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.

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.

Social-environmental factors as mediators of IQ and achievement differences across race groups in adolescents with high risk congenital heart disease.

An increasing number of neuropsychologists are evaluating children with congenital heart disease (CHD). When conceptualizing results, the provider must consider medical risks such as abnormal neuroimaging and comorbidities, along with social risks such as socioeconomic status. The aim of the current study was to examine the influence of parent income and education on IQ and achievement across race groups in adolescents with CHD, while also accounting for medical risk (e.g., gestational age, number of ventricles, neuroimaging). This is a single-center cross-sectional study, including 92 children ages 12-19 years (median 14.9 years; 59% male; 71% White; 29% Black) with high risk CHD (i.e., cardiac surgery <12 months) who were referred for a neuropsychological evaluation. Retrospective data were retrieved from a larger clinical registry. Patients completed an intellectual assessment (WISC-V; WAIS-IV; WASI-II), Word Reading and Math Calculation tests. Parents completed questionnaires assessing the family environment [income, parent education]. Results revealed significant differences in IQ when comparing children who were Black versus White (11.4 point IQ difference); however, around 70% of this variance was explained by parent income and education. Medical variables accounted for 12% of the variance in IQ. For academics, parent income and education accounted for 91.5% and 78.8% of the variance in race group differences for reading and math, respectively. Medical risk and sex explained 11.7% and 14.7% of the variance in reading and math, respectively. Findings suggest that sociodemographic factors should be weighed heavily during the neuropsychological evaluation, including prioritizing risk, making recommendations, and facilitating referrals.

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.

[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.

Osteopontin as a biomarker for COVID-19 severity and multisystem inflammatory syndrome in children: A pilot study.

This study sought to evaluate the candidacy of plasma osteopontin (OPN) as a biomarker of COVID-19 severity and multisystem inflammatory condition in children (MIS-C) in children. A retrospective analysis of 26 children (0-21 years of age) admitted to Children's Healthcare of Atlanta with a diagnosis of COVID-19 between March 17 and May 26, 2020 was undertaken. The patients were classified into three categories based on COVID-19 severity levels: asymptomatic or minimally symptomatic (control population, admitted for other non-COVID-19 conditions), mild/moderate, and severe COVID-19. A fourth category of children met the Centers for Disease Control and Prevention's case definition for MIS-C. Residual blood samples were analyzed for OPN, a marker of inflammation using commercial ELISA kits (R&D), and results were correlated with clinical data. This study demonstrates that OPN levels are significantly elevated in children hospitalized with moderate and severe COVID-19 and MIS-C compared to OPN levels in mild/asymptomatic children. Further, OPN differentiated among clinical levels of severity in COVID-19, while other inflammatory markers including maximum erythrocyte sedimentation rate, C-reactive protein and ferritin, minimum lymphocyte and platelet counts, soluble interleukin-2R, and interleukin-6 did not. We conclude OPN is a potential biomarker of COVID-19 severity and MIS-C in children that may have future clinical utility. The specificity and positive predictive value of this marker for COVID-19 and MIS-C are areas for future larger prospective research studies.

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.

Utility of ventriculogallbladder shunts in complex cases of hydrocephalus related to extreme prematurity.

OBJECTIVE: The management of hydrocephalus resulting from intraventricular hemorrhage related to extreme prematurity remains demanding. Given the complexities of controlling hydrocephalus in this population, less commonly used procedures may be required. The authors examined the utility of ventriculogallbladder (VGB) shunts in a series of such children. METHODS: The authors retrospectively reviewed the medical records of all children who underwent surgery for hydrocephalus in the period from 2011 through 2019 at Children's Healthcare of Atlanta. Six patients who underwent VGB shunt placement were identified among a larger cohort of 609 patients who had either a new shunt or a newly changed distal terminus site. The authors present an analysis of this series, including a case of laparoscopy-assisted distal VGB shunt revision. RESULTS: The mean age at initial shunt placement was 5.1 months (range 3.0-9.4 months), with patients undergoing a mean of 11.8 shunt procedures (range 5-17) prior to the initial VGB shunt placement at a mean age of 5.3 years (range 7.9 months-12.8 years). All 6 patients with VGB shunt placement had hydrocephalus related to extreme prematurity (gestational age < 28 weeks). At the time of VGB shunt placement, all had complex medical and surgical histories, including poor venous access due to congenital or iatrogenic thrombosis or thrombophlebitis and a peritoneum hostile to distal shunt placement related to severe necrotizing enterocolitis. VGB complications included 1 case of shunt infection, identified at postoperative day 6, and 2 cases of distal shunt failure due to retraction of the distal end of the VGB shunt. In all, there were 3 conversions back to ventriculoperitoneal or ventriculoatrial shunts due to the 2 previously mentioned complications, plus 1 patient who outgrew their initial VGB shunt. Three of 6 patients remain with a VGB shunt, including 1 who underwent laparoscopy-assisted distal shunt revision 110.5 months after initial VGB shunt insertion. CONCLUSIONS: Placement of VGB shunts should be considered in the armamentarium of procedures that may be used in the particularly difficult cohort of children with hydrocephalus related to extreme prematurity. VGB shunts show utility as both a definitive treatment and as a "bridge" procedure until the patient is larger and comorbid abdominal and/or vascular issues have resolved sufficiently to allow conversion back to ventriculoperitoneal or ventriculoatrial shunts, if needed.

