Emotional facial expression and perioral motor functions of the human auditory cortex.

OBJECTIVE: We investigated the role of transverse temporal gyrus and adjacent cortex (TTG+) in facial expressions and perioral movements. METHODS: In 31 patients undergoing stereo-electroencephalography monitoring, we describe behavioral responses elicited by electrical stimulation within the TTG+. Task-induced high-gamma modulation (HGM), auditory evoked responses, and resting-state connectivity were used to investigate the cortical sites having different types of responses on electrical stimulation. RESULTS: Changes in facial expressions and perioral movements were elicited on electrical stimulation within TTG+ in 9 (29%) and 10 (32%) patients, respectively, in addition to the more common language responses (naming interruptions, auditory hallucinations, paraphasic errors). All functional sites showed auditory task induced HGM and evoked responses validating their location within the auditory cortex, however, motor sites showed lower peak amplitudes and longer peak latencies compared to language sites. Significant first-degree connections for motor sites included precentral, anterior cingulate, parahippocampal, and anterior insular gyri, whereas those for language sites included posterior superior temporal, posterior middle temporal, inferior frontal, supramarginal, and angular gyri. CONCLUSIONS: Multimodal data suggests that TTG+ may participate in auditory-motor integration. SIGNIFICANCE: TTG+ likely participates in facial expressions in response to emotional cues during an auditory discourse.

Vorinostat, temozolomide or bevacizumab with irradiation and maintenance BEV/TMZ in pediatric high-grade glioma: A Children's Oncology Group Study.

Background: Outcomes for children with high-grade gliomas (HGG) remain poor. This multicenter phase II trial evaluated whether concurrent use of vorinostat or bevacizumab with focal radiotherapy (RT) improved 1-year event-free survival (EFS) compared to temozolomide in children with newly diagnosed HGG who received maintenance temozolomide and bevacizumab. Methods: Patients ≥ 3 and < 22 years with localized, non-brainstem HGG were randomized to receive RT (dose 54-59.4Gy) with vorinostat, temozolomide, or bevacizumab followed by 12 cycles of bevacizumab and temozolomide maintenance therapy. Results: Among 90 patients randomized, the 1-year EFS for concurrent bevacizumab, vorinostat, or temozolomide with RT was 43.8% (±8.8%), 41.4% (±9.2%), and 59.3% (±9.5%), respectively, with no significant difference among treatment arms. Three- and five-year EFS for the entire cohort was 14.8% and 13.4%, respectively, with no significant EFS difference among the chemoradiotherapy arms. IDH mutations were associated with more favorable EFS (P = .03), whereas H3.3 K27M mutations (P = .0045) and alterations in PIK3CA or PTEN (P = .025) were associated with worse outcomes. Patients with telomerase- and alternative lengthening of telomeres (ALT)-negative tumors (n = 4) had an EFS of 100%, significantly greater than those with ALT or telomerase, or both (P = .002). While there was no difference in outcomes based on TERT expression, high TERC expression was associated with inferior survival independent of the telomere maintenance mechanism (P = .0012). Conclusions: Chemoradiotherapy with vorinostat or bevacizumab is not superior to temozolomide in children with newly diagnosed HGG. Patients with telomerase- and ALT-negative tumors had higher EFS suggesting that, if reproduced, mechanism of telomere maintenance should be considered in molecular-risk stratification in future studies.

MRI and pathology comparisons in Rasmussen's encephalitis: a multi-institutional examination of hemispherotomy outcomes relative to imaging and histological severity.

