Low Doses of Ionizing Radiation as a Treatment for Alzheimer's Disease: A Pilot Study.

BACKGROUND: In 2015, a patient in hospice with Alzheimer's disease (AD) was treated with ionizing radiation to her brain using repeated CT scans. Improvement in cognition, speech, movement, and appetite was observed. These improvements were so momentous that she was discharged from the hospice to a long-term care home. Based on this case, we conducted a pilot clinical trial to examine the effect of low-dose ionizing radiation (LDIR) in severe AD. OBJECTIVE: To determine whether the previously reported benefits of LDIR in a single case with AD could be observed again in other cases with AD when the same treatments are given. METHODS: In this single-arm study, four patients were treated with three consecutive treatments of LDIR, each spaced two weeks apart. Qualitative changes in communication and behavior with close relatives were observed and recorded. Quantitative measures of cognition and behavior were administered pre and post LDIR treatments. RESULTS: Minor improvements on quantitative measures were noted in three of the four patients following treatment. However, the qualitative observations of cognition and behavior suggested remarkable improvements within days post-treatment, including greater overall alertness. One patient showed no change. CONCLUSION: LDIR may be a promising, albeit controversial therapy for AD. Trials of patients with less severe AD, double-blind and placebo-controlled, should be carried out to determine the benefits of LDIR. Quantitative measures are needed that are sensitive to the remarkable changes induced by LDIR, such as biological markers of oxidative stress that are associated with AD.

Incidence of Dural Venous Sinus Thrombosis in Patients with Glioblastoma and Its Implications.

OBJECTIVE: Glioblastoma (GBM) is associated with increased risk of developing dural venous sinus thrombosis (DVST), which often goes undiagnosed as symptoms are readily attributed to tumor. The purpose of this study was to investigate the incidence of DVST, potential predictive features on imaging, complications, its effect on survival, and time of greatest risk for developing DVST. METHODS: A retrospective search of patients with GBM who had surgery followed by chemotherapy and/or radiation therapy between 2009 and 2015 at our institution was performed. Magnetic resonance imaging studies of the brain were reviewed on volumetric postgadolinium T1-weighted sequences for DVST. Tumors were characterized using the Visually Accessible REMBRANDT (Repository for Molecular Brain Neoplasia Data) Images classification, and identified thromboses were tracked for propagation, regression, or resolution. Statistical analyses were directed at identifying clinical predictors and survival differences between the DVST and no-DVST groups. RESULTS: In total, 163 cases totaling 1637 scans, were reviewed; 12 patients (7.4%) developed DVST, of whom 11 presented with thrombus before any treatment. Tumor invasion of dural sinuses and greater T1/fluid-attenuated inversion recovery ratios were significantly associated with thrombus development (P = 0.02 and P = 0.02, respectively). In patients who developed DVST, thrombosis was more likely to develop ipsilateral to tumor side (P = 0.01) and was associated with a greater likelihood of developing extracranial venous thromboembolism (P = 0.012). There were no venous infarcts and no significant difference in survival between groups (P = 0.83). CONCLUSIONS: Patients with GBM have increased risk of developing DVST, independent of surgical treatment or chemoradiation. DVST presence does not affect survival. Tumor invasion of dural sinuses and greater T1/fluid-attenuated inversion recovery ratio on preoperative imaging were the most significant predictors of DVST development.

Temporal evolution of perfusion parameters in brain metastases treated with stereotactic radiosurgery: comparison of intravoxel incoherent motion and dynamic contrast enhanced MRI.

Intravoxel incoherent motion (IVIM) is a magnetic resonance imaging (MRI) technique that is seeing increasing use in neuro-oncology and offers an alternative to contrast-enhanced perfusion techniques for evaluation of tumor blood volume after stereotactic radiosurgery (SRS). To date, IVIM has not been validated against contrast enhanced techniques for brain metastases after SRS. In the present study, we measure blood volume for 20 brain metastases (15 patients) at baseline, 1 week and 1 month after SRS using IVIM and dynamic contrast enhanced (DCE)-MRI. Correlation between blood volume measurements made with IVIM and DCE-MRI show poor correlation at baseline, 1 week, and 1 month post SRS (r = 0.33, 0.14 and 0.30 respectively). At 1 week after treatment, no significant change in tumor blood volume was found using IVIM or DCE-MRI (p = 0.81 and 0.41 respectively). At 1 month, DCE-MRI showed a significant decrease in blood volume (p = 0.0002). IVIM, on the other hand, demonstrated the opposite effect and showed a significant increase in blood volume at 1 month (p = 0.03). The results of this study indicate that blood volume measured with IVIM and DCE-MRI are not equivalent. While this may relate to differences in the type of perfusion information each technique is providing, it could also reflect a limitation of tumor blood volume measurements made with IVIM after SRS. IVIM measurements of tumor blood volume in the month after SRS should therefore be interpreted with caution.

