Intracranial Mapping of Response Latencies and Task Effects for Spoken Syllable Processing in the Human Brain.

Prior lesion, noninvasive-imaging, and intracranial-electroencephalography (iEEG) studies have documented hierarchical, parallel, and distributed characteristics of human speech processing. Yet, there have not been direct, intracranial observations of the latency with which regions outside the temporal lobe respond to speech, or how these responses are impacted by task demands. We leveraged human intracranial recordings via stereo-EEG to measure responses from diverse forebrain sites during (i) passive listening to /bi/ and /pi/ syllables, and (ii) active listening requiring /bi/-versus-/pi/ categorization. We find that neural response latency increases from a few tens of ms in Heschl's gyrus (HG) to several tens of ms in superior temporal gyrus (STG), superior temporal sulcus (STS), and early parietal areas, and hundreds of ms in later parietal areas, insula, frontal cortex, hippocampus, and amygdala. These data also suggest parallel flow of speech information dorsally and ventrally, from HG to parietal areas and from HG to STG and STS, respectively. Latency data also reveal areas in parietal cortex, frontal cortex, hippocampus, and amygdala that are not responsive to the stimuli during passive listening but are responsive during categorization. Furthermore, multiple regions-spanning auditory, parietal, frontal, and insular cortices, and hippocampus and amygdala-show greater neural response amplitudes during active versus passive listening (a task-related effect). Overall, these results are consistent with hierarchical processing of speech at a macro level and parallel streams of information flow in temporal and parietal regions. These data also reveal regions where the speech code is stimulus-faithful and those that encode task-relevant representations.

Thalamic stereoelectroencephalography for neuromodulation target selection: Proof of concept and review of literature of pulvinar direct electrical stimulation.

In patients with drug-resistant epilepsy (DRE) who are not candidates for resective surgery, various thalamic nuclei, including the anterior, centromedian, and pulvinar nuclei, have been extensively investigated as targets for neuromodulation. However, the therapeutic effects of different targets for thalamic neuromodulation on various types of epilepsy are not well understood. Here, we present a 32-year-old patient with multifocal bilateral temporoparieto-occipital epilepsy and bilateral malformations of cortical development (MCDs) who underwent bilateral stereoelectroencephalographic (SEEG) recordings of the aforementioned three thalamic nuclei bilaterally. The change in the rate of interictal epileptiform discharges (IEDs) from baseline were compared in temporal, central, parietal, and occipital regions after direct electrical stimulation (DES) of each thalamic nucleus. A significant decrease in the rate of IEDs (33% from baseline) in the posterior quadrant regions was noted in the ipsilateral as well as contralateral hemisphere following DES of the pulvinar. A scoping review was also performed to better understand the current standpoint of pulvinar thalamic stimulation in the treatment of DRE. The therapeutic effect of neuromodulation can differ among thalamic nuclei targets and epileptogenic zones (EZs). In patients with multifocal EZs with extensive MCDs, personalized thalamic targeting could be achieved through DES with thalamic SEEG electrodes.

Safety of Concomitant Cortical and Thalamic Stereoencephalography Explorations in Patients With Drug-Resistant Epilepsies.

BACKGROUND AND OBJECTIVES: Intracranial electrophysiology of thalamic nuclei has demonstrated involvement of thalamic areas in the propagation of seizures in focal drug-resistant epilepsy. Recent studies have argued that thalamus stereoencephalography (sEEG) may aid in understanding the epileptogenic zone and treatment options. However, the study of thalamic sEEG-associated hemorrhage incidence has not been investigated in a cohort study design. In this article, we present the largest retrospective cohort study of sEEG patients and compare hemorrhage rates between those with and without thalamic sEEG monitoring. METHODS: Retrospective chart review of clinical and epilepsy history, electrode implantation, rationale, and outcomes was performed for 76 patients (age 20-69 years) with drug-resistant epilepsy who underwent sEEG monitoring at our institution (2019-2022). A subset of 38% of patients (n = 30) underwent thalamic monitoring of the anterior thalamic nucleus (n = 14), pulvinar nucleus (n = 25), or both (n = 10). Planned perisylvian orthogonal sEEG trajectories were extended to 2- to 3-cm intraparenchymally access thalamic area(s).The decision to incorporate thalamic monitoring was made by the multidisciplinary epilepsy team. Statistical comparison of hemorrhage rate, type, and severity between patients with and without thalamic sEEG monitoring was made. RESULTS: Our approach for thalamic monitoring was not associated with local intraparenchymal hemorrhage of thalamic areas or found along extended cortical trajectories, and symptomatic hemorrhage rates were greater for patients with thalamic coverage (10% vs 0%, P = .056), although this was not found to be significant. Importantly, patients with perisylvian electrode trajectories, with or without thalamic coverage, did not experience a higher incidence of hemorrhage (P = .34). CONCLUSION: sEEG of the thalamus is a safe and valuable tool that can be used to interrogate the efficacy of thalamic neuromodulation for drug-resistant epilepsy. While patients with thalamic sEEG did have higher incidence of hemorrhage at any monitoring site, this finding was apparently not related to the method of perisylvian implantation and did not involve any trajectories targeting the thalamus.

