Larry A. Kramer

Neuroimaging, Physical, and Developmental Findings After Inflicted and Noninflicted Traumatic Brain Injury in Young Children

Objective. To characterize neuroimaging, physical, neurobehavioral, and developmental findings in children with inflicted and noninflicted traumatic brain injury (TBI) and to identify characteristic features of inflicted TBI. Methods and Patients. Forty children, 0 to 6 years of age, hospitalized for TBI who had no documented history of previous brain injury were enrolled in a prospective longitudinal study. TBI was categorized as either inflicted (n = 20) or noninflicted (n = 20) based on the assessment of hospital and county protective services. Glasgow Coma Scale scores and neonatal history were comparable in both groups. Outcome Measures. Acute computed tomography/magnetic resonance imaging studies and physical findings were evaluated. Glasgow Outcome Scale scores, cognitive development, and motor functioning were assessed an average of 1.3 months after TBI. χ2 analyses assessed differences in the distribution of findings in the inflicted and noninflicted TBI groups. Results. Signs of preexisting brain injury, including cerebral atrophy, subdural hygroma, and ex vacuo ventriculomegaly, were present in 45% of children with inflicted TBI and in none of the children with noninflicted TBI. Subdural hematomas and seizures occurred significantly more often in children with inflicted TBI. Intraparenchymal hemorrhage, edema, skull fractures, and cephalohematomas were similar in both groups. Retinal hemorrhage was only identified in the inflicted TBI group. Glasgow Outcome Scale scores indicated a significantly less favorable outcome after inflicted than noninflicted TBI. Mental deficiency was present in 45% of the inflicted and 5% of the noninflicted TBI groups. Conclusions. Characteristic features of inflicted TBI included acute computed tomography/magnetic resonance imaging findings of preexisting brain injury, extraaxial hemorrhages, seizures, retinal hemorrhages, and significantly impaired cognitive function without prolonged impairment of consciousness.

Optic Disc Edema, Globe Flattening, Choroidal Folds, and Hyperopic Shifts Observed in Astronauts after Long-duration Space Flight

PURPOSE To describe the history, clinical findings, and possible etiologies of ophthalmic findings discovered in 7 astronauts after long-duration space flight, and document vision changes in approximately 300 additional astronauts. DESIGN Retrospective, observational examination of ophthalmic findings in 7 astronauts and analysis of postflight questionnaires regarding in-flight vision changes in approximately 300 additional astronauts. PARTICIPANTS Seven astronauts with ophthalmic anomalies upon return from long-duration space missions to the International Space Station and 300 additional astronauts who completed postflight questionnaires regarding in-flight vision changes. METHODS Before and after long-duration space flight, all 7 subjects underwent complete eye examinations, including cycloplegic and/or manifest refraction and fundus photography. Six underwent postmission optical coherence tomography (OCT) and magnetic resonance imaging (MRI); 4 had lumbar punctures (LP). Approximately 300 astronauts were queried regarding visual changes during space missions. MAIN OUTCOME MEASURES Refractive change, fundus photograph examination, retina OCT, orbital MRI, LP opening pressures, and examination of visual acuity data. RESULTS After 6 months of space flight, 7 astronauts had ophthalmic findings, consisting of disc edema in 5, globe flattening in 5, choroidal folds in 5, cotton wool spots (CWS) in 3, nerve fiber layer thickening by OCT in 6, and decreased near vision in 6 astronauts. Five of 7 with near vision complaints had a hyperopic shift ≥+0.50 diopters (D) between pre/postmission spherical equivalent refraction in 1 or both eyes (range, +0.50 to +1.75 D). These 5 showed globe flattening on MRI. Lumbar punctures performed in the 4 with disc edema documented opening pressures of 22, 21, 28, and 28.5 cm H(2)O performed 60, 19, 12, and 57 days postmission, respectively. The 300 postflight questionnaires documented that approximately 29% and 60% of astronauts on short and long-duration missions, respectively, experienced a degradation in distant and near visual acuity. Some of these vision changes remain unresolved years after flight. CONCLUSIONS We hypothesize that the optic nerve and ocular changes we describe may result from cephalad fluid shifts brought about by prolonged microgravity exposure. The findings we report may represent parts of a spectrum of ocular and cerebral responses to extended microgravity exposure. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Reduced Anterior Corpus Callosum White Matter Integrity is Related to Increased Impulsivity and Reduced Discriminability in Cocaine-Dependent Subjects: Diffusion Tensor Imaging

