James L. Leach

Pediatric Sports-Related Concussion Produces Cerebral Blood Flow Alterations

Objectives: The pathophysiology of sports-related concussion (SRC) is incompletely understood. Human adult and experimental animal investigations have revealed structural axonal injuries, decreases in the neuronal metabolite N-acetyl aspartate, and reduced cerebral blood flow (CBF) after SRC and minor traumatic brain injury. The authors of this investigation explore these possibilities after pediatric SRC. Patients And Methods: Twelve children, ages 11 to 15 years, who experienced SRC were evaluated by ImPACT neurocognitive testing, T1 and susceptibility weighted MRI, diffusion tensor imaging, proton magnetic resonance spectroscopy, and phase contrast angiography at <72 hours, 14 days, and 30 days or greater after concussion. A similar number of age- and gender-matched controls were evaluated at a single time point. Results: ImPACT results confirmed statistically significant differences in initial total symptom score and reaction time between the SRC and control groups, resolving by 14 days for total symptom score and 30 days for reaction time. No evidence of structural injury was found on qualitative review of MRI. No decreases in neuronal metabolite N-acetyl aspartate or elevation of lactic acid were detected by proton magnetic resonance spectroscopy. Statistically significant alterations in CBF were documented in the SRC group, with reduction in CBF predominating (38 vs 48 mL/100 g per minute; P = .027). Improvement toward control values occurred in only 27% of the participants at 14 days and 64% at >30 days after SRC. Conclusions: Pediatric SRC is primarily a physiologic injury, affecting CBF significantly without evidence of measurable structural, metabolic neuronal or axonal injury. Further study of CBF mechanisms is needed to explain patterns of recovery.

Multimodality imaging in the surgical treatment of children with nonlesional epilepsy

Objectives: To evaluate the diagnostic value of individual noninvasive presurgical modalities and to study their role in surgical management of nonlesional pediatric epilepsy patients. Methods: We retrospectively studied 14 children (3–18 years) with nonlesional intractable focal epilepsy. Clinical characteristics, surgical outcome, localizing features on 3 presurgical diagnostic tests (subtraction peri-ictal SPECT coregistered to MRI [SISCOM], statistical parametric mapping [SPM] analysis of [18F] FDG-PET, magnetoencephalography [MEG]), and intracranial EEG (iEEG) were reviewed. The localization of each individual test was determined for lobar location by visual inspection. Concordance of localization between each test and iEEG was scored as follows: 2 = lobar concordance; 1 = hemispheric concordance; 0 = discordance or nonlocalization. Total concordance score in each patient was measured by the summation of concordance scores for all 3 tests. Results: Seven (50%) of 14 patients were seizure-free for at least 12 months after surgery. One (7%) had only rare seizures and 6 (43%) had persistent seizures. MEG (79%, 11/14) and SISCOM (79%, 11/14) showed greater lobar concordance with iEEG than SPM-PET (13%, 3/14) (p < 0.05). SPM-PET provided hemispheric lateralization (71%, 10/14) more often than lobar localization. Total concordance score tended to be greater for seizure-free patients (4.7) than for non–seizure-free patients (3.9). Conclusions: Our data suggest that MEG and SISCOM are better tools for lobar localization than SPM analysis of FDG-PET in children with nonlesional epilepsy. A multimodality approach may improve surgical outcome as well as selection of surgical candidates in patients without MRI abnormalities.

The Acetazolamide Challenge: Techniques and Applications in the Evaluation of Chronic Cerebral Ischemia

SUMMARY: The acetazolamide (ACZ) challenge test is a useful clinical tool and a reliable predictor of critically reduced perfusion. In patients with chronic steno-occlusive disease, the ability to maintain normal cerebral blood flow by reducing vascular resistance secondary to autoregulatory vasodilation is compromised. Identification of the presence and degree of autoregulatory vasodilation (reflecting the cerebrovascular reserve) is a significant prognostic factor in patients with chronic cerebrovascular disease. The pharmacologic challenge of a vasodilatory stimulus such as ACZ can also be used to optimize the treatment strategies for these patients. The pathophysiology, methods, and clinical applications of the ACZ challenge test are discussed in this article.

Resection of ictal high-frequency oscillations leads to favorable surgical outcome in pediatric epilepsy

Purpose:  Intracranial electroencephalography (EEG) is performed as part of an epilepsy surgery evaluation when noninvasive tests are incongruent or the putative seizure‐onset zone is near eloquent cortex. Determining the seizure‐onset zone using intracranial EEG has been conventionally based on identification of specific ictal patterns with visual inspection. High‐frequency oscillations (HFOs, >80 Hz) have been recognized recently as highly correlated with the epileptogenic zone. However, HFOs can be difficult to detect because of their low amplitude. Therefore, the prevalence of ictal HFOs and their role in localization of epileptogenic zone on intracranial EEG are unknown.

