Traumatic brain injury (TBI) causes heterogeneous patterns of neurocognitive deficits. In an attempt to identify homogenous subgroups within this heterogeneity, cluster analysis was used to examine memory and attention abilities as measured by the Test of Memory and Learning (TOMAL) in 300 children, 150 with TBI and 150 matched nonbrain injured controls (standardization sample [SS]). Significant differences were present between the TBI and the SS groups on all TOMAL subscale and index scores, with the TBI groups performing approximately 1.3 SD below the SS. Factor analysis of the TOMAL indicated six factors that assessed various aspects of verbal and nonverbal learning and memory, as well as attention/concentration. Cluster analyses of TOMAL factor scores indicated that a four-cluster solution was optimal for the SS group, and a five-cluster solution for the TBI group. For the TBI clusters, differences were present for clinical, achievement, neurocognitive, and behavioral variables, providing some support for the validity of the cluster solution. These findings suggest that TBI results in unique patterns of neurocognitive impairment that are not accounted for by individual differences in test performance commonly observed in normal populations. Additionally, neurocognitive profiles identified using cluster analysis may prove useful for identifying homogeneous subgroups of children with TBI that are differentiated by a number of important clinical, cognitive, and behavioral variables associated with treatment and outcomes.

Mucolipidosis type IV (MLIV) is an autosomal recessive disorder resulting from mutations in the MCOLN1 gene. This gene encodes the endosomal/lysosomal transient receptor potential channel protein mucolipin-1 (TRPML1). Affected patients suffer from neurodevelopmental abnormalities and progressive retinal dystrophy. In a prospective natural history study we hypothesized the presence of an additional slow cerebral neurodegenerative process. We have recruited 5 patients, tested their neurodevelopmental status, and measured cerebral regional volumes and white matter integrity using MRI yearly. Over a period of up to 3 years, MLIV patients remained neurologically stable. There was a trend for increased cortical and subcortical gray matter volumes, and increased ventricular size, while white matter and cerebellar volumes decreased. Mean diffusivity (MD) was increased and fractional anisotropy (FA) values were below normal in all analyzed brain regions. There was a positive correlation between motor scores of the Vineland scale and the FA values in the corticospinal tract (corr coef 0.39) and a negative correlation with the MD values (corr coef. −0.50) in the same brain region. We conclude from these initial findings that deficiency in mucolipin-1 affects the entire brain but that there might be a selective regional cerebral neurodegenerative process in MLIV. In addition, these data suggest that diffusion-weighted imaging might be a good biomarker for following patients with MLIV. Therefore, our findings may be helpful for designing of future clinical trials.

Key PointsQuestionDo children with previously normal neurocognitive function who survive an episode of acute respiratory failure requiring intensive care and invasive mechanical ventilation have worse long-term neurocognitive function than their matched siblings?FindingsIn this cohort study that included 121 sibling pairs, children discharged from intensive care hospitalization for respiratory failure without severe cognitive dysfunction compared with their matched siblings had a mean IQ score of 101.5 vs 104.3, a difference that was statistically significant.MeaningAcute respiratory failure in early childhood was associated with a slightly, but statistically significant, lower subsequent IQ score.