Hemispheric functional organization, as revealed by naturalistic neuroimaging, in pediatric epilepsy patients with cortical resections.

Functional changes in the pediatric brain following neural injuries attest to remarkable feats of plasticity. Investigations of the neurobiological mechanisms that underlie this plasticity have largely focused on activation in the penumbra of the lesion or in contralesional, homotopic regions. Here, we adopt a whole-brain approach to evaluate the plasticity of the cortex in patients with large unilateral cortical resections due to drug-resistant childhood epilepsy. We compared the functional connectivity (FC) in patients' preserved hemisphere with the corresponding hemisphere of matched controls as they viewed and listened to a movie excerpt in a functional magnetic resonance imaging (fMRI) scanner. The preserved hemisphere was segmented into 180 and 200 parcels using two different anatomical atlases. We calculated all pairwise multivariate statistical dependencies between parcels, or parcel edges, and between 22 and 7 larger-scale functional networks, or network edges, aggregated from the smaller parcel edges. Both the left and right hemisphere-preserved patient groups had widespread reductions in FC relative to matched controls, particularly for within-network edges. A case series analysis further uncovered subclusters of patients with distinctive edgewise changes relative to controls, illustrating individual postoperative connectivity profiles. The large-scale differences in networks of the preserved hemisphere potentially reflect plasticity in the service of maintained and/or retained cognitive function.

A survey of child neurologists about reproductive healthcare for adolescent women with epilepsy.

OBJECTIVE: To evaluate child neurologists' knowledge, attitudes, and practices regarding sexual and reproductive health (SRH) care for adolescent and young adult women with epilepsy (WWE). METHODS: Child neurologists (including attending physicians, residents, fellows, and advanced practitioners) completed an online survey distributed through subspecialty listservs. We analyzed results using descriptive statistics, chi-square, and logistic regression. RESULTS: Two hundred eight child neurologists completed the survey. Most believed that child neurologists should counsel young WWE on: teratogenesis (99%, n = 206/207), contraception-antiseizure medication interactions (96%, n = 194/202), pregnancy (95%, n = 198/206), contraception (89%, n = 184/206) and folic acid supplementation (70%, n = 144/205). Fewer respondents felt confident with such counseling (teratogenesis: 90%, n = 188/208, drug interactions: 65%, n = 133/208, pregnancy 75%, n = 156/208, contraception: 47-64%, n = 96-134/208, p < 0.05). Ninety-five percent (n = 172/181) reported ever discussing SRH with typically developing young WWE, compared to 78% (n = 141/181) for young WWE with mild intellectual disability (p < 0.01). One third (n = 56/170) who ever discussed SRH did not do so routinely. Respondents correctly answered 87% ±â€¯5% of knowledge questions about SRH for WWE, 80% ±â€¯4% of questions about teratogenic antiseizure medications, and 61% ±â€¯7% of questions about contraception-antiseizure drug interactions. The greatest barrier to SRH care was time constraints (80%, n = 149/186). The majority (64%, n = 119/186) identified solutions including longer appointment times and co-managing SRH care with other specialties. CONCLUSIONS: Findings reveal gaps in SRH care by child neurologists for adolescent and young adult WWE, especially those with mild intellectual disability. Provider-identified barriers and solutions may serve as targets to improve SRH care for this population.

Perceptual Function and Category-Selective Neural Organization in Children with Resections of Visual Cortex.