Nonconvulsive Status Epilepticus: The Encephalopathic Pediatric Patient

OBJECTIVE: A high prevalence of nonconvulsive status epilepticus (NCSE) has been reported in critically ill adults and neonates. Recent prospective pediatric studies focus on critically ill children and show wide variability in the frequency of NCSE. This study examines prevalence of pediatric NCSE regardless of inpatient setting and retrospectively identifies risk factors indicating a need for urgent continuous EEG. METHODS: Medical records from patients aged 3 months to 21 years were identified either by (1) searching a clinical EEG database (n = 18) or (2) consecutive inpatient EEG referrals for NCSE over an 8-month period (n = 57). RESULTS: Seventy-five children, mean age of 7.8 years, were studied. NCSE was identified in 26 patients (35%) and in 8 of 57 (14%) patients referred for possible NCSE. More than half of the patients referred were outside of the ICU. A witnessed clinical seizure was observed in 24 of 26 (92%) patients with NCSE. Acute cortical neuroimaging abnormalities were significantly more frequent in patients with NCSE. The presence of clinical seizures and acute neuroimaging abnormality was associated with an 82% probability of NCSE. All but 1 patient with NCSE had electrographic or electroclinical seizures within the first hour of monitoring. CONCLUSIONS: A high prevalence of NCSE was observed, comparable to adult studies, but within a wider range of inpatient settings. Children with acute encephalopathy should undergo continuous EEG. This evaluation is more urgent if certain clinical risk factors are present. Optimal duration of monitoring and the effect of NCSE on prognosis should be studied.

Overnight Preliminary Head CT Interpretations Provided by Residents: Locations of Misidentified Intracranial Hemorrhage

BACKGROUND AND PURPOSE: Our aim was to determine the patterns of error of radiology residents in the detection of intracranial hemorrhage on head CT examinations while on call. Follow-up studies were reviewed to determine if there was any adverse effect on patient outcome as a result of these preliminary interpretations. MATERIALS AND METHODS: Radiology residents prospectively interpreted 22,590 head CT examinations while on call from January 1, 2002, to July 31, 2006. The following morning, the studies were interpreted by staff neuroradiologists, and discrepancies from the preliminary report were documented. Patients’ charts were reviewed for clinical outcomes and any imaging follow-up. RESULTS: There were a total of 1037 discrepancies identified, of which 141 were due to intracranial hemorrhage. The most common types of intracranial hemorrhage that were missed were subdural and subarachnoid hemorrhage occurring in 39% and 33% of the cases, respectively. The most common location for missed subdural hemorrhage was either parafalcine or frontal. The most common location of missed subarachnoid hemorrhage was in the interpeduncular cistern. There was 1 case of nontraumatic subarachnoid hemorrhage that was not described in the preliminary report. Fourteen patients were brought back to the emergency department for short-term follow-up imaging after being discharged. We did not observe any adverse clinical outcomes that resulted from a discrepant reading. CONCLUSION: Discrepancies due to intracranial hemorrhage are usually the result of subdural or subarachnoid hemorrhage. A more complete understanding of the locations of the missed hemorrhage can hopefully help decrease the discrepancy rate to help improve patient care.

Everolimus alters white matter diffusion in tuberous sclerosis complex

Objective: Diffusion tensor imaging (DTI) analysis was performed on patients with tuberous sclerosis complex (TSC) to investigate potential changes in normal-appearing white matter after treatment with everolimus, a mammalian target of rapamycin (mTOR) inhibitor. Methods: Recently, a phase I/II trial of everolimus demonstrated significant reductions in subependymal giant cell astrocytoma (SEGA) volume and decreased seizure frequency. Subgroup analysis was performed on DTI data available from this study. TSC patients with SEGA received everolimus, titrated to tolerability to achieve target trough concentrations of 5–15 ng/mL. DTI (1.5 T, 15 directions) was used to calculate fractional anisotropy (FA) and axial, radial, and mean diffusivity within regions of interest (ROIs). Baseline scans were compared to 12–18 months post-treatment and compared to a TSC age- and gender-matched nontreatment control cohort. Results: Of 28 enrolled patients, 20 had sufficient DTI data. Comparing baseline values with those acquired 12–18 months after treatment, a significant change in FA was observed in the corpus callosum, internal capsule, and geniculo-calcarine region (p < 0.05). Mean change in FA was 0.04 (p < 0.01), driven primarily by a significant decrease in radial diffusivity. Mean diffusivity of the combined ROIs decreased slightly (p < 0.05), axial diffusivity remained stable. The control group showed no change over time. Conclusion: Significant changes in FA and radial diffusivity were observed after treatment with everolimus in patients with TSC, suggesting that the genetic defect of TSC in the brain may be modified pharmacologically, even in normal-appearing white matter.

