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Objective: To critically examine the assumption that protective orders are adequately protective of sensitive psychological/neuropsychological test information. Attorneys at times claim that to adequately cross-examine neuropsychological experts, they require direct access to protected test information, rather than having test data analyzed by retained neuropsychological experts. As a compromise, judges sometimes order that protected test information be released to attorneys under a protective order., Method: An appointed writing group of forensic experts developed a position paper addressing the history of protective orders and their presumed effectiveness in protecting psychological and neuropsychological test content. The expert panel consisted of 12 forensic neuropsychologists, a forensic neuropsychologist/attorney, and a forensic psychologist/attorney., Results: Eight reasons are enumerated as to why protective orders do not sufficiently safeguard protected psychological/neuropsychological information and thereby jeopardize future use of the tests. Recommendations are provided to the expert witness practitioner for navigating demands by non-psychologists for direct access to protected test information., Conclusions: There is strong agreement within the practicing neuropsychology community that test security is a vital matter, which, if properly enforced, can ensure the validity of present and future psychological and neuropsychological assessments but, if ineffectively managed, will undermine such evaluations. Because the effectiveness of protective orders has not been, and cannot be, guaranteed, protected psychological and neuropsychological test information should not be released under a protective order., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The cell cycle is a fundamental process involved in bacterial reproduction and cellular differentiation. For Sinorhizobium meliloti , cell cycle outcomes depend on its growth environment. This bacterium shows a tight coupling of DNA replication initiation with cell division during free-living growth. In contrast, it undergoes a novel program of endoreduplication and terminal differentiation during symbiosis within its host. While several DivK regulators at the top of its CtrA pathway have been shown to play an important role in this differentiation process, there is a lack of resolution regarding the downstream molecular activities required and whether they could be unique to the symbiosis cell cycle. The DivK kinase CbrA is a negative regulator of CtrA activity and is required for successful symbiosis. In this work, spontaneous symbiosis suppressors of Δ cbrA were identified as alleles of divL and cckA . In addition to rescuing symbiotic development, they restore wild-type cell cycle progression to free-living Δ cbrA cells. Biochemical characterization of the S. meliloti hybrid histidine kinase CckA in vitro demonstrates that it has both kinase and phosphatase activities. Specifically, CckA on its own has autophosphorylation activity, and phosphatase activity is induced by the second messenger c-di-GMP. Importantly, the CckA A373S suppressor protein of Δ cbrA has a significant loss in kinase activity, and this is predicted to cause decreased CtrA activity in vivo . These findings deepen our understanding of the CbrA regulatory pathway and open new avenues for further molecular characterization of a network pivotal to the free-living cell cycle and symbiotic differentiation of S. meliloti .IMPORTANCE Sinorhizobium meliloti is a soil bacterium able to form a nitrogen-fixing symbiosis with certain legumes, including the agriculturally important Medicago sativa . It provides ammonia to plants growing in nitrogen-poor soils and is therefore of agricultural and environmental significance as this symbiosis negates the need for industrial fertilizers. Understanding mechanisms governing symbiotic development is essential to either engineer a more effective symbiosis or extend its potential to non-leguminous crops. Here, we identify mutations within cell cycle regulators and find that they control cell cycle outcomes during both symbiosis and free-living growth. As regulators within the CtrA two-component signal transduction pathway, this study deepens our understanding of a regulatory network shaping host colonization, cell cycle differentiation, and symbiosis in an important model organism., Competing Interests: The authors declare no conflict of interest.

Meningiomas are the most common intracranial tumors, predominantly affecting adults, with a higher incidence in female and elderly populations. Despite their prevalence, research on neurocognitive impairment in meningioma patients remains limited compared to intra-axial tumors such as gliomas. We conducted a comprehensive systematic review of the current literature on neurocognitive outcomes in meningioma patients pre- and post-surgery. Our review revealed significant disparities in reported neurocognitive outcomes, with prospective studies suggesting tumor-related factors as the primary contributors to postoperative deficits, while retrospective studies imply surgical intervention plays a significant role. Regardless of study design or specifics, most studies lack baseline preoperative neurocognitive assessments and standardized protocols for evaluating neurocognitive function. To address these gaps, we advocate for standardized neurocognitive assessment protocols, consensus on neurocognitive domains to be targeted in this population by tailored test batteries, and more prospective studies to elucidate correlations between tumor characteristics, patient attributes, surgical interventions, neurocognitive status, and planning for implementing tailored neurocognitive rehabilitation strategies early in the postoperative course which is crucial for achieving optimal long-term neurocognitive outcomes and enhancing patients' quality of life., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Depression is prevalent in epilepsy patients and their intracranial brain activity recordings can be used to determine the types of brain activity that are associated with comorbid depression. We performed case-control comparison of spectral power and phase amplitude coupling (PAC) in 34 invasively monitored drug resistant epilepsy patients' brain recordings. The values of spectral power and PAC for one-minute segments out of every hour in a patient's study were correlated with pre-operative assessment of depressive symptoms by Beck Depression Inventory-II (BDI). We identified an elevated PAC signal (theta-alpha-beta phase (5-25 Hz)/gamma frequency (80-100 Hz) band) that is present in high BDI scores but not low BDI scores adult epilepsy patients in brain regions implicated in primary depression, including anterior cingulate cortex, amygdala and orbitofrontal cortex. Our results showed the application of PAC as a network-specific, electrophysiologic biomarker candidate for comorbid depression and its potential as treatment target for neuromodulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The Mapping Imaging Spectrometer for Europa (MISE) is an infrared compositional instrument that will fly on NASA's Europa Clipper mission to the Jupiter system. MISE is designed to meet the Level-1 science requirements related to the mission's composition science objective to "understand the habitability of Europa's ocean through composition and chemistry" and to contribute to the geology science and ice shell and ocean objectives, thereby helping Europa Clipper achieve its mission goal to "explore Europa to investigate its habitability." MISE has a mass of 65 kg and uses an energy per flyby of 75.2 W-h. MISE will detect illumination from 0.8 to 5 μm with 10 nm spectral resolution, a spatial sampling of 25 m per pixel at 100 km altitude, and 300 cross-track pixels, enabling discrimination among the two principal states of water ice on Europa, identification of the main non-ice components of interest: salts, acids, and organics, and detection of trace materials as well as some thermal signatures. Furthermore, the spatial resolution and global coverage that MISE will achieve will be complemented by the higher spectral resolution of some Earth-based assets. MISE, combined with observations collected by the rest of the Europa Clipper payload, will enable significant advances in our understanding of how the large-scale structure of Europa's surface is shaped by geological processes and inform our understanding of the surface at microscale. This paper describes the planned MISE science investigations, instrument design, concept of operations, and data products., Competing Interests: Competing InterestsThe authors have no competing interests to declare that are relevant to the content of this article., (© The Author(s) 2024.)

