving as an employee of Praxis Precision Medicines. Mr. Snyder has received stock or an ownership interest from Praxis Precision Medicines. Dr. G Matthews has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Praxis Precision Medicines. Dr. G Matthews has stock in Praxis Precision Medicines. Dr. Oldham has received personal compensation for serving as an employee of Praxis Precision Medicines. Steven Petrou has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Praxis Precision Medicines. Steven Petrou has stock in Praxis Precision Medicines. The institution of Steven Petrou has received research support from Praxis Precision Medicines. The institution of Steven Petrou has received research support from Medical Research Future Fund. Steven Petrou has received intellectual property interests from a discovery or technology relating to health care. Steven Petrou has received intellectual property interests from a discovery or technology relating to health care. Dr. Souza has received personal compensation for serving as an employee of Praxis Precision Medicines. Dr. Souza has stock in Praxis Precision Medicines.

Thalamostriatal disconnection underpins long-term seizure freedom in frontal lobe epilepsy surgery.

Around 50% of patients undergoing frontal lobe surgery for focal drug-resistant epilepsy become seizure free post-operatively; however, only about 30% of patients remain seizure free in the long-term. Early seizure recurrence is likely to be caused by partial resection of the epileptogenic lesion, whilst delayed seizure recurrence can occur even if the epileptogenic lesion has been completely excised. This suggests a coexistent epileptogenic network facilitating ictogenesis in close or distant dormant epileptic foci. As thalamic and striatal dysregulation can support epileptogenesis and disconnection of cortico-thalamostriatal pathways through hemispherotomy or neuromodulation can improve seizure outcome regardless of focality, we hypothesize that projections from the striatum and the thalamus to the cortex may contribute to this common epileptogenic network. To this end, we retrospectively reviewed a series of 47 consecutive individuals who underwent surgery for drug-resistant frontal lobe epilepsy. We performed voxel-based and tractography disconnectome analyses to investigate shared patterns of disconnection associated with long-term seizure freedom. Seizure freedom after 3 and 5 years was independently associated with disconnection of the anterior thalamic radiation and anterior cortico-striatal projections. This was also confirmed in a subgroup of 29 patients with complete resections, suggesting these pathways may play a critical role in supporting the development of novel epileptic networks. Our study indicates that network dysfunction in frontal lobe epilepsy may extend beyond the resection and putative epileptogenic zone. This may be critical in the pathogenesis of delayed seizure recurrence as thalamic and striatal networks may promote epileptogenesis and disconnection may underpin long-term seizure freedom.

Use of antiseizure medications after traumatic brain injury

Background: Post-traumatic seizures and epilepsy are major complications that increase the mortality rate among patients with traumatic brain injury (TBI) and hinder functional recovery. It is important to establish prophylaxis and treatment strategies for high-risk patients. The use of antiseizure medications may not only adversely affect the cognitive function following TBI but also may be associated with a worse rehabilitation outcome.Current Concepts: The level of evidence in the current international guidelines related to the prophylaxis and management of post-traumatic seizure is not robust. Furthermore, the use of antiseizure medications after TBI remains unclear, indicating substantial variations in clinical practice.Discussion and Conclusion: Prophylactic antiseizure medications can reduce the risk of early seizures and partially prevent the secondary injury process of TBI; however, they do not seem to inhibit epileptogenesis. Therefore, if the benefits of preventing early seizures outweigh the potential risks associated with antiseizure medication, it is recommended to use them for a short period of about one week after the injury. Then, it is not recommended to continue using them routinely without considering the individual risk of seizure recurrence and potential adverse effects of long-term use. The treatment duration of anticonvulsant in patients with post-traumatic epilepsy should also be determined based on the individual risk of seizure recurrence, and the decision should take into account the opinions of both the patient and the caregiver, while considering not only the potential benefits but also the risks associated with long-term use.

Factors associated with pre-operative and early and late post-operative seizures in patients with supratentorial meningiomas.

