Neurovascular Compression in the Anterior Visual Pathway: A Case Series.

A retrospective review of 29 patients with neurovascular compression syndrome (NVCS) involving the anterior visual pathway was conducted. Various patterns of NVCS and visual defects were identified, most commonly involving the optic nerve and internal carotid artery. Most patients were stable, except one with progressive visual field defects. Although mostly asymptomatic, NVCS can rarely cause compressive optic neuropathy. NVCS should be kept in the differential diagnosis of normal tension glaucoma, especially with progressive visual loss despite treatment. Patients with progressive visual loss may require decompression surgery. Non-contrast computed tomography scan may miss NVCS, and magnetic resonance imaging is diagnostic.

Memory retrieval brain-behavior disconnection in mild traumatic brain injury: A magnetoencephalography and diffusion tensor imaging study.

Mild traumatic brain (mTBI) injury is often associated with long-term cognitive and behavioral complications, including an increased risk of memory impairment. Current research challenges include a lack of cross-modal convergence regarding the underlying neural-behavioral mechanisms of mTBI, which hinders therapeutics and outcome management for this frequently under-treated and vulnerable population. We used multi-modality imaging methods including magnetoencephalography (MEG) and diffusion tensor imaging (DTI) to investigate brain-behavior impairment in mTBI related to working memory. A total of 41 participants were recruited, including 23 patients with a first-time mTBI imaged within 3 months of injury (all male, age = 29.9, SD = 6.9), and 18 control participants (all male, age = 27.3, SD = 5.3). Whole-brain statistics revealed spatially concomitant functional-structural disruptions in brain-behavior interactions in working memory in the mTBI group compared with the control group. These disruptions are located in the hippocampal-prefrontal region and, additionally, in the amygdala (measured by MEG neural activation and DTI measures of fractional anisotropy in relation to working memory performance; p < .05, two-way ANCOVA, nonparametric permutations, corrected). Impaired brain-behavior connections found in the hippocampal-prefrontal and amygdala circuits indicate brain dysregulation of memory, which may leave mTBI patients vulnerable to increased environmental demands exerting memory resources, leading to related cognitive and emotional psychopathologies. The findings yield clinical implications and highlight a need for early rehabilitation after mTBI, including attention- and sensory-based behavioral exercises.

Endovascular and Antithrombotic Treatment in Blunt Cerebrovascular Injuries: A Systematic Review and Meta-Analysis.

OBJECTIVES: Ischemic stroke has been estimated to occur in up to 26% of patients with blunt cerebrovascular injury (BCVI). Antithrombotic therapy (AT) may be used for stroke prevention, but the role of endovascular treatment (ET) remains unclear. We systematically reviewed the literature on AT and ET for the treatment of patients with BCVIs. MATERIALS AND METHODS: PubMed, EMBASE, Web of Science, and Cochrane were searched upon the PRISMA guidelines to include studies reporting the use of ET in BCVI patients. Post-ET neurologic outcomes, radiographic responses, and complication rates were assessed. A fixed-effect model meta-analysis was performed to compare treatment-related post-BCVI ischemic stroke rates between AT and ET protocols. RESULTS: We included 16 studies comprising 352 patients undergoing ET for BCVI. Mean post-ET rates of good neurologic outcomes and radiologic responses were 86.9% (range, 63.6-100%) and 94.0% (range 57.1-100%), respectively. Mean post-ET complication rate was 5.2% (range, 0-66.7%). Seven studies compared the roles of AT (delivered in 805 patients) and ET (performed in 235 patients) for preventing the onset of post-BCVI ischemic strokes. No significant difference in rates of post-BCVI ischemic stroke was found between patients receiving AT vs patients undergoing ET (OR 0.71, 95% CI: 0.35-1.42, p = 0.402). CONCLUSION: AT and ET may be comparable in preventing the occurrence of ischemic stroke following BCVIs. AT may be preferred as the less-invasive first-line therapy, but ET showed favorable rates of post-treatment clinical and radiologic outcomes, coupled with low rates of treatment-related complications.

Access-site complications in ultrasound-guided endovascular thrombectomy: a single-institution retrospective cohort study.