Brain imaging studies find evidence of prefrontal cortical dysfunction in cocaine-dependent subjects. Similarly, cocaine-dependent subjects have problems with behaviors related to executive function and impulsivity. Since prefrontal cortical axonal tracts cross between hemispheres in the corpus callosum, it is possible that white matter integrity in the corpus callosum could also be diminished in cocaine-dependent subjects. The purpose of this study was to compare corpus callosum white matter integrity as measured by the fractional anisotropy (FA) on diffusion tensor imaging (DTI) between 18 cocaine-dependent subjects and 18 healthy controls. The Barratt Impulsiveness Scale (BIS-11) and a continuous performance test: the Immediate and Delayed Memory Task (IMT/DMT) were also collected. Results of the DTI showed significantly reduced FA in the genu and rostral body of the anterior corpus callosum in cocaine-dependent subjects compared to controls. Cocaine-dependent subjects also had significantly higher BIS-11 scores, greater impulsive (commission) errors, and reduced ability to discriminate target from catch stimuli (discriminability) on the IMT/DMT. Within cocaine dependent subjects there was a significant negative correlation between FA in the anterior corpus callosum and behavioral laboratory measured impulsivity, and there was a positive correlation between FA and discriminability. The finding that reduced integrity of anterior corpus callosum white matter in cocaine users is related to impaired impulse control and reduced ability to discriminate between target and catch stimuli is consistent with prior theories regarding frontal cortical involvement in impaired inhibitory control in cocaine-dependent subjects.

Increased Pelvic Vein Thrombi in Cryptogenic Stroke Results of the Paradoxical Emboli From Large Veins in Ischemic Stroke (PELVIS) Study

Background and Purpose— Cryptogenic stroke is associated with an increased prevalence of patent foramen ovale. The Paradoxical Emboli From Large Veins in Ischemic Stroke (PELVIS) study hypothesized that patients with cryptogenic stroke have an increased prevalence of pelvic deep venous thrombosis (DVT). Methods— At 5 sites, patients 18 to 60 years of age received an MRI venogram (MRV) of the pelvis within 72 hours of new symptom onset. Clinical data were then determined. Radiologists blinded to clinical data later read the scans. Results— The 95 patients who met entry criteria were scanned. Their mean±SD age was 46±10 years, and time from stroke onset to pelvic MRV scan was 49±16 hours. Compared with those with stroke of determined origin (n=49), patients with cryptogenic stroke (n=46) were significantly younger, had a higher prevalence of patent foramen ovale (61% versus 19%), and had less atherosclerosis risk factors. Cryptogenic patients had more MRV scans with a high probability for pelvic DVT (20%) than patients with stroke of determined origin (4%, P <0.03), with most having an appearance of a chronic DVT. Conclusions— In this study of young stroke patients evaluated early after stroke, patients with cryptogenic stroke showed differences in several clinical features compared with patients with stroke of determined origin, including increased prevalence of pelvic DVT. The results require confirmation but suggest that paradoxical embolus from the pelvic veins may be the cause of stroke in a subset of patients classified as having cryptogenic stroke.

Arrested development and disrupted callosal microstructure following pediatric traumatic brain injury: relation to neurobehavioral outcomes.

Chronic pediatric traumatic brain injury (TBI) is associated with significant and persistent neurobehavioral deficits. Using diffusion tensor imaging (DTI), we examined area, fractional anisotropy (FA), radial diffusion, and axial diffusion from six regions of the corpus callosum (CC) in 41 children and adolescents with TBI and 31 comparison children. Midsagittal cross-sectional area of the posterior body and isthmus was similar in younger children irrespective of injury status; however, increased area was evident in the older comparison children but was obviated in older children with TBI, suggesting arrested development. Similarly, age was correlated significantly with indices of tissue microstructure only for the comparison group. TBI was associated with significant reduction in FA and increased radial diffusivity in the posterior third of the CC and in the genu. The axial diffusivity did not differ by either age or group. Logistic regression analyses revealed that FA and radial diffusivity were equally sensitive to post-traumatic changes in 4 of 6 callosal regions; radial diffusivity was more sensitive for the rostral midbody and splenium. IQ, working memory, motor, and academic skills were correlated significantly with radial diffusion and/or FA from the isthmus and splenium only in the TBI group. Reduced size and microstructural changes in posterior callosal regions after TBI suggest arrested development, decreased organization, and disrupted myelination. Increased radial diffusivity was the most sensitive DTI-based surrogate marker of the extent of neuronal damage following TBI; FA was most strongly correlated with neuropsychological outcomes.

Estimation of CSF, white and gray matter volumes in hydrocephalic children using fuzzy clustering of MR images.

An algorithm and set of procedures for measuring volumes of cerebrospinal fluid (CSF), white matter, and gray matter from transaxial magnetic resonance images (MRI) of the brain are described. The algorithm is a variant of the fuzzy c-means clustering method for texture identification. This technique is used mainly to solve the problem of volume averaging of tissue compartments, but also has other advantages. It is fast, accurate, and relatively operator independent. Furthermore, it does not depend on statistical assumptions such as data normality, nor does it require any a priori heuristics. The procedure was tested successfully on imaged phantoms of known volume composition and compared with results achieved using a standard morphometric measurement approach. The procedure was also applied to brain MRIs of three clinically normal children and three age-matched children with hydrocephalus using both proton density and T2-weighted images. The algorithm was able to detect the expected increased amounts of CSF and decreased amounts of white matter characteristic of the hydrocephalic brain.

