Development of the Corpus Callosum: An MRI Study.

The size and shape of the corpus callosum and its major components (genu, body, and splenium) were measured by magnetic resonance imaging (MRI) in 118 normocephalic individuals aged from 1 postnatal week to 18.7 years. Genu, body, splenial, and total corpus callosal areas increased by 40-100% during the first year of life (p < 0.05). The genu expanded to a greater extent than the splenium during the first 6 years, while the splenium expanded to a greater extent between 7 and 18 years. The age-related difference in the maximal expansion of these structures indicated an anterior to posterior wave of corpus callosal enlargement during maturation, probably the consequence of differential axonal myelination. No sex differences existed during these two developmental phases for the genu, splenial, or total corpus callosal areas with or without scaling to the cerebral hemispheric volume. During infancy (0-24 months), however, the mean female splenial ratio (length/height) of 0.79 was greater than the male ratio of 0.65 (p = 0.024). The cerebral hemispheric length/height ratio was also greater in females, indicating that during infancy the female brain (and its component the corpus callosal splenium) is relatively longer than the male brain. This sex difference was confined to the splenium and disappeared with increasing age.

Factors associated with delayed recovery in athletes with concussion treated at a pediatric neurology concussion clinic.

PURPOSE: With the increase in knowledge and management of sport-related concussion over the last 15 years, there has been a shift from a grading scale approach to an individualized management approach. As a result, there is an increased need to better understand the factors involved in delayed recovery of concussion. The purpose of this retrospective study was to examine factors that may be associated with recovery from sport-related concussion in student athletes aged 11 to 18 years old. METHODS: Of the 366 patients who met the inclusion criteria, 361 were included in our analysis. The primary dependent variable included days until athlete was able to return to play (RTP). Independent variables of interest included age, gender, academic performance, comorbid factors, sports, on-field markers, days until initial neurological evaluation, Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT®) scores, acute headache rescue medications, chronic headache medication, sleep medication, and referral to concussion rehabilitation program. RESULTS: Variables associated with longer median RTP were being female (35 days), having a referral to concussion rehabilitation program (53 days), being prescribed acute headache rescue therapy (34 days), and having chronic headache treatment (53 days) (all p < 0.05). Variables associated with shorter RTP were on-field marker of headache (23 days) and evaluation within 1 week of concussion by a concussion specialist (16 days) (Both p < 0.05). CONCLUSION: This study supports the need for a concussed athlete to have access to a provider trained in concussion management in a timely fashion in order to prevent delayed recovery and return to play.

Frontal brain expansion during development using MRI and endocasts: relation to microcephaly and Homo floresiensis.

A major hall of hominid brain evolution is an expansion of the frontal lobes. To determine if a similar trajectory occurs during modern human development, the MRI scans of 118 living infants, children, and adolescents were reviewed and three specific measurements obtained: frontal width (FW), maximal cerebral width (MW), and maximal cerebral length (ML). The infantile brain is uniformly wide but relatively short, with near equal FW and MW. The juvenile brain exhibits a wider MW than FW, while FW of the adolescent brain expands to nearly equal MW, concurrent with an increase in ML. The preferential frontal lobe expansion during modern human development parallels that observed during the evolution of Homo. In 17 microcephalic individuals, only 6 (35%) exhibited preferential frontal lobe hypoplasia, presumably a reflection of multiple etiologies that adversely affect differing brain regions. Compared to 79 modern human adult endocasts and 12 modern microcephalic endocasts, LB1 (Homo floresiensis) clustered more consistently with the microcephalic sample than with the normocephalic sample.

Craniometric measures of microcephaly using MRI.

BACKGROUND: Microcephalic brains exhibit varying sizes, shapes, and dimensions when compared to normocephalic counterparts, but the extent of these differences is unresolved. AIMS: To ascertain developmental changes in brain morphology using craniometric (linear brain) measures derived from MRI in microcephalic individuals and in normocephalic controls. STUDY DESIGN: A retrospective, cross-sectional cohort study. SUBJECTS: Twenty-one primary and secondary microcephalic individuals ages 2 postnatal weeks to 8.5 years with occipito-frontal circumference<2nd percentile for age; 83 age-equivalent normocephalic controls. OUTCOME MEASURES: Age, sex, weight, height, body mass index, occipito-frontal circumference, and diagnosis prompting the MRI scan. Sixteen craniometric measures to determine specific ratios and age-related changes in brain shape and size. RESULTS: Microcephalic infants and children not only have abnormally small brains but also proportionately lower weights and heights. The brain volumes of both primary and secondary microcephalics were quite variable, ranging from 266 to 723 cm(3) and 440 to 730 cm(3), respectively (p=0.34). Despite their smaller sizes, the shapes of 15/21 (71%) microcephalic brains were similar to those of age-equivalent controls. Cerebral hemispheric configurations were not consistent among the 6 misshapen brains, which included 2 primary, 3 secondary, and 1 unknown microcephalics. Older microcephalic brains could be distinguished from their normocephalic counterparts by two specific craniometric ratios (frontal cerebellar pole/sagittal cerebral length; axial temporal width/axial cerebellar width), each incorporating cerebral and cerebellar dimensions in either length or width. CONCLUSIONS: The findings should provide useful information for distinguishing the characteristics of both modern and ancient microcephalic from normocephalic brains.

