Knowledge and attitudes of neurologists toward epilepsy surgery: an Italian survey.

The current study, conceived with the contribution of the Commission for Epilepsy Surgery of the Italian League Against Epilepsy (LICE) and the Epilepsy Study Group of the Italian Neurological Society (SIN), aimed to assess potential physician-related barriers to refer subjects for epilepsy surgery. All the members of SIN and LICE were invited by email to complete a 28-item online questionnaire. The survey items included: (1) individual and medical practice characteristics, (2) knowledge of current indications to select candidates for epilepsy surgery, (3) factors potentially affecting the attitude toward epilepsy surgery. Overall, 210 physicians completed the survey. More than half (63.3%) of the participants showed proper knowledge of the ILAE drug-resistance. Definition and almost two-thirds of them (71.9%) considered themselves adequately informed about indications, risks, and benefits of epilepsy surgery. Surgery was regarded as a valid option to be used as early as possible by 84.8% of the interviewees, and 71% of them estimated its complication rate to be low. However, more than half (63%) of the respondents reportedly referred patients for surgery only after the failure of 3-5 antiseizure medications. Overestimation of risks/complications of surgery and inadequate healthcare resources were identified as the main factor contrasting the patient referral for surgery by 43% and 40.5% of the participants, respectively. In conclusion, this survey confirms the existence of knowledge gap within both physicians and the healthcare system, as well as an educational need regarding epilepsy surgery. Further researches are warranted to define learning outcomes and optimize educational tools.

Temporal lobe epilepsy surgery in children and adults: A multicenter study.

OBJECTIVE: To assess seizure and cognitive outcomes and their predictors in children (<16 years at surgery) and adults undergoing temporal lobe epilepsy (TLE) surgery in eight Italian centers. METHODS: This is a retrospective multicenter study. We performed a descriptive analysis and subsequently carried out multivariable mixed-effect models corrected for multiple comparisons. RESULTS: We analyzed data from 511 patients (114 children) and observed significant differences in several clinical features between adults and children. The possibility of achieving Engel class IA outcome and discontinuing antiepileptic drugs (AEDs) at last follow-up (FU) was significantly higher in children (P = .006 and < .0001). However, percentages of children and adults in Engel class I at last FU (mean ± SD, 45.9 ± 17 months in children; 45.9 ± 20.6 months in adults) did not differ significantly. We identified different predictors of seizure outcome in children vs adults and at short- vs long-term FU. The only variables consistently associated with class I outcome over time were postoperative electroencephalography (EEG) in adults (abnormal, improved,odds ratio [OR] = 0.414, P = .023, Q = 0.046 vs normal, at 2-year FU and abnormal, improved, OR = 0.301, P = .001, Q = 0.002 vs normal, at last FU) and the completeness of resection of temporal magnetic resonance (MR) abnormalities other than hippocampal sclerosis in children (OR = 7.93, P = .001, Q = 0.003, at 2-year FU and OR = 45.03, P < .0001, Q < 0.0001, at last FU). Cognitive outcome was best predicted by preoperative performances in either age group. SIGNIFICANCE: Clinical differences between adult and pediatric patients undergoing TLE surgery are reflected in differences in long-term outcomes and predictors of failures. Children are more likely to achieve sustained seizure freedom and withdraw AEDs after TLE surgery. Earlier referral should be encouraged as it can improve surgical outcome.

The surgical treatment of epilepsy.

In 2009, the Commission for Epilepsy Surgery of the Italian League Against Epilepsy (LICE) conducted an overview about the techniques used for the pre-surgical evaluation and the surgical treatment of epilepsies. The recognition that, in selected cases, surgery can be considered the first-line approach, suggested that the experience gained by the main Italian referral centers should be pooled in order to provide a handy source of reference. In light of the progress made over these past years, some parts of that first report have accordingly been updated. The present revision aims to harmonize the general principles regulating the patient selection and the pre-surgical work-up, as well as to expand the use of epilepsy surgery, that still represents an underutilized resource, regrettably. The objective of this contribution is drawing up a methodological framework within which to integrate the experiences of each group in this complex and dynamic sector of the neurosciences.

Management of epilepsy in brain tumors.

