The Use of Methylphenidate During Inpatient Rehabilitation After Pediatric Traumatic Brain Injury: Population Characteristics and Prescribing Patterns.

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.

Objective Neurophysiologic Markers of Cognition After Pediatric Brain Injury.

Background and Objectives: Following brain injury, clinical assessments of residual and emerging cognitive function are difficult and fraught with errors. In adults, recent American Academy of Neurology (AAN) practice guidelines recommend objective neuroimaging and neurophysiologic measures to support diagnosis. Equivalent measures are lacking in pediatrics-an especially great challenge due to the combined heterogeneity of both brain injury and pediatric development. Therefore, we aim to establish quantitative, clinically practicable measures of cognitive function following pediatric brain injury. Methods: Participants with and without brain injury were aged 8-18 years, clinically classified according to cognitive recovery state: N = 8 in disorders of consciousness (DoC), N = 7 in confusional state, N = 19 cognitively impaired, and N = 13 typically developing uninjured controls. We prospectively measured electroencephalographic markers of sensory processing and attention in an auditory oddball paradigm, and of covert movement attempts in a command-following paradigm. Results: In 3 participants with DoC, EEG markers of active attempted command following revealed cognitive function that clinical assessment had failed to detect. These same 3 individuals could also be distinguished from the rest of their group by 2 event-related potentials that correlate with sensory processing and orienting attention in the oddball paradigm. Considered across the whole participant group, magnitudes of these 2 ERP markers significantly increased as cognitive recovery progressed (ANOVA: each p < 0.001); viewed jointly, the 2 ERP markers cleanly delineated the 4 cognitive states. Discussion: Despite heterogeneity of brain injuries and brain development, our objective EEG markers reflected cognitive recovery independent of motor function. Two of these markers required no active participation. Together, they allowed us to identify 3 individuals who meet the criteria for cognitive-motor dissociation. To diagnose, prognose, and track cognitive recovery accurately, such markers should be used in pediatrics.

Cognitive-Motor Dissociation Following Pediatric Brain Injury: What About the Children?

Background and Objectives: Following severe brain injury, up to 16% of adults showing no clinical signs of cognitive function nonetheless have preserved cognitive capacities detectable via neuroimaging and neurophysiology; this has been designated cognitive-motor dissociation (CMD). Pediatric medicine lacks both practice guidelines for identifying covert cognition and epidemiologic data regarding CMD prevalence. Methods: We applied a diverse battery of neuroimaging and neurophysiologic tests to evaluate 2 adolescents (aged 15 and 18 years) who had shown no clinical evidence of preserved cognitive function following brain injury at age 9 and 13 years, respectively. Clinical evaluations were consistent with minimally conscious state (minus) and vegetative state, respectively. Results: Both participants' EEG, and 1 participant's fMRI, provided evidence that they could understand commands and make consistent voluntary decisions to follow them. Both participants' EEG demonstrated larger-than-expected responses to auditory stimuli and intact semantic processing of words in context. Discussion: These converging lines of evidence lead us to conclude that both participants had preserved cognitive function dissociated from their motor output. Throughout the 5+ years since injury, communication attempts and therapy had remained uninformed by such objective evidence of their cognitive abilities. Proper diagnosis of CMD is an ethical imperative. Children with covert cognition reflect a vulnerable and isolated population; the methods outlined here provide a first step in identifying such persons to advance efforts to alleviate their condition.

Prescribing Patterns of Amantadine During Pediatric Inpatient Rehabilitation After Traumatic Brain Injury: A Multicentered Retrospective Review From the Pediatric Brain Injury Consortium.

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.

Acute Imaging Findings Predict Recovery of Cognitive and Motor Function after Inpatient Rehabilitation for Pediatric Traumatic Brain Injury: A Pediatric Brain Injury Consortium Study.

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.