Risk of meningomyelocele mediated by the common 22q11.2 deletion.

Meningomyelocele is one of the most severe forms of neural tube defects (NTDs) and the most frequent structural birth defect of the central nervous system. We assembled the Spina Bifida Sequencing Consortium to identify causes. Exome and genome sequencing of 715 parent-offspring trios identified six patients with chromosomal 22q11.2 deletions, suggesting a 23-fold increased risk compared with the general population. Furthermore, analysis of a separate 22q11.2 deletion cohort suggested a 12- to 15-fold increased NTD risk of meningomyelocele. The loss of Crkl, one of several neural tube-expressed genes within the minimal deletion interval, was sufficient to replicate NTDs in mice, where both penetrance and expressivity were exacerbated by maternal folate deficiency. Thus, the common 22q11.2 deletion confers substantial meningomyelocele risk, which is partially alleviated by folate supplementation.

Three genes controlling streptomycin susceptibility in Agrobacterium fabrum.

Streptomycin (Sm) is a commonly used antibiotic for its efficacy against diverse bacteria. The plant pathogen Agrobacterium fabrum is a model for studying pathogenesis and interkingdom gene transfer. Streptomycin-resistant variants of A. fabrum are commonly employed in genetic analyses, yet mechanisms of resistance and susceptibility to streptomycin in this organism have not previously been investigated. We observe that resistance to a high concentration of streptomycin arises at high frequency in A. fabrum, and we attribute this trait to the presence of a chromosomal gene (strB) encoding a putative aminoglycoside phosphotransferase. We show how strB, along with rpsL (encoding ribosomal protein S12) and rsmG (encoding a 16S rRNA methyltransferase), modulates streptomycin sensitivity in A. fabrum. IMPORTANCE The plant pathogen Agrobacterium fabrum is a widely used model bacterium for studying biofilms, bacterial motility, pathogenesis, and gene transfer from bacteria to plants. Streptomycin (Sm) is an aminoglycoside antibiotic known for its broad efficacy against gram-negative bacteria. A. fabrum exhibits endogenous resistance to somewhat high levels of streptomycin, but the mechanism underlying this resistance has not been elucidated. Here, we demonstrate that this resistance is caused by a chromosomally encoded streptomycin-inactivating enzyme, StrB, that has not been previously characterized in A. fabrum. Furthermore, we show how the genes rsmG, rpsL, and strB jointly modulate streptomycin susceptibility in A. fabrum.

Scoping Review on the Diagnosis, Prognosis, and Treatment of Pediatric Disorders of Consciousness.

BACKGROUND AND OBJECTIVES: Comprehensive guidelines for the diagnosis, prognosis, and treatment of disorders of consciousness (DoC) in pediatric patients have not yet been released. We aimed to summarize available evidence for DoC with >14 days duration to support the future development of guidelines for children, adolescents and young adults aged 6 months-18 years. METHODS: This scoping review was reported based on Preferred Reporting Items for Systematic reviews and Meta-Analyses-extension for Scoping Reviews guidelines. A systematic search identified records from 4 databases: PubMed, Embase, Cochrane Library, and Web of Science. Abstracts received 3 blind reviews. Corresponding full-text articles rated as "in-scope" and reporting data not published in any other retained article (i.e., no double reporting) were identified and assigned to 5 thematic evaluating teams. Full-text articles were reviewed using a double-blind standardized form. Level of evidence was graded, and summative statements were generated. RESULTS: On November 9, 2022, 2,167 documents had been identified; 132 articles were retained, of which 33 (25%) were published over the past 5 years. Overall, 2,161 individuals met the inclusion criteria; female patients were 527 of 1,554 (33.9%) cases included, whose sex was identifiable. Of 132 articles, 57 (43.2%) were single case reports and only 5 (3.8%) clinical trials; the level of evidence was prevalently low (80/132; 60.6%). Most studies included neurobehavioral measures (84/127; 66.1%) and neuroimaging (81/127; 63.8%); 59 (46.5%) were mainly related to diagnosis, 56 (44.1%) to prognosis, and 44 (34.6%) to treatment. Most frequently used neurobehavioral tools included the Coma Recovery Scale-Revised, Coma/Near-Coma Scale, Level of Cognitive Functioning Assessment Scale, and Post-Acute Level of Consciousness scale. EEG, event-related potentials, structural CT, and MRI were the most frequently used instrumental techniques. In 29/53 (54.7%) cases, DoC improvement was observed, which was associated with treatment with amantadine. DISCUSSION: The literature on pediatric DoCs is mainly observational, and clinical details are either inconsistently presented or absent. Conclusions drawn from many studies convey insubstantial evidence and have limited validity and low potential for translation in clinical practice. Despite these limitations, our work summarizes the extant literature and constitutes a base for future guidelines related to the diagnosis, prognosis, and treatment of pediatric DoC.

