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Jennifer A. Sweet, Keming Gao, Zhengyi Chen, Curtis Tatsuoka, Joseph R. Calabrese, Martha Sajatovic, Jonathan P. Miller, and Cameron C. McIntyre

OBJECTIVE

The clinical response of patients with bipolar disorder to medical treatment is variable. A better understanding of the underlying neural circuitry involved in bipolar treatment responsivity subtypes may provide insight into treatment resistance and aid in identifying an effective surgical target for deep brain stimulation (DBS) specific to the disorder. Despite considerable imaging research related to the disease, a paucity of comparative imaging analyses of treatment responsiveness exists. There are also no DBS targets designed expressly for patients with bipolar disorder. Therefore, the authors analyzed cingulum bundle axonal connectivity in relation to cortico-striatal-thalamo-cortical (CSTC) loops implicated in bipolar disorder across subjects who are responsive to treatment (RSP) and those who are refractory to therapy (REF), compared to healthy controls (HCs).

METHODS

Twenty-five subjects with bipolar disorder (13 RSP and 12 REF), diagnosed using the Mini International Neuropsychiatric Interview and classified with standardized rating scales, and 14 HCs underwent MRI with diffusion sequences for probabilistic diffusion-weighted tractography analysis. Image processing and tractography were performed using MRTrix. Region of interest (ROI) masks were created manually for 10 anterior cingulum bundle subregions, including surgical targets previously evaluated for the treatment of bipolar disorder (cingulotomy and subgenual cingulate DBS targets). Cortical and subcortical ROIs of brain areas thought to be associated with bipolar disorder and described in animal tract-tracing models were created via FreeSurfer. The number of axonal projections from the cingulum bundle subregion ROIs to cortical/subcortical ROIs for each group was compared.

RESULTS

Significant differences were found across groups involving cingulum bundle and CSTC loops. Subjects in the RSP group had increased connections from rostral cingulum bundle to medial orbitofrontal cortex, which is part of the limbic CSTC loop, whereas subjects in the REF group had increased connectivity from rostral cingulum bundle to thalamus. Additionally, compared to HCs, both RSP and REF subjects had decreased cingulum bundle dorsal connectivity (dorsal anterior/posterior cingulate, dorsomedial/lateral frontal cortex) and increased cingulum bundle ventral connectivity (subgenual cingulate, frontal pole, lateral orbitofrontal cortex) involving limbic and associative CSTC loops.

CONCLUSIONS

Findings demonstrate that bipolar treatment responsivity may be associated with significant differences in cingulum bundle connectivity in relation to CSTC loops, which may help identify a surgical target for bipolar disorder treatment via DBS in the future.

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Jessica C. Eaton, Madeline E. Greil, Dominic Nistal, David J. Caldwell, Emily Robinson, Zaid Aljuboori, Nancy Temkin, Robert H. Bonow, and Randall M. Chesnut

OBJECTIVE

Cranioplasty is a technically simple procedure, although one with potentially high rates of complications. The ideal timing of cranioplasty should minimize the risk of complications, but research investigating cranioplasty timing and risk of complications has generated diverse findings. Previous studies have included mixed populations of patients undergoing cranioplasty following decompression for traumatic, vascular, and other cerebral insults, making results challenging to interpret. The objective of the current study was to examine rates of complications associated with cranioplasty, specifically for patients with traumatic brain injury (TBI) receiving this procedure at the authors’ high-volume level 1 trauma center over a 25-year time period.

METHODS

A single-institution retrospective review was conducted of patients undergoing cranioplasty after decompression for trauma. Patients were identified and clinical and demographic variables obtained from 2 neurotrauma databases. Patients were categorized into 3 groups based on timing of cranioplasty: early (≤ 90 days after craniectomy), intermediate (91–180 days after craniectomy), and late (> 180 days after craniectomy). In addition, a subgroup analysis of complications in patients with TBI associated with ultra-early cranioplasty (< 42 days, or 6 weeks, after craniectomy) was performed.

