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OBJECTIVE: Epilepsy is common in patients with PIGN diseases due to biallelic variants; however, limited epilepsy phenotyping data have been reported. We describe the epileptology of PIGN encephalopathy. METHODS: We recruited patients with epilepsy due to biallelic PIGN variants and obtained clinical data regarding age at seizure onset/offset and semiology, development, medical history, examination, electroencephalogram, neuroimaging, and treatment. Seizure and epilepsy types were classified. RESULTS: Twenty six patients (13 female) from 26 families were identified, with mean age 7 years (range = 1 month to 21 years; three deceased). Abnormal development at seizure onset was present in 25 of 26. Developmental outcome was most frequently profound (14/26) or severe (11/26). Patients presented with focal motor (12/26), unknown onset motor (5/26), focal impaired awareness (1/26), absence (2/26), myoclonic (2/26), myoclonic-atonic (1/26), and generalized tonic-clonic (2/26) seizures. Twenty of 26 were classified as developmental and epileptic encephalopathy (DEE): 55% (11/20) focal DEE, 30% (6/20) generalized DEE, and 15% (3/20) combined DEE. Six had intellectual disability and epilepsy (ID+E): two generalized and four focal epilepsy. Mean age at seizure onset was 13 months (birth to 10 years), with a lower mean onset in DEE (7 months) compared with ID+E (33 months). Patients with DEE had drug-resistant epilepsy, compared to 4/6 ID+E patients, who were seizure-free. Hyperkinetic movement disorder occurred in 13 of 26 patients. Twenty-seven of 34 variants were novel. Variants were truncating (n = 7), intronic and predicted to affect splicing (n = 7), and missense or inframe indels (n = 20, of which 11 were predicted to affect splicing). Seven variants were recurrent, including p.Leu311Trp in 10 unrelated patients, nine with generalized seizures, accounting for nine of the 11 patients in this cohort with generalized seizures. SIGNIFICANCE: PIGN encephalopathy is a complex autosomal recessive disorder associated with a wide spectrum of epilepsy phenotypes, typically with substantial profound to severe developmental impairment.

Background:\ud The pathophysiology of changes in magnetic resonance imaging (MRI) detected after a seizure is not fully understood.\ud \ud Objective:\ud To characterize and describe seizure‐induced changes detected by MRI.\ud \ud Animals:\ud Eighty‐one client‐owned dogs diagnosed with idiopathic epilepsy.\ud \ud Methods:\ud Data collected retrospectively from medical records and included anatomical areas affected, T1‐, T2‐weighted and T2‐FLAIR (fluid‐attenuated inversion recovery) appearance, whether changes were unilateral or bilateral, symmetry, contrast enhancement, mass effect, and, gray and white matter distribution. Diffusion‐ and perfusion weighted maps were evaluated, if available.\ud \ud Results:\ud Seizure‐induced changes were T2‐hyperintense with no suppression of signal on FLAIR. Lesions were T1‐isointense (55/81) or hypointense (26/81), local mass effect (23/81) and contrast enhancement (12/81). The majority of changes were bilateral (71/81) and symmetrical (69/71). The most common areas affected were the hippocampus (39/81) cingulate gyrus (33/81), hippocampus and piriform lobes (32/81). Distribution analysis suggested concurrence between cingulate gyrus and pulvinar thalamic nuclei, the cingulate gyrus and parahippocampal gyrus, hippocampus and piriform lobe, and, hippocampus and parahippocampal gyrus. Diffusion (DWI) characteristics were a mixed‐pattern of restricted, facilitated, and normal diffusion. Perfusion (PWI) showed either hypoperfusion (6/9) or hyperperfusion (3/9).\ud \ud Conclusions and Clinical Importance:\ud More areas, than previously reported, have been identified that could incur seizure‐induced changes. Similar to human literature, DWI and PWI changes have been identified that could reflect the underlying metabolic and vascular changes.