OBJECTIVE: Mechanical endovascular thrombectomy (EVT) is an increasingly relied-on treatment for clot retrieval in the context of ischemic strokes, which otherwise are associated with significant morbidity and mortality. Despite several known risks associated with this procedure, there is a high degree of technical heterogeneity across both centers and operators. The most common procedural complications occur at the point of transfemoral access (the common femoral artery), and include access-site hematomas, dissections, and pseudoaneurysms. Other interventional fields have previously popularized the use of ultrasound to enhance the anatomical localization of structures relevant to vascular access and thereby reducing access-site complications. In this study, the authors aimed to describe the ultrasound-guided EVT technique performed at a large, quaternary neurovascular referral center, and to characterize the effects of ultrasound guidance on access-site complications. METHODS: A retrospective chart review of all patients treated with EVT at a single center between January 2013 and August 2020 was performed. Patients in this cohort were treated using a universal, unique, ultrasound-guided, single-wall puncture technique, which bears several theoretical advantages over the standard technique of arterial puncture via palpation. RESULTS: There were 479 patients treated with EVT within the study period. Twenty patients in the cohort were identified as having experienced some form of access-site complication. Eight (1.67%) of these patients experienced minor access-site complications, all of which were groin hematomas and none of which were clinically significant, as defined by requiring surgical or interventional management or transfusion. The remaining 12 patients experienced arterial dissection (n = 5), arterial pseudoaneurysm (n = 4), retroperitoneal hematoma (n = 2), or arterial occlusion (n = 1), with only 1.04% (5/479) requiring surgical or interventional management or transfusion. CONCLUSIONS: The authors found an overall reduction in total access-site complications as well as minor access-site complications in the study cohort compared with previously published randomized controlled trials and observational studies in the recent literature. The findings suggested that there may be a role for routine use of ultrasound-guided puncture techniques in EVT to decrease rates of complications.

Gaining Access to the Superior Ophthalmic Vein for Endovascular Embolization of Indirect Carotid-Cavernous Fistulas.

ABSTRACT: Carotid-cavernous fistulas (CCFs) are abnormal connections between the carotid arterial system and the cavernous sinus. These acquired vascular malformations may result in severe orbital congestion and sight-threatening complications. The authors present their experience in gaining access to the superior ophthalmic vein to embolize indirect CCFs in three different patients. Surgical exposure and cannulation of the SOV were successful in all 3 cases. One patient developed an orbital compartment syndrome towards the end of the embolization process, after the irrigation cannula was inadvertently dislodged from the SOV. He required a lateral canthotomy and inferior cantholysis but did not suffer from any related sequelae. Signs and symptoms resolved gradually in all patients and cosmetic results were excellent. In our experience, the SOV offers a reliable access to indirect CCFs, but patients should be monitored closely during the embolization process to prevent ophthalmic complications.

Local and large-scale beta oscillatory dysfunction in males with mild traumatic brain injury.

Mild traumatic brain injury (mTBI) is impossible to detect with standard neuroradiological assessment such as structural magnetic resonance imaging (MRI). Injury does, however, disrupt the dynamic repertoire of neural activity indexed by neural oscillations. In particular, beta oscillations are reliable predictors of cognitive, perceptual, and motor system functioning, as well as correlating highly with underlying myelin architecture and brain connectivity-all factors particularly susceptible to dysregulation after mTBI. We measured local and large-scale neural circuit function by magnetoencephalography (MEG) with a data-driven model fit approach using the fitting oscillations and one-over f algorithm in a group of young adult men with mTBI and a matched healthy control group. We quantified band-limited regional power and functional connectivity between brain regions. We found reduced regional power and deficits in functional connectivity across brain areas, which pointed to the well-characterized thalamocortical dysconnectivity associated with mTBI. Furthermore, our results suggested that beta functional connectivity data reached the best mTBI classification performance compared with regional power and symptom severity [measured with Sport Concussion Assessment Tool 2 (SCAT2)]. The present study reveals the relevance of beta oscillations as a window into neurophysiological dysfunction in mTBI and also highlights the reliability of neural synchrony biomarkers in disorder classification.NEW & NOTEWORTHY Mild traumatic brain injury (mTBI) disrupts the dynamic repertoire of neural oscillations, but so far beta activity has not been studied. In mTBI, we found reductions in frontal beta and large-scale beta networks, indicative of thalamocortical dysconnectivity and disrupted information flow through cortico-basal ganglia-thalamic circuits. Relatively, connectivity more accurately classifies individual mTBI cases compared with regional power. We show the relevance of beta oscillations in mTBI and the reliability of these markers in classification.

