Overexpression of inflammatory-related and nitric oxide synthase genes in olfactory bulbs from frontal lobe epilepsy patients.

Neuroinflammation has been shown to constitute a crucial mechanism in the pathophysiology of epileptic brain and several genes of inflammatory mediators have been detected in surgically resected hippocampus tissue but not in non-related seizure brain regions. Interestingly, it has been reported an olfactory dysfunction in frontal lobe epilepsy (FLE). Our aim was to quantify the gene expression of inflammatory-related and nitric oxide synthase genes in olfactory bulbs (OB) tissue from FLE patients. RNA was isolated from OB resection of FLE patients and autopsy subjects without any neurological disease (n = 7, each). After cDNA synthesis, we performed qPCR for interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nuclear factor κB p65 (RELA), Toll-like receptor 4 (TLR 4), its agonist high mobility group box 1 (HMGB 1) as well nitric oxide synthase isozymes (NOS 1, 2 and 3). We found a significant increase in gene expression of pro-inflammatory cytokines (IL-1ß, IL-6 and TNFα), TLR4 receptor and in its agonist HMGB1 and the downstream transcription factor NFκB p65. Moreover, we observed an increase of both NOS1 and NOS3 and a slightly increase of NOS2; however, it was not significant. Our study describes the overexpression of inflammatory-related genes and NOS isozymes in OB from FLE patients. Even though, the number of patients was limited, our findings could point out that neuroinflammation and nitrosative stress-related genes in the OB could be produced in general manner in all brain regions and thus contribute in part, to the olfactory dysfunction observed in FLE patients.

Parahippocampectomy as a New Surgical Approach to Mesial Temporal Lobe Epilepsy Caused By Hippocampal Sclerosis: A Pilot Randomized Comparative Clinical Trial.

BACKGROUND AND OBJECTIVE: The parahippocampal gyrus plays an important role in the epileptogenic pathways of mesial temporal lobe epilepsy caused by hippocampal sclerosis (mTLE-HS); its resection could prevent epileptic seizures with fewer complications. This study evaluates the initial efficacy and safety of anterior temporal lobectomy (ATL), selective amygdalohipppocampectomy (SAH), and parahippocampectomy (PHC) surgical approaches in mTLE-HS. METHODS: A randomized comparative pilot clinical trial (2008-2011) was performed that included patients with mTLE-HS who underwent ATL, trans-T3 SAH, and trans-T3 PHC. Their sociodemographic characteristics, visual field profiles, verbal and visual memory profiles, and Engel scale outcome at baseline and at 1 and 5 years are described, using descriptive statistics along with parametric and nonparametric tests. RESULTS: Forty-three patients with a mean age of 35.2 years (18-56 years), 65% female, were analyzed: 14 underwent PHC, 14 ATL, and 15 SAH. The following percentages refer to those patients who were seizure free (Engel class IA) at 1-year and 5-year follow-up, respectively: 42.9% PHC, 71.4% ATL, and 60% SAH (P = 0.304); 28.6% PHC, 50% ATL, and 53.3% SAH (P = 0.353). Postoperative visual field deficits were 0% PHC, 85.7% ATL, and 46.7% SAH (P = 0.001). Verbal and/or visual memory worsening were present in 21.3% PHC, 42.8% ATL, and 33.4% SAH (P = 0.488) and preoperative and postoperative visual memory scores were significantly different in the SAH group only (P = 0.046). CONCLUSIONS: PHC, ALT, and SAH show a preliminary similar efficacy in short-term seizure-free rates in patients with mTLE-HS. However, PHC efficacy in the long-term decreases compared with the other surgical techniques. PHC does not produce postoperative visual field deficits.

Electrocorticographic Patterns in Epilepsy Surgery and Long-Term Outcome.

PURPOSE: The role of intraoperative electrocorticography (iECoG) and of its patterns in epilepsy surgery have shown contradictory results. Our aim was to describe iECoG patterns and their association with outcome in epilepsy surgery. METHODS: We retrospectively analyzed 104 patients who underwent epilepsy surgery (2009-2015) with pre- and postresection iECoG. We described clinical findings, type of surgery, preresection iECoG patterns according to Palmini et al., 1995 (sporadic, continuous, burst, and recruiting interictal epileptiform discharges-IEDs) and postresection iECoG outcome (de novo, residual, and without IEDs). The Engel scale was used to evaluate the outcome. Descriptive statistics, Kaplan-Meier, the logistic regression model, and analysis of variance tests were used. RESULTS: We included 60.6% (63/104) females, with a mean age of 35 (±10.2) years at the time of epilepsy surgery. The etiologies were hippocampal sclerosis (63.5%), cavernomas (14.4%), cortical dysplasia (11.5%), and low-grade tumors (10.6%). The most common preresection iECoG pattern was sporadic IEDs (47%). Postresection iECoG patterns were de novo (55.7%), residual (27.8%), and without IEDs (16.3%). Mean follow-up was 19.2 months. Engel scale was as follows: Engel I (91 patients, 87.5%), Engel II (10 patients, 9.6%), and Engel III (three patients, 2.9%). Analysis by mixed-design analysis of variance showed a significant difference between etiology groups with a strong size effect (P = 0.021, η = 0.513) and also between preresection iECoG patterns (P = 0.008, η = 0.661). CONCLUSIONS: Preresection iECoG patterns and etiology influence Engel scale outcome in lesional epilepsy surgery.

