Potential of focal cortical dysplasia in migraine pathogenesis.

Focal cortical dysplasias are abnormalities of the cerebral cortex associated with an elevated risk of neurological disturbances. Cortical spreading depolarization/depression is a correlate of migraine aura/headache and a trigger of migraine pain mechanisms. However, cortical spreading depolarization/depression is associated with cortical structural changes, which can be classified as transient focal cortical dysplasias. Migraine is reported to be associated with changes in various brain structures, including malformations and lesions in the cortex. Such malformations may be related to focal cortical dysplasias, which may play a role in migraine pathogenesis. Results obtained so far suggest that focal cortical dysplasias may belong to the causes and consequences of migraine. Certain focal cortical dysplasias may lower the threshold of cortical excitability and facilitate the action of migraine triggers. Migraine prevalence in epileptic patients is higher than in the general population, and focal cortical dysplasias are an established element of epilepsy pathogenesis. In this narrative/hypothesis review, we present mainly information on cortical structural changes in migraine, but studies on structural alterations in deep white matter and other brain regions are also presented. We develop the hypothesis that focal cortical dysplasias may be causally associated with migraine and link pathogeneses of migraine and epilepsy.

Post-Traumatic Epilepsy and Comorbidities: Advanced Models, Molecular Mechanisms, Biomarkers, and Novel Therapeutic Interventions.

Post-traumatic epilepsy (PTE) is one of the most devastating long-term, network consequences of traumatic brain injury (TBI). There is currently no approved treatment that can prevent onset of spontaneous seizures associated with brain injury, and many cases of PTE are refractory to antiseizure medications. Post-traumatic epileptogenesis is an enduring process by which a normal brain exhibits hypersynchronous excitability after a head injury incident. Understanding the neural networks and molecular pathologies involved in epileptogenesis are key to preventing its development or modifying disease progression. In this article, we describe a critical appraisal of the current state of PTE research with an emphasis on experimental models, molecular mechanisms of post-traumatic epileptogenesis, potential biomarkers, and the burden of PTE-associated comorbidities. The goal of epilepsy research is to identify new therapeutic strategies that can prevent PTE development or interrupt the epileptogenic process and relieve associated neuropsychiatric comorbidities. Therefore, we also describe current preclinical and clinical data on the treatment of PTE sequelae. Differences in injury patterns, latency period, and biomarkers are outlined in the context of animal model validation, pathophysiology, seizure frequency, and behavior. Improving TBI recovery and preventing seizure onset are complex and challenging tasks; however, much progress has been made within this decade demonstrating disease modifying, anti-inflammatory, and neuroprotective strategies, suggesting this goal is pragmatic. Our understanding of PTE is continuously evolving, and improved preclinical models allow for accelerated testing of critically needed novel therapeutic interventions in military and civilian persons at high risk for PTE and its devastating comorbidities. SIGNIFICANCE STATEMENT: Post-traumatic epilepsy is a chronic seizure condition after brain injury. With few models and limited understanding of the underlying progression of epileptogenesis, progress is extremely slow to find a preventative treatment for PTE. This study reviews the current state of modeling, pathology, biomarkers, and potential interventions for PTE and comorbidities. There's new optimism in finding a drug therapy for preventing PTE in people at risk, such as after traumatic brain injury, concussion, and serious brain injuries, especially in military persons.

Bi-allelic variants in SPATA5L1 lead to intellectual disability, spastic-dystonic cerebral palsy, epilepsy, and hearing loss.

Spermatogenesis-associated 5 like 1 (SPATA5L1) represents an orphan gene encoding a protein of unknown function. We report 28 bi-allelic variants in SPATA5L1 associated with sensorineural hearing loss in 47 individuals from 28 (26 unrelated) families. In addition, 25/47 affected individuals (53%) presented with microcephaly, developmental delay/intellectual disability, cerebral palsy, and/or epilepsy. Modeling indicated damaging effect of variants on the protein, largely via destabilizing effects on protein domains. Brain imaging revealed diminished cerebral volume, thin corpus callosum, and periventricular leukomalacia, and quantitative volumetry demonstrated significantly diminished white matter volumes in several individuals. Immunofluorescent imaging in rat hippocampal neurons revealed localization of Spata5l1 in neuronal and glial cell nuclei and more prominent expression in neurons. In the rodent inner ear, Spata5l1 is expressed in the neurosensory hair cells and inner ear supporting cells. Transcriptomic analysis performed with fibroblasts from affected individuals was able to distinguish affected from controls by principal components. Analysis of differentially expressed genes and networks suggested a role for SPATA5L1 in cell surface adhesion receptor function, intracellular focal adhesions, and DNA replication and mitosis. Collectively, our results indicate that bi-allelic SPATA5L1 variants lead to a human disease characterized by sensorineural hearing loss (SNHL) with or without a nonprogressive mixed neurodevelopmental phenotype.

