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Background and Objectives: Identification of an epileptogenic lesion on structural neuroimaging in individuals with focal epilepsy is important for management and treatment planning. The objective of this study was to determine the frequency of MRI-identified potentially epileptogenic structural abnormalities in a large multicenter study of adolescent and adult patients with newly diagnosed focal epilepsy., Methods: Patients with a new diagnosis of focal epilepsy enrolled in the Human Epilepsy Project observational cohort study underwent 3 T brain MRI using a standardized protocol. Imaging findings were classified as normal, abnormal, or incidental. Abnormal findings were classified as focal or diffuse and as likely epilepsy-related or of unknown relationship to epilepsy. Fisher exact tests were performed to determine whether abnormal imaging or abnormality type was associated with clinical characteristics., Results: A total of 418 participants were enrolled. Two hundred eighteen participants (59.3%) had no abnormalities detected, 149 (35.6%) had abnormal imaging, and 21 (5.0%) had incidental findings. Seventy-eight participants (18.7%) had abnormalities that were considered epilepsy-related, and 71 (17.0%) had abnormalities of unknown relationship to epilepsy. Older participants were more likely to have imaging abnormalities, while participants with focal and epilepsy-related imaging abnormalities were younger than those without these abnormalities. One hundred thirty-one participants (31.3%) had a family history of epilepsy. Epilepsy-related abnormalities were not associated with participant sex, family history of epilepsy, or seizure type., Discussion: We found that 1 in 5 patients with newly diagnosed focal epilepsy has an MRI finding that is likely causative and may alter treatment options. An additional 1 in 5 patients has abnormalities of unknown significance. This information is important for patient counseling, prognostication, and management., (© 2022 American Academy of Neurology.)

Background and Objectives: MRI and PET imaging enables subgroups of temporal lobe epilepsy (TLE) to be defined on the basis of structural pathology. Few studies have examined the variation in electroclinical seizure spread patterns based on imaging findings. We performed a retrospective cohort study to investigate the electroclinical differences among 3 specific groups of TLE: MRI-negative PET-positive TLE (MRI-negative TLE), temporal lobe lesion TLE (lesional TLE), and unilateral hippocampal sclerosis TLE (HS-TLE)., Methods: Patients with an electroclinical diagnosis of TLE who had video-scalp EEG recordings of seizures were identified from the retrospective database of the Austin Comprehensive Epilepsy Program between 2005 and 2019. The cohort was further selected into the 3 defined groups based on imaging findings, using MRI and FDG-PET. Timings of clinical and electrographic seizure progression were measured, considering the onset, ipsilateral lobar spread, contralateral spread, and termination. Durations were compared between groups using linear mixed models with inclusion of demographic and clinical covariates., Results: A total of 105 patients (137 seizures) were included, comprising 36 with MRI-negative TLE (54 seizures), 36 with lesional TLE (18 lateral vs 16 mesial lesions; 44 seizures), and 33 with HS-TLE (39 seizures). Seizure duration was similar between MRI-negative TLE and lesional TLE (mean 75.9 vs 71.7 seconds; p = 0.91). Further dividing lesional TLE into medial vs lateral temporal revealed no timing difference. However, the HS-TLE group had longer total seizure duration (114 seconds) compared with both MRI-negative TLE ( p < 0.001) and lesional TLE ( p < 0.001). Progression of electrographic spread also reflected this pattern, with involvement of extratemporal regions and then the contralateral hemisphere each taking significantly longer in HS-TLE., Discussion: MRI-negative TLE appears electrographically similar to lesional TLE, whether mesial or lateral, in the duration of seizures and the timing of electrographic spread. Both appear electrographically different from HS-TLE, where propagation is slower, suggesting engagement of different epileptogenic networks or seizure suppression mechanisms., Classification of Evidence: This study provides Class II evidence that the electroclinical features of seizures in HS-TLE are different than MRI-negative TLE and lesional TLE., (© 2022 American Academy of Neurology.)

Objective: To analyze the clinical syndromes and inheritance patterns of multiplex families with epilepsy toward the ultimate aim of uncovering the underlying molecular genetic basis., Methods: Following the referral of families with 2 or more relatives with epilepsy, individuals were classified into epilepsy syndromes. Families were classified into syndromes where at least 2 family members had a specific diagnosis. Pedigrees were analyzed and molecular genetic studies were performed as appropriate., Results: A total of 211 families were ascertained over an 11-year period in Israel. A total of 169 were classified into broad familial epilepsy syndrome groups: 61 generalized, 22 focal, 24 febrile seizure syndromes, 33 special syndromes, and 29 mixed. A total of 42 families remained unclassified. Pathogenic variants were identified in 49/211 families (23%). The majority were found in established epilepsy genes (e.g., SCN1A, KCNQ2, CSTB), but in 11 families, this cohort contributed to the initial discovery (e.g., KCNT1, PCDH19, TBC1D24). We expand the phenotypic spectrum of established epilepsy genes by reporting a familial LAMC3 homozygous variant, where the predominant phenotype was epilepsy with myoclonic-atonic seizures, and a pathogenic SCN1A variant in a family where in 5 siblings the phenotype was broadly consistent with Dravet syndrome, a disorder that usually occurs sporadically., Conclusion: A total of 80% of families were successfully classified, with pathogenic variants identified in 23%. The successful characterization of familial electroclinical and inheritance patterns has highlighted the value of studying multiplex families and their contribution towards uncovering the genetic basis of the epilepsies., (© 2016 American Academy of Neurology.)

Objective: There is evidence for comorbidity of migraine and epilepsy. We used transcranial magnetic stimulation (TMS) to assess cortical excitability in migraine compared with control subjects and patients with epilepsy., Methods: Twenty-six patients drug-naive patients with newly diagnosed migraine were studied. These were compared with 19 healthy control subjects and 50 patients with new onset epilepsy. Motor threshold (MT) and responses to paired pulse stimulation at short (2, 5, 10, and 15 milliseconds) and long (50-400 milliseconds) interstimulus intervals (ISIs) were measured., Results: Compared with control subjects, cortical excitability was higher in migraine only at 250 milliseconds (P < 0.05; effect size 0.7), while in epilepsy, it was higher at 2, 5, 250, and 300 milliseconds. Compared with epilepsy, cortical excitability was lower in migraine only at 250 milliseconds (P < 0.05; effect size 0.6 compared with focal epilepsy and 1.1 compared with idiopathic generalized epilepsy [IGE])., Conclusions: Cortical excitability increases in migraine suggesting the involvement of intracortical inhibitory circuits. This may be a common feature underlying some of the similarities observed in migraine and epilepsy.

Background: Malformations of cortical development have characteristic interictal discharges, yet the mechanisms of generation of these discharges are not known in humans. Interictal discharges in malformations of cortical development were studied with EEG-fMRI., Methods: Six subjects with malformations of cortical development and seizures were studied using spike-triggered fMRI at 3 T. The blood oxygen level-dependent (BOLD) signal changes associated with interictal discharges were measured., Results: All subjects showed spike-related BOLD signal changes. In four subjects, the signal increases were seen in the lesion, and in four subjects, decreases were seen surrounding the lesion. Five subjects had BOLD signal changes at distant cortical sites and three had subcortical changes (basal ganglia, reticular formation, or thalamic)., Conclusion: BOLD signal changes may be directly correlated with overall synaptic activity. Changes were found in and around the lesion of malformations of cortical development and in distant cortical and subcortical structures. The results suggest that EEG-fMRI studies might help elucidate the mechanisms of epileptic discharges in humans.