Traumatic microbleeds persist for up to five years following traumatic brain injury despite resolution of other acute findings on MRI.

OBJECTIVE: The primary objective of this study was to track the incidence and progression of traumatic microbleeds (TMBs) for up to five years following traumatic brain injury (TBI). METHODS: Thirty patients with mild, moderate, or severe TBI received initial MRI within 48 h of injury and continued in a longitudinal study for up to five years. The incidence and progression of MRI findings was assessed across the five year period. In addition to TMBs, we noted the presence of other imaging findings including diffusion weighted imaging (DWI) lesions, extra-axial and intraventricular hemorrhage, hematoma, traumatic meningeal enhancement (TME), fluid-attenuated inversion recovery (FLAIR) hyperintensities, and encephalomalacia. RESULTS: TMBs were observed in 60% of patients at initial presentation. At one-year follow-up, TMBs were more persistent than other neuroimaging findings, with 83% remaining visible on MRI. In patients receiving serial MRI 2-5 years post-injury, acute TMBs were visible on all follow-up scans. In contrast, most other imaging markers of TBI had either resolved or evolved into ambiguous abnormalities on imaging by one year post-injury. CONCLUSIONS: These findings suggest that TMBs may serve as a uniquely persistent indicator of TBI and reinforce the importance of acute post-injury imaging for accurate characterization of persistent imaging findings.

Lumbar Spine Surgery and What We Lost in the Era of the Coronavirus Pandemic: A Survey of the Lumbar Spine Research Society.

STUDY DESIGN: This was a survey of the surgeon members of the Lumbar Spine Research Society (LSRS). OBJECTIVE: The purpose of this study was to assess trends in surgical practice and patient management involving elective and emergency surgery in the early months of the coronavirus pandemic. SUMMARY OF BACKGROUND DATA: The novel coronavirus has radically disrupted medical care in the first half of 2020. Little data exists regarding the exact nature of its effect on spine care. METHODS: A 53-question survey was sent to the surgeon members of the LSRS. Respondents were contacted via email 3 times over a 2-week period in late April. Questions concentrated on surgical and clinical practice patterns before and after the pandemic. Other data included elective surgical schedules and volumes, as well as which emergency cases were being performed. Surgeons were asked about the status of coronavirus disease 2019 (COVID-19) virus testing. Circumstances for performing surgical intervention on patients with and without testing as well as patients testing positive were explored. RESULTS: A total of 43 completed surveys were returned of 174 sent to active surgeons in the LSRS (25%). Elective lumbar spine procedures decreased by 90% in the first 2 months of the pandemic, but emergency procedures did not change. Patients with "stable" lumbar disease had surgeries deferred indefinitely, even beyond 8 weeks if necessary. In-person outpatient visits became increasingly rare events, as telemedicine consultations accounted for 67% of all outpatient spine appointments. In total, 91% surgeons were under some type of confinement. Only 11% of surgeons tested for the coronavirus on all surgical patients. CONCLUSIONS: Elective lumbar surgery was significantly decreased in the first few months of the coronavirus pandemic, and much of outpatient spine surgery was practiced via telemedicine. Despite these constraints, spine surgeons performed emergency surgery when indicated, even when the COVID-19 status of patients was unknown. LEVEL OF EVIDENCE: Level IV.

Prehospital Detection of Life-Threatening Intracranial Pathology: An Unmet Need for Severe TBI in Austere, Rural, and Remote Areas.

Severe traumatic brain injury (TBI) is a leading cause of death and disability worldwide, especially in low- and middle-income countries, and in austere, rural, and remote settings. The purpose of this Perspective is to challenge the notion that accurate and actionable diagnosis of the most severe brain injuries should be limited to physicians and other highly-trained specialists located at hospitals. Further, we aim to demonstrate that the great opportunity to improve severe TBI care is in the prehospital setting. Here, we discuss potential applications of prehospital diagnostics, including ultrasound and near-infrared spectroscopy (NIRS) for detection of life-threatening subdural and epidural hemorrhage, as well as monitoring of cerebral hemodynamics following severe TBI. Ultrasound-based methods for assessment of cerebrovascular hemodynamics, vasospasm, and intracranial pressure have substantial promise, but have been mainly used in hospital settings; substantial development will be required for prehospital optimization. Compared to ultrasound, NIRS is better suited to assess certain aspects of intracranial pathology and has a smaller form factor. Thus, NIRS is potentially closer to becoming a reliable method for non-invasive intracranial assessment and cerebral monitoring in the prehospital setting. While one current continuous wave NIRS-based device has been FDA-approved for detection of subdural and epidural hemorrhage, NIRS methods using frequency domain technology have greater potential to improve diagnosis and monitoring in the prehospital setting. In addition to better technology, advances in large animal models, provider training, and implementation science represent opportunities to accelerate progress in prehospital care for severe TBI in austere, rural, and remote areas.