RESULTS

Of 435 patients identified, 141 patients underwent early cranioplasty, 187 patients received intermediate cranioplasty, and 107 patients underwent late cranioplasty. A total of 54 patients underwent ultra-early cranioplasty. Among the total cohort, the mean rate of postoperative hydrocephalus was 2.8%, the rate of seizure was 4.6%, the rate of postoperative hematoma was 3.4%, and the rate of infection was 6.0%. The total complication rate for the entire population was 16.8%. There was no significant difference in complications between any of the 3 groups. No significant differences in postoperative complications were found comparing the ultra-early cranioplasty group with all other patients combined.

CONCLUSIONS

In this cohort of patients with TBI, early cranioplasty, including ultra-early procedures, was not associated with higher rates of complications. Early cranioplasty may confer benefits such as shorter or fewer hospitalizations, decreased financial burden, and overall improved recovery, and should be considered based on patient-specific factors.

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Logan E. Miller, Jillian E. Urban, Mark A. Espeland, Michael P. Walkup, James M. Holcomb, Elizabeth M. Davenport, Alexander K. Powers, Christopher T. Whitlow, Joseph A. Maldjian, and Joel D. Stitzel

OBJECTIVE

Youth football athletes are exposed to repetitive subconcussive head impacts during normal participation in the sport, and there is increasing concern about the long-term effects of these impacts. The objective of the current study was to determine if strain-based cumulative exposure measures are superior to kinematic-based exposure measures for predicting imaging changes in the brain.

METHODS

This prospective, longitudinal cohort study was conducted from 2012 to 2017 and assessed youth, male football athletes. Kinematic data were collected at all practices and games from enrolled athletes participating in local youth football organizations in Winston-Salem, North Carolina, and were used to calculate multiple risk-weighted cumulative exposure (RWE) kinematic metrics and 36 strain-based exposure metrics. Pre- and postseason imaging was performed at Wake Forest School of Medicine, and diffusion tensor imaging (DTI) measures, including fractional anisotropy (FA), and its components (CL, CP, and CS), and mean diffusivity (MD), were investigated. Included participants were youth football players ranging in age from 9 to 13 years. Exclusion criteria included any history of previous neurological illness, psychiatric illness, brain tumor, concussion within the past 6 months, and/or contraindication to MRI.

RESULTS

A total of 95 male athletes (mean age 11.9 years [SD 1.0 years]) participated between 2012 and 2017, with some participating for multiple seasons, resulting in 116 unique athlete-seasons. Regression analysis revealed statistically significant linear relationships between the FA, linear coefficient (CL), and spherical coefficient (CS) and all strain exposure measures, and well as the planar coefficient (CP) and 8 strain measures. For the kinematic exposure measures, there were statistically significant relationships between FA and RWE linear (RWEL) and RWE combined probability (RWECP) as well as CS and RWEL. According to area under the receiver operating characteristic (ROC) curve (AUC) analysis, the best-performing metrics were all strain measures, and included metrics based on tensile, compressive, and shear strain.

CONCLUSIONS

Using ROC curves and AUC analysis, all exposure metrics were ranked in order of performance, and the results demonstrated that all the strain-based metrics performed better than any of the kinematic metrics, indicating that strain-based metrics are better discriminators of imaging changes than kinematic-based measures. Studies relating the biomechanics of head impacts with brain imaging and cognitive function may allow equipment designers, care providers, and organizations to prevent, identify, and treat injuries in order to make football a safer activity.

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Han Yan, Lior M. Elkaim, Flavia Venetucci Gouveia, Joelene F. Huber, Jurgen Germann, Aaron Loh, Juan Carlos Benedetti-Isaac, Paresh K. Doshi, Cristina V. Torres, David J. Segar, Gavin J. B. Elias, Alexandre Boutet, G. Rees Cosgrove, Alfonso Fasano, Andres M. Lozano, Abhaya V. Kulkarni, and George M. Ibrahim

OBJECTIVE

Individuals with autism spectrum disorder (ASD) may display extreme behaviors such as self-injury or aggression that often become refractory to psychopharmacology or behavioral intervention. Deep brain stimulation (DBS) is a surgical alternative that modulates brain circuits that have yet to be clearly elucidated. In the current study the authors performed a connectomic analysis to identify brain circuitry engaged by DBS for extreme behaviors associated with ASD.