The consequences of cortical resection, a treatment for humans with pharmaco-resistant epilepsy, provide a unique opportunity to advance our understanding of the nature and extent of cortical (re)organization. Despite the importance of visual processing in daily life, the neural and perceptual sequellae of occipitotemporal resections remain largely unexplored. Using psychophysical and fMRI investigations, we compared the neural and visuoperceptual profiles of 10 children or adolescents following unilateral cortical resections and their age- and gender-matched controls. Dramatically, with the exception of two individuals, both of whom had relatively greater cortical alterations, all patients showed normal perceptual performance on tasks of intermediate- and high-level vision, including face and object recognition. Consistently, again with the exception of the same two individuals, both univariate and multivariate fMRI analyses revealed normal selectivity and representational structure of category-selective regions. Furthermore, the spatial organization of category-selective regions obeyed the typical medial-to-lateral topographic organization albeit unilaterally in the structurally preserved hemisphere rather than bilaterally. These findings offer novel insights into the malleability of cortex in the pediatric population and suggest that, although experience may be necessary for the emergence of neural category-selectivity, this emergence is not necessarily contingent on the integrity of particular cortical structures.SIGNIFICANCE STATEMENT One approach to reduce seizure activity in patients with pharmaco-resistant epilepsy involves the resection of the epileptogenic focus. The impact of these resections on the perceptual behaviors and organization of visual cortex remain largely unexplored. Here, we characterized the visuoperceptual and neural profiles of ventral visual cortex in a relatively large sample of post-resection pediatric patients. Two major findings emerged. First, most patients exhibited preserved visuoperceptual performance across a wide-range of visual behaviors. Second, normal topography, magnitude, and representational structure of category-selective organization were uncovered in the spared hemisphere. These comprehensive imaging and behavioral investigations uncovered novel evidence concerning the neural representations and visual functions in children who have undergone cortical resection, and have implications for cortical plasticity more generally.

Effects of unilateral cortical resection of the visual cortex on bilateral human white matter.

Children with unilateral resections of ventral occipito-temporal cortex (VOTC) typically do not evince visual perceptual impairments, even when relatively large swathes of VOTC are resected. In search of possible explanations for this behavioral competence, we evaluated white matter microstructure and connectivity in eight pediatric epilepsy patients following unilateral cortical resection and 15 age-matched controls. To uncover both local and broader resection-induced effects, we analyzed tractography data using two complementary approaches. First, the microstructural properties were measured in the inferior longitudinal and the inferior fronto-occipital fasciculi, the major VOTC association tracts. Group differences were only evident in the ipsilesional, and not in the contralesional, hemisphere, and single-subject analyses revealed that these differences were limited to the site of the resection. Second, graph theory was used to characterize the connectivity of the contralesional occipito-temporal regions. There were no changes to the network properties in patients with left VOTC resections nor in patients with resections outside the VOTC, but altered network efficiency was observed in two cases with right VOTC resections. These results suggest that, in many, although perhaps not all, cases of unilateral VOTC resections in childhood, the white matter profile in the preserved contralesional hemisphere along with residual neural activity might be sufficient for normal visual perception.

Morphometrics of the preserved post-surgical hemisphere in pediatric drug-resistant epilepsy.

Importance: Structural integrity of cortex following cortical resection for epilepsy management has been previously characterized, but only in adult patients. Objective: This study sought to determine whether morphometrics of the preserved hemisphere in pediatric cortical resection patients differ from non-neurological controls. Design: This was a case-control study, from 2013-2022. Setting: This was a single-site study. Participants: 32 patients with childhood epilepsy surgery and 51 age- and gender-matched controls participated. Main Measures: We quantified morphometrics of the preserved hemisphere at the level of gross anatomy (lateral ventricle size, volume of gray and white matter). Additionally, cortical thickness, volume, and surface area were measured for 34 cortical regions segmented with the Desikan-Killiany atlas, and, last, volumes of nine subcortical regions were also quantified. Results: 13 patients with left hemisphere (LH) surgery and a preserved right hemisphere (RH) (median age/median absolute deviation of age: 15.7/1.7 yr; 6 females, 7 males) and 19 patients with RH surgery and a preserved LH (15.4/3.7 yr; 11 females, 8 males) were compared to 51 controls (14.8/4.9 yr; 24 females, 27 males). Patient groups had larger ventricles and reduced total white matter volume relative to controls, and only patients with a preserved RH, but not patients with a preserved LH, had reduced total gray matter volume relative to controls. Furthermore, patients with a preserved RH had lower cortical thickness and volume and greater surface area of several cortical regions, relative to controls. Patients with a preserved LH had no differences in thickness, volume, or area, of any of the 34 cortical regions, relative to controls. Moreover, both LH and RH patients showed reduced volumes in select subcortical structures, relative to controls. Conclusions and Relevance: That left-sided, but not right-sided, resection is associated with more pronounced reduction in cortical thickness and volume and increased cortical surface area relative to typically developing, age-matched controls suggests that the preserved RH undergoes structural plasticity to an extent not observed in cases of right-sided pediatric resection. Future work probing the association of the current findings with neuropsychological outcomes will be necessary to understand the implications of these structural findings for clinical practice.