Sleep Characteristics in Pediatric Anti-N-methyl-d-aspartate (NMDA) Receptor Encephalitis: A Retrospective Cohort Study.

Background: Rates of sleep problems in children with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis are unknown. Methods: We used a retrospective observational cohort database of children with a diagnosis of NMDA receptor encephalitis at a single freestanding institution. One-year outcomes were assessed with the pediatric modified Rankin Score (mRS), with 0 to 2 as good and 3 or greater as poor outcome. Results: Ninety-five percent (39/41) of children with NMDA receptor encephalitis had sleep dysfunction at onset; 34% (11/32) reported sleep problems at 1 year. Sleep problems at onset and propofol use were not associated with poor outcomes at 1 year. Poor sleep at 1 year correlated with mRS scores (range 2-5) at 1 year. Discussion: High rates of sleep dysfunction occur in children with NMDA receptor encephalitis. Persistent sleep problems at 1 year may correlate with outcomes as assessed by mRS at 1 year. Further studies comparing the relationship of poor sleep with outcomes in NMDA receptor encephalitis are needed.

Evaluation, Treatment, and Outcomes of Viral and Autoimmune Encephalitis in Children.

Viral encephalitis and autoimmune encephalitis are currently the most common causes of encephalitis. Determining the causative agent is helpful in initiating medical treatment that may help reduce long-term sequelae. Cerebrospinal fluid, neuroimaging, serologic, and electroencephalogram in combination with clinical manifestations play a role in determining the cause of the encephalitis. Although motor dysfunction tends to improve, there is a significant risk of long-term neurologic and cognitive sequelae. These persistent deficits that occur in childhood indicate the importance for ongoing rehabilitative services to maximize functional skills, improve cognitive deficits, and assist with community integration.

Assessment of cognitive status in pediatric anti-NMDA receptor encephalitis during inpatient rehabilitation: A retrospective cohort.

OBJECTIVES: Anti-NMDA receptor autoimmune encephalitis (NMDARE) is a common pediatric encephalitis, resulting in neuropsychiatric symptoms. Predicting severity and course is challenging, with objective cognitive assessments lacking in NMDARE, especially in children. The CASE (Clinical Assessment Scale in Autoimmune Encephalitis) measures severity in autoimmune encephalitis. The CALS (Cognitive and Linguistic Scale) assesses cognitive-linguistic recovery in children with acquired brain injury. This study examines severity and cognitive status in pediatric NMDARE by comparing objectives measures: modified Rankin score (mRS), CASE, and CALS. METHODS: Twenty-one patients were identified via retrospective chart review with a confirmed NMDARE diagnosis (ages of 3-18 years) who required inpatient rehabilitation. The mRS, CASE, and CALS were assessed at admission and discharge. RESULTS: Scores demonstrated improvement from admission to discharge, with variability in individual recovery trajectories. CALS identified three clusters of patients with differential rates of early recovery. CALS <30 was associated with minimal improvement and poor outcomes. CALS ≥30 had a likelihood ratio score of 12.0 to predict improvement. CASE and CALS were moderately correlated, but neither correlated with mRS. DISCUSSION: CALS and CASE appear to be complementary measures for assessing severity and cognitive status in pediatric NMDARE, including those with low responsiveness, with implications for treatment and outcomes.

A large-scale genetic screen identifies genes essential for motility in Agrobacterium fabrum.

The genetic and molecular basis of flagellar motility has been investigated for several decades, with innovative research strategies propelling advances at a steady pace. Furthermore, as the phenomenon is examined in diverse bacteria, new taxon-specific regulatory and structural features are being elucidated. Motility is also a straightforward bacterial phenotype that can allow undergraduate researchers to explore the palette of molecular genetic tools available to microbiologists. This study, driven primarily by undergraduate researchers, evaluated hundreds of flagellar motility mutants in the Gram-negative plant-associated bacterium Agrobacterium fabrum. The nearly saturating screen implicates a total of 37 genes in flagellar biosynthesis, including genes of previously unknown function.

The role of the Neuropsychologist across the stages of recovery from acquired brain injury: a summary from the pediatric rehabilitation Neuropsychology collaborative.