Executive functions following traumatic brain injury in young children: A preliminary analysis

To examine executive processes in young children with traumatic brain injury (TBI), we evaluated performance of 44 children who sustained moderate-to-severe TBI prior to age 6 and to 39 comparison children on delayed response (DR), stationary boxes, and spatial reversal (SR) tasks. The tasks have different requirements for holding mental representations in working memory (WM) over a delay, inhibiting prepotent responses, and shifting response set. Age at the time of testing was divided into 10- to 35- and 36- to 85-month ranges. In relation to the community comparison group, children with moderate-to-severe TBI scored significantly lower on indexes of WM/inhibitory control (IC) on DR and stationary boxes tasks. On the latter task, the Age × Group interaction indicated that performance efficiency was significantly reduced in the older children with TBI relative to the older comparison group; performance was similar in younger children irrespective of injury status. The TBI and comparison groups did not differ on the SR task, suggesting that shifting response set was not significantly altered by TBI. In both the TBI and comparison groups, performance improved with age on the DR and stationary boxes tasks. Age at testing was not significantly related to scores on the SR task. The rate of acquisition of working memory (WM) and IC increases steeply during preschool years, but the abilities involved in shifting response set show less increase across age groups (Espy, Kaufmann, & Glisky, 2001; Luciana & Nelson, 1998). The findings of our study are consistent with the rapid development hypothesis, which predicts that skills in a rapid stage of development will be vulnerable to disruption by brain injury.

Acute neuroradiologic findings in young children with inflicted or noninflicted traumatic brain injury

Abstract Acute CT/MRI findings were examined in a prospective, longitudinal study of 60 children 0–6 years of age hospitalized for moderate to severe traumatic brain injury (TBI). TBI was categorized as either inflicted (n=31) or noninflicted (n=29). Glasgow Coma Scale scores and perinatal history were comparable in both groups. Acute CT/MRI studies were visually inspected by a radiologist blind to group membership. Compared with the noninflicted TBI group, the inflicted TBI group had significantly elevated rates of subdural interhemispheric and convexity hemorrhages as well as signs of pre-existing brain abnormality, including cerebral atrophy, subdural hygroma, and ex vacuo ventriculomegaly. Intraparenchymal hemorrhage, shear injury, and skull fractures were more frequent after noninflicted TBI. Subarachnoid hemorrhage and infarct/edema occurred with comparable frequency in both groups. Characteristic acute neuroimaging findings of inflicted TBI included multiple extraaxial hemorrhages in addition to the mild atrophy, subdural hygromas, and ventriculomegaly that suggest prior brain abnormality.

Development and Aging of the Healthy Human Brain Uncinate Fasciculus across the Lifespan using Diffusion Tensor Tractography

The human brain uncinate fasciculus (UF) is an important cortico-cortical white matter pathway that directly connects the frontal and temporal lobes, although there is a lack of conclusive support for its exact functional role. Using diffusion tensor tractography, we extracted the UF, calculated its volume and normalized it with respect to each subjects intracranial volume (ICV) and analyzed its corresponding DTI metrics bilaterally on a cohort of 108 right-handed children and adults aged 7-68 years. Results showed inverted U-shaped curves for fractional anisotropy (FA) with advancing age and U-shaped curves for radial and axial diffusivities reflecting white matter progressive and regressive myelination and coherence dynamics that continue into young adulthood. The mean FA values of the UF were significantly larger on the left side in children (p=0.05), adults (p=0.0012) and the entire sample (p=0.0002). The FA leftward asymmetry (Left>Right) is shown to be due to increased leftward asymmetry in the axial diffusivity (p<0.0001) and a lack of asymmetry (p>0.23) for the radial diffusivity. This is the first study to provide baseline normative macro and microstructural age trajectories of the human UF across the lifespan. Results of this study may lend themselves to better understanding of UF role in future behavioral and clinical studies.

Diffusion tensor tractography quantification of the human corpus callosum fiber pathways across the lifespan

Several anatomical attributes of the human corpus callosum (CC) including the midsagittal cross-sectional area, thickness, and volume, have been used to assess CC integrity. We extended our previous lifespan quantitative diffusion tensor imaging (DTI) study of the regional CC midsagittal areas to include the CC volumes obtained from DTI fiber tracking. In addition to the entire CC tracked subvolumes we normalized volume with respect to each subjects intracranial volume (ICV) and the corresponding DTI metrics of the different specialized fiber pathways of the CC on a cohort of 99 right-handed children and adults aged 7-59 years. Results indicated that the CC absolute volume, the normalized volume fraction, and the fractional anisotropy followed inverted U-shaped curves, while the radial diffusivities followed a U-shaped curve reflecting white matter progressive and regressive myelination dynamics that continue into young adulthood. Our study provides for the first time normative baseline macro- and microstructural age trajectories of the human CC subvolumes across the lifespan that can be helpful for normative behavioral and clinical studies.