Limited information is known about neuropsychological outcomes in Alexander disease, a rare leukodystrophy. Two pediatric cases are summarized. Case 1 (evaluations at 6, 7, 9, and 12 years of age) represents Type I Alexander disease with associated seizures. Case 2 (evaluations at 12, 13, and 16 years of age) represents Type II Alexander disease without additional complications. Case 1 experienced declines in intellectual functioning, visual motor skills, receptive vocabulary, verbal memory, and academic achievement. Case 2 experienced variable neurocognitive change and academic functioning, with average word reading and spelling. Verbal memory also remained intact. Taken together, individuals with Alexander disease may experience cognitive decline to variable degrees. Type I Alexander disease, associated with earlier onset and additional neurological complications, may presage greater cognitive decline than Type II. Due to variability in functioning over time, it is critical to follow individuals across development to make recommendations for educational and treatment planning.
Objective: To determine whether exposure to traumatic brain injury (TBI) before 10 years of age is associated with development of a mood or anxiety disorder by 25 years of age, and whether sex or injury severity influences this risk. Setting: Olmsted County, Minnesota. Participants: A total of 5518 persons born from January 1, 1976, through December 31, 1982. Design: Population-based, birth cohort study. Children sustaining TBI before 10 years of age (index date) were confirmed by manual record review and classified by injury severity using the Mayo Classification System. Each TBI case was age- and sex-matched to 2 referents from the same birth cohort without a history of TBI at the index date. Cox proportional hazards models were fit to compare the risk of a subsequent clinically diagnosed mood or anxiety disorder by 25 years of age between TBI cases and referents. Separate analysis was performed stratified by sex and injury severity. Main Measures: Incidence of mood and anxiety disorders determined through clinical diagnostic codes and manual record review. Results: The study included 562 children (238 females [42.3%] and 324 males [57.7%]) with TBI before 10 years of age (mean [SD] age at TBI: 4.7 [2.8] years). At least 1 mood or anxiety disorder was diagnosed for 115 persons with TBI and 215 referents. No statistically significant association existed between childhood TBI status and anxiety disorder (adjusted hazard ratio [aHR], 1.01 [95% confidence interval (CI), 0.71-1.43]; P = .97) or mood disorder (aHR, 1.16 [95% CI, 0.92-1.47]; P = .21). However, females who sustained TBI had a significantly increased risk of a subsequently diagnosed mood disorder compared with age-matched female referents (aHR, 1.40 [95% CI, 1.04-1.89]; P = .03). Conclusions: This study suggests that isolated TBI before 10 years of age is not significantly associated with an increased risk of anxiety or mood disorder by 25 years of age, though females may be at an increased risk.
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