Neuropsychologists working in a pediatric neurorehabilitation setting provide care for children and adolescents with acquired brain injuries (ABI) and play a vital role on the interdisciplinary treatment team. This role draws on influences from the field of clinical neuropsychology and its pediatric subspecialty, as well as rehabilitation psychology. This combination of specialties is uniquely suited for working with ABI across the continuum of recovery. ABI recovery often involves a changing picture that spans across stages of recovery (e.g., disorders of consciousness, confusional state, acute cognitive impairment), where each stage presents with distinctive characteristics that warrant a specific evidence-based approach. Assessment and intervention are used reciprocally to inform diagnostics, treatment, and academic planning, and to support patient and family adjustment. Neuropsychologists work with the interdisciplinary teams to collect and integrate data related to brain injury recovery and use this data for treatment planning and clinical decision making. These approaches must often be adapted and adjusted in real time as patients recover, demanding a dynamic expertise that is currently not supported through formal training curriculum or practice guidelines. This paper outlines the roles and responsibilities of pediatric rehabilitation neuropsychologists across the stages of ABI recovery with the goal of increasing awareness in order to continue to develop and formalize this role.

The neutrophil-to-lymphocyte ratio is associated with intubation in pediatric anti-NMDA receptor encephalitis: A retrospective study.

Background The neutrophil-to-lymphocyte ratio (NLR) may predict poor outcomes in adult anti-NMDAR encephalitis (NMDARE). The association of NLR with outcomes in pediatric NMDARE was examined. Methods Pediatric NMDARE patients (N = 36) were retrospectively studied. Results High NLR (>6) had a higher proportion of tumors (43% versus 7%) and higher intubation rates (100% versus 38%, p = 0.008). Multivariate analyses showed that high NLR did not correlate with one-year outcomes, inpatient length of stay (LOS), or with tumor, but was associated with intubation and rehabilitation LOS. Conclusion NLR is associated with intubation and rehabilitation LOS. Further investigation is needed for prognostic biomarkers in NMDARE.

Cognitive recovery of children and adolescents with moderate to severe TBI during inpatient rehabilitation.

OBJECTIVE: Traumatic brain injury (TBI) is the leading cause of morbidity and mortality in children and adolescents. This study examines the early cognitive-linguistic recovery of pediatric patients who sustained TBI and required inpatient rehabilitation and investigates the contribution of various demographic, clinical, and preinjury factors to recovery. METHODS: A retrospective chart review of children and adolescents, ages 3-20 years, admitted to an inpatient rehabilitation unit. Acute outcomes were assessed at admission and discharge using the WeeFIM and CALS. Premorbid measures of behavioral and emotional functioning were also collected. RESULTS: One hundred and one children and adolescents (mean age = 12.31, SD = 4.46) diagnosed with TBI requiring inpatient rehabilitation were included. Patients displayed significant improvements on cognitive-linguistic skills and functional independence between admission and discharge, with medium to large effect sizes. Premorbid behavioral-emotional functioning was not found to be associated with early cognitive recovery. CONCLUSION: Results suggest that significant functional improvements can be expected for pediatric patients with TBI during inpatient rehabilitation. Consistent with previous literature, injury severity was significantly related to acute outcomes. In conjunction with the WeeFIM, the CALS appears to be a meaningful complement for assessing and monitoring cognitive-linguistic skills during inpatient rehabilitation.Implications for RehabiliationOur study provides support for the utility of the CALS to assess cognitive recovery during inpatient rehabilitation following moderate to severe TBI.Injury severity and not pre-injury functioning or demographic variables was related to worse scores on the CALS at discharge.Using a measure sensitive to change over admission, such as the CALS, can inform treatment planning.

[Formula: see text]Neuropsychological outcomes in children and adolescents following anti-NMDA receptor encephalitis.