Neuropathological Insights into Unexpected Cognitive Decline in Epilepsy.

OBJECTIVE: Some patients unexpectedly display an unfavorable cognitive course after epilepsy surgery subsequent to any direct cognitive sequelae of the surgical treatment. Therefore, we conducted in-depth neuropathological examinations of resective specimens from corresponding patients to provide insights as to the underlying disease processes. METHODS: In this study, cases with significant cognitive deterioration following a previous postoperative assessment were extracted from the neuropsychological database of a longstanding epilepsy surgical program. An extensive reanalysis of available specimens was performed using current, state-of-the-art neuropathological examinations. Patients without cognitive deterioration but matched in regard to basic pathologies served as controls. RESULTS: Among the 355 operated patients who had undergone more than one postoperative neuropsychological examination, 30 (8%) showed significant cognitive decline in the period after surgery. Of the 24 patients with available specimens, 71% displayed further neuropathological changes in addition to the typical spectrum (ie, hippocampal sclerosis, focal cortical dysplasias, vascular lesions, and low-grade tumors), indicating (1) a secondary, putatively epilepsy-independent neurodegenerative disease process; (2) limbic inflammation; or (3) the enigmatic pathology pattern of "hippocampal gliosis" without segmental neurodegeneration. In the controls, the matched individual principal epilepsy-associated pathologies were not found in combination with the secondary pathology patterns of the study group. INTERPRETATION: Our findings indicate that patients who unexpectedly displayed unfavorable cognitive development beyond any direct surgical effects show rare and very particular pathogenetic causes or parallel, presumably independent, neurodegenerative alterations. A multicenter collection of such cases would be appreciated to discern presurgical biomarkers that help with surgical decision-making. ANN NEUROL 2023;93:536-550.

Which terms should be used to describe medications used in the treatment of seizure disorders? An ILAE position paper.

A variety of terms, such as "antiepileptic," "anticonvulsant," and "antiseizure" have been historically applied to medications for the treatment of seizure disorders. Terminology is important because using terms that do not accurately reflect the action of specific treatments may result in a misunderstanding of their effects and inappropriate use. The present International League Against Epilepsy (ILAE) position paper used a Delphi approach to develop recommendations on English-language terminology applicable to pharmacological agents currently approved for treating seizure disorders. There was consensus that these medications should be collectively named "antiseizure medications". This term accurately reflects their primarily symptomatic effect against seizures and reduces the possibility of health care practitioners, patients, or caregivers having undue expectations or an incorrect understanding of the real action of these medications. The term "antiseizure" to describe these agents does not exclude the possibility of beneficial effects on the course of the disease and comorbidities that result from the downstream effects of seizures, whenever these beneficial effects can be explained solely by the suppression of seizure activity. It is acknowledged that other treatments, mostly under development, can exert direct favorable actions on the underlying disease or its progression, by having "antiepileptogenic" or "disease-modifying" effects. A more-refined terminology to describe precisely these actions needs to be developed.

Epilepsy phenotype and its reproducibility after lateral fluid percussion-induced traumatic brain injury in rats: Multicenter EpiBioS4Rx study project 1.

OBJECTIVE: This study was undertaken to assess reproducibility of the epilepsy outcome and phenotype in a lateral fluid percussion model of posttraumatic epilepsy (PTE) across three study sites. METHODS: A total of 525 adult male Sprague Dawley rats were randomized to lateral fluid percussion-induced brain injury (FPI) or sham operation. Of these, 264 were assigned to magnetic resonance imaging (MRI cohort, 43 sham, 221 traumatic brain injury [TBI]) and 261 to electrophysiological follow-up (EEG cohort, 41 sham, 220 TBI). A major effort was made to harmonize the rats, materials, equipment, procedures, and monitoring systems. On the 7th post-TBI month, rats were video-EEG monitored for epilepsy diagnosis. RESULTS: A total of 245 rats were video-EEG phenotyped for epilepsy on the 7th postinjury month (121 in MRI cohort, 124 in EEG cohort). In the whole cohort (n = 245), the prevalence of PTE in rats with TBI was 22%, being 27% in the MRI and 18% in the EEG cohort (p > .05). Prevalence of PTE did not differ between the three study sites (p > .05). The average seizure frequency was .317 ± .725 seizures/day at University of Eastern Finland (UEF; Finland), .085 ± .067 at Monash University (Monash; Australia), and .299 ± .266 at University of California, Los Angeles (UCLA; USA; p < .01 as compared to Monash). The average seizure duration did not differ between UEF (104 ± 48 s), Monash (90 ± 33 s), and UCLA (105 ± 473 s; p > .05). Of the 219 seizures, 53% occurred as part of a seizure cluster (≥3 seizures/24 h; p >.05 between the study sites). Of the 209 seizures, 56% occurred during lights-on period and 44% during lights-off period (p > .05 between the study sites). SIGNIFICANCE: The PTE phenotype induced by lateral FPI is reproducible in a multicenter design. Our study supports the feasibility of performing preclinical multicenter trials in PTE to increase statistical power and experimental rigor to produce clinically translatable data to combat epileptogenesis after TBI.

