Wide-field calcium imaging reveals widespread changes in cortical functional connectivity following mild traumatic brain injury in the mouse.

>2.5 million individuals in the United States suffer mild traumatic brain injuries (mTBI) annually. Mild TBI is characterized by a brief period of altered consciousness, without objective findings of anatomic injury on clinical imaging or physical deficit on examination. Nevertheless, a subset of mTBI patients experience persistent subjective symptoms and repeated mTBI can lead to quantifiable neurological deficits, suggesting that each mTBI alters neurophysiology in a deleterious manner not detected using current clinical methods. To better understand these effects, we performed mesoscopic Ca2+ imaging in mice to evaluate how mTBI alters patterns of neuronal interactions across the dorsal cerebral cortex. Spatial Independent Component Analysis (sICA) and Localized semi-Nonnegative Matrix Factorization (LocaNMF) were used to quantify changes in cerebral functional connectivity (FC). Repetitive, mild, controlled cortical impacts induce temporary neuroinflammatory responses, characterized by increased density of microglia exhibiting de-ramified morphology. These temporary neuro-inflammatory changes were not associated with compromised cognitive performance in the Barnes maze or motor function as assessed by rotarod. However, long-term alterations in functional connectivity (FC) were observed. Widespread, bilateral changes in FC occurred immediately following impact and persisted for up to 7 weeks, the duration of the experiment. Network alterations include decreases in global efficiency, clustering coefficient, and nodal strength, thereby disrupting functional interactions and information flow throughout the dorsal cerebral cortex. A subnetwork analysis shows the largest disruptions in FC were concentrated near the impact site. Therefore, mTBI induces a transient neuroinflammation, without alterations in cognitive or motor behavior, and a reorganized cortical network evidenced by the widespread, chronic alterations in cortical FC.

Readmission risk of malignant brain tumor patients undergoing laser interstitial thermal therapy (LITT) and stereotactic needle biopsy (SNB): a covariate balancing weights analysis of the National Readmissions Database (NRD).

PURPOSE: Despite procedural similarities between laser interstitial thermal therapy (LITT) and stereotactic needle biopsy (SNB), LITT induces delayed, pro-inflammatory responses not associated with SNB that may increase the risk of readmission within 30- or 90- days. Here, we explore this hypothesis. METHODS: We queried the National Readmissions Database (NRD, 2010-18) for malignant brain tumor patients who underwent elective LITT or SNB using International Classification of Diseases codes. Readmissions were defined as non-elective inpatient hospitalizations. Survey regression methods and a weighted analysis were utilized to adjust for demographic and clinical differences between LITT and SNB cohorts. RESULTS: During the study period, an estimated 685 malignant brain patients underwent elective LITT and 15,177 underwent elective SNB. Patients undergoing LITT and SNB exhibited comparable median lengths of hospital stay [IQR; LITT = 2 (1, 3); SNB = 1 (1, 2); p = 0.820]. Likelihood of routine discharge was not significantly different between the two procedures (p = 0.263). No significant differences were observed in the odds of 30- or 90-day unplanned readmission between the LITT and SNB cohorts after multivariable adjustment (all p ≥ 0.177). The covariate balancing weighted analysis confirmed comparable 30 or 90-day readmission risk between LITT and SNB treated patients (all p ≥ 0.201). CONCLUSION: The likelihood of 30- and 90-day readmission for malignant brain tumor patients who underwent LITT or SNB are comparable, supporting the safety profile of LITT as therapy for malignant brain cancers.

Percutaneous n-butyl cyanoacrylate embolization of cervical metastatic disease via an anterolateral approach.

Symptomatic vascular spinal metastases will benefit from pre-operative tumor embolization - percutaneous with or without adjunct endovascular embolization. However, when a transpedicular approach is not feasible, an anterolateral approach may be a viable alternative. The authors report a 57-year-old woman with prior C3-T1 instrumentation who presented with acute cord compression from a pathologic C5 vertebral body fracture related to metastatic renal cell carcinoma. The patient underwent CT-guided direct tumor embolization with 33% n-butyl-2-cyanoacrylate via an anterolateral approach, followed by C5-corpectomy and anterior cervical C4-C6 fusion and plating with minimal blood loss (est. 20 cc) and a stable neurological exam post-operatively. In patients with highly vascular cervical metastatic disease who lack a viable transpedicular approach for preoperative tumor embolization, a CT-guided anterolateral approach is a viable alternative.

Prediction of Obliteration After the Gamma Knife Radiosurgery of Arteriovenous Malformations Using Hand-Crafted Radiomics and Deep-Learning Methods.

INTRODUCTION: Brain arteriovenous malformations (bAVMs) are vascular abnormalities that can be treated with embolization or radiotherapy to prevent the risk of future rupture. In this study, we use hand-crafted radiomics and deep learning techniques to predict favorable vs. unfavorable outcomes following Gamma Knife radiosurgery (GKRS) of bAVMs and compare their prediction performances. METHODS: One hundred twenty-six patients seen at one academic medical center for GKRS obliteration of bAVMs over 15 years were retrospectively reviewed. Forty-two patients met the inclusion criteria. Favorable outcomes were defined as complete nidus obliteration demonstrated on cerebral angiogram and asymptomatic recovery. Unfavorable outcomes were defined as incomplete obliteration or complications relating to the AVM that developed after GKRS. Outcome predictions were made using a random forest model with hand-crafted radiomic features and a fine-tuned ResNet-34 convolutional neural network (CNN) model. The performance was evaluated by using a ten-fold cross-validation technique. RESULTS: The average accuracy and area-under-curve (AUC) values of the Random Forest Classifier (RFC) with radiomics features were 68.5 ±9.80% and 0.705 ±0.086, whereas those of the ResNet-34 model were 60.0 ±11.9% and 0.694 ±0.124. Four radiomics features used with RFC discriminated unfavorable response cases from favorable response cases with statistical significance. When cropped images were used with ResNet-34, the accuracy and AUC decreased to 59.3 ± 14.2% and 55.4 ±10.4%, respectively. CONCLUSIONS: A hand-crafted radiomics model and a pre-trained CNN model can be fine-tuned on pre-treatment MRI scans to predict clinical outcomes of AVM patients undergoing GKRS with equivalent prediction performance. The outcome predictions are promising but require further external validation on more patients.