PURPOSE: Rasmussen encephalitis (RE) is a very rare chronic neurological disorder of unilateral inflammation of the cerebral cortex. Hemispherotomy provides the best chance at achieving seizure freedom in RE patients, but with significant risks and variable long-term outcomes. The goal of this study is to utilize our multicenter pediatric cohort to characterize if differences in pathology and/or imaging characterization of RE may provide a window into post-operative seizure outcomes, which in turn could guide decision-making for parents and healthcare providers. METHODS: This multi-institutional retrospective review of medical record, imaging, and pathology samples was approved by each individual institution's review board. Data was collected from all known pediatric cases of peri-insular functional hemispherotomy from the earliest available electronic medical records. Mean follow-up time was 4.9 years. Clinical outcomes were measured by last follow-up visit using both Engel and ILAE scoring systems. Relationships between categorical and continuous variables were analyzed with Pearson correlation values. RESULTS: Twenty-seven patients met study criteria. No statistically significant correlations existed between patient imaging and pathology data. Pathology stage, MRI brain imaging stages, and a combined assessment of pathology and imaging stages showed no statistically significant correlation to post-operative seizure freedom rates. Hemispherectomy Outcome Prediction Scale scoring demonstrated seizure freedom in only 71% of patients receiving a score of 1 and 36% of patients receiving a score of 2 which were substantially lower than predicted. CONCLUSIONS: Our analysis did not find evidence for either independent or combined analysis of imaging and pathology staging being predictive for post peri-insular hemispherotomy seizure outcomes, prompting the need for other biomarkers to be explored. Our data stands in contrast to the recently proposed Hemispherectomy Outcome Prediction Scale and does not externally validate this metric for an RE cohort.

Incidental Thalamic Lesions Identified on Brain MRI in Pediatric and Young Adult Patients: Imaging Features and Natural History.

BACKGROUND AND PURPOSE: Nonspecific, localized thalamic signal abnormalities of uncertain significance are occasionally found on pediatric brain MR imaging. The goal of this study is to describe the MR imaging appearance and natural history of these lesions in children and young adults. MATERIALS AND METHODS: This retrospective study evaluated clinically acquired brain MR imaging examinations obtained from February 1995 to March 2022 at a large, tertiary care pediatric hospital. Examinations with non-mass-like and nonenhancing thalamic lesions were identified based on term search of MR imaging reports. A total of 221 patients formed the initial group for imaging assessment. Additional exclusions during imaging review resulted in 171 patients. Imaging appearance and size changes were assessed at baseline and at follow-up examinations. RESULTS: A total of 171 patients (102 male) at a median age of 11 years (range: 1-23 years), 568 MR imaging examinations, and 180 thalamic lesions were included. Median time from baseline to the last follow-up MR imaging was 542 days (range: 46-5730 days). No lesion enhanced at any time point. On imaging follow-up, 11% of lesions (18/161) became smaller, 10% (16/161) resolved, 73% (118/161) remained stable, and 6% (9/161) increased in size at some point during evaluation. Median time interval from baseline to enlargement was 430 days (range: 136-1074 days). CONCLUSIONS: Most incidental, non-mass-like thalamic signal abnormalities were stable, decreased in size, or resolved on follow-up imaging and are likely of no clinical significance. Surveillance strategies with longer follow-up intervals may be adequate in the management of such findings.

Neuropsychological outcomes after epilepsy surgery: A comparison of stereo electroencephalography and subdural electrodes.

BACKGROUND AND PURPOSE: We analyzed the association of neuropsychological outcomes after epilepsy surgery with the intracranial electrode type (stereo electroencephalography [SEEG] and subdural electrodes [SDE]), and electrical stimulation mapping (ESM) of speech/language. METHODS: Drug-resistant epilepsy patients who underwent comprehensive neuropsychological evaluation before and 1 year after epilepsy surgery were included. SEEG and SDE subgroups were matched by age, handedness, operated hemisphere, and seizure freedom. Postsurgical neuropsychological outcomes (adjusted for presurgical scores) and reliable change indices were analyzed as functions of electrode type and ESM. RESULTS: Ninety-nine patients aged 6-29 years were included with similar surgical resection/ablation volumes in the SEEG and SDE subgroups. Most of the neuropsychological outcomes were comparable between SEEG and SDE subgroups; however, Working Memory and Processing Speed were significantly improved in the SEEG subgroup. Undergoing language ESM was associated with significant improvements in Spelling, Letter-Word Identification, Vocabulary, Verbal Comprehension, Verbal Learning, and Story Memory scores, but a decline in Calculation scores. CONCLUSIONS: Intracranial evaluations with SEEG and SDE are comparable in terms of long-term postsurgical neuropsychological outcomes. Our data suggest that SEEG may be associated with improvements in working memory and processing speed, representing cognitive domains served by spatially distributed networks. Our study also supports wider use of language ESM before epilepsy surgery, preferably using other language tasks in addition to visual naming. Rather than the type of electrode, postsurgical neuropsychological outcomes are driven by whether language ESM was performed or not, with beneficial effects of language mapping.

