Abstract Objective Epileptogenic Index (EI) is a promising index to evaluate the epileptogenicity of the brain tissue and is useful in planning epilepsy surgery. We aimed to evaluate whether EI maps are consistent across seizures within patients and whether EI‐derived measures are affected by the vigilance state and anti‐seizure medication (ASM) dose. Methods We analyzed 127 stereoelectroencephalography (SEEG) seizures from 19 patients. EI was calculated in all seizures. Within‐patient EI consistency was assessed using pairwise Spearman correlations between seizure‐specific EI maps. To assess the effects of vigilance and ASM on EI consistency, we calculated a contact‐level p _weighted EI score that combines the frequency of suprathreshold EI involvement and mean EI magnitude, separately across vigilance states and in a subset of patients with different ASM states. Results Mean seizure‐to‐seizure EI correlations ranged from 0.11 to 0.81, indicating substantial variability in within‐patient EI consistency. Seven patients showed high consistency (≥0.6) and four showed low consistency (≤0.3). At the contact level, no differences in p _weighted EI were found between wakefulness and sleep. In contrast, p _weighted EI was significantly higher during reduced ASM compared with full ASM doses. Significance EI maps are not uniformly stable across seizures. ASM reduction may broaden or intensify EI‐defined epileptogenic involvement, suggesting that ASM status should be considered when interpreting EI during SEEG evaluation. These findings are hypothesis‐generating and require prospective validation to determine their clinical utility for surgical planning. Plain Language Summary The Epileptogenic Index (EI) measures the involvement of a recorded brain area during a specific seizure. This study shows that EI patterns can vary significantly between different seizures in the same patient. While sleep states do not change these patterns, reducing a patient's anti‐seizure medications increases EI values, making seizures appear to spread more broadly. These medication‐induced changes must be carefully considered to accurately map the epileptic network for surgical decisions.
Abstract Recent neuroimaging studies have suggested that epilepsy may show progressive brain structural changes over time. However, longitudinal hippocampal volume changes in temporal lobe epilepsy (TLE) have not been adequately compared with those observed in normal aging. In this study, we enrolled 46 patients with unilateral TLE and 25 healthy controls with longitudinal structural MRI scans using the same scanner. Hippocampal volumes were quantified using the Hipposeg software, and the annual percentage volume reduction relative to baseline (%Reduction/year) was calculated for each hippocampus. Compared to healthy hippocampi (median −0.37% per year, IQR = 3.97), both ipsilateral (median −1.04% per year, IQR = 3.65) and contralateral (median −1.08% per year, IQR = 3.17) hippocampi in TLE showed significantly greater volume reduction over time (both p < 0.05). Furthermore, annual ipsilateral hippocampal volume reduction was significantly correlated with disease duration (Spearman's r s = 0.366, FDR‐corrected p = 0.036), suggesting that hippocampal atrophy progresses more rapidly during the early stage after epilepsy onset. These findings indicate that hippocampal volume loss in TLE exceeds that expected from normal aging and provide further evidence supporting progressive structural alterations during the course of the disease. Plain Language Summary Temporal lobe epilepsy may cause progressive changes in the brain beyond those expected from normal aging. Using repeated MRI scans, we found that the hippocampus showed greater volume loss over time in people with temporal lobe epilepsy than in healthy individuals. This volume loss occurred bilaterally and appeared to be greater during the earlier stages of the disease. These results provide further evidence supporting progressive structural brain changes in TLE and contribute to a better understanding of disease progression and abnormal brain aging in epilepsy.
Abstract Objective Characterization of early neuropsychological outcomes following SEEG with radiofrequency thermocoagulation (RFTHC) is essential to guide patient expectations around return to work, study, and caregiving. The current study aimed to describe the early neurocognitive sequelae of SEEG. Methods Consecutive patients undergoing SEEG were prospectively recruited from two tertiary epilepsy centers in Melbourne, Australia. Patients were administered the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) via telehealth before and 3 weeks after SEEG ( M = 19.69 days, SD = 4.41). Given the telehealth platform, the coding subtest was substituted for the Symbol Digit Modalities Test, and a modified score of global cognitive function was calculated. To evaluate group changes, paired sample t ‐tests were performed. Reliable change indices were computed to explore individual‐level changes. Pearson's correlation coefficients evaluated relationships between change in global cognitive function and SEEG admission variables. SEEG patients were invited to complete a semi‐structured interview canvassing the recovery following SEEG. Results Twenty‐eight patients completed the neuropsychological examination ( M = 37.89 years, SD = 9.72, range = 17–56 years, 54% female). All patients underwent RFTHC with a mean of 11.43 (SD = 6.87, range = 2–28) coagulation sites. At a whole group level, 3‐weeks post SEEG there was no evidence for global nor domain‐specific cognitive change. Reliable change indices with 90% confidence revealed only 4% (1/28) declined on at least two measures and 10% (3/28) showed psychometric improvement. Pearson's correlational coefficients showed no evidence for association between change in global cognitive function with SEEG factors including admission length, number of spontaneous or stimulated seizures, number of electrodes, or number of RFTHC sites. Subjective reports of language change tended to be accompanied by a decline on the RBANS language index that did not meet reliable change criteria. Most patients reported returning to work around 4 weeks post SEEG. Significance By 3 weeks, gross cognitive functioning tends to be in keeping with pre‐SEEG performances for most patients. These findings have direct clinical implications for SEEG neuropsychological counseling. Plain Language Statement SEEG is increasingly used to guide epilepsy surgery. Despite this, little is known about the cognitive recovery in the weeks following the procedure. We found that for most patients, broad cognitive functioning 3 weeks after SEEG with coagulation was consistent with function before SEEG, with only a small minority showing significant changes. Some people who reported language difficulties also showed a decline on language testing, although this was often small. Of those patients working before SEEG, most returned to work by 4 weeks. These results provide important evidence to guide patient counseling, recovery planning, and management after SEEG.