Perfusion reduction in the absence of structural differences in cognitively impaired versus unimpaired RRMS patients.

BACKGROUND: Cognitive impairment affects 40%-68% of relapsing-remitting multiple sclerosis (RRMS) patients. Gray matter (GM) demyelination is complicit in cognitive impairment, yet cortical lesions are challenging to image clinically. We wanted to determine whether cortical cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) differences exist between cognitively impaired (CI) and unimpaired (NI) RRMS. METHODS: Prospective study of healthy controls (n = 19), CI (n = 20), and NI (n = 19) undergoing magnetic resonance imaging (MRI) and cognitive testing <1 week apart. White matter (WM) T2 hyperintense lesions and T1 black holes were traced. General linear regression assessed the relationship between lobar WM volume and cortical and WM CBF, CBV, and MTT. Relationship between global and lobar cortical CBF, CBV, and MTT and cognitive impairment was tested using a generalized linear model. Adjusted Bonferroni p < 0.005 was considered significant. RESULTS: No significant differences for age, gender, disease duration, and any fractional brain or lesion volume were demonstrated for RRMS subgroups. Expanded Disability Status Scale (EDSS) and Hospital Anxiety and Depression Scale-Depression (HADS-D) were higher in CI. Lobar cortical CBF and CBV were associated with cognitive impairment (p < 0.0001) after controlling for confounders. Cortical CBV accounted for 7.2% of cognitive impairment increasing to 8.7% with cortical CBF (p = 0.06), while WM and cortical CBF accounted for 8.2% of variance (p = 0.04). CONCLUSION: Significant cortical CBF and CBV reduction was present in CI compared to NI in the absence of structural differences.

Diffusion Tensor Imaging Tractography of the Facial Nerve in Patients With Cerebellopontine Angle Tumors.

OBJECTIVE: To demonstrate the utility of diffusion tensor imaging (DTI) fiber tractography of the facial nerve in patients with cerebellopontine angle (CPA) tumors. STUDY DESIGN: Prospective. SETTING: Tertiary referral center. PATIENTS: DTI technique was established in 113 patients without tumors and in 28 patients with CPA tumors. Subsequently, DTI results were compared with intraoperative findings in 21 patients with medium and large-sized tumors, treated surgically via a translabyrinthine approach. INTERVENTION: Three Tesla magnetic resonance (MR) was used for DTI tractography. For patients without CPA tumors, the scanning protocol was 32 directions with a 3 × 3 × 3 mm voxel size. For CPA tumor patients, scanning protocol was 32 directions with a 2 × 2 × 2 mm voxel size. DTI data were used to track the facial nerve. MAIN OUTCOME MEASURES: Facial nerve identification rate. RESULTS: Facial nerve identification rate in MR-DTI was 97% and 100% in patients without tumors and in patients with tumors of the CPA of the internal auditory canal that were not treated surgically, respectively. MR-DTI identification of the facial nerve was successful in 20 patients who were treated surgically (95%). Good agreement between surgical findings and MR-DTI results was found in 19 patients (90%). CONCLUSION: MR DTI tractography is an effective technique in positively identifying the position of the facial nerve in patients with CPA tumors.

Radiologic Differences between Human Papillomavirus-Related and Human Papillomavirus-Unrelated Oropharyngeal Carcinoma on Diffusion-Weighted Imaging.

BACKGROUND AND PURPOSE: Human papilloma virus-related oropharyngeal carcinoma (HPV+ OPC) is a unique entity compared to HPV-unrelated (HPV-) OPC. Previous studies were inconclusive regarding the differences between HPV+ and HPV- OPCs on diffusion-weighted imaging (DWI). This study sought to determine if there is an association between HPV status and apparent diffusion coefficient (ADC) values as an imaging biomarker in OPCs. MATERIALS AND METHODS: OPC patients with pretreatment MRI including DWI were retrospectively reviewed and analyzed as a blinded, controlled cohort. HPV status was biopsy-ascertained with p16 staining. ADC values were determined by placing the largest possible circular region of interest in solid portions of primary tumors and/or metastatic lymph nodes. Necrotic and cystic portions were excluded. RESULTS: Twenty-eight HPV+ and 12 HPV- patients were included. Adjusted for age and sex, ADC values were significantly lower in HPV+ OPC primary tumors (p = 0.013) and lymph node metastases (p = 0.013). The area under the curve (AUC) was 0.85 and 0.90, respectively. A model with a linear combination of the 2 variables yielded an AUC of 0.92. CONCLUSION: ADC values were significantly lower in both the primary tumors and lymph node metastases in HPV+ OPCs compared to HPV- OPCs. These results confirm the results of prior studies.

