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.

Electroclinical Features of Infantile Epileptic Spasms Syndrome.

Epileptic spasms are a unique, age-dependent manifestation of epilepsies in infancy and early childhood, commonly occurring as part of infantile epileptic spasms syndrome. Developmental stagnation and subsequent decline may occur in children with epileptic spasms, partly due to the abundant high-amplitude interictal epileptiform and slow wave abnormalities. Early recognition and treatment of epileptic spasms, along with the reversal of the electroencephalography (EEG) findings, are critical for improving outcomes. Recognizing hypsarrhythmia and its variations is key to confirming the diagnosis. The various patterns of hypsarrhythmia are not etiology specific, but could indicate the severity of the disease. Several scoring systems have been proposed to improve the inter-rater reliability of recognizing hypsarrhythmia and to assess EEG progress in response to treatment. Ictal patterns during spasms are brief and composed of slow waves, sharp transients, fast activity, and voltage attenuation, either in isolation or more commonly as a combination of these waveforms. Ictal patterns are commonly diffuse, but may be lateralized to one hemisphere in children with structural etiology. A subset of patients with epileptic spasms has a surgically remediable etiology, with readily identifiable lesions on neuroimaging in most cases. Asymmetry in epileptic spasms, concurrent focal seizures, and asymmetric interictal and ictal EEG findings may be present, but a lack of focality in electrophysiological findings is not uncommon. Intracranial EEG features of epileptic spasms have been described, but the utility of intracranial EEG monitoring in surgical candidates with overt focal epileptogenic lesions on magnetic resonance imaging is questionable, and surgery could be performed using noninvasive data.

Epilepsy surgery for children with epileptic spasms: A systematic review and meta-analysis with focus on predictors and outcomes.

To conduct a systematic review of the literature regarding rates and predictors of favorable seizure outcome after resective surgery for epileptic spasms (ES) in pediatric patients. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards were followed. We searched PubMed, EMBASE, and Cochrane CENTRAL for articles published on the prevalence or incidence of epileptic spasm since 1985. Abstract, full-text review, and data extraction were conducted by two independent reviewers. Meta-analysis was performed to assess overall seizure freedom rate. Subject-level analysis was performed on a subset of studies to identify prognostic indicators. A total of 21 retrospective studies (n = 531) were included. Meta-analysis of all studies demonstrated a pooled seizure freedom rate of 68.8%. Subject-level analysis on 18 studies (n = 360) demonstrated a significant association between duration of spasms and recurrence of spasms after surgery, with an estimated increased risk of 7% per additional year of spasms prior to operation. Patients who underwent resective surgery that was not a hemispherectomy (i.e., lobectomy, lesionectomy, etc.) had an increased recurrence risk of 57% compared to patients who had undergone hemispherectomy. Resective surgery results in seizure freedom for the majority of pediatric patients with epileptic spasms. Patients who undergo hemispherectomy have lower risk of recurrence than patients who undergo other types of surgical resection. Increased duration of spasms prior to surgery is associated with increased recurrence risk after surgery. PLAIN LANGUAGE SUMMARY: Children with epileptic spasms (ES) that do not respond to medications may benefit from surgical treatment. Our study reviewed existing research to understand how effective surgery is in treating ES in children and what factors predict better outcomes. Researchers followed strict guidelines to search for and analyze studies published since 1985, finding 21 studies with a total of 531 patients. They found that, on average, nearly 70% of children became seizure-free after surgery. Further individual analysis of 360 patients showed that longer duration of spasms before surgery increased the risk of spasms returning by 7% per year. Additionally, children who had less extensive surgeries, such as removal of only a specific part of the brain, had a 57% higher risk of seizure recurrence compared to those who had a hemispherectomy, which removed or disconnected half of the brain. Overall, the study concludes that surgery can often stop seizures, especially when more extensive surgery is performed and when the surgery is done sooner rather than later.

Electroclinical Features in Epilepsy Surgery Candidates With Epileptic Spasms.

SUMMARY: Electroclinical features in surgical candidates with epileptic spasms differ significantly from the other focal epilepsy phenotypes. EEG findings tend to be more diffuse and less localizing in children with epileptic spasms. These are illustrated with five case studies to highlight three different categories of findings on interictal and ictal EEG: lateralizing , nonlateralizing , and false lateralizing . Hemihypsarrhythmia on interictal EEG is the most striking lateralizing abnormality that occurs in a minority of surgical candidates. Persistent focal epileptiform discharges in one region or asymmetric physiologic rhythms decreased over the abnormal hemisphere may provide localization clues. Ictal EEG patterns are diffuse and nonlocalizing in over half of the patients. Ictal patterns are best expressed in the posterior head regions even in patients with epileptogenic zone in anterior regions. Semiologically, epileptic spasms tend to be symmetrical in majority of surgical candidates. Asymmetric spasms and coexisting focal seizures (concurrent or remote), when present, may provide localization findings. False lateralizing interictal or ictal EEG abnormalities, paradoxically higher over the healthier hemisphere, occur in the setting of large encephaloclastic/volume loss lesions. In these patients, the diffuse discharges are less expressed over the abnormal hemisphere with less cerebral tissue. Recognition of such false lateralizing findings is important to avoid excluding appropriate surgical candidates based on the EEG findings alone. Epileptogenic lesions are visible on brain MRI in majority of surgical candidates with epileptic spasms. Electroclinical findings are often concordant with the lesion, but discordant findings are not uncommon in children with epileptic spasms.

Surgical candidates in children with epileptic spasms can be selected without invasive monitoring: A report of 70 cases.

OBJECTIVE: Prior surgical series in children with drug-resistant epileptic spasms have reported use of intracranial EEG monitoring in up to two-third of patients. We report outcome after epilepsy surgery for drug-resistant epileptic spasms in a cohort of children without the use of intracranial EEG monitoring in any of the patients. METHODS: Medical records of all consecutive children aged 5 years or under who had epilepsy surgery for epileptic spasms at Cleveland Clinic between 2000 and 2018 were reviewed. Post-operative seizure outcome and predictors of prognosis of seizure outcome were analyzed. RESULTS: Seventy children with active epileptic spasms underwent surgical resections during the study period. Mean age at seizure onset was 6.8 (+9.31) months and median age at surgery was 18.5 months. An epileptogenic lesion was identified on brain MRI in all patients; 17 (24%) had bilateral abnormalities. Etiologies included malformations of cortical development (58%), perinatal infarct/encephalomalacia (39%), and tumor (3%). None of the patients had intracranial EEG. Surgical procedures included hemispherectomy (44%), lobectomy/ lesionectomy (33%), and multilobar resections (23%). Twelve children needed repeat surgery; six (50%) became seizure free after the second surgery. At six months follow-up, 73% (51/70) were seizure-free since surgery. At a mean follow-up of 4.7 years, 60% (42/70) had Engel 1 outcome. In those with seizure recurrence, 17 (60%) reported improvement. Shorter epilepsy duration (p = 0.05) and lobar or sub-lobar epileptogenic lesions (p = 0.02) predicted favorable seizure outcome at 6 months after surgery. For long term outcome, patients with bilateral abnormalities on MRI (p = 0.001), and multilobar extent on MRI (p = 0.02) were at higher risk for recurrence. SIGNIFICANCE: Children with drug-resistant epileptic spasms secondary to an epileptogenic lesion detected on MRI could be selected for epilepsy surgery without undergoing intracranial EEG monitoring. A surgical selection paradigm without intracranial monitoring may allow early surgery without the risks of invasive monitoring.