Risk factors for epilepsy in meningioma patients are not yet clearly defined, however, seizure freedom is a significant factor for quality of life after surgery. We performed a retrospective study of the 333 adult patients who received surgery for supratentorial meningioma at our centre. Various clinical, radiological, and surgical variables were included in the multivariate regression, and the outcomes measured were the occurrence of seizure(s) pre-operatively, during the hospitalization, and during the follow-up period. A total of 89 (26,7%) patients experienced pre-operative seizures, of whom 62.9% were seizure-free after the surgery. Of 244 patients without epilepsy before surgery, 11.9% had at least one seizure post-operatively. In total, 63 of our patients (18.9%) experienced seizures after the surgery, of whom 20 had refractory epilepsy. Multivariate analysis identified the following predictors of pre-operative seizures: absence of headache (OR: 0.23, CI: 2.55-8.50), the presence of significant peritumoural oedema (OR: 4.35, CI: 2.57-7.35), and younger age (OR: 0.97 per year increase, CI: 0.95-0.99). Factors associated with early post-operative seizures were: younger age (OR: 0.96 per year increase, CI: 0.93-0.99) and presence of pre-operative seizures (OR: 2.73, CI: 1.13-6.57), while the presence of pre-operative seizures (OR: 4.73, CI: 2,05-10.92), tumour progression (OR: 5.38, CI: 2.25-12.89) and neurological worsening (OR: 5.21 CI: 1.72-15.81) were significant for late post-operative seizures. Our results from a single-centre meningioma cohort confirm, in general, data from some previous studies regarding patients' characteristics for both pre-operative and overall post-operative epilepsy. Besides previously described risk factors, younger age was important for pre-operative and early post-operative seizures. Epilepsy is common in patients with recurrence of meningioma, but the variables of significance for refractory seizures in these patients require further examination.

775 The Effect of Anti-Seizure Medication Administration on Mortality and Early Post Traumatic Seizures In Critically Ill Older Adults With Traumatic Brain Injury

INTRODUCTION: Older adults (≥65-years) are an understudied and growing TBI population. Guidelines support prophylactic antiseizure medication (ASM) to reduce early posttraumatic seizures (ePTS) (within 7-days of injury) in severe TBI. Whether ASM decreases mortality or ePTS in this population remains unclear. This study assesses association between ASM administration, mortality, and seizure in older TBI patients. METHODS: This retrospective cohort study utilized data from the Massachusetts Institute of Technology, Medical Information Mart for Intensive Care-III (MIMIC). Our cohort included patients 65-years or older. Primary exposure was early ASM administration in TBI patients admitted to an ICU at a Level 1 trauma center from 2001-2012. A double-robust inverse propensity scale weighted model based on proportional hazard and logistic regression models assessed the association between ASM administration and risk of death within 7-days of admission. RESULTS: Of 1,145 patients, 783 (68.4%) received ASM within the first 24 hours. TBI severity, classified by Glasgow Coma Score (GCS), was predominantly mild (71.2%) followed by moderate (16.8%), and severe (11.3%). Patients who received ASM were less likely to have died at 7-days (adjusted Death HR = 0.48 [95% CI 0.28–0.88] P = 0.005), at 30 days (adjusted HR 0.67 [0.45–0.99] P = 0.045) and at one year (adjusted HR 0.72 [0.54–0.97] P = 0.029). There was no difference in seizure (adjusted Seizure OR 1.18 [0.61–2.26] compared with those who did not receive ASM. CONCLUSIONS: Early ASM administration was associated with reduced mortality at 7-days, 30-days, and one-year, but did not affect early seizure risk. This observed benefit in older adults with all TBI severity suggest broader recommendations for ASM use.

337 Quantitative Analysis of Admission Electroencephalography Predicts Post-Traumatic Epilepsy After Severe Traumatic Brain Injury

INTRODUCTION: Up to one-third of severe traumatic brain injury (TBI) patients develop post-traumatic epilepsy (PTE), often years after their injury. Currently, there is no validated predictive model to identify patients at high risk for PTE. METHODS: We retrospectively analyzed a prospective database of severe TBI patients treated at a single level one trauma center from 2012 through 2018. Outcomes were recorded with the Expanded Glasgow Outcomes Scale (GOSE) at 6- and 12-months post-injury. We identified a cohort of patients who survived to two years and did not have an early post-traumatic seizure, defined as a seizure within 7 days of initial injury. From this cohort, we matched patients with PTE to those without using age and Glasgow coma scale score at admission. All patients underwent continuous EEG for 3-5 days upon admission, and a board-certified epileptologist identified 5-minute artifact-free segment for analysis. We extracted qEEG features, described them with qualitative statistics, and developed a logistic regression model using backwards selection. RESULTS: We identified 27 patients with PTE and 23 without who survived two years post-injury. The median time to onset of PTE was 7.2 months post-trauma and GOSE was similar when stratified by PTE at 6- and 12-months (p &gt; 0.73). On qEEG analysis, patients with PTE had higher spectral power in the delta frequencies (p = 0.003), more variance in the delta and theta frequencies (p &lt; 0.04), a higher mean amplitude (p = 0.01), and peak envelope (p = 0.01). On multivariate modeling, delta power (Odds Ratio [OR] 1.8), theta power (OR 0.2), and rhythmic spectrum (1.7) all increased risk of PTE and had an AUC of 0.85 for predicting PTE. CONCLUSIONS: In a cohort of severe TBI patients, quantitative qEEG features in the acute phase after injury identified future risk of PTE.