Validation of the 9-Point and 24-Point Hematoma Expansion Prediction Scores and Derivation of the PREDICT A/B Scores.

BACKGROUND AND PURPOSE: Nine- and 24-point prediction scores have recently been published to predict hematoma expansion (HE) in acute intracerebral hemorrhage. We sought to validate these scores and perform an independent analysis of HE predictors. METHODS: We retrospectively studied 301 primary or anticoagulation-associated intracerebral hemorrhage patients presenting <6 hours post ictus prospectively enrolled in the Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus Computed Tomography (PREDICT) study. Patients underwent baseline computed tomography angiography and 24-hour noncontrast computed tomography follow-up for HE analysis. Discrimination and calibration of the 9- and 24-point scores was assessed. Independent predictors of HE were identified using multivariable regression and incorporated into the PREDICT A/B scores, which were then compared with existing scores. RESULTS: The 9- and 24-point HE scores demonstrated acceptable discrimination for HE>6 mL or 33% and >6 mL, respectively (area under the curve of 0.706 and 0.755, respectively). The 24-point score demonstrated appropriate calibration in the PREDICT cohort (χ2 statistic, 11.5; P=0.175), whereas the 9-point score demonstrated poor calibration (χ2 statistic, 34.3; P<0.001). Independent HE predictors included spot sign number, time from onset, warfarin use or international normalized ratio>1.5, Glasgow Coma Scale, and National Institutes of Health Stroke Scale and were included in PREDICT A/B scores. PREDICT A showed improved discrimination compared with both existing scores, whereas performance of PREDICT B varied by definition of expansion. CONCLUSIONS: The 9- and 24-point expansion scores demonstrate acceptable discrimination in an independent multicenter cohort; however, calibration was suboptimal for the 9-point score. The PREDICT A score showed improved discrimination for HE prediction but requires independent validation.

Neoplastic meningitis presenting with dysphagia and bilateral vocal cord paralysis.

Neoplastic meningitis is the infiltration of the leptomeninges and subarachnoid space by tumor cells occurring in 3% to 5% of patients with systemic malignancies. Most cases present with multifocal neurological symptoms that vary according to the central nervous system territory involved. Here, we describe the first reported case to our knowledge of neoplastic meningitis causing bilateral vocal cord paralysis. Early diagnosis of this progressive disease process is essential to achieving a better treatment response and improved survival. This report demonstrates that neoplastic meningitis should be considered in the investigation of bilateral vocal cord paralysis, particularly in patients with a history of metastatic disease.

Multicenter accuracy and interobserver agreement of spot sign identification in acute intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Rapid, accurate, and reliable identification of the computed tomography angiography spot sign is required to identify patients with intracerebral hemorrhage for trials of acute hemostatic therapy. We sought to assess the accuracy and interobserver agreement for spot sign identification. METHODS: A total of 131 neurology, emergency medicine, and neuroradiology staff and fellows underwent imaging certification for spot sign identification before enrolling patients in 3 trials targeting spot-positive intracerebral hemorrhage for hemostatic intervention (STOP-IT, SPOTLIGHT, STOP-AUST). Ten intracerebral hemorrhage cases (spot-positive/negative ratio, 1:1) were presented for evaluation of spot sign presence, number, and mimics. True spot positivity was determined by consensus of 2 experienced neuroradiologists. Diagnostic performance, agreement, and differences by training level were analyzed. RESULTS: Mean accuracy, sensitivity, and specificity for spot sign identification were 87%, 78%, and 96%, respectively. Overall sensitivity was lower than specificity (P<0.001) because of true spot signs incorrectly perceived as spot mimics. Interobserver agreement for spot sign presence was moderate (k=0.60). When true spots were correctly identified, 81% correctly identified the presence of single or multiple spots. Median time needed to evaluate the presence of a spot sign was 1.9 minutes (interquartile range, 1.2-3.1 minutes). Diagnostic performance, interobserver agreement, and time needed for spot sign evaluation were similar among staff physicians and fellows. CONCLUSIONS: Accuracy for spot identification is high with opportunity for improvement in spot interpretation sensitivity and interobserver agreement particularly through greater reliance on computed tomography angiography source data and awareness of limitations of multiplanar images. Further prospective study is needed.

