Add-On Deep Brain Stimulation versus Continued Vagus Nerve Stimulation for Childhood Epilepsy (ADVANCE): A Partially Randomized Patient Preference Trial.

Outcomes following vagus nerve stimulation (VNS) improve over years after implantation in children with drug-resistant epilepsy. The added value of deep brain stimulation (DBS) instead of continued VNS optimization is unknown. In a prospective, non-blinded, randomized patient preference trial of 18 children (aged 8-17 years) who did not respond to VNS after at least 1 year, add-on DBS resulted in greater seizure reduction compared with an additional year of VNS optimization (51.9% vs. 12.3%, p = 0.047). Add-on DBS also resulted in less bothersome seizures (p = 0.03), but no change in quality of life. DBS may be considered earlier for childhood epilepsy after non-response to VNS. ANN NEUROL 2024.

Surgical outcomes in children with drug-resistant epilepsy and hippocampal sclerosis.

BACKGROUND: Hippocampal sclerosis (HS) is a common surgical substrate in adult epilepsy surgery cohorts but variably reported in various pediatric cohorts. OBJECTIVE: We aimed to study the epilepsy phenotype, radiological and pathological variability, seizure and neurocognitive outcomes in children with drug-resistant epilepsy and hippocampal sclerosis (HS) with or without additional subtle signal changes in anterior temporal lobe who underwent surgery. METHODS: This retrospective study enrolled children with drug-resistant focal epilepsy and hippocampal sclerosis with or without additional subtle T2-Fluid Attenuated Inversion Recovery (FLAR)/Proton Density (PD) signal changes in anterior temporal lobe who underwent anterior temporal lobectomy with amygdalohippocampectomy. Their clinical, EEG, neuropsychological, radiological and pathological data were reviewed and summarized. RESULTS: Thirty-six eligible patients were identified. The mean age at seizure onset was 3.7 years; 25% had daily seizures at time of surgery. Isolated HS was noted in 22 (61.1%) cases and additional subtle signal changes in ipsilateral temporal lobe in 14 (38.9%) cases. Compared to the normative population, the group mean performance in intellectual functioning and most auditory and visual memory tasks were significantly lower than the normative sample. The mean age at surgery was 12.3 years; 22 patients (61.1%) had left hemispheric surgeries. ILAE class 1 outcomes was seen in 28 (77.8%) patients after a mean follow up duration of 2.3 years. Hippocampal sclerosis was noted pathologically in 32 (88.9%) cases; type 2 (54.5%) was predominant subtype where further classification was possible. Additional pathological abnormalities were seen in 11 cases (30.6%); these had had similar rates of seizure freedom as compared to children with isolated hippocampal sclerosis/gliosis (63.6% vs 84%, p=0.21). Significant reliable changes were observed across auditory and visual memory tasks at an individual level post surgery. CONCLUSIONS: Favourable seizure outcomes were seen in most children with isolated radiological hippocampal sclerosis. Patients with additional pathological abnormalities had similar rates of seizure freedom as compared to children with isolated hippocampal sclerosis/gliosis.

Intraoperative changes in large-scale thalamic circuitry following laser ablation of hypothalamic hamartomas.

BACKGROUND AND OBJECTIVES: Gelastic seizures due to hypothalamic hamartomas (HH) are challenging to treat, in part due to an incomplete understanding of seizure propagation pathways. Although magnetic resonance imaging-guided laser interstitial thermal therapy (MRgLITT) is a promising intervention to disconnect HH from ictal propagation networks, the optimal site of ablation to achieve seizure freedom is not known. In this study, we investigated intraoperative post-ablation changes in resting-state functional connectivity to identify large-scale networks associated with successful disconnection of HH. METHODS: Children who underwent MRgLITT for HH at two institutions were consecutively recruited and followed for a minimum of one year. Seizure freedom was defined as Engel score of 1A at the last available follow-up. Immediate pre- and post- ablation resting-state functional MRI scans were acquired while maintaining a constant depth of general anesthetic. Multivariable generalized linear models were used to identify intraoperative changes in large-scale connectivity associated with seizure outcomes. RESULTS: Twelve patients underwent MRgLITT for HH, five of whom were seizure-free at their last follow-up. Intraprocedural changes in thalamocortical circuitry involving the anterior cingulate cortex were associated with seizure-freedom. Children who were seizure-free demonstrated an increase and decrease in connectivity to the pregenual and dorsal anterior cingulate cortices, respectively. In addition, children who became seizure-free demonstrated increased thalamic connectivity to the periaqueductal gray immediately following MRgLITT. DISCUSSION: Successful disconnection of HH is associated with intraoperative, large-scale changes in thalamocortical connectivity. These changes provide novel insights into the large-scale basis of gelastic seizures and may represent intraoperative biomarkers of treatment success.

