Intraoperative MRI in pediatric epilepsy and neuro-oncology: a systematic review and meta-analysis.

OBJECTIVE: Intraoperative magnetic resonance imaging (iMRI) use is becoming increasingly widespread in neurosurgical practice, and most of the data reporting its use are in adult populations. There is less evidence on the use of iMRI in pediatric neurosurgery. The aim of this paper was to synthesize the available literature into a systematic review and meta-analysis to evaluate the evidence for iMRI in pediatric neurosurgery, with a particular focus on neuro-oncology and epilepsy surgery. METHODS: This review was registered on PROSPERO and conducted according to PRISMA guidelines. A comprehensive search strategy of Medline via Ovid and Embase was conducted with predetermined key terms. Studies in English reporting the outcomes of patients < 21 years of age who underwent neuro-oncological or epilepsy surgery with the use of iMRI were included in the study. The types of studies eligible for inclusion were observational case-control and cohort studies, randomized clinical trials, cross-sectional studies, editorials, case series, and commentaries. Articles were de-duplicated and abstracts independently screened for inclusion by two reviewers. Full texts were screened, and data on demographic characteristics, etiology, outcome (extent of resection for neuro-oncology and Engel class for epilepsy), and technical iMRI data were extracted. RESULTS: Thirty-five articles were included in the review, 25 of which were observational cohort studies. Four articles were suitable for meta-analysis. In total, 1217 patients underwent iMRI-guided neuro-oncology surgery in 26 studies, most commonly for gliomas (n = 443). A total of 148 patients underwent iMRI-guided epilepsy surgery in 9 studies, with focal cortical dysplasia being the most common diagnosis (n = 95). The mean ± SD operating time was 357 ± 94 minutes (12 studies), with a mean of 1.32 scans per patient. There was a mean re-entry rate into the operative field of 42% (across 20 studies). Complications were noted in 21% of epilepsy surgery patients and 11% of neuro-oncology surgery patients. Meta-analysis of 4 eligible studies revealed that iMRI was more likely to lead to better Engel outcomes in terms of seizure freedom (OR 3.84, 95% CI 1.38-10.68, p = 0.69) and complete tumor resection (OR 3.19, 95% CI 0.28-36.92, p = 0.06). CONCLUSIONS: iMRI appears to be a useful adjunct in optimizing resective pediatric epilepsy and neuro-oncology surgery, with a low complication rate.

Characterizing Frontal Lobe Seizure Semiology in Children.

OBJECTIVE: The objective was to analyze seizure semiology in pediatric frontal lobe epilepsy patients, considering age, to localize the seizure onset zone for surgical resection in focal epilepsy. METHODS: Fifty patients were identified retrospectively, who achieved seizure freedom after frontal lobe resective surgery at Great Ormond Street Hospital. Video-electroencephalography recordings of preoperative ictal seizure semiology were analyzed, stratifying the data based on resection region (mesial or lateral frontal lobe) and age at surgery (≤4 vs >4). RESULTS: Pediatric frontal lobe epilepsy is characterized by frequent, short, complex seizures, similar to adult cohorts. Children with mesial onset had higher occurrence of head deviation (either direction: 55.6% vs 17.4%; p = 0.02) and contralateral head deviation (22.2% vs 0.0%; p = 0.03), ictal body-turning (55.6% vs 13.0%; p = 0.006; ipsilateral: 55.6% vs 4.3%; p = 0.0003), and complex motor signs (88.9% vs 56.5%; p = 0.037). Both age groups (≤4 and >4 years) showed hyperkinetic features (21.1% vs 32.1%), contrary to previous reports. The very young group showed more myoclonic (36.8% vs 3.6%; p = 0.005) and hypomotor features (31.6% vs 0.0%; p = 0.003), and fewer behavioral features (36.8% vs 71.4%; p = 0.03) and reduced responsiveness (31.6% vs 78.6%; p = 0.002). INTERPRETATION: This study presents the most extensive semiological analysis of children with confirmed frontal lobe epilepsy. It identifies semiological features that aid in differentiating between mesial and lateral onset. Despite age-dependent differences, typical frontal lobe features, including hyperkinetic seizures, are observed even in very young children. A better understanding of pediatric seizure semiology may enhance the accuracy of onset identification, and enable earlier presurgical evaluation, improving postsurgical outcomes. ANN NEUROL 2024;95:1138-1148.