Neurological morbidity of surgery for suprasylvian operculoinsular epilepsy.

OBJECTIVE: The objective of this study was to identify risk factors associated with surgery-related neurological morbidity in patients with drug-resistant epilepsy undergoing suprasylvian operculoinsular resections. As secondary outcomes, we also analyzed the risk factors for ischemic lesion (IL) of corona radiata and seizure recurrence. METHODS: A retrospective analysis was conducted on a cohort of patients who underwent suprasylvian operculoinsular resections for drug-resistant epilepsy. The association of several presurgical, surgical, and postsurgical factors with both primary (persistent neurological deficits) and secondary (structural abnormalities on postoperative magnetic resonance imaging [MRI] and seizure recurrence) postoperative outcomes was investigated with univariate and multivariate statistical analysis. RESULTS: The study included a total of 65 patients; 46.2% of patients exhibited postoperative neurological deficits, but only 12.3% experienced persistent deficits. On postoperative MRI, IL in the corona radiata and corticospinal tract Wallerian degeneration (CSTWd) were seen in 68% and 29% of cases, respectively. Only CSTWd was significantly associated with persistent neurological deficits (relative risk [RR] = 2.6). Combined operculoinsular resection (RR = 3.62) and surgery performed on the left hemisphere (RR = .37) were independently associated with IL in the corona radiata. Variables independently associated with CSTWd were the presence of malacic components in the IL (RR = 1.96), right central operculum resection (RR = 1.79), and increasing age at surgery (RR = 1.03). Sixty-two patients had a postoperative follow-up > 12 months (median = 56, interquartile range = 30.75-73.5), and 62.9% were in Engel class I at last outpatient control. The risk of seizure recurrence was reduced by selective opercular resection (RR = .25) and increased by the histological diagnosis of aspecific gliosis (RR = 1.39). SIGNIFICANCE: This study provides insights into the risk factors associated with surgery-related neurological morbidity, as well as further evidence on the postoperative occurrence of subcortical injury and seizure recurrence in epileptic patients undergoing suprasylvian operculoinsular resections. The findings highlighted in this study may be useful to better understand the processes supporting the increased surgical risk in the operculoinsular region.

Association of outdoor air and noise pollution with unprovoked seizures and new onset epilepsy: A systematic review and meta-analysis.

Research has indicated that certain environmental exposures may increase the risk of unprovoked seizures and new onset epilepsy. This study aimed to synthesize the literature that has estimated the associations between short- and long-term exposure to outdoor air and noise pollution and the risk of unprovoked seizures and new onset epilepsy. We searched Embase, MEDLINE, Scopus, Web of Science, BIOSIS Previews, Latin American and Caribbean Health Sciences Literature, Proquest Dissertations and Theses, conference abstracts, and the gray literature and conducted citation tracing in June 2023. Observational and ecological studies assessing the associations of air and noise pollution with unprovoked seizures or new onset epilepsy were eligible. One reviewer extracted summary data. Using fixed and random effects models, we calculated the pooled risk ratios (RRs) for the studies assessing the associations between short-term exposure to air pollution and unprovoked seizures. Seventeen studies were included, 16 assessing the association of air pollution with seizures and one with epilepsy. Eight studies were pooled quantitatively. Ozone (O3; RR = .99, 95% confidence interval [CI] = .99-.99) and nitrogen dioxide (NO2) exposure adjusted for particulate matter (RR = 1.02, 95% CI = 1.01-1.02) on the same day, and carbon monoxide (CO) exposure 2 days prior (RR = 1.12, 95% CI = 1.02-1.22), were associated with seizure risk. A single study of air pollution and epilepsy did not report a significant association. The risk of bias and heterogeneity across studies was moderate or high. Short-term exposure to O3, NO2, and CO may affect the risk of seizures; however, the effect estimates for O3 and NO2 were minimal. Additional research should continue to explore these and the associations between outdoor air pollution and epilepsy and between noise pollution and seizures and epilepsy.