Delayed Thrombectomy Center Arrival is Associated with Decreased Treatment Probability.

BACKGROUND: Endovascular thrombectomy (EVT) is effective in reducing disability in selected patients with stroke and large vessel occlusion (LVO), but access to this treatment is suboptimal. AIM: We examined the proportion of patients with LVO who did not receive EVT, the reasons for non-treatment, and the association between time from onset and probability of treatment. METHODS: We conducted a retrospective cohort study of consecutive patients with acute stroke and LVO presenting between January 2017 and June 2018. We used multivariable log-binomial models to determine the association between time and probability of treatment with and without adjustment for age, sex, dementia, active cancer, baseline disability, stroke severity, and evidence of ischemia on computerized tomography. RESULTS: We identified 256 patients (51% female, median age 74 [interquartile range, IQR 63.5, 82.5]), of whom 59% did not receive EVT. The main reasons for not treating with EVT were related to occlusion characteristics or infarct size. The median time from onset to EVT center arrival was longer among non-treated patients (218 minutes [142, 302]) than those who were treated (180 minutes [104, 265], p = 0.03). Among patients presenting within 6 hours of onset, the relative risk (RR) of receiving EVT decreased by 3% with every 10-minute delay in arrival to EVT center (adjusted RR 0.97 CI95 [0.95, 0.99]). This association was not found in the overall cohort. CONCLUSIONS: The proportion of patients with acute stroke and confirmed LVO who do not undergo EVT is substantial. Minimizing delays in arrival to EVT center may optimize the delivery of this treatment.

Outcomes of Endovascular Thrombectomy for Basilar Artery Occlusion.

BACKGROUND AND PURPOSE: Large prospective observational studies have cast doubt on the common assumption that endovascular thrombectomy (EVT) is superior to intravenous thrombolysis for patients with acute basilar artery occlusion (BAO). The purpose of this study was to retrospectively review our experience for patients with BAO undergoing EVT with modern endovascular devices. METHODS: All consecutive patients undergoing EVT with either a second-generation stent retriever or direct aspiration thrombectomy for BAO at our regional stroke center from January 1, 2013 to March 1, 2019 were included. The primary outcome measure was functional outcome at 1 month using the modified Rankin Scale (mRS) score. Multivariable logistic regression was used to assess the association between patient characteristics and dichotomized mRS. RESULTS: A total of 43 consecutive patients underwent EVT for BAO. The average age was 67 years with 61% male patients. Overall, 37% (16/43) of patients achieved good functional outcome. Successful reperfusion was achieved in 72% (31/43) of cases. The median (interquartile range) stroke onset to treatment time was 420 (270-639) minutes (7 hours) for all patients. The procedure-related complication rate was 9% (4/43). On multivariate analysis, posterior circulation Alberta stroke program early computed tomography score and Basilar Artery on Computed Tomography Angiography score were associated with improved functional outcome. CONCLUSION: EVT appears to be safe and feasible in patients with BAO. Our finding that time to treatment and successful reperfusion were not associated with improved outcome is likely due to including patients with established infarcts. Given the variability of collaterals in the posterior circulation, the paradigm of utilizing a tissue window may assist in patient selection for EVT. Magnetic resonance imaging may be a reasonable option to determine the extent of ischemia in certain situations.

Qualitative Posttreatment Diffusion-Weighted Imaging as a Predictor of 90-day Outcome in Stroke Intervention.

