Aaron F. Struck

Estimated risk of perihippocampal disease progression after hippocampal avoidance during whole-brain radiotherapy: Safety profile for RTOG 0933

BACKGROUND AND PURPOSE RTOG 0933 is a phase II clinical trial of hippocampal avoidance during whole-brain radiotherapy (HA-WBRT) to prevent radiation-induced neurocognitive decline. By quantifying baseline incidence of perihippocampal or hippocampal metastasis, we sought to estimate the risk of developing metastases in the hippocampal avoidance region (the hippocampus plus 5mm margin). MATERIALS/METHODS Patients with < or = 10 brain metastases treated at two separate institutions were reviewed. Axial images from pre-treatment, post-contrast MRIs were used to contour each metastasis and hippocampus according to a published protocol. Clinical and radiographic variables were correlated with perihippocampal metastasis using a binary logistical regression analysis, with two-sided p<0.05 for statistical significance. RESULTS 1133 metastases were identified in 371 patients. Metastases within 5mm of the hippocampus were observed in 8.6% of patients (95% CI 5.7-11.5%) and 3.0% of brain metastases. None of the metastases lay within the hippocampus. A 1-cm(3) increase in the aggregate volume of intra-cranial metastatic disease was associated with an odds ratio of 1.02 (95% CI 1.006-1.034, p=0.003) for the presence of perihippocampal metastasis. CONCLUSION With an estimated perihippocampal metastasis risk of 8.6%, we deem HA-WBRT safe for clinical testing in patients with brain metastases as part of RTOG 0933.

Idiopathic syringomyelia: phase-contrast MR of cerebrospinal fluid flow dynamics at level of foramen magnum.

PURPOSE To measure cerebrospinal fluid (CSF) flow velocities in the foramen magnum in patients with idiopathic syringomyelia (IS). MATERIALS AND METHODS Patient consent for this retrospective study was waived by the institutional review board within the guidelines of HIPAA. The authors reviewed the medical records of a neurosurgery specialty clinic to identify patients with IS-that is, syringomyelia without evidence of Chiari malformation, tumor, or substantial spine trauma. Patients without syringomyelia or Chiari malformation identified from the review served as control subjects. The data of patients and control subjects who had undergone phase-contrast magnetic resonance (MR) imaging were included in the study. MR flow images were inspected for evidence of synchronous bidirectional CSF flow and heterogeneous spatial and temporal flow patterns. Peak CSF flow velocities in the IS and control groups were calculated, and differences were tested for statistical significance by using the Wilcoxon rank sum test. RESULTS Eight patients who met the criteria for IS and six who met the criteria to serve as control subjects were identified. The phase-contrast MR images obtained in five of the eight patients with IS and in none of the control subjects depicted synchronous bidirectional flow and/or large flow jets. Mean peak systolic (caudal) CSF flow velocities were 6.7 cm/sec in the IS group and 3.6 cm/sec in the control group; the difference was significant (P < .01). Mean peak diastolic (cephalic) velocities were 3.9 and 3.4 cm/sec in the IS and control groups, respectively; the difference was not significant (P = .36). CONCLUSION Some patients with IS have increased peak systolic CSF flow velocities.

Surgical decision making in temporal lobe epilepsy: A comparison of [18F]FDG-PET, MRI, and EEG

OBJECTIVES The goals of this work were (1) to determine the effect of [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET), MRI, and EEG on the decision to perform temporal lobe epilepsy (TLE) surgery, and (2) to determine if FDG-PET, MRI, or EEG predicts surgical outcome. METHODS All PET scans ordered (2000-2010) for epilepsy or seizures were tabulated. Medical records were investigated to determine eligibility and collect data. Statistical analysis included odds ratios, κ statistics, univariate analysis, and logistic regression. RESULTS Of the 186 patients who underwent FDG-PET, 124 had TLE, 50 were surgical candidates, and 34 had surgery with post-operative follow-up. Median length of follow-up was 24 months. MRI, FDG-PET, and EEG were significant predictors of surgical candidacy (P<0.001) with odds ratios of 42.8, 20.4, and 6.3, respectively. FDG-PET was the only significant predictor of postoperative outcome (P<0.01). CONCLUSION MRI showed a trend toward having the most influence on surgical candidacy, but only FDG-PET predicted surgical outcome.