Face validity study of an artificial temporal bone for simulation surgery.

HYPOTHESIS: Using the rapid prototype (RP) technology, a physical construct of a human temporal bone was developed based on cadaveric tissue to permit simulated surgical training. The objective of the study was to test the face validity of the model. BACKGROUND: The cost and access to human cadaveric temporal bones is becoming increasingly challenging, particularly if there are religious and regulatory restrictions. There is a need to develop alternative strategies to improve accessibility. METHODS: Ultra high-resolution computed tomography (CT) images (0.15-mm resolution) were obtained from a cadaver temporal bone. Manual segmentation and conversion into a stereolithography file format permitted printing on a RP stereolithography printer. A 3-dimensional physical model was hardened to achieve the desired consistency. Eight practicing otologists were recruited to evaluate this model. Respondents were asked to drill the artificial bone and complete a rating survey upon completion. RESULTS: In using a Likert scale between 1 and 5, results for anatomic accuracy were favorable, with the best scores for overall morphology (4.63) and for lateral structures within the bone (4.5). The poorest scores were for the semicircular canals (3.75) and chorda tympani (3.25). Scores for haptic realism were good as well. The average score for the question "overall, how valuable is the model as a surgical simulator" was 4.1. The experts felt that junior residents (PGY 1-3) would benefit most from this surgical education model. CONCLUSION: The outer structures of the RP artificial temporal bone can be considered to have face validity. Improvements will continue to be made to address some of the deficiencies in the anatomic and haptic realism of this model.

Hemorrhagic epidermoid cyst in a patient with generalized tonic clonic seizure.

Epidermoid cysts account for approximately 1% of all intracranial tumors. Hemorrhage into an epidermoid cyst is extremely rare, and has only been reported a few times. To our knowledge, there are no reports of a hemorrhagic epidermoid cyst presenting with a first generalized tonic clonic seizure. We present a 68-year old female with an epidermoid cyst with intracystic hemorrhage who presented with a first time generalized tonic clonic seizure. When complicated with hemorrhage, the diagnosis of an epidermoid cyst is challenging and there is a potential for misdiagnosis.

NASCET percent stenosis semi-automated versus manual measurement on CTA.

PURPOSE: To compare North American Symptomatic Carotid Endarterectomy Trial (NASCET) stenosis values and NASCET grade categorization (mild, moderate, severe) of semi-automated vessel analysis software versus manual measurements on computed tomography angiography (CTA). METHODS: There were four observers. Two independently analyzed 81 carotid artery CTAs using semi-automated vessel analysis software according to a blinded protocol. The software measured the narrowest stenosis in millimeters (mm), distal internal carotid artery (ICA) in mm, and calculated percent stenosis based on NASCET criteria. One of these two observers performed this task twice on each carotid, the second analysis was delayed two months in order to mitigate recall bias. Two other observers manually measured the narrowest stenosis in mm, distal ICA in mm, and calculated NASCET percent stenosis in a blinded fashion. The calculated NASCET stenoses were categorized into mild, moderate, or severe. Chi square and analysis of variance (ANOVA) were used to test for statistical differences. RESULTS: ANOVA did not find a statistically significant difference in the mean percent stenosis when comparing the two manual measurements, the two semi-automated measurements, and the repeat semi-automated. Chi square demonstrated that the distribution of grades of stenosis were statistically different (p<0.05) between the manual and semiautomated grades. Semi-automated vessel analysis tended to underestimate the degree of stenosis compared to manual measurement. CONCLUSION: The mean percentage stenosis determined by semi-automated vessel analysis is not significantly different from manual measurement. However, when the data is categorized into mild, moderate and severe stenosis, there is a significant difference between semi-automated and manual measurements. The semi-automated software tends to underestimate the stenosis grade compared to manual measurement.

Rare frontal lobe intraparenchymal epidermoid cyst with atypical imaging.

Epidermoid cysts are slow-growing benign tumors derived from ectodermal tissue that are hypothesized to have been inwardly displaced from the ectodermal surfaces during embryologic development. These cysts represent 1% to 2% of all intracranial tumors, and occur most commonly in the cerebellopontine angle, parasellar region, and subarachnoid spaces of the basal cisterns. Epidermoid cysts that are exclusively intraparenchymal are very rare, and can be difficult to diagnose as they often do not have classic radiologic findings, and share many similar radiologic features to other tumors such as astrocytomas, arachnoid cysts, dermoid cysts, and cavernomas. The authors present a patient with a rare intraparenchymal epidermoid cyst of the frontal lobe with atypical imaging features.