Tumor-related epilepsy in high-grade glioma: a large series survival analysis.

PURPOSE: Seizures are a common clinical occurrence in high-grade glioma (HGG). While many studies have explored seizure incidence and prevalence in HGG, limited studies have examined the prognostic effect of seizures occurring in the post-diagnosis setting. This study aims to assess the impact of seizure presentation on HGG survival outcomes. METHODS: Single-center retrospective review identified 950 patients with histologically-confirmed high-grade glioma. Seizure presentation was determined by clinical history and classified as early onset (occurring within 30 days of HGG presentation) or late onset (first seizure occurring after beginning HGG treatment). The primary outcome, hazard ratios for overall survival and progression-free survival, was assessed with multivariable Cox proportional-hazards models. IDH1 mutation status (assessed through immunohistochemistry) was only consistently available beginning in 2015; subgroup analyses were performed in the subset of patients with known IDH1 status. RESULTS: Epileptic activity before (HR = 0.81, 95% CI = 0.68-0.96, P = 0.017) or after (HR = 0.74, 95% CI = 0.60-0.91, P = 0.005) HGG diagnosis associated with improved overall survival. Additionally, late seizure onset significantly associated with lower odds of achieving partial (OR = 0.25, 95% CI = 0.12-0.53, P = < 0.001) or complete (OR = 0.30, 95% CI = 0.18-0.50, P < 0.001) seizure control than patients with early seizure onset. CONCLUSIONS: Clinical seizures both at the time of diagnosis and later during the HGG treatment course are associated with improved overall survival. This association potentially persists for both IDH1-wildtype and IDH1-mutant patients, but further study is required.

Efficacy of rTMS for poststroke epilepsy and its effects on patients' cognitive function and depressive status.

OBJECTIVE: This study aimed to investigate the efficacy of rTMS in the treatment of poststroke epilepsy and the effect of rTMS on patients' cognitive function and depressive status. METHODS: One hundred and twenty-one poststroke epilepsy patients with mild cognitive impairment and depressive status admitted to the Department of Neurology of the Second People's Hospital of Nanning from January 1, 2017, to April 31, 2023, were selected and divided into the rTMS treatment group (treated group) and the control group. MMSE scores and HAMD scores were recorded before and after treatment. The frequency of EEG spiky waves recorded before and after treatment within 24 h and the frequency of any clinical seizure form (the number of clinical seizures within 1 month after treatment) and changes in observed indices before and after treatment were calculated. The differences between the data of the two groups were analyzed, to further assess the efficacy of rTMS in the treatment of poststroke epilepsy and the rTMS' effects on cognition and depression. RESULTS: Compared with drug treatment alone, rTMS significantly decreased clinical seizures and epileptiform discharges after stroke, especially in patients with lesions in the frontal, temporal, and parietal lobes. Compared with drug treatment alone, rTMS treatment can effectively reduce cognitive impairment and mood disorders, such as depression, especially for patients with lesions in the frontal and temporal lobes. The results of this experiment suggest that rTMS treatment does not increase adverse effects. CONCLUSION: rTMS reduces clinical seizures while improving cognitive impairment and depression in patients with epilepsy. Therefore, we suggest that low-frequency rTMS can be used as an adjunctive treatment for patients with epilepsy and provide some ideas and references for the treatment of epilepsy with cognitive impairment and depression.

A rare case of lupus cerebritis presenting as ictal epileptic headache: A case report.

Ictal epileptic headache, characterized by headache as the sole symptom of a seizure attack, is a rare condition. In this case report, we present a 52-year-old female with a history of systemic lupus erythematosus who sought medical attention at the headache clinic due to a new type of headache. The headache was described as an intense painful wave followed by a dull headache, without autonomic symptoms or migrainous features. Magnetic resonance imaging revealed an enhancing lesion in the left hippocampus in addition to two other lesions in the corpus callosum and left parieto-occipital lobe. Electroencephalography during the headache episodes showed epileptic discharges originating from the left fronto-temporal region. The patient was initiated on levetiracetam, which resulted in the resolution of both the epileptic discharges and the headaches. This case underscores the significance of considering ictal epileptic headache as a potential secondary cause for headaches, particularly in patients with underlying conditions that may predispose them to epilepsy, such as systemic lupus erythematosus.