Abstract Corpus callosotomy is an established palliative operation for drug‐resistant epilepsy dominated by drop attacks, and it is performed in three extents: anterior, usually of the anterior two‐thirds; total, in one or two stages; and selective posterior, which preserves the genu and rostral body. Meta‐analysis finds no difference between them in overall seizure reduction, a difference in drop attack control favoring the posterior approach, and a graded difference in disconnection syndrome, but there has never been a prospective head‐to‐head comparison, and the optimal extent of section remains undefined. A search of PubMed, Embase, and the Web of Science Core Collection identified 62 experimental studies in which the corpus callosum or another forebrain commissure was sectioned with an epilepsy‐related outcome, spanning 1948–2026 across six species and every major seizure model. This literature is neither absent nor recent. What it has almost never done is vary the extent of section: the few studies that varied it took the laterality of kindling transfer or of interictal synchrony as the endpoint, never seizure control and never cognitive cost. No study compares the three extents against a common outcome; none models the selective posterior operation as it is defined clinically; none randomizes between extents; and none combines graded disconnection with time‐locked bilateral electrophysiology, diffusion‐based verification of the fibers divided, and a behavioral read‐out in the same animals. The effect of section is also bidirectional: focal seizures may intensify through loss of transcallosal inhibition, and in the pentylenetetrazol model callosal section paradoxically facilitates convulsions, which limits chemoconvulsant preparations. The asymmetry between the clinical and experimental literatures is therefore one of method rather than of volume or attention: the two answered different questions, and the question the clinical field now asks requires a manipulation the experimental literature has never performed. Plain Language Summary Surgeons can treat severe epilepsies by cutting the bundle of fibers that joins the two halves of the brain, but they do not agree on how much of it to cut. We searched three databases and found 62 animal studies of this operation going back to 1948. Almost none of them compared different amounts of cutting, and none looked at the newest version of the operation. Answering the surgeons' question will require a new kind of animal experiment rather than more reading of the old ones.
Abstract Objective Guanidinoacetate methyltransferase (GAMT) deficiency is a rare autosomal recessive creatine biosynthesis disorder. Reports specifically focusing on adult patients remain scarce. Methods We report a 52‐year‐old female (the oldest documented case of GAMT deficiency to date) presenting with severe intellectual disability, refractory epilepsy, and adult‐onset disease progression. Whole‐exome sequencing identified novel compound heterozygous GAMT variants (c.265_267del and c.253G>T), and magnetic resonance spectroscopy confirmed cerebral creatine depletion. Remarkably, initiating oral creatine supplementation at age 52 achieved complete seizure freedom, normalization of the electroencephalogram (EEG), and significant motor function recovery. Results A comprehensive review revealed that untreated adult patients face a high risk of progressive neurological deterioration. Compared to the pediatric cohort, adults exhibited a significantly higher prevalence of movement disorders (69.2% vs. 33.1%, p < 0.001) and a trend toward a higher prevalence of epilepsy (92.3% vs. 74.2%). Especially, atonic seizures (drop attacks) are particularly characteristic of adult GAMT deficiency, with EEGs frequently demonstrating background slowing, multifocal epileptiform discharges, and electrodecremental patterns. Significance This study underscores that continuous disease progression and prolonged neurotoxicity still could compromise the well‐being of adult GAMT deficiency patients. Accurate diagnosis is essential for adults presenting with developmental and epileptic encephalopathy (DEE) phenotype, as even late treatment for GAMT deficiency can still dramatically alleviate the epileptic burden and reverse motor decline. Plain Language Summary We report the oldest known adult diagnosed with GAMT deficiency. Our case demonstrates that starting creatine treatment even at age 52 can dramatically reduce seizures and restore motor function. Literature shows that untreated adults suffer from more severe epilepsy and movement disorders than children, with symptoms worsening over time. These findings highlight the critical need for genetic testing in adults with unexplained severe epilepsy; timely creatine supplementation can halt cognitive decline and significantly restore quality of life.