Recurrent Herpes Simplex Virus Encephalitis After Neurologic Surgery.

BACKGROUND: The herpes simplex virus (HSV) is the most common cause of sporadic encephalitis worldwide. Even with proper treatment, this infection is associated with a mortality rate of 19%-30% and with potential neurologic sequelae. Recurrences of encephalitis are rare and limited to a few cases in the literature. Although the mechanism of reactivation has not yet been clarified, in our patient, the surgery might have acted as a precipitating factor. CASE DESCRIPTION: The case involved a female 10-year-old patient with a history of type 1 HSV encephalitis since 24 months of age. Secondarily, the patient developed postherpetic epilepsy in the following years. At 10 years old, she was referred to the epilepsy surgery service, and an elective right temporal lobectomy was performed. After surgery, the patient experienced severe clinical deterioration characterized by fever, severe headache, and altered state of consciousness. Encephalitis was diagnosed based on a positive polymerase chain reaction for HSV in the cerebrospinal fluid. The symptoms remitted after 8 weeks of treatment with acyclovir. The histopathologic diagnosis was a chronic encephalitic process with late secondary parenchymal changes without specific viral cytopathic findings. The only limitation that persisted was related to fine movements of the left hand. One year after surgery, the patient rejoined her school activities and is currently free of seizures. CONCLUSIONS: HSV encephalitis is a rare but serious complication that should be suspected in cases of unexplained postoperative fever with altered consciousness, especially in patients with histories of encephalitic states.

Self-reported quality of life in pharmacoresistant temporal lobe epilepsy: correlation with clinical variables and memory evaluation.

AIM: This work explores the effects of clinical variables on self-reported quality of life (QoL) in pharmacoresistant temporal lobe epilepsy (TLE), correlating this information with results from the Quality of Life in Epilepsy questionnaire (QOLIE-31) and selective memory tests of the Barcelona Battery and the Rey-Osterrieth figure. METHODS: We retrospectively analysed the records of 60 TLE patients and correlated patient variables (e.g. gender, aetiology; mesial TLE with hippocampal sclerosis [HS] versus lesional TLE, side of ictal onset, age, age at onset, duration of epilepsy, seizure frequency, and use of AEDs) with selective memory test scores and self-reported QoL. RESULTS: Right ictal onset was associated with lower emotional well-being scores. MTLE-HS patients had lower QOLIE-31 scores for seizure worry, social function, overall QoL, energy/fatigue, cognitive function, and obtained a lower overall score, compared to those with lesional TLE. Older age at epilepsy onset was associated with worse emotional well-being, energy/fatigue, medication effects, and seizure worry outcomes. Higher seizure frequency and older age at time of evaluation were associated with lower cognitive function scores. Generalised seizures were associated with lower scores based on the variables: seizure worry, overall quality of life, emotional well-being, and cognitive function. Regarding memory tests, only visuospatial memory correlated positively with cognitive function score. Patients with MTLE-HS underwent evaluation for pharmacoresistant epilepsy, on average, 10 years later than those with lesional TLE. CONCLUSIONS: MTLE-HS, right-sided epileptogenic zone, late onset, and higher seizure frequency were associated with worse QoL. Objective testing revealed specific memory deficits that were not reflected in self-reported QoL scores.

Surgical management of cavernous malformations presenting with drug-resistant epilepsy.

Cerebral cavernous malformations (CMs) are dynamic lesions characterized by continuous size changes and repeated bleeding. When involving cortical tissue, CMs pose a significant risk for the development of drug-resistant epilepsy, which is thought to be result of an altered neuronal network caused by the lesion itself and its blood degradation products. Preoperative evaluation should comprise a complete seizure history, neurological examination, epilepsy-oriented MRI, EEG, video-EEG, completed with SPECT, PET, functional MRI, and/or invasive monitoring as needed. Radiosurgery shows variable rates of seizure freedom and a high incidence of complications, thus microsurgical resection remains the optimal treatment for CMs presenting with drug-resistant epilepsy. Two thirds of patients reach Engel I class at 3-year follow-up, regardless of lobar location. Those with secondarily generalized seizures, a higher seizure frequency, and generalized abnormalities on preoperative or postoperative EEG, show poorer outcomes, while factors such as gender, duration of epilepsy, lesion size, age, bleeding at the time of surgery, do not correlate consistently with seizure outcome. Electrocorticography and a meticulous removal of all cortical hemosiderin - beyond pure lesionectomy - reduce the risk of symptomatic recurrences.

Chronic intermittent vagal nerve stimulation in the treatment of refractory epilepsy: experience in Mexico with 35 cases.