Patient-Centered Management of Brain Tumor-Related Epilepsy.

PURPOSE OF REVIEW: Brain tumor-related epilepsy is a heterogenous syndrome involving variability in incidence, timing, pathophysiology, and clinical risk factors for seizures across different brain tumor pathologies. Seizure risk and disability are dynamic over the course of disease and influenced by tumor-directed treatments, necessitating individualized patient-centered management strategies to optimize quality of life. RECENT FINDINGS: Recent translational findings in diffuse gliomas indicate a dynamic bidirectional relationship between glioma growth and hyperexcitability. Certain non-invasive measures of hyperexcitability are correlated with survival outcomes, however it remains uncertain how to define and measure clinically relevant hyperexcitability serially over time. The extent of resection, timing of pre-operative and/or post-operative seizures, and the likelihood of tumor progression are critical factors impacting the risk of seizure recurrence. Newer anti-seizure medications are generally well-tolerated with similar efficacy in this population, and several rapid-onset seizure rescue agents are in development and available. Seizures in patients with brain tumors are strongly influenced by the underlying tumor biology and treatment. An improved understanding of the interactions between tumor cells and the spectrum of hyperexcitability will facilitate targeted therapies. Multidisciplinary management of seizures should occur with consideration of tumor-directed therapy and prognosis, and anti-seizure medication decision-making tailored to the individual priorities and quality of life of the patient.

Epileptogenesis in tuberous sclerosis complex-related developmental and epileptic encephalopathy.

Epileptogenesis in infants with tuberous sclerosis complex (TSC) is a gradual and dynamic process, leading to early onset and difficult-to-treat seizures. Several cellular, molecular and pathophysiologic mechanisms, including mammalian target of rapamycin (mTOR) dysregulation, GABAergic dysfunction and abnormal connectivity, may play a role in this epileptogenic process and may also contribute to the associated developmental encephalopathy. Disease-specific antiseizure medications or drugs targeting the mTOR pathway have proved to be effective in TSC-associated epilepsy. Pre-symptomatic administration of vigabatrin, a GABAergic drug, delays seizure onset and reduces the risk of a subsequent epileptic encephalopathy, such as infantile spasms syndrome or Lennox-Gastaut syndrome. Everolimus, a rapamycin-derived mTOR inhibitor, reduces seizure frequency, especially in younger patients. This evidence suggests that everolimus should be considered early in the course of epilepsy. Future trials are needed to optimize the use of everolimus and determine whether earlier correction of mTOR dysregulation can prevent progression to developmental and epileptic encephalopathies or mitigate their severity in infants with TSC. Clinical trials of several other potential antiseizure drugs (cannabidiol and ganaxolone) that target contributing mechanisms are also underway. This review provides an overview of the different biological mechanisms occurring in parallel and interacting throughout the life course, even beyond the epileptogenic process, in individuals with TSC. These complexities highlight the challenges faced in preventing and treating TSC-related developmental and epileptic encephalopathy.

The incidence and predictive factors of secondary epilepsy in patients with supratentorial brain metastases (st-BMs) after stereotactic radiosurgery: A multicenter retrospective study.

OBJECTIVE: To evaluate the incidence and the independent risk factors of SRS-related epilepsy in patients with supratentorial brain metastases (st-BMs), providing evidences for prevention or reduction secondary epilepsy after SRS. METHODS: Patients with st-BMs from four gamma knife centers who developed secondary epilepsy after SRS were retrospectively studied between January 1, 2017 and June 31, 2023. The incidence and clinical characteristics of the patients with secondary epilepsy were analyzed. The predictive role of baseline clinical-demographic variables was evaluated according to univariate and multivariate logistic regression model. The impact of secondary epilepsy on patients' OS was evaluated as well by log-rank test. RESULTS: 11.3 % (126/1120) of the patients with totally 158 st-BMs experienced secondary epilepsy after SRS in median 21 days. 61.9 % (78/126) of the patients experienced simple partial seizures. 91.3 % (115/126) patients achieved good seizure control after received 1-2 kinds of AEDs for median 90 days, while 7.1 % (9/126) of the patients suffered from refractory epilepsy. Patients had higher risk of secondary epilepsy if the tumor located in cortex and/or hippocampus, peri-tumor edema larger than 20.3 cm3 before SRS, had epilepsy history, and failed to receive bevacizumab prior to SRS. There was no difference in the OS of patients who experience secondary epilepsy or not after SRS. CONCLUSIONS: The incidence of SRS-related secondary epilepsy is 11.3 % in patients with st-BMs in this retrospective study. The risk of secondary epilepsy is higher in patients with st-BM located in cortex and/or hippocampus area, peri-tumor edema larger than 20.3 cm3 before SRS, and epilepsy history. Bevacizumab is suggested prior to SRS therapy, as it could be used for the control of peri-tumor edema and SRS-related damage, hence reduce the risk of secondary epilepsy. However, whether or not patients suffered from secondary epilepsy after SRS does not affect their OS.