The changing landscape of palliative epilepsy surgery for Lennox Gastaut Syndrome.

Lennox Gastaut Syndrome (LGS) is characterized by drug-resistant epilepsy that typically leads to decreased quality of life and deleterious neurodevelopmental comorbidities from medically refractory seizures. In recent years there has been a dramatic increase in the development and availability of novel treatment strategies for Lennox Gastaut Syndrome patient to improve seizure. Recent advances in neuromodulation and minimally invasive magnetic resonance guided laser interstitial thermal therapy (MRgLITT) have paved the way for new treatments strategies including deep brain stimulation (DBS), responsive neurostimulation (RNS), and MRgLITT corpus callosum ablation. These new strategies offer hope for children with drug-resistant generalized epilepsies, but important questions remain about the safety and effectiveness of these new approaches. In this review, we describe the opportunities presented by these new strategies and how each treatment strategy is currently being employed. Next, we will critically assess available evidence for these new approaches compared to traditional palliative epilepsy surgery approaches, such as vagus nerve stimulation (VNS) and open microsurgical corpus callosotomy (CC). Finally, we will describe future directions that would help define which of the available strategies should be employed and when.

Clinical outcomes of MR-guided laser interstitial thermal therapy corpus callosum ablation in drug-resistant epilepsy: a systematic review and meta-analysis.

OBJECTIVE: The goal of this systematic review and meta-analysis was to provide an updated analysis of studies investigating outcomes, morbidity, and mortality associated with MR-guided laser interstitial thermal therapy (MRgLITT) corpus callosum ablation (CCA). METHODS: Study inclusion criteria for screening required that studies report on human subjects only, including patients aged 1-52 years diagnosed with drug-resistant epilepsy who underwent CCA. Sixteen articles published between 2016 and 2023 were included for the systematic review and analysis, including 4 case reports, 11 case series, and 1 case-control study. Altogether, 85 pediatric and adult patients undergoing CCA were included in the systematic review (46 patients younger and 39 patients older than 21 years). The main outcome of seizure freedom was measured using the decrease in the frequency of atonic seizures following surgery, percentage of atonic seizure freedom following surgery, and percentage of overall seizure freedom following surgery. These measurements were made using data from the last follow-up for patients with at least 6 months of follow-up post-CCA. RESULTS: The extent of CCA differed across the pooled cohorts, including anterior two-thirds CCA (38.89%, n = 35) and posterior one-third CCA for completion of a prior partial CCA (22.22%, n = 20), complete CCA (27.78%, n = 25), or CCA of residual white matter in the case of subtotal initial ablation (5.56%, n = 5). Overall, 12.94% of the patients undergoing CCA experienced operational complications. The most common operative complications across 90 CCA operations were probe malpositioning (n = 6), hemorrhage (n = 5), off-target extension of splenium ablation to the thalamus (n = 1), infection (n = 1), and postoperative CSF leak (n = 1). Neurological deficits following CCA were reported as transient in 18.82% and permanent in 4.71% of patients across all studies. The most common neurological deficits were disconnection syndrome (n = 4) or transient hemiplegia (supplementary motor area-like syndrome; n = 4). The 6-month overall seizure freedom rate was 18.87% of 53 patients, and the atonic seizure freedom rate was 46.28% of 52 patients postoperatively. CCA resulted in an average decrease in atonic seizure rate from 8.30 to 1.65 atonic seizures per day (average decrease 80.12%). CONCLUSIONS: CCA is associated with an acceptable complication profile, and most patients experience a meaningful reduction in target seizure semiologies. Accurate MRgLITT probe placement is likely important for maximizing CCA while avoiding collateral damage. Avoidable complications of CCA include off-target ablation (and associated deficits), hemorrhage, and future surgery for residual CCA to palliate continued seizures.

