Key Points Question What are the risks to stable neurocognitive outcome after allogeneic hematopoietic stem cell transplantation for childhood cerebral X-linked adrenoleukodystrophy? Findings This single-center case series involving 36 boys with cerebral X-linked adrenoleukodystrophy found that all patients with favorable neuroimaging and matched bone marrow transplant had stable neurocognitive survival. In contrast, the disease progressed for all patients without these factors, and many developed major functional disabilities. Meaning Patients without matched bone marrow transplant or with unfavorable neuroimaging findings may need therapeutic options other than hematopoietic stem cell transplantation.

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BackgroundA number of studies have investigated cognitive impairment in paediatric patients with multiple sclerosis (MS) but deficits regarding executive functions have not been comprehensively assessed up to now. This study was meant to explore cognitive impairment in German paediatric MS patients with a focus on deficits in executive functions and relate these to clinical disease parameters.Methods and findingsForty paediatric MS patients, which presented at the German centre for MS in childhood and adolescence, were assessed for cognitive deficits applying a very comprehensive battery of cognitive tests including the Wechsler Intelligence scale and subtests of the D-KEFS for executive functions. The performance of MS patients was compared with a group of age and sex matched healthy controls using between-subjects ANOVAs. Paediatric MS patients performed worse in tests assessing verbal comprehension and fluency, processing speed, memory, calculation skills and other executive functions. Arranged by the cognitive domain, group differences were most pronounced regarding verbal comprehension and fluency for the WISC subtests Comprehension (p = 0.000), Vocabulary (p = 0.003) and Information (p = 0.005); regarding processing speed for the written SDMT (p = 0.001) and the WISC subtest Coding (p = 0.005); regarding memory for the VLMT training (p = 0.007) and the BASIC MLT pattern learning training (p = 0.009); regarding executive functions including working memory for the WISC subtest Arithmetics (p = 0.002), the D-KEFS Design Fluency (p = 0.003) and the Corsi block tapping backward task (p = 0.003). Fluid reasoning was largely intact. Relations of cognitive performance and clinical parameters were assessed in MS patients. Disease duration was associated with a reduced performance in tests belonging to the domains verbal comprehension and fluency (WISC Vocabulary: p = 0.034, WISC Information: p = 0.015) and fluid reasoning (WISC Picture Completion: p = 0.003) as well as the WISC Working Memory Index (p = 0.047). Patients with a disease onset between 11 and 14 years performed better in fluid reasoning (WISC matrix reasoning: p = 0.024) than patients with a disease onset at an age above 14. The number of relapses negatively influenced the visual spatial memory performance (BASIC MLT pattern learning training: p = 0.009).ConclusionsThe distribution of cognitive deficits in a representative group German of paediatric MS patients was similar to the pattern known from other European and North-American cohorts. Paediatric MS patients do have cognitive deficits in executive functions and key qualities necessary for successful school performance. Disease duration, age of onset and the number of relapses influence cognitive performance. Cognitive screenings should be implemented on a regular basis for paediatric MS patients, enabling early intervention.

Background and objectiveStudy evaluating Betaferon(R)'s safety and tolerability in paediatric patients with multiple sclerosis (BETAPAEDIC) is a prospective, open-label observational multicentre study to assess the safety and effectiveness of interferon beta-1b in paediatric patients with relapsing–remitting multiple sclerosis.MethodsTreatment-naïve patients (12–16 years) scheduled to start interferon beta-1b were enrolled with follow-up visits every six months for two years. Effectiveness was evaluated by annualised relapse rate, Expanded Disability Status Scale progression, cranial magnetic resonance imaging and cognitive testing. Fatigue was assessed by the Fatigue Severity Scale.ResultsSixty-eight patients were screened and 67 enrolled, with mean (standard deviation) age 14.2 (1.3) years (n=65 in the effectiveness analysis). Mean disease duration was 11 months before study enrolment; at baseline, mean (standard deviation) Expanded Disability Status Scale was 0.6 (1.0); T2 lesion number 18.3 (15.1). Mean annualised relapse rate during the study was 0.7 (n=57), 28/57 patients (49.1%) had no relapses and for 40/52 (76.9%) no Expanded Disability Status Scale progression was observed; 23/56 (41.1%) were relapse- and progression-free to last follow-up. Neuropsychological test and fatigue scores were within normal ranges (baseline and last follow-up). Eighteen patients had fatigue at some point. New T2 and gadolinium-enhancing (Gd+) lesions were seen in 43/55 (66.2%) and 29/55 (52.7%) patients respectively. Most frequent adverse events were influenza-like illness, headache, injection-site reactions and elevated liver enzymes.ConclusionInterferon beta-1b is an effective treatment with a favourable safety profile for paediatric patients.