Diffuse damage in pediatric traumatic brain injury: a comparison of automated versus operator-controlled quantification methods.

This investigation had two main objectives: 1) to assess the comparability of volumes determined by operator-controlled image quantification with automated image analysis in evaluating atrophic brain changes related to traumatic brain injury (TBI) in children, and 2) to assess the extent of diffuse structural changes throughout the brain as determined by reduced volume of a brain structure or region of interest (ROI). Operator-controlled methods used ANALYZE software for segmentation and tracing routines of pre-defined brain structures and ROIs. For automated image analyses, the open-access FreeSurfer program was used. Sixteen children with moderate-to-severe TBI were compared to individually matched, typically developing control children and the volumes of 18 brain structures and/or ROIs were compared between the two methods. Both methods detected atrophic changes but differed in the magnitude of the atrophic effect with the best agreement in subcortical structures. The volumes of all brain structures/ROIs were smaller in the TBI group regardless of method used; overall effect size differences were minimal for caudate and putamen but moderate to large for all other measures. This is reflective of the diffuse nature of TBI and its widespread impact on structural brain integrity, indicating that both FreeSurfer and operator-controlled methods can reliably assess cross-sectional volumetric changes in pediatric TBI.

Telephone interview for cognitive status: Creating a crosswalk with the Mini-Mental State Examination.

BACKGROUND: Brief cognitive screening measures are valuable tools for both research and clinical applications. The most widely used instrument, the Mini-Mental State Examination (MMSE), is limited in that it must be administered face-to-face, cannot be used in participants with visual or motor impairments, and is protected by copyright. Screening instruments such as the Telephone Interview for Cognitive Status (TICS) were developed to provide a valid alternative, with comparable cut-point scores to rate global cognitive function. METHODS: The MMSE, TICS-30, and TICS-40 scores from 746 community-dwelling elders who participated in the Aging, Demographics, and Memory Study (ADAMS) were analyzed with equipercentile equating, a statistical process of determining comparable scores based on percentile equivalents for different forms of an examination. RESULTS: Scores from the MMSE and TICS-30 and TICS-40 corresponded well, and clinically relevant cut-point scores were determined. For example, an MMSE score of 23 is equivalent to 17 and 20 on the TICS-30 and TICS-40, respectively. CONCLUSIONS: These findings indicate that TICS and MMSE scores can be linked directly. Clinically relevant and important MMSE cut points and the respective ADAMS TICS-30 and TICS-40 cut-point scores are included, to identify the degree of cognitive impairment among respondents with any type of cognitive disorder. These results will help in the widespread application of TICS in both research and clinical practice.

Phenomenological subtypes of delirium in older persons: patterns, prevalence, and prognosis.

BACKGROUND: Delirium is an acute confusional state that is common, preventable, and life-threatening. OBJECTIVE: The authors investigated the phenomenology of delirium severity as measured with the Memorial Delirium Assessment Scale among 441 older patients (age 65 and older) admitted with delirium in post-acute care. METHODS: Using latent class analysis, they identified four classes of psychomotor-severity subtypes of delirium: 1) hypoactive/mild; 2) hypoactive/severe; 3) mixed, with hyperactive features/severe; and 4) normal/mild. RESULTS: Among those with dementia (N=166), the hypoactive/mild class was associated with a higher risk of mortality. Among those without dementia (N=275), greater severity was associated with mortality, regardless of psychomotor features, when compared with the normal/mild class. CONCLUSION: The data suggest that instruments measuring delirium severity and psychomotor features provide important prognostic information and should be integrated into the assessment of delirium.

Persistent delirium predicts greater mortality.