PURPOSE: The aim was to assess the ability of post-treatment diffusion-weighted imaging (DWI) to predict 90-day functional outcome in patients with endovascular therapy (EVT) for large vessel occlusion in acute ischemic stroke (AIS). METHODS: We examined a retrospective cohort from March 2016 to January 2018, of consecutive patients with AIS who received EVT. Planimetric DWI was obtained and infarct volume calculated. Four blinded readers were asked to predict modified Rankin Score (mRS) at 90 days post-thrombectomy. RESULTS: Fifty-one patients received endovascular treatment (mean age 65.1 years, median National Institutes of Health Stroke Scale (NIHSS) 18). Mean infarct volume was 43.7 mL. The baseline NIHSS, 24-hour NIHSS, and the DWI volume were lower for the mRS 0-2 group. Also, the thrombolysis in cerebral infarction (TICI) 2b/3 rate was higher in the mRS 0-2 group. No differences were found in terms of the occlusion level, reperfusion technique, or recombinant tissue plasminogen activator use. There was a significant association noted between average infarct volume and mRS at 90 days. On multivariable analysis, higher infarct volume was significantly associated with 90-day mRS 3-5 when adjusted to TICI scores and occlusion location (OR 1.01; CI 95% 1.001-1.03; p = 0.008). Area under curve analysis showed poor performance of DWI volume reader ability to qualitatively predict 90-day mRS. CONCLUSION: The subjective impression of DWI as a predictor of clinical outcome is poorly correlated when controlling for premorbid status and other confounders. Qualitative DWI by experienced readers both overestimated the severity of stroke for patients who achieved good recovery and underestimated the mRS for poor outcome patients. Infarct core quantitation was reliable.

BOLD-based cerebrovascular reactivity vascular transfer function isolates amplitude and timing responses to better characterize cerebral small vessel disease.

Cerebrovascular reactivity (CVR) is a dynamic measure of the cerebral blood vessel response to vasoactive stimulus. Conventional CVR measures amplitude changes in the blood-oxygenation-level-dependent (BOLD) signal per unit change in end-tidal CO2 (PET CO2 ), effectively discarding potential timing information. This study proposes a deconvolution procedure to characterize CVR responses based on a vascular transfer function (VTF) that separates amplitude and timing CVR effects. We implemented the CVR-VTF to primarily evaluate normal-appearing white matter (WM) responses in those with a range of small vessel disease. Comparisons between simulations of PET CO2 input models revealed that boxcar and ramp hypercapnia paradigms had the lowest relative deconvolution error. We used a T2 * BOLD-MRI sequence on a 3 T MRI scanner, with a boxcar delivery model of CO2 , to test the CVR-VTF approach in 18 healthy adults and three white matter hyperintensity (WMH) groups: 20 adults with moderate WMH, 12 adults with severe WMH, and 10 adults with genetic WMH (CADASIL). A subset of participants performed a second CVR session at a one-year follow-up. Conventional CVR, area under the curve of VTF (VTF-AUC), and VTF time-to-peak (VTF-TTP) were assessed in WM and grey matter (GM) at baseline and one-year follow-up. WMH groups had lower WM VTF-AUC compared with the healthy group (p < 0.0001), whereas GM CVR did not differ between groups (p > 0.1). WM VTF-TTP of the healthy group was less than that in the moderate WMH group (p = 0.016). Baseline VTF-AUC was lower than follow-up VTF-AUC in WM (p = 0.013) and GM (p = 0.026). The intraclass correlation for VTF-AUC in WM was 0.39 and coefficient of repeatability was 0.08 [%BOLD/mm Hg]. This study assessed CVR timing and amplitude information without applying model assumptions to the CVR response; this approach may be useful in the development of robust clinical biomarkers of CSVD.

Isolated Traumatic Subarachnoid Hemorrhage: An Evaluation of Critical Care Unit Admission Practices and Outcomes From a North American Perspective.