802 The Predictive Role of Initial Brain Imaging on Seizure Development in Pediatric Traumatic Brain Injury

INTRODUCTION: Pediatric traumatic brain injury (TBI) poses risk for early post-traumatic seizures (EPTS). Antiepileptic drugs are often prescribed prophylactically, though limited evidence exists regarding their effectiveness in pediatric TBI. Neuroimaging has been predictive of EPTS in adult TBI, but this is not well studied in children. Given the heterogeneous nature of TBIs, injury type and location may serve as predictors of seizure development. METHODS: This is a single-center retrospective analysis of 348 pediatric patients with TBI from January 2011 to June 2021 treated with levetiracetam. Factors analyzed include age, sex, GCS, dosage and date of levetiracetam administration, presence of seizures, medical and surgical management, and findings on CT imaging. The primary outcome was the prevalence of seizures within 7 days of injury. RESULTS: On multivariate analysis, the risk of having seizures any time within 7 days of injury was decreased in children with contusions (OR .425 [.205-.880], p = 0.021), simple skull fractures (OR .226 [.079-.648], p = 0.006), and complex skull fractures (OR .370 [.175-.784], p = 0.009). Findings of SDH, traumatic SAH, and pneumocephalus did not significantly increase the risk of EPTS. On univariate analysis of patients who developed seizures after levetiracetam, the only significant imaging factor for EPTS was SDH (OR 4.398 [1.447-13.370], p = 0.009). On multivariate analysis, no imaging characteristics were predictive of EPTS, but older children had a decreased risk of EPTS (1-2 yo OR .095 [.016-.560], p = 0.009; 3-18 yo; OR .006 [0-.132], p = 0.001) despite levetiracetam prophylaxis. CONCLUSIONS: This study demonstrates that regardless of initial neuroimaging, younger age is associated with an increased risk of seizures despite prophylaxis. Further studies are needed to determine the predictive value of imaging characteristics in developing EPTS in pediatric TBI patients.

513 Presurgical Identification of Seizure Onset and Propagative Zones Without Ictal Recordings: A Combined Diffusion MRI and SEEG Study

INTRODUCTION: Increasing evidence has suggested that identification of regions involved in early seizure propagation (“Propagation Zones”, PZ) is important to predict seizure freedom after epilepsy surgery (Andrews 2019). Resting-state connectivity analyses using stereo-electroencephalography (SEEG) have shown promise in efficiently characterizing seizure onset zones (SOZ) but have found difficulty in distinguishing both SOZs and PZs from non-involved brain regions. Recently, evidence has suggested that ictal structure-function coupling can be used to delineate brain regions important in seizure dynamics (Shah 2019). METHODS: We calculated the resting-state SEEG directed connectivity of 26 consented patients with focal epilepsy undergoing presurgical evaluation. Using preoperative diffusion MRI, we then implemented a custom technique to obtain structural connectivity metrics between SEEG contacts. We calculated the structural connectivity and structure-function coupling of SOZs, PZs (spread within 10 seconds), and non-involved regions over a range of Euclidean distances. Finally, we generated models using a support vector machine to classify SOZs, PZs, and non-involved regions. RESULTS: SOZs and PZs exhibit comparably high local structural connectivity compared to non-involved regions despite SOZs demonstrating significantly greater functional connectivity to both PZs and non-involved regions. However, PZs exhibit significantly higher local structure-function coupling to that of non-involved regions, with SOZs exhibiting the highest local structure-function coupling. A support vector machine to classify SOZs, PZs, and non-involved regions and was able to significantly increase model accuracy by incorporating local structure-function coupling. CONCLUSIONS: SOZs and PZs demonstrate a distinct local structure-function coupling to that of non-involved regions and each other. This distinct coupling profile can be used to accurately classify SOZs, PZs and non-involved regions.