OBJECTIVES: To examine the association between persistent delirium and 1-year mortality in newly admitted postacute care (PAC) facility patients with delirium who were followed regardless of residence. DESIGN: Observational cohort study. SETTING: Eight greater-Boston skilled nursing facilities specializing in PAC. PARTICIPANTS: Four hundred twelve PAC patients with delirium at admission after an acute hospitalization. MEASUREMENTS: Assessments were done at baseline and four follow-up times: 2, 4, 12, and 26 weeks. Delirium, defined using the Confusion Assessment Method, was assessed, as were factors used as covariates in analyses: age, sex, comorbidity, functional status, and dementia. The outcome was 1-year mortality determined according to the National Death Index and corroborated using medical record and proxy telephone interview. RESULTS: Nearly one-third of subjects remained delirious at 6 months. Cumulative 1-year mortality was 39%. Independent of age, sex, comorbidity, functional status, and dementia, subjects with persistent delirium were 2.9 (95% confidence interval 51.9-4.4) times as likely to die during the 1-year follow-up as subjects whose delirium resolved. This association remained strong and significant in groups with and without dementia. Additionally, when delirium resolved, the risk of death diminished thereafter. CONCLUSION: In patients who were delirious at the time of PAC admission, persistent delirium was a significant independent predictor of 1-year mortality.

Morphometric MRI findings in the thalamus and brainstem in children after moderate to severe traumatic brain injury.

Generalized whole brain volume loss is well documented in moderate to severe traumatic brain injury. Whether this atrophy occurs in the thalamus and brainstem has not been systematically studied in children. Magnetic resonance imaging (MRI) quantitative analysis was used to investigate brain volume loss in the thalamus and brainstem in 16 traumatic brain injury subjects (age range 9-16 years) compared with 16 age and demo-graphically matched controls. Based on multiple analysis of covariance, controlling for age and head size, reduced volume in the thalamus and the midbrain region of the brainstem were found. General linear model analyses revealed a relation between processing speed on a working memory task and midbrain and brain stem volumes. Reduced volume in thalamic and brainstem structures were associated with traumatic brain injury. Reduction in midbrain and thalamic volume is probably a reflection of the secondary effects of diffuse axonal injury and reduction in cortical volume from brain injury.

Participation in activity and risk for incident delirium.

OBJECTIVES: To examine the mediating role between educational attainment and risk for incidence delirium of activity participation and to examine the contribution of participation in specific activities to the development of delirium. DESIGN: Prospective cohort study. SETTING: Urban teaching hospital in New Haven, Connecticut. PARTICIPANTS: Participants were drawn from two prospective cohort studies of 779 newly hospitalized patients aged 70 and older without dementia. MEASUREMENTS: The main outcome was delirium, measured using the full Confusion Assessment Method (CAM) algorithm, which consisted of acute onset and fluctuating course, inattention, and disorganized thinking or altered level of consciousness, as rated by trained clinical interviewers. RESULTS: Bivariable results indicated a significant relationship between education and the development of delirium (odds ratio (OR)=0.92, 95% confidence interval (CI)=0.88-0.97) and between activity and delirium (OR= 0.60, 95% CI=0.46-0.79). In multivariable analysis, activity mediated the relationship between education and risk for delirium. Considering each activity separately, multivariable logistic regression analysis showed that regular exercise significantly lowered the risk for developing delirium (OR=0.76, 95% CI=0.60-0.96). CONCLUSION: In older persons without dementia, activity participation before hospitalization is a mediator between education and incidence of delirium. Specifically, it was found that participation in regular exercise was found to be significantly protective against delirium.

The Confusion Assessment Method: a systematic review of current usage.