Frequency and spatial characteristics of high-frequency neuromagnetic signals in childhood epilepsy

PURPOSE Invasive intracranial recordings have suggested that high-frequency oscillation is involved in epileptogenesis and is highly localized to epileptogenic zones. The aim of the present study is to characterize the frequency and spatial patterns of high-frequency brain signals in childhood epilepsy using a non-invasive technology. METHODS Thirty children with clinically diagnosed epilepsy were studied using a whole head magnetoencephalography (MEG) system. MEG data were digitized at 4,000 Hz. The frequency and spatial characteristics of high-frequency neuromagnetic signals were analyzed using continuous wavelet transform and beamformer. Three-dimensional magnetic resonance imaging (MRI) was obtained for each patient to localize magnetic sources. RESULTS Twenty-six patients showed high-frequency (100-1,000 Hz) components (26/30, 86%). Nineteen patients showed more than one high-frequency component (19/30, 63%). The frequency range of high-frequency components varied across patients. The highest frequency band was identified around 910 Hz. The loci of high-frequency epileptic activities were concordant with the lesions identified by magnetic resonance imaging for 21 patients (21/30, 70%). The MEG source localizations of high-frequency components were found to be concordant with intracranial recordings for nine of the eleven patients who underwent epilepsy surgery (9/11, 82%). CONCLUSION The results have demonstrated that childhood epilepsy was associated with high-frequency epileptic activity in a wide frequency range. The concordance of MEG source localization, MRI and intracranial recordings suggests that measurement of high-frequency neuromagnetic signals might provide a novel approach for clinical management of childhood epilepsy.

Brain Parenchymal Signal Abnormalities Associated with Developmental Venous Anomalies: Detailed MR Imaging Assessment

BACKGROUND AND PURPOSE: The occurrence of brain parenchymal signal-intensity changes within the drainage territory of developmental venous anomalies (DVAs) in the absence of cavernous malformations (CMs) has been incompletely assessed. This study was performed to evaluate the prevalence of brain parenchymal signal-intensity abnormalities subjacent to DVA, correlating with DVA morphology and location. MATERIALS AND METHODS: One hundred sixty-four patients with brain MR imaging with contrast studies performed from July 2005 through June 2006 formed the study group. The examinations were reviewed and data were collected regarding the following: location, depth, size of draining vein, associated increased signal intensity on fluid-attenuated inversion recovery and T2-weighted images, associated CMs, and associated signal intensity on gradient recalled-echo sequences. RESULTS: Of the 175 DVAs identified, 28 had associated signal-intensity abnormalities in the drainage territory. Seven of 28 DVAs with signal-intensity abnormalities were excluded because of significant adjacent white matter signal-intensity changes related to other pathology overlapping the drainage territory. Of the remaining DVAs imaged in this study, 21/168 (12.5%) had subjacent signal-intensity abnormalities. An adjusted prevalence rate of 9/115 (7.8%) was obtained by excluding patients with white matter disease more than minimal in degree. Periventricular location and older age were associated with DVA signal-intensity abnormality. CONCLUSION: Signal-intensity abnormalities detectable by standard clinical MR images were identified in association with 12.5% of consecutively identified DVAs. Excluding patients with significant underlying white matter disease, we adjusted the prevalence to 7.8%. The etiology of the signal-intensity changes is unclear but may be related to edema, gliosis, or leukoaraiosis secondary to altered hemodynamics in the drainage area.

Maximizing the extent of tumor resection during transsphenoidal surgery for pituitary macroadenomas: can endoscopy replace intraoperative magnetic resonance imaging?

OBJECT Endoscopic approaches to pituitary tumors have become an effective alternative to traditional microscopic transsphenoidal approaches. Despite a proven potential to decrease unexpected residual tumor, intraoperative MR (iMR) imaging is infrequently used even in the few operating environments in which such technology is available. Its use is prohibitive because of its cost, increased complexity, and longer operative times. The authors assessed the potential of intrasellar endoscopy to replace the need for iMR imaging without sacrificing the maximum extent of resection. METHODS In this retrospective study, 27 consecutive patients underwent fully endoscopic resection of pituitary macroadenomas. Intrasellar endoscopy was used to determine the presence of residual tumor within the sella turcica and tumor cavity. Intraoperative MR imaging was used to identify rates of unexpected residual tumor and the need for further tumor resection. RESULTS Intraoperative estimates of the extent of tumor resection were correct in 23 patients (85%). Of 4 patients with unacceptable tumor residuals, 3 underwent further tumor resection. After iMR imaging, the rate of successful completion of the planned extent of resection increased to 26 patients (96%). Rates of both endocrinopathy reversal and postoperative complications were consistent with previously published results for microscopic and endoscopic resection techniques. CONCLUSIONS The findings in this study provided quantitative evidence that intrasellar endoscopy has significant promise for maximizing the extent of tumor resection and is a useful adjunct to surgical approaches to pituitary tumors, particularly when iMR imaging is unavailable. A larger prospective study on the extent of resection following endoscopic transsphenoidal surgery would strengthen these findings.