Long-term neuropsychological trajectories in children with epilepsy: does surgery halt decline?

Neuropsychological impairments are common in children with drug-resistant epilepsy. It has been proposed that epilepsy surgery might alleviate these impairments by providing seizure freedom; however, findings from prior studies have been inconsistent. We mapped long-term neuropsychological trajectories in children before and after undergoing epilepsy surgery, to measure the impact of disease course and surgery on functioning. We performed a retrospective cohort study of 882 children who had undergone epilepsy surgery at Great Ormond Street Hospital (1990-2018). We extracted patient information and neuropsychological functioning [obtained from IQ tests (domains: full-scale IQ, verbal IQ, performance IQ, working memory and processing speed) and tests of academic attainment (reading, spelling and numeracy)] and investigated changes in functioning using regression analyses. We identified 500 children (248 females) who had undergone epilepsy surgery [median age at surgery = 11.9 years, interquartile range = (7.8, 15.0)] and neuropsychological assessment. These children showed declines in all domains of neuropsychological functioning in the time leading up to surgery (all P-values ≤0.001; e.g. ßFSIQ = -1.9, SEFSIQ = 0.3, PFSIQ < 0.001). Children lost on average one to four points per year, depending on the domain considered; 27%-43% declined by ≥10 points from their first to their last preoperative assessment. At the time of presurgical evaluation, most children (46%-60%) scored one or more standard deviations below the mean (<85) on the different neuropsychological domains; 37% of these met the threshold for intellectual disability (full-scale IQ < 70). On a group level, there was no change in performance from pre- to postoperative assessment on any of the domains (all P-values ≥0.128). However, children who became seizure free through surgery showed higher postoperative neuropsychological performance (e.g. rrb-FSIQ = 0.37, P < 0.001). These children continued to demonstrate improvements in neuropsychological functioning over the course of their long-term follow-up (e.g. ßFSIQ = 0.9, SEFSIQ = 0.3, PFSIQ = 0.004). Children who had discontinued antiseizure medication treatment at 1-year follow-up showed an 8- to 13-point advantage in postoperative working memory, processing speed and numeracy, and greater improvements in verbal IQ, working memory, reading and spelling (all P-values ≤0.034) over the postoperative period compared with children who were seizure free and still receiving antiseizure medication. In conclusion, by providing seizure freedom and the opportunity for antiseizure medication cessation, epilepsy surgery might not only halt but reverse the downward trajectory that children with drug-resistant epilepsy display in neuropsychological functioning. To halt this decline as soon as possible or, potentially, to prevent it from occurring in the first place, children with focal epilepsy should be considered for epilepsy surgery as early as possible after diagnosis.

Lesion detection in epilepsy surgery: Lessons from a prospective evaluation of a machine learning algorithm.

AIM: To evaluate a lesion detection algorithm designed to detect focal cortical dysplasia (FCD) in children undergoing stereoelectroencephalography (SEEG) as part of their presurgical evaluation for drug-resistant epilepsy. METHOD: This was a prospective, single-arm, interventional study (Idea, Development, Exploration, Assessment, and Long-Term Follow-Up phase 1/2a). After routine SEEG planning, structural magnetic resonance imaging sequences were run through an FCD lesion detection algorithm to identify putative clusters. If the top three clusters were not already sampled, up to three additional SEEG electrodes were added. The primary outcome measure was the proportion of patients who had additional electrode contacts in the SEEG-defined seizure-onset zone (SOZ). RESULTS: Twenty patients (median age 12 years, range 4-18 years) were enrolled, one of whom did not undergo SEEG. Additional electrode contacts were part of the SOZ in 1 out of 19 patients while 3 out of 19 patients had clusters that were part of the SOZ but they were already implanted. A total of 16 additional electrodes were implanted in nine patients and there were no adverse events from the additional electrodes. INTERPRETATION: We demonstrate early-stage prospective clinical validation of a machine learning lesion detection algorithm used to aid the identification of the SOZ in children undergoing SEEG. We share key lessons learnt from this evaluation and emphasize the importance of robust prospective evaluation before routine clinical adoption of such algorithms. WHAT THIS PAPER ADDS: The focal cortical dysplasia detection algorithm collocated with the seizure-onset zone (SOZ) in 4 out of 19 patients. The algorithm changed the resection boundaries in 1 of 19 patients undergoing stereoelectroencephalography for drug-resistant epilepsy. The patient with an altered resection due to the algorithm was seizure-free 1 year after resective surgery. Overall, the algorithm did not increase the proportion of patients in whom SOZ was identified.