OBJECTIVES: To examine the psychometric properties, adaptations, translations, and applications of the Confusion Assessment Method (CAM), a widely used instrument and diagnostic algorithm for identification of delirium. DESIGN: Systematic literature review. SETTING: Not applicable. MEASUREMENTS: Electronic searches of PubMED, EMBASE, PsychINFO, CINAHL, Ageline, and Google Scholar, augmented by reviews of reference listings, were conducted to identify original English-language articles using the CAM from January 1, 1991, to December 31, 2006. Two reviewers independently abstracted key information from each article. PARTICIPANTS: Not applicable. RESULTS: Of 239 original articles, 10 (4%) were categorized as validation studies, 16 (7%) as adaptations, 12 (5%) as translations, and 222 (93%) as applications. Validation studies evaluated performance of the CAM against a reference standard. Results were combined across seven high-quality studies (N=1,071), demonstrating an overall sensitivity of 94% (95% confidence interval (CI)=91-97%) and specificity of 89% (95% CI=85-94%). The CAM has been adapted for use in the intensive care unit, emergency, and institutional settings and for scoring severity and subsyndromal delirium. The CAM has been translated into 10 languages where published articles are available. In application studies, CAM-rated delirium is most commonly used as a risk factor or outcome but also as an intervention or reference standard. CONCLUSION: The CAM has helped to improve identification of delirium in clinical and research settings. To optimize performance, the CAM should be scored based on observations made during formal cognitive testing, and training is recommended. Future action is needed to optimize use of the CAM and to improve the recognition and management of delirium.

Autopsy-confirmed Alzheimer's disease versus clinically diagnosed Alzheimer's disease in the Cache County Study on Memory and Aging: a comparison of quantitative MRI and neuropsychological findings.

Atrophy of specific, regional, and generalized brain structures occurs as a result of the Alzheimer's disease (AD) process. Comparing AD patients with histopathological confirmation of the disease at autopsy to those without autopsy but who were clinically diagnosed using the same antemortem criteria will provide further evidence of the utility and accuracy of neuropsychological assessments at the time of diagnosis, as well as the efficacy of quantitative magnetic resonance imaging (qMRI) in demonstrating gross neuropathological changes associated with the disease. The Cache County Study of Aging provides a unique opportunity to determine how closely AD subjects with only the clinical diagnosis match similarly diagnosed AD subjects but with postmortem confirmation of the disease. qMRI volumes of various brain structures, as well as neuropsychological outcome measures from an expanded battery, were obtained in 31 autopsy-confirmed AD subjects and 45 clinically diagnosed AD subjects. Of the various qMRI variables examined, only total temporal lobe volume was different, where those with postmortem confirmation had reduced volume. No significant differences between the two groups were found with any of the neuropsychological outcome measures. These findings confirm the similarity in neuroimaging and neuropsychological assessment findings between those with just the clinical diagnosis of AD and those with an autopsy-confirmed diagnosis in the moderate-to-severe stage of the disease at the time of diagnosis.

Hippocampus, amygdala, and basal ganglia morphometrics in children after moderate-to-severe traumatic brain injury.

While closed head injury frequently results in damage to the frontal and temporal lobes, damage to deep cortical structures, such as the hippocampus, amygdala, and basal ganglia, has also been reported. Five deep central structures (hippocampus, amygdala, globus pallidus, putamen, and caudate) were examined in 16 children (eight males, eight females; aged 9-16y), imaged 1 to 10 years after moderate-to-severe traumatic brain injury (TBI), and in 16 individually-matched uninjured children. Analysis revealed significant volume loss in the hippocampus, amydala, and globus pallidus of the TBI group. Investigation of relative volume loss between these structures and against five cortical areas (ventromedial frontal, superomedial frontal, lateral frontal, temporal, and parieto-occipital) revealed the hippocampus to be the most vulnerable structure following TBI (i.e. greatest relative difference between the groups). In a separate analysis excluding children with focal hippocampal abnormalities (e.g. lesions), group differences in hippocampal volume were still evident, suggesting that hippocampal damage may be diffuse rather than focal.

Diffusion tensor imaging in the corpus callosum in children after moderate to severe traumatic brain injury.