Objective: Epilepsy is one of the most common reasons for referral for a pediatric neuropsychological evaluation due its high prevalence in childhood and our well-established clinical role in tertiary care settings. Emerging evidence indicates that racial and ethnic minority populations experience increased epilepsy burden compared with White peers. Although there has been heightened recognition in our specialty regarding the dire need for culturally and linguistically responsive evaluations, the scientific evidence to support effective neuropsychological service delivery for bi/multilingual and bi/multicultural youth with epilepsy is comparatively scant and of poor quality. As a result, significant patient and clinical challenges exist, particularly in high stakes presurgical pediatric epilepsy evaluations of bi/multilingual and bi/multicultural children., Method: Given that Spanish is the most common language spoken in the United States after English, this paper will focus on Spanish and English measures, but will provide evidence-based practice considerations that can inform practices with other non-English speaking communities. Cultural and linguistic factors that affect clinical decision-making regarding test selection, test interpretation, and feedback with families are highlighted., Results: We offer a review of neuropsychological profiles associated with pediatric epilepsy as well as a flexible, multimodal approach for the assessment of linguistically and culturally diverse children with epilepsy based on empirical evidence and the clinical experiences of pediatric neuropsychologists from diverse backgrounds who work with children with epilepsy., Conclusion: Limitations to this approach are discussed, including the lack of available measures and resources for culturally and linguistically diverse pediatric populations. A case illustration highlights a culturally informed assessment approach., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Clinical neuropsychology has been a valuable asset to neurologic surgery, contributing to lateralization and localization of pathologic brain tissue, identification of eloquent cortex, and evaluation of postoperative neuropsychological functioning. Moreover, neuropsychologists provide empirically driven interventions aimed at supporting preparation and/or recovery of neurosurgery patients. Nonetheless, several challenges may limit the reliability, validity, and generalizability of the assessment data obtained and reduce the usefulness of other neuropsychological services provided. Specifically, linguistic, cultural, educational, and other biases associated with demographic characteristics can lead to a narrowed view of an individual's life experiences, which must be confronted to fulfill the mission of ensuring that all patients have access to care that is appropriate to their needs. Instead of perceiving these challenges as insurmountable barriers, such issues can be viewed as opportunities to catalyze change and foster innovation for the future of neuropsychological care in neurosurgical settings. In addition to reviewing the possible mechanisms of these obstacles, the current article offers tangible solutions at both a macro level (e.g., discipline-wide transformations) and micro level (e.g., individualized patient-centric approaches). Outlined are practical techniques to potentially improve consensus and standardization of methods, advance and globalize research, expand representativeness of measures and practices to serve diverse individuals, and increase treatment adherence through engagement of patients and their families., (Copyright © 2022. Published by Elsevier Inc.)

Over the last century, collaboration between clinical neuropsychologists and neurosurgeons has advanced the state of the science in both disciplines. These advances have provided the field of neuropsychology with many opportunities for innovation in the care of patients prior to, during, and following neurosurgical intervention. Beyond giving a general overview of how present-day advances in technology are being applied in the practice of neuropsychology within a neurological surgery department, this article outlines new developments that are currently unfolding. Improvements in remote platform, computer interface, "real-time" analytics, mobile devices, and immersive virtual reality have the capacity to increase the customization, precision, and accessibility of neuropsychological services. In doing so, such innovations have the potential to improve outcomes and ameliorate health care disparities., (Copyright © 2022. Published by Elsevier Inc.)

The disciplines of neuropsychology and neurosurgery have a history of partnership that has improved prognoses for patients with neurologic diagnoses that once had poor outcomes. This article outlines the evolution of this relationship and describes the current role that clinical neuropsychology has within a department of neurological surgery across the preoperative, intraoperative, and postoperative stages of treatment. Understanding the foundations of collaboration between neuropsychology and neurosurgery contextualizes present challenges and future innovations for advancing excellence along the continuum of care for all neurosurgical patients., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: Compare the detection rate of seizures on scalp EEG with simultaneous intracranial stereo EEG (SEEG) recordings., Methods: Twenty-seven drug-resistant epilepsy patients undergoing SEEG with simultaneous scalp EEG as part of their surgical work-up were included. A total of 172 seizures were captured., Results: Of the 172 seizures detected on SEEG, 100 demonstrated scalp ictal patterns. Focal aware and subclinical seizures were less likely to be seen on scalp, with 33% of each observed when compared with focal impaired aware (97%) and focal to bilateral tonic-clonic seizures (100%) (P < 0.001). Of the 72 seizures without ictal scalp correlate, 32 demonstrated an abnormality during the SEEG seizure that was identical to an interictal abnormality. Seizures from patients with MRI lesions were statistically less likely to be seen on scalp than seizures from nonlesional patients (P = 0.0162). Stereo EEG seizures not seen on scalp were shorter in duration (49 seconds) compared with SEEG seizures seen on scalp (108.6 seconds) (P < 0.001)., Conclusions: Scalp EEG is not a sensitive tool for the detection of focal aware and subclinical seizures but is highly sensitive for the detection of focal impaired aware and focal to bilateral tonic-clonic seizures. Longer duration of seizure and seizures from patients without MRI lesions were more likely to be apparent on scalp. Abnormalities seen interictally may at times represent an underlying seizure. The cognitive, affective, and behavioral long-term effects of ongoing difficult-to-detect seizures are not known., Competing Interests: F. E. Panov has received lecture fees from Zimmer Biomet and Neuropace, outside the related work. S. Ghatan has received personal fees from Neuropace, outside the submitted work. J. Y. Yoo has received personal compensation for serving on the advisory board of Zimmer Biomet. The other authors have no funding or conflicts of interest to disclose., (Copyright © 2020 by the American Clinical Neurophysiology Society.)