METHODS

A systematic review was performed to identify prior reports of DBS as a treatment for extreme behaviors in patients with ASD. Individual patients’ perioperative imaging was collected from corresponding authors. DBS electrode localization and volume of tissue activated modeling were performed. Volumes of tissue activated were used as seed points in high-resolution normative functional and structural imaging templates. The resulting individual functional and structural connectivity maps were pooled to identify networks and pathways that are commonly engaged by all targets.

RESULTS

Nine patients with ASD who were receiving DBS for symptoms of aggression or self-injurious behavior were identified. All patients had some clinical improvement with DBS. Connectomic analysis of 8 patients (from the systematic review and unpublished clinical data) demonstrated a common anatomical area of shared circuitry within the anterior limb of the internal capsule. Functional analysis of 4 patients identified a common network of distant brain areas including the amygdala, insula, and anterior cingulate engaged by DBS.

CONCLUSIONS

This study presents a comprehensive synopsis of the evidence for DBS in the treatment of extreme behaviors associated with ASD. Using network mapping, the authors identified key circuitry common to DBS targets.

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Tackeun Kim, Young-Gon Kim, Seyeon Park, Jae-Koo Lee, Chang-Hyun Lee, Seung-Jae Hyun, Chi Heon Kim, Ki-Jeong Kim, and Chun Kee Chung

OBJECTIVE

Magnetic resonance imaging (MRI) is the gold-standard tool for diagnosing lumbar spinal stenosis (LSS), but it is difficult to promptly examine all suspected cases with MRI considering the modality’s high cost and limited accessibility. Although radiography is an efficient screening technique owing to its low cost, rapid operability, and wide availability, its diagnostic accuracy is relatively poor. In this study, the authors aimed to develop a deep learning model with a convolutional neural network (CNN) for diagnosing severe central LSS using radiography and to evaluate radiological diagnostic features using gradient-weighted class activation mapping (Grad-CAM).

METHODS

Patients who had undergone both spinal MRI and radiography in the period from May 1, 2005, to December 31, 2017, were screened. According to the formal MRI report, participants were consecutively included in the severe central LSS or healthy control group, and radiographs for both groups were collected. A CNN-based transfer learning algorithm was developed to classify radiographic findings as LSS or normal (binary classification). The proposed models were evaluated using six performance metrics: area under the receiver operating characteristic curve (AUROC), accuracy, sensitivity, specificity, and positive and negative predictive values.

RESULTS

The VGG19 model achieved the highest accuracy with an AUROC of 90.0% (95% CI 89.8%–90.3%) by training 12,442 images. Accuracy was 82.8% (95% CI 82.5%–83.1%) by averaging 5-fold models. Feature points on Grad-CAM were reasonable, and the features could be categorized into reduced disc height, narrow foramina, short pedicle, and hyperdense facet joint. The AUROC in the extra validation was 89.3% (95% CI 88.7%–90.0%). Accuracy was 81.8% (95% CI 80.6%–83.0%) by averaging 5-fold models. Multivariate logistic regression analysis showed that a combination of demographic factors (age and sex) did not improve the model performance.

CONCLUSIONS

The algorithm trained by a CNN to identify central LSS on radiographs showed high diagnostic accuracy and is expected to be useful as a triage tool. The algorithm could accurately localize the stenotic lesion to assist physicians in the identification of LSS.

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Abdelsimar T. Omar II, Adrian I. Espiritu, and Julian Spears

OBJECTIVE

While ventriculoperitoneal shunt (VPS) insertion is the standard treatment for myelomeningocele-associated hydrocephalus (MAH), it can be complicated by infection and shunt malfunction. As such, endoscopic third ventriculostomy (ETV), with or without choroid plexus coagulation (CPC), has been proposed as an alternative. The aim of this review was to determine the success, technical failure, and complication rates of ETV with or without CPC in patients with MAH.

METHODS

PubMed, Scopus, and Cochrane Central Register of Controlled Trials databases were searched from inception to June 2020 for case series, cohort studies, or randomized controlled trials reporting success, technical failure, or complication rates. Random-effects analysis was performed to determine the estimates for these outcome measures. Studies were evaluated using the Newcastle-Ottawa Scale for quality and risk of bias.