Evaluating the Current State of Epilepsy Care in the Province of Ontario.

There are numerous challenges pertaining to epilepsy care across Ontario, including Epilepsy Monitoring Unit (EMU) bed pressures, surgical access and community supports. We sampled the current clinical, community and operational state of Ontario epilepsy centres and community epilepsy agencies post COVID-19 pandemic. A 44-item survey was distributed to all 11 district and regional adult and paediatric Ontario epilepsy centres. Qualitative responses were collected from community epilepsy agencies. Results revealed ongoing gaps in epilepsy care across Ontario, with EMU bed pressures and labour shortages being limiting factors. A clinical network advising the Ontario Ministry of Health will improve access to epilepsy care.

Longitudinal point-of-care assessment of psychomotor vigilance in children in the epilepsy monitoring unit.

The epilepsy monitoring unit (EMU) is a complex and dynamic operational environment, where the cognitive and behavioural consequences of medical and environmental changes often go unnoticed. The psychomotor vigilance task (PVT) has been used to detect changes in cognition and behaviour in numerous contexts, including among astronauts on spaceflight missions, pilots, and commercial drivers. Here, we piloted serial point-of-care administration of the PVT in children undergoing invasive monitoring in the EMU. Seven children completed the PVT throughout their hospital admission and their performance was associated with daily seizure counts, interictal epileptiform discharges, number of antiseizure medications (ASMs) administered, and sleep quality metrics. Using mixed-effects models, we found that PVT reaction time and accuracy were adversely affected by greater number of ASMs and interictal epileptiform activity. We show that serial point-of-care PVT is simple and feasible in the EMU and may enable greater understanding of individual patient responses to medical and environmental alterations, inform clinical decision-making, and support quality-improvement and research initiatives.

Stimulation-Induced Seizures in Children Undergoing Stereo-EEG Evaluation.

PURPOSE: This study reports our center's initial experience with the use of low-frequency stimulation in provoking stimulation-induced seizures (SIS) in children with drug-resistant epilepsy undergoing stereo-EEG evaluations. METHODS: This retrospective study enrolled children aged 2 to 18 years with drug-resistant focal epilepsy who underwent stereo-EEG evaluation and extraoperative direct electrical cortical stimulation to elicit seizures. The low-frequency stimulation parameters consisted of biphasic square waveforms at frequency of 1 Hz, pulse width 1 millisecond, current 1 to 3 mA, and train duration of 20 seconds. Various epilepsy-related, imaging, neurophysiology, and surgery-related variables were collected and summarized. RESULTS: Fourteen children (mean age 13 years; 57.1% girls) were included, 10 of whom had unilateral stereo-EEG coverage. Cortical stimulation for provoking seizures was performed after a median of 5 days after electrode implantation. The median number of electrode-contacts stimulated per patient was 42. Four patients (28.6%) experienced habitual SIS (all extratemporal). The etiology in three patients was focal cortical dysplasia. Interictal high-frequency oscillations at electrode-contacts provoking SIS were observed in three cases (75%). Two of these individuals (50%) had class 1 International League Against Epilepsy seizure outcome at last follow-up, after the resection of the brain regions generating SIS. CONCLUSIONS: Low-frequency (1-Hz) stimulation could provoke habitual SIS in nearly one-fourth of children with focal epilepsy undergoing stereo-EEG monitoring. This study provides a limited pediatric experience with the low-frequency cortical stimulation and SIS.

Contralateral hippocampal sclerosis following functional hemispherectomy in children: A report of three cases.