Decline in cognitive functioning among rescue and recovery workers who responded in the aftermath of the September 11, 2001, World Trade Center (WTC) attacks is of emerging interest. Responders are vulnerable to cognitive decline from exposure to airborne toxins present at the WTC site, as well as from WTC-related mental and physical health conditions. To better understand the relationship between occupational WTC exposure, mental health, physical health and subjective cognitive functioning, we examined the mediating role of health status in the association between exposure and subjective cognitive concerns in a multi-site, longitudinal investigation of the WTC General Responder cohort (n = 16,380 responders; n = 58,575 visits) for the period 2002-2015. Through latent class analyses, we identified a four-level marker of cognitive concerns based on information from a Self-Administered Mental Health Questionnaire. Using generalized linear mixed models with random intercepts, we observed that a higher intensity WTC exposure composite was associated with greater cognitive concerns, and that this association was operating almost entirely through mental health comorbidities, not physical health comorbidities. In fully adjusted models, the inclusion of probable depression, anxiety, PTSD and use of psychotropic medications attenuated the association between highest WTC exposure and greatest cognitive concerns. Physical health did not appear to be on the pathway between WTC exposure and cognitive concerns. Understanding the underlying sources of cognitive concerns may help identify vulnerable members of the General Responder cohort and potentially aid clinical decision-making, such as treatment choice and enhanced screening options. Earlier diagnosis and symptom treatment may help preserve functional independence., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: In pediatric neuropsychology multiple barriers such as long wait times until an appointment, insurance coverage, and limited providers who are bilingual/bicultural or who sub-specialize in pediatric neuropsychology, often slow families from receiving diagnoses and interventions in a timely and affordable manner. This paper focuses on increasing accessibility through the development of a video-based, pediatric teleneuropsychology (TeleNP) practice model that was developed in a private practice 2 years before the COVID-19 pandemic., Method: 'Design thinking' methodology to problem-solving was utilized to innovate the traditional neuropsychology practice model in under-served areas who may have limited financial and healthcare resources. The practice model approach to include a virtual diagnostic clinic with increased patient and provider efficiency was created to enhance accessibility for patients and sustainability for providers., Results: Video-based TeleNP screenings were conducted for 67 children with developmental (i.e., attention deficit hyperactivity disorder, autism spectrum disorder) and language disorders, as well as concussion and psychiatric diagnoses. Additional comorbidities were identified in 65.6% of children. Follow-up data approximately 2 months later revealed 98.5% of children were receiving new interventions as a result of the video-based TeleNP assessment., Conclusion: Video-based TeleNP benefits the consumer as it can reduce wait times, decrease family financial burden (i.e., travel and parent time off work), expedite referrals for interventions, and provide geographically under-served populations access to providers who are linguistically and culturally responsive. For providers, this model revealed improvements with direct implications for cost-saving, thereby facilitating long-term economic sustainability within a private practice healthcare marketplace., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Host-associated microbiomes, the microorganisms occurring inside and on host surfaces, influence evolutionary, immunological, and ecological processes. Interactions between host and microbiome affect metabolism and contribute to host adaptation to changing environments. Meta-analyses of host-associated bacterial communities have the potential to elucidate global-scale patterns of microbial community structure and function. It is possible that host surface-associated (external) microbiomes respond more strongly to variations in environmental factors, whereas internal microbiomes are more tightly linked to host factors., Results: Here, we use the dataset from the Earth Microbiome Project and accumulate data from 50 additional studies totaling 654 host species and over 15,000 samples to examine global-scale patterns of bacterial diversity and function. We analyze microbiomes from non-captive hosts sampled from natural habitats and find patterns with bioclimate and geophysical factors, as well as land use, host phylogeny, and trophic level/diet. Specifically, external microbiomes are best explained by variations in mean daily temperature range and precipitation seasonality. In contrast, internal microbiomes are best explained by host factors such as phylogeny/immune complexity and trophic level/diet, plus climate., Conclusions: Internal microbiomes are predominantly associated with top-down effects, while climatic factors are stronger determinants of microbiomes on host external surfaces. Host immunity may act on microbiome diversity through top-down regulation analogous to predators in non-microbial ecosystems. Noting gaps in geographic and host sampling, this combined dataset represents a global baseline available for interrogation by future microbial ecology studies.

Direct electrical stimulation (DES) is sometimes used in epilepsy surgery to identify areas that may result in language deficits if resected. Extraoperative language mapping is usually performed using electrocorticography (ECOG) - grids and strip electrodes; however, given the better safety profile of stereoelectroencephalogaphy (SEEG), it would be desirable to determine if mapping using SEEG is also effective. We report a case series of fifteen patients that underwent language mapping with either ECOG (5), SEEG (9), or both (1). Six patients in the SEEG group underwent resection or ablation with only mapping via SEEG. No patients in the SEEG group that underwent resective or ablative surgery experienced persistent language deficits. These results suggest that language mapping with SEEG may be considered as a clinically useful alternative to language mapping with ECOG., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The authors sought to determine baseline neurocognition before transcatheter aortic valve replacement (TAVR) and its correlations with pre-TAVR brain imaging., Background: TAVR studies have not shown a correlation between diffusion-weighted image changes and neurocognition. The authors wanted to determine the extent to which there was already impairment at baseline that correlated with cerebrovascular disease., Methods: SENTINEL (Cerebral Protection in Transcatheter Aortic Valve Replacement) trial patients had cognitive assessments of attention, processing speed, executive function, and verbal and visual memory. Z-scores were based on normative means and SDs, combined into a primary composite z-score. Brain magnetic resonance images were obtained pre-TAVR on 3-T scanners with a T2 fluid-attenuated inversion recovery (FLAIR) sequence. Scores ≤-1.5 SD below the normative mean (7th percentile) were considered impairment. Paired t tests compared within-subject scores, and chi-square goodness-of-fit compared the percentage of subjects below -1.5 SD. Correlation and regression analyses assessed the relationship between neurocognitive z-scores and T2 lesion volume., Results: Among 234 patients tested, the mean composite z-score was -0.65 SD below the normative mean. Domain scores ranged from -0.15 SD for attention to -1.32 SD for executive function. On the basis of the ≥1.5 SD normative reference, there were significantly greater percentages of impaired scores in the composite z-score (13.2%; p = 0.019), executive function (41.9%; p < 0.001), verbal memory (p < 0.001), and visual memory (p < 0.001). The regression model between FLAIR lesion volume and baseline cognition showed statistically significant negative correlations., Conclusions: There was a significant proportion of aortic stenosis patients with impaired cognition before TAVR, with a relationship between baseline cognitive function and lesion burden likely attributable to longstanding cerebrovascular disease. These findings underscore the importance of pre-interventional testing and magnetic resonance imaging in any research investigating post-surgical cognitive outcomes in patients with cardiovascular disease., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