Epilepsy in brain tumors (BTE) may require medical attention for a variety of unique concerns: epileptic seizures, possible serious adverse effects of antineoplastic and antiepileptic drugs (AEDs), physical disability, and/or neurocognitive disturbances correlated to tumor site. Guidelines for the management of tumor-related epilepsies are lacking. Treatment is not standardized, and overall management might differ according to different specialists. The aim of this document was to provide directives on the procedures to be adopted for a correct diagnostic-therapeutic path of the patient with BTE, evaluating indications, risks, and benefits. A board comprising neurologists, epileptologists, neurophysiologists, neuroradiologists, neurosurgeons, neuro-oncologists, neuropsychologists, and patients' representatives was formed. The board converted diagnostic and therapeutic problems into seventeen questions. A literature search was performed in September-October 2017, and a total of 7827 unique records were retrieved, of which 148 constituted the core literature. There is no evidence that histological type or localization of the brain tumor affects the response to an AED. The board recommended to avoid enzyme-inducing antiepileptic drugs because of their interference with antitumoral drugs and consider as first-choice newer generation drugs (among them, levetiracetam, lamotrigine, and topiramate). Valproic acid should also be considered. Both short-term and long-term prophylaxes are not recommended in primary and metastatic brain tumors. Management of seizures in patients with BTE should be multidisciplinary. The panel evidenced conflicting or lacking data regarding the role of EEG, the choice of therapeutic strategy, and timing to withdraw AEDs and recommended high-quality long-term studies to standardize BTE care.

Epilepsy surgery of "low grade epilepsy associated neuroepithelial tumors": A retrospective nationwide Italian study.

OBJECTIVE: To analyze the attitude and results of Italian epilepsy surgery centers in the surgical management of "low grade epilepsy associated neuroepithelial tumors" (LEATs). METHODS: We conducted a retrospective study enrolling 339 consecutive patients with LEATs who underwent surgery between January 2009 and June 2015 at eight Italian epilepsy surgery centers. We compared demographic, clinical, pathologic, and surgical features of patients with favorable (Engel class I) and unfavorable (Engel class II, III, and IV) seizure outcome. In addition, we compared patients with tumor-associated focal cortical dysplasia (FCD) and patients with solitary tumors to identify factors correlated with FCD diagnosis. RESULTS: Fifty-five (98.2%) of 56 patients with medically controlled epilepsy were seizure-free after surgery, compared to 249 (88.0%) of 283 patients with refractory epilepsy. At multivariate analysis, three variables independently predict unfavorable seizure outcome in the drug-resistant group. Age at surgery is largely the most significant (p = 0.001), with an odds ratio (OR) of 1.04. This means that the probability of seizure recurrence grows by 4% for every waited year. The resection site is also significant (p = 0.039), with a relative risk (RR) of 1.99 for extratemporal tumors. Finally, the completeness of tumor resection has a trend toward significance (p = 0.092), with an RR of 1.82 for incomplete resection. Among pediatric patients, a longer duration of epilepsy was significantly associated with preoperative neuropsychological deficits (p < 0.001). A statistically significant association was observed between FCD diagnosis and the following variables: tailored surgery (p < 0.001), temporal resection (p = 0.001), and surgical center (p = 0.012). SIGNIFICANCE: Our nationwide LEATs study gives important insights on factors predicting seizure outcome in refractory epilepsy and determining variability in FCD detection. Timely surgery, regardless of pharmacoresistance and oriented to optimize epileptologic, neuropsychological, and oncologic outcomes should be warranted.

Increasing volume and complexity of pediatric epilepsy surgery with stable seizure outcome between 2008 and 2014: A nationwide multicenter study.

