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1.
Neural Regen Res ; 20(6): 1644-1664, 2025 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-39104096

RESUMO

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1ß cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasome-dependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

2.
J Head Trauma Rehabil ; 39(3): E122-E131, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38709832

RESUMO

OBJECTIVE: To understand how methylphenidate (MPH) is used in youth with traumatic brain injury (TBI) during inpatient pediatric rehabilitation. SETTING: Inpatient pediatric rehabilitation. PARTICIPANTS: In total, 234 children with TBI; 62 of whom received MPH and 172 who did not. Patients were on average 11.6 years of age (range, 2 months to 21 years); 88 of 234 were female; the most common mechanism of injury was motor vehicle collision (49%); median (IQR) acute hospital length of stay (LOS) and inpatient rehabilitation LOS were 16 (10-29) and 23 (14-39), respectively; 51 of 234 were in a disorder of consciousness cognitive state at time of inpatient rehabilitation admission. DESIGN: Multicenter, retrospective medical record review. MAIN MEASURES: Patient demographic data, time to inpatient pediatric rehabilitation admission (TTA), cognitive state, MPH dosing (mg/kg/day). RESULTS: Patients who received MPH were older (P = .011); TTA was significantly longer in patients who received MPH than those who did not (P =.002). The lowest recorded dose range by weight was 0.05 to 0.89 mg/kg/d, representing an 18-fold difference; the weight-based range for the maximum dose was 0.11 to 0.97 mg/kg/d, a 9-fold difference. Patients in lower cognitive states at admission (P = .001) and at discharge (P = .030) were more likely to receive MPH. Five patients had side effects known to be associated with MPH; no serious adverse events were reported. CONCLUSION: This multicenter study indicates that there is variable use of MPH during acute inpatient rehabilitation for children with TBI. Children who receive MPH tend to be older with lower cognitive states. Dosing practices are likely consistent with underdosing. Clinical indications for MPH use during inpatient pediatric rehabilitation should be better defined. The use of MPH, as well as its combination with other medications and treatments, during inpatient rehabilitation needs to be further explored.


Assuntos
Lesões Encefálicas Traumáticas , Estimulantes do Sistema Nervoso Central , Metilfenidato , Padrões de Prática Médica , Humanos , Metilfenidato/uso terapêutico , Metilfenidato/administração & dosagem , Criança , Feminino , Lesões Encefálicas Traumáticas/reabilitação , Masculino , Adolescente , Pré-Escolar , Estudos Retrospectivos , Estimulantes do Sistema Nervoso Central/uso terapêutico , Estimulantes do Sistema Nervoso Central/administração & dosagem , Lactente , Padrões de Prática Médica/estatística & dados numéricos , Adulto Jovem , Pacientes Internados , Tempo de Internação , Centros de Reabilitação
4.
Front Public Health ; 12: 1339394, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38566791

RESUMO

Background: Firearm-related injuries (FRI) are an increasing cause of death and injury in children. The etiology for this rise is multifactorial and includes socioeconomic factors. Despite its prevalence and documented increase over COVID-19, there is a paucity of research on disparities and the influence of social determinants of health (SDH) in pediatric FRI. This study aims to explore the epidemiology of this vulnerable population in Atlanta, trends over time and relevant dates such as COVID-19 and a state firearm law, and disparities in clinical outcomes. Methods: Retrospective cohort of patients with FRI (0-20 years-old, x̄=9.8, Median = 11) presenting to our hospital EDs from January 2014 to April 2023 (N = 701) and eligible for the Trauma Registry. This period includes two major events, namely the COVID-19 pandemic (March 2020), and passage of state law Constitutional Carry Act (SB 319) (April 2022), allowing for permit-less concealed firearm carry. Single series interrupted time series (ITS) models were run and clinical outcome differences between race and insurance groups were calculated unadjusted and adjusted for confounders using inverse propensity treatment weights (IPTW). The primary outcome was mortality; secondary are admission and discharge. Results: Majority of FRI involved patients who were male (76.7%), Black (74.9%), publicly insured (82.6%), ≤12 years-old (61.8%), and injured by unintentional shootings (45.6%) or assault (43.7%). During COVID-19, there was a sustained increase in FRI rate by 0.42 patients per 1,000 trauma visits per month (95% CI 0.02-0.82, p = 0.042); post-SB 319 it was 2.3 patients per 1,000 trauma visits per month (95% CI 0.23-4.31, p = 0.029). Publicly insured patients had 58% lower odds of mortality than privately insured patients (OR 0.42, 95% CI 0.18-0.99, p = 0.047). When controlled for race and mechanism of injury, among other confounding factors, this association was not significant (p = 0.652). Conclusion: Pediatric FRI are increasing over time, with disproportionate burdens on Black patients, at our hospitals. Disparities in mortality based on insurance necessitate further study. As social and economic repercussions of COVID-19 are still present, and state firearm law SB 319 is still in effect, assessment of ongoing trends is warranted to inform preventative strategies.