Tolerability of transcranial magnetic stimulation language mapping in children.

OBJECTIVE: Transcranial Magnetic Stimulation (TMS) has emerged as a viable non-invasive method for mapping language networks. Little is known about the tolerability of transcranial magnetic stimulation language mapping in children. METHODS: Children aged 5-18 years underwent bilateral language mapping using repetitive transcranial magnetic stimulation (rTMS) to target 33 sites/hemisphere. Stimulation was delivered at 5 Hz, in 1-2 second bursts, during visual naming and auditory verb generation. Pain unpleasantness and pain intensity were assessed using an unpleasantness visual analog scale (VAS). RESULTS: 49 participants tolerated motor mapping and had repetitive transcranial magnetic stimulation. 35/49 (71%) completed visual naming and 26/49 (53%) completed both visual naming and verb generation. Mean electrical field per participant was 115 V/m. Young age and lower language ability were associated with lower completion. Visual analogue scale scores were significantly higher (6.1 vs. 2.8) in participants who withdrew early compared to those who completed at least visual naming. CONCLUSIONS: Pain measured by VAS was a major contributor to early withdrawal. However, a complete bilateral map was obtained with one paradigm in 71% of participants. Future studies designed to reduce pain during repetitive transcranial magnetic stimulation over language cortex will boost viability. SIGNIFICANCE: This study represents the first attempt to characterize tolerability of bilateral repetitive transcranial magnetic stimulation language mapping in healthy children.

Comparing electrical stimulation functional mapping with subdural electrodes and stereoelectroencephalography.

OBJECTIVE: Electrical stimulation mapping (ESM) is the clinical standard for functional localization with subdural electrodes (SDE). As stereoelectroencephalography (SEEG) has emerged as an alternative option, we compared functional responses, afterdischarges (ADs), and unwanted ESM-induced seizures (EISs) between the two electrode types. METHODS: Incidence and current thresholds for functional responses (sensory, motor, speech/language), ADs, and EISs were compared between SDE and SEEG using mixed models incorporating relevant covariates. RESULTS: We identified 67 SEEG ESM and 106 SDE ESM patients (7207 and 4980 stimulated contacts, respectively). We found similar incidence of language and motor responses between electrode types; however, more SEEG patients reported sensory responses. ADs and EISs occurred less commonly with SEEG than SDE. Current thresholds for language, face motor, and upper extremity (UE) motor responses and EIS significantly decreased with age. However, they were not affected by electrode type, premedication, or dominant hemispheric stimulation. AD thresholds were higher with SEEG than with SDE. For SEEG ESM, language thresholds remained below AD thresholds up to 26 years of age, whereas this relationship was inverse for SDE. Also, face and UE motor thresholds fell below AD thresholds at earlier ages for SEEG than SDE. AD and EIS thresholds were not affected by premedication. SIGNIFICANCE: SEEG and SDE have clinically relevant differences for functional brain mapping with electrical stimulation. Although evaluation of language and motor regions is comparable between SEEG and SDE, SEEG offers a higher likelihood of identifying sensory areas. A lower incidence of ADs and EISs, and a favorable relationship between functional and AD thresholds suggest superior safety and neurophysiologic validity for SEEG ESM than SDE ESM.

Posterior Quadrant Disconnection Procedure for Intractable Epilepsy: A Case Series of 5 Young Pediatric Patients.

BACKGROUND: Posterior quadrant disconnection (PQD) has been described as a treatment for patients with refractory posterior quadrant subhemispheric epilepsy. Surgical outcomes are difficult to interpret because of limited literature. OBJECTIVE: To provide insight regarding the operative technique and postsurgical seizure freedom in young pediatric patients who underwent surgical disconnection for the treatment of posterior quadrant subhemispheric epilepsy at our institution. METHODS: The authors retrospectively analyzed a series of 5 patients who underwent PQD between 2019 and 2021. Charts were reviewed for preoperative workup including noninvasive/invasive testing, operative reports, and postoperative follow-up data which included degree of seizure freedom, completion of disconnection, and complications. RESULTS: Five patients were included in this series. The median age at seizure onset was 12 months (range 3-24 months), and the median age at surgery was 36 months (range 22-72 months). Histopathology confirmed focal cortical dysplasia in 3 of 5 patients (2 patients with type IB; 1 with type IIID). The average length of follow-up after surgery was 16.8 months (range 12-24 months). All patients underwent complete disconnection of the posterior quadrant without complications. Four of 5 patients (80%) had Engel score of I, while the remaining patient had an Engel score of IIB. CONCLUSION: Our early results demonstrate that complete PQD can be successful at providing excellent seizure freedom and functional outcomes in carefully selected young pediatric patients who have concordant seizure semiology, noninvasive/invasive testing, and imaging findings with primary seizure onset zone within the ipsilateral posterior quadrant. Meticulous surgical planning and thorough understanding of the surgical anatomy and technique are critical to achieving complete disconnection.

