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Introducción. La interrelación entre la inflamación, el estrés oxidativo y la muerte neuronal constituye un tema creciente de investigación sobre epilepsia del lóbulo temporal farmacorresistente (ELTF). Objetivo: profundizar en los mecanismos moleculares que participan en la fisiopatología de la ELTF correlacionando variables clínicas con inmunológicas, estrés oxidativo y muerte neuronal. Métodos. Por inmunocitoquímica fueron medidos los marcadores CD3, CD4, CD8, CD19, CD25, HLA-DR; por nefelometría: IgG, IgM, IgA y albúmina; por ensayos inmunoenzimáticos, IL-1β, IL-6, TNF-α y óxido nítrico; por Western blot: NFκB, JNK, 4-hidroxi-2-nonenal, 3-nitrotirosina; por espectrofotometría: malonildialdehído, productos avanzados de glicación (AGE), productos avanzados de oxidación proteínas, ácido úrico, superóxido dismutasa (SOD), glutatión y vitamina C; por inmunohistoquímica: Anexina V, TUNEL, sinaptofisina, caspasa 3, p53 y bcl-2; por HPLC, glutamato, y por autorradiografía: 5-HT, 5-HT1A, 5-HT7. Resultados. Se demuestra que las crisis son el substrato patogénico de los trastornos inmunológicos, inflamatorios y de estrés oxidativo en la ELTF. Las variables clínicas se relacionan con los estudios moleculares y de proteínas realizados y todos en su conjunto evidencian la muerte neuronal en la ELTF.

Objective: to present the postsurgical outcome of extratemporal epilepsy (ExTLE) patients submitted to preoperative multimodal evaluation and intraoperative sequential electrocorticography (ECoG). Subjects and methods: thirty-four pharmaco-resistant patients with lesional and non-lesional ExTLE underwent comprehensive pre-surgical evaluation including multimodal neuroimaging such as ictal and interictal perfusion single photon emission computed tomography (SPECT) scans, subtraction of ictal and interictal SPECT co-registered with magnetic resonance imaging (SISCOM) and electroencephalography (EEG) source imaging (ESI) of ictal epileptic activity. Surgical procedures were tailored by sequential intraoperative ECoG, and absolute spike frequency (ASF) was calculated in the pre- and post-resection ECoG. Postoperative clinical outcome assessment for each patient was carried out one year after surgery using Engel scores. Results: frontal and occipital resection were the most common surgical techniques applied. In addition, surgical resection encroaching upon eloquent cortex was accomplished in 41% of the ExTLE patients. Pre-surgical magnetic resonance imaging (MRI) did not indicate a distinct lesion in 47% of the cases. In the latter number of subjects, SISCOM and ESI of ictal epileptic activity made it possible to estimate the epileptogenic zone. After one- year follow up, 55.8% of the patients was categorized as Engel class I–II. In this study, there was no difference in the clinical outcome between lesional and non lesional ExTLE patients. About 43.7% of patients without lesion were also seizure- free, p = 0.15 (Fischer exact test). Patients with satisfactory seizure outcome showed lower absolute spike frequency in the pre-resection intraoperative ECoG than those with unsatisfactory seizure outcome, (Mann– Whitney U test, p = 0.005). Conclusions: this study has shown that multimodal pre-surgical evaluation based, particularly, on data from SISCOM and ESI alongside sequential intraoperative ECoG, allow seizure control to be achieved in patients with pharmacoresistant ExTLE epilepsy.