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.

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.

Daily pain in adolescents with CF: Effects on adherence, psychological symptoms, and health-related quality of life.

BACKGROUND: Cystic fibrosis (CF) is a progressive, life-shortening disease currently treated symptomatically. Among the consequences of daily treatments and long-term progression of the disease is significant discomfort and pain. This study measured pain systematically in adolescents with CF using a pain diary, and evaluated its associations with treatment adherence, psychological symptoms, and health-related quality of life (HRQOL). METHODS: This study was part of a larger, multi-center study. Ninety-five adolescents with a mean age of 15.8 were enrolled. A total of 413 online pain diaries were completed for 6 days following a routine clinic visit. Diaries measured pain intensity, location, duration, affective ratings, and coping responses. Adherence to pulmonary medications was measured using prescription refill data; other measures included ratings of depression, anxiety and HRQOL. RESULTS: Pain was reported by 74.5% of participants, generally in the mild range, averaging 2.1 on a 10-point scale. Daily pain ratings were highly variable both within and between participants. Pain was significantly associated with worse adherence, more psychological distress, and worse HRQOL. CONCLUSIONS: Results indicated that pain is a common problem for adolescents with CF and negatively affects their disease management, psychological symptoms and health outcomes. Routine assessment of pain and systematic studies of interventions to treat pain are recommended. Pediatr Pulmonol. 2015; 50:244-251. © 2014 Wiley Periodicals, Inc.

Prevalence of depression and anxiety in patients with cystic fibrosis and parent caregivers: results of The International Depression Epidemiological Study across nine countries.

BACKGROUND: Individuals with chronic diseases and parent caregivers are at increased risk for symptoms of depression and anxiety. Prevalence of psychological symptoms was evaluated in adolescents and adults with cystic fibrosis (CF) and parent caregivers across nine countries. METHODS: Patients with CF, ages 12 years and older, and caregivers of children with CF, birth to18 years of age, completed measures of depression and anxiety across 154 CF centres in Europe and the USA. Psychological symptoms were compared across countries using χ(2). Logistic regression examined extent of comorbid symptoms, predictors of depression and anxiety, and concordance between parent and adolescent symptomatology. RESULTS: Psychological symptoms were reported by 6088 patients with CF and 4102 parents. Elevated symptoms of depression were found in 10% of adolescents, 19% of adults, 37% of mothers and 31% of fathers. Elevations in anxiety were found in 22% of adolescents, 32% of adults, 48% of mothers and 36% of fathers. Overall, elevations were 2-3 times those of community samples. Participants reporting elevated anxiety were more likely to report depression (ORs: adolescents=14.97, adults=13.64, mothers=15.52, fathers=9.20). Significant differences in reports of depression and anxiety were found by patient age and parent respondent. Concordance between 1122 parent-teen dyads indicated that adolescents whose parents reported depression were more likely to be elevated on depression (OR=2.32). Similarly, adolescents whose parents reported anxiety were more likely to score in the elevated range on the anxiety measure (OR=2.22). CONCLUSIONS: Symptoms of depression and anxiety were elevated in both patients with CF and parents across several European countries and the USA. Annual screening of psychological symptoms is recommended for both patients and parents.

Utilization of patient-reported outcomes as a step towards collaborative medicine.

Patient-reported outcomes (PROs) have been successfully developed for a variety of chronic respiratory diseases, such as asthma and cystic fibrosis (CF). They have recently been used to evaluate the efficacy of new medications and assess current patient functioning. Although regulatory bodies have favored PROs that measures symptoms, other domains of functioning, such as treatment burden, should be considered. This review examines current guidelines for the development and application of PROs in clinical trials, describes methods for selecting appropriate measures for paediatric populations, and presents a model incorporating PROs into clinical practice. Guidance on interpretation of these measures and graphic presentation of results are illustrated. PROs can serve as the link between the health care provider and patient to foster collaborative and personalized medicine. This model promotes greater patient responsibility, facilitates communication with providers, encourages shared decision-making, and enhances adherence.

Lung transplantation for cystic fibrosis.

Lung transplantation is a complex, high-risk, potentially life-saving therapy for the end-stage lung disease of cystic fibrosis (CF). The decision to pursue transplantation involves comparing the likelihood of survival with and without transplantation as well as assessing the effect of wait-listing and transplantation on the patient's quality of life. Although recent population-based analyses of the US lung allocation system for the CF population have raised controversies about the survival benefits of transplantation, studies from the United Kingdom and Canada have suggested a definite survival advantage for those receiving transplants. In response to these and other controversies, leaders in transplantation and CF met together in Lansdowne, Virginia, to consider the state of the art in lung transplantation for CF in an international context, focusing on advances in surgical technique, measurement of outcomes, use of prognostic criteria, variations in local control over listing, and prioritization among the United States, Canada, the United Kingdom, and The Netherlands, patient adherence before and after transplantation and other issues in the broader context of lung transplantation. Finally, the conference members carefully considered how efforts to improve outcomes for lung transplantation for CF lung disease might best be studied. This Roundtable seeks to communicate the substance of our discussions.