Comparison of outcomes after stereoelectroencephalography and subdural grid monitoring in pediatric tuberous sclerosis complex.

OBJECTIVE: Patients with tuberous sclerosis complex (TSC) epilepsy present with unique clinical challenges such as early seizure onset and high rates of intractability and multifocality. Although there are numerous studies about the safety and efficacy of stereoelectroencephalography (SEEG), this topic has not been studied in TSC patients who have distinct epilepsy profiles. The authors investigated subdural grid (SDG) and SEEG monitoring to determine whether these procedures lead to similar seizure and safety outcomes and to identify features unique to this pediatric population. METHODS: TSC patients who underwent SDG or SEEG placement and a second epilepsy surgery during the period from 2007 to 2021 were included in this single-center retrospective cohort analysis. Various patient, hospitalization, and epilepsy characteristics were collected. RESULTS: A total of 50 TSC patients were included in this study: 30 were included in the SDG cohort and 20 in the SEEG cohort. Baseline weekly seizure count did not significantly differ between the 2 groups (p = 0.412). The SEEG group had a greater mean baseline number of antiepileptic drugs (AEDs) (3.0 vs 2.0, p = 0.003), higher rate of previous surgical interventions (25% vs 0%, p = 0.007), and larger proportion of patients who underwent bilateral monitoring (50% vs 13.3%, p = 0.005). Despite this, there was no significant difference in seizure freedom between the SDG and SEEG cohorts. The mean reduction in seizure count was 84.9% and 47.8% of patients were seizure free at last follow-up (mean 79.4 months). SEEG trended toward being a safer procedure than SDG monitoring, with a shorter mean ICU stay (0.7 days vs 3.9 days, p < 0.001), lower blood transfusion rate (0% vs 13.3%, p = 0.140), and lower surgical complication rate (0% vs 10%, p = 0.265). CONCLUSIONS: In the comparison of the SDG and SEEG cohorts, the SEEG group included patients who appeared to receive more aggressive management and have a higher rate of multifocality, more prior surgical interventions, more AEDs at baseline, and a higher rate of bilateral invasive monitoring. Despite this, the SEEG cohort had similar seizure outcomes and a trend toward increased safety. Based on these findings, SEEG appears to allow for monitoring of a wider breadth of TSC patients given its minimally invasive nature and its relative simplicity for monitoring numerous regions of the brain.

Functional MRI and electrical stimulation mapping for language localization: A comparative meta-analysis.

OBJECTIVE: This systematic review and meta-analysis evaluated the diagnostic validity of functional magnetic resonance imaging (fMRI) compared to electrical stimulation mapping (ESM) for pre-surgical language mapping. METHODS: A structured literature search was performed and studies with electrode-level data comparing fMRI and ESM for language localization were analyzed. Outcome measures included pooled estimates of diagnostic odds ratio (DOR), sensitivity, and specificity. Sources of heterogeneity were explored with a meta-regression framework. RESULTS: Nine studies were included in the analysis having 5-40 patients with mean age 11.3-43.4 years. Verb generation and picture naming were the most common fMRI tasks, while picture naming was the most common ESM task. Sensitivity (0.37-0.95), specificity (0.36-0.97), and DOR (1.9-44.6) for fMRI compared to ESM varied widely across studies with statistically significant heterogeneities. Pooled estimates were: sensitivity 0.71 (95% confidence interval 0.54, 0.83), specificity 0.74 (0.58, 0.85), and DOR 7.0 (3.5, 13.8), from a valid meta-analysis (area under the summary receiver-operating-curve 0.78). fMRI was noted to have higher sensitivity in studies using higher maximal ESM currents. fMRI variables could not be included in the meta-regression because of substantial methodological differences among studies. CONCLUSIONS: fMRI is moderately sensitive and moderately specific for language localization compared to ESM in well-designed studies. However, because the confidence limits for sensitivity and DOR are close to the line of no effect, and there is high unmeasured heterogeneity, fMRI cannot perhaps be used as the only modality for language localization to inform neurosurgical decisions at present.