Anti-N-methyl-d-aspartate receptor encephalitis (ANMDARE) is a neurologic disorder that is becoming more recognized in children and adolescents. Early studies suggested that patients typically recover well, but more recent data suggests that children may experience persistent cognitive deficits, especially in verbal memory and executive functioning. The aims of this study are to evaluate areas of impairment and to characterize neuropsychological outcomes in pediatric patients with ANMDARE. This was a multi-centered retrospective chart review. We identified 23 pediatric patients who were, on average, 18.5 months from diagnosis. Patients underwent comprehensive neuropsychological assessment, including measures of intellectual functioning, memory, reading, verbal fluency, visuomotor skills, attention, and working memory. Caregiver ratings and information regarding resource utilization were also collected (e.g., formal school services, outpatient rehabilitation, psychological support). Neuropsychological impairment index (NPI) scores were calculated for each patient. Neuropsychological outcomes highlighted variability across individuals. Memory and fine motor dexterity were particularly impacted. Almost 90% of caregivers reported more concerns than average on at least one measure of emotional-behavioral, adaptive, or executive functioning. More than two-thirds of the sample were considered impaired based on NPI scores on performance measures. More than three quarters of the sample received outpatient intervention, most often consisting of school-based services. Our findings provide additional quantitative evidence that pediatric patients recovering from ANMDARE demonstrate ongoing cognitive concerns. While most patients experience remarkable recoveries following appropriate diagnosis and treatment, ongoing monitoring and support is recommended over time for these patients.

Electroencephalography characteristics to predict one-year outcomes in pediatric anti-NMDA receptor encephalitis.

BACKGROUND: Electrographic characteristics (extreme delta brush, posterior dominant rhythm and slow waves) may predict outcomes in anti-NMDA receptor encephalitis (NMDARE). However, whether changes in EEG sleep architecture predict outcomes are unknown. We examine electrophysiological characteristics including sleep architecture in a pediatric NMDARE population and correlate with outcomes at one year. METHODS: Retrospective chart and EEG review was performed in pediatric NMDARE patients at a single center. Patients with first EEGs available within 48 h of admission, prior to treatment, and one-year follow-up data were included. EEGs were independently reviewed by two epileptologists, and a third when disagreement occurred. Clinical outcomes included modified Rankin scale (mRS) at one year. RESULTS: Nine patients (6 females) (range 1.9-16.7 years) were included. Five of nine patients had loss of posterior dominant rhythm (PDR) and three of nine patients had absent sleep architecture. Loss of PDR correlated with a worse mRS score at one year (2.8 versus 0.5, p = 0.038). Loss of PDR and loss of sleep architecture was associated with increased inpatient rehabilitation stay and in higher number of immunotherapy treatments administered. In multivariate analysis, absence of sleep architecture (p = 0.028), absence of PDR (p = 0.041), and epileptiform discharges (p = 0.041) were predictors of mRS at one year. CONCLUSIONS: Loss of normal PDR, absence of sleep architecture, and epileptiform discharges are associated with worse outcomes at one year which has not been reported before. EEG characteristics may help prognosticate in NMDARE. Larger studies are needed to confirm these findings.

Neuropsychological Phenotypes of Pediatric Anti-Myelin Oligodendrocyte Glycoprotein Associated Disorders: A Case Series.

Emerging research has demonstrated that anti-myelin oligodendrocyte associated disorders (MOG-AD) are associated with a less severe clinical course than demyelinating conditions associated with the presence of aquaporin-4 antibodies. While a heterogeneity of neuropsychological outcomes in pediatric demyelinating conditions have been described in the literature, no studies to date have investigated the neuropsychological sequelae of pediatric MOG-AD specifically. The objective of the present case series was to describe the clinical and neuropsychological phenotypes of seven pediatric patients (ages 3-15 years) with MOG-AD of different diagnoses (e.g., acute disseminated encephalomyelitis, optic neuritis, multiple sclerosis, and neuromyelitis spectrum disorders). Neuropsychological outcomes were evaluated by retrospective chart review. Results indicated largely intact neuropsychological profiles in five of the seven patients, with mild weaknesses in attention, executive functioning, processing speed, visual-motor/fine-motor skills, and mood concerns being observed. Two patients with a Kurtzke Extended Disability Status Scale of 0 still demonstrated findings on neuropsychological testing. Of the other two patients, one demonstrated higher levels of impairment in the context of a complex medical history and premorbid learning difficulties, while the other demonstrated declines in functioning likely associated with an earlier age of onset. Findings suggest that neuropsychological outcomes may be correspondingly less severe in this population compared with what has previously been described in the pediatric demyelinating disease literature. This differential impact may contribute to the heterogeneity of neuropsychological outcomes found in previous studies, and future research should separate participants with myelin oligodendrocyte antibodies given the difference in clinical course, treatment outcomes, and neuropsychological sequelae.

Pharmacologic Treatment and Early Rehabilitation Outcomes in Pediatric Patients With Anti-NMDA Receptor Encephalitis.