PURPOSE: Hippocampal Sclerosis (HS) may co-exist with temporal or extratemporal lesions (dual pathology) in children and is usually ipsilateral to the radiological lesion. Here were report three cases with extensive hemispheric cortical malformation and drug resistant epilepsy who had persistent seizures after functional hemispherectomy (FH) and developed contralateral HS after the surgery. METHODS: This retrospective study enrolled children who underwent FH and developed contralateral HS after surgery. Their clinical, EEG, radiological and pathological data were reviewed and summarized. RESULTS: Ninety-five children underwent FH during the study period; Three cases (3.2%) were eligible. They all had unilateral extensive hemispheric cortical malformation who underwent FH between 3 and 5 months of age with no clinical, EEG or radiological suggestion for involvement of contralateral hemisphere prior to FH. All three patients had persisting seizures after FH. Contralateral HS was detected between 2.2 to 3.7 years after FH in all three cases. Two of the patients showed pathogenic variants in GATOR1 pathway genes. CONCLUSIONS: The genesis of contralateral HS in the reported patients remains unexplained. The presence and distribution of "second-hit" somatic mutations may play an important role in governing the seizure outcomes of epilepsy surgery in patients with apparently unilateral malformations of cortical development.

Which is more deleterious to cognitive performance? Interictal epileptiform discharges vs anti-seizure medication.

Children with epilepsy commonly have comorbid neurocognitive impairments that severely affect their psychosocial well-being, education, and future career prospects. Although the provenance of these deficits is multifactorial, the effects of interictal epileptiform discharges (IEDs) and anti-seizure medications (ASMs) are thought to be particularly severe. Although certain ASMs can be leveraged to inhibit IED occurrence, it remains unclear whether epileptiform discharges or the medications themselves are most deleterious to cognition. To examine this question, 25 children undergoing invasive monitoring for refractory focal epilepsy performed one or more sessions of a cognitive flexibility task. Electrophysiological data were recorded to detect IEDs. Between repeated sessions, prescribed ASMs were either continued or titrated to <50% of the baseline dose. Hierarchical mixed-effects modeling assessed the relationship between task reaction time (RT), IED occurrence, ASM type, and dose while controlling for seizure frequency. Both presence (ß ± SE = 49.91 ± 16.55 ms, p = .003) and number of IEDs (ß ± SE = 49.84 ± 12.51 ms, p < .001) were associated with slowed task RT. Higher dose oxcarbazepine significantly reduced IED frequency (p = .009) and improved task performance (ß ± SE = -107.43 ± 39.54 ms, p = .007). These results emphasize the neurocognitive consequences of IEDs independent of seizure effects. Furthermore, we demonstrate that inhibition of IEDs following treatment with select ASMs is associated with improved neurocognitive function.

Vagus Nerve Stimulation Modulates Phase-Amplitude Coupling in Thalamic Local Field Potentials.

OBJECTIVE: The antiseizure effects of vagus nerve stimulation (VNS) are thought to be mediated by the modulation of afferent thalamocortical circuitry. Cross-frequency phase-amplitude coupling (PAC) is a mechanism of hierarchical network coordination across multiple spatiotemporal scales. In this study, we leverage local field potential (LFP) recordings from the centromedian (CM) (n = 3) and anterior (ATN) (n = 2) nuclei in five patients with tandem thalamic deep brain stimulation and VNS to study neurophysiological changes in the thalamus in response to VNS. MATERIALS AND METHODS: Bipolar LFP data were recorded from contact pairs spanning target nuclei in VNS "on" and "off" states. RESULTS: Active VNS was associated with increased PAC between theta, alpha, and beta phase and gamma amplitude in CM (q < 0.05). Within the ATN, PAC changes also were observed, although these were less robust. In both nuclei, active VNS also modulated interhemispheric bithalamic functional connectivity. CONCLUSIONS: We report that VNS is associated with enhanced PAC and coordinated interhemispheric interactions within and between thalamic nuclei, respectively. These findings advance understanding of putative neurophysiological effects of acute VNS and contextualize previous animal and human studies showing distributed cortical synchronization after VNS.

Epilepsy disrupts hippocampal phase precision and impairs working memory.