OBJECTIVES: Traumatic subarachnoid hemorrhage is a common radiographic finding associated with traumatic brain injury. The objective of this investigation is to evaluate the association between hospital-level ICU admission practices and clinically important outcomes for patients with isolated traumatic subarachnoid hemorrhage and mild clinical traumatic brain injury. DESIGN: Multicenter observational cohort. SETTING: Trauma centers participating in the American College of Surgeons Trauma Quality Improvement Program spanning January 2012 to March 2014. PATIENTS: A total of 14,146 subjects, 16 years old and older, admitted to 215 trauma centers with isolated traumatic subarachnoid hemorrhage and Glasgow Coma Scale score 13 or greater. Patients with concurrent intracranial injuries, severe injury to other body regions, or tests positive for alcohol or illicit substances were excluded. INTERVENTION: ICU admission. MEASUREMENTS AND MAIN RESULTS: The primary outcome was need for neurosurgical intervention, defined as insertion of an intracranial monitor/drain or craniectomy/craniotomy. Secondary outcomes describing the clinical course included hospital discharge disposition, in-hospital mortality, and length of stay. Admission to ICU was common within the cohort (44.6%), yet the need for neurosurgical intervention was rare (0.24%). Variability was high between centers and remained so after adjusting for differences in case-mix and hospital-level characteristics (median odds ratio, 4.1). No significant differences in neurosurgical interventions, mortality, or discharge disposition to home under self-care were observed between groups of the highest and lowest ICU admitting hospitals. However, those in highest admitting group "stayed" in hospital 1.13 (95% CI, 1.07-1.20; p < 0.001) times that of the lowest admitting group. CONCLUSIONS: Critical care admission for mild traumatic brain injury patients with isolated traumatic subarachnoid hemorrhage is frequent and highly variable despite low probability of requiring neurosurgical intervention. Reevaluation of hospital-level practices may represent an opportunity for resource optimization when managing patients with mild clinical traumatic brain injury and associated isolated traumatic subarachnoid hemorrhage.

An Algorithm for Managing Intraosseous Vascular Anomalies of the Craniofacial Skeleton.

BACKGROUND: Intraosseous vascular anomalies (IOVA) are rare in the craniofacial skeleton and present a diagnostic and therapeutic challenge. This study aims to describe the clinical management based on a large case series. METHODS: A retrospective chart review was performed and 9 IOVA were identified over a 15-year period. Data on demographics, diagnostic features, clinical management, and outcomes were reviewed. RESULTS: Five frontal bone IOVA and 4 orbital IOVA were identified. The postoperative follow-up ranged from 4 months to 4 years. All 9 lesions were diagnosed with computed tomography (CT) imaging. Magnetic resonance imaging (MRI) was used to delineate soft tissue involvement in 2 patients presenting with oculo-orbital dystopia and ophthalmoplegia. En bloc excision was performed in all patients. Preoperative interventional embolization was critical in the successful resection of an orbital IOVA following 2 previously failed attempts that were aborted secondary to hemorrhage. Intraoperative 3-dimensional stereotactic navigation was used for the accurate en bloc excision of a frontal IOVA to prevent injury to the frontal sinus. Reconstruction of esthetic and functional deformities was successfully accomplished. CONCLUSION: The diagnosis of IOVA relies primarily on clinical assessment and CT imaging. Further interpretation of the involvement of periorbital, facial, and intracranial soft tissue is best defined by MRI. Multidisciplinary care with interventional radiology and neurosurgery must be considered for ensuring the safe and adequate en bloc excision of craniofacial IOVA.

Somatosensory evoked potentials after decompressive craniectomy for traumatic brain injury.

Somatosensory evoked potentials (SSEPs) are used for neuroprognosis after severe traumatic brain injury (TBI). However decompressive craniectomy (DC), involving removal of a portion of the skull to alleviate elevated intracranial pressure, is associated with an increase in SSEP amplitude. Accordingly, SSEPs are not available for neuroprognosis over the hemisphere with DC. We aim to determine the degree to which SSEP amplitudes are increased in the absence of cranial bone. This will serve as a precursor for translation to clinically prognostic ranges. Intra-operative SSEPs were performed before and after bone flap replacement in 22 patients with severe TBI. SSEP measurements were also performed in a comparison non-traumatic group undergoing craniotomy for tumor resection. N20/P25 amplitudes and central conduction time were measured with the bone flap in (BI) and out (BO). Linear regressions, adjusting for skull thickness and study arm, were performed to evaluate the contribution of bone presence to SSEP amplitudes. Latencies were not different between BO or BI trials in either group. Mean N20/P25 amplitudes recorded with BO were statistically different (p = 0.0001) from BI in both cohorts, showing an approximate doubling in BO amplitudes. For contralateral-ipsilateral montages r2 was 0.28 and for frontal pole montages r2 was 0.62. Cortical SSEP amplitudes are influenced by the presence of cortical bone as is particularly evident in frontal pole montages. Larger, longitudinal trials to assess feasibility of neuroprognosis over the hemisphere with DC in severe TBI patients are warranted.