Comparison of magnetic resonance-guided laser interstitial thermal therapy corpus callosum ablation to open microsurgical corpus callosotomy: A single-center retrospective cohort study.

OBJECTIVE: Corpus callosotomy (CC) is an important treatment for atonic seizures in patients with generalized or multifocal drug-resistant epilepsy (DRE). Traditionally, CC is performed via an open microsurgical approach, but more recently, MR-guided stereotactic laser interstitial thermal therapy (LITT) corpus callosum ablation (CCA) has been developed to leverage the safety and minimally invasive nature of LITT. Given the recent adoption of CCA at select centers, how CCA compares to CC is unknown. We aim to compare the clinical seizure outcomes of CCA and CC after extended follow-up. METHODS: We performed a retrospective cohort study to compare the effectiveness and safety of CC to CCA from 1994 to 2022. The primary outcome was a 50% reduction in target seizure. Secondary outcome measures were postoperative length of stay, adverse events, and other effectiveness metrics. Comparative statistics were executed using Stata. Normality for continuous variables was assessed, and parametric statistics were utilized as needed. Frequency was compared with chi-squared or Fischer's exact tests, when applicable. RESULTS: Data from 47 operations performed on 36 patients were included in this study, of which 13 (36%) patients underwent 17 CCA. Patients who received CCA had similar rates of meaningful reduction (>50%) of atonic seizures as their CC counterparts (55% vs 70% P = 0.15). Patients undergoing CCA had significantly shorter hospitalizations than those receiving CC (2.5 vs 6.0 days P < 0.001). There was no significant difference in rates of postoperative complications between the groups, although the magnitude of the complication rates was lower in the CCA cohort (12% vs 28%). SIGNIFICANCE: This early experience suggests CCA has similar outcomes to traditional CC, albeit with a shorter hospital stay. However, future studies are necessary to investigate the noninferiority between these two approaches. Large multicenter studies are necessary to investigate differences in adverse events and whether these findings generalize across other centers.

Characterization of low-grade epilepsy-associated tumor from implanted stereoelectroencephalography electrodes.

Low-grade epilepsy-associated tumors (LEATs) are a common cause of drug-resistant epilepsy in children. Herein, we demonstrate the feasibility of using tumor tissue derived from stereoelectroencephalography (sEEG) electrodes upon removal to molecularly characterize tumors and aid in diagnosis. An 18-year-old male with focal epilepsy and MRI suggestive of a dysembryoplastic neuroepithelial tumor (DNET) in the left posterior temporal lobe underwent implantation of seven peri-tumoral sEEG electrodes for peri-operative language mapping and demarcation of the peri-tumoral ictal zone prior to DNET resection. Using electrodes that passed through tumor tissue, we show successful isolation of tumor DNA and subsequent analysis using standard methods for tumor classification by DNA, including Glioseq targeted sequencing and DNA methylation array analysis. This study provides preliminary evidence for the feasibility of molecular diagnosis of LEATs or other lesions using a minimally invasive method with microscopic tissue volumes. The implications of sEEG electrodes in tumor characterization are broad but would aid in diagnosis and subsequent targeted therapeutic strategies.

Serial Neuroendoscopic Lavage for the Treatment of Elevated Cerebrospinal Fluid Protein Levels in Infants with Gram-Negative Rod Ventriculitis.

INTRODUCTION: Gram-negative rod (GNR) bacterial ventriculitis is a rare complication of shunt-dependent hydrocephalus, often requiring an extended and invasive treatment course. Accumulation of purulent material, as well as empyema and septation formation, limits circulation of antibiotics and infection clearance. Supplementation of standard care with neuroendoscopic-guided intraventricular lavage with lactated Ringer solution and fenestration of septations may facilitate infection clearance and simplify the eventual shunt construct required. Here, the utility of serial lavage for ventriculitis is described in a population of shunt-dependent neonates and infants at high risk for morbidity and mortality. METHODS: Five infants with shunt-dependent hydrocephalus and subsequent GNR ventriculitis were treated with standard care measures with the addition of serial neuroendoscopic lavage. A retrospective chart review was performed to collect patient characteristics, shunt dependency, and shunt revisions within a year of ventriculitis resolution. RESULTS: Patients demonstrated a mean 74% decrease in cerebrospinal fluid (CSF) protein following each neuroendoscopic lavage and trended toward a shorter time to infection clearance in comparison to previously published literature. Patients required 0-2 shunt revisions at 1-year follow-up following hospitalization for shunt-related ventriculitis (mean 0.8 +/- 0.8). CONCLUSIONS: Serial neuroendoscopic lavage is an effective technique, used alone or in combination with fenestration of septations, to reduce the CSF protein and bacterial load in the treatment of ventriculitis, decreasing time until eradication of infection. Serial lavage may reduce the risk of future shunt malfunction, simplify the future shunt construct, and decrease duration of infection.