OBJECTIVE: The objective of the study was to assess common practice in pediatric epilepsy surgery in Italy between 2008 and 2014. METHODS: A survey was conducted among nine Italian epilepsy surgery centers to collect information on presurgical and postsurgical evaluation protocols, volumes and types of surgical interventions, and etiologies and seizure outcomes in pediatric epilepsy surgery between 2008 and 2014. RESULTS: Retrospective data on 527 surgical procedures were collected. The most frequent surgical approaches were temporal lobe resections and disconnections (133, 25.2%) and extratemporal lesionectomies (128, 24.3%); the most frequent etiologies were FCD II (107, 20.3%) and glioneuronal tumors (105, 19.9%). Volumes of surgeries increased over time independently from the age at surgery and the epilepsy surgery center. Engel class I was achieved in 73.6% of patients (range: 54.8 to 91.7%), with no significant changes between 2008 and 2014. Univariate analyses showed a decrease in the proportion of temporal resections and tumors and an increase in the proportion of FCDII, while multivariate analyses revealed an increase in the proportion of extratemporal surgeries over time. A higher proportion of temporal surgeries and tumors and a lower proportion of extratemporal and multilobar surgeries and of FCD were observed in low (<50surgeries/year) versus high-volume centers. There was a high variability across centers concerning pre- and postsurgical evaluation protocols, depending on local expertise and facilities. SIGNIFICANCE: This survey reveals an increase in volume and complexity of pediatric epilepsy surgery in Italy between 2008 and 2014, associated with a stable seizure outcome.

The long-term effect of vagus nerve stimulation on quality of life in patients with pharmacoresistant focal epilepsy: the PuLsE (Open Prospective Randomized Long-term Effectiveness) trial.

OBJECTIVE: To evaluate whether vagus nerve stimulation (VNS) as adjunct to best medical practice (VNS + BMP) is superior to BMP alone in improving long-term health-related quality of life (HRQoL). METHODS: PuLsE (Open Prospective Randomized Long-term Effectiveness) was a prospective, randomized, parallel-group, open-label, and long-term effectiveness study (conducted at 28 sites in Europe and Canada). Adults with pharmacoresistant focal seizures (n = 112) received VNS + BMP or BMP (1:1 ratio). Medications and VNS parameters could be adjusted as clinically indicated for optimal seizure control while minimizing adverse effects. Primary endpoint was mean change from baseline HRQoL (using Quality of Life in Epilepsy Inventory-89 total score; QOLIE-89). Secondary endpoints included changes in seizure frequency, responder rate (≥50% decrease in seizure frequency), Centre for Epidemiologic Studies Depression scale (CES-D), Neurological Disorders Depression Inventory-Epilepsy scale (NDDI-E), Clinical Global Impression-Improvement scale (CGI-I), Adverse Event Profile (AEP), and antiepileptic drug (AED) load. The study was prematurely terminated due to recruitment difficulties prior to completing the planned enrollment of n = 362. Results for n = 96 who had baseline and at least one follow-up QOLIE-89 assessment (from months 3-12) were included in this analysis. Mixed model repeated measures (MMRM) analysis of variance was performed on change from baseline for the primary and secondary endpoints. RESULTS: Significant between-group differences in favor of VNS + BMP were observed regarding improvement in HRQoL, seizure frequency, and CGI-I score (respective p-values < 0.05, 0.03, and 0.01). More patients in the VNS + BMP group (43%) reported adverse events (AEs) versus BMP group (21%) (p = 0.01), a difference reflecting primarily mostly transient AEs related to VNS implantation or stimulation. No significant difference between treatment groups was observed for changes in CES-D, NDDI-E, AEP, and AED load. SIGNIFICANCE: VNS therapy as a treatment adjunct to BMP in patients with pharmacoresistant focal seizures was associated with a significant improvement in HRQoL compared with BMP alone. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Long-Term Outcome in Adult Patients with Drug-Resistant Epilepsy Submitted to Vagus Nerve Stimulation.

Epilepsy treatment primarily involves antiseizure medications (ASMs) to eliminate seizures and improve the quality of life, but many patients develop drug-resistant epilepsy (DRE), necessitating alternative interventions. This study aimed to evaluate the long-term efficacy and safety of vagus nerve stimulation (VNS) in managing DRE. We retrospectively analyzed data from 105 adult patients treated at Agostino Gemelli Hospital from 1994 to 2022. Among the 73 patients with follow-up data, 80.8% were responders, experiencing significant reductions in seizure frequency over an average follow-up period of 9.4 years. Although 19.2% were non-responders, many of these patients still opted for generator replacements due to improvements in quality of life, such as fewer falls and shorter post-ictal periods. The overall complication rate was 12.3%, with most complications being mild and manageable. These findings suggest that VNS offers substantial long-term benefits for patients with DRE, improving seizure control and quality of life. This study underscores the importance of VNS as a viable long-term treatment option for DRE, highlighting its potential to significantly enhance patient outcomes and quality of life.