e-Consent: approaching surgical consent with mobile technology

Background: Patient recall of information about procedures, including risks and benefits and potential outcomes, is often insufficient. We sought to determine whether a multimedia educational tool enhances the informed consent discussion for elective neurosurgical procedures by increasing patient knowledge of the procedure. Methods: Adult patients from a single neurosurgical site eligible for 4 neurosurgical procedures (lumbar spine or cervical spine decompression for degenerative disease, craniotomy for brain tumour or trigeminal neuralgia treatment) were offered enrolment. Patients were randomly assigned to either the control arm (standard consent discussion) or the intervention arm (review of an e-book containing information tailored to their disease/injury plus standard consent discussion). Participants completed a 14-item questionnaire before and after the consent discussion. Results: Questionnaires were completed by 38 participants, 18 in the control group and 20 in the intervention group. The mean age was 62.2 (standard deviation [SD] 13.6) years and did not differ significantly between the 2 groups. The mean baseline questionnaire scores were similar for the control and intervention groups (20.4 [SD 7.3] v. 20.6 [SD 6.7]). However, the mean scores on the follow-up questionnaire were significantly different between the 2 groups (20.2 [SD 4.0] v. 23.2 [SD 4.9], p = 0.02). There was no change in the scores on the 2 questionnaires in the control group, whereas, in the intervention group, the mean score was significantly higher after the intervention (p = 0.03). Conclusion: The use of an electronic booklet appears to improve patients' knowledge of their surgical procedure. The use of multimedia booklets in clinical practice could help standardize and optimize the consent process, ensuring that patients receive the relevant information to make a truly informed decision.

Contexte: Ce que les patients retiennent au sujet de leurs interventions, incluant les risques, les avantages et les résultats potentiels sont souvent insuffisants. Nous avons voulu déterminer si un outil d'enseignement multimédia peut faciliter la discussion entourant le consentement éclairé en prévision d'interventions neurochirurgicales non urgentes, en renseignant davantage les patients au sujet de leurs interventions. Méthodes: On a invité les patients adultes d'un centre de neurochirurgie admissibles à 4 types de différents d'interventions neurochirurgicale (décompression de la colonne lombaire ou cervicale pour maladie dégénérative, craniotomie pour tumeur cérébrale ou traitement de la névralgie du trijumeau) à s'inscrire à l'étude. Les patients ont été assignés aléatoirement soit au groupe témoin (discussion standard sur le consentement), soit au groupe soumis à l'intervention (utilisation d'une publication électronique contenant de l'information adaptée à leur maladie/lésion en plus de la discussion standard sur le consentement). Les participants ont répondu à un questionnaire en 14 points avant et après la discussion sur le consentement. Résultats: Trente-huit participants ont répondu au questionnaire, 18 dans le groupe témoin et 20 dans le groupe soumis à l'intervention. L'âge moyen était de 62,2 ans (écart-type [É.-T.] 13,6 ans) et n'était pas significativement différent entre les 2 groupes. Les scores moyens au questionnaire de départ étaient similaires pour les 2 groupes (20,4 [É.-T. 7,3] c. 20,6 [É.-T. 6,7]). Par contre, les scores moyens au questionnaire de suivi ont été significativement différents entre les 2 groupes (20,2 [É.-T. 4,0] c. 23,2 [É.-T. 4,9], p = 0,02). On n'a observé aucun changement des scores entre les 2 questionnaires du groupe témoin, tandis que dans le groupe soumis à l'intervention, le score moyen a été significativement plus élevé après l'intervention (p = 0,03). Conclusion: L'utilisation d'un document électronique semble améliorer les connaissances des patients au sujet de leurs interventions chirurgicales. L'utilisation de documents multimédias dans la pratique clinique pourrait aider à standardiser et optimiser le processus de consentement et faire en sorte que les patients reçoivent une information pertinente pour prendre une décision réellement éclairée.

Post-Traumatic Stress Constrains the Dynamic Repertoire of Neural Activity.