Effects of Propofol on Cortical Electroencephalograms in the Operation of Glioma-Related Epilepsy

A cortical electroencephalogram (ECoG) is often used for the intraoperative monitoring of epilepsy surgery, and propofol is an important intravenous anesthetic, but its effect on EEGs is unclear. To further clarify the effect of propofol on cortical ECoGs during glioma-related epilepsy surgery and to clarify the possible clinical value. A total of 306 patients with glioma were included in the study. Two hundred thirty-nine with glioma-related epilepsy were included in the epilepsy group, and 67 without glioma-related epilepsy were included in the control group. All patients experienced continuous, real-time ECoG monitoring and long-term follow-up after surgery. After injection of low-dose propofol, the rate of activated ECoGs in the epilepsy group (74%) was significantly higher than in the control group (9%). Furthermore, compared with patients in the untreated group, patients in the treated group had lower rates of early and long-term postoperative seizure frequencies and fewer interictal epileptiform discharges (IEDs). Low-dose infusion of propofol can specifically activate ECoGs in epilepsy patients. Therefore, activated ECoGs might provide an accurate and reliable method for identifying potential epileptic zones during glioma-related epilepsy surgery, resulting in better early and long-term prognoses after epilepsy surgery.

Association of Early Seizure Prophylaxis With Posttraumatic Seizures and Mortality: A Meta-analysis With Evidence Quality Assessment.

To evaluate the quality of evidence about the association of primary seizure prophylaxis with antiseizure medication (ASM) within 7 days postinjury and the 18- or 24-month epilepsy/late seizure risk or all-cause mortality in adults with new-onset traumatic brain injury (TBI), in addition to early seizure risk. Twenty-three studies met the inclusion criteria (7 randomized and 16 nonrandomized studies). We analyzed 9,202 patients, including 4,390 in the exposed group and 4,812 in the unexposed group (894 in placebo and 3,918 in no ASM groups). There was a moderate to serious bias risk based on our assessment. Within the limitations of existing studies, our data revealed a lower risk for early seizures in the ASM prophylaxis group compared with placebo or no ASM prophylaxis (risk ratio [RR] 0.43, 95% confidence interval [CI] 0.33-0.57, p < 0.00001, I 2 = 3%). We identified high-quality evidence in favor of acute, short-term primary ASM use to prevent early seizures. Early ASM prophylaxis was not associated with a substantial difference in the 18- or 24-month risk of epilepsy/late seizures (RR 1.01, 95% CI 0.61-1.68, p = 0.96, I 2 = 63%) or mortality (RR 1.16, 95% CI 0.89-1.51, p = 0.26, I 2 = 0%). There was no evidence of strong publication bias for each main outcome. The overall quality of evidence was low and moderate for post-TBI epilepsy risk and all-cause mortality, respectively. Our data suggest that the evidence showing no association between early ASM use and 18- or 24-month epilepsy risk in adults with new-onset TBI was of low quality. The analysis indicated a moderate quality for the evidence showing no effect on all-cause mortality. Therefore, higher-quality evidence is needed as a supplement for stronger recommendations.

The Role of Decompressive Craniectomy on Functional Outcome, Mortality and Seizure Onset after Traumatic Brain Injury