GNAQ/GNA11 Mosaicism Is Associated with Abnormal Serum Calcium Indices and Microvascular Neurocalcification.

Mosaic mutations in genes GNAQ or GNA11 lead to a spectrum of diseases including Sturge-Weber syndrome and phakomatosis pigmentovascularis with dermal melanocytosis. The pathognomonic finding of localized "tramlining" on plain skull radiography, representing medium-sized neurovascular calcification and associated with postnatal neurological deterioration, led us to study calcium metabolism in a cohort of 42 children. In this study, we find that 74% of patients had at least one abnormal measurement of calcium metabolism, the commonest being moderately low serum ionized calcium (41%) or high parathyroid hormone (17%). Lower levels of ionized calcium even within the normal range were significantly associated with seizures, and with specific antiepileptics despite normal vitamin D levels. Successive measurements documented substantial intrapersonal fluctuation in indices over time, and DEXA scans were normal in patients with hypocalcemia. Neurohistology from epilepsy surgery in five patients revealed not only intravascular, but perivascular and intraparenchymal mineral deposition and intraparenchymal microvascular disease in addition to previously reported findings. Neuroradiology review clearly demonstrated progressive calcium deposition in individuals over time. These findings and those of the adjoining paper suggest that calcium deposition in the brain of patients with GNAQ/GNA11 mosaicism may not be a nonspecific sign of damage as was previously thought, but may instead reflect the central postnatal pathological process in this disease spectrum.

Extent of piriform cortex resection in children with temporal lobe epilepsy.

OBJECTIVE: A greater extent of resection of the temporal portion of the piriform cortex (PC) has been shown to be associated with higher likelihood of seizure freedom in adults undergoing anterior temporal lobe resection (ATLR) for drug-resistant temporal lobe epilepsy (TLE). There have been no such studies in children, therefore this study aimed to investigate this association in a pediatric cohort. METHODS: A retrospective, neuroimaging cohort study of children with TLE who underwent ATLR between 2012 and 2021 was undertaken. The PC, hippocampal and amygdala volumes were measured on the preoperative and postoperative T1-weighted MRI. Using these volumes, the extent of resection per region was compared between the seizure-free and not seizure-free groups. RESULTS: In 50 children (median age 9.5 years) there was no significant difference between the extent of resection of the temporal PC in the seizure-free (median = 50%, n = 33/50) versus not seizure-free (median = 40%, n = 17/50) groups (p = 0.26). In a sub-group of 19 with ipsilateral hippocampal atrophy (quantitatively defined by ipsilateral-to-contralateral asymmetry), the median extent of temporal PC resection was greater in children who were seizure-free (53%) versus those not seizure-free (19%) (p = 0.009). INTERPRETATION: This is the first study demonstrating that, in children with TLE and hippocampal atrophy, more extensive temporal PC resection is associated with a greater chance of seizure freedom-compatible with an adult series in which 85% of patients had hippocampal sclerosis. In a combined group of children with and without hippocampal atrophy, the extent of PC resection was not associated with seizure outcome, suggesting different epileptogenic networks within this cohort.

Intracranial invasive group A streptococcus: a neurosurgical emergency in children.

OBJECTIVE: Invasive group A streptococcus (iGAS) infections are associated with a high rate of morbidity and mortality. CNS involvement is rare, with iGAS accounting for only 0.2%-1% of all childhood bacterial meningitis. In 2022, a significant increase in scarlet fever and iGAS was reported globally with a displacement of serotype, causing a predominance of the emm1.0 subtype. Here, the authors report on iGAS-related suppurative intracranial complications requiring neurosurgical intervention and prolonged antibiotic therapy. METHODS: The authors performed a retrospective chart review of consecutive cases of confirmed GAS in pediatric neurosurgical patients. RESULTS: Five children with a median age of 9 years were treated for intracranial complications of GAS infection over a 2-month period between November 2022 and December 2022. All patients had preceding illnesses, including chicken pox and upper respiratory tract infections. Infections included subdural empyema with associated encephalitis (n = 2), extradural empyema (n = 1), intracranial abscess (n = 1), and diffuse global meningoencephalitis (n = 1). Streptococcus pyogenes was cultured from 4 children, and 2 were of the emm1.0 subtype. Antimicrobial therapy in all patients included a third-generation cephalosporin but varied in adjunctive therapy, often including a toxin synthesis inhibitor antibiotic such as clindamycin. Neurological outcomes varied; 3 patients returned to near neurological baseline, 1 had significant residual neurological deficits, and 1 patient died. CONCLUSIONS: Despite the worldwide increased incidence, intracranial complications remain rarely reported resulting in a lack of awareness of iGAS-related intracranial disease. Awareness of intracranial complications of iGAS and prompt referral to a pediatric neurology/neurosurgical center is crucial to optimize neurological outcomes.

