Visual outcomes after bevacizumab-based therapy for optic pathway glioma.

In optic pathway glioma (OPG), bevacizumab-based therapy (BBT) has promising effects on radiographic tumor burden, but the impact on vision is less clear. This single-institution study characterized visual acuity (VA) and visual field (VF) outcomes in 17 pediatric OPG patients treated with BBT. VA was stable or improved in 14 patients. Nine patients had evaluable VF data, six of whom experienced stability or improvement. Among six patients with vision deterioration as a treatment indication, stable or improved was observed for both VA and VF in five patients. In summary, BBT was associated with favorable visual outcomes in this cohort of patients with OPG.

Adult Neurology Rotations for Child Neurology Residents: Exploring the Resident Perspective.

BACKGROUND: In 2014 the Accreditation Council for Graduate Medical Education modified adult training requirements for child neurology certification to reduce the number of hospital-based rotations and require inclusion of outpatient clinic and electives. We aimed to identify how these training requirements are being met and explored its impact on residents. METHODS: A REDCap questionnaire surveying resident opinion on impact of adult training on resident education, professional development, and wellness was e-mailed to 79 program directors in the United States for distribution in 2020. Results were analyzed using descriptive statistics and t test calculations. Qualitative analysis of narrative responses involved theme identification. RESULTS: A total of 116 child neurology residents participated (30.2% PGY-3, 37.9% PGY-4, and 31.9% PGY-5 residents); 20.9% had all adult rotations during the PGY-3 year, and 79.1% had adult rotations spread throughout residency. Adult training had a small positive impact on resident autonomy and a negative impact on resident wellness regardless of training structure. However, residents with 12 months of adult training during PGY-3 year scored worse on burnout, mood changes, work-life balance, and social well-being (P < 0.05). Some themes identified included residents feeling unsafe due to lack of supervision, that education was not prioritized, and that adult patient care lacked relevance to long-term career goals. CONCLUSIONS: Adult neurology training was found to negatively affect child neurology resident wellness, with a larger negative impact when adult training was completed in 12 months during PGY-3 year. Other identified areas where change could be implemented include improving feelings of resident safety and prioritizing quality and relevance of education.

Adult Neurology Rotations for Child Neurology Residents: A Survey of Program Directors.

BACKGROUND AND OBJECTIVES: We aimed to identify how child neurology and neurodevelopmental disabilities residency program directors (PDs) implemented revised Accreditation Council for Graduate Medical Education requirements for adult neurology training for child neurology residents. Before 2014, the American Board of Psychiatry and Neurology certification for child neurology required an adult year, with no specified rotation requirements. At that point, programs scheduled a median of 10 months of adult neurology rotations during the third postgraduate year (PGY-3). In 2014, the adult neurology requirements were modified to include 6 months of hospital-based, 3 months of outpatient, and 3 months of other elective (may include neurophysiology, neuropathology, and/or neuroradiology) rotations. However, the effects of these changes on child neurology residency training nationally have not been characterized. METHODS: A 16-item online survey was emailed to 79 PDs in the United States in September 2020. Survey responses were collected from September to October 2020. Descriptive statistics were calculated, and associations with departmental affiliation (pediatrics/neurology), graduate medical education (GME) funding source, and program size were compared using nonparametric tests. RESULTS: The response rate was 72% (53 pediatric neurology, 3 neurodevelopmental disabilities). The median adult months per year of training were as follows: 9 PGY-3, 2 PGY-4, and 1 PGY-5. Nearly all had both hospital inpatient and consult rotations with night and/or weekend shifts; 57% included neurocritical care and 36% epilepsy monitoring units. 48% of programs scheduled night and weekend shifts (including 25% that scheduled 24-hour calls) for residents on outpatient and elective rotations. Few programs required adult neurophysiology (20%), neuropathology (32%), or neuroradiology (25%). Programs with children's hospital GME funding (for either 2 or 3 years) tended to be larger (p = 0.008). Otherwise, departmental affiliation, funding source, and program size were not associated with rotation timing. DISCUSSION: Most child neurology residency programs still consolidate adult training in the PGY-3 year and often schedule additional hospital shifts during outpatient and elective months. However, there is a small shift toward adult neurology rotations occurring in the PGY-4 and PGY-5. Departmental affiliation, funding source, and program size do not consistently affect training practices. Few programs mandate adult neurophysiology, neuropathology, or neuroradiology rotations.