Decompressive craniectomy (DC) to treat increased intracranial pressure after a traumatic brain injury (TBI) is a common but controversial choice in clinical practice. This study aimed to determine the impact of DC on functional outcomes, mortality and the occurrence of seizures in a large cohort of patients with TBI. This retrospective study included patients with TBI consecutively admitted for a 6-month neurorehabilitation program between 1 January 2009 and 31 December 2018. The radiological characteristics of brain injury were determined with the Marshall computed tomographic classification. The neurological status and rehabilitation outcome were assessed using the Glasgow Coma Scale (GCS) and the Functional Independence Measure (FIM), which were both assessed at baseline and on discharge. Furthermore, the GCS was recorded on arrival at the emergency department. The DC procedure, prophylactic antiepileptic drug (AED) use, the occurrence of early or late seizures (US, unprovoked seizures) and death during hospitalization were also recorded. In our cohort of 309 adults with mild-to-severe TBI, DC was performed in 98 (31.7%) patients. As expected, a craniectomy was more frequently performed in patients with severe TBI (p < 0.0001). However, after adjusting for the confounding variables including GCS scores, age and the radiological characteristics of brain injury, there was no association between DC and poor functional outcomes or mortality during the inpatient rehabilitation period. In our cohort, the independent predictors of an unfavorable outcome at discharge were the occurrence of US (β = -0.14, p = 0.020), older age (β = -0.13, p = 0.030) and the TBI severity on admission (β = -0.25, p = 0.002). Finally, DC (OR 3.431, 95% CI 1.233-9.542, p = 0.018) and early seizures (OR = 3.204, 95% CI 1.176-8.734, p = 0.023) emerged as the major risk factors for US, independently from the severity of the brain injury and the prescription of a primary prophylactic therapy with AEDs. DC after TBI represents an independent risk factor for US, regardless of the prescription of prophylactic AEDs. Meanwhile, there is no significant association between DC and mortality, or a poor functional outcome during the inpatient rehabilitation period.

Phenobarbital as Anticonvulsant Prophylaxis in Patients With Traumatic Brain Injury at Risk for Alcohol Withdrawal Syndrome.

Background: Anticonvulsant prophylaxis (ACP) for early post-traumatic seizures (PTS) is recommended in patients with traumatic brain injury (TBI). Phenobarbital (PB) may be used to prevent alcohol withdrawal syndrome (AWS) in at-risk patients. The dual-purpose use of PB in the TBI population would allow for consolidation of pharmacotherapy. Objective: The primary objective of this study was to determine the frequency of early PTS in TBI patients at risk of AWS treated with PB as ACP. Secondary objectives included determining rates of over sedation and endotracheal intubation. Methods: Patients received an intravenous (IV) loading dose of PB at 15-20mg/kg followed by 1mg/kg every 12hours for 7days with a goal level of 15-20mcg/mL. Medication data, seizure frequency, and episodes of over sedation and endotracheal intubation were collected. Results: Eighty patients were treated with PB over a 1-year period. Thirty-nine patients were analyzed. Median loading dose was 19.9 (Interquartile Range 19.1-20.0) mg/kg with a median post load level of 21.7mcg/mL (IQR 18.3-25.8) mcg/mL. One patient (2.6%) had electrographic evidence for early PTS. PB was discontinued in 4 (10.3%) patients out of concern for over sedation. One patient required endotracheal intubation after rapid PB loading. Conclusion: The frequency of early PTS was low when PB was used as primary ACP in patients with TBI at risk for AWS. Over sedation is a potential adverse effect that should be considered in the choice of ACP. No conclusions can be drawn as to the effectiveness of PB in preventing AWS.

A Retrospective Case Series on Valproic Acid for Early Post-Traumatic Seizure Prophylaxis After Traumatic Brain Injury in Patients With Concomitant Agitation.

Purpose: Early post-traumatic seizures occur within 7 days following a traumatic brain injury and may lead to additional brain damage and poor outcomes. Levetiracetam or phenytoin is often used for seizure prophylaxis in this patient population, but valproic acid may be an appropriate therapeutic alternative in patients with concomitant agitation. Evidence for the use of valproic acid for both early post-traumatic seizure prophylaxis and agitation is limited. The purpose of this study is to examine the safety and efficacy of valproic acid for both early post-traumatic seizure prophylaxis and agitation. Methods: This single-center, retrospective case series includes 18 patients who received valproic acid for both early post-traumatic seizure prophylaxis and agitation. Efficacy for early post-traumatic seizure prophylaxis is assessed by the incidence of seizures within 7 days of injury. Efficacy for agitation is assessed by changes in Riker Sedation-Agitation Scale scores during valproic acid therapy. The safety of valproic acid is defined by the incidence of selected adverse events. Results: Among 18 patients with traumatic brain injuries receiving valproic acid for both early post-traumatic seizures and agitation, one patient experienced a seizure during the period of prophylaxis and thrombocytopenia was the most common adverse event. Conclusion: In this small cohort of patients, valproic acid appears be a potential option to prevent early post-traumatic seizures in patients with traumatic brain injuries and concomitant agitation with minimal adverse effects. Randomized, controlled studies are needed to further investigate the role of valproic acid for this indication, including standards for dosing regimens, serum drug monitoring, and the relationship between valproic acid treatment and mortality.