Health Technology Assessment report on the presurgical evaluation and surgical treatment of drug-resistant epilepsy.

PURPOSE: Epilepsy is a neurologic disorder with major social impact. Surgery is a valuable option in patients who are not responding to antiepileptic drugs. The literature reports demonstrate that a proportion ranging from 40 to 100% of patients with epilepsy achieve seizure remission after surgery. A presurgical evaluation (clinical and instrumental) must be performed in all patients with drug-resistant epilepsy to assess their suitability for surgical intervention. Health Technology Assessment (HTA) represents a modern approach to the analysis of technologies used for health care. HTA could be considered a bridge between science that produces evidence and the decisions that can be taken on the basis of that evidence at different levels of the health care system. The aim of this study is the HTA of epilepsy surgery including clinical, ethical, social, and economic features. METHODS: The present study includes an analysis of the diagnostic and surgical workup performed at the Italian centers for the diagnosis and treatment of drug-resistant epilepsy (DRE). The study includes the following issues: (1) social, ethical impact, and costs of the disease; (2) clinical results, efficacy, and safety of surgery; (3) ethics and quality of life after surgery; and (4) economic impact and productivity regained after surgery. The cost of managing a patient with DRE included in the presurgical study was estimated by the bottom-up microcosting technique that starts from a detailed collection of data on consumption of resources and full costing. The phases analyzed were (1) noninvasive diagnostic workup; (2) neurosurgical intervention; and (3) follow-up. KEY FINDINGS: The literature reports indicate epilepsy surgery as an effective treatment both on clinical results and on ethical, social, and quality of life aspects. The workup including the noninvasive presurgical study followed by surgery has a total cost of €20,827. Management of short-term follow-up increases the overhead to €22,291 at the first year, and then to €23,571 after 5 years. According to the estimates made in this survey, funding based on diagnosis-related group (DRG) tariff for the noninvasive diagnostic stage involving hospital admission is not remunerative in Italy either at regional or national levels. Effectively the difference between full cost and DRG has a delta of €3,402 and €2,537 respectively. The total cost of the presurgical, surgical, and follow-up evaluation is not remunerative for €10,554 (national data). SIGNIFICANCE: Economic surveys in Italy have shown that surgery for DRE is an advantageous treatment from the standpoint of third-party payers and is cost-effective for society. DRE presurgical evaluation and surgery are not remunerative either at regional or national levels.

Overview of presurgical assessment and surgical treatment of epilepsy from the Italian League Against Epilepsy.

The Commission for Epilepsy Surgery of the Italian League Against Epilepsy (LICE) presents an overview of the techniques and methodologies of presurgical evaluation and of the surgical treatment of epilepsies. This overview is the result of the experience developed in the past years in the major Italian centers where programs of epilepsy surgery have been established, and it has the aim of offering a quick and easy reference tool for those involved in the treatment of patients with epilepsy. The sharing of different experiences has the additional aim of conforming and disseminating the employed techniques as well as the methods of selection and evaluation of patients. The synthetic coverage of the main issues concerning the presurgical workup and the available surgical options will hopefully provide a framework that may integrate and develop the contributions of every single center, in one of the more complex, challenging, and dynamic areas of neurological sciences.

Vagus nerve stimulation in drug-resistant epilepsies. Analysis of potential prognostic factors in a cohort of patients with long-term follow-up.

BACKGROUND: The results of vagus nerve stimulation (VNS) for the treatment of drug-resistant epilepsies are highly variable due to the lack of defined patient's selection criteria and a follow-up of published studies being generally too short. Here we report the outcome of VNS in a series with long-term follow-up and try to identify subgroups of patients who could be better candidates for this procedure. METHOD: We studied 53 patients (33 male, 20 female) with a prospectively recorded follow-up (mean, 55.96 ± 43.53 months). The monthly average seizure frequency for each patient at baseline, 3, 6, 12 months, and each year until the latest follow-up after implant was measured and the percentage of "responders" and response time (RT) were calculated. We investigated the following potential prognostic role of these factors: age of onset of epilepsy, pre-implant epilepsy duration, etiology, and age at implant. RESULTS: Globally, 40 % of patients responded to VNS (mean RT, 14.85 ± 16.85 months). Lesional etiology (p = 0.0179, logrank test), particularly ischemia (p = 0.011, Fisher exact test) and tuberous sclerosis (p = 0.0229, Fisher exact test), and age at implant <18 years (p = 0.0242, logrank test) were associated to better response to VNS. In the lesional subgroup the best results were observed in patients with a pre-implant epilepsy duration <15 years (p = 0.0204, logrank test) and an age at implant <18 years (p = 0.0187 logrank test). CONCLUSIONS: The best candidate to VNS seems to be a patient with lesional etiology epilepsy (particularly post-ischemic and tuberous sclerosis) and a short duration of epilepsy who undergo VNS younger than 18 years.