Relationship of cervical soft tissue injury and surgical predication following pediatric cervical spinal trauma and its sequelae on long-term neurologic outcome.

Within the sample of 181 patients with cervical CT, CT identified unstable injury with a sensitivity of 100% and specificity of 95%. CT identified operable injury at the CCJ with 86% sensitivity and 91% specificity. CT was considered the gold standard for identification of fractures. Together, the presence of CT imaging suggestive of unstable injury or persistent neurologic complaint had a 100% sensitivity and 81% specificity. Finally, across all patients MRI had 100% sensitivity and 89% specificity for detection of unstable injury requiring surgery.

Prevalence, severity, and neurosurgical management of abusive head trauma during the COVID-19 pandemic.

OBJECTIVE: Reports published during the severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) pandemic suggest that hospitals potentially experienced an increased incidence in the presentation of abusive head trauma (AHT) in children; however, it remains unknown if the pandemic influenced the severity or need for neurosurgical intervention during this time. METHODS: This study is a post hoc analysis of a prospectively collected database of pediatric patients who sustained traumatic head injuries from 2018 to 2021 and were treated at the Children's Hospital of Pittsburgh that was screened for concern of AHT at the time of presentation. Pairwise univariate analysis of AHT prevalence, Glasgow Coma Scale (GCS) score, intracranial pathology, and neurosurgical interventions was performed to investigate differences before, during, and after the initial lockdown in Pennsylvania, which was defined as March 23, 2020, to August 26, 2020. RESULTS: Of 2181 pediatric patients who presented with head trauma, 263 (12.1%) with AHT were identified. Prevalence of AHT did not differ during (12.4% before vs 10.0% during, p = 0.31) or following (12.2% after, p = 0.92) lockdown. Need for neurosurgery after AHT remained unchanged during lockdown (10.7% before vs 8.3% during, p = 0.72) and after (10.5% after, p = 0.97). Patients did not differ in terms of sex, age, or race between periods. Average GCS score was lower after lockdown (13.9 before vs 11.9 after, p = 0.008) but not during (12.3, p = 0.062). In this cohort, mortality associated with AHT was 4.8 times higher during lockdown (4.3% before vs 20.8% during, p = 0.002) and returned to pre-lockdown rates thereafter (7.8%, p = 0.27). The primary contributor to mortality was ischemic brain injury (5% before vs 20.8% during, p = 0.005). Patients were 5.5 times more likely to undergo decompressive hemicraniectomy in the months after lockdown compared with prior (1.2% vs 6.6%, p = 0.035). CONCLUSIONS: The authors have presented the findings of the first study to examine the prevalence and neurosurgical management of AHT during the Sars-Cov-2 lockdown in Pennsylvania. The overall prevalence of AHT was not affected by lockdown; however, patients were more likely to experience mortality or traumatic ischemia during lockdown. The GCS score of AHT patients was significantly lower, and these patients were more likely to require decompressive hemicraniectomy after the initial lockdown period.

Tetra-compartmental spinal infection with conus medullaris syndrome: illustrative case.

BACKGROUND: Recent literature suggests that spinal infections are increasing in prevalence. Any compartment can be infected in the spine; however, multicompartmental infections are rare. OBSERVATIONS: To the authors' knowledge, this report is the only reported case of a tetra-compartmental spinal infection consisting of epidural, subdural, subarachnoid, and intramedullary components with a contiguous lumbar spondylodiscitis resulting in conus medullaris syndrome requiring surgical intervention. LESSONS: This case highlights the importance of surgical intervention in severe cases such as the one illustrated in this report. Second, magnetic resonance imaging with and without contrast is required to check for spreading of the infection as these findings may change the surgical approach. Last, the use of intraoperative ultrasound is paramount to evaluate the subdural and intramedullary compartments in severe cases.