Post-traumatic stress disorder (PTSD) is an anxiety disorder arising from exposure to a traumatic event. Although primarily defined in terms of behavioral symptoms, the global neurophysiological effects of traumatic stress are increasingly recognized as a critical facet of the human PTSD phenotype. Here we use magnetoencephalographic recordings to investigate two aspects of information processing: inter-regional communication (measured by functional connectivity) and the dynamic range of neural activity (measured in terms of local signal variability). We find that both measures differentiate soldiers diagnosed with PTSD from soldiers without PTSD, from healthy civilians, and from civilians with mild traumatic brain injury, which is commonly comorbid with PTSD. Specifically, soldiers with PTSD display inter-regional hypersynchrony at high frequencies (80-150 Hz), as well as a concomitant decrease in signal variability. The two patterns are spatially correlated and most pronounced in a left temporal subnetwork, including the hippocampus and amygdala. We hypothesize that the observed hypersynchrony may effectively constrain the expression of local dynamics, resulting in less variable activity and a reduced dynamic repertoire. Thus, the re-experiencing phenomena and affective sequelae in combat-related PTSD may result from functional networks becoming "stuck" in configurations reflecting memories, emotions, and thoughts originating from the traumatizing experience. SIGNIFICANCE STATEMENT: The present study investigates the effects of post-traumatic stress disorder (PTSD) in combat-exposed soldiers. We find that soldiers with PTSD exhibit hypersynchrony in a circuit of temporal lobe areas associated with learning and memory function. This rigid functional architecture is associated with a decrease in signal variability in the same areas, suggesting that the observed hypersynchrony may constrain the expression of local dynamics, resulting in a reduced dynamic range. Our findings suggest that the re-experiencing of traumatic events in PTSD may result from functional networks becoming locked in configurations that reflect memories, emotions, and thoughts associated with the traumatic experience.

Detecting Mild Traumatic Brain Injury Using Resting State Magnetoencephalographic Connectivity.

Accurate means to detect mild traumatic brain injury (mTBI) using objective and quantitative measures remain elusive. Conventional imaging typically detects no abnormalities despite post-concussive symptoms. In the present study, we recorded resting state magnetoencephalograms (MEG) from adults with mTBI and controls. Atlas-guided reconstruction of resting state activity was performed for 90 cortical and subcortical regions, and calculation of inter-regional oscillatory phase synchrony at various frequencies was performed. We demonstrate that mTBI is associated with reduced network connectivity in the delta and gamma frequency range (>30 Hz), together with increased connectivity in the slower alpha band (8-12 Hz). A similar temporal pattern was associated with correlations between network connectivity and the length of time between the injury and the MEG scan. Using such resting state MEG network synchrony we were able to detect mTBI with 88% accuracy. Classification confidence was also correlated with clinical symptom severity scores. These results provide the first evidence that imaging of MEG network connectivity, in combination with machine learning, has the potential to accurately detect and determine the severity of mTBI.

Catecholamines as outcome markers in isolated traumatic brain injury: the COMA-TBI study.

BACKGROUND: Elevated catecholamine levels might be associated with unfavorable outcome after traumatic brain injury (TBI). We investigated the association between catecholamine levels in the first 24 h post-trauma and functional outcome in patients with isolated moderate-to-severe TBI. METHODS: A cohort of 174 patients who sustained isolated blunt TBI was prospectively enrolled from three Level-1 Trauma Centers. Epinephrine (Epi) and norepinephrine (NE) concentrations were measured at admission (baseline), 6, 12 and 24 h post-injury. Outcome was assessed at 6 months by the extended Glasgow Outcome Scale (GOSE) score. Fractional polynomial plots and logistic regression models (fixed and random effects) were used to study the association between catecholamine levels and outcome. Effect size was reported as the odds ratio (OR) associated with one logarithmic change in catecholamine level. RESULTS: At 6 months, 109 patients (62.6%) had an unfavorable outcome (GOSE 5-8 vs. 1-4), including 51 deaths (29.3%). Higher admission levels of Epi were associated with a higher risk of unfavorable outcome (OR, 2.04, 95% CI: 1.31-3.18, p = 0.002) and mortality (OR, 2.86, 95% CI: 1.62-5.01, p = 0.001). Higher admission levels of NE were associated with higher risk of unfavorable outcome (OR, 1.59, 95% CI: 1.07-2.35, p = 0.022) but not mortality (OR, 1.45, 95% CI: 0.98-2.17, p = 0.07). There was no relationship between the changes in Epi levels over time and mortality or unfavorable outcome. Changes in NE levels with time were statistically associated with a higher risk of mortality, but the changes had no relation to unfavorable outcome. CONCLUSIONS: Elevated circulating catecholamines, especially Epi levels on hospital admission, are independently associated with functional outcome and mortality after isolated moderate-to-severe TBI.