Assuntos
COVID-19 , Armas de Fogo , Ferimentos por Arma de Fogo , Criança , Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Adolescente , Adulto Jovem , Adulto , Ferimentos por Arma de Fogo/epidemiologia , Estudos Retrospectivos , Pandemias , COVID-19/epidemiologia
5.
Front Neurol ; 15: 1339255, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38550344

RESUMO

Introduction: Social determinants of health (SDH) are factors that may impact outcomes following pediatric traumatic brain injuries (TBI). The purpose of this study was to investigate the relationship between race and functional outcomes in a diverse pediatric population. We further explored how this association may be modified by SDH factors, including insurance status, social vulnerability, and child opportunity. Methods: A cohort study (N = 401) of children aged 0-18 [median = 9.22 years (IQR: 3.56-13.59)] presenting to the Emergency Department at Level I and II Trauma Centers with mild to severe head injuries. Geocoded variables were used to evaluate SDH. The sample was described overall and by racial/ethnic group, which were adjusted for confounders using inverse propensity treatment weights (IPTW). Weighted and unweighted Firth logistic regression models (mortality) and generalized linear regression models (GOS-E scores) were reported without and then with potential effect modifiers. Results: The sample is majority male (65.84%); race/ethnicity are as follows: White (52.37%), Black/African Americans (35.91%), and Hispanic (11.72%). Black (31.25%) and Hispanic (27.66%) patients had higher rates of severe TBI. 35.89% of White patients were categorized as more socially vulnerable compared to 62.68% Black and 70.21% Hispanic patients. A total 63.64% of White patients were from higher opportunity neighborhoods, compared to 25.87% of Black and 51.06% of Hispanic patients. A total 50.95% of White patients, 25.87% of Black patients, and 17.02% of Hispanic patients were privately insured. There were no differences found between racial and ethnic groups on mortality or GOS-E scores. Discussion: Patients from minority backgrounds had more severe injuries, many resulting from pedestrian vs. motor vehicle accidents. Additionally, patients from minority backgrounds experience more social vulnerability and lower opportunity. Despite these discrepancies, we did not observe differences on rates of mortality or functional outcomes in either racial or ethnic groups. SDH were not found to impact outcomes. Further research is needed to determine how these complex social and environmental variables impact health outcomes.

6.
Biomedicines ; 11(8)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37626664

RESUMO

Blood based traumatic brain injury (TBI) biomarkers offer additional diagnostic, therapeutic, and prognostic utility. While adult studies are robust, the pediatric population is less well studied. We sought to determine whether plasma osteopontin (OPN) and S100B alone or in combination predict mortality, head Computed tomography (CT) findings, as well as 6-month functional outcomes after TBI in children. This is a prospective, observational study between March 2017 and June 2021 at a tertiary pediatric hospital. The sample included children with a diagnosed head injury of any severity admitted to the Emergency Department. Control patients sustained trauma-related injuries and no known head trauma. Serial blood samples were collected at admission, as well as at 24, 48, and 72 h. Patient demographics, acute clinical symptoms, head CT, and 6-month follow-up using the Glasgow outcome scale, extended for pediatrics (GOSE-Peds), were also obtained. The cohort included 460 children (ages 0 to 21 years) and reflected the race and sex distribution of the population served. Linear mixed effect models and logistic regressions were utilized to evaluate the trajectory of biomarkers over time and predictors of dichotomous outcomes. Both OPN and S100B correlated with injury severity based on GCS. S100B and OPN showed lower AUC values (0.59) in predicting positive head CT. S100B had the largest AUC (0.87) in predicting mortality, as well as 6-month outcomes (0.85). The combination of the two biomarkers did not add meaningfully to the model. Our findings continue to support the utility of OPN as a marker of injury severity in this population. Our findings also show the importance of S100B in predicting mortality and 6-month functional outcomes. Continued work is needed to examine the influence of age-dependent neurodevelopment on TBI biomarker profiles in children.

7.
Pediatr Neurol ; 148: 215-222, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37652817

RESUMO

Traumatic brain injury (TBI) is a serious public health concern impacting millions of children and adolescents each year. Experiencing a brain injury during key critical periods of brain development can affect the normal formation of brain networks that are responsible for a range of complex neurocognitive outcomes. In addition, there are multiple pre- and postinjury factors that influence the trajectory of recovery and outcomes. In this review, we will focus on the current state of the literature within pediatric TBI; systematically review the available research on developmental aspects of TBI in children, focusing on the pathophysiology of the injury and its impact on the developing brain; and highlight knowledge gaps for further exploration.