Rate of Leptomeningeal Enhancement in Pediatric Myelin Oligodendrocyte Glycoprotein Antibody-Associated Encephalomyelitis.

INTRODUCTION: Myelin oligodendrocyte glycoprotein antibodies (MOG-abs) are associated with demyelinating diseases. Leptomeningeal enhancement occurs in 6% of adult MOG-abs patients but rates in pediatric MOG-abs patients are unknown. METHODS: Retrospective review of pediatric MOG-abs patients was performed. RESULTS: Twenty-one patients (7 boys, 14 girls) were included with an average age of 8.6 years (range 2-15 years). Seven of 21 (33%) pediatric MOG-abs patients had leptomeningeal enhancement. Two patients' relapses were manifested by leptomeningeal enhancement alone and another patient presented with seizures, encephalopathy, and aseptic meningitis without demyelinating lesions. Cerebrospinal fluid pleocytosis was seen in both leptomeningeal (4/7 patients) and nonleptomeningeal enhancement (10/14 patients). Interestingly, 3 patients with leptomeningeal enhancement had normal cerebrospinal fluid white blood cell count. Cortical edema was more likely in patients with leptomeningeal enhancement (P = .0263). CONCLUSION: We expand the clinical spectrum of anti-MOG antibody-associated disorder. Patients with recurrent leptomeningeal enhancement without demyelinating lesions should be tested for MOG antibodies.

Reducing Prescribing Errors in Hospitalized Children on the Ketogenic Diet.

BACKGROUND: Children on the ketogenic diet must limit carbohydrate intake to maintain ketosis and reduce seizure burden. Patients on ketogenic diet are vulnerable to harm in the hospital setting where carbohydrate-containing medications are commonly prescribed. We developed clinical decision support to reduce inappropriate prescription of carbohydrate-containing medications in hospitalized children on ketogenic diet. METHODS: A clinical decision support alert was developed through formative and summative usability testing. The alert warned prescribers when they entered an order for a carbohydrate-containing medication in patients on ketogenic diet. The alert was implemented using a quasi-experimental design with sequential crossover from control to intervention at two tertiary care pediatric hospitals within a single health system. The primary outcome was carbohydrate-containing medication orders per patient-day. RESULTS: During the study period, there were 280 ketogenic diet patient admissions totaling 1219 patient-days. The carbohydrate-containing medication order rate declined from 0.69 to 0.35 orders per patient-day (absolute rate reduction 0.34, 95% confidence interval 0.25-0.43), corresponding to 256 inappropriate orders prevented. The alert fired 398 times and was accepted (i.e., the order was removed) 227 times for an overall acceptance rate of 57%. CONCLUSIONS: Implementation of a clinical decision support alert at order-entry resulted in a sustained reduction in carbohydrate-containing medication orders for hospitalized patients on ketogenic diet without an increase in alert burden. Clinical decision support developed with user-centered design principles can improve patient safety for children on ketogenic diet by influencing prescriber behavior.

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.

Fate of Pediatric Renal Angiomyolipoma During mTOR Inhibitor Treatment in Tuberous Sclerosis Complex.