The number of seizures needed in the EMU

The purpose of this study was to develop a quantitative framework to estimate the likelihood of multifocal epilepsy based on the number of unifocal seizures observed in the epilepsy monitoring unit (EMU).

Time‐dependent risk of seizures in critically ill patients on continuous electroencephalogram

Find the optimal continuous electroencephalographic (CEEG) monitoring duration for seizure detection in critically ill patients.

Extreme delta brush evolving into status epilepticus in a patient with anti-NMDA encephalitis

Extreme delta brush (EDB) is an EEG pattern unique to anti-NMDA encephalitis. It is correlated with seizures and status epilepticus in patients who have a prolonged course of illness. The etiology of the underlying association between EDB and seizures is not understood. We present a patient with anti-NMDA encephalitis who developed status epilepticus evolving from the high frequency activity of the extreme delta brush. This case demonstrates that EDB is not only a marker for a greater propensity for seizures but also directly implicated in seizure generation.

Association of an Electroencephalography-Based Risk Score With Seizure Probability in Hospitalized Patients

Importance Continuous electroencephalography (EEG) use in critically ill patients is expanding. There is no validated method to combine risk factors and guide clinicians in assessing seizure risk. Objective To use seizure risk factors from EEG and clinical history to create a simple scoring system associated with the probability of seizures in patients with acute illness. Design, Setting, and Participants We used a prospective multicenter (Emory University Hospital, Brigham and Women’s Hospital, and Yale University Hospital) database containing clinical and electrographic variables on 5427 continuous EEG sessions from eligible patients if they had continuous EEG for clinical indications, excluding epilepsy monitoring unit admissions. We created a scoring system model to estimate seizure risk in acutely ill patients undergoing continuous EEG. The model was built using a new machine learning method (RiskSLIM) that is designed to produce accurate, risk-calibrated scoring systems with a limited number of variables and small integer weights. We validated the accuracy and risk calibration of our model using cross-validation and compared its performance with models built with state-of-the-art logistic regression methods. The database was developed by the Critical Care EEG Research Consortium and used data collected over 3 years. The EEG variables were interpreted using standardized terminology by certified reviewers. Exposures All patients had more than 6 hours of uninterrupted EEG recordings. Main Outcomes and Measures The main outcome was the average risk calibration error. Results There were 5427 continuous EEGs performed on 4772 participants (2868 men, 49.9%; median age, 61 years) performed at 3 institutions, without further demographic stratification. Our final model, 2HELPS2B, had an area under the curve of 0.819 and average calibration error of 2.7% (95% CI, 2.0%-3.6%). It included 6 variables with the following point assignments: (1) brief (ictal) rhythmic discharges (B[I]RDs) (2 points); (2) presence of lateralized periodic discharges, lateralized rhythmic delta activity, or bilateral independent periodic discharges (1 point); (3) prior seizure (1 point); (4) sporadic epileptiform discharges (1 point); (5) frequency greater than 2.0 Hz for any periodic or rhythmic pattern (1 point); and (6) presence of “plus” features (superimposed, rhythmic, sharp, or fast activity) (1 point). The probable seizure risk of each score was 5% for a score of 0, 12% for a score of 1, 27% for a score of 2, 50% for a score of 3, 73% for a score of 4, 88% for a score of 5, and greater than 95% for a score of 6 or 7. Conclusions and Relevance The 2HELPS2B model is a quick accurate tool to aid clinical judgment of the risk of seizures in critically ill patients.