Craniometric ratios of microcephaly and LB1, Homo floresiensis, using MRI and endocasts.

The designation of Homo floresiensis as a new species derived from an ancient population is controversial, because the type specimen, LB1, might represent a pathological microcephalic modern Homo sapiens. Accordingly, two specific craniometric ratios (relative frontal breadth and cerebellar protrusion) were ascertained in 21 microcephalic infants and children by using MRI. Data on 118 age-equivalent control (normocephalic) subjects were collected for comparative purposes. In addition, the same craniometric ratios were determined on the endocasts of 10 microcephalic individuals, 79 normal controls (anatomically modern humans), and 17 Homo erectus specimens. These ratios were then compared with those of two LB1 endocasts. The findings showed that the calculated cerebral/cerebellar ratios of the LB1 endocast [Falk D, et al. (2007) Proc Natl Acad Sci USA 104:2513-2518] fall outside the range of living normocephalic individuals. The ratios derived from two LB1 endocasts also fall largely outside the range of modern normal human and H. erectus endocasts and within the range of microcephalic endocasts. The findings support but do not prove the contention that LB1 represents a pathological microcephalic Homo sapiens rather than a new species, (i.e., H. floresiensis).

Craniometric measures during development using MRI.

Developmental changes in brain volume and shape in infants, children, and adolescents were ascertained with MRI, using craniometric (linear brain) measures in 118 individuals, ages 1 postnatal week to 18.7years. Collected clinical data included age, sex, weight, height, body mass index, occipito-frontal circumference (OFC), and diagnosis prompting the MRI scan. Twenty craniometric measures were obtained to allow for the determination of specific ratios as well as sex and age-related changes in brain shape and size. Analysis of the cohort showed that OFC is larger today than 40years ago, likely related to a concomitant increase in body stature. The data indicated a wide variation in the maturational pattern of several specific craniometric ratios, which reflects changes in the volume and configuration of the brain with advancing age. The increases in brain volume and changes in brain shape were most dramatic during infancy, with continued minor escalations in volume and reshaping during childhood and adolescence. Sex differences existed both in brain volume and shape, as well as evidence of sexual dimorphism. Changes in cerebellar volume and shape lagged behind the corresponding changes in the cerebral hemispheres. These collective data in living developing individuals allow for comparisons of clinical or craniometric measures in distant and more recent humans.

Early onset of ataxia in a child with a pathogenic SCA8 allele.

This case report describes a child with an expanded CTA/CTG repeat in one allele of the spinocerebellar ataxia 8 gene. This patient presented with ataxia at a much earlier age than is typical for patients with this condition. This unique patient further highlights the complexity of the role that this molecular defect plays in the onset and course of the disease.

Childhood ischemic stroke in a nonurban population.

A 10-year, retrospective review of the etiology, outcome, and complications of ischemic stroke in children from a nonurban population was conducted. Twenty-seven children were identified (14 boys, 13 girls), ages 1.25 to 17 years (mean 7.7 years). Etiologies included undetermined (22%), arterial dissection (19%), coagulopathy (15%), embolism (15%), moyamoya disease (11%), sickle cell disease (11%), isolated angiitis of the central nervous system or vasculitis (11%), or other known source (11%; two fibromuscular dysplasia, one L-asparaginase). More than one risk factor was present in five children. Seventeen (65%) children were anticoagulated, with no adverse events occurring. Nine children were anticoagulated initially with low-molecular-weight heparin. Other treatments included corticosteroids; physical, occupational, and speech therapy; and anticonvulsants for concomitant seizures. Follow-up ranged from 3 to 60 months (mean 17 months) and was as follows: 6 (22%) were normal, 9 (33%) had mild impairment, and 12 (44%) had moderate to severe deficits. There were no deaths. Neurologic complications included seizure (two), behavioral problems (two), and hemorrhagic conversion (one). In this population, the outcome from ischemic stroke was similar to that of other studies, with the majority of children demonstrating persistent neurologic deficits. Etiology could be determined for the majority of patients, with 19% having more than one risk factor.

The use of enoxaparin in children with acute, nonhemorrhagic ischemic stroke.

The use of low-molecular-weight heparin offers multiple advantages over unfractionated heparins in pediatric patients with acute ischemic stroke. The safety and efficacy of low-molecular-weight heparin have been demonstrated in adults, but less is known about their use in children. This study reviews retrospectively the use of low-molecular-weight heparin in children with acute, ischemic, nonhemorrhagic strokes. A database search was used to locate all children who experienced an ischemic stroke between July 1991 and January 2001 and who were subsequently treated with low-molecular-weight heparin. Eight children were identified (aged 37 months to 17 years; median age, 133 months) who were treated with the low-molecular-weight heparin enoxaparin. Enoxaparin was used in one case as the sole treatment, in six cases as a bridge to oral anticoagulant therapy with warfarin, and in one case as a replacement treatment after several days of warfarin therapy. The median duration of treatment with enoxaparin was 4 days. During this period, no major bleeding complications were observed, and no new thrombi or extensions of thrombi occurred. One patient did experience mild oozing at an intravenous site, and another experienced an episode of epistaxis. Enoxaparin was discontinued in one patient because of discomfort associated with the subcutaneous injections. Although the number of patients was limited, it appears that enoxaparin is a safe and efficacious alternative to the use of unfractionated heparin in children with acute, nonhemorrhagic ischemic stroke.