In adults, left temporal lobe pathology is typically associated with verbal memory deficits, whereas right temporal lobe pathology is thought to produce visual memory deficits in right-handed individuals. However, in children and adolescents with temporal lobe pathology, conclusions regarding material specificity of memory deficits remain unclear. The goal of the present case series is to examine the profile of verbal and visual memory impairment in children with temporal lobe tumors. Three patients with identified right temporal tumors and three patients with left temporal tumors are included. The Wide Range Assessment of Memory and Learning-Second Edition (WRAML-2) was administered as part of a larger neuropsychological battery. As anticipated, participants with right temporal lesions showed impaired visual memory relative to intact verbal memory. Interestingly, although the discrepancies between verbal and visual indices were less extreme, those with left temporal lesions showed a similar memory profile. These seemingly counterintuitive findings among left temporal tumor patients likely reflect less hemispheric specialization in children in comparison to adults and the fact that early developmental lesions in the left hemisphere may lead to functional reorganization of language-based skills.

We aimed to investigate functional connectivity and variability across multiple frequency bands in brain networks underlying cognitive deficits in primary-progressive multiple sclerosis (PP-MS) and to explore how they are affected by the presence of cortical lesions (CLs). We analyzed functional connectivity and variability (measured as the standard deviation of BOLD signal amplitude) in resting state networks (RSNs) associated with cognitive deficits in different frequency bands in 25 PP-MS patients (12 M, mean age 50.9 ± 10.5 years) and 20 healthy subjects (9 M, mean age 51.0 ± 9.8 years). We confirmed the presence of a widespread cognitive deterioration in PP-MS patients, with main involvement of visuo-spatial and executive domains. Cognitively impaired patients showed increased variability, reduced synchronicity between networks involved in the control of cognitive macro-domains and hyper-synchronicity limited to the connections between networks functionally more segregated. CL volume was higher in patients with cognitive impairment and was correlated with functional connectivity and variability. We demonstrate, for the first time, that a functional reorganization characterized by hypo-synchronicity of functionally-related/hyper-synchronicity of functionally-segregated large scale networks and an abnormal pattern of neural activity underlie cognitive dysfunction in PP-MS, and that CLs possibly play a role in variability and functional connectivity abnormalities.

The Boston Naming Test (BNT) was designed to present items in order of difficulty based on word frequency. Changes in word frequencies over time, however, would frustrate extrapolation in clinical and research settings based on the theoretical construct because performance on the BNT might reflect changes in ecological frequency of the test items, rather than performance across items of increasing difficulty. This study identifies the ecological frequency of BNT items at the time of publication using the American Heritage Word Frequency Book and determines changes in frequency over time based on the frequency distribution of BNT items across a current corpus, the Corpus of Contemporary American English. Findings reveal an uneven distribution of BNT items across 2 corpora and instances of negligible differentiation in relative word frequency across test items. As BNT items are not presented in order from least to most frequent, clinicians and researchers should exercise caution in relying on the BNT as presenting items in increasing order of difficulty. A method is proposed for distributing confrontation-naming items to be explicitly measured against test items that are normally distributed across the corpus of a given language.

Children and adolescents with epilepsy are known to demonstrate executive function deficits. Despite prior work that has shown that cognitive estimation tasks are sensitive to executive dysfunction in children, such tasks have not been studied in children with epilepsy. This is particularly important given the fact that executive tasks have heretofore shown poor ecological validity, and it has been speculated that estimation tasks may show stronger ecological validity than other executive tests. One hundred and thirteen clinically referred children and adolescents with epilepsy were included. The Biber Cognitive Estimations Test was sensitive to cognitive dysfunction, with about half showing impairments on this task in comparison to age-matched normative data; the most frequently impaired subscales were quantity estimation and time estimation. Moreover, the Biber Cognitive Estimation Test showed moderate correlations with not only overall intellectual functions and academic achievement but also other commonly administered tests of executive functions, including digit span, Trailmaking, and the Tower of London but not with the contingency naming test. Cognitive estimations were also modestly correlated with age of epilepsy onset but not other epilepsy-severity variables such as number of antiepilepsy drugs (AEDs) or seizure frequency. Unfortunately, the hypothesis that the Biber Cognitive Estimation Test would show strong ecological validity was not supported, as it showed weak relations with parent-reported executive function deficits. The significance and limitations of this investigation are discussed.

Background: Identification and quantification of fibrillar amyloid in brain using positron emission tomography (PET) imaging and Amyvid™ ([18 F] Amyvid, [18 F] florbetapir, 18 F-AV-45) was recently approved by the US Food and Drug Administration as a clinical tool to estimate brain amyloid burden in patients being evaluated for cognitive impairment or dementia. Imaging with [18 F] florbetapir offers in vivo confirmation of the presence of cerebral amyloidosis and may increase the accuracy of the diagnosis and likely cause of cognitive impairment (CI) or dementia. Most importantly, amyloid imaging may improve certainty of etiology in situations where the differential diagnosis cannot be resolved on the basis of standard clinical and laboratory criteria., Results: A consecutive case series of 30 patients (age 50-89; 16 M/14 F) were clinically evaluated at a cognitive evaluation center of urban dementia center and referred for [18 F] florbetapir PET imaging as part of a comprehensive dementia workup. Evaluation included neurological examination and neuropsychological assessment by dementia experts. [18 F] florbetapir PET scans were read by trained nuclear medicine physicians using the qualitative binary approach. Scans were rated as either positive or negative for the presence of cerebral amyloidosis. In addition to a comprehensive dementia evaluation, post [18 F] florbetapir PET imaging results caused diagnoses to be changed in 10 patients and clarified in 9 patients. Four patients presenting with SCI were negative for amyloidosis. These results show that [18 F] florbetapir PET imaging added diagnostic clarification and discrimination in over half of the patients evaluated., Conclusions: Amyloid imaging provided novel and essential data that: (1) caused diagnosis to be revised; and/or (2) prevented the initiation of incorrect or suboptimal treatment; and/or (3) avoided inappropriate referral to an anti-amyloid clinical trial.