OBJECTIVE: Working memory deficits are prevalent in childhood epilepsy. Working memory processing is thought to be supported by the phase of hippocampal neural oscillations. Disruptions in working memory have previously been linked to the occurrence of transient epileptic activity. This study aimed to resolve the associations between oscillatory neural activity, transient epileptiform events, and working memory in children with epilepsy. METHODS: Intracranial recordings were acquired from stereotactically implanted electrodes in the hippocampi, epileptogenic zones, and working memory-related networks of children with drug-resistant epilepsy during a 1-back working memory task. Interictal epileptic activity was captured using automated detectors. Hippocampal phase and interregional connectivity within working memory networks were indexed by Rayleigh Z and the phase difference derivative, respectively. Trials with and without transient epileptiform events were compared. RESULTS: Twelve children (mean age = 14.3 ± 2.8 years) with drug-resistant epilepsy were included in the study. In the absence of transient epileptic activity, significant delta and theta hippocampal phase resetting occurred in response to working memory stimulus presentation (Rayleigh z-score = 9, Rayleigh z-score = 8). Retrieval trials that were in phase with the preferred phase angle were associated with faster reaction times (p = .01, p = .03). Concurrently, delta and theta coordinated interactions between the hippocampi and working memory-related networks were enhanced (phase difference derivative [PDD] z-scores = 6-11). During retrieval trials with pre-encoding or pre-retrieval transient epileptic activity, phase resetting was attenuated (Rayleigh z-score = 5, Rayleigh z-score = 1), interregional connectivity was altered (PDD z-scores = 1-3), and reaction times were prolonged (p = .01, p = .03). SIGNIFICANCE: This work highlights the role of hippocampal phase in working memory. We observe poststimulus hippocampal phase resetting coincident with enhanced interregional connectivity. The precision of hippocampal phase predicts optimal working memory processing, and transient epileptic activity prolongs working memory processing. These findings can help guide future treatments aimed at restoring memory function in this patient population.

The Child & Youth CompreHensIve Longitudinal Database for Deep Brain Stimulation (CHILD-DBS).

PURPOSE: Deep brain stimulation (DBS) is a common tool for the treatment of movement disorders in adults; however, it remains an emerging treatment modality in children with a growing number of indications, including epilepsy and dystonia. The Child & Youth CompreHensIve Longitudinal Database of DBS (CHILD-DBS) study aims to prospectively collect relevant data on quality of life (QoL), safety, efficacy, and long-term neurodevelopmental outcomes following DBS in children. METHODS: Data are collected and managed using the Research Electronic Data Capture (REDCap). This database aims to collect multicentre comprehensive and longitudinal clinical, QoL, imaging and electrophysiologic data for children under the age of 19 undergoing DBS. RESULTS: Both general and indication-specific measures are collected at baseline and at four time points postoperatively: 6 months, 1 year, 2 years, and 3 years. The database encompasses QoL metrics for children, including the PedsQL (Pediatric Quality of Life Inventory, generic), QOLCE (Quality of Life in Childhood Epilepsy Questionnaire, parent-rated), CHU 9D (Child Health Utility 9D), and KIDSCREEN. Caregiver clinical and QoL metrics, including QIDS (Quick Inventory of Depressive Symptomatology), GAD-7 (Generalized Anxiety Disorder 7-item scale), and CarerQoL-7D (The Care-related Quality of Life Instrument), are similarly prospectively collected. Healthcare resource utilization is also assessed before and after DBS. Lastly, stimulation parameters and radiographic and electrophysiologic data are collected within the database. CONCLUSIONS: The development of the current prospective paediatric DBS database with carefully selected physical and psychosocial outcomes and assessments will complement existing efforts to enhance and facilitate multisite collaboration to further understand the role of DBS in childhood.

Brainstem Associated Somatosensory Evoked Potentials and Response to Vagus Nerve Stimulation: An Investigation of the Vagus Afferent Network.

Despite decades of clinical usage, selection of patients with drug resistant epilepsy who are most likely to benefit from vagus nerve stimulation (VNS) remains a challenge. The mechanism of action of VNS is dependent upon afferent brainstem circuitry, which comprises a critical component of the Vagus Afferent Network (VagAN). To evaluate the association between brainstem afferent circuitry and seizure response, we retrospectively collected intraoperative data from sub-cortical recordings of somatosensory evoked potentials (SSEP) in 7 children with focal drug resistant epilepsy who had failed epilepsy surgery and subsequently underwent VNS. Using multivariate linear regression, we demonstrate a robust negative association between SSEP amplitude (p < 0.01), and seizure reduction. There was no association between SSEP latency and seizure outcomes. Our findings provide novel insights into the mechanism of VNS and inform our understanding of the importance of brainstem afferent circuitry within the VagAN for seizure responsiveness following VNS.

