Neurological morbidity of surgery for suprasylvian operculoinsular epilepsy.

OBJECTIVE: The objective of this study was to identify risk factors associated with surgery-related neurological morbidity in patients with drug-resistant epilepsy undergoing suprasylvian operculoinsular resections. As secondary outcomes, we also analyzed the risk factors for ischemic lesion (IL) of corona radiata and seizure recurrence. METHODS: A retrospective analysis was conducted on a cohort of patients who underwent suprasylvian operculoinsular resections for drug-resistant epilepsy. The association of several presurgical, surgical, and postsurgical factors with both primary (persistent neurological deficits) and secondary (structural abnormalities on postoperative magnetic resonance imaging [MRI] and seizure recurrence) postoperative outcomes was investigated with univariate and multivariate statistical analysis. RESULTS: The study included a total of 65 patients; 46.2% of patients exhibited postoperative neurological deficits, but only 12.3% experienced persistent deficits. On postoperative MRI, IL in the corona radiata and corticospinal tract Wallerian degeneration (CSTWd) were seen in 68% and 29% of cases, respectively. Only CSTWd was significantly associated with persistent neurological deficits (relative risk [RR] = 2.6). Combined operculoinsular resection (RR = 3.62) and surgery performed on the left hemisphere (RR = .37) were independently associated with IL in the corona radiata. Variables independently associated with CSTWd were the presence of malacic components in the IL (RR = 1.96), right central operculum resection (RR = 1.79), and increasing age at surgery (RR = 1.03). Sixty-two patients had a postoperative follow-up > 12 months (median = 56, interquartile range = 30.75-73.5), and 62.9% were in Engel class I at last outpatient control. The risk of seizure recurrence was reduced by selective opercular resection (RR = .25) and increased by the histological diagnosis of aspecific gliosis (RR = 1.39). SIGNIFICANCE: This study provides insights into the risk factors associated with surgery-related neurological morbidity, as well as further evidence on the postoperative occurrence of subcortical injury and seizure recurrence in epileptic patients undergoing suprasylvian operculoinsular resections. The findings highlighted in this study may be useful to better understand the processes supporting the increased surgical risk in the operculoinsular region.

Dendritic pathology, spine loss and synaptic reorganization in human cortex from epilepsy patients.

Neuronal dendritic arborizations and dendritic spines are crucial for a normal synaptic transmission and may be critically involved in the pathophysiology of epilepsy. Alterations in dendritic morphology and spine loss mainly in hippocampal neurons have been reported both in epilepsy animal models and in human brain tissues from patients with epilepsy. However, it is still unclear whether these dendritic abnormalities relate to the cause of epilepsy or are generated by seizure recurrence. We investigated fine neuronal structures at the level of dendritic and spine organization using Golgi impregnation, and analysed synaptic networks with immunohistochemical markers of glutamatergic (vGLUT1) and GABAergic (vGAT) axon terminals in human cerebral cortices derived from epilepsy surgery. Specimens were obtained from 28 patients with different neuropathologically defined aetiologies: type Ia and type II focal cortical dysplasia, cryptogenic (no lesion) and temporal lobe epilepsy with hippocampal sclerosis. Autoptic tissues were used for comparison. Three-dimensional reconstructions of Golgi-impregnated neurons revealed severe dendritic reshaping and spine alteration in the core of the type II focal cortical dysplasia. Dysmorphic neurons showed increased dendritic complexity, reduction of dendritic spines and occasional filopodia-like protrusions emerging from the soma. Surprisingly, the intermingled normal-looking pyramidal neurons also showed severe spine loss and simplified dendritic arborization. No changes were observed outside the dysplasia (perilesional tissue) or in neocortical postsurgical tissue obtained in the other patient groups. Immunoreactivities of vGLUT1 and vGAT showed synaptic reorganization in the core of type II dysplasia characterized by the presence of abnormal perisomatic baskets around dysmorphic neurons, in particular those with filopodia-like protrusions, and changes in vGLUT1/vGAT expression. Ultrastructural data in type II dysplasia highlighted the presence of altered neuropil engulfed by glial processes. Our data indicate that the fine morphological aspect of neurons and dendritic spines are normal in epileptogenic neocortex, with the exception of type II dysplastic lesions. The findings suggest that the mechanisms leading to this severe form of cortical malformation interfere with the normal dendritic arborization and synaptic network organization. The data argue against the concept that long-lasting epilepsy and seizure recurrence per se unavoidably produce a dendritic pathology.

