Jacqueline A. Bello

Multifocal White Matter Ultrastructural Abnormalities in Mild Traumatic Brain Injury with Cognitive Disability: A Voxel-Wise Analysis of Diffusion Tensor Imaging

The purpose of the present study is to identify otherwise occult white matter abnormalities in patients suffering persistent cognitive impairment due to mild traumatic brain injury (TBI). The study had Institutional Review Board (IRB) approval, included informed consent and complied with the U.S. Health Insurance Portability and Accountability Act (HIPAA) of 1996. We retrospectively analyzed diffusion tensor MRI (DTI) of 17 patients (nine women, eight men; age range 26-70 years) who had cognitive impairment due to mild TBI that occurred 8 months to 3 years prior to imaging. Comparison was made to 10 healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) images derived from DTI (1.5 T; 25 directions; b = 1000) were compared using whole brain histogram and voxel-wise analyses. Histograms of white matter FA show an overall shift toward lower FA in patients. Areas of significantly decreased FA (p < 0.005) were found in the subject group in corpus callosum, subcortical white matter, and internal capsules bilaterally. Co-located elevation of mean diffusivity (MD) was found in the patients within each region. Similar, though less extensive, findings were demonstrated in each individual patient. Multiple foci of low white matter FA and high MD are present in cognitively impaired mild TBI patients, with a distribution that conforms to that of diffuse axonal injury. Evaluation of single subjects also reveals foci of low FA, suggesting that DTI may ultimately be useful for clinical evaluation of individual patients.

Cerebral hyperemia, stroke, and transfusion in sickle cell disease

To investigate cerebral hemodynamics in sickle cell disease (SCD), we used the 133Xenon inhalation technique of quantifying cerebral blood flow (CBF) in 67 patients. Clinical examinations and cerebral magnetic resonance imaging also were performed in all patients. Compared with age-matched healthy controls, CBF was elevated by 68% in patients, and inversely related to hematocrit. An experimental index of cerebral blood volume, pr4, was also elevated in the patients in a similar manner. Cerebral blood volume was positively correlated to CBF in SCD patients but not in controls. History of stroke and current neurologic symptoms were associated with lower flow and higher cerebral blood volume. Transfusion therapy reduced the hyperemia, the reduction being greater than expected by hematocrit elevation alone. These findings document a vasodilatory hyperemia in SCD. This dilatation may be a risk factor for ischemic distal-field infarctions, as visualized by MRI, due to a limitation of cerebrovascular reserve capacity.

MRI abnormalities following febrile status epilepticus in children The FEBSTAT study

Objective: The FEBSTAT study is a prospective study that seeks to determine the acute and long-term consequences of febrile status epilepticus (FSE) in childhood. Methods: From 2003 to 2010, 199 children age 1 month to 5 years presenting with FSE (>30 minutes) were enrolled in FEBSTAT within 72 hours of the FSE episode. Of these, 191 had imaging with emphasis on the hippocampus. All MRIs were reviewed by 2 neuroradiologists blinded to clinical details. A group of 96 children with first simple FS who were imaged using a similar protocol served as controls. Results: A total of 22 (11.5%) children had definitely abnormal (n = 17) or equivocal (n = 5) increased T2 signal in the hippocampus following FSE compared with none in the control group (p < 0.0001). Developmental abnormalities of the hippocampus were more common in the FSE group (n = 20, 10.5%) than in controls (n = 2, 2.1%) (p = 0.0097) with hippocampal malrotation being the most common (15 cases and 2 controls). Extrahippocampal imaging abnormalities were present in 15.7% of the FSE group and 15.6% of the controls. However, extrahippocampal imaging abnormalities of the temporal lobe were more common in the FSE group (7.9%) than in controls (1.0%) (p = 0.015). Conclusions: This prospective study demonstrates that children with FSE are at risk for acute hippocampal injury and that a substantial number also have abnormalities in hippocampal development. Follow-up studies are in progress to determine the long-term outcomes in these children.

Hippocampal sclerosis after febrile status epilepticus: The FEBSTAT study

Whether febrile status epilepticus (FSE) produces hippocampal sclerosis (HS) and temporal lobe epilepsy (TLE) has long been debated. Our objective is to determine whether FSE produces acute hippocampal injury that evolves to HS.

Diffusion tensor imaging abnormalities in patients with mild traumatic brain injury and neurocognitive impairment.

Objective: To determine if diffusion tensor imaging can differentiate patients with chronic cognitive impairment after mild traumatic brain injury (TBI) from normal controls. Methods: Ten patients with persistent cognitive impairment after mild TBI were evaluated at least 2 years after injury. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured at white matter regions susceptible to axonal injury after TBI. Comparison was made to 10 normal controls. Results: Fractional anisotropy was significantly lower (4.5%; P = 0.01) and ADC higher (7.1%; P = 0.04) in patients at the left side of the genu of the corpus callosum. The mild TBI group also demonstrated a significant increase in FA within the posterior limb of the internal capsule bilaterally (left, 5.1%; P = 0.03; right, 1.9%; P = 0.04). Conclusions: These results demonstrate low FA and high ADC in the genu of the corpus callosum of mild TBI patients with persistent cognitive impairment, suggesting that permanent white matter ultrastructural damage occurs in mild TBI, and that such damage may be associated with persistent cognitive disability. Further longitudinal studies are warranted to elucidate the full importance of the findings.

