Objective: Stereoelectroencephalography (SEEG) is a technique for preoperative evaluation of patients with difficult-to-localise refractory focal epilepsy (DLRFE), enabling the study of deep cortical structures. The procedure, which is increasingly used in international epilepsy centres, has not been fully developed in Spain. We describe our experience with SEEG in the preoperative evaluation of DLRFE. Material and methods: In the last 8 years, 71 patients with DLRFE were evaluated with SEEG in our epilepsy centre. We prospectively analysed our results in terms of localisation of the epileptogenic zone (EZ), surgical outcomes, and complications associated with the procedure. Results: The median age of the sample was 30 years (range, 4-59 years); 27 patients (38%) were women. Forty-five patients (63.4%) showed no abnormalities on brain MR images. A total of 627 electrodes were implanted (median, 9 electrodes per patient; range, 1-17), and 50% of implantations were multilobar. The EZ was identified in 64 patients (90.1%), and was extratemporal or temporal plus in 66% of the cases. Follow-up was over one year in 55 of the 61 patients undergoing surgery: in the last year of follow-up, 58.2% were seizure-free (Engel Epilepsy Surgery Outcome Scale class I) and 76.4% had good outcomes (Engel I-II). Three patients (4.2%) presented brain haemorrhages. Conclusion: SEEG enables localisation of the EZ in patients in whom this was previously impossible, offering better surgical outcomes than other invasive techniques while having a relatively low rate of complications.

Purpose We hypothesized that epilepsy associated with temporal pole encephaloceles (ETPE) could be the consequence and an unrecognized manifestation of idiopathic intracranial hypertension (IIH). To test this hypothesis in patients with ETPEs we evaluated: 1) the frequency of two radiological signs of IIH and 2) whether these patients develop over time clinical manifestations suggestive of elevated intracranial pressure (ICP). Methods Case-control study comparing two cardinal radiological signs of IIH pituitary gland height (PGH) and the diameter of the two optic nerve sheaths (ONS) between 29 patients with ETPEs (TPE group) and 29 patients with focal epilepsy of other etiologies (control group), adjusted by age, sex, body mass index ( BMI), age at epilepsy onset and epilepsy duration. Analysis was performed using conventional and ordinal logistic regression. The measurements in both groups were compared with validated radiological criteria of IIH. Results Of the patients 17 (63%) in the TPE group had all three measurements over the cut-off values for IIH, while no patients in the control group had all three findings. The TPE group patients had lower PGH (3.2 +/- 1.0mm vs. 4.9 +/- 1.3mm, p< 0.001) and larger diameter of ONS than controls (p< 0.001), being similar to validated data of IIH. No patient with TPE had clinical manifestations of elevated ICP (mean follow-up 15.1 +/- 11.7 years). Conclusion Patients with ETPEs frequently had radiological signs of IIH while not developing typical manifestations of elevated ICP over time. In this way, ETPEs could be an unrecognized manifestation of IIH, and temporal lobe seizures the only clinical expression of this epilepsy syndrome.

The broad and heterogeneous clinical spectrum that characterizes common variable immunodeficiency (CVID) is associated with quite different disease course and prognosis, highlighting the need to develop tools that predict complications. We developed a multianalyte VISUAL score (variable immunodeficiency score upfront analytical link) aimed to predict severity using individual CVID patient data at baseline of a cohort of 50 CVID patients from two different centers in Portugal and Spain. We retrospectively applied VISUAL to the CVID clinical severity scores proposed by Ameratunga and Grimbacher after 15 years follow-up of our cohort. VISUAL score at CVID diagnosis showed adequate performance for predicting infectious and non-infectious severe complications (Cluster B). Compared to switched memory B lymphocyte phenotype alone, VISUAL provided a more accurate identification of clinically meaningful outcome, with significantly higher sensitivity (85% vs 55%, p=0.01), and negative predictive value (77% vs 58%) and AUC of the ROC curves (0.72 vs 0.64), with optimal cut-off level of 10. For every increase of 1 point in the VISUAL scale, the odds of being in the higher risk category (Cluster B) increased in 1.3 (p=0.005) for Ameratunga's severity score and 1.26 (p=0.004) for Grimbacher's severity score. At diagnosis of CVID, VISUAL score >= 10 showed 8.94-fold higher odds of severe prognosis than below this threshold. Kaplan-Meier estimates for the VISUAL >= 10 points showed significantly earlier progression to Cluster B than those with VISUAL<10 (p=0.0002). This prognostic laboratory score might allow close monitoring and more aggressive treatment in patients with scores<greater than or equal to>10 on a personalized basis approach. Further studies are needed to prospectively validate VISUAL score.