Responsive neurostimulation device therapy in pediatric patients with complex medically refractory epilepsy.

OBJECTIVE: Pediatric epilepsy is characterized as drug resistant in 20%-30% of patients and defined as persistent seizures despite adequate treatment with two first-line antiepileptic medications. The American Academy of Neurology advocates surgical options earlier in the treatment of epilepsy to provide long-term seizure reduction. The new development of minimally invasive approaches has recently allowed for surgical options to patients not previously deemed surgical candidates. These may include patients with bilateral, deep, eloquent, or poorly localizing epileptogenic foci. To this end, responsive neurostimulation (RNS) is an FDA-approved closed-loop neuromodulation device for adjuvant treatment of adults with medically intractable epilepsy arising from one or multiple foci. METHODS: In this study, the authors describe their initial institutional experience with the use of RNS in pediatric patients with drug-resistant epilepsy. An IRB-approved retrospective review was conducted of 8 pediatric patients who underwent RNS implantation at Cincinnati Children's Hospital Medical Center between 2019 and 2021. RESULTS: Eight patients met the inclusion criteria for the study. The average age at the time of surgery was 14.7 years (range 8-18 years) with a mean follow-up of 16.5 months. All patients underwent invasive monitoring with stereo-EEG, subdural grid placement, or a combination of both. All patients had either bilateral or eloquent cortex targets. Trajectories were based on noninvasive (phase 1) and invasive (phase 2) seizure onset zone localization data. Four (50%) of the 8 patients underwent surgical intervention for epilepsy prior to RNS placement. RNS electrodes were placed with robot-assisted guidance in a hybrid operating room with intraoperative CT and electrocorticography. The authors demonstrated individualized RNS electrode trajectory and placement with targets in the amygdala/hippocampus, bilateral insula, bilateral parietal and occipital targets, and frontoparietal regions for a total of 14 implanted electrodes. One adverse event occurred, a wound infection requiring return to the operating room for removal of the RNS implant. All patients demonstrated a reduction in seizure frequency. All patients achieved > 50% reduction in seizure frequency at last follow-up. CONCLUSIONS: RNS implantation in carefully selected pediatric patients appears safe and efficacious in reducing seizure burden with a low rate of operative complications.

Cerebral Arterial Growth in Childhood.

BACKGROUND: Improved understanding of cerebral arterial growth in children may lead to advances in the diagnosis and treatment of pediatric cerebrovascular disease. We correlated cross-sectional diameters of major cerebral arterial structures with age, sex, head circumference, weight, and height in children without cerebrovascular disease. METHODS: Children with normal brain magnetic resonance imaging (MRI) were retrospectively identified and stratified into 23 age cohorts from birth to age 18 years. Absence of vascular disease was verified by medical record review. Demographic and biometric data were obtained from medical records. Intracranial arterial diameter (IAD) was measured on T2-weighted fast spin echo brain MRI of vertebral, basilar, internal carotid artery, and circle of Willis arterial segments. RESULTS: A total of 307 subjects are included in the analysis, including 5833 vessel segments (mean age 8.4 years, 53% female). Indications for imaging were headache (73%), seizure (26%) and concussion (1%). IAD rapidly increased during the first year of life (mean growth velocity 0.064 to 0.213 mm/month) and then plateaued or slightly decreased between age one and 18 years (mean growth velocity -0.002 to 0.003 mm/month). Multivariable analysis shows strongest correlation with head circumference as a predictor of IAD. Weaker correlations are associated with weight and age. Height and sex are not well correlated with IAD. CONCLUSIONS: Intracranial arteries grow rapidly during the first year of life and then sharply plateau or slightly decrease in luminal diameter between infancy and early adulthood. IAD is more closely correlated with head circumference than age.

Neuronal Circuits Supporting Development of Visual Naming Revealed by Intracranial Coherence Modulations.

