Neurological and cognitive outcomes after antibody-negative autoimmune encephalitis in children.

AIM: To characterize the neurological and cognitive outcomes in children with antibody-negative autoimmune encephalitis (Ab-negative AE). METHOD: A cohort of children presenting to our institution over a 10-year period with autoimmune encephalitis was identified by structured retrospective review of medical records. Clinical features at presentation and final follow-up were recorded. Neuropsychological testing was performed in a subset of patients. Outcomes after Ab-negative AE were compared with outcomes after N-methyl-D-aspartate receptor antibody encephalitis (NMDARE). RESULTS: Forty-four patients (26 females, 18 males, median age 9y 2mo [interquartile range 4y 5mo-11y 8mo], 23 with NMDARE) with a diagnosis of autoimmune encephalitis were included. Postencephalitic epilepsy was more frequent after Ab-negative AE compared to NMDARE (61% vs 14%, p=0.002). Cognitive testing was performed in a subset of patients (n=21; Ab-negative AE=11, NMDARE=10). Full-scale IQ was lower after Ab-negative AE than NMDARE (mean IQ 75 vs 92, p=0.02), primarily because of reduced verbal comprehension index (80 vs 98, p=0.01) and working memory index (77 vs 95, p=0.09). The cognitive function most commonly impaired was executive function (80% [8/10] vs 22% [2/9]). INTERPRETATION: Ab-negative AE was associated with poorer cognitive outcomes than NMDARE at 1-year follow-up. Further studies are required to evaluate if immunotherapy can be optimized to improve outcome.

Unusual Presentations of Dystrophinopathies in Childhood.

X-linked recessive mutations in the dystrophin gene are one of the most common causes of inherited neuromuscular disorders in humans. Duchenne muscular dystrophy, the most common phenotype, and Becker muscular dystrophy are often recognizable by certain clinical features; however, less frequent presentations require a higher degree of suspicion. In this article, we describe a series of 6 children (4 boys, 2 girls) referred to a tertiary pediatric neuromuscular clinic for isolated elevated creatine kinase levels (range: 720-7000 IU/L) identified on initial assessment for otherwise unexplained transaminase elevations (n = 2), a social communication disorder (n = 3), and exertional myalgia and/or rhabdomyolysis (n = 1). There was no preceding family history of neuromuscular disease. One boy had an additional history of severe cerebral palsy and cyclical vomiting, and 1 girl had a history of maternal hepatitis C. There was no significant weakness at presentation, and the majority remained stable over a prolonged period of follow-up (age range at last follow-up: 9-16 years). All 6 children were found to carry dystrophin gene mutations resulting in milder phenotypes. This series highlights that dystrophinopathies may not uncommonly present with features distinct from the classic Duchenne muscular dystrophy and Becker muscular dystrophy phenotypes in both boys and girls. Pediatricians should be aware of such atypical presentations to initiate a timely and adequate diagnostic process. Establishing the correct genetic diagnosis of a dystrophinopathy is important to allow appropriate genetic counseling, to implement relevant surveillance and management strategies, and to avoid unnecessary investigations in search of an incorrect alternative diagnosis.