Cost-effectiveness of invasive monitoring strategies in epilepsy surgery.

OBJECTIVE: Drug-resistant epilepsy occurs in up to 40% of patients with epilepsy who may be considered for epilepsy surgery. For drug-resistant focal epilepsy, up to 50% of patients require invasive monitoring prior to surgery. Of the most common invasive monitoring strategies (subdural electrodes [SDEs] and stereo-electroencephalography [sEEG]), the most cost-effective strategy is unknown despite substantial differences in morbidity profiles. METHODS: Using data collected from an internationally representative sample published in available systematic reviews and meta-analyses, this economic evaluation study employs a decision analysis model to simulate the risks and benefits of SDE and sEEG invasive monitoring strategies. In this model, patients faced differing risks of morbidity, mortality, resection, and seizure freedom depending on which invasive monitoring strategy they underwent. A range of cost values was obtained from a recently published single-center cost-utility analysis. The model considers a base case simulation of a characteristic patient with drug-resistant epilepsy using clinical parameters obtained from systematic reviews of invasive monitoring available in the literature. The main outcome measure was the probability of a positive outcome after invasive monitoring, which was defined as improvement in seizures without a complication. Cost-effectiveness was measured using an incremental cost-effectiveness ratio (ICER). RESULTS: Invasive monitoring with sEEG had an increased cost of $274 and increased probability of effectiveness of 0.02 compared with SDEs, yielding an ICER of $12,630 per positive outcome obtained. Sensitivity analyses varied parameters widely and revealed consistent model results across the range of clinical parameters reported in the literature. One-way sensitivity analyses revealed that invasive monitoring strategy costs were the most influential parameter for model outcome. CONCLUSIONS: In this analysis, based on available observational data and estimates of complication costs, invasive monitoring with either SDEs or sEEG was nearly equivalent in terms of cost-effectiveness.

Electrocorticography reveals the dynamics of famous voice responses in human fusiform gyrus.

Voice and face processing occur through convergent neural systems that facilitate speaker recognition. Neuroimaging studies suggest that familiar voice processing engages early visual cortex, including the bilateral fusiform gyrus (FG) on the basal temporal lobe. However, what role the FG plays in voice processing and whether it is driven by bottom-up or top-down mechanisms is unresolved. In this study we directly examined neural responses to famous voices and faces in human FG with direct cortical surface recordings (electrocorticography) in epilepsy surgery patients. We tested the hypothesis that neural populations in human FG respond to famous voices and investigated the temporal properties of voice responses in FG. Recordings were acquired from five adult participants during a person identification task using visual and auditory stimuli from famous speakers (U.S. Presidents Barack Obama, George W. Bush, and Bill Clinton). Patients were presented with images of presidents or clips of their voices and asked to identify the portrait/speaker. Our results demonstrate that a subset of face-responsive sites in and near FG also exhibit voice responses that are both lower in magnitude and delayed (300-600 ms) compared with visual responses. The dynamics of voice processing revealed by direct cortical recordings suggests a top-down feedback-mediated response to famous voices in FG that may facilitate speaker identification.NEW & NOTEWORTHY Interactions between auditory and visual cortices play an important role in person identification, but the dynamics of these interactions remain poorly understood. We performed direct brain recordings of fusiform face cortex in human epilepsy patients performing a famous voice naming task, revealing the dynamics of famous voice processing in human fusiform face cortex. The findings support a model of top-down interactions from auditory to visual cortex to facilitate famous voice recognition.

Responsive neurostimulation for pediatric patients with drug-resistant epilepsy: a case series and review of the literature.