Background: Improvement in visual naming abilities throughout the childhood and adolescence supports development of higher-order linguistic skills. We investigated neuronal circuits underlying improvement in the speed of visual naming with age, and age-related dynamics of these circuits. Methods: Response times were electronically measured during an overt visual naming task in epilepsy patients undergoing stereo-EEG monitoring. Coherence modulations among pairs of neuroanatomic parcels were computed and analyzed for relationship with response time and age. Results: During the overt visual naming task, mean response time (latency) significantly decreased from 4 to 23 years of age. Coherence modulations during visual naming showed that increased connectivity between certain brain regions, particularly that between left fusiform gyrus/left parahippocampal gyrus and left frontal operculum, is associated with improvement in naming speed. Also, decreased connectivity in other brain regions, particularly between left angular and supramarginal gyri, is associated with decreased mean response time. Further, coherence modulations between left frontal operculum and both left fusiform and left posterior cingulate gyri significantly increase, while that between left angular and supramarginal gyri significantly decrease, with age. Conclusion: Naming speed continues to improve from pre-school years into young adulthood. This age-related improvement in efficiency of naming environmental objects occurs likely because of strengthened direct connectivity between semantic and phonological nodes, and elimination of intermediate higher-order cognitive steps.

Volumetric endpoints in diffuse intrinsic pontine glioma: comparison to cross-sectional measures and outcome correlations in the International DIPG/DMG Registry.

BACKGROUND: Cross-sectional tumor measures are traditional clinical trial endpoints; however volumetric measures may better assess tumor growth. We determined the correlation and compared the prognostic impact of cross-sectional and volumetric measures of progressive disease (PD) among patients with DIPG. METHODS: Imaging and clinical data were abstracted from the International DIPG Registry. Tumor volume and cross-sectional product (CP) were measured with mint Lesion™ software using manual contouring. Correlation between CP and volume (segmented and mathematical [ellipsoid] model) thresholds of PD were assessed by linear regression. Landmark analyses determined differences in survival (via log-rank) between patients classified as PD versus non-PD by CP and volumetric measurements at 1, 3, 5, 7, and 9 months postradiotherapy (RT). Hazard ratios (HR) for survival after these time points were calculated by Cox regression. RESULTS: A total of 312 MRIs (46 patients) were analyzed. Comparing change from the previous smallest measure, CP increase of 25% (PD) correlated with a segmented volume increase of 30% (R2 = 0.710), rather than 40% (spherical model extrapolation). CP-determined PD predicted survival at 1 month post-RT (HR = 2.77), but not other time points. Segmented volumetric-determined PD (40% threshold) predicted survival at all imaging timepoints (HRs = 2.57, 2.62, 3.35, 2.71, 16.29), and 30% volumetric PD threshold predicted survival at 1, 3, 5, and 9 month timepoints (HRs = 2.57, 2.62, 4.65, 5.54). Compared to ellipsoid volume, segmented volume demonstrated superior survival associations. CONCLUSIONS: Segmented volumetric assessments of PD correlated better with survival than CP or ellipsoid volume at most time points. Semiautomated tumor volume likely represents a more accurate, prognostically-relevant measure of disease burden in DIPG.

Extraneural Metastases of Diffuse Midline Glioma, H3 K27M-Mutant at Diagnosis: Case Report, Review of the Literature, and Identifying Targetable Alterations.

Extraneural metastases are rare in pediatric high-grade gliomas and little is known about the genomic profiles of tumors that disseminate beyond the central nervous system. We describe a pediatric patient with H3 K27M-mutant diffuse midline glioma of the brain and spine with biopsy-confirmed osseous metastases present at diagnosis and suspected metastatic parenchymal pulmonary disease. Several potentially clinically and/or therapeutically relevant genomic alterations were identified, including H3F3A and TP53 mutations as well as MET, CDK6, EMSY, and PIK3CG amplifications. Sequencing is critical to improve our understanding of the molecular drivers of distant metastases and discover therapeutic targets that penetrate all disease sites.

Accuracy of central neuro-imaging review of DIPG compared with histopathology in the International DIPG Registry.

BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) remains a clinico-radiologic diagnosis without routine tissue acquisition. Reliable imaging distinction between DIPG and other pontine tumors with potentially more favorable prognoses and treatment considerations is essential. METHODS: Cases submitted to the International DIPG registry (IDIPGR) with histopathologic and/or radiologic data were analyzed. Central imaging review was performed on diagnostic brain MRIs (if available) by two neuro-radiologists. Imaging features suggestive of alternative diagnoses included nonpontine origin, <50% pontine involvement, focally exophytic morphology, sharply defined margins, and/or marked diffusion restriction throughout. RESULTS: Among 286 patients with pathology from biopsy and/or autopsy, 23 (8%) had histologic diagnoses inconsistent with DIPG, most commonly nondiffuse low-grade gliomas and embryonal tumors. Among 569 patients with centrally-reviewed diagnostic MRIs, 40 (7%) were classified as non-DIPG, alternative diagnosis suspected. The combined analysis included 151 patients with both histopathology and centrally-reviewed MRI. Of 77 patients with imaging classified as characteristic of DIPG, 76 (99%) had histopathologic diagnoses consistent with DIPG (infiltrating grade II-IV gliomas). Of 57 patients classified as likely DIPG with some unusual imaging features, 55 (96%) had histopathologic diagnoses consistent with DIPG. Of 17 patients with imaging features suggestive of an alternative diagnosis, eight (47%) had histopathologic diagnoses inconsistent with DIPG (remaining patients were excluded due to nonpontine tumor origin). Association between central neuro-imaging review impression and histopathology was significant (p < 0.001), and central neuro-imaging impression was prognostic of overall survival. CONCLUSIONS: The accuracy and important role of central neuro-imaging review in confirming the diagnosis of DIPG is demonstrated.

A distributed network supports spatiotemporal cerebral dynamics of visual naming.

OBJECTIVE: Cerebral spatiotemporal dynamics of visual naming were investigated in epilepsy patients undergoing stereo-electroencephalography (SEEG) monitoring. METHODS: Brain networks were defined by Parcel-Activation-Resection-Symptom matching (PARS) approach by matching high-gamma (50-150 Hz) modulations (HGM) in neuroanatomic parcels during visual naming, with neuropsychological outcomes after resection/ablation of those parcels. Brain parcels with >50% electrode contacts simultaneously showing significant HGM were aligned, to delineate spatiotemporal course of naming-related HGM. RESULTS: In 41 epilepsy patients, neuroanatomic parcels showed sequential yet temporally overlapping HGM course during visual naming. From bilateral occipital lobes, HGM became increasingly left lateralized, coursing through limbic system. Bilateral superior temporal HGM was noted around response time, and right frontal HGM thereafter. Correlations between resected/ablated parcels, and post-surgical neuropsychological outcomes showed specific regional groupings. CONCLUSIONS: Convergence of data from spatiotemporal course of HGM during visual naming, and functional role of specific parcels inferred from neuropsychological deficits after resection/ablation of those parcels, support a model with six cognitive subcomponents of visual naming having overlapping temporal profiles. SIGNIFICANCE: Cerebral substrates supporting visual naming are bilaterally distributed with relative hemispheric contribution dependent on cognitive demands at a specific time. PARS approach can be extended to study other cognitive and functional brain networks.

Evaluation of the Effectiveness of Newer Helmet Designs with Emergent Shell and Padding Technologies Versus Older Helmet Models for Preserving White Matter Following a Season of High School Football.

We aimed to objectively compare the effects of wearing newer, higher-ranked football helmets (HRank) vs. wearing older, lower-ranked helmets (LRank) on pre- to post-season alterations to neuroimaging-derived metrics of athletes' white matter. Fifty-four high-school athletes wore an HRank helmet, and 62 athletes wore an LRank helmet during their competitive football season and completed pre- and post-season diffusion tensor imaging (DTI). Longitudinal within- and between-group DTI metrics [fractional anisotropy (FA) and mean/axial/radial diffusivity (MD, AD, RD)] were analyzed using tract-based spatial statistics. The LRank helmet group exhibited significant pre- to post-season reductions in MD, AD, and RD, the HRank helmet group displayed significant pre- to post-season increases in FA, and both groups showed significant pre- to post-season increases in AD (p's < .05 [corrected]). Between-group analyses revealed the pre- to post-season increase in AD was significantly less for athletes wearing HRank compared to LRank (p < .05 [corrected]). These data provide in vivo evidence that wearing an HRank helmet may be efficacious for preserving white matter from head impact exposure during high school football. Future prospective longitudinal investigations with complimentary imaging and behavioral outcomes are warranted to corroborate these initial in vivo findings.