Palliative Surgery for Drug-Resistant Epilepsy in Adult Patients. A Systematic Review of the Literature and a Pooled Analysis of Outcomes.

BACKGROUND: Several types of palliative surgery to treat drug-resistant epilepsy (DRE) have been reported, but the evidence that is available is insufficient to help physicians redirect patients with DRE to the most appropriate kind of surgery. METHODS: A systematic search in the PubMed and Scopus databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to compare different clinical features, outcomes, and complications of adult patients submitted to callosotomy, vagal nerve stimulation, multiple subpial transections, deep brain stimulation, or responsive neurostimulation. RESULTS: After 3447 articles were screened, 36 studies were selected, including the data of 1628 patients: 76 were treated with callosotomy, 659 were treated with vagal nerve stimulation, 416 were treated with deep brain stimulation, and 477 were treated with responsive neurostimulation. No studies including patients treated with multiple subpial transections met the inclusion criteria. The global weighted average seizure frequency reduction was 50.23%, and the global responder rate was 52.12%. There were significant differences among the palliative surgical procedures in term of clinical features of patients and epilepsy, seizure frequency reduction, and percentage of responders. Complications were differently distributed as well. CONCLUSIONS: Our analysis highlights the necessity of prospective studies, possibly randomized controlled trials, to compare different forms of palliative epilepsy surgery. Moreover, by identifying the outcome predictors associated with each technique, the best responder may be profiled for each procedure.

Focal Cortical Dysplasia IIIa in Hippocampal Sclerosis-Associated Epilepsy: Anatomo-Electro-Clinical Profile and Surgical Results From a Multicentric Retrospective Study.

BACKGROUND: Hippocampal sclerosis (HS) may be associated with focal cortical dysplasia IIIa (FCD IIIa) in patients undergoing surgery for temporal lobe epilepsy (TLE). OBJECTIVE: To investigate whether the anatomo-electro-clinical profile and surgical outcome in patients with HS-related TLE are affected by coexisting FCD IIIa. METHODS: A total of 220 patients, operated in 5 centers, with at least 24 mo follow-up (FU), were retrospectively studied. Preliminary univariate and subsequent multivariate analyses were performed to investigate possible associations between several potential presurgical, surgical, and postsurgical predictors and different variables (Engel's class I and Engel's class Ia, co-occurrence of FCD IIIa). RESULTS: At last available postoperative control (FU: range 24-95 mo, median 47 mo), 182 (82.7%) patients were classified as Engel's class I and 142 (64.5%) as Engel's class Ia. At multivariate analysis, extension of neocortical resection and postoperative electroencephalogram were significantly associated with Engel's class I, whereas length of FU had a significant impact on class Ia in the whole cohort and in isolated HS (iHS) patients, but not in the FCD IIIa group. No differences emerged in the anatomo-electro-clinical profile and surgical results between patients with FCD IIIa and with iHS. CONCLUSION: Coexistence of FCD IIIa did not confer a distinct anatomo-electro-clinical profile to patients with HS-related epilepsy. Postoperative seizure outcome was similar in FCD IIIa and iHS cases. These findings indicate limited clinical relevance of FCD IIIa in HS-related epilepsy and might be useful for refining future FCD classifications. Further studies are needed to clarify the correlation of class Ia outcome with the duration of FU.

Radiotherapy and concomitant temozolomide during the first and last weeks in high grade gliomas: long-term analysis of a phase II study.