Early focal electroencephalogram and neuroimaging findings predict epilepsy development after aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Seizures are a common complication of subarachnoid hemorrhage (SAH) in both acute and late stages: 10-20 % acute symptomatic seizures, 12-25 % epilepsy rate at five years. Our aim was to identify early electroencephalogram (EEG) and computed tomography (CT) findings that could predict long-term epilepsy after SAH. MATERIAL AND METHODS: This is a multicenter, retrospective, longitudinal study of adult patients with aneurysmal SAH admitted to two tertiary care hospitals between January 2011 to December 2022. Routine 30-minute EEG recording was performed in all subjects during admission period. Exclusion criteria were the presence of prior structural brain lesions and/or known epilepsy. We documented the presence of SAH-related cortical involvement in brain CT and focal electrographic abnormalities (epileptiform and non-epileptiform). Post-SAH epilepsy was defined as the occurrence of remote unprovoked seizures ≥ 7 days from the bleeding. RESULTS: We included 278 patients with a median follow-up of 2.4 years. The mean age was 57 (+/-12) years, 188 (68 %) were female and 49 (17.6 %) developed epilepsy with a median latency of 174 days (IQR 49-479). Cortical brain lesions were present in 189 (68 %) and focal EEG abnormalities were detected in 158 patients (39 epileptiform discharges, 119 non-epileptiform abnormalities). The median delay to the first EEG recording was 6 days (IQR 2-12). Multiple Cox regression analysis showed higher risk of long-term epilepsy in those patients with CT cortical involvement (HR 2.6 [1.3-5.2], p 0.009), EEG focal non-epileptiform abnormalities (HR 3.7 [1.6-8.2], p 0.002) and epileptiform discharges (HR 6.7 [2.8-15.8], p < 0.001). Concomitant use of anesthetics and/or antiseizure medication during EEG recording had no influence over its predictive capacity. ROC-curve analysis of the model showed good predictive capability at 5 years (AUC 0.80, 95 %CI 0.74-0.87). CONCLUSIONS: Focal electrographic abnormalities (both epileptiform and non-epileptiform abnormalities) and cortical involvement in neuroimaging predict the development of long-term epilepsy. In-patient EEG and CT findings could allow an early risk stratification and facilitate a personalized follow-up and management of SAH patients.

Clinical characteristics and surgical outcomes of epilepsy associated with temporal encephalocele: A systematic review.

Temporal encephaloceles (TE) are an under-identified, potentially intervenable cause of epilepsy. This systematic review consolidates the current data to identify the major clinical, neuroimaging, and EEG features and surgical outcomes of epilepsy associated with TE. Literature searches were carried out using MEDLINE, Embase, PsycINFO, Scopus, and Cochrane Library databases from inception to December 7, 2023. Studies were included if they described clinical, neuroimaging, EEG, or surgical data in ≥5 patients with TE and epilepsy. Of 562 studies identified in the search, 24 met the eligibility criteria, reporting 423 unique patients with both epilepsy and TE. Compared to epilepsy patients without TE, those with TE had a higher mean age of seizure onset and were less likely to have a history of febrile seizures. Seizure semiologies were variable, but primarily mirrored temporal lobe onset patterns. Epilepsy patients with TE had a higher likelihood of having clinical or radiographic features of idiopathic intracranial hypertension (IIH) than those without. Brain MRI may show ipsilateral mesial temporal sclerosis (16 %). CT scans of the skull base usually revealed bony defects near the TE (90 %). Brain PET scans primarily showed ipsilateral temporal lobe hypometabolism (80 %), mostly in the anterior temporal lobe (67 %). Scalp EEG mostly lateralized ipsilateral to the implicated TE (92 % seizure onset) and localized to the temporal lobe (96 %). Intracranial EEG revealed seizure onset near the TE (11 of 12 cases including TE-adjacent electrodes) with variable timing of spread to the ipsilateral hippocampus. After surgical treatment of the TE, the rate of Engel I or ILAE 1 outcomes at one year was 75 % for lesionectomy, 85 % for anterior temporal lobectomy (ATL), and 80 % for ATL with amygdalohippocampectomy. Further studies are needed to better elucidate the relationship between IIH, TE, and epilepsy, improve the identification of TE, and optimize surgical interventions.