The relations between attention-deficit hyperactivity disorder (ADHD) and motor skills are well documented, with research indicating both early and lifelong motor deficits in children with this disorder. Despite neuroanatomical and neurodevelopmental differences, which may predict differential rates of motor impairment between ADHD subtypes, evaluation of motor skill deficits in children with different presentations are limited in scope and equivocal in findings. The present investigation evaluated early motor development history and objectively measured motor skills in children with ADHD-Inattentive subtype (ADHD-I) and ADHD-Combined subtype (ADHD-C). One hundred and one children with ADHD-I (n = 53) and ADHD-C (n = 48) were included. Variables included Full-Scale IQ (FSIQ), history of motor delays, and utilization of early intervention services, as well as objectively measured motor impairment as assessed via tasks of fine-motor coordination. No between-group differences were found for FSIQ, but differences in age emerged, with the ADHD-I group being older. No differences in early motor delays were observed, though a considerably higher percentage of children with ADHD-C demonstrated early difficulties. Surprisingly, although children and adolescents with ADHD-C reported more frequent utilization of early intervention services, those with ADHD-I exhibited greater levels of current motor impairment on objective tasks. Given the over-representation of older children in the ADHD-I group, data were reanalyzed after excluding participants older than 10 years of age. Although the between-group differences were no longer significant, more than twice the number of parents of children with ADHD-C reported early motor delays, as compared with the ADHD-I group. Overall, children with ADHD-I were more likely to exhibit current objectively measured motor impairment, possibly due to later identification, less intervention, and/or different neurodevelopmental substrates underlying this disorder subtype.

The present study examined the relationship between various sociocultural factors (e.g., acculturation, education), neurological variables (e.g., epilepsy duration and seizure frequency) and nonverbal neuropsychological (NP) test performance in a sample of 305 Latino/a and Non-Latino/a White adults with and without epilepsy. All participants completed nonverbal NP measures of visuospatial skills, memory, executive functioning, and psychomotor speed. An acculturation scale was administered to Spanish-speaking epilepsy patients and controls. Education was strongly correlated with performance on all but one of the nonverbal measures across the entire sample. Among Spanish-speaking Latino/a patients with epilepsy, level of acculturation to U.S. culture was associated with a measure of behavioral inflexibility (p < .05) and with a composite measure of nonverbal NP test performance (p < .05). Finally, the results of hierarchical regression models showed that sociocultural factors accounted for a greater proportion of variance in nonverbal NP test performance than did neurological factors. These results provide further evidence that sociocultural factors are strong predictors of NP test performance in clinical populations, even on nonverbal tests. Assessment of acculturation may be as critical as assessment of disease factors in interpreting cognitive performance in Latino/a individuals.

Abnormal neurodevelopment has been widely reported in combined methylmalonic aciduria (MMA) and homocystinuria, cblC type (cblC disease), but neurodevelopmental phenotypes in cblC have not previously been systematically studied. We sought to further characterize developmental neurology in children with molecularly-confirmed cblC. Thirteen children at our center with cblC, born since implementation of expanded newborn screening in New York State, undertook standard-of-care evaluations with a pediatric neurologist and pediatric ophthalmologist. At most recent follow-up (mean age 50 months, range 9-84 months), of twelve children with early-onset cblC, three (25%) had a history of clinical seizures and two (17%) meet criteria for microcephaly. A majority of children had hypotonia and nystagmus. Twelve out of thirteen (92%) underwent neurodevelopmental evaluation (mean age 41 months; range 9-76 months), each child tested with standardized parental interviews and, where possible, age- and disability-appropriate neuropsychological batteries. All patients showed evidence of developmental delay with the exception of one patient with a genotype predictive of attenuated disease and near-normal biochemical parameters. Neurodevelopmental deficits were noted most prominently in motor skills, with relative preservation of socialization and communication skills. Nine children with early-onset cblC underwent magnetic resonance imaging and spectroscopy (MRI/MRS) at mean age of 47 months (range 6-81 months); common abnormalities included callosal thinning, craniocaudally short pons, and increased T2 FLAIR signal in periventricular and periatrial white matter. Our study further characterizes variable neurodevelopmental phenotypes in treated cblC, and provides insights into the etiopathogenesis of disordered neurodevelopment frequently encountered in cblC. Plasma homocysteine and MMA, routinely measured at clinical follow-up, may be poor predictors for neurodevelopmental outcomes. Additional data from large, prospective, multi-center natural history studies are required to more accurately define the role of these metabolites and others, as well as that of other genetic and environmental factors in the etiopathogenesis of the neurologic components of this disorder., (© 2013.)

The assessment of effort is an important aspect of a comprehensive neuropsychological evaluation, as this can significantly impact data interpretation. While recent work has validated the appropriateness of adult-derived cutoffs for standalone effort measures in younger populations, little research has focused on embedded effort measures in children. The present study includes 54 clinically referred children and adolescents (32 males/22 females; aged 6-17) with a confirmed diagnosis of epilepsy. Reliable Digit Spans (RDSs) were calculated and the Test of Memory Malingering (TOMM) was administered in the context of a comprehensive neuropsychological evaluation. Using a previously published RDS cutoff of ≤6, a pass rate of only 65% was obtained, well below the recommended 90% pass rate for an effective effort index. In contrast, when adult criteria were used on TOMM Trial 2, a 90% pass rate was observed. RDS scores were significantly correlated with IQ estimates (r = .59, p < .001) and age (r = .61, p < .001). The difference between RDS and the TOMM on the participant outcome was statistically significant (χ(2) = 9.05, p = .003). These results suggest that RDS appears to yield a large number of false positives and, therefore, may be of limited utility in detecting poor effort in a pediatric epilepsy population. These findings likely extend to other pediatric populations that are known to have significant cognitive loss.