We tested the efficacy and safety of temozolomide (TMZ) when given concomitantly to radiotherapy only in the first and last weeks of treatment to patients affected by high grade gliomas. Conformal radiotherapy (CTV1: tumor bed + residual tumor if present + 1.5 cm, 5,940 cGy, 180 cGy/day; CTV2: oedema, 3,960 cGy, 180 cGy/day) was associated with TMZ, 75 mg/m(2) x 5 days, the first and last weeks of radiotherapy. Adjuvant chemotherapy with TMZ (150 mg/mq daily x 5 days, q28 on the first cycle, 200 mg/mq daily x 5 days, q28 for the following cycles) was given, after chemoradiation, until disease progression or up to 6 cycles. From October 2000 to December 2003, 29 patients (25 GBL, 86.2%; 4 AA, 13.8%) were enrolled in this study. Twenty-two patients (75.8%) received a median 6 cycles of adjuvant chemotherapy with TMZ (range 1-20). Hematological toxicity was absent during concomitant chemoradiation and mild in adjuvant therapy, while neurological toxicity (seizures) was observed only in one case. At a median follow-up of 66 months (range 3-96), median progression-free survival (PFS) was 8 months, with a 1- and 2-year PFS of 46.7 and 28.7%, respectively; median overall survival (OS) time was 21 months, with a 1- and 2-year OS of 69.2 and 42.3%, respectively. In our experience, TMZ proved to be effective even when given only during the first and the last week of radiotherapy, with lower hematological toxicity.

Vagal nerve stimulation for drug-resistant epilepsies in different age, aetiology and duration.

PURPOSE: The aim of the study was to compare the outcome with respect to age of implant, aetiology and duration of epilepsy. METHODS: One hundred thirty-five drug-resistant epileptic patients, excluded from ablative surgery, were submitted to vagal nerve stimulation (1995-2007). Aetiology was cryptogenic in 57 and symptomatic in 78 patients. Ages of implant were 0.5-6 years (18 patients), 7-12 years (32 patients), 13-18 years (31 patients) and more than 18 years (54 patients). Epilepsy types were Lennox-Gastaut (18 patients), severe multifocal epilepsy (33 patients) and partial (84 patients). Duration of epilepsy is 3 months to 57 years. Clinical outcome was determined by comparing the seizure frequency after stimulation at 3-6-12-18-24-36 months with the previous 3 months. 'Responders' were the patients experiencing a seizure frequency reduction of 50% or more during follow-up. In statistical analysis, Wilcoxon and McNemar tests, general linear model for repeated measures, logistic regression and survival analysis were used. RESULTS: The seizure frequency reduction was significant in the group as a whole between baseline and the first follow-up (Wilcoxon test). The percentage of responder increases with time (McNemar test p = 0.04). Univariate analysis showed a significant effect of the age of implant on seizure frequency reduction: Adult patient had worst clinical outcome than children (p < 0.001) and adolescents (p = 0.08). Patients with severe multifocal epilepsy had better percentage seizure reduction compared with Lennox-Gastaut and partial (p = 0.03). Lesser duration of epilepsy had positive influence on outcome. Multivariate analysis confirmed age of implant to be the strongest factor influencing prognosis. Furthermore, positive is the association between lesional aetiology and young age. CONCLUSIONS: The best responder could be a young lesional epileptic patient; after 3 years of follow-up, the percentage of responders is still in progress.

Health Technology Assessment Report on Vagus Nerve Stimulation in Drug-Resistant Epilepsy.

Background: Vagus nerve stimulation (VNS) is a palliative treatment for medical intractable epileptic syndromes not eligible for resective surgery. Health technology assessment (HTA) represents a modern approach to the analysis of technologies used for healthcare. The purpose of this study is to assess the clinical, organizational, financial, and economic impact of VNS therapy in drug-resistant epilepsies and to establish the congruity between costs incurred and health service reimbursement. Methods: The present study used an HTA approach. It is based on an extensive detailed bibliographic search on databases (Medline, Pubmed, Embase and Cochrane, sites of scientific societies and institutional sites). The HTA study includes the following issues: (a) social impact and costs of the disease; (b) VNS eligibility and clinical results; (c) quality of life (QoL) after VNS therapy; (d) economic impact and productivity regained after VNS; and (e) costs of VNS. Results: Literature data indicate VNS as an effective treatment with a potential positive impact on social aspects and on quality of life. The diagnosis-related group (DRG) financing, both on national and regional levels, does not cover the cost of the medical device. There was an evident insufficient coverage of the DRG compared to the full cost of implanting the device. Conclusions: VNS is a palliative treatment for reducing seizure frequency and intensity. Despite its economic cost, VNS should improve patients' quality of life and reduce care needs.