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.

Epilepsy surgery in infants up to 3 months of age: Safety, feasibility, and outcomes: A multicenter, multinational study.

OBJECTIVE: Drug-resistant epilepsy (DRE) during the first few months of life is challenging and necessitates aggressive treatment, including surgery. Because the most common causes of DRE in infancy are related to extensive developmental anomalies, surgery often entails extensive tissue resections or disconnection. The literature on "ultra-early" epilepsy surgery is sparse, with limited data concerning efficacy controlling the seizures, and safety. The current study's goal is to review the safety and efficacy of ultra-early epilepsy surgery performed before the age of 3 months. METHODS: To achieve a large sample size and external validity, a multinational, multicenter retrospective study was performed, focusing on epilepsy surgery for infants younger than 3 months of age. Collected data included epilepsy characteristics, surgical details, epilepsy outcome, and complications. RESULTS: Sixty-four patients underwent 69 surgeries before the age of 3 months. The most common pathologies were cortical dysplasia (28), hemimegalencephaly (17), and tubers (5). The most common procedures were hemispheric surgeries (48 procedures). Two cases were intentionally staged, and one was unexpectedly aborted. Nearly all patients received blood products. There were no perioperative deaths and no major unexpected permanent morbidities. Twenty-five percent of patients undergoing hemispheric surgeries developed hydrocephalus. Excellent epilepsy outcome (International League Against Epilepsy [ILAE] grade I) was achieved in 66% of cases over a median follow-up of 41 months (19-104 interquartile range [IQR]). The number of antiseizure medications was significantly reduced (median 2 drugs, 1-3 IQR, p < .0001). Outcome was not significantly associated with the type of surgery (hemispheric or more limited resections). SIGNIFICANCE: Epilepsy surgery during the first few months of life is associated with excellent seizure control, and when performed by highly experienced teams, is not associated with more permanent morbidity than surgery in older infants. Thus surgical treatment should not be postponed to treat DRE in very young infants based on their age.

Temporal lobe epilepsy: A never-ending story.

INTRODUCTION: Semiology and anatomo-electroclinical correlations remain invaluable for maintaining the level of excellence in temporal lobe epilepsy (TLE) surgery, in parallel to the constantly evolving technical progress. The aim of this study was to address semiological frequent and not so frequent signs, rarities and red flags in a long follow-up surgical series of patients suffering from TLE. METHODS: Patients operated within the boundaries of the TL at our center, with presurgical video-EEG recorded seizures and seizure free after a postoperative follow-up of at least 24 months were included. Ictal semiology was systematically described and new red flags were explored by comparing with a second group of patients with the same inclusion criteria but whose outcome had been unfavorable (Engel II-IV). RESULTS: Sixty-two patients were included, 46 seizure free and 16 with outcome Engel II-IV. Most seizure-free patients had a classical semiological presentation including aura (69.6%, abdominal the most frequent), followed by loss of responsiveness (90.2%) oral automatisms (90.7%), ipsilateral gestural automatisms (53.5%), contralateral upper limb dystonia (37.5%) or immobility (39.1%), and early ipsilateral non-versive head orientation (33.3%). More infrequent presentations were also present in the group of seizure-free patients: ictal language disturbance (13%), maintenance of responsiveness during seizures (9.8%), and contralateral rhythmic non manipulative automatism (6.9%). The presence of an isolated viscerosensory and/or psychic aura was significantly more frequent in the seizure-free group (p = 0.017), as well as oroalimentary automatisms (p = 0.005). Two signs were only present in the group with outcome Engel II-IV, constituting possible red flags (0.06 < p < 0.07): inferior limbs stepping-like automatisms and postictal dysarthria. CONCLUSION: An adequate clinical exam during seizures and a careful analysis of video recordings allow to recognize infrequent but well-characterized ictal signs that are part of the range of semiology in TLE, together with the most frequent and classical ictal presentations. Special attention to the localization hypothesis must be paid in the absence of oroalimentary automatisms or when the signs classified as possible red flags emerge.