Attention-deficit hyperactivity disorder (ADHD) is a frequent comorbidity in children with epilepsy. Despite similarities in behavioral manifestations of inattention and hyperactivity, it is unclear whether the neuropsychological endophenotypes of children with developmental ADHD differ from those with ADHD in the context of epilepsy. The present study compared groups of clinically referred children with both ADHD-Inattentive subtype (ADHD-I) and ADHD-Combined subtype (ADHD-C) to children with ADHD-I and ADHD-C and epilepsy on neuropsychological measures of intellectual functioning, auditory attention, working memory, and sustained attention and response inhibition. Those with ADHD and epilepsy performed more poorly on measures of intellectual function (e.g., Full-Scale IQ, Verbal IQ, Performance IQ) as well as auditory attention and working memory. Differences across the groups were also seen on a continuous performance test. Follow-up correlational analyses showed that variables such as seizure frequency and number of antiepilepsy medications predicted cognitive dysfunction in the epilepsy groups. Overall results suggest that the neuropsychological endophenotypes in developmental ADHD versus ADHD in epilepsy differ with seizure-related variables predicting cognitive dysfunction.

Children and adolescents with epilepsy are known to demonstrate executive function dysfunction, including working memory deficits and planning deficits. Accordingly, assessing specific executive function skills is important when evaluating these individuals. The present investigation examined the utility of two measures of executive functions-the Tower of London and the Behavioral Rating Inventory of Executive Functioning (BRIEF)-in a pediatric epilepsy sample. Ninety clinically referred children and adolescents with seizures were included. Both the Tower of London and BRIEF identified executive dysfunction in these individuals, but only the Tower of London variables showed significant relations with epilepsy severity variables such as age of epilepsy onset, seizure frequency, number of antiepileptic medications, etc. Further, the Tower of London and BRIEF variables were uncorrelated. Results indicate that objective measures of executive function deficits are more closely related to epilepsy severity but may not predict observable deficits, as reported by parents. Comprehensive evaluation of such deficits, therefore, should include both objective measures as well as subjective ratings from caregivers.

The authors characterized the cognitive, adaptive, and behavioral sequelae of Coffin-Siris (CS) syndrome and epilepsy in a 7.5-year-old child. Little is known about the early neurobehavioral presentation of CS. Clinical features consistent with this genetic anomaly include underdeveloped tips and nails of the fifth fingers, extended infranasal depression, and craniofacial abnormalities. MRI findings often reveal callosal agenesis. The authors conducted a neuropsychological evaluation and obtained parental ratings of behavioral and adaptive functioning. Attentional abilities were limited. As assessed by the Mullen Scales of Early Learning, receptive language abilities (age equivalent [AE]: 3-3) were relatively stronger than expressive skills (AE: 1-4). Adaptive functioning was low across all domains (Vineland Adaptive Behavior Composite AE: 1-9). On the Behavior Assessment for Children (BASC-2), social skills dysfunction, stereotyped and self-stimulatory behaviors, restricted interests, ritualistic play, and inappropriate object usage were noted. No significant mood disturbances were endorsed. Study findings indicate a diffuse pattern of neurobehavioral deficits in a child with CS and epilepsy. Further clinical assessment and research should include multidimensional assessment techniques, including evaluation of adaptive behavior, in an effort to capture the full range developmental sequelae in children with CS.

Tuberous sclerosis complex (TSC) is often associated with epilepsy, mental retardation, and autism spectrum disorders (ASDs). Thus, screening for ASDs is important when evaluating these individuals. We examined the utility of the Social Responsiveness Scale (SRS) and Social Communication Questionnaire (SCQ), two measures for screening for ASDs, in a TSC population. Twenty-one children were evaluated, with 52.4% classified as having ASDs on the SRS and 42.9% classified as such on the SCQ. Number of antiepileptic drugs significantly correlated with SRS Total score, as did level of intellectual functioning. Evidence for convergent validity was obtained between the SRS and SCQ Total scores (r=0.605). Moreover, all SRS subscales correlated with SCQ Total score (r>0.400). All SCQ subscales except for Communication correlated with SRS total. Overall, the results demonstrate that these questionnaires appear to be effective screens for ASDs in a TSC population and are measuring similar constructs., (Copyright 2010 Elsevier Inc. All rights reserved.)

Few neuropsychological tests have been developed specifically for non-English speakers. Rather, assessment measures are often derived from English source texts (STs) and translated into foreign language target texts (TTs). An abundant literature describes the potential for translation error occurring in test construction. While the neuropsychology community has striven to correct these inadequacies, interdisciplinary approaches to test translation have been largely ignored. Translation studies, which has roots in linguistics, semiotics, computer science, anthropology, and philosophy, may provide a much-needed framework for test development. We aim to apply specific aspects of Descriptive Translation Studies to present unique and heretofore unapplied frameworks to the socio-cultural conceptualizations of translated tests. In doing so, a more theoretical basis for test construction will be explored. To this end, translation theory can provide valuable insights toward the development of linguistically and culturally relevant neuropsychological test measures suitable for an increasingly diverse patient base.

Single shot diffraction patterns using a 250-fs-long electron beam have been obtained at the UCLA Pegasus laboratory. High quality images with spatial resolution sufficient to distinguish closely spaced peaks in the Debye-Scherrer ring pattern have been recorded by scattering the 1.6 pC 3.5 MeV electron beam generated in the rf photoinjector off a 100-nm-thick Au foil. Dark current and high emittance particles are removed from the beam before sending it onto the diffraction target using a 1 mm diameter collimating hole. These results open the door to the study of irreversible phase transformations by single shot MeV electron diffraction.

Fatigue and quality of life are significant concerns in adult multiple sclerosis (MS) but little is known about these factors in pediatric MS. The present investigation evaluates fatigue and quality of life in 51 pediatric MS patients to determine the rate of fatigue and reduced quality of life and assesses the relations between these variables and clinical factors. Fatigue and quality of life were assessed by self- and parent-report via the PedsQL Multidimensional Fatigue Scale and the PedsQL Quality of Life Scale. One-sample t-tests determined if scores were below published data for healthy individuals. Moreover, scores falling one standard deviation from norms were considered mildly affected, with severe difficulties being defined as scores falling two or more standard deviations from norms. Associations between self- and parent-reported difficulties and clinical factors were examined via Pearson correlation analyses. In comparison with healthy samples, pediatric MS patients reported greater difficulties with respect to fatigue, sleep, cognition, physical limitations, and academics. In addition to significant difficulties on these factors, parents reported problems with respect to emotional functioning, and tended to report greater fatigue, sleep, and cognitive difficulties than were self-reported. Expanded Disability Status Scale score was the only neurologic variable significantly related to fatigue or quality of life scores. Fatigue was significantly correlated with reports of sleep difficulties, cognitive problems, and quality of life variables. These findings suggest that fatigue and poorer quality of life is a clear concern in pediatric MS, and is related to overall physical disability.