Long-term cognitive outcomes after cerebral sinovenous thrombosis in childhood.

AIM: To assess long-term cognitive function in children after cerebral sinovenous thrombosis (CSVT). METHOD: Children with CSVT, who had neuropsychological testing for intellectual ability, executive function, attention, language, or behavior, were included in a prospective observational study. Outcomes were compared with normative means using one-sample t-tests. Predictors of abnormal function were examined using logistic regression. RESULTS: Fifty children with CSVT were included (median age at diagnosis 2y 10mo, interquartile range 7d-6y 10mo; 35 males, 15 females). The median follow-up time was 4 years 2 months (interquartile range 2y 8mo-6y 4mo). Compared with normative means, children with CSVT had lower mean (± standard deviation) full-scale IQ, working memory, and processing speed scores (93.3±16, p=0.01; 93.6±16, p=0.04; 93.7±15.3, p=0.02 respectively). They also had lower scores in executive function, attention, and language domains. Refractory seizure at presentation was associated with a trend in behavioral problems (odds ratio [OR] 6.3, 95% confidence interval [CI] 0.9-46, p=0.07). Females were less likely to experience processing speed difficulties (OR 0.22, 95% CI 0.04-1.3, p=0.09). Incomplete recanalization was associated with a greater risk of abnormal verbal comprehension (OR 5.3, 95% CI 0.93-30.5, p=0.059). INTERPRETATION: Children with CSVT as a group performed below age expectations on standardized neuropsychological tests, although there was variability across individuals and cognitive domains. Larger studies are needed to evaluate predictors of cognitive deficits in children with CSVT.

Generator replacement with cardiac-based VNS device in children with drug-resistant epilepsy: An observational study.

PURPOSE: This study evaluated the seizure outcomes in children with drug-resistant epilepsy (DRE), having a pre-existing VNS device, after generator replacement with cardiac-based VNS device. METHODS: This retrospective study enrolled 30 children with DRE from 2 centers with an existing VNS device nearing end-of-service who underwent generator replacement with cardiac-based VNS device and had at least 1 year follow up. Seizure outcomes and adverse effects were studied. RESULTS: The mean age at insertion of cardiac-based VNS device was 15.03 years. 26.7 % patients showed at least one class improvement at last follow up (mean 2.08 years) and half of the patients maintained their McHugh seizure-outcome class. Thirty-six percent of patients had > 50 % seizure reduction at last follow up. Ten patients reported improvement in ictal severity. Most of the patients tolerated the replacement well. CONCLUSIONS: Nearly one-third of patients with DRE showed additional improvement after replacement with cardiac based VNS device. Half of the patients maintained their seizure control.

Somatosensory evoked fields predict response to vagus nerve stimulation.

There is an unmet need to develop robust predictive algorithms to preoperatively identify pediatric epilepsy patients who will respond to vagus nerve stimulation (VNS). Given the similarity in the neural circuitry between vagus and median nerve afferent projections to the primary somatosensory cortex, the current study hypothesized that median nerve somatosensory evoked field(s) (SEFs) could be used to predict seizure response to VNS. Retrospective data from forty-eight pediatric patients who underwent VNS at two different institutions were used in this study. Thirty-six patients ("Discovery Cohort") underwent preoperative electrical median nerve stimulation during magnetoencephalography (MEG) recordings and 12 patients ("Validation Cohort") underwent preoperative pneumatic stimulation during MEG. SEFs and their spatial deviation, waveform amplitude and latency, and event-related connectivity were calculated for all patients. A support vector machine (SVM) classifier was trained on the Discovery Cohort to differentiate responders from non-responders based on these input features and tested on the Validation Cohort by comparing the model-predicted response to VNS to the known response. We found that responders to VNS had significantly more widespread SEF localization and greater functional connectivity within limbic and sensorimotor networks in response to median nerve stimulation. No difference in SEF amplitude or latencies was observed between the two cohorts. The SVM classifier demonstrated 88.9% accuracy (0.93 area under the receiver operator characteristics curve) on cross-validation, which decreased to 67% in the Validation cohort. By leveraging overlapping neural circuitry, we found that median nerve SEF characteristics and functional connectivity could identify responders to VNS.

Detection of epileptogenic focus using advanced dynamic statistical parametric mapping with magnetoencephalography in a patient with MRI-negative focal cortical dysplasia type IIB.

