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

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

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

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

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

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

[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.

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

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

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

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

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

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

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

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

The utility of parent report in the assessment of working memory among childhood brain tumor survivors.

Childhood brain tumor survivors are at increased risk for neurocognitive impairments, including working memory (WM) problems. WM is typically assessed using performance measures. Little is known about the value of parent ratings for identifying WM difficulties, the relationship between rater and performance measures, or predictors of parent-reported WM problems in this population. Accordingly, the current study examined the utility of parent report in detecting WM difficulties among childhood brain tumor survivors treated with conformal radiation therapy (n = 50) relative to siblings (n = 40) and solid tumor survivors not receiving central nervous system-directed therapy (n = 40). Parents completed the Behavior Rating Inventory of Executive Function (BRIEF). Participants were administered WM measures (digit span, self-ordered search tasks). Findings revealed parents rated brain tumor survivors as having significantly more WM problems (p < .01) compared to controls. However, the BRIEF-WM scale demonstrated poor sensitivity and specificity for detecting performance-based problems. Significant, albeit modest, correlations were found between the BRIEF-WM scale and performance measures (r = -.24-.22; p < .05) for the combined group. Age at testing, socioeconomic status, and IQ were significant predictors of parent reported WM problems. Rater and performance measures offer complimentary yet different information in assessing WM, which reiterates the importance of using both within the context of clinical assessment.

Working memory performance among childhood brain tumor survivors.

While longitudinal studies of children treated for brain tumors have consistently revealed declines on measures of intellectual functioning, greater specification of cognitive changes following treatment is imperative for isolating vulnerable neural systems and developing targeted interventions. Accordingly, this cross-sectional study evaluated the performance of childhood brain tumor survivors (n = 50) treated with conformal radiation therapy, solid tumor survivors (n = 40) who had not received central nervous system (CNS) -directed therapy, and healthy sibling controls (n = 40) on measures of working memory [Digit Span and computerized self-ordered search (SOS) tasks]. Findings revealed childhood brain tumor survivors were impaired on both traditional [Digit Span Backward- F(2,127) = 5.98; p < .01] and experimental [SOS-Verbal- F(2,124) = 4.18; p < .05; SOS-Object- F(2,126) = 5.29; p < .01] measures of working memory, and performance on working memory measures correlated with intellectual functioning (Digit Span Backward- r = .45; p < .0001; SOS- r = -.32 to -.26; p < .01). Comparison of performance on working memory tasks to recognition memory tasks (computerized delayed match-to-sample) offered some support for greater working memory impairment. This pattern of findings is consistent with vulnerability in functional networks that include prefrontal brain regions and has implications for the clinical management of children with brain tumors.