Brain volumes and cortical thickness and associations with cognition in children born extremely preterm.

BACKGROUND: Children born extremely preterm (EPT) have altered brain volumes and cortical thickness and lower cognition than children born at term. Associations between these have remained largely unexplored, due to the lack of studies focusing on children born EPT. METHODS: Children underwent brain magnetic resonance imaging (MRI) at term and/or 10 years and cognitive assessments at 12 years. The study comprised of 42 children born EPT and 29 term-born controls with cognitive data and MRI data at 10 years, 25 children born EPT had MRI data at term age and 20 had longitudinal MRI data. RESULTS: Cognition was positively associated with brain volumes at 10 years, but negatively associated with cortical thickness at 10 years. Most associations between term age brain volumes and cognitive outcomes were non-significant for children born EPT. Growth from term to 10 years in children born EPT was not associated with cognition. Insular volume was positively associated with cognition in children born EPT. CONCLUSION: Imaging assessments at 10 years had similar associations to cognition in children born EPT and term-born controls. Insular volume could be a biomarker for cognitive outcome. Associations between brain volumetric growth and cognition require further investigation. IMPACT: This study investigated brain volumes, volumetric growth, and cortical thickness in children born extremely preterm, who have rarely been studied exclusively, and compared the data with term-born controls. In both groups, brain volumes at 10 years were positively associated with cognitive outcome at 12 years, but cortical thickness at 10 years was negatively associated with cognitive outcome at 12 years. Volumetric growth from term age to 10 years was not associated with cognitive outcome in the subset of children born extremely preterm with longitudinal data. Insular volume may be a potential biomarker for cognitive outcome in children born extremely preterm.

Language performance and brain volumes, asymmetry, and cortical thickness in children born extremely preterm.

BACKGROUND: Children born preterm are more prone to have language difficulties. Few studies focus on children born extremely preterm (EPT) and the structural differences in language-related regions between these children and children born at term. METHODS: Our study used T1-weighted magnetic resonance imaging (MRI) scans to calculate the brain volumetry, brain asymmetry, and cortical thickness of language-related regions in 50 children born EPT and 37 term-born controls at 10 years of age. The language abilities of 41 of the children born EPT and 29 term-born controls were then assessed at 12 years of age, using the Wechsler Intelligence Scale for Children, Fifth Edition and the Clinical Evaluations of Language Fundamentals, Fourth Edition. The differences between MRI parameters and their associations with language outcomes were compared in the two groups. RESULTS: Brain volume and cortical thickness of language-related regions were reduced in children born EPT, but volumetric asymmetry was not different between children born EPT and at term. In children born EPT the brain volume was related to language outcomes, prior to adjustments for full-scale IQ. CONCLUSIONS: These findings expand our understanding of the structural correlates underlying impaired language performance in children born with EPT. IMPACT: The article expands understanding of the structure-function relationship between magnetic resonance imaging measurements of language-related regions and language outcomes for children born extremely preterm beyond infancy. Most literature to date has focused on very preterm children, but the focus in this paper is on extreme prematurity and language outcomes. While the brain volume and cortical thickness of language-related regions were reduced in children born EPT only the volume, prior to adjustment for full-scale IQ, was associated with language outcomes. We found no differences in volumetric asymmetry between children born EPT and at term.

Changes in prevalence of non-optimal neurological condition between 6.5 and 12 years in children born extremely preterm.