Advanced dynamic statistical parametric mapping (AdSPM) with magnetoencephalography (MEG) was used to identify MRI-negative epileptogenic lesions in this report. A 15-year-old girl had MRI-negative and pharmacology-resistant focal-onset epilepsy. She experienced two types of seizures. Type I consisted of her arousal from sleep, staring, and a forced head-turning movement to the left, followed by secondary generalization. Type II began with an aura of dizziness followed by staring and postictal headache with fatigue. Scalp video-electroencephalography (EEG) captured two type I seizures originating from the right frontocentral region. MEG showed scattered dipoles over the right frontal region. AdSPM identified the spike source at the bottom of the right inferior frontal sulcus. Intracranial video-EEG captured one type I seizure, which originated from the depth electrode at the bottom of the sulcus and correlated with the AdSPM spike source. Accordingly, the patient underwent resection of the middle and inferior frontal gyri, including the AdSPM-identified spike source. Histopathological examination revealed that the patient had focal cortical dysplasia type IIB. To date, the patient has been seizure free for 2 years while receiving topiramate treatment. This is the first preliminary report to identify MRI-negative epilepsy using AdSPM. Further investigation of AdSPM would be valuable for cases of MRI-negative focal epilepsy.

Connectomic Profiling Identifies Responders to Vagus Nerve Stimulation.

OBJECTIVE: Vagus nerve stimulation (VNS) is a common treatment for medically intractable epilepsy, but response rates are highly variable, with no preoperative means of identifying good candidates. This study aimed to predict VNS response using structural and functional connectomic profiling. METHODS: Fifty-six children, comprising discovery (n = 38) and validation (n = 18) cohorts, were recruited from 3 separate institutions. Diffusion tensor imaging was used to identify group differences in white matter microstructure, which in turn informed beamforming of resting-state magnetoencephalography recordings. The results were used to generate a support vector machine learning classifier, which was independently validated. This algorithm was compared to a second classifier generated using 31 clinical covariates. RESULTS: Treatment responders demonstrated greater fractional anisotropy in left thalamocortical, limbic, and association fibers, as well as greater connectivity in a functional network encompassing left thalamic, insular, and temporal nodes (p < 0.05). The resulting classifier demonstrated 89.5% accuracy and area under the receiver operating characteristic (ROC) curve of 0.93 on 10-fold cross-validation. In the external validation cohort, this model demonstrated an accuracy of 83.3%, with a sensitivity of 85.7% and specificity of 75.0%. This was significantly superior to predictions using clinical covariates alone, which exhibited an area under the ROC curve of 0.57 (p < 0.008). INTERPRETATION: This study provides the first multi-institutional, multimodal connectomic prediction algorithm for VNS, and provides new insights into its mechanism of action. Reliable identification of VNS responders is critical to mitigate surgical risks for children who may not benefit, and to ensure cost-effective allocation of health care resources. ANN NEUROL 2019;86:743-753.

The role of surgery in refractory epilepsy secondary to polymicrogyria in the pediatric population.

OBJECTIVE: Polymicrogyria (PMG) is a common malformation of cortical development. Many patients with PMG will have medically refractory epilepsy but the role of epilepsy surgery is unclear. The objective of this study was to assess the efficacy of surgical resection/disconnection in achieving seizure control in pediatric patients with PMG. METHODS: A retrospective review of children undergoing epilepsy surgery for PMG between 2002 and 2017 at The Hospital for Sick Children in Toronto, Canada, was performed. RESULTS: A total of 12 children aged 6 months to 17.8 years (median 8.8 years) underwent resective surgery (7 children) or functional hemispherectomy (5 children). Gross total resection or complete disconnection of PMG was carried out in 7 of 12 children. Follow-up duration was between 1 and 9 years (median 2.1 years). Nine children remained seizure-free at last follow-up. Complete resection or disconnection of PMG led to seizure freedom in 6 of 7 patients (86%), whereas subtotal resection produced seizure freedom in 3 of 5 patients (60%). SIGNIFICANCE: We present one of the largest surgical series of pediatric PMG patients. Seizure outcomes were best with complete resection/disconnection of PMG. However, tailored resections based on electroclinical and neuroradiologic data can produce good outcomes and remain an appropriate strategy for patients with extensive PMG.