RESULTS

Thirteen studies with a total of 325 patients who underwent either ETV or ETV+CPC were included in the review. Using random-effects modeling, the pooled estimate of the success rate was 56% (95% CI 44%–68%, I2 = 78%), while the technical failure rate was 2% (95% CI 0%–6%, I2 = 32%). The estimate for the success rate had high heterogeneity, due to the type of surgical intervention (ETV vs ETV+CPC, p < 0.001). Random-effects analysis of 9 studies with 117 patients who underwent ETV alone yielded an estimated success rate of 48% (95% CI 0.39–0.57, I2 = 0%), while analysis of 4 studies with 166 patients who underwent ETV+CPC revealed a success rate of 75% (95% CI 67%–82%, I2 = 21%). The estimates for the mild/moderate, severe, and fatal complication rates were 0 (95% CI 0%–4%, I2 = 0%), 2% (95% CI 0%–10%, I2 = 52%), and 0 (95% CI 0%–1%, I2 = 0%), respectively.

CONCLUSIONS

ETV+CPC was associated with a higher success rate than ETV alone for MAH in a meta-analysis of published studies. ETV, with or without CPC, was technically feasible and safe for this patient population.

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Chad E. Cook, Steven Z. George, Anthony L. Asher, Erica F. Bisson, Avery L. Buchholz, Mohamad Bydon, Andrew K. Chan, Regis W. Haid, Praveen V. Mummaneni, Paul Park, Christopher I. Shaffrey, Khoi D. Than, Luis M. Tumialan, Michael Y. Wang, and Oren N. Gottfried

OBJECTIVE

High-impact chronic pain (HICP) is a recently proposed metric that indicates the presence of a severe and troubling pain-related condition. Surgery for cervical spondylotic myelopathy (CSM) is designed to halt disease transition independent of chronic pain status. To date, the prevalence of HICP in individuals with CSM and their HICP transition from presurgery is unexplored. The authors sought to define HICP prevalence, transition, and outcomes in patients with CSM who underwent surgery and identify predictors of these HICP transition groups.

METHODS

CSM surgical recipients were categorized as HICP at presurgery and 3 months if they exhibited pain that lasted 6–12 months or longer with at least one major activity restriction. HICP transition groups were categorized and evaluated for outcomes. Multivariate multinomial modeling was used to predict HICP transition categorization.

RESULTS

A majority (56.1%) of individuals exhibited HICP preoperatively; this value declined to 15.9% at 3 months (71.6% reduction). The presence of HICP was also reflective of other self-reported outcomes at 3 and 12 months, as most demonstrated notable improvement. Higher severity in all categories of self-reported outcomes was related to a continued HICP condition at 3 months. Both social and biological factors predicted HICP translation, with social factors being predominant in transitioning to HICP (from none preoperatively).

CONCLUSIONS

Many individuals who received CSM surgery changed HICP status at 3 months. In a surgical population where decisions are based on disease progression, most of the changed status went from HICP preoperatively to none at 3 months. Both social and biological risk factors predicted HICP transition assignment.

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Yasunori Nagahama, Allyson L. Alexander, and Brent R. O’Neill

Stereoelectroencephalography (SEEG) has become increasingly employed as a critical component of epilepsy workups for patients with drug-resistant epilepsy when information from noninvasive studies is not conclusive and sufficient to guide epilepsy surgery. Although exceedingly rare, clinically significant hemorrhagic complications can be caused during SEEG implantation procedures. Intracranial hemorrhage (ICH) can be difficult to recognize due to the minimally invasive nature of SEEG. The authors describe their technique using a commercially available intraparenchymal intracranial pressure (ICP) monitor as a method for early intraoperative detection of ICH during SEEG implantation.

Between May 2019 and July 2021, 18 pediatric patients underwent SEEG implantation at a single, freestanding children’s hospital with the use of an ICP monitor during the procedure. No patients experienced complications resulting from this technique. The authors have relayed their rationale for ICP monitor use during SEEG, the technical considerations, and the safety profile. In addition, they have reported an illustrative case in which the ICP monitor proved crucial in early detection of ICH during SEEG implantation.

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Tiit Mathiesen, Jeppe Haslund-Vinding, Jane Skjøth-Rasmussen, Lars Poulsgaard, Kåre Fugleholm, Christian Mirian, Andrea Daniela Maier, Thomas Santarius, Frantz Rom Poulsen, Vibeke Andrée Larsen, Bjarne Winther Kristensen, David Scheie, Ian Law, and Morten Ziebell