Functional Resilience of the Neural Visual Recognition System Post-Pediatric Occipitotemporal Resection.

In the typically developing (TD) brain, neural representations for visual stimulus categories (e.g., faces, objects, and words) emerge in bilateral occipitotemporal cortex (OTC), albeit with weighted asymmetry; in parallel, recognition behavior continues to be refined. A fundamental question is whether two hemispheres are necessary or redundant for the emergence of neural representations and recognition behavior typically distributed across both hemispheres. The rare population of patients undergoing unilateral OTC resection in childhood offers a unique opportunity to evaluate whether neural computations for visual stimulus individuation suffice for recognition with only a single developing OTC. Here, using functional magnetic resonance imaging, we mapped category selectivity (CS) and neural representations for individual stimulus exemplars using repetition suppression (RS) in the non-resected hemisphere of pediatric OTC resection patients (n = 9) and control patients with resection outside of OTC (n = 12), as well as in both hemispheres of TD controls (n = 21). There were no univariate group differences in the magnitude of CS or RS or any multivariate differences (per representational similarity analysis) in neural activation to faces, objects, or words across groups. Notwithstanding their comparable neural profiles, accuracy of OTC resection patients on face and object recognition, but not word recognition, was statistically inferior to that of controls. The comparable neural signature of the OTC resection patients' preserved hemisphere and the other two groups highlights the resilience of the system following damage to the contralateral homologue. Critically, however, a single OTC does not suffice for normal behavior, and, thereby, implicates the necessity for two hemispheres.

Holistic processing and face expertise after pediatric resection of occipitotemporal cortex.

The nature and extent of hemispheric lateralization and its potential for reorganization continues to be debated, although there is general agreement that there is a right hemisphere (RH) advantage for face processing in human adults. Here, we examined face processing and its lateralization in individuals with a single preserved occipitotemporal cortex (OTC), either in the RH or left hemisphere (LH), following early childhood resection for the management of drug-resistant epilepsy. The matched controls and those with a lesion outside of OTC evinced the standard superiority in processing upright over inverted faces and the reverse sensitivity to a nonface category (bicycles). In contrast, the LH and the RH patient groups were significantly less accurate than the controls and showed mild orientation sensitivities at best (and not always in the predicted directions). For the two patient groups, the accuracies of face and bicycle processing did not differ from each other and were not obviously related to performance on intermediate level global form tasks with, again, poorer thresholds for both patient groups than controls and no difference between the patient groups. These findings shed light on the complexity of hemispheric lateralization and face and nonface object processing in individuals following surgical resection of OTC. Overall, this study highlights the unique dynamics and potential for plasticity in those with childhood cortical resection.

Differential functional reorganization of ventral and dorsal visual pathways following childhood hemispherectomy.

Hemispherectomy is a surgical procedure in which an entire hemisphere of a patient's brain is resected or functionally disconnected to manage seizures in individuals with drug-resistant epilepsy. Despite the extensive loss of input from both ventral and dorsal visual pathways of one hemisphere, pediatric patients who have undergone hemispherectomy show a remarkably high degree of perceptual function across many domains. In the current study, we sought to understand the extent to which functions of the ventral and dorsal visual pathways reorganize to the contralateral hemisphere following childhood hemispherectomy. To this end, we collected fMRI data from an equal number of left and right hemispherectomy patients who completed tasks that typically elicit lateralized responses from the ventral or the dorsal pathway, namely, word (left ventral), face (right ventral), tool (left dorsal), and global form (right dorsal) perception. Overall, there was greater evidence of functional reorganization in the ventral pathway than in the dorsal pathway. Importantly, because ventral and dorsal reorganization was tested in the very same patients, these results cannot be explained by idiosyncratic factors such as disease etiology, age at the time of surgery, or age at testing. These findings suggest that because the dorsal pathway may mature earlier, it may have a shorter developmental window of plasticity than the ventral pathway and, hence, be less malleable.