OBJECTIVE: To evaluate the clinical and radiographic follow-up of renal angiomyolipoma (AML) in pediatric patients with tuberous sclerosis complex (TSC) on mTOR inhibitors. METHODS: We performed retrospective chart review of children who were diagnosed with TSC between 2000 and 2019 and prescribed everolimus at age ≤18 years. Treatment assessment was performed in patients who were medically-compliant by serum drug trough levels and who had at least a baseline and one subsequent renal imaging study. RESULTS: Nineteen patients were analyzed. Average age of everolimus initiation was 9 years, and indication was neurologic in 17 (90%). Fourteen patients (73.6%) had AML with average size of 1.9 (0.4-5) cm. Medication was discontinued due to side effects in 3 (16%) patients. Treatment assessment was analyzed for 15 patients with median medication exposure 5.1 (0.8-8.5) years. Among 13 with AML, the dominant lesion decreased in size in 9 (69%) and stayed stable in 4 (31%). Greatest absolute size decrease was seen for lesions ≥2 cm. No new AML lesions formed during treatment. CONCLUSION: Although not currently approved for this indication, everolimus appears to be well-tolerated with similar efficacy for pediatric AML as in adult AML. Use may be most warranted in children with AML ≥2 cm.

Congenital Toxoplasmosis Presenting as Eosinophilic Encephalomyelitis With Spinal Cord Hemorrhage.

A 4-week-old male neonate with a history of intermittent hypothermia in the newborn nursery presented with an acute onset of bilateral lower extremity paralysis and areflexia. Extensive workup demonstrated eosinophilic encephalomyelitis and multifocal hemorrhages of the brain and spinal cord. Funduscopic examination revealed bilateral chorioretinitis with macular scarring. The laboratory values were notable for peripheral eosinophilia and cerebrospinal fluid eosinophilic pleocytosis (28 white blood cells/µL, 28% eosinophils), markedly elevated protein (1214 mg/dL), and hypoglycorrhachia (20 mg/dL). Toxoplasma gondii immunoglobulin M (IgM) test result was positive. Reference testing obtained at the Palo Alto Medical Foundation Toxoplasma Serology Laboratory confirmed the diagnosis of congenital toxoplasmosis in the infant with a positive immunoglobulin G (IgG) dye test result, immunoglobulin A enzyme-linked immunosorbent assay, and IgM immunosorbent agglutination assay. The diagnosis of an infection acquired during gestation in the mother was established by a positive maternal IgG dye test result, IgM enzyme-linked immunosorbent assay, immunoglobulin A, immunoglobulin E, and low IgG avidity. At 6-month follow-up, the infant had marginal improvement in his retinal lesions and residual paraplegia with hyperreflexia and clonus of the lower extremities. A repeat MRI demonstrated interval development of encephalomalacia with suspected cortical laminar necrosis and spinal cord atrophy in the areas of previous hemorrhage. Clinicians should be aware of this severe spectrum of congenital toxoplasmosis disease and should remain vigilant for subtler signs that may prompt earlier testing, diagnosis, and treatment.

Timing of Antiretroviral Therapy Initiation Determines Rectal Natural Killer Cell Populations.

Despite antiretroviral therapy (ART), innate and adaptive immunologic damage persists in the periphery and gut. T memory stem cells (Tscm) and natural killer (NK) cells are pivotal for host defense. Tscm are memory cells capable of antigen response and self-renewal, and circulating and gut NK cell populations may facilitate HIV control. The impact of early ART on circulating and gut Tscm and NK cells is unknown. We enrolled participants who initiated ART during acute versus chronic HIV-1 infection versus no ART in chronic infection. We performed flow cytometry to identify NK and Tscm cells in the blood and rectum and polymerase chain reaction to quantify the HIV-1 reservoir in both sites. We used the Mann-Whitney U-test and Spearman correlation coefficients for analysis. Participants who started ART in acute infection had lower rectal CD56brightCD16dim cell frequencies than participants who started ART in chronic HIV-1 infection and lower CD56bright and CD56brightCD16- cell frequencies than participants with chronic infection without ART. Higher circulating NK cell, CD56-CD16bright, CD56dim, and CD56dimCD16bright frequencies correlated with higher HIV-1 DNA levels in rectal CD4+ T cells, whereas higher circulating CD4+ T cell counts correlated with higher rectal NK, CD56brightCD16dim, and CD56dimCD16bright frequencies. Peripheral CD56brightCD16- cells were inversely associated with rectal CD56-CD16bright cells. Rectal CD8+ Tscm frequencies were higher in participants without ART than participants with chronic infection on ART. Timing of ART initiation determines rectal NK cell populations, and ART may influence rectal Tscm populations. Whether the gut reservoir contributes to NK cell activation requires further study.