OBJECTIVES: To describe the immunotherapy and pharmacologic treatments administered to pediatric patients with N-methyl-D-aspartate receptor encephalitis (NMDARE) during inpatient rehabilitation as well as to examine clinical and demographic variables associated with early functional outcomes. DESIGN: Retrospective chart review and post hoc analysis. SETTING: Pediatric inpatient rehabilitation unit. PARTICIPANTS: Pediatric patients (N=26; mean age, 10.79±5.17y) admitted to an inpatient rehabilitation unit with a confirmed diagnosis of NMDARE. INTERVENTIONS: Inpatient rehabilitation; pharmacologic treatments. MAIN OUTCOME MEASURE: FIM for Children (WeeFIM) Developmental Functional Quotient (DFQ). RESULTS: All patients received first-line immunotherapies to treat NMDARE, and 69% also received second-line immunotherapies. Patients were prescribed an average of 8 medications for symptom management (range, 3-15 per patient), most often for the treatment of agitation (100%), psychiatric symptoms (92%), and seizures (65%). Sixty-five percent of patients demonstrated an improvement in Total WeeFIM DFQ over the course of inpatient rehabilitation, with 35% demonstrating limited to no change in Total WeeFIM DFQ ("unfavorable early outcome"). Those with unfavorable early outcome were significantly younger than those showing more favorable outcome. Pharmacologic treatment for seizures, movement disorders, and decreased arousal or level of consciousness were each associated with unfavorable early outcome independent of age differences. CONCLUSION: Findings highlight the symptomatic heterogeneity and polypharmacy involved in the care and treatment of patients with NMDARE, with patients receiving a variety of immunotherapies and medications for symptom management. The presence of (and treatment for) seizures, movement disorders, and deteriorated neurologic status may each be associated with poor early outcomes in this population. Further investigation is needed to better classify presentations and treatments for this disease and to determine how differences are associated with long-term outcomes.

COVID-19 issues related to pediatric neuropsychology and inpatient rehabilitation - challenges to usual care and solutions during the pandemic.

Objective: To describe the challenges related to COVID-19 affecting pediatric neuropsychologists practicing in inpatient brain injury rehabilitation settings, and offer solutions focused on face-to-face care and telehealth.Methods: A group of pediatric neuropsychologists from 12 pediatric rehabilitation units in North America and 2 in South America have met regularly since COVID-19 stay-at-home orders were initiated in many parts of the world. This group discussed challenges to clinical care and collaboratively problem-solvedsolutions.Results: Three primary challenges to usual care were identified, these include difficulty providing 1) neurobehavioral and cognitive assessments; 2) psychoeducation for caregivers and rapport building; and 3) return to academic instruction and home. Solutions during the pandemic for the first two areas focus on the varying service provision models that include 1) face-to-face care with personal protective equipment (PPE) and social distancing and 2) provision of care via remote methods, with a focus on telehealth. During the pandemic,neuropsychologists generally combine components of both the face-to-face and remote care models. Solutions to the final challenge focus on issues specific to returning to academic instruction and home after an inpatient stay.Conclusions: By considering components of in-person and telehealth models of patient care during the pandemic, neuropsychologists successfully serve patients within the rehabilitation setting, as well as the patient's family who may be limited in their ability to be physically present due to childcare, illness, work-related demands, or hospital restrictions.

Acute Flaccid Myelitis: A Single Pediatric Center Experience From 2014 to 2019.

BACKGROUND: Acute flaccid myelitis has emerged as the leading cause of acute flaccid paralysis in children. Acute flaccid myelitis leads to significant physical disability; hence, objective outcome measures to study disease severity and progression are desirable. In addition, nerve transfer to improve motor function in affected children needs further study. METHODS: Retrospective study of acute flaccid myelitis subjects managed at Children's Healthcare of Atlanta from August 2014 to December 2019. Clinical, electromyography and nerve conduction study, neuropsychological functional independence (WeeFIM), and nerve transfer data were reviewed. RESULTS: Fifteen children (11 boys and 4 girls) mean age 5.1±3.2 years (range 14 months to 12 years) were included. All subjects (n = 15) presented with severe asymmetric motor weakness and absent tendon reflexes. Motor nerve conduction study of the affected limbs in 93% (n = 14) showed absent or markedly reduced amplitude. Ten patients received comprehensive inpatient rehabilitation and neuropsychological evaluation. Admission and discharge WeeFIM scores showed deficits most consistent and pronounced in the domains of self-care and mobility. Multiple nerve transfer surgery was performed on 13 limbs (9 upper and 4 lower extremities) in 6 children. Postsurgery (mean duration of 10.4 ± 5.7 months) follow-up demonstrated improvement on active movement scale (AMS) in 4 subjects. CONCLUSION: Acute flaccid myelitis affects school-age children with asymmetric motor weakness, absent tendon reflexes, and reduced or absent motor amplitude on nerve conduction study. Comprehensive rehabilitation and nerve transfer led to improvement in motor function on neuropsychology WeeFIM and AMS scores.