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.

HSV-1 encephalitis relapse after epilepsy surgery: a case report and review of the literature.

Herpes simplex encephalitis relapses have been rarely reported, with only few cases occurring after neurosurgical interventions. A young man presented a late herpes simplex encephalitis relapse after left antero-mesial temporal resection for his refractory temporal lobe epilepsy. Eight days after surgery, he developed fever and aphasia. CSF PCR revealed more than 12,000 copies/ml of HSV-1 DNA. Intravenous acyclovir was immediately started with a complete recovery. Postoperative herpes simplex encephalitis can occur as primary infection or as relapse of previous infection. Surgical manipulation of brain parenchyma in the site of a previous infection can act as a trigger for viral reactivation. Early onset of antiviral therapy is fundamental and it is a strong predictor of clinical outcome. Despite no studies on prophylactic treatment with acyclovir in patients with previous herpes simplex encephalitis candidate to neurosurgery are available, we suggest that prophylactic treatment should be recommended.

pCREB expression in human tissues from epilepsy surgery.

OBJECTIVE: Activity-dependent changes have been reported in animal models and in human epileptic specimens and could potentially be used as tissue biomarkers to evaluate the propensity of a tissue to generate seizure activity. In this context, cAMP-response element binding protein (CREB) activation was specifically reported in human epileptic foci and related mainly to interictal spike activity. To get further insights into CREB activation in human epilepsy, we analyzed pCREB expression on brain tissue samples from patients who underwent surgery for drug-resistant focal epilepsy, correlating this expression with intracranial stereo-electroencephalography (SEEG) recording in a subgroup. METHODS: Neocortical specimens from patients with neuropathological diagnosis of no lesion (cryptogenic), malformations of cortical development,mainly type II focal cortical dysplasia (FCD), and hippocampi with and without hippocampal sclerosis have been analyzed by immunohistochemistry. Peritumoral cortex from non-epileptic patients and autoptic samples were used as controls, whereas rat brains were used to test possible loss of pCREB antigenicity due to fixation procedures and postmortem delay. RESULTS: pCREB was consistently expressed in layer II neuronal nuclei in regions with normal cortical lamination both in epileptic and non-epileptic surgical tissues. In patients with SEEG recordings, this anatomical pattern was unrelated to the presence of interictal spike activity. Conversely, in the core of type II FCD, as well as in other developmental malformations, pCREB was scattered without any laminar specificity. Furthermore, quantitative data did not reveal significant differences between epileptic and non-epileptic tissues, except for an increased immunoreactivity in the core of type IIB FCD lesion related mainly to reactive glial and balloon cells. SIGNIFICANCE: The present data argue against the reliability of pCREB immunohistochemistry as a marker of epileptic focus but underscores its layer-related expression, suggesting a potential application in the study of malformations of cortical development, a wide range of diseases arising from perturbations of normal brain development.

Trends in pediatric epilepsy surgery in Europe between 2008 and 2015: Country-, center-, and age-specific variation.