Differential functional reorganization of ventral and dorsal visual pathways following childhood hemispherectomy.

Hemispherectomy is a surgical procedure in which an entire hemisphere of a patient's brain is resected or functionally disconnected to manage seizures in individuals with drug-resistant epilepsy. Despite the extensive loss of both ventral and dorsal visual pathways in one hemisphere, pediatric patients who have undergone hemispherectomy show a remarkably high degree of perceptual function across many domains. In the current study, we sought to understand the extent to which functions of the ventral and dorsal visual pathways reorganize to the contralateral hemisphere following childhood hemispherectomy. To this end, we collected fMRI data from an equal number of left and right hemispherectomy patients who completed tasks that typically elicit lateralized responses from the ventral or the dorsal pathway, namely, word (left ventral), face (right ventral), tool (left dorsal), and global form (right dorsal) perception. Overall, there was greater evidence of functional reorganization in the ventral pathway than in the dorsal pathway. Importantly, because ventral and dorsal reorganization was tested within the very same patients, these results cannot be explained by idiosyncratic factors such as disease etiology, age at the time of surgery, or age at testing. These findings suggest that because the dorsal pathway may mature earlier, it may have a shorter developmental window of plasticity than the ventral pathway and, hence, be less malleable after perturbation.

Acute Adrenal Hemorrhage as the Initial Manifestation of Metastatic Lung Adenocarcinoma: A Cautionary Tale.

Adrenal gland metastatic disease is the most commonly occurring malignancy of the adrenal glands. Although metastatic disease is common, adrenal hemorrhage is a rare but potentially fatal manifestation of malignancy. The objectives of this case report are to highlight the unusual presentation of metastatic lung adenocarcinoma as spontaneous adrenal hemorrhage in a 64-year-old female who was otherwise asymptomatic. As well as to support the reasoning that metastatic disease should be considered as a differential in patients with this clinical presentation as this may have altered this fatal outcome.

Unilateral resection of both cortical visual pathways in a pediatric patient alters action but not perception.

The human cortical visual system consists of two major pathways, a ventral pathway which subserves perception and a dorsal pathway which primarily subserves visuomotor control. Previous studies have found that children with cortical resections of the ventral visual pathway retain largely normal visuoperceptual abilities. Whether visually guided actions, supported by computations carried out by the dorsal pathway, follow a similar pattern of preservation remains unknown. To address this question, we examined visuoperceptual and visuomotor behaviors in a pediatric patient, TC, who underwent a cortical resection that included portions of the left ventral and dorsal pathways. We collected kinematic data when TC used her right and left hands to perceptually estimate the width of blocks that varied in width and length, and, separately, to grasp the same blocks. TC's perceptual estimation performance was comparable to that of controls, independent of the hand used. In contrast, relative to controls, she showed reduced visuomotor sensitivity to object shape and this was more evident when she grasped the objects with her contralesional right hand. These results provide novel evidence for a striking difference in the competence of the two visual pathways to cortical injuries acquired in childhood.

Development of the awareness, skills, knowledge: General (ASK-G) scale for measuring cultural competence in the general population.

Measuring cultural competence has been difficult for conceptual and practical reasons. Yet, professional guidelines and stated values call for training to improve cultural competence. To develop a strong evidence-base for training and improving cultural competence, professionals need reliable and valid measures to capture meaningful changes in cultural competence training. We developed a measure for cultural competence that could be used in a general population to measure changes in awareness, knowledge, and skills in interacting with culturally diverse others. We built an 81-item scale with items conceptually categorized into awareness, knowledge, and skills and was presented to an expert panel for feedback. For evaluation, a national panel of 204 adults responded to the new scale and other measures associated with cultural competence. Factor analysis revealed four factors with strong reliabilities: Awareness of Self, Awareness of Others, Proactive Skills Development, and Knowledge (as = .87 - .92). The final overall scale, Awareness, Knowledge, Skills-General (ASK-G) had 37 items and strong reliability (a = .94). The ASK-G was then compared to validated scales to provide evidence of concurrent, convergent, and divergent validity. Strong evidence emerged for these. The ASK-G is a promising tool to measure cultural competence in a general population.