BACKGROUND: The role of vagal nerve stimulation (VNS) in the treatment of refractory epilepsy is still evolving and requires precision through extensive description of acute and chronic results, adverse effects and complications in specific populations. METHODS: We selected patients with refractory epilepsy subjected to VNS who had completed at least a 12-month followup. Descriptive and inferential statistics were used to review and assess the effects of VNS on seizure frequency/intensity, memory, alertness, mood, postictal recovery, and quality of life (subjective scale, QoL IE-31 inventory) as well as factors (gender, age, age of onset, time of surgery, stimulation parameters, seizure frequency and type) associated with clinical response. We describe stimulation parameters, complications and adverse effects compared to other series. RESULTS: We selected 35 patients with an age range of 5-48 years; 18 patients presented partial epilepsy and 17 generalized epilepsy. All procedures and wound healing were uneventful, and no infections were reported. Median reduction in seizure frequency was 55.65% (p <0.001). Four patients showed improvement of >90%. Two patients became seizure free, whereas seizure frequency increased in two patients. The subjectively qualified response to treatment was good in 33 patients. The mean global increase in the QoLIE-31 Scale was 12.6 (p = 0.020). Improvements in memory, mood, alertness and postictal recovery period were documented. Only seizure type showed statistically significant association with clinical response. Adverse effects were transitory and responded to changes in stimulation parameters. CONCLUSIONS: VNS is a safe, feasible, well-tolerated and effective palliative treatment in appropriately selected cases of refractory partial and multifocal generalized seizures.

Estimulación crónica intermitente del nervio vago en el tratamiento de epilepsia refractaria: experiencia en México con 35 casos / Chronic intermittent vagal nerve stimulation in the treatment of refractory epilepsy: experience in Mexico with 35 cases

Introducción: El papel de la estimulación crónica intermitente del nervio vago (ECINV) en el tratamiento de la epilepsia refractaria está evolucionando y requiere precisarse mediante la descripción de resultados, efectos adversos y complicaciones en poblaciones específicas. Material y métodos: Se seleccionaron los pacientes con epilepsia refractaria sometidos a ECINV con mínimo 12 meses de seguimiento, utilizando estadística descriptiva e inferencial para valorar el efecto sobre la frecuencia e intensidad de las crisis, memoria, ánimo, estado de alerta, recuperación postictal y calidad de vida (escala subjetiva, cuestionario QoLIE-31), y los factores (sexo, edad, tiempo de evolución, número/tipo crisis, parámetros de estimulación) asociados a la respuesta clínica. Se describen los parámetros de estimulación usados, empleo del magneto, complicaciones y efectos adversos. Resultados: Se seleccionaron 35 pacientes, edad de cinco a 48 años, 18 con epilepsia parcial, 17 con generalizada. No hubo complicaciones, infección o alteración de la cicatrización en los procedimientos quirúrgicos. La reducción promedio en crisis fue de 55.65 % (p < 0.001). En epilepsias generalizadas hubo 58.8 % de respondedores y 88.9 % en parciales. Cuatro sujetos presentaron mejoría > 90 %, con control total; en dos pacientes aumentó la frecuencia de las crisis. La respuesta al tratamiento fue buena subjetivamente en 33 pacientes. La calificación global de QoLIE-31 aumentó 12.6 puntos (p = 0.020). Solo el tipo de crisis se asoció con la respuesta clínica. Los efectos adversos fueron transitorios y respondieron al cambio de parámetros de estimulación. Conclusiones: la ECINV es segura, bien tolerada y eficaz para el tratamiento paliativo en casos seleccionados de crisis parciales y generalizadas multifocales refractarias.

BACKGROUND: The role of vagal nerve stimulation (VNS) in the treatment of refractory epilepsy is still evolving and requires precision through extensive description of acute and chronic results, adverse effects and complications in specific populations. METHODS: We selected patients with refractory epilepsy subjected to VNS who had completed at least a 12-month followup. Descriptive and inferential statistics were used to review and assess the effects of VNS on seizure frequency/intensity, memory, alertness, mood, postictal recovery, and quality of life (subjective scale, QoL IE-31 inventory) as well as factors (gender, age, age of onset, time of surgery, stimulation parameters, seizure frequency and type) associated with clinical response. We describe stimulation parameters, complications and adverse effects compared to other series. RESULTS: We selected 35 patients with an age range of 5-48 years; 18 patients presented partial epilepsy and 17 generalized epilepsy. All procedures and wound healing were uneventful, and no infections were reported. Median reduction in seizure frequency was 55.65% (p <0.001). Four patients showed improvement of >90%. Two patients became seizure free, whereas seizure frequency increased in two patients. The subjectively qualified response to treatment was good in 33 patients. The mean global increase in the QoLIE-31 Scale was 12.6 (p = 0.020). Improvements in memory, mood, alertness and postictal recovery period were documented. Only seizure type showed statistically significant association with clinical response. Adverse effects were transitory and responded to changes in stimulation parameters. CONCLUSIONS: VNS is a safe, feasible, well-tolerated and effective palliative treatment in appropriately selected cases of refractory partial and multifocal generalized seizures.