High School Sports-Related Concussion and the Effect of a Jugular Vein Compression Collar: A Prospective Longitudinal Investigation of Neuroimaging and Neurofunctional Outcomes.

Sports-related concussion (SRC) can exert serious acute and long-term consequences on brain microstructure, function, and behavioral outcomes. We aimed to quantify the alterations in white matter (WM) microstructure and global network organization, and the decrements in behavioral and cognitive outcomes from pre-season to post-concussion in youth athletes who experienced SRC. We also aimed to evaluate whether wearing a jugular compression neck collar, a device designed to mitigate brain "slosh" injury, would mitigate the pre-season to post-concussion alterations in neuroimaging, behavioral, and cognitive outcomes. A total of 488 high school football and soccer athletes (14-18 years old) were prospectively enrolled and assigned to the non-collar group (n = 237) or the collar group (n = 251). The outcomes of the study were the pre-season to post-concussion neuroimaging, behavioral, and cognitive alterations. Forty-six participants (non-collar: n = 24; collar: n = 22) were diagnosed with a SRC during the season. Forty of these 46 athletes (non-collar: n = 20; collar: n = 20) completed neuroimaging assessment. Significant pre-season to post-concussion alterations in WM microstructural integrity and brain network organization were found in these athletes (corrected p < 0.05). The alterations were significantly reduced in collar-wearing athletes compared to non-collar-wearing athletes (corrected p < 0.05). Concussion and collar main effects were identified for some of the behavioral and cognitive outcomes, but no collar by SRC interaction effects were observed in any outcomes. In summary, young athletes exhibited significant WM microstructural and network organizational, and cognitive alterations following SRC. The use of the jugular vein compression collar showed promising evidence to reduce these alterations in high school contact sport athletes.

Subtraction ictal SPECT co-registered to MRI (SISCOM) patterns in children with temporal lobe epilepsy.

OBJECTIVE: We evaluated SISCOM patterns and their relationship with surgical outcome in children with temporal lobe epilepsy (TLE) who had undergone a temporal lobe surgery. METHODS: This was an observational study evaluating SISCOM patterns in 40 children with TLE. We classified SISCOM patterns into 4 categories; (i) unilateral anteromesial and/or anterolateral temporal pattern; (ii) unilateral anteromesial and/or anterolateral temporal plus posterior extension pattern; (iii) bilateral anteromesial and/or anterolateral temporal pattern; and (iv) atypical pattern. Determinants of SISCOM pattern and correlation between postoperative outcomes and SISCOM patterns were evaluated. RESULTS: Pattern (i), (ii), (iii), and (iv) were identified in 10 (25%), 14 (35%), 0 (0%), and 16 (40%) patients, respectively. There was no significant correlation between patterns and postoperative outcomes. SISCOM patterns significantly associated with the presence of hippocampal sclerosis and type of focal cortical dysplasia (p-value = 0.048 and 0.036, respectively). Patients with HS had 5 times the odds of having unilateral temporal pattern, compared to patients with other neuropathology (OR = 5, 95% CI 0.92 to 27.08). Patients with FCD type 2 had 9.71 times the odds of having atypical pattern, compared to patients with other types of FCD (OR = 9.71, 95% CI 0.92 to 103.04). Lobar concordance of SISCOM and ictal and interictal scalp EEG significantly correlated with postoperative outcomes (p-value = 0.018 and 0.013, respectively). CONCLUSION: Three SISCOM patterns were seen. Patients with HS had increased odds of having unilateral temporal pattern while patients with FCD type 2 had increased odds of having atypical pattern. However, there was no significant correlation between SISCOM patterns and postoperative outcomes. Lobar concordance of SISCOM and ictal and interictal scalp EEG significantly correlated with postoperative outcome. SIGNIFICANCE: This study shows that the distribution of SISCOM patterns and their relationship with postoperative outcomes in children with TLE are different from adult population. Besides, SISCOM may add only limited diagnostic and prognostic information in children with drug-resistant TLE undergoing epilepsy surgery. Further evaluation to identify patient populations that may benefit from SISCOM is desirable.