OBJECTIVE: To profile European trends in pediatric epilepsy surgery (<16 years of age) between 2008 and 2015. METHODS: We collected information on volumes and types of surgery, pathology, and seizure outcome from 20 recognized epilepsy surgery reference centers in 10 European countries. RESULTS: We analyzed retrospective aggregate data on 1859 operations. The proportion of surgeries significantly increased over time (P < .0001). Engel class I outcome was achieved in 69.3% of children, with no significant improvement between 2008 and 2015. The proportion of histopathological findings consistent with glial scars significantly increased between the ages of 7 and 16 years (P for trend = .0033), whereas that of the remaining pathologies did not vary across ages. A significant increase in unilobar extratemporal surgeries (P for trend = .0047) and a significant decrease in unilobar temporal surgeries (P for trend = .0030) were observed between 2008 and 2015. Conversely, the proportion of multilobar surgeries and unrevealing magnetic resonance imaging cases remained unchanged. Invasive investigations significantly increased, especially stereo-electroencephalography. We found different trends comparing centers starting their activity in the 1990s to those whose programs were developed in the past decade. Multivariate analysis revealed a significant variability of the proportion of the different pathologies and surgical approaches across countries, centers, and age groups between 2008 and 2015. SIGNIFICANCE: Between 2008 and 2015, we observed a significant increase in the volume of pediatric epilepsy surgeries, stability in the proportion of Engel class I outcomes, and a modest increment in complexity of the procedures.

Stereoelectroencephalography: retrospective analysis of 742 procedures in a single centre.

This retrospective description of a surgical series is aimed at reporting on indications, methodology, results on seizures, outcome predictors and complications from a 20-year stereoelectroencephalography (SEEG) activity performed at a single epilepsy surgery centre. Prospectively collected data from a consecutive series of 742 SEEG procedures carried out on 713 patients were reviewed and described. Long-term seizure outcome of SEEG-guided resections was defined as a binomial variable: absence (ILAE classes 1-2) or recurrence (ILAE classes 3-6) of disabling seizures. Predictors of seizure outcome were analysed by preliminary uni/bivariate analyses followed by multivariate logistic regression. Furthermore, results on seizures of these subjects were compared with those obtained in 1128 patients operated on after only non-invasive evaluation. Survival analyses were also carried out, limited to patients with a minimum follow-up of 10 years. Resective surgery has been indicated for 570 patients (79.9%). Two-hundred and seventy-nine of 470 patients operated on (59.4%) were free of disabling seizures at least 2 years after resective surgery. Negative magnetic resonance and post-surgical lesion remnant were significant risk factors for seizure recurrence, while type II focal cortical dysplasia, balloon cells, glioneuronal tumours, hippocampal sclerosis, older age at epilepsy onset and periventricular nodular heterotopy were significantly associated with seizure freedom. Twenty-five of 153 patients who underwent radio-frequency thermal coagulation (16.3%) were optimal responders. Thirteen of 742 (1.8%) procedures were complicated by unexpected events, including three (0.4%) major complications and one fatality (0.1%). In conclusion, SEEG is a safe and efficient methodology for invasive definition of the epileptogenic zone in the most challenging patients. Despite the progressive increase of MRI-negative cases, the proportion of seizure-free patients did not decrease throughout the years.

Surgery in patients with childhood-onset epilepsy: analysis of complications and predictive risk factors for a severely complicated course.

OBJECT: To compare the occurrence of surgery-related complications in patients with childhood-onset focal epilepsy operated on in the paediatric or in the adult age. To investigate risk factors for surgery-related complications in the whole cohort, with special attention to age at surgery and severe morbidity. METHODS: A cohort of 1282 patients operated on for childhood-onset focal epilepsy was retrospectively analysed. Occurrence of surgery-related complications, including a severely complicated course (SCC: surgical complication requiring reoperation and/or permanent neurological deficit and/or death), was compared between patients operated on in the paediatric age (<16 year-old; 452 cases) and, respectively, in adulthood (≥16 year-old; 830 cases). The whole cohort of patients was also evaluated for risk factors for a SCC. RESULTS: At last contact (median follow-up 98 months), 74.5% of patients were in Engel's class I (78.0% of children and 73.0% of adults). One hundred patients (7.8%) presented a SCC (6.4% for children and 8.6% for adult patients). Postoperative intracranial haemorrhages occurred more frequently in adult cases. At multivariate analysis, increasing age at operation, multilobar surgery, resections in the rolandic/perirolandic and in insulo-opercular regions were independent risk factors for a SCC. CONCLUSIONS: Surgery for childhood-onset focal epilepsy provides excellent results on seizures and an acceptable safety profile at any age. Nevertheless, our results suggest that increasing age at surgery is associated with an increase in odds of developing severe surgery-related complications. These findings support the recommendation that children with drug-resistant, symptomatic (or presumed symptomatic) focal epilepsy should be referred for a surgical evaluation as early as possible after seizure onset.