Early Functional Outcomes for Pediatric Patients Diagnosed with Anti-N-Methyl-D-Aspartate Receptor Encephalitis during Inpatient Rehabilitation.

OBJECTIVE: The aims of the current study were to characterize the demographic and clinical presentation of pediatric patients diagnosed with anti-N-methyl-D-aspartate receptor encephalitis who require inpatient rehabilitation, to examine early functional outcomes, and to investigate predictors of early recovery. DESIGN: A retrospective chart review was conducted for 27 pediatric patients diagnosed with anti-N-methyl-D-aspartate receptor encephalitis who received intensive inpatient neurorehabilitation. RESULTS: On average, patients were 10.6 yrs of age (range, 2-18 yrs) at the time of symptom onset. Average time to treatment from symptom onset was 27.2 days (range, 5-91 days). Patients displayed significant improvements between admission and discharge Functional Independence Measure for Children (WeeFIM) Developmental Functional Quotient (DFQ) scores across patients (P < 0.01). Mean Functional Independence Measure for Children Total Developmental Functional Quotient score at admission was 28.6 (range, 15.0-62.6) and at discharge was 54.3 (range, 14.2-91.9). Younger age at onset, seizures, and number of treatments received were associated with worse functional outcomes at discharge. Time to initiate treatment was not found to be associated with early functional outcomes. CONCLUSION: Pediatric patients diagnosed with anti-N-methyl-D-aspartate receptor encephalitis displayed significant functional gains during inpatient rehabilitation, despite persistent functional deficits at discharge, suggesting the need for ongoing monitoring and intervention. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to (1) Recognize the clinical presentation of anti-N-methyl-D-aspartate receptor encephalitis in pediatric patients, (2) Appreciate the role of rehabilitation in the care of the pediatric patient with anti-N-methyl-D-aspartate receptor encephalitis, and (3) Identify demographic and clinical variables that predict poor functional outcomes after rehabilitation in pediatric patients with anti-N-methyl-D-aspartate receptor encephalitis. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Neurocognitive improvements following endovascular repair of vein of Galen malformation in a child.

Cognitive regression is a well-described presentation of vein of Galen aneurysmal malformations (VGAMs) in childhood. However, it remains unclear whether successful treatment of the malformation can reverse cognitive regression. Here, the authors present the case of a 5-year-old girl with a VGAM that was treated with staged endovascular embolization procedures. Comprehensive neurocognitive assessments were completed before intervention and approximately 6 years after initial presentation. There were significant age-matched improvements in this child's neurocognitive profile over this period. The authors believe that timely and successful treatment of VGAM in children may not only stabilize the associated cognitive deterioration but, in some cases, may ameliorate these deficits. Details of this case and a discussion of neurocognitive deficits related to VGAM are presented.

Investigating the relationship between COMT polymorphisms and working memory performance among childhood brain tumor survivors.

BACKGROUND: Survivors of childhood brain tumors are at increased risk for neurocognitive impairments, including deficits in abilities supported by frontal brain regions. Catechol-O-methyltransferase (COMT) metabolizes dopamine in the prefrontal cortex, with the Met allele resulting in greater dopamine availability and better performance on frontally mediated tasks compared to the Val allele. Given the importance of identifying resiliency factors against the emergence of cognitive late effects, the current study examined the relationship between COMT genotype and working memory performance among childhood brain tumor survivors. PROCEDURE: Children treated for a brain tumor with conformal radiation therapy (N = 50; mean age at irradiation = 7.41 ± 3.41; mean age at assessment = 13.18 ± 2.88) were administered two computerized measures of working memory (self-ordered search verbal and object tasks). Buccal (cheek) swabs were used to provide tissue from which DNA was extracted. RESULTS: Findings revealed an association between COMT genotype and performance on the self-ordered verbal (P = 0.03) but not object task (P = 0.33). Better performance was found for the Met/Val group compared to either Met/Met or Val/Val. CONCLUSIONS: COMT may indicate a potential resiliency factor against neurocognitive effects of cancer and its treatment; however, there is a need for replication with larger samples of childhood brain tumor survivors.