Objective: Interictal high resolution (HR-) electric source imaging (ESI) and magnetic source imaging (MSI) are non-invasive tools to aid epileptogenic zone localization in epilepsy surgery candidates. We carried out a systematic review on the diagnostic accuracy and quality of evidence of these modalities. Methods: Embase, Pubmed and the Cochrane database were searched on 13 February 2017. Diagnostic accuracy studies taking post-surgical seizure outcome as reference standard were selected. Quality appraisal was based on the QUADAS-2 framework. Results: Eleven studies were included: eight MSI (n = 267), three HR-ESI (n = 127) studies. None was free from bias. This mostly involved: selection of operated patients only, interference of source imaging with surgical decision, and exclusion of indeterminate results. Summary sensitivity and specificity estimates were 82% (95% CI: 75–88%) and 53% (95% CI: 37–68%) for overall source imaging, with no statistical difference between MSI and HR-ESI. Specificity is higher when partially concordant results were included as non-concordant (p < 0.05). Inclusion of indeterminate test results as non-concordant lowered sensitivity (p < 0.05). Conclusions: Source imaging has a relatively high sensitivity but low specificity for identification of the epileptogenic zone. Significance: We need higher quality studies allowing unbiased test evaluation to determine the added value and diagnostic accuracy of source imaging in the presurgical workup of refractory focal epilepsy.

Purpose: To study possible detection of structural abnormalities on 7T MRI that were not detected on 3T MRI and estimate the added value of MEG-guidance. For abnormalities found, analysis of convergence between clinical, MEG and 7T MRI localization of suspected epileptogenic foci.Methods: In adult patients with well-documented localization-related epilepsy in whom a previous 3T MRI did not demonstrate an epileptogenic lesion but MEG indicated a plausible epileptogenic focus, 7T MRI was performed. Based on semiologic data, visual analysis of the 7T images was performed as well as based on prior MEG results. Correlation with other data from the patient charts, for as far as these were available, was analysed. To establish the level of concordance between the three observers the generalized or Fleiss kappa was calculated.Results: In 3/19 patients abnormalities that, based on semiology, could plausibly represent an epileptogenic lesion were detected using 7T MRI. In an additional 3/19 an abnormality was detected after MEG-guidance. However, in these later cases there was no concordance among the three observers with regard to the presence of a structural abnormality. In one of these three cases intracranial recording was performed, proving the possible abnormality on 7T MRI to be the epileptogenic focus.Conclusions: In 32% of patients 7T MRI showed abnormalities that could indicate an epileptogenic lesion whereas previous 3T MRI did not, especially when visual inspection was guided by the presence of focal interictal MEG abnormalities.

Objectives: To evaluate the diagnostic value and characteristic features of FCD epileptogenic zones using a novel sequence called fluid and white matter suppression (FLAWS)., Materials and methods: Thirty-nine patients with pathologically confirmed FCD and good surgery outcomes (class I or II, according to the Engel Epilepsy Surgery Outcome Scale) were retrospectively included in the study. All the patients underwent a preoperative whole-brain MRI examination that included conventional sequences (T2WI, T1WI, two-dimensional (2D) axial, coronal fluid-attenuated inversion recovery [FLAIR]) and FLAWS. An additional 3D-FLAIR MRI sequence was performed in 17 patients. To evaluate the sensitivity and specificity of FLAWS and investigate the cause of false-positives, 36 healthy volunteers were recruited as normal controls. Two radiologists evaluated all the image data. The detection rates of the FCD epileptogenic zone on different sequences were compared based on five criteria: abnormal cortical morphology (thickening, thinning, or abnormally deep sulcus); abnormal cortical signal intensity; blurred gray-white matter junction; abnormal signal intensity of the subcortical white matter, and the transmantle sign. The sensitivity and specificity of FLAWS for detecting the FCD lesions were calculated with the reviewers blinded to all the clinical information, i.e. to the patient identity and the location of the resected regions. To explore how many features were sufficient for the diagnosis of the epileptogenic zones, the frequency of each criterion in the resected regions and their combinations were assessed on FLAWS, according to the results of the assessment when the reviewers were aware of the location of the resected regions. Based on the findings of the 17 patients with an additional 3D-FLAIR scan when the reviewers were aware of the location of the resected regions, quantitative analysis of the regions of interest was used to compare the tissue contrast among 2D-axial FLAIR, 3D-FLAIR, and the FLAWS sequence. Visualization score analysis was used to evaluate the visualization of the five features on conventional, 3D-FLAIR, and FLAWS images. Finally, to explore the reason for false-positive results, a further evaluation of the whole brain FLAWS images was conducted for all the subjects., Results: The sensitivity and specificity for detecting the FCD lesions on the FLAWS sequence were 71.9% and 71.1%, respectively. When the reviewers were blinded to the location of the resected regions, the detection rate of the FLAWS sequence was significantly higher than that of the conventional sequences (P = 0.00). In the 17 patients who underwent an additional 3D FLAIR scan, no statistically significant difference was found between the FLAWS and the 3D-FLAIR (P = 0.25). All the patients had at least two imaging features, one of which was "the blurred junction of the gray-white matter." The transmantle sign, which is widely believed to be a specific feature of FCD type II, could also be observed in type I on the FLAWS sequence. The relative tissue contrast of FLAWS was higher than that of the 2D-FLAIR with respect to lesion/white matter (WM), deep gray matter (GM)/WM, and cortex/WM (P = 0.00 for all three measures) and higher than that of the 3D-FLAIR with respect to the lesion/WM (P = 0.01). The visualization score analysis showed that the visualization of FLAWS was more enhanced than that of the conventional and 3D-FLAIR images with respect to the blurred junction (P = 0.00 for both comparisons) and the abnormal signal intensity of the subcortical white matter (P = 0.01 for both comparisons). The thin-threadlike signal and individual FCD features outside the epileptogenic regions were considered the primary cause of the false-positive results of FLAWS., Conclusions: FLAWS can help in the detection of FCD epileptogenic zones. It is recommended that epileptogenic zone on FLAWS be diagnosed based on a combination of two features, one of which should be the "blurred junction of the gray-white matter" in types I and II. In type III, the combination of "the blurred junction of the gray-white matter" with "abnormal signal intensity of subcortical white matter" is recommended.