Quantitative Electroencephalography (EEG) Predicting Acute Neurologic Deterioration in the Pediatric Intensive Care Unit: A Case Series.

Introduction: Continuous neurologic assessment in the pediatric intensive care unit is challenging. Current electroencephalography (EEG) guidelines support monitoring status epilepticus, vasospasm detection, and cardiac arrest prognostication, but the scope of brain dysfunction in critically ill patients is larger. We explore quantitative EEG in pediatric intensive care unit patients with neurologic emergencies to identify quantitative EEG changes preceding clinical detection. Methods: From 2017 to 2020, we identified pediatric intensive care unit patients at a single quaternary children's hospital with EEG recording near or during acute neurologic deterioration. Quantitative EEG analysis was performed using Persyst P14 (Persyst Development Corporation). Included features were fast Fourier transform, asymmetry, and rhythmicity spectrograms, "from-baseline" patient-specific versions of the above features, and quantitative suppression ratio. Timing of quantitative EEG changes was determined by expert review and prespecified quantitative EEG alert thresholds. Clinical detection of neurologic deterioration was defined pre hoc and determined through electronic medical record documentation of examination change or intervention. Results: Ten patients were identified, age 23 months to 27 years, and 50% were female. Of 10 patients, 6 died, 1 had new morbidity, and 3 had good recovery; the most common cause of death was cerebral edema and herniation. The fastest changes were on "from-baseline" fast Fourier transform spectrograms, whereas persistent changes on asymmetry spectrograms and suppression ratio were most associated with morbidity and mortality. Median time from first quantitative EEG change to clinical detection was 332 minutes (interquartile range: 201-456 minutes). Conclusion: Quantitative EEG is potentially useful in earlier detection of neurologic deterioration in critically ill pediatric intensive care unit patients. Further work is required to quantify the predictive value, measure improvement in outcome, and automate the process.

Pediatric Neurologists' Perspectives on Sexual and Reproductive Health Care for Adolescent and Young Adult Women With Epilepsy and Intellectual Disability.

OBJECTIVE: To explore perspectives of pediatric neurologists regarding sexual and reproductive health care for adolescent women with epilepsy (WWE) and intellectual disability. METHODS: We interviewed pediatric neurologists regarding sexual and reproductive health for WWE with intellectual disability. We audio-recorded and transcribed interviews and conducted qualitative analysis. RESULTS: 16 pediatric neurologists participated. Themes included the following: (1) Pediatric neurologists have differing perspectives about how intellectual disability affects WWE's sexual and reproductive health needs, (2) pediatric neurologists provide sexual and reproductive health counseling variable in content and frequency to this population, (3) pediatric neurologists tend to recommend longer-term methods of contraception for this population, and (4) pediatric neurologists are asked to be involved in decision-making around sterilization, yet express ethico-legal reservations. CONCLUSION: Our findings suggest pediatric neurologists provide variable, often suboptimal, sexual and reproductive health care for WWE and intellectual disability. Themes reveal ethical concerns among neurologists about sexual and reproductive health practices including sterilization. More tailored clinical guidelines and provider training on sexual and reproductive health for this population may be beneficial.

Low-cost gastrointestinal manometry via silicone-liquid-metal pressure transducers resembling a quipu.

The evaluation of the tone and contractile patterns of the gastrointestinal (GI) tract via manometry is essential for the diagnosis of GI motility disorders. However, manometry is expensive and relies on complex and bulky instrumentation. Here we report the development and performance of an inexpensive and easy-to-manufacture catheter-like device for capturing manometric data across the dynamic range observed in the human GI tract. The device, which we designed to resemble the quipu-knotted strings used by Andean civilizations for the capture and transmission of information-consists of knotted piezoresistive pressure sensors made by infusing a liquid metal (eutectic gallium-indium) through thin silicone tubing. By exploring a range of knotting configurations, we identified optimal design schemes that led to sensing performances comparable to those of commercial devices for GI manometry, as we show for the sensing of GI motility in multiple anatomic sites of the GI tract of anaesthetized pigs. Disposable and customizable piezoresistive catheters may broaden the use of GI manometry in low-resource settings.