Diffusion tensor imaging (DTI) is a recent imaging technique that assesses the microstructure of the cerebral white matter (WM) based on anisotropic diffusion (i.e., water molecules move faster in parallel to nerve fibers than perpendicular to them). Fractional anisotropy (FA), which ranges from 0 to 1.0, increases with myelination of WM tracts and is sensitive to diffuse axonal injury (DAI) in adults with traumatic brain injury (TBI). However, previous DTI studies of pediatric TBI were case reports without detailed outcome measures. Using mean FA derived from DTI fiber tractography, we compared DTI findings of the corpus callosum for 16 children who were at least 1 year (mean 3.1 years) post-severe TBI and individually matched, uninjured children. Interexaminer and intraexaminer reliability in measuring FA was satisfactory. FA was significantly lower in the patients for the genu, body, and splenium of the corpus callosum. Higher FA was related to increased cognitive processing speed and faster interference resolution on an inhibition task. In the TBI patients, higher FA was related to better functional outcome as measured by the dichotomized Glasgow Outcome Scale (GOS). FA also increased as a function of the area of specific regions of the corpus callosum such as the genu and splenium, and FA in the splenium was reduced with greater volume of lesions in this region. DTI may be useful in identifying biomarkers related to DAI and outcome of TBI in children.

Basal ganglia lesions following carbon monoxide poisoning.

PRIMARY OBJECTIVES: Carbon monoxide (CO) is the most common cause of poisoning and may result in basal ganglia lesions. This study reviewed the literature of carbon monoxide poisoning and basal ganglia lesions and prospectively assessed the prevalence of basal ganglia lesions in a cohort of patients with CO poisoning. RESEARCH DESIGN: Literature review and prospective cohort study. METHODS: This study conducted a comprehensive review of the literature and assessed 73 CO-poisoned patients for basal ganglia lesions on sequential MR scans. Magnetic resonance scans were obtained on day 1, 2 weeks and 6 months post-CO poisoning. RESULTS: The literature review found basal ganglia lesions occur in 4-88% of subjects. Only one patient was found with globus pallidus lesions at 2 weeks and 6 months following CO poisoning, that were not present on the initial day 1 MR scan. CONCLUSIONS: Basal ganglia lesions, including lesions of the globus pallidus, may be less common than previously reported.

The role of neuroimaging in elucidating delirium pathophysiology.

Understanding of delirium pathogenesis remains limited despite improved diagnosis, and elucidation of risk factors and prognosis. Major advances in neuroimaging offer the possibility of probing the mechanisms and networks involved in delirium and hence improving understanding of this often devastating syndrome. This review describes the current literature of imaging studies in delirium and related conditions, introduces some of the newer capabilities of neuroimaging with magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography, and discusses how these techniques may be applied to the study of delirium. Despite considerable challenges in patient recruitment, study design, intersubject variability, and scanner and contrast agent availability, imaging offers great potential for the identification and clarification of pathogenic mechanisms of delirium and its long-term sequelae.

Frontal and temporal morphometric findings on MRI in children after moderate to severe traumatic brain injury.

In vivo MRI volumetric analysis enables investigators to evaluate the extent of tissue loss following traumatic brain injury (TBI). However, volumetric studies of pediatric TBI are sparse, and there have been no volumetric studies to date in children examining specific subregions of the prefrontal and temporal lobes. In this study, MRI volumetry was used to evaluate brain volume differences in the whole brain, and prefrontal, temporal, and posterior regions of children following moderate to severe TBI as compared to uninjured children of similar age and demographic characteristics. The TBI group had significantly reduced whole brain, and prefrontal and temporal regional tissue volumes as well as increased cerebrospinal fluid (CSF). Confidence interval testing further revealed group differences on gray matter (GM) and white matter (WM) in the superior medial and ventromedial prefrontal regions, WM in the lateral frontal region, and GM, WM, and CSF in the temporal region. Whole brain volume and total brain GM were reduced, and total ventricular volume, total CSF volume, and ventricle-to-brain ratio (VBR) were increased in the TBI group. Additional analyses comparing volumetric data from typically developing children and subgroups of TBI patients with and without regional focal lesions suggested that GM loss in the frontal areas was primarily attributable to focal injury, while WM loss in the frontal and temporal lobes was related to both diffuse and focal injury. Finally, volumetric measures of preserved frontotemporal tissue were related to functional recovery as measured by the Glasgow Outcome Scale (adapted for children) with greater tissue preservation predicting better recovery.