Background and purpose: Accurate localization of the epileptic focus is essential for surgical treatment of patients with drug-resistant epilepsy. Electric source imaging (ESI) is increasingly used in pre-surgical evaluation. However, most previous studies have analysed interictal (II) discharges. Prospective studies comparing the feasibility and accuracy of II and ictal (IC) ESI are lacking. Methods: We prospectively analysed long-term video-electroencephalography recordings (LTM) of patients admitted for pre-surgical evaluation. We performed ESI of II and IC signals using two methods, i.e. equivalent current dipole (ECD) and a distributed source model (DSM). LTM recordings employed the standard 25-electrode array (including inferior temporal electrodes). An age-matched template head model was used for source analysis. Results were compared with intracranial recordings, conventional neuroimaging methods [magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT)] and outcome at 1 year after surgery. Results: A total of 87 consecutive patients were analysed. ECD gave a significantly higher proportion of patients with localized focal abnormalities (94%) compared with MRI (70%), PET (66%) and SPECT (64%). Agreement between the ESI methods and intracranial recording was moderate to substantial (k = 0.56–0.79). A total of 54 patients were operated (47 patients more than 1 year ago) and 62% of them became seizure-free. The localization accuracy of II-ESI was 51% for DSM and 57% for ECD, and that for IC-ESI was 51% for DSM and 62% for ECD. The differences between the ESI methods were not significant. Differences in localization accuracy between ESI and MRI (55%), PET (33%) and SPECT (40%) were not significant. Conclusions: The II-ESI and IC-ESI of LTM data have high feasibility and their localization accuracy is similar to that of conventional neuroimaging methods.

SummaryObjective We aimed to investigate the long-term seizure outcome of children and adolescents who were undergoing epilepsy surgery in the parietooccipital cortex and determine their predictive factors. Methods We retrospectively analyzed the data of 50 consecutive patients aged 11.1 (mean) ± 5.1 (standard deviation) years at surgery. All patients but one had a magnetic resonance imaging (MRI)–visible lesion. Resections were parietal in 40%, occipital in 32%, and parietooccipital in 28% cases; 24% patients additionally underwent a resection of the posterior border of the temporal lobe. Etiology included focal cortical dysplasia in 44%, benign tumors (dysembryoplastic neuroepithelial tumor, ganglioglioma, angiocentric glioma, and pilocystic astrocytoma) in 32%, peri- or postnatal ischemic lesions in 16%, and tuberous sclerosis in 8% cases. Results At last follow-up (mean 8 years, range 1.5–18 years), 60% patients remained seizure-free (Engel class I): 30% had discontinued and 20% had reduced antiepileptic drugs. Most seizure recurrences (71%) occurred within the first 6 months, and only three patients presented with seizures ≥2 years after surgery. Independent predictors of seizure recurrence included left-sided as well as parietal epileptogenic zones and resections. Longer epilepsy duration to surgery was identified as the only modifiable independent predictor of seizure recurrence. Significance Our study demonstrates that posterior cortex epilepsy surgery is highly effective in terms of lasting seizure control and antiepileptic drug cessation in selected pediatric candidates. Most importantly, our data supports the early consideration of surgical intervention in children and adolescents with refractory posterior cortex epilepsy.