The Role of Magnetoencephalography and Single-Photon Emission Computed Tomography in Evaluation of Children With Drug-Resistant Epilepsy.

Surgery holds the best outcomes for drug-resistant epilepsy in children, making localization of a seizure focus essential. However, there is limited research on the contribution of magnetoencephalography and single-photon emission computed tomography (SPECT) to the presurgical evaluation of lesional and nonlesional pediatric patients. This study proposed to evaluate the concordance of SPECT and magnetoencephalography (MEG) to scalp electroencephalography (EEG) to determine their effective contribution to the presurgical evaluation. On review, MEG and SPECT studies for 28 drug-resistant epilepsy cases were completed at Children's Hospital of Pittsburgh from May 2012 to August 2018. Although not reaching statistical significance, MEG had increased lobar concordance with EEG compared with SPECT (68% vs 46%). MEG or SPECT results effectively provided localization data leading to 6 surgical evaluations and 3 resections with outcomes of Engel class I or II at 12 months. This study suggests MEG and SPECT provide valuable localizing information for presurgical epilepsy evaluation of children with drug-resistant epilepsy.

Large-scale resculpting of cortical circuits in children after surgical resection.

Despite the relative successes in the surgical treatment of pharmacoresistant epilepsy, there is rather little research on the neural (re)organization that potentially subserves behavioral compensation. Here, we examined the post-surgical functional connectivity (FC) in children and adolescents who have undergone unilateral cortical resection and, yet, display remarkably normal behavior. Conventionally, FC has been investigated in terms of the mean correlation of the BOLD time courses extracted from different brain regions. Here, we demonstrated the value of segregating the voxel-wise relationships into mutually exclusive populations that were either positively or negatively correlated. While, relative to controls, the positive correlations were largely normal, negative correlations among networks were increased. Together, our results point to reorganization in the contralesional hemisphere, possibly suggesting competition for cortical territory due to the demand for representation of function. Conceivably, the ubiquitous negative correlations enable the differentiation of function in the reduced cortical volume following a unilateral resection.

Successful Reorganization of Category-Selective Visual Cortex following Occipito-temporal Lobectomy in Childhood.

Investigations of functional (re)organization in children who have undergone large cortical resections offer a unique opportunity to elucidate the nature and extent of cortical plasticity. We report findings from a 3-year investigation of a child, U.D., who underwent surgical removal of the right occipital and posterior temporal lobes at age 6 years 9 months. Relative to controls, post-surgically, U.D. showed age-appropriate intellectual performance and visuoperceptual face and object recognition skills. Using fMRI at five different time points, we observed a persistent hemianopia and no visual field remapping. In category-selective visual cortices, however, object- and scene-selective regions in the intact left hemisphere were stable early on, but regions subserving face and word recognition emerged later and evinced competition for cortical representation. These findings reveal alterations in the selectivity and topography of category-selective regions when confined to a single hemisphere and provide insights into dynamic functional changes in extrastriate cortical architecture.

Pediatric Epilepsy: Neurology, Functional Imaging, and Neurosurgery.

In this chapter we provide a comprehensive review of the current role that functional imaging can have in the care of the pediatric epilepsy patient from the perspective of the epilepsy neurologist and the epilepsy neurosurgeon. In the neurology section, the diagnosis and classification of epilepsy adapted by the International League Against Epilepsy as well as the etiology and incidence of the disease is presented. The neuroimaging section describes how advanced nuclear medicine imaging methods can be synergized to provide a maximum opportunity to localize an epileptogenic focus. This section described the value of FDG-PET and regional cerebral blood flow SPECT in the identification of an epileptogenic focus. The imaging section also emphasizes the importance on developing a dedicated epilepsy management team, comprised of an epilepsy imaging specialist, epilepsy neurologist and epilepsy neurosurgeon, to provide the maximum benefit to each child with epilepsy. An emphasis is placed on preparation for ictal SPECT injection procedures, including the critical role of an automated injector well as the use of state-of-the-art dedicated nuclear medicine imaging and analysis protocols to correctly localize the epileptogenic focus location. In the final section, surgical options, approaches and expected outcomes for the different classes of epilepsy is presented.