Decision analysis of intracranial monitoring in non-lesional epilepsy

PURPOSE Up to one third of epilepsy patients develop pharmacoresistant seizures and many benefit from resective surgery. However, patients with non-lesional focal epilepsy often require intracranial monitoring to localize the seizure focus. Intracranial monitoring carries operative morbidity risk and does not always succeed in localizing the seizures, making the benefit of this approach less certain. We performed a decision analysis comparing three strategies for patients with non-lesional focal epilepsy: (1) intracranial monitoring, (2) vagal nerve stimulator (VNS) implantation and (3) medical management to determine which strategy maximizes the expected quality-adjusted life years (QALYs) for our base cases. METHOD We constructed two base cases using parameters reported in the medical literature: (1) a young, otherwise healthy patient and (2) an elderly, otherwise healthy patient. We constructed a decision tree comprising strategies for the treatment of non-lesional epilepsy and two clinical outcomes: seizure freedom and no seizure freedom. Sensitivity analyses of probabilities at each branch were guided by data from the medical literature to define decision thresholds across plausible parameter ranges. RESULTS Intracranial monitoring maximizes the expected QALYs for both base cases. The sensitivity analyses provide estimates of the values of key variables, such as the surgical risk or the chance of localizing the focus, at which intracranial monitoring is no longer favored. CONCLUSION Intracranial monitoring is favored over VNS and medical management in young and elderly patients over a wide, clinically-relevant range of pertinent model variables such as the chance of localizing the seizure focus and the surgical morbidity rate.

Variability in clinical assessment of neuroimaging in temporal lobe epilepsy.

PURPOSE Neuroimaging is critical in deciding candidacy for epilepsy surgery. Currently imaging is primarily assessed qualitatively, which may affect patient selection and outcomes. METHOD The epilepsy surgery database at MGH was reviewed for temporal lobectomy patients from the last 10 years. Radiology reports for MRI and FDG-PET were compared to the epilepsy conference consensus. First, specific findings of ipsi/contra hippocampal atrophy and T2 signal changes were directly compared. Next the overall impression of presence of hippocampal sclerosis (HS) for MRI and temporal hypometabolism for PET was used for sensitivity/specificity analysis. To assess predictive power of imaging findings logistic regression was used. RESULTS 104 subjects were identified. 70% of subjects were ILAE class I at 1-year. Radiology reports and the conference consensus differed in 31% of FDG-PET studies and 41% of MRIs. For PET most disagreement (50%) stemmed for discrepancy regarding contralateral temporal hypometabolism. For MRI discrepancy in ipsilateral hippocampal atrophy/T2 signal accounted for 59% of disagreements. When overall impression of the image was used the overall reliability between groups was high with only MRI sensitivity to detect HS (0.75 radiology, 0.91 conference, p=0.02) was significantly different between groups. On logistic regression MRI was a significant predictor of HS, but still 36% of patients with normal MRI as read by both groups had HS on pathology. CONCLUSION Despite some difference in specific radiologic findings, overall accuracy for MRI and PET is similar in clinical practice between radiology and conference; nonetheless there are still cases of hippocampal pathology not detected by standard imaging methods.

Does the Use of IV Contrast Enhanced CT for Attenuation Correction Affect Clinical Interpretation of Head and Neck PET/CT?

Purpose of Report: Evaluate the effect of IV contrast use with FDG PET/CT on clinical interpretation of PET images for head and neck cancer. Procedures: 20 consecutive patients referred for PET/CT and contrast enhanced CT of the head and neck had two sets of PET images obtained. One set used standard low dose CT for attenuation correction, and the other used IV contrast enhanced diagnostic quality CT for attenuation correction. Two blinded nuclear medicine physicians interpreted the results. Results: No statistically significant difference in clinical interpretation of the PET images was found. It was noted that PET scans attenuation corrected with IV contrast CTs had greater incidence of abnormal appearing lesions (P<0.01). Conclusion: It is reasonable to use contrast enhanced CT for attenuation correction in PET/CT of head and neck cancer. This would allow for a reduction in radiation dose delivered to patient.