Clinical features of sleep-related hypermotor epilepsy in relation to the seizure-onset zone: A review of 135 surgically treated cases.

OBJECTIVES: Sleep-related hypermotor epilepsy (SHE), formerly nocturnal frontal lobe epilepsy, is characterized by abrupt and typically sleep-related seizures with motor patterns of variable complexity and duration. They seizures arise more frequently in the frontal lobe than in the extrafrontal regions but identifying the seizure onset-zone (SOZ) may be challenging. In this study, we aimed to describe the clinical features of both frontal and extrafrontal SHE, focusing on ictal semiologic patterns in order to increase diagnostic accuracy. METHODS: We retrospectively analyzed the clinical features of patients with drug-resistant SHE seen in our center for epilepsy surgery. Patients were divided into frontal and extrafrontal SHE (temporal, operculoinsular, and posterior SHE). We classified seizure semiology according to four semiology patterns (SPs): elementary motor signs (SP1), unnatural hypermotor movements (SP2), integrated hypermotor movements (SP3), and gestural behaviors with high emotional content (SP4). Early nonmotor manifestations were also assessed. RESULTS: Our case series consisted of 91 frontal SHE and 44 extrafrontal SHE cases. Frontal and extrafrontal SHE shared many features such as young age at onset, high seizure-frequency rate, high rate of scalp electroencephalography (EEG) and magnetic resonance imaging (MRI) abnormalities, similar histopathologic substrates, and good postsurgical outcome. Within the frontal lobe, SPs were organized in a posteroanterior gradient (SP1-4) with respect to the SOZ. In temporal SHE, SP1 was rare and SP3-4 frequent, whereas in operculoinsular and posterior SHE, SP4 was absent. Nonmotor manifestations were frequent (70%) and some could provide valuable localizing information. SIGNIFICANCE: Our study shows that the presence of certain SP and nonmotor manifestations may provide helpful information to localize seizure onset in patients with SHE.

Outcome after hemispherotomy in patients with intractable epilepsy: Comparison of techniques in the Italian experience.

OBJECTIVE: The objective of the study was to evaluate clinical characteristics and outcome of hemispherotomy in children and adolescents with hemispheric refractory epilepsy in an Italian cohort of patients. METHODS: We retrospectively evaluated the clinical course and outcome of 92 patients with refractory epilepsy who underwent hemispherotomy in three Italian epilepsy centers between 2006 and 2016. Three different approaches for hemispherotomy were used: parasagittal, modified parasagittal, and lateral. RESULTS: Mean age at epilepsy onset was 1.8 ±â€¯2.51 years, and mean duration of epilepsy prior to surgery was 7.4 ±â€¯5.6 years. Mean age at surgery was 9.2 ±â€¯8.0 years. After a mean follow-up of 2.81 ±â€¯2.4 years, 66 of 90 patients (two lost from follow-up, 73.3%) were seizure-free (Engel class I). The etiology of epilepsy was related to acquired lesions (encephalomalacia or gliosis) in 44 patients (47.8%), congenital malformations (cortical dysplasia, hemimegalencephaly, other cortical malformations) in 38 (41.3%), and progressive conditions (Rasmussen or Sturge-Weber syndrome) in 10 patients (10.9%). Regarding seizure outcome, we could not identify statistically significant differences between vertical and lateral approaches (p = 0.154). Seizure outcome was not statistically different in patients with congenital vs acquired or progressive etiologies (p = 0.43). Acute postoperative seizures (APOS) correlated with poor outcome (p < 0.05). On multivariate analysis, presurgical focal to bilateral tonic-clonic seizures (Odds Ratio (OR) = 3.63, 95% Confidence Interval (CI): 1.86-15.20, p = 0.048) independently predicted seizure recurrence. Twenty-one patients (22.8%) exhibited postoperative complications, with no unexpected and persistent neurological deficit. More than 50% of the patients completely tapered drugs. SIGNIFICANCE: Our data confirm hemispherotomy to be a safe and effective procedure in patients with drug resistant epilepsies due to hemispheric lesions. Presurgical focal to bilateral tonic-clonic seizures are the strongest predictor of seizure recurrence after surgery, independently from the type of hemispherotomy.