Neuropsychological outcome after frontal surgery for pediatric-onset epilepsy with focal cortical dysplasia in adolescent and young adult.

OBJECTIVE: We investigated neuropsychological outcome in patients with pharmacoresistant pediatric-onset epilepsy caused by focal cortical dysplasia (FCD), who underwent frontal lobe resection during adolescence and young adulthood. METHODS: Twenty-seven patients were studied, comprising 15 patients who underwent language-dominant side resection (LDR) and 12 patients who had languagenondominant side resection (n-LDR). We evaluated intelligence (language function, arithmetic ability, working memory, processing speed, visuo-spatial reasoning), executive function, and memory in these patients before and two years after resection surgery. We analyzed the relationship between neuropsychological outcome and resected regions (side of language dominance and location). RESULTS: Although 75% of the patients showed improvement or no change in individual neuropsychological tests after surgical intervention, 25% showed decline. The cognitive tests that showed improvement or decline varied between LDR and n-LDR. In patients who had LDR, decline was observed in Vocabulary and Phonemic Fluency (both 5/15 patients), especially after resection of ventrolateral frontal cortex, and improvement was observed in WCST-Category (7/14 patients), Block Design (6/15 patients), Digit Symbol (4/15 patients), and Delayed Recall (3/9 patients). In patients who underwent n-LDR, improvement was observed in Vocabulary (3/12 patients), but decline was observed in Block Design (2/9 patients), and WCST-Category (2/9 patients) after resection of dorsolateral frontal cortex; and Arithmetic (3/10 patients) declined after resection of dorsolateral frontal cortex or ventrolateral frontal cortex. General Memory (3/8 patients), Visual Memory (3/8 patients), Delayed Recall (3/8 patients), Verbal Memory (2/9 patients), and Digit Symbol (3/12 patients) also declined after n-LDR. CONCLUSION: Postoperative changes in cognitive function varied depending on the location and side of the resection. For precise presurgical prediction of neuropsychological outcome after surgery, further prospective studies are needed to accumulate data of cognitive changes in relation to the resection site.

Tuberous sclerosis complex in adulthood: focus on epilepsy prognosis.

OBJECTIVE: Typically diagnosed in early childhood or adolescence, TSC is a chronic, multisystemic disorder with age-dependent manifestations posing a challenge for transition and for specific surveillance throughout the lifetime. Data on the clinical features and severity of TSC in adults and on the prognosis of epilepsy are scarce. We analyzed the clinical and genetic features of a cohort of adult patients with TSC, to identify the prognostic predictors of seizure remission after a long follow-up. METHOD: We conducted a retrospective analysis of patients diagnosed with TSC according to the updated international diagnostic criteria. Pearson's chi-square or Fisher's exact test and Mann Whitney U test were used to compare variables among the Remission (R) and Non-Remission (NR) group. Univariate and multivariate logistic regression analyses were performed. RESULTS: We selected 43 patients with TSC and neurological involvement in terms of epilepsy and/or brain lesions, attending the Epilepsy Center of our Institute: of them, 16 (37.2%) were transitioning from the pediatric care and 6 (13.9%) were referred by other specialists. Multiorgan involvement includes cutaneous (86.0%), nephrological (70.7%), hepatic (40.0%), ocular (34.3%), pneumological (28.6%) and cardiac (26.3%) manifestations. Thirty-nine patients (90.7 %) had epilepsy. The mean age at seizure onset was 4 ± 7.3 years: most patients (29, 76.3 %) presented with focal seizures or spasms by age 3 years; only 2 (5.3 %) had seizure onset in adulthood. Twenty-seven patients (69.2 %) experienced multiple seizure types overtime, 23 (59.0 %) had intellectual disability (ID). At last assessment, 14 (35.9 %) were seizure free (R group) and 25 (64.1 %) had drug-resistant seizures (NR group). At logistic regression univariate analysis, ID (OR 7.9, 95 % CI 1.8--34.7), multiple seizure types lifelong (OR 13.2, 95 % CI 2.6- 67.2), spasms/tonic seizures at presentation (OR 6.5, 95 % CI 1.2--35.2), a higher seizure frequency at onset (OR 5.4, 95 % CI 1.2--24.3), abnormal neurological examination (OR 9.8, 95 % CI 1.1--90.6) and pathogenic variants in TSC2 (OR 5.4, 95 % CI 1.2--24.5) were significantly associated with non-remission. In the multivariate analysis, both ID and multiple seizure types lifelong were confirmed as independent predictors of poor seizure outcome. CONCLUSIONS: In our cohort of adult patients with TSC, epilepsy remains one of the main neurological challenges with only 5.3% of cases manifesting in adulthood. Approximately 64% of these patients failed to achieve seizure remission. ID and multiple seizure types were the main predictors of poor outcome. Nephrological manifestations require continuous specific follow-up in adults.