AIM: To assess prevalence of non-optimal neurological condition and associations with motor function in children born extremely preterm (EPT) up to early adolescence, and to examine potential changes in neurological condition between 6.5 and 12 years. METHOD: A prospective cohort of one hundred six children (EPT n = 62, term n = 44) was assessed at 6.5 and 12 years. Four domains derived from the Touwen Neurological Examination (coordination and balance, posture and muscle tone, reflexes, and nerve function of the eyes and face) were used to assess the presence of a non-optimal neurological condition (defined as the presence of any abnormal domain). The Movement Assessment Battery for Children 2nd ed. was used to evaluate motor function. RESULTS: Twenty-seven children born EPT (44%) were assessed as having a non-optimal neurological condition compared with 4 (9%) in the control group (p=<0.001) at 12 years. Between age 6.5 and 12 years the number of children born EPT with a non-optimal neurological condition decreased from 37 to 27 (p = 0.007). At 12 years these children also had significantly lower MABC-2 total test scores, compared to those with normal neurology: median (range) 57 (32-79) versus 75 (43-99), respectively (p=<0.001). The same was shown for subscale scores; manual dexterity (p=<0.001), aiming/catching (p = 0.004), and balance (p = 0.004). CONCLUSION: The prevalence of a non-optimal neurological condition reduced with increasing age. However, still, at 12 years, these neurological impairments remained significantly more common in the EPT group than in their term-born peers and was shown to be related to a reduced motor function.

Discrete white matter abnormalities at age 8-11 years in children born extremely preterm are not associated with adverse cognitive or motor outcomes.

AIM: Little is known about the prevalence of discrete white matter abnormalities (WMA) beyond the first years in children born extremely preterm (EPT) and the relation to neurodevelopmental outcomes. Our aim was to investigate the prevalence of discrete WMA in children born EPT and the relationship to neonatal white matter injuries (WMI), white matter (WM) volume, WM diffusivity and neurodevelopment. METHODS: The study was a part of a longitudinal follow-up study of EPT neonates. All children were scanned at Karolinska University hospital 2004-2007 (neonates) and 2014-2015 (children at 8-11 years). WMA was qualitatively assessed by visual inspection. Developmental assessment was conducted at 12 years. RESULTS: In total, 112 children (median age 10.3 years, 56 girls) underwent MRI of the brain (68 EPT, 45 controls). In the EPT group, a subset had MRI around term equivalent age (n = 61). In the EPT group, the prevalence of discrete WMA at 8-11 years was 52%. There was a positive association between WMI at TEA and 8-11 years. There was no association between WMI and WM volumes or diffusivity at 8-11 years. Discrete WMA was not related to neurodevelopmental outcomes. CONCLUSION: Discrete WMA was prevalent in children born EPT at 8-11 years but were not related to neurodevelopmental outcomes.

Deep Brain Stimulation of the Pedunculopontine Nucleus Area in Parkinson Disease: MRI-Based Anatomoclinical Correlations and Optimal Target.

BACKGROUND: Experimental studies led to testing of deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) as a new therapy to treat freezing of gait (FOG) in Parkinson disease (PD). Despite promising initial results fueling a growing interest toward that approach, several clinical studies reported heterogeneity in patient responses. Variation in the position of electrode contacts within the rostral brainstem likely contributes to such heterogeneity. OBJECTIVE: To provide anatomoclinical correlations of the effect of DBS of the caudal mesencephalic reticular formation (cMRF) including the PPN to treat FOG by comparing the normalized positions of the active contacts among a series of 11 patients at 1- and 2-yr follow-up and to provide an optimal target through an open-label study. METHODS: We defined a brainstem normalized coordinate system in relation to the pontomesencephalic junction. Clinical evaluations were based on a composite score using objective motor measurements and questionnaires allowing classification of patients as "bad responders" (2 patients), "mild responders" (1 patient) and "good responders" (6 patients). Two patients, whose long-term evaluation could not be completed, were excluded from the analysis. RESULTS: Most effective DBS electrode contacts to treat FOG in PD patients were located in the posterior part of the cMRF (encompassing the posterior PPN and cuneiform nucleus) at the level of the pontomesencephalic junction. CONCLUSION: In the present exploratory study, we performed an anatomoclinical analysis using a new coordinate system adapted to the brainstem in 9 patients who underwent PPN area DBS. We propose an optimal DBS target that allows a safe and efficient electrode implantation in the cMRF.