Multicenter study of predictors of disease course in Alzheimer disease (the "predictors study"). I. Study design, cohort description, and intersite comparisons.

Clinicians should be able to provide the patient with Alzheimer disease (AD) and the family with an accurate prediction of what to expect, but the variability in the rate of disease progression precludes this. In several previous studies, specific clinical signs such as muscular rigidity, myoclonus, and hallucinations or delusions were associated with rapid progression to a more severe stage of dementia or death. The “Predictors Study,” a longitudinal study at three independent sites, was designed to develop a predictor model of the natural history of Alzheimer disease. The study was conducted at three study sites, New York, Baltimore, and Boston in a cohort of 224 patients with early probable AD. This article describes the design and implementation of the Predictors Study, and compares features of the study cohort at baseline across sites. Patients were all at the mild stage of disease at entry and were relatively comparable across sites. Extrapyramidal signs and delusions were common, but myoclonus was rarely observed.

The use of magnetic resonance angiography prior to pharyngeal flap surgery in patients with velocardiofacial syndrome

&NA; Twenty consecutive patients with velocardiofacial syndrome underwent magnetic resonance angiography (MRA) to determine if abnormalities of the neck arteries would contraindicate pharyngeal flap surgery. All 20 patients were found to have anomalies of the carotid arteries, vertebral arteries, or both. Anomalies included tortuous or kinked vertebral arteries, medially placed internal carotids, low carotid bifurcations, and tortuous or kinked internal carotids. The internal carotids were found to be almost directly under the mucous membrane of the pharynx in two patients. In these two patients, the arteries were close to the pharyngeal midline at the base of the first cervical vertebra and might easily be severed during the raising of a pharyngeal flap. Hypoplastic vertebral arteries also were found. One patient had an extra neck vessel. The anomalies of the internal carotids did not have a strong correlation with endoscopically observed pulsations in the posterior pharyngeal wall. It also was found that head position affected the location of the internal carotid arteries when they were located close to the pharyngeal mucous membrane. The information provided in the MRA studies allowed assessment of the arterial anomalies in relation to the flap donor site so that the patients in the sample who underwent pharyngeal flap surgery using a short superiorly based flap had no major bleeding complications. (Plast. Reconstr. Surg. 97: 908, 1996.)

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part III. Reliability of a standardized MRI evaluation of Alzheimer's disease

The Consortium to Establish a Registry for Alzheimers Disease (CERAD) has developed procedures for standardized imaging and reporting of magnetic resonance (MR) findings in Alzheimers disease (AD) for use by neuroradiologists in multiple medical centers using a variety of MR equipment and field strengths. After initial pretesting, we revised the protocol, expanded the summary rating scale to seven points, and added more illustrations. Fourteen participating neuroradiologists evaluated 28 MR scans of elderly patients, giving us the basis for judging interrater agreement. We obtained acceptable intraclass correlations (>0.79) for rating the size of the lateral and third ventricles and the temporal horn. Less satisfactory intraclass correlations occurred when rating other areas, including (1) global atrophy of the brain (0.70); (2) dilatation of the sulci of the temporal lobe (0.66); (3) frequency, location, and severity of white matter lesions (0.77); (4) sylvian fissure enlargement (0.70); and (5) cerebral sulcal dilatation (0.64). We also saw considerable variation in the reporting of cortical and lacunar infarcts. Despite careful design of the rating methodology and readings by experienced neuroradiologists, we did not find satisfactory interrater agreement for interpreting MR findings in elderly subjects. These findings may explain the difficulties encountered in applying similar subjective rating techniques that meet with success at one institution to multicenter studies. More objective and reproducible procedures are needed for interpretation of neuroimaging findings of AD in multicenter studies.

Imaging Recommendations for Acute Stroke and Transient Ischemic Attack Patients: A Joint Statement by the American Society of Neuroradiology, the American College of Radiology, and the Society of NeuroInterventional Surgery

SUMMARY: Stroke is a leading cause of death and disability worldwide. Imaging plays a critical role in evaluating patients suspected of acute stroke and transient ischemic attack, especially before initiating treatment. Over the past few decades, major advances have occurred in stroke imaging and treatment, including Food and Drug Administration approval of recanalization therapies for the treatment of acute ischemic stroke. A wide variety of imaging techniques has become available to assess vascular lesions and brain tissue status in acute stroke patients. However, the practical challenge for physicians is to understand the multiple facets of these imaging techniques, including which imaging techniques to implement and how to optimally use them, given available resources at their local institution. Important considerations include constraints of time, cost, access to imaging modalities, preferences of treating physicians, availability of expertise, and availability of endovascular therapy. The choice of which imaging techniques to employ is impacted by both the time urgency for evaluation of patients and the complexity of the literature on acute stroke imaging. Ideally, imaging algorithms should incorporate techniques that provide optimal benefit for improved patient outcomes without delaying treatment.

Design and phenomenology of the FEBSTAT study.

Purpose:  Febrile status epilepticus (FSE) has been associated with hippocampal injury and subsequent hippocampal sclerosis (HS) and temporal lobe epilepsy. The FEBSTAT study was designed to prospectively examine the association between prolonged febrile seizures and development of HS and associated temporal lobe epilepsy, one of the most controversial issues in epilepsy. We report on the baseline phenomenology of the final cohorts as well as detailed aims and methodology.