Intraoperative MRI Assessment of the Tissue Damage during Laser Ablation of Hypothalamic Hamartoma.

Laser ablation for treatment of hypothalamic hamartoma (HH) is a minimally invasive and effective technique used to destroy hamartomatous tissue and disconnect it from the functioning brain. Currently, the gold standard to evaluate the amount of tissue being "burned" is the use of heat maps during the ablation procedure. However, these maps have low spatial resolution and can be misleading in terms of extension of the tissue damage. The aim of this study is to use different MRI sequences immediately after each laser ablation and correlate the extension of signal changes with the volume of malacic changes in a long-term follow-up scan. During the laser ablation procedure, we imaged the hypothalamic region with high-resolution axial diffusion-weighted images (DWI) and T2-weighted images (T2WI) after each ablation. At the end of the procedure, we also added a post-contrast T1-weighted image (T1WI) of the same region. We then correlated the product of the maximum diameters on axial showing signal changes (acute oedema on T2WI, DWI restriction rim, DWI hypointense core and post-contrast T1WI rim) with the product of the maximum diameters on axial T2WI of the malacic changes in the follow-up scan, both as a fraction of the total area of the hamartoma. The area of the hypointense core on DWI acquired immediately after the laser ablation statistically correlated better with the final area of encephalomalacia, while the T2WI, hyperintense oedema, DWI rim and T1WI rim of enhancement tended to overestimate the encephalomalacic damage. In conclusion, the use of intraoperative sequences (in particular DWI) during laser ablation can give surgeons valuable information in real time about the effective heating damage on the hamartomatous tissue, with better spatial resolution in comparison to the thermal maps.

Pediatric epilepsy surgery from 2000 to 2018: Changes in referral and surgical volumes, patient characteristics, genetic testing, and postsurgical outcomes.

OBJECTIVE: Neurosurgery is a safe and effective form of treatment for select children with drug-resistant epilepsy. Still, there is concern that it remains underutilized, and that seizure freedom rates have not improved over time. We investigated referral and surgical practices, patient characteristics, and postoperative outcomes over the past two decades. METHODS: We performed a retrospective cohort study of children referred for epilepsy surgery at a tertiary center between 2000 and 2018. We extracted information from medical records and analyzed temporal trends using regression analyses. RESULTS: A total of 1443 children were evaluated for surgery. Of these, 859 (402 females) underwent surgical resection or disconnection at a median age of 8.5 years (interquartile range [IQR] = 4.6-13.4). Excluding palliative procedures, 67% of patients were seizure-free and 15% were on no antiseizure medication (ASM) at 1-year follow-up. There was an annual increase in the number of referrals (7%, 95% confidence interval [CI] = 5.3-8.6; p < .001) and surgeries (4% [95% CI = 2.9-5.6], p < .001) over time. Duration of epilepsy and total number of different ASMs trialed from epilepsy onset to surgery were, however, unchanged, and continued to exceed guidelines. Seizure freedom rates were also unchanged overall but showed improvement (odds ratio [OR] 1.09, 95% CI = 1.01-1.18; p = .027) after adjustment for an observed increase in complex cases. Children who underwent surgery more recently were more likely to be off ASMs postoperatively (OR 1.04, 95% CI = 1.01-1.08; p = .013). There was a 17% annual increase (95% CI = 8.4-28.4, p < .001) in children identified to have a genetic cause of epilepsy, which was associated with poor outcome. SIGNIFICANCE: Children with drug-resistant epilepsy continue to be put forward for surgery late, despite national and international guidelines urging prompt referral. Seizure freedom rates have improved over the past decades, but only after adjustment for a concurrent increase in complex cases. Finally, genetic testing in epilepsy surgery patients has expanded considerably over time and shows promise in identifying patients in whom surgery is less likely to be successful.