Introducción: La presente investigación aborda por vez primera en nuestro país el estudio de las consecuencias del tratamiento quirúrgico en pacientes con epilepsia del lóbulo temporal fármaco-resistente para el funcionamiento de los sistemas sensoriales auditivo y visual. Objetivos: evaluar los cambios anatómicos y funcionales de los sistemas auditivo y visual secundarios a la lobectomía temporal anterior. Métodos: Se estudió una muestra de 28 pacientes con epilepsia del lóbulo temporal mesial fármaco-resistente intervenidos quirúrgicamente en el Centro Internacional de Restauración Neurológica entre los años 2002 y 2012. Resultados: Se constató la existencia de alteraciones funcionales en los sistemas sensoriales auditivo y visual antes de la intervención quirúrgica. Luego de la resección se detectaron cambios en el funcionamiento de la vía auditiva mediante los potenciales evocados auditivos, probablemente mediados por un efecto indirecto y a largo plazo de la remoción de estructuras específicas como la amígdala y el polo temporal medio. En la vía visual ocurrieron defectos del campo visual evidenciados por las técnicas de potenciales evocados visuales con estimulación por cuadrantes en combinación con la perimetría, y en correspondencia con la magnitud del tejido neocortical removido. La lesión de la vía visual pudo ser corroborada mediante la tractografía de la radiación óptica y el estado de su conectividad. Conclusiones: Los resultados evidenciaron cambios funcionales indirectos y a largo plazo de la vía auditiva, y se confirman las afectaciones directas de la vía visual con métodos de exploración objetivos y en correspondencia con la magnitud de la resección quirúrgica.

Increasing amounts of evidence support the role of inflammation in epilepsy. This study was done to evaluate serum follow-up of IL-1β and IL-6 levels, as well as their concentration in the neocortex, and the relationship of central inflammation with NF-κB and annexin V in drug-resistant temporal lobe epileptic (DRTLE) patients submitted to surgical treatment. Peripheral and central levels of IL-1β and IL-6were measured by ELISA in 10 DRTLE patients. The sera from patients were taken before surgery, and 12 and 24 months after surgical treatment. The neocortical expression of NF-κB was evaluated by western blotting and annexin V co-localization with synaptophysin by immunohistochemistry. The neocortical tissues from five patients who died by non-neurological causes were used as control. Decreased serum levels of IL-1 and IL-6 were observed after surgery; at this time, 70% of patients were seizure-free. No values of IL-1 and IL-6 were detected in neocortical control tissue, whereas cytokine levels were evidenced in DRTLE. Increased NF-κB neocortex expression was found and the positive annexin V neurons were more obvious in the DRTLE tissue, correlating with IL-6 levels. The follow-up study confirmed that the inflammatory alterations disappeared one year after surgery, when the majority of patients were seizure-free, and the apoptotic death process correlated with inflammation.

The purpose of this paper is to present a long- term electroclinical and employment follow up in temporal lobe epilepsy (TLE) patients in a comprehensive epilepsy surgery program. Forty adult patients with pharmacoresistant TLE underwent detailed presurgical evaluation. Electroencephalogram (EEG) and clinical follow up assessment for each patient were carried out. The occurrence of interictal epileptiform activity (IEA) and absolute spike frequency (ASF) were tabulated before and after 1, 6, 12, 24 and 72 months surgical treatment. Employment status pre- to post-surgery at the last evaluated period was also examined. Engel scores follow-up was described as follows: at 12 months 70% (28) class I, 10% (4) class II and 19% (8) class III-IV; at 24 months after surgery 55.2% (21) of the patients were class I, 28.9% (11) class II and 15.1% (6) class III-IV. After one- year follow up 23 (57.7%) patients were seizure and aura-free (Engel class IA). These figures changed to 47.3%, and 48.6% respectively two and five years following surgery whereas 50% maintained this condition in the last follow up period. A decline in the ASF was observed from the first year until the sixth year after surgery in relation to the preoperative EEG. The ASF one year after surgery allowed to distinguish “satisfactory” from “unsatisfactory” seizure relief outcome at the last follow up. An adequate social functioning in terms of education and employment in more than 50% of the patients was also found. Results revealed the feasibility of conducting a successful epilepsy surgery program with favorable long term electroclinical and psychosocial functioning outcomes in a developing country as well.