Utilizing kinematic analysis of postural instability as an objective measure to aid in distinguishing between normal pressure hydrocephalus and Parkinson's disease.

Objective: Patients with normal pressure hydrocephalus (NPH) and Parkinson's Disease (PD) can clinically appear quite similar at baseline evaluation. We sought to investigate the use of kinematic assessment of postural instability (PI) using inertial measurement units (IMUs) as a mechanism of differentiation between the two disease processes. Methods: 20 patients with NPH, 55 patients with PD, and 56 age-matched, healthy controls underwent quantitative pull test examinations while wearing IMUs at baseline. Center of mass and foot position data were used to compare velocity and acceleration profiles, pull test step length, and reaction times between groups and as a function of Unified Parkinson's disease Rating Scale Pull Test (UPDRSPT) score. Results: Overall, the reactive postural response of NPH patients was characterized by slower reaction times and smaller steps compared to both PD patients and healthy controls. However, when patients were grouped by UPDRSPT scores, no reliable objective difference between groups was detected. Conclusion: At their initial evaluation, very few NPH patients demonstrate "normal" or "mild" PI as they appear to be older upon presentation compared to PD patients. As a result, kinematic assessment utilizing IMUs may not be helpful for differentiating between NPH and PD as a function of UPDRSPT score, but rather as a more fine-tuned method to define disease progression. We emphasize the need for further evaluation of incorporating objective kinematic data collection as a way to evaluate PI and improve patient outcomes.

Real world validation of activity recognition algorithm and development of novel behavioral biomarkers of falls in aged control and movement disorder patients.

The use of wearable sensors in movement disorder patients such as Parkinson's disease (PD) and normal pressure hydrocephalus (NPH) is becoming more widespread, but most studies are limited to characterizing general aspects of mobility using smartphones. There is a need to accurately identify specific activities at home in order to properly evaluate gait and balance at home, where most falls occur. We developed an activity recognition algorithm to classify multiple daily living activities including high fall risk activities such as sit to stand transfers, turns and near-falls using data from 5 inertial sensors placed on the chest, upper-legs and lower-legs of the subjects. The algorithm is then verified with ground truth by collecting video footage of our patients wearing the sensors at home. Our activity recognition algorithm showed >95% sensitivity in detection of activities. Extracted features from our home monitoring system showed significantly better correlation (~69%) with prospectively measured fall frequency of our subjects compared to the standard clinical tests (~30%) or other quantitative gait metrics used in past studies when attempting to predict future falls over 1 year of prospective follow-up. Although detecting near-falls at home is difficult, our proposed model suggests that near-fall frequency is the most predictive criterion in fall detection through correlation analysis and fitting regression models.

Rates of operative intervention for infection after synthetic or autologous cranioplasty: a National Readmissions Database analysis.

OBJECTIVE: The aim of this study was to characterize the clinical utilization and associated charges of autologous bone flap (ABF) versus synthetic flap (SF) cranioplasty and to characterize the postoperative infection risk of SF versus ABF using the National Readmissions Database (NRD). METHODS: The authors used the publicly available NRD to identify index hospitalizations from October 2015 to December 2018 involving elective ABF or SF cranioplasty after traumatic brain injury (TBI) or stroke. Subsequent readmissions were further characterized if patients underwent neurosurgical intervention for treatment of infection or suspected infection. Survey Cox proportional hazards models were used to assess risk of readmission. RESULTS: An estimated 2295 SF and 2072 ABF cranioplasties were performed from October 2015 to December 2018 in the United States. While the total number of cranioplasty operations decreased during the study period, the proportion of cranioplasties utilizing SF increased (p < 0.001), particularly in male patients (p = 0.011) and those with TBI (vs stroke, p = 0.012). The median total hospital charge for SF cranioplasty was $31,200 more costly than ABF cranioplasty (p < 0.001). Of all first-time readmissions, 20% involved surgical treatment for infectious reasons. Overall, 122 SF patients (5.3%) underwent surgical treatment of infection compared with 70 ABF patients (3.4%) on readmission. After accounting for confounders using a multivariable Cox model, female patients (vs male, p = 0.003), those discharged nonroutinely (vs discharge to home or self-care, p < 0.001), and patients who underwent SF cranioplasty (vs ABF, p = 0.011) were more likely to be readmitted for reoperation. Patients undergoing cranioplasty during more recent years (e.g., 2018 vs 2015) were less likely to be readmitted for reoperation because of infection (p = 0.024). CONCLUSIONS: SFs are increasingly replacing ABFs as the material of choice for cranioplasty, despite their association with increased hospital charges. Female sex, nonroutine discharge, and SF cranioplasty are associated with increased risk for reoperation after cranioplasty.