Successful Treatment of a Child With Epileptic Encephalopathy With Spike-Wave Activation in Sleep and GRIN2A Variant Using Sulthiame.

Epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS) and developmental EE-SWAS (DEE-SWAS) are characterized by variable combinations of cognitive, language, behavioral, and/or motor regression associated with continuous or near-continuous diffuse spike-and-wave complexes during sleep. Glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) variants have been associated with EE-SWAS. It encodes the most relevant GluN2 subunit of the N-methyl-D-aspartate receptor (NMDAR). Sulthiame reduces NMDAR-mediated neuronal excitability and has been progressively used as monotherapy in self-limited epilepsy with centrotemporal spikes (SeLECTS) or as add-ontherapy in EE-SWAS/DEE-SWAS. A five-year-old female, with family history of epilepsy, was initially diagnosed with SeLECTS and medicated with valproic acid (VPA). One year later, she presented a focal to bilateral tonic-clonic seizure during sleep and learning difficulty. The electroencephalogram revealed continuous spike-and-wave during sleep leading to the diagnosis of EE-SWAS. Prednisolone was effective, but there was repeated recurrence after its discontinuation and associated adverse effects. As an alternative, sulthiame was added to VPA. Four years later, she remains clinically stable. Genetic testing revealed a GRIN2A missense variant, C.3228C>A (p.Asn1076Lys). Sulthiame appeared effective in this recurrent EE-SWAS child, who presented a GRIN2A missense variant with possible NMDAR gain-of-function and adverse effects of corticosteroids. Functional studies​​​​​​​ of GRIN2A variants might become a future tool for individualized therapies.

Lacsogram: A New EEG Tool to Diagnose Alzheimer's Disease.

This work proposes the application of a new electroencephalogram (EEG) signal processing tool - the lacsogram - to characterize the Alzheimer's disease (AD) activity and to assist on its diagnosis at different stages: Mild Cognitive Impairment (MCI), Mild and Moderate AD (ADM) and Advanced AD (ADA). Statistical analyzes are performed to lacstral distances between conventional EEG subbands to find measures capable of discriminating AD in all stages and characterizing the AD activity in each electrode. Cepstral distances are used for comparison. Comparing all AD stages and Controls (C), the most important significances are the lacstral distances between subbands θ and α ( p = 0.0014 0.05). The topographic maps show significant differences in parietal, temporal and frontal regions as AD progresses. Machine learning models with a leave-one-out cross-validation process are applied to lacstral/cepstral distances to develop an automatic method for diagnosing AD. The following classification accuracies are obtained with an artificial neural network: 95.55% for All vs All, 98.06% for C vs MCI, 95.99% for C vs ADM, 93.85% for MCI vs ADM-ADA. In C vs MCI, C vs ADM and MCI vs ADM-ADA, the proposed method outperforms the state-of-art methods by 5%, 1%, and 2%, respectively. In All vs All, it outperforms the state-of-art EEG and non-EEG methods by 6% and 2%, respectively. These results indicate that the proposed method represents an improvement in diagnosing AD.

cTnI, BNP and CRP profiling after seizures in patients with drug-resistant epilepsy.

PURPOSE: To profile serum levels of high sensitivity Troponin I (hs-cTnI), B-Type Natriuretic Peptide (BNP), and high sensitivity C Reactive Protein (hs-CRP), after epileptic seizures in patients with focal drug-resistant epilepsy, relating the results to the revised SUDEP-7 inventory. METHODS: We prospectively evaluated patients admitted to our Epilepsy Monitoring Unit. hs-cTnI, BNP, and hs-CRP were measured at admission and after the first seizure. The revised SUDEP-7 Risk Inventory was calculated. The statistical significance level was set at 0.05. RESULTS: Fifty-eight patients were included (53.4 % female). The index seizure was a focal to bilateral tonic-clonic seizure (FBTCS) in 25.9 % of the patients, and 17.5 % had post-ictal generalized EEG suppression (PGES). After the seizure, 25.9 % had a significant (above 50 %) increase in hs-cTnI, 23.3 % in BNP, and 4.3 % in hs-CRP. About 40 % had cardiovascular risk factors (CRF), without known cardiac disease. The elevation of one biomarker did not compel the elevation of another. hs-cTnI increase was associated with FBTCS, PGES, longer seizures, maximal ictal heart rate, and HR change. Increases in BNP were associated with CRF. hs-CRP increase was associated with PGES. We found no significant association between SUDEP-7 and any biomarker increase. SIGNIFICANCE: Several patients had increases in biomarkers of myocardial necrosis/dysfunction after seizures, without significant association with the SUDEP-7 inventory. Different patterns of biomarkers' elevations point to multifactorial pathophysiologies hypothetically associated with incipient myocardial lesions. A larger cohort with follow-up data could help to clarify the clinical relevance of these findings.