Strategies for treatment of childhood primary angiitis of the central nervous system.

Objective: Childhood primary angiitis of the CNS (cPACNS) is a devastating neurologic disease. No standardized treatment protocols exist, and evidence is limited to open-label cohort studies and case reports. The aim of this review is to summarize the literature and provide informed treatment recommendations. Methods: A scoping review of cPACNS literature from January 2000 to December 2018 was conducted using Ovid, MEDLINE, PubMed, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Vasculitis Foundation, European Vasculitis Society, CanVasc, Google Scholar, and Web of Science. Potentially relevant articles were selected for full-text review using the STROBE checklist if they met the following inclusion criteria: (1) reported treatment, (2) addressed pediatrics, (3) focused on the disease of interest, (4) included ≥5 patients, (5) original research, and (6) full-length articles. Reviews, expert opinions, editorials, case reports with <5 patients, articles lacking treatment information, or non-English articles were excluded. A standardized assessment tool measured study quality. Treatment and outcomes were summarized. Results: Of 2,597 articles screened, 7 studies were deemed high quality. No trials were available so no meta-analysis was possible. Overall, treatment strategies recommended are induction with acute antithrombotic therapy subsequently followed by high-dose oral prednisone taper over 3-12 months and long-term platelet therapy. In angiography-positive progressive-cPACNS and angiography-negative-cPACNS, we also recommend 6 months of IV cyclophosphamide therapy, with trimethoprim/sulfamethoxazole as part of induction, and maintenance therapy with mycophenolate mofetil/mycophenolic acid. Conclusion: No grade-A evidence exists; however, this review provides recommendations for treatment of cPACNS.

Cognitive outcomes of childhood primary CNS vasculitis.

OBJECTIVE: To characterize the clinical cognitive phenotypes and severity of cognitive burden according to disease subtype in children with primary central nervous system vasculitis (cPACNS). METHOD: This retrospective multicenter inflammatory brain disease database study examined the neuropsychological outcomes of 80 children (44 male; mean age = 7.89 years, SD = 4.17) consecutively diagnosed with primary CNS vasculitis between 1992 and 2016. Twenty-one children had small-vessel disease (AN_cPACNS), and 59 had large-vessel disease (including 49 nonprogressive [APNP_cPACNS] and 10 progressive [APP_cPACNS]). Neuroimaging revealed MRI abnormalities in 100% and 90% of children with large- and small-vessel vasculitis, respectively. The primary outcomes were Full Scale IQ (FSIQ) and the index scores from the Wechsler Intelligence Scale for Children-III (WISC-III, WISC-IV, and WISC-V). Analyses explored the effect of disease subtype. RESULTS: Intellectual functioning was assessed on average 2.82 years after symptom onset. Children with small-vessel CNS vasculitis had significantly lower FSIQ scores than did those with large-vessel CNS vasculitis (Ms = 81.90 vs. 94.82; p = .04). Intellectual disability (FSIQ < 70) was more frequent in children with small-vessel disease (24% vs. 5%). All groups displayed lower Working Memory and Processing Speed index scores relative to Verbal Comprehension and Perceptual Reasoning index scores. Group differences in FSIQ remained significant after controlling for the presence of seizures. CONCLUSION: Children with small-vessel CNS vasculitis are more likely to demonstrate deficits in intellectual functioning than are those with large-vessel disease, and children with both types of CNS vasculitis demonstrate relatively poor working memory and processing speed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Health-related quality of life in children with inflammatory brain disease.

OBJECTIVE: To quantify the impact of inflammatory brain diseases in the pediatric population on health-related quality of life, including the subdomains of physical, emotional, school and social functioning. METHODS: This was a multicenter, observational cohort study of children (< 18 years of age) diagnosed with inflammatory brain disease (IBrainD). Patients were included if they had completed at least one Health Related Quality of Life Questionnaire (HRQoL). HRQoL was measured using the Pediatric Quality of Life Inventory Version 4.0 (PedsQL) Generic Core Scales, which provided a total score out of 100. Analyses of trends were performed using linear regression models adjusted for repeated measures over time. RESULTS: In this study, 145 patients were included of which 80 (55%) were females. Cognitive dysfunction was the most common presenting symptoms (63%), and small vessel childhood primary angiitis of the CNS was the most common diagnosis (33%). The mean child's self-reported PedsQL total score at diagnosis was 68.4, and the mean parent's proxy-reported PedsQL score was 63.4 at diagnosis. Child's self-reported PedsQL scores reflected poor HRQoL in 52.9% of patients at diagnosis. Seizures or cognitive dysfunction at presentation was associated with statistically significant deficits in HRQoL. CONCLUSION: Pediatric IBrainD is associated with significantly diminished health-related quality of life. Future research should elucidate why these deficits occur and interventions should focus on improving HRQoL in the most affected subdomains, in particular for children presenting with seizures and cognitive dysfunction.