OBJECTIVE: Responsive neurostimulation (RNS) is a promising treatment for pediatric patients with drug-resistant epilepsy for whom resective surgery is not an option. The relative indications and risk for pediatric patients undergoing RNS therapy require further investigation. Here, the authors report their experience with RNS implantation and therapy in pediatric patients. METHODS: The authors performed a retrospective chart review to identify patients implanted with RNS depth or strip electrodes for the treatment of drug-resistant epilepsy at their institution between 2020 and 2022. Patient demographics, surgical variables, and patient seizure outcomes (Engel class and International League Against Epilepsy [ILAE] reporting) were evaluated. RESULTS: The authors identified 20 pediatric patients ranging in age from 8 to 21 years (mean 15 [SD 4] years), who underwent RNS implantation, including depth electrodes (n = 15), strip electrodes (n = 2), or both (n = 3). Patient seizure semiology, onset, and implantation strategy were heterogeneous, including bilateral centromedian nucleus (n = 5), mesial temporal lobe (n = 4), motor cortex or supplementary motor area (n = 7), or within an extratemporal epileptogenic zone (n = 4). There were no acute complications of RNS implantation (hemorrhage or stroke) or device malfunctions. One patient required rehospitalization for postoperative infection. At the longest follow-up (mean 10 [SD 7] months), 13% patients had Engel class IIB, 38% had Engel class IIIA, 6% had Engel class IIIB, 19% had Engel class IVA, 19% had Engel class IVB, and 6% had Engel class IVC outcomes. Using ILAE metrics, 6% were ILAE class 3, 25% were ILAE class 4, and 69% were ILAE class 5. CONCLUSIONS: This case series supports current literature suggesting that RNS is a safe and potentially effective surgical intervention for pediatric patients with drug-resistant epilepsy. The authors report comparable rates of serious adverse events to current RNS literature in pediatric and adult populations. Seizure outcomes may continue to improve with follow-up as stimulation strategy is refined and the chronic neuromodulatory effect evolves, as previously described in patients with RNS. Further large-scale, multicenter case series of RNS in pediatric patients with drug-resistant epilepsy are required to determine long-term pediatric safety and effectiveness.

Neural responses in human superior temporal cortex support coding of voice representations.

The ability to recognize abstract features of voice during auditory perception is an intricate feat of human audition. For the listener, this occurs in near-automatic fashion to seamlessly extract complex cues from a highly variable auditory signal. Voice perception depends on specialized regions of auditory cortex, including superior temporal gyrus (STG) and superior temporal sulcus (STS). However, the nature of voice encoding at the cortical level remains poorly understood. We leverage intracerebral recordings across human auditory cortex during presentation of voice and nonvoice acoustic stimuli to examine voice encoding at the cortical level in 8 patient-participants undergoing epilepsy surgery evaluation. We show that voice selectivity increases along the auditory hierarchy from supratemporal plane (STP) to the STG and STS. Results show accurate decoding of vocalizations from human auditory cortical activity even in the complete absence of linguistic content. These findings show an early, less-selective temporal window of neural activity in the STG and STS followed by a sustained, strongly voice-selective window. Encoding models demonstrate divergence in the encoding of acoustic features along the auditory hierarchy, wherein STG/STS responses are best explained by voice category and acoustics, as opposed to acoustic features of voice stimuli alone. This is in contrast to neural activity recorded from STP, in which responses were accounted for by acoustic features. These findings support a model of voice perception that engages categorical encoding mechanisms within STG and STS to facilitate feature extraction.

Stereotactic laser interstitial thermal therapy for the treatment of pediatric drug-resistant epilepsy: indications, techniques, and safety.

BACKGROUND: MRI-guided laser interstitial thermal therapy (MRgLITT) is a promising alternative to open surgery for treatment of drug-resistant epilepsy, offering significant advantages over traditional approaches for candidate patients, including minimally invasive approach, shorter hospitalization, and decreased patient post-operative discomfort. LITT uses a stereotactically placed fiber optic laser probe to ablate tissue under real-time MR thermometry. METHODS: Retrospective chart review of intraoperative and perioperative characteristics was performed for 28 cases of MRgLITT in 25 pediatric patients, ages 4-21 years old, at our institution between 2019 and 2021. MRgLITT ablation of the mesial temporal lobe was performed in 8 cases, extratemporal epileptogenic foci in 9 cases, and for corpus callosotomy in 11 cases. RESULTS: At 1 year of follow-up, 53% of all patients experienced improvement in seizure frequency (Engel I or II) (class I: 38%, class II: 15%, class III: 17%, class IV: 31%), including 37% of MTL ablations and 80% extratemporal SOZ ablations. After MRgLITT corpus callosotomy, 71% of patients were free from atonic seizures at most recent follow-up. Median length of hospitalization was 2 days (1-3), including a median ICU stay of 1 day (1-2). CONCLUSION: This series demonstrates the safety of MRgLITT as an approach for seizure control in drug-resistant epilepsy. We provide additional evidence that MRgLITT is an effective procedure that is well-tolerated by pediatric patients and is accompanied by an acceptable rate of complications and relatively short hospital stay.