Surgical treatment for drug-resistant epilepsy due to early brain injury in children.

BACKGROUND: The study aimed to summarize the indications and clinical features of pediatric drug-resistant epilepsy associated with early brain injury, surgical outcomes, and prognostic factors. METHODS: We retrospectively analyzed children diagnosed with drug-resistant epilepsy due to early brain injury, who had undergone surgery at the Pediatric Epilepsy Center of Peking University First Hospital from May 2014 to May 2021. Clinical data of vasculogenic and non-vasculogenic injuries from early brain damage were compared and analyzed. The surgical outcomes were assessed using the Engel grading system. RESULTS: The median ages at acquiring injury, seizure onset, and surgery among 65 children were 19.0 (0-120) days, 8.6 (0-136.5) months, and 62.9 (13.5-234) months, respectively. Of the 14 children with non-vasculogenic injuries, 12 had posterior ulegyria. Unilateral or bilateral synchronous interictal epileptiform discharges were located mainly in the posterior quadrant in 10 children (71 %), and unilateral posterior quadrant or non-lateralized ictal region in eight children (57 %). The surgical approach was mainly temporo-parieto-occipital or parieto-occipital disconnection in nine children. Of 49 children with vasculogenic injuries, magnetic resonance imaging revealed hemispheric abnormalities in 38. Unilaterally hemispheric or bilateral interictal epileptiform discharges were observed in 36 children (73 %), whereas 42 (86 %) had unilateral hemispheric or non-lateralized ictal onset. The surgical procedure involved hemispherotomy in 38 children (78 %) and lobectomy or disconnection, multilobectomy or disconnection and hemispherotomy in 5, 20, and 40 children, respectively. Fifty-five patients (84.6 %) achieved remission from seizure during follow-up at 5.4 years. Age at surgery (odds ratio = 1.022, 95 % confidence interval = 1.003-1.042, P = 0.023) and etiology (odds ratio = 17.25, 95 % confidence interval = 2.778-107.108, P = 0.002) affected the seizure outcomes. CONCLUSION: Children with drug-resistant epilepsy due to early brain injury can successfully be treated with surgery after rigorous preoperative screening. Good surgical outcomes are associated with an early age at surgery and an etiology of vasculogenic injury.

Risk factors for epilepsy following arterial ischemic stroke childhood: A retrospective cohort study.

AIM: PSE is reported more frequently in childhood than in adults. In this study, we aimed to investigate potential risk factors for the development of post-stroke epilepsy (PSE) in children with arterial ischemic stroke (AIS). MATERIAL METHODS: The current retrospective cohort study included the medical records of 50 pediatric participants (aged 29 days to 18 years) diagnosed with AIS at a university hospital between January 2006 and December 2023. All information of the patients who were followed for at least two years for the development of PSE after AIS was entered into the hospital database and recorded in a pre-designed questionnaire. Acute symptomatic seizures were defined as seizures occurring within 7 days after stroke. Two or more late seizures occurring after the acute period (>7 days) were classified as PSE. The incidence of PSE and potential risk factors were investigated. RESULTS: After AIS, more than half of the patients (58 %) developed acute seizures and almost one-third (38 %) developed PSE. Risk factors associated with the development of PSE, very early seizures (within the first six hours), high stroke severity, cortical lesions, neurological deficits and low serum vitamin D levels were detected (p = 0.05, p = 0.036, p = 0.011, p < 0.001, p < 0.001, respectively). CONCLUSION: Seizures within the first six hours, high stroke severity, and neurological deficits are important risk factors for the development of PSE in children. Knowing the potential risk factors of PSE may be helpful for clinicians to identify high-risk patients. It can also contribute to treatment decision-making and post-discharge follow-up planning.