Seizure duration and latency of hypermotor manifestations distinguish frontal from extrafrontal onset in sleep-related hypermotor epilepsy.

Sleep-related hypermotor epilepsy (SHE) is an epilepsy syndrome that is characterized by the occurrence of sleep-related hypermotor seizures of variable complexity and duration. Seizures usually arise in the frontal lobe, but extrafrontal seizure onset zones are well described. To identify clinically relevant ictal features of SHE that could distinguish a frontal from an extrafrontal onset zone, we conducted a retrospective analysis of seizure characteristics in 58 patients with drug-resistant SHE (43 frontal and 15 extrafrontal) who underwent video-stereo-electroencephalographic recordings and became seizure-free after epilepsy surgery. We found that the mean duration of electrographic seizures and clinically observable ictal manifestations were significantly shorter in frontal SHE compared to extrafrontal SHE. The mean latency between electrographic seizure onset and the onset of hypermotor manifestations was also shorter in frontal SHE. Accordingly, a latency > 5 seconds between the first video-detectable movement (eg, eye opening or a minor motor event) and the onset of hypermotor manifestations yielded a sensitivity of 75% and a specificity of 90% for an extrafrontal onset, thereby indicating that specific ictal features in SHE can provide clinically useful clues to increase diagnostic accuracy in this syndrome.

Prolonged skin retention of clobetasol propionate by bio-based microemulsions: a potential tool for scalp psoriasis treatment.

Novel effective and cosmetically acceptable formulations are needed for the treatment of scalp psoriasis, due to the poor efficacy of the current products. The challenge in developing safe, efficient, and convenient delivery systems for this drug was addressed in the present work by formulating clobetasol propionate-loaded W/O microemulsions (MEs). Pseudo-ternary phase diagrams were constructed by using a combination of biocompatible and biodegradable excipients. Characterization studies demonstrated that selected MEs had suitable technological features such as being Newtonian fluids, possessing low viscosity, and high thermodynamic stability. Photomicrographs showed a significant alteration of the skin structure after treatment with MEs, and a preferential concentration of these in the stratum corneum and epidermis. These data, together with ex vivo permeation results, suggested an enhanced topical targeted effect due to an increased drug retention efficacy in the upper skin layers, as desired. Moreover, the bio-based excipients selected could contribute to the healing of the psoriatic scalp. In this way, the improvement of clobetasol efficacy is combined with the useful properties of the microemulsion components and with environmental safety.

Perisylvian, including insular, childhood epilepsy: Presurgical workup and surgical outcome.

OBJECTIVE: To report the presurgical workup, surgical procedures, and outcomes in a series of pediatric patients with drug-resistant epilepsy involving the perisylvian/insular regions. METHODS: We retrospectively assessed 16 pediatric patients affected by drug-resistant focal epilepsy involving perisylvian/insular regions, who consecutively underwent tailored resective surgery. All patients underwent a detailed presurgical workup, which included the analysis of the anatomoelectroclinical correlations with scalp electroencephalography (EEG) and/or with stereo-electroencephalography (SEEG), brain magnetic resonance imaging (MRI), and comprehensive cognitive and neuropsychological evaluations. After surgery, all patients underwent serial clinical and laboratory evaluations. RESULTS: Focal motor seizures restricted to perioral area, associated with symptoms related to the surrounding areas (as auditory hallucinations, unpleasant paresthesia, fear, and epigastric sensation), characterized the ictal semiology in 75% of patients. In 50%, autonomic manifestations were present and in 56% subjective manifestations were reported. The 50% of the patients underwent SEEG with insular sampling to better define the epileptogenic zone. In all patients, the insular cortex was always part of the epileptogenic zone, and tailored resections also involved, with variable degree, the frontal, parietal, and temporal opercula. Preoperatively, the neuropsychological assessment revealed impairments in specific cognitive functions and mild or moderate cognitive compromise in 88% of the patients. Postoperatively, one patient had permanent slight hemiparesis. At the most recent follow-up (median 39 months), seizure outcome was satisfactory in 69% of patients: seven patients were completely seizure-free (Engel class Ia), two were free of disabling seizure (class Ic), and two had rare disabling seizures (class II). The cognitive functioning remained unchanged in 62%, and improved in 38%. SIGNIFICANCE: The assessment of perisylvian/insular epilepsy in children is particularly challenging. However, tailored resections based on a careful presurgical evaluation, including SEEG recording, may lead to a good seizure control and to a better overall outcome.