Imaging of Children With Nontraumatic Headaches.

OBJECTIVE: Headache in children is a common symptom and often is worrisome for clinicians and parents because of the breadth of possible underlying significant abnormalities, including meningitis, brain neoplasms, and intracranial hemorrhage. For this reason, many children with headaches undergo neuroimaging. Most neuroimaging studies performed of children with headaches have normal findings but may lead to significant downstream effects, including unnecessary exposure to ionizing radiation or sedation, as well as unnecessary cost to the health care system. In this article, we review the current evidence and discuss the role of neuroimaging in the diagnosis and management of pediatric headaches, with a special focus on tools that may aid in increasing the rate of positive findings, such as classification systems, algorithms, and red flag criteria. CONCLUSION: Many tools exist that can help in improving the appropriateness of neuroimaging in pediatric headache. The main issues that remain to be addressed include scientific proof of safety and validity of these tools and clarity regarding the risks, benefits, and cost-effectiveness of CT versus MRI in various clinical settings and scenarios.

High-dose glucocorticoid therapy in the management of seizures in neonatal incontinentia pigmenti: a case report.

Incontinentia pigmenti is an X-linked dominant disorder resulting from a mutation of IKBKG. This disorder has a classic dermatologic presentation, but neurologic involvement, with seizures and cortical infarction, can arise shortly after birth. There are no specific therapies available for the manifestations of incontinentia pigmenti. Here, we describe the clinical, electrographic, and neuroradiologic effect of systemic glucocorticoid therapy in a neonate with incontinentia pigmenti manifesting an epileptic encephalopathy. Treatment with dexamethasone led to a dramatic reduction in seizure activity and improvement in bullous lesions. A novel mutation in IKBKG is also reported.

Endoscopic retrograde cholangiopancreatography for suspected choledocholithiasis: testing the current guidelines.

BACKGROUND: Current guidelines include an algorithm for predicting choledocholithiasis. Presence of any very strong predictor or both strong predictors confers a high (>50%) probability of choledocholithiasis. Absence of predictors confers low risk (<10%) of choledocholithiasis. Other combinations have an intermediate risk of choledocholithiasis. AIM: Determine accuracy of the proposed algorithm in predicting choledocholithiasis. METHODS: Retrospective analysis of all endoscopic retrograde cholangiopancreatographies performed for suspected choledocholithiasis in 3 years in a Tertiary care hospital and a community hospital serviced by The University of Texas Health Science Center at Houston Division of Gastroenterology. Application of the guidelines, and comparing results to endoscopic retrograde cholangiopancreatography findings. RESULTS: A total of 1080 endoscopic retrograde cholangiopancreatographies were performed; 521 for choledocholithiasis. Most patients were Hispanic and female. Univariate analysis: presence of any very strong predictor and both strong predictors had an OR for choledocholithiasis of 3.30 and 2.36 respectively. Multivariate analysis: odds of choledocholithiasis with any very strong predictor was 2.87, and both strong predictors 3.24. Choledocholithiasis was present in 71.5%, and 41% of patients with high, and intermediate risk respectively. CONCLUSION: This study confirms the utility of clinical predictors for the diagnosis of choledocholithiasis. All of the very strong predictors and one of the strong predictors increased the odds of choledocholithiasis. Patients with high risk for choledocholithiasis had a probability of 79% of choledocholithiasis. Sensitivity and specificity of current predictors are too low to obviate the possible need of non-invasive tests to confirm or exclude choledocholithiasis in all risk groups.