8.
J Child Neurol ; 38(5): 298-306, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37203168

RESUMO

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.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Distúrbios do Início e da Manutenção do Sono , Transtornos do Sono-Vigília , Criança , Humanos , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Ácido D-Aspártico , N-Metilaspartato , Receptores de N-Metil-D-Aspartato , Estudos Retrospectivos , Sono , Transtornos do Sono-Vigília/complicações
9.
J Neuroimmunol ; 376: 578048, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36774765

RESUMO

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.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Humanos , Criança , Pré-Escolar , Adolescente , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Pacientes Internados , Estudos Retrospectivos , Receptores de N-Metil-D-Aspartato , Cognição
10.
Child Neuropsychol ; 29(7): 1003-1020, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-36109848

RESUMO

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.


Assuntos
Logro , Cardiopatias Congênitas , Criança , Humanos , Masculino , Adolescente , Feminino , Estudos Retrospectivos , Estudos Transversais , Escolaridade
11.
J Neuroimmunol ; 370: 577931, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-35872506

RESUMO

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.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Adulto , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Criança , Humanos , Intubação Intratraqueal , Linfócitos , Neutrófilos , Receptores de N-Metil-D-Aspartato , Estudos Retrospectivos
12.
Exp Biol Med (Maywood) ; 247(2): 145-151, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34565198

RESUMO

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.


Assuntos
COVID-19/complicações , Osteopontina/sangue , Índice de Gravidade de Doença , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Adolescente , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/análise , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/patologia , Criança , Pré-Escolar , Feminino , Ferritinas/sangue , Humanos , Lactente , Recém-Nascido , Subunidade alfa de Receptor de Interleucina-2/sangue , Interleucina-6/sangue , Contagem de Linfócitos , Masculino , Contagem de Plaquetas , Estudos Retrospectivos , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica/patologia , Adulto Jovem
13.
Child Neuropsychol ; 28(2): 212-223, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34435553

RESUMO

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.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Transtornos Cognitivos , Adolescente , Criança , Função Executiva , Humanos , Testes Neuropsicológicos , Estudos Retrospectivos
14.
Disabil Rehabil ; 44(7): 1035-1041, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-32649219

RESUMO

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.


Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Adolescente , Adulto , Lesões Encefálicas/reabilitação , Lesões Encefálicas Traumáticas/reabilitação , Criança , Pré-Escolar , Cognição , Humanos , Pacientes Internados , Recuperação de Função Fisiológica , Estudos Retrospectivos , Adulto Jovem
15.
J Head Trauma Rehabil ; 37(4): 240-248, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34320554

RESUMO

OBJECTIVES: To describe dosing practices for amantadine hydrochloride and related adverse effects among children and young adults with traumatic brain injury (TBI) admitted to pediatric inpatient rehabilitation units. SETTING: Eight pediatric acute inpatient rehabilitation units located throughout the United States comprising the Pediatric Brain Injury Consortium. PARTICIPANTS: Two-hundred thirty-four children and young adults aged 2 months to 21 years with TBI. DESIGN: Retrospective data revie. MAIN OUTCOME MEASURES: Demographic variables associated with the use of amantadine, amantadine dose, and reported adverse effects. RESULTS: Forty-nine patients (21%) aged 0.9 to 20 years received amantadine during inpatient rehabilitation. Forty-five percent of patients admitted to inpatient rehabilitation with a disorder of consciousness (DoC) were treated with amantadine, while 14% of children admitted with higher levels of functioning received amantadine. Children with DoC who were not treated with amantadine were younger than those with DoC who received amantadine (median 3.0 vs 11.6 years, P = .008). Recorded doses of amantadine ranged from 0.7 to 13.5 mg/kg/d; the highest total daily dose was 400 mg/d. Adverse effects were reported in 8 patients (16%); nausea/abdominal discomfort and agitation were most common, each reported in 3 patients. The highest reported dose without an adverse effect was 10.1 mg/kg/d. CONCLUSION: During pediatric inpatient rehabilitation, amantadine was prescribed to children across a range of ages and injury severity and was most commonly prescribed to older children with DoC. Dosing varied widely, with weight-based dosing for younger/smaller children at both lower and higher doses than what had been previously reported. Prospective studies are needed to characterize the safety and tolerability of higher amantadine doses and optimize amantadine dosing parameters for children with TBI.


Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Adolescente , Amantadina/uso terapêutico , Lesões Encefálicas/reabilitação , Lesões Encefálicas Traumáticas/complicações , Criança , Humanos , Pacientes Internados , Estudos Retrospectivos , Estados Unidos , Adulto Jovem
16.
Epilepsy Res ; 178: 106787, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34715485

RESUMO

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.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Adolescente , Encefalite Antirreceptor de N-Metil-D-Aspartato/terapia , Criança , Pré-Escolar , Eletroencefalografia , Feminino , Humanos , Imunoterapia , Lactente , Masculino , Receptores de N-Metil-D-Aspartato , Estudos Retrospectivos
18.
J Head Trauma Rehabil ; 36(4): 253-263, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33656473

RESUMO

OBJECTIVES: To characterize the demographics, clinical course, and predictors of cognitive recovery among children and young adults receiving inpatient rehabilitation following pediatric traumatic brain injury (TBI). DESIGN: Retrospective observational, multicenter study. SETTING: Eight acute pediatric inpatient rehabilitation facilities in the United States with specialized programs for treating patients with TBI. PARTICIPANTS: Children and young adults (0-21 years) with TBI (n = 234) receiving inpatient rehabilitation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Admission and discharge status assessed by the WeeFIM Cognitive Developmental Functional Quotient (DFQ) and Cognitive and Linguistic Scale (CALS). RESULTS: Patients admitted to pediatric inpatient rehabilitation are diverse in cognitive functioning. While the majority of patients make improvements, cognitive recovery is constrained for those admitted with the most severe cognitive impairments. Age, time since injury to rehabilitation admission, and admission WeeFIM Cognitive DFQ are significant predictors of cognitive functioning at discharge from inpatient rehabilitation. CONCLUSIONS: This work establishes a multicenter Pediatric Brain Injury Consortium and characterized the demographics and clinical course of cognitive recovery during inpatient rehabilitation of pediatric patients with TBI to aid in prospective study design.


Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Lesões Encefálicas Traumáticas/diagnóstico , Criança , Cognição , Humanos , Pacientes Internados , Tempo de Internação , Estudos Prospectivos , Recuperação de Função Fisiológica , Centros de Reabilitação , Estudos Retrospectivos , Estados Unidos , Adulto Jovem
19.
J Neurosurg Pediatr ; 27(5): 511-517, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33636696

RESUMO

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.


Assuntos
Derivações do Líquido Cefalorraquidiano/métodos , Hidrocefalia/cirurgia , Doenças do Prematuro/cirurgia , Feminino , Vesícula Biliar , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Masculino , Estudos Retrospectivos , Resultado do Tratamento
20.
J Neurotrauma ; 38(14): 1961-1968, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33504256

RESUMO

Traumatic brain injury (TBI) is a major cause of morbidity and mortality in children; survivors experience long-term cognitive and motor deficits. To date, studies predicting outcome following pediatric TBI have primarily focused on acute behavioral responses and proxy measures of injury severity; unsurprisingly, these measures explain very little of the variance following heterogenous injury. In adults, certain acute imaging biomarkers help predict cognitive and motor recovery following moderate to severe TBI. This multi-center, retrospective study, characterizes the day-of-injury computed tomographic (CT) reports of pediatric, adolescent, and young adult patients (2 months to 21 years old) who received inpatient rehabilitation services for TBI (n = 247). The study also determines the prognostic utility of CT findings for cognitive and motor outcomes assessed by the Pediatric Functional Independence Measure, converted to age-appropriate developmental functional quotient (DFQ), at discharge from rehabilitation. Subdural hematomas (66%), contusions (63%), and subarachnoid hemorrhages (59%) were the most common lesions; the majority of subjects had less severe Rotterdam CT scores (88%, ≤ 3). After controlling for age, gender, mechanism of injury, length of acute hospital stay, and admission DFQ in multivariate regression analyses, the highest Rotterdam score (ß = -25.2, p < 0.01) and complete cisternal effacement (ß = -19.4, p < 0.05) were associated with lower motor DFQ, and intraventricular hemorrhage was associated with lower motor (ß = -3.7, p < 0.05) and cognitive DFQ (ß = -4.9, p < 0.05). These results suggest that direct detection of intracranial injury provides valuable information to aid in prediction of recovery after pediatric TBI, and needs to be accounted for in future studies of prognosis and intervention.


Assuntos
Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/psicologia , Transtornos Cognitivos/reabilitação , Transtornos Motores/reabilitação , Tomografia Computadorizada por Raios X , Adolescente , Lesões Encefálicas Traumáticas/reabilitação , Criança , Pré-Escolar , Transtornos Cognitivos/diagnóstico por imagem , Transtornos Cognitivos/etiologia , Feminino , Hospitalização , Humanos , Lactente , Masculino , Transtornos Motores/diagnóstico por imagem , Transtornos Motores/etiologia , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Estudos Retrospectivos , Adulto Jovem
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