Stereotactic laser interstitial thermal therapy corpus callosotomy for the treatment of pediatric drug-resistant epilepsy.

OBJECTIVE: Corpus callosotomy is a safe and effective procedure for reducing the frequency of drop attacks. MR-guided laser interstitial thermal therapy (MRgLITT) offers a minimally invasive alternative to conventional open craniotomy for callosotomy. We hypothesized that MRgLITT callosotomy could be safely performed in pediatric patients with similar seizure control. METHODS: We present an institutional case series of 11 procedures in 10 patients for the treatment of drop attacks in drug-refractory primary generalized epilepsy. MRgLITT was used for complete callosotomy, anterior two-thirds, posterior, or ablation of residual callosal fibers following prior callosotomy (open or MRgLITT). We retrospectively reviewed clinical course, operative details, radiographic imaging, clinical outcomes, and complications. RESULTS: Operative time ranged from 4-8 hours, and median hospitalization was 2 days. No complications were encountered. Among the 7 patients with at least 3 months of follow-up, 71% experienced freedom from drop attacks at longest follow-up and 57% of cases showed improvement in their other seizure semiologies as well (Engel Class II: 28%, Class III: 28%, Class IV: 43%). SIGNIFICANCE: MR-guided LITT callosotomy is safe and effective modality in the management of pediatric patients with medically intractable epilepsy characterized by drop attacks. While this is among the largest pediatric series to date, further studies are required to delineate its safety and efficacy among such patients.

Deep brain stimulation of the centromedian thalamic nucleus for the treatment of FIRES.

Febrile infection-related epilepsy syndrome (FIRES) is a rare, life-threatening complication of febrile illness in previously healthy individuals followed by super-refractory status epilepticus. Deep brain stimulation (DBS) has been demonstrated to be a promising therapy for the treatment of intractable epilepsy. Here, we present a pediatric patient with FIRES whose seizures were mitigated by acute DBS of the bilateral centromedian thalamic nucleus (CMTN). This is a previously healthy 11-year-old female who presented emergently with altered mental status, fever, and malaise after 1 week of lethargy, anorexia, fever, and abdominal pain. The patient began having seizures shortly after admission. After thorough workup for encephalitis and other potential etiologies, this patient was diagnosed with FIRES due to super-refractory status epilepticus. Status epilepticus persisted despite pharmacologic management, immunotherapy, and vagus nerve stimulation. DBS of the bilateral CMTN (CM-DBS) was pursued after 56 days of hospitalization, and she demonstrated considerable improvement in baseline mental status 30 days after DBS insertion. This report highlights application of CM-DBS for super-refractory status epilepticus in FIRES. This region is a diffusely connected brain region and has been shown to modulate neural networks contributing to seizure propagation and consciousness; therefore, neurostimulation is a potential therapeutic intervention for patients with super-refractory status epilepticus.

Interactive relations between maternal prenatal stress, fetal brain connectivity, and gestational age at delivery.

Studies reporting significant associations between maternal prenatal stress and child outcomes are frequently confounded by correlates of prenatal stress that influence the postnatal rearing environment. The major objective of this study is to identify whether maternal prenatal stress is associated with variation in human brain functional connectivity prior to birth. We utilized fetal fMRI in 118 fetuses [48 female; mean age 32.9 weeks (SD = 3.87)] to evaluate this association and further addressed whether fetal neural differences were related to maternal health behaviors, social support, or birth outcomes. Community detection was used to empirically define networks and enrichment was used to isolate differential within- or between-network connectivity effects. Significance for χ2 enrichment was determined by randomly permuting the subject pairing of fetal brain connectivity and maternal stress values 10,000 times. Mixtures modelling was used to test whether fetal neural differences were related to maternal health behaviors, social support, or birth outcomes. Increased maternal prenatal negative affect/stress was associated with alterations in fetal frontoparietal, striatal, and temporoparietal connectivity (ß = 0.82, p < 0.001). Follow-up analysis demonstrated that these associations were stronger in women with better health behaviors, more positive interpersonal support, and lower overall stress (ß = 0.16, p = 0.02). Additionally, magnitude of stress-related differences in neural connectivity was marginally correlated with younger gestational age at delivery (ß = -0.18, p = 0.05). This is the first evidence that negative affect/stress during pregnancy is reflected in functional network differences in the human brain in utero, and also provides information about how positive interpersonal and health behaviors could mitigate prenatal brain programming.