CD34 Expression in Low-Grade Epilepsy-Associated Tumors: Relationships with Clinicopathologic Features.

OBJECTIVE: To analyze relationships between CD34 expression and several demographic, clinical, and pathologic features in patients with histopathologic evidence of low-grade epilepsy-associated tumors who underwent epilepsy surgery. METHODS: A retrospective study enrolling 187 patients with low-grade epilepsy-associated tumors who underwent surgery between January 2009 and June 2015 at 8 Italian epilepsy surgery centers was conducted. All cases were histologically diagnosed according to the World Health Organization classification of central nervous system tumors. Univariate and multivariate analyses were performed to identify variables associated with CD34 expression. RESULTS: Of 187 patients, 95 (50.8%) were CD34 positive. Tumor type and duration of epilepsy were independently associated with CD34 expression on multivariate analysis. Ganglioglioma and pleomorphic xanthoastrocytoma were the histologic types with the strongest association with CD34 positivity with an odds ratio of 9.2 and 10.4, respectively, compared with dysembryoplastic neuroepithelial tumors. Patients with a duration of epilepsy >10 years had a significantly greater likelihood to show CD34 expression, with an odds ratio of 2.8 compared with patients with a duration of epilepsy <2 years. On univariate analysis, CD34 expression appeared to be significantly related to older age at surgery, higher antiepileptic drug intake, and female sex. CONCLUSIONS: CD34 expression holds promise as a useful biomolecular marker for patients with low-grade epilepsy-associated tumors with evidence of a link with clinicopathologic features. This study confirmed the association between CD34 expression and tumor type and demonstrated a significantly higher probability of CD34 expression in patients with longer duration of epilepsy, independent of histology.

Detection of Hyperexcitability by Functional Magnetic Resonance Imaging after Experimental Traumatic Brain Injury.

Diagnosis of ongoing epileptogenesis and associated hyperexcitability after brain injury is a major challenge. Given that increased neuronal activity in the brain triggers a blood oxygenation level-dependent (BOLD) response in functional magnetic resonance imaging (fMRI), we hypothesized that fMRI could be used to identify the brain area(s) with hyperexcitability during post-injury epileptogenesis. We applied fMRI to detect onset and spread of BOLD activation after pentylenetetrazol (PTZ)-induced seizures (PTZ, 30 mg/kg, intraperitoneally) in 16 adult male rats at 2 months after lateral fluid percussion (FPI)-induced traumatic brain injury (TBI). In sham-operated controls, onset of the PTZ-induced BOLD response was bilateral and first appeared in the cortex. After TBI, 5 of 9 (56%) rats exhibited ipsilateral perilesional cortical BOLD activation, followed by activation of the contralateral cortex. In 4 of 9 (44%) rats, onset of BOLD response was bilateral. Interestingly, latency from the PTZ injection to onset of the BOLD response increased in the following order: sham-operated controls (ipsilateral 132 ± 57 sec, contralateral 132 ± 57 sec; p > 0.05) < TBI with bilateral BOLD onset (ipsilateral 176 ± 54 sec, contralateral 178 ± 52 sec; p > 0.05) < TBI with ipsilateral BOLD onset (ipsilateral 406 ± 178 sec, contralateral 509 ± 140 sec; p < 0.05). Cortical lesion area did not differ between rats with ipsilateral versus bilateral BOLD onset (p > 0.05). In the group of rats with ipsilateral onset of PTZ-induced BOLD activation, none of the rats showed a robust bilateral thalamic BOLD response, only 1 of 5 rats had robust ipsilateral thalamic calcifications, and 4 of 5 rats had perilesional astrocytosis. These findings suggest the evolution of the epileptogenic zone in the perilesional cortex after TBI, which is sensitive to PTZ-induced hyperexcitability. Further studies are warranted to explore the evolution of thalamo-cortical pathology as a driver of epileptogenesis after lateral FPI.