Introduction: Hippocampal volumetry can discriminate normal subjects from patients with amnestic mild cognitive impairment (MCI) or Alzheimer disease (AD). We have analyzed the effects of different methods of hippocampal volume (HV) adjustment on the diagnostic accuracy of this technique. Methods: Cross-sectional analysis of 148 subjects of the ADNI database (48 normal, 66 MCI, 34 AD). Brain volumes were calculated from 3T MRI scans with gm extractor, a fully automated script based on FSL. A series of logistic regression models was obtained using 9 volumes of reference and 3 methods of adjustment (normalization, covariance, bilinear regression). Diagnostic accuracy was evaluated with the receiver operating characteristic curve method. External validity was assessed with 10-fold cross-validation. Results: The models with the highest area under the curve (AUC) were those including the HV normalized by total intracranial volume (TIV). The differences with bilinear regression and the covariance method adjusted by TIV were minor and not statistically significant. The lowest AUCs corresponded to the models based on raw (unadjusted) HVs. The results were qualitatively similar in two clinical settings (normal versus MCI, and normal versus AD), but the differences were higher in the normal versus MCI context. Conclusion: The accuracy of hippocampal volumetry for the differential diagnosis between normal subjects and patients with MCI or AD was maximized by normalizing the HV by the TIV. Our results do not exclude the potential superiority of non-linear models.

Objective: This study aimed to evaluate the access to advanced diagnostic tests in patients with epilepsy and intellectual disability, with special focus on genetics. Methods: Patients with epilepsy and intellectual disability evaluated between 2016 and 2018 at the Epilepsy Unit of two hospitals in Madrid. Spain were included. The main inclusion criterion was an undetermined etiological diagnosis after clinical assessment, neuroimaging, and electroencephalogram (EEG). Results: Two hundred and five patients with epilepsy and intellectual disability were evaluated, with 124 fulfilling the inclusion criteria (mean age: 33.9 years). Regarding the etiological workup, advanced neuroimaging, prolonged video-EEG, and any type of genetic test had been performed in 58%, 41%, and 40%, respectively. An etiological diagnosis was reached in 18.5%. The workup was considered incomplete in 67%. Variables that showed the strongest association with an incomplete diagnostic workup in the multivariate analysis were current age and seizure freedom. Conclusions: Despite the multiple implications of modern diagnostic techniques, especially genetic testing, there is a large proportion of patients with epilepsy and intellectual disability who do not have access to them. Older age and seizure freedom seem to be associated with the highest diagnostic gap.

Objective To assess the effectiveness and tolerability of perampanel (PER) monotherapy in routine clinical practice for the treatment of focal onset and generalized tonic-clonic seizures (GTCS). Methods This multicenter, retrospective, observational study was conducted in patients aged >= 12 years treated with PER as primary monotherapy or converted to PER monotherapy by progressive reduction of background antiepileptic drugs. Outcomes included retention, responder, and seizure-free rate after 3, 6, and 12 months and tolerability throughout the follow-up. Results A total of 98 patients (mean age = 49.6 +/- 21.7 years, 51% female) with focal seizures and/or GTCS were treated with PER monotherapy for a median exposure of 14 months (range = 1-57) with a median dose of 4 mg (range = 2-10). The retention rates at 3, 6, and 12 months and last follow-up were 93.8%, 89.3%, 80.9%, and 71.4%, respectively. The retention rates according to the type of monotherapy (primary vs conversion) did not differ (log-rank P value = .57). Among the 98 patients, 61.2% patients had seizures throughout the baseline period, with a median seizure frequency of 0.6 seizures per month (range = 0.3-26). Responder rates at 3, 6, and 12 months were 79.6%, 70.1%, and 52.8%, respectively, and seizure freedom rates at the same points were 62.7%, 56.1%, and 41.5%. Regarding the 33 patients who had GTCS in the baseline period, 87.8% were seizure-free at 3 months, 78.1% at 6 months, and 55.1% at 12 months. Over the entire follow-up, PER monotherapy was generally well tolerated, and only 16% of patients discontinued PER due to adverse events (AEs). Female patients were found to be at a higher risk of psychiatric AEs (female vs male odds ratio = 2.85, 95% confidence interval = 1-8.33, P = .046). Significance PER demonstrated good effectiveness and a good safety profile when used as primary therapy or conversion to monotherapy at relatively low doses, in a clinical setting with patients with focal seizures and GTCS.