Increased Frontal Lobe Activation After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: Neurocognitive deficits are common among survivors of aneurysmal subarachnoid hemorrhage, even among those with good outcomes and no structural lesions. This study aims to probe the neurophysiological underpinnings of cognitive dysfunction among patients with ruptured intracranial aneurysms using magnetoencephalography (MEG). METHODS: Thirteen patients who had undergone uncomplicated coiling for aneurysmal subarachnoid hemorrhage and 13 matched controls were enrolled. Neuropsychological tests were done before magnetoencephalography scans. Magnetoencephalography data were acquired in a 151-channel, whole-head magnetoencephalography system for resting state and 2 cognitive tasks (go-no-go and set-shifting). Mean time from treatment to test was 18.8 months. RESULTS: Cognitive tasks of inhibition (go-no-go) indicated greater activation in the right anterior cingulate and inferior frontal gyrus, and cognitive set-shifting tasks (mental flexibility) indicated greater activity in the bilateral anterior cingulate cortex and right medial frontal gyrus among aneurysmal subarachnoid hemorrhage patients, with significantly different timing of activation between groups. Resting-state, beta-band connectivity of the anterior cingulate correlated negatively with Montreal Cognitive Assessment scores (left: r=-0.56; P<0.01 and right: r=-0.55; P<0.01): higher connectivity of this region was linked to poorer cognitive test performance. CONCLUSIONS: We have shown increased activation in areas of the anterior cingulate gyrus and frontobasal regions during the execution of more demanding tasks in good grade. The degree of activation in the anterior cingulate gyrus has a negative correlation with cognitive (Montreal Cognitive Assessment) scores. These subtle differences may be related to the common neurocognitive and behavioral complaints seen in this patient population.

Delayed and disorganised brain activation detected with magnetoencephalography after mild traumatic brain injury.

BACKGROUND: Awareness to neurocognitive issues after mild traumatic brain injury (mTBI) is increasing, but currently no imaging markers are available for mTBI. Advanced structural imaging recently showed microstructural tissue changes and axonal injury, mild but likely sufficient to lead to functional deficits. Magnetoencephalography (MEG) has high temporal and spatial resolution, combining structural and electrophysiological information, and can be used to examine brain activation patterns of regions involved with specific tasks. METHODS: 16 adults with mTBI and 16 matched controls were submitted to neuropsychological testing (Wechsler Abbreviated Scale of Intelligence (WASI); Conners; Alcohol Use Disorders Identification Test (AUDIT); Generalised Anxiety Disorder Seven-item Scale (GAD-7); Patient Health Questionnaire (PHQ-9); Symptom Checklist and Symptom Severity Score (SCAT2)) and MEG while tested for mental flexibility (Intra-Extra Dimensional set-shifting tasks). Three-dimensional maps were generated using synthetic aperture magnetometry beamforming analyses to identify differences in regional activation and activation times. Reaction times and accuracy between groups were compared using 2×2 mixed analysis of variance. FINDINGS: While accuracy was similar, patients with mTBI reaction time was delayed and sequence of activation of brain regions disorganised, with involvement of extra regions such as the occipital lobes, not used by controls. Examination of activation time showed significant delays in the right insula and left posterior parietal cortex in patients with mTBI. CONCLUSIONS: Patients with mTBI showed significant delays in the activation of important areas involved in executive function. Also, more regions of the brain are involved in an apparent compensatory effort. Our study suggests that MEG can detect subtle neural changes associated with cognitive dysfunction and thus, may eventually be useful for capturing and tracking the onset and course of cognitive symptoms associated with mTBI.