Neutrophil to lymphocyte ratio is associated with the epilepsy after primary intracerebral hemorrhage

BackgroundPost-stroke epilepsy (PSE) is one of the major sequelae of stroke. Inflammation has been implicated in the development of stroke. The study aimed to explore the relationship between neutrophil-to-lymphocyte ratio (NLR) levels and epilepsy in patients with primary intracerebral hemorrhage (ICH). MethodsA retrospective study was performed on 1132 patients with first-time ICH. Blood samples were obtained at admission after ICH. Patients included in the study were classified into three groups according to NLR tertiles. Logistic regression was used to analyze the relationship between NLR levels and the occurrence of PSE. ResultsThe occurrence of PSE was significantly correlated with NLR levels (r = 0.118, P < 0.001). Patients with PSE had higher NLR levels than those without PSE. After adjusting for potential confounders, high NLR was independently associated with an increased risk of PSE (OR = 1.861, 95% CI 1.032–3.355, P = 0.039). Neutrophil-to-lymphocyte ratio levels were independently associated with the occurrence of PSE in the poor functional outcome group, while this association was not significant in the favorable functional outcome group. The model (cortical involvement + hematoma volume + early seizures + NLR) showed good prognostic performance. ConclusionHigh NLR at admission is associated with an increased risk of PSE, which suggests that NLR may play a role in risk stratification in patients with ICH.

The phenotypic and genotypic spectrum of epilepsy and intellectual disability in adults: Implications for genetic testing.

The phenotypic and genotypic spectrum of adult patients with epilepsy and intellectual disability (ID) is less clear than in children. We investigated an adult patient cohort to further elucidate this and inform the genetic testing approach. Fifty-two adult patients (30 male, 22 female) with epilepsy, at least mild ID and no known genetic or acquired cause were included and phenotyped. Variants identified through exome sequencing were evaluated using ACMG criteria. Identified variants were compared with commercially available gene panels. Cluster analysis of two features, age at seizure onset and age at ascertainment of cognitive deficits, was performed. Median age was 27 years (range 20-57 years) with median seizure onset at 3 years and median ascertainment of cognitive deficits at 1 year. Likely pathogenic/pathogenic variants were identified in 16/52 patients (31%) including 14 (27%) single nucleotide variants and 2 (4%) copy number variants. Simulated yield of commercial gene panels varied between 13% in small (≤144 genes) and 27% in large panels (≥1478 genes). Cluster analysis (optimal number 3 clusters) identified a cluster with early seizure onset and early developmental delay (developmental and epileptic encephalopathy, n=26), a cluster with early developmental delay but late seizure onset (ID with epilepsy, n=16) and a third cluster with late ascertainment of cognitive deficits and variable seizure onset (n=7). The smaller gene panels particularly missed the genes identified in the cluster with early ascertainment of cognitive deficits and later onset of epilepsy (0/4) as opposed to the cluster with developmental and epileptic encephalopathy (7/10). Our data indicates that adult patients with epilepsy and ID represent a heterogeneous cohort that includes grown-up patients with DEE but also patients with primary ID and later onset of epilepsy. To maximize diagnostic yield in this cohort either large gene panels or exome sequencing should be used.

Attenuation of initial pilocarpine-induced electrographic seizures by methionine sulfoximine pretreatment tightly correlates with the reduction of extracellular taurine in the hippocampus.