Stereo-EEG-guided radiofrequency thermocoagulations.

The rationale and the surgical technique of stereo-electroencephalography (SEEG)-guided radiofrequency thermocoagulation (RF-TC) in the epileptogenic zone (EZ) of patients with difficult-to-treat focal epilepsy are described in this article. The application of the technique in pediatric patients is also detailed. Stereotactic ablative procedures by RF-TC have been employed in the treatment of epilepsy since the middle of the last century. This treatment option has gained new popularity in recent decades, mainly because of the availability of modern imaging techniques, which allow accurate targeting of intracerebral epileptogenic structures. SEEG is a powerful tool for identifying the EZ in the most challenging cases of focal epilepsy by recording electrical activity with tailored stereotactic implantation of multilead intracerebral electrodes. The same recording electrodes may be used to place thermocoagulative lesions in the EZ, following the indications provided by intracerebral monitoring. The technical details of SEEG implantation and of SEEG-guided RF-TC are described herein, with special attention to the employment of the procedure in pediatric cases. SEEG-guided RF-TC offers a potential therapeutic option based on robust electroclinical evidence with acceptable risks and costs. The procedure may be performed in patients who, according to SEEG recording, are not eligible for resective surgery, and it may be an alternative to resective surgery in a small subset of operable patients.

Stereo-EEG: Diagnostic and therapeutic tool for periventricular nodular heterotopia epilepsies.

OBJECTIVE: Periventricular nodular heterotopias (PNHs) are malformations of cortical development related to neuronal migration disorders, frequently associated with drug-resistant epilepsy (DRE). Stereo-electroencephalography (SEEG) is considered a very effective step of the presurgical evaluation, providing the recognition of the epileptogenic zone (EZ). At the same time, via the intracerebral electrodes it is possible to perform radiofrequency thermocoagulation (SEEG-guided RF-TC) with the aim of ablating and/or disrupting the EZ. The purpose of this study was to evaluate both the relationships between PNH and the EZ, and the efficacy of SEEG-guided RF-TC. METHODS: Twenty patients with DRE related to PNHs were studied. Inclusion criteria were the following: (1) patients with epilepsy and PNHs (unilateral or bilateral, single or multiple nodules) diagnosed on brain magnetic resonance imaging (MRI); (2) SEEG recordings available as part of the presurgical investigations, with at least one intracerebral electrode inside the heterotopia; (3) complete surgical workup with SEEG-guided RF-TC and/or with traditional neurosurgery, with a follow-up of at least 12 months. RESULTS: Complex and heterogenic epileptic networks were found in these patients. SEEG-guided RF-TC both into the nodules and/or the cortex was efficacious in the 76% of patients. Single or multiple, unilateral or bilateral PNHs are the most suitable for this procedure, whereas patients with PNHs associated with complex cortical malformations obtained excellent outcome only with traditional resective surgery. SIGNIFICANCE: Each patient had a specific epileptogenic network, independent from the number, size, or location of nodules and from the cortical malformation associated with. SEEG-guided RF-TC appears as a new and very effective diagnostic and therapeutic approach for DRE related to PNHs.

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.