Neuroanatomical correlates of working memory performance in Neurofibromatosis 1

Introduction: Neurofibromatosis 1 (NF1) is a single-gene disorder associated with cognitive impairments, particularly with deficits inworking memory. Prior research indicates that brain structure is affected in NF1, but it is unclear how these changes relate to aspectsof cognition.Methods: 29 adolescents aged 11-17 years were compared to age and sex-matched controls. NF1 subjects were assessed using detailedmultimodal measurements of working memory at baseline followed by a 3T MR scan. A voxel-based morphometry approach was usedto estimate the total and regional gray matter(GM) volumetric differences between the NF1 and control groups. The working memory metrics were subjected to a principal component analysis (PCA) approach.Results: The NF1 groups showed increased gray matter volumes in the thalamus, corpus striatum, dorsal midbrain and cerebellumbilaterally in the NF1 group as compared to controls. Principal component analysis on the working memory metrics in the NF1 groupyielded three independent factors ref lecting high memory load, low memory load and auditory working memory. Correlation analysesrevealed that increased volume of posterior cingulate cortex, a key component of the default mode network (DMN) was significantlyassociated with poorer performance on low working memory load tasks.Conclusion: These results are consistent with prior work showing larger subcortical brain volumes in the NF1 cohort. The strongassociation between posterior cingulate cortex volume and performance on low memory load conditions supports hypotheses of deficient DMN structural development, which in turn may contribute to the cognitive impairments in NF1

Quantification of structural changes in the corpus callosumin children with profound hypoxic-ischaemic brain injury

Background Birth-related acute profound hypoxic–ischaemic brain injury has specific patterns of damage including the paracentral lobules. Objective To test the hypothesis that there is anatomically coherent regional volume loss of the corpus callosum as a result of this hemispheric abnormality. Materials and methods Study subjects included 13 children with proven acute profound hypoxic–ischaemic brain injury and 13 children with developmental delay but no brain abnormalities. A computerised system divided the corpus callosum into 100 segments, measuring each width. Principal component analysis grouped the widths into contiguous anatomical regions. We conducted analysis of variance of corpus callosum widths as well as support vector machine stratification into patient groups. Results There was statistically significant narrowing of the mid–posterior body and genu of the corpus callosum in children with hypoxic–ischaemic brain injury. Support vector machine analysis yielded over 95% accuracy in patient group stratification using the corpus callosum centile widths. Conclusion Focal volume loss is seen in the corpus callosum of children with hypoxic–ischaemic brain injury secondary to loss of commissural fibres arising in the paracentral lobules. Support vector machine stratification into the hypoxic–ischaemic brain injury group or the control group on the basis of corpus callosum width is highly accurate and points towards rapid clinical translation of this technique as a potential biomarker of hypoxic–ischaemic brain injur

Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation

Purpose By incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) and to establish diagnostic criteria for Legius syndrome (LGSS). Methods We used a multistep process, beginning with a Delphi method involving global experts and subsequently involving non-NF experts, patients, and foundations/patient advocacy groups. Results We reached consensus on the minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS, which have phenotypic overlap in young patients with pigmentary findings. Criteria for the mosaic forms of these conditions are also recommended. Conclusion The revised criteria for NF1 incorporate new clinical features and genetic testing, whereas the criteria for LGSS were created to differentiate the two conditions. It is likely that continued refinement of these new criteria will be necessary as investigators (1) study the diagnostic properties of the revised criteria, (2) reconsider criteria not included in this process, and (3) identify new clinical and other features of these conditions. For this reason, we propose an initiative to update periodically the diagnostic criteria for NF1 and LGSS