Effort assessment is of particular importance in pediatric epilepsy where neuropsychological findings may influence treatment decisions, especially if surgical interventions are being considered. The present investigation examines the Test of Memory Malingering (TOMM) in 60 children and adolescents with epilepsy. The overall pass rate for the sample was 90%. TOMM scores were unrelated to age, though there was a significant correlation between TOMM Trial 2 scores and intelligence estimates. Overall, the TOMM appears to be a valid measure of effort in young epilepsy patients, though caution should be used when interpreting scores for those with very low IQ, especially if behavioral problems are also evident. Caution should also be exercised in interpreting scores in children with ongoing interictal epileptiform activity that may disrupt attention.

The Neuropsychological Screening Battery for Hispanics (NeSBHIS) was developed to address the growing need for linguistically appropriate Spanish-language assessment measures. Despite the potential benefits to clinical practice, no prior study has assessed its diagnostic validity in populations with epilepsy. One hundred and fifteen patients with confirmed epilepsy were evaluated via the NeSBHIS; these data were standardized according to age- and education-based norms. Performance decrements were observed in more than 40% of participants on measures of processing speed and naming. Deficits in verbal and visual recall were also exhibited by 29 and 26% of the sample, respectively. No significant differences in test performance emerged between patients with VEEG evidence of left (N=48) versus right (N=24) temporal lobe epilepsy. Although the NeSBHIS is sensitive to the cognitive impairments commonly observed in populations with epilepsy, there are limitations to its ability to identify lateralized neuropsychological impairment in patients with temporal lobe epilepsy.

Epidemiological studies suggest that the Hispanic population is at increased risk for neurological disorders. Yet, few assessment measures have been developed for, adapted to, or normalized with Spanish-speakers. The Neuropsychological Screening Battery for Hispanics (NeSBHIS) was developed to address the lack of resources available to this underserved community. Although the NeSBHIS possesses robust construct validity and clinical utility in a community-based sample, these properties remain largely untested in neurological populations. One hundred and twenty-seven Spanish-speaking Hispanic patients with confirmed epilepsy (mean age = 37.8, SD = 13.3) were evaluated using the NeSBHIS. All participants self-identified as "Hispanic" and immigrated from Spanish-speaking countries. Data were analyzed using confirmatory factor analysis with the a priori assumption that variables would load according to theoretical expectations reported by Pontón and colleagues (2000). The overall model fit indices were in the desired range: Comparative Fit Index = 0.936, Tucker Lewis Index = 0.915, RMSEA = 0.090, and SRMR = 0.069. All NeSBHIS subtests loaded significantly (p < .001) on their respective factors; the standardized loadings were high, ranging from 0.562 to 0.995, with the exception of Block Design (-0.308). Overall, findings suggest that the NeSBHIS has robust construct validity in a neurological sample.

Neuropsychologic test scores from a group of children with epilepsy were compared to the standardization sample of the NEPSY: A Developmental Neuropsychological Assessment, a relatively new neuropsychologic testing instrument. Nineteen children with a confirmed diagnosis of epilepsy (11 boys, 8 girls), aged 3-12 years, participated. Attention/executive function, language, sensorimotor, visuospatial, and learning/memory domain scores were examined, as well as individual subtest scores. The mean scores on the attention/executive function, language, and sensorimotor domains were >1.5 standard deviations below the normative mean, and significantly lower than the mean visuospatial domain score (P < 0.05). The mean language domain score was also significantly lower than the learning/memory score (P < 0.05). Mean subdomain scores varied, with impairment on two tasks measuring rapid automatic processing and graphomotor precision, respectively. On the majority of subtests, 15% or more of the sample scored in the impaired range. Associations between patient age, seizure onset age, seizure frequency, and antiepileptic medication status were not associated with outcome, perhaps due in part to the small sample size. The strengths and weaknesses of the NEPSY as a measure of neuropsychologic functioning in children with epilepsy, and its utility in highlighting risks to academic achievement are discussed.

Background: Studies of school-aged children, adolescents, and adults with Attention Deficit/Hyperactivity Disorder (ADHD) have variably shown ADHD-related impairment in both inhibitory control and sustained attention. However, few studies have examined ADHD-associated patterns of performance on these tasks among younger children (below age 7 years)., Methods: A combined continuous performance test and go/no-go task (CPT/GNG) and the Day-Night Stroop Task (DNST) were administered to an ethnically diverse sample of 3.44- to 6.95-year-old children rated by parents and teachers as being either high risk or low risk for ADHD. All children performed the DNST (N = 71) and a subset of the sample (N = 44) performed the CPT/GNG. Analyses assessed task validity as well as the effects of age and risk status., Results: Significant main effects for age and risk status were found on all tasks. In addition, age x condition interactions were found for the CPT and DNST, which suggest that the tasks were sensitive to age-related changes in sustained attention and inhibitory control respectively. No significant risk status x condition interactions were found, suggesting that young children at risk for ADHD do not exhibit specific deficits in either inhibitory control or sustained attention. The most consistent effect related to risk status across tasks was the greater number of errors and longer and more variable reaction times on the part of children at risk for ADHD irrespective of condition., Conclusions: ADHD-associated decrements in performance on these tasks appear to be attributable either to generalized behavioral dysregulation or poor state regulation rather than to deficient inhibitory control.

Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked overgrowth syndrome caused by deletions in glypican 3 (GPC3). SGBS is characterized by pre- and postnatal overgrowth, a characteristic facial appearance, and a spectrum of congenital malformations which overlaps that of other overgrowth syndromes. We performed GPC3 deletion screening on 80 male patients with somatic overgrowth in the following categories: SGBS (n = 19), possible SGBS (n = 26), including families in which individuals had previously been diagnosed with other overgrowth syndromes, and Wiedemann-Beckwith syndrome (WBS) (n = 35). Using exon-specific PCR and Southern blot analysis, we identified seven GPC3 deletions. In most cases a clear X-linked family history was not present. In two cases, GPC3 deletions were identified in patients belonging to pedigrees published previously as other overgrowth syndromes: one with a diagnosis of Sotos syndrome and the other Perlman syndrome with nephroblastomatosis. A third patient developed hepatoblastoma, a tumor type not previously described in SGBS. No GPC3 deletions were identified among the WBS patients. Direct sequencing of all GPC3 exons in the remaining 13 SGBS patients without GPC3 deletions did not identify any further mutations, raising the possibility of alternative silencing mechanisms and/or other genes in the pathogenesis of SGBS. Our results validate the clinical specificity of the facial appearance, skeletal/hand anomalies, and supernumerary nipples in patients with GPC3 deletions. Our data also suggest that nephroblastomatosis and hepatoblastoma are included in the phenotypic spectrum of GPC3 deletions and SGBS, underscoring the importance of tumor surveillance in these children., (Copyright 2001 Wiley-Liss, Inc.)

We measured an emission of 6 mJ/pulse at 13.5 nm produced by the Li(2+) Lyman-? transition excited by a fast capillary discharge, using a lithium hydride capillary. 75% of the energy emanated from a spot size of 0.6 mm. The emission is narrow band and would thus be useful in extreme-ultraviolet lithography imaging systems that use Mo:Si multilayer mirrors. The output within the bandwidth of Mo:Si mirrors was comparable with that of a laser-produced plasma (LPP), and the wallplug efficiency of 0.1% was nearly an order of magnitude better than that of a LPP.

Debris from laser-produced plasmas created with solid Sn and Au targets has been characterized according to speed and particulate size. Conditions for the experiments were those appropriate for producing an optimum laser-produced plasma emission at 13.5 nm for use in extreme-ultraviolet lithography. Results in the form of histogram data show that the speed distribution of the debris particulates is quite varied and in general exhibits an upper limit of ~640 m/s. In the case of Sn a peak in the velocity distribution is observed near 300 m/s. Small particulates, of the order of 1 µm or less, constitute the majority of the particulate emission in both materials. The implications for debris reduction based on the measurements are also discussed.

Studies are performed to determine an upper limit on the optical damage threshold of a soft-x-ray molybdenum-silicon multilayer reflective coating by the use of a 308-nm, 15-ns pulse from a Xe-Cl excimer laser in order to simulate the potential damage induced by the x-ray flux from a pulsed laser-produced plasma. Experimental results yield a value of 0.26 J/cm(2) to produce visible signs of damage as determined by optical microscopy. Experiments are conducted first on silicon, as a reference point of a bulk material, and then applied to molybdenum-silicon in an effort to facilitate a theoretical comparison between a simple and a more complicated material. Theoretical predictions are in reasonable agreement with experimental results, but suggest that a lower value of 0.085 J/cm(2) might cause significant thermal-induced damage.

Laser plasmas are intrinsically an attractive soft-x-ray source for projection lithography. Compact, flexible, and small enough to be dedicated to a single installation, they offer an alternative to costly multi-installation synchrotron sources. For laser plasmas to provide ideal sources of soft x rays for projection lithography, their properties must be tuned to optimize several critical parameters. High x-ray conversion in the spectral band relevant to projection lithography is obviously required and has already received the attention of several studies. However, other features, such as the spectral content and direction of the x-ray emission, the plasma and particulate emission, the technology of the target, and efficient laser design, must also be optimized. No systematic study of all these features specifically for projection lithography has yet been made. It is our purpose to optimize these parameters in a coordinated approach, which leads to the design of a source that satisfies all the demanding requirements of an operating lithographic installation. We make an initial investigation of the plasma and particle emission of plasmas that have previously been shown to be good x-ray converters to the 13-nm band. The importance of the results reported may well force new approaches to the design of laser plasma soft-x-ray sources for projection lithography.

Sixteen cases of terminal deletions and 17 cases of interstitial deletions of the long arm of chromosome 7 have been reported to date. We present two new cases of the former and three of the latter. The somatic changes in these patients are tabulated and an update on the anomalies associated with the various cytogenetic entities is presented. Changes found in over one-third of patients with 7q terminal deletion syndrome include: developmental delay, pre- and postnatal growth retardation, generalized hypotonia, abnormal electroencephalograms with or without seizures, feeding problems in infancy, microcephaly, prominent forehead, ocular hypertelorism, eye defects, broad nasal bridge, bulbous nasal tip, auricular malformations, micrognathia, chest abnormalities, genital malformations in males, and abnormal palmar and plantar creases. Evidence for the localization of the Kidd blood group gene on chromosome 7 distal to band q32, as suggested by previous reports, is reviewed; we conclude that the evidence does not warrant placement of the gene in this region of the genome.

We describe two unrelated patients with a severe form of acrofacial dysostosis. Facial defects in both include coloboma of the lids, micrognathia, lateral oral clefting, palatal clefting, and severe auricular anomalies, with one showing bilateral cleft lip and right oblique facial clefting as well. Both have absent forearms and thumbs. Lower limbs were severely reduced in both infants with the feet attached either to the femur or directly to the trunk. Parental consanguinity was present in one case. The condition in these two infants appears to represent either a severe form of Nager acrofacial dysostosis or a new type of acrofacial dysostosis.

We describe an infant with Hirschsprung disease (congenital aganglionosis of the intestine) involving the colon and terminal ileum. Midtrimester prenatal diagnosis of this disorder in this infant was attempted utilizing amniotic fluid disaccharidase analyses, ultrasound, and amniography. Decreased disaccharidase activities in amniotic fluid have been reported previously in association with other forms of intestinal obstruction. At 15 weeks' gestation, normal amniotic fluid disaccharidase levels were obtained. Serial ultrasound evaluations did not indicate any pathology, and the results from amniography were inconclusive. The implication of the normal disaccharidase values is that Hirschsprung disease may in some cases result from degeneration of intestinal ganglia after 16 weeks' gestation rather than from faulty migration of neural crest cells. The inheritance of Hirschsprung disease is generally consistent with sex-modified multifactorial inheritance with a lower threshold of expression in males. The case we report has a family history of three affected first- and second-degree relatives. Autosomal dominance with variable expressivity is a possible explanation in this family.