Initiation and development of early seizures by chemical stimuli is associated with brain cell swelling resulting in edema of seizure-vulnerable brain regions. We previously reported that pretreatment with a nonconvulsive dose of glutamine (Gln) synthetase inhibitor methionine sulfoximine (MSO) mitigates the intensity of initial pilocarpine (Pilo)-induced seizures in juvenile rats. We hypothesized that MSO exerts its protective effect by preventing the seizure-initiating and seizure-propagating increase of cell volume. Taurine (Tau) is an osmosensitive amino acid, whose release reflects increased cell volume. Therefore, we tested whether the poststimulus rise of amplitude of Pilo-induced electrographic seizures and their attenuation by MSO are correlated with the release of Tau from seizure-affected hippocampus. Lithium-pretreated animals were administered MSO (75 mg/kg ip) 2.5h before the induction of convulsions by Pilo (40 mg/kg ip). Electroencephalographic (EEG) power was analyzed during 60 min post-Pilo, at 5-min intervals. Extracellular accumulation of Tau (eTau) served as a marker of cell swelling. eTau, extracellular Gln (eGln), and extracellular glutamate (eGlu) were assayed in the microdialysates of the ventral hippocampal CA1 region collected at 15-min intervals during the whole 3.5-h observation period. The first EEG signal became apparent at ~10min post-Pilo. The EEG amplitude across most frequency bands peaked at ~40 min post-Pilo, and showed strong (r~ .72-.96) temporal correlation with eTau, but no correlation with eGln or eGlu. MSO pretreatment delayed the first EEG signal in Pilo-treated rats by ~10min, and depressed the EEG amplitude across most frequency bands, to values that remained strongly correlated with eTau (r> .92) and moderately correlated (r~ -.59) with eGln, but not with eGlu. Strong correlation between attenuation of Pilo-induced seizures and Tau release indicates that the beneficial effect of MSO is due to the prevention of cell volume increase concurrent with the onset of seizures.

Perinatal stroke and overlapping clinical presentation with HIE; studying practical diagnostic and management challenges through observational analysis of a single tertiary centre stroke patients

Background: While therapeutic hypothermia is accepted as a standard of care for improving neurological outcome for HIE patients, evidence of its benefits for neonatal stroke is lacking. Neurological presentations of HIE and neonatal stroke can be difficult to distinguish and indeed neonatal stroke can coexist with HIE. Our observational analysis of a single centre cohort of stroke infants with MRI diagnosis highlights the practical challenges for distinguishing between the two groups and reaching an early definitive diagnosis to inform appropriate treatment. Methods: A retrospective cohort study of term neonates &gt;37 weeks gestation born between May 2011 and April 2020 born at a specialised NICU network in the East of England with a principal diagnosis of neonatal stroke were obtained from Badgernet data. Results: 81% of infants (13/16) had sentinel events around delivery. 50% (8/16) of infants were therapeutically cooled. Of the 8 cooled infants only 3 (37%) of cooled infants fulfilled both Toby A and B criteria. Infants who received therapeutic hypothermia were more likely to present with early onset seizures (5/8) than infants who were not cooled (1/8) (p=0.019) . 6 of the 8 non-cooled infants compared to 2of the 8 cooled infants (p=0.03) had a higher seizure burden requiring escalation of antiepileptic medication to second line or need for maintenance treatment. Conclusion: Infants with neonatal stroke who present with early seizures are more likely to receive therapeutic hypothermia despite failure to fulfil both Toby A and B criteria. Early suspicion to inform management can be obtained more effectively from CFM while cranial ultrasound findings are generally non-specific. A normal CFM background, unilateral abnormal background and unilateral seizure activity are highly suggestive of neonatal stroke.

Specificity and sensitivity of the SeLECT score in predicting late seizures in patients undergoing intravenous thrombolytic treatment and the effect of diabetes mellitus and leukoaraiosis

Seizures after stroke can negatively affect the prognosis of ischemic stroke and cause a decrease in quality of life. The efficacy of intravenous (IV) recombinant tissue plasminogen activator (rt-PA) treatment in acute ischemic stroke has been demonstrated in many studies, and IV rt-PA treatment has been increasingly used around the world. The SeLECT score is a useful score for the prediction of late seizures after stroke and includes the severity of stroke (Se), large artery atherosclerosis (L), early seizure (E), cortical involvement (C), and the territory of the middle cerebral artery (T). However, the specificity and sensitivity of the SeLECT score have not been studied in acute ischemic stroke patients that received IV rt-PA treatment. In the present study, we aimed to validate and develop the SeLECT score in acute ischemic stroke patients receiving IV rt-PA treatment. The present study included 157 patients who received IV thrombolytic treatment in our third-stage hospital. The 1-year seizure rates of the patients were detected. SeLECT scores were calculated. In our study, we found that the SeLECT score had low sensitivity but high specificity for predicting the likelihood of late seizure after stroke in patients administered IV rt-PA therapy. In addition to the SeLECT score, we found that the specificity and sensitivity were higher when we evaluated diabetes mellitus (DM) and leukoaraiosis. We found that DM was an independent risk factor for late seizures after stroke in a patient group receiving thrombolytic therapy, and late seizures after stroke were less frequent in patients with leukoaraiosis.