Mild traumatic brain injury induced by primary blast overpressure produces dynamic regional changes in [18F]FDG uptake.

Changes in 18F-fluorodeoxyglucose ([18F]FDG) measured by positron emission tomography (PET) can be used for the noninvasive detection of metabolic dysfunction following mild traumatic brain injury (mTBI). This study examined the time course of metabolic changes induced by primary blast injury by measuring regional [18F]FDG uptake. Adult, male rats were exposed to blast overpressure (15 psi) or sham injury, and [18F]FDG uptake was measured before injury and again at 1-3 h and 7 days post-injury, using both volume-of-interest (VOI) and voxel-based analysis. VOI analysis revealed significantly increased [18F]FDG uptake in corpus callosum and amygdala at both 1-3 h and 7 days following blast, while a transient decrease in uptake was observed in the midbrain at 1-3 h only. Voxel-based analysis revealed similar significant differences in uptake between sham and blast-injured rats at both time points. At 1-3 h post-injury, clusters of increased uptake were found in the amygdala, somatosensory cortex, and corpus callosum, while regions of decreased uptake were observed in midbrain structures (inferior colliculus, ventrolateral tegmental area) and dorsal auditory cortex. At day 7, a region of increased uptake in blast-injured rats was found in a cluster centered on the cortex-amygdala transition zone, while no regions of decreased uptake were observed. These results suggest that a relatively mild primary blast injury results in altered brain metabolism in multiple brain regions and that post-injury time of assessment is an important factor in observing regional changes in [18F]FDG uptake.

Mechanisms of anterograde and retrograde memory impairment following experimental traumatic brain injury.

Memory impairment is common following traumatic brain injury. However, the specific processes underlying the impairments remain unknown. Traumatic brain injury may interfere with several of the stages of the learning and memory process. In two separate experiments, we examined the specific nature of both anterograde and retrograde memory dysfunction following fluid percussion brain injury in rats. In Experiment 1, we examined the retention of spatial memory in the MWM after equating initial learning between sham and injured animals. Animals were trained to criterion and then tested for retention 4, 8, or 24 h post-training. Although injured animals displayed deficits in task acquisition, retention performance was not significantly different between groups. In Experiment 2, we examined the effects of injury on the retention of retrograde spatial memories in the MWM. Animals were injured either 1 or 14 days post-training and then received retention probe trials followed by a reminding procedure and second probe trial 14 days post-injury. All injured animals displayed retention deficits in the probe trials 14 days post-injury. However, after the reminding procedure, injured animals displayed sham-level performance during the second probe trial. The results of these experiments suggest that with anterograde memory impairment induced by traumatic brain injury, the primary deficit lies in task acquisition, not the retention of information within long-term memory. Retrograde memory impairment following injury appears to be mediated primarily by deficits in memory retrieval.

Traumatic brain injury produces delay-dependent memory impairment in rats.

Memory impairment following traumatic brain injury (TBI) is common in both humans and animals. A noteworthy feature of memory dysfunction in human TBI is impaired memory performance that is dependent on the delay between initial learning and recall of information. However, previous studies of TBI-induced memory impairment in animals have failed to control for the initial amount of learning between sham and injured animals. The present study demonstrates that experimental TBI in rats produces delay-dependent memory impairment, even when the initial degree of learning is controlled for. Animals were injured at a moderate level of lateral fluid percussion (LFP) injury (n = 10) or received a sham injury (n = 9), and then trained in a water T-maze version of the delayed-non-matching-to-place (DNMP) task beginning 10 days post-injury. Acquisition training consisted of 15 trials per day on post-injury days 11-15 using a minimal (7-sec) delay between the sample and choice phases of the task. Following acquisition, the delay between the sample and choice phases of the task was progressively increased to 15, 30, and 120 sec. Injured animals acquired the task at the same rate as sham animals and performed equally well at the 15-sec delay (p > 0.05). However, as the delay increased to 30 and 120 sec, the performance of the injured animals deteriorated (p < 0.05). These results indicate that LFP injury produces delay-dependent memory impairments in rats. This is therefore a valid model of an important feature of memory impairment in human TBI, and should be a useful addition to the available methods for assessing memory impairment and the effect of therapeutic interventions after TBI.

Delayed, post-injury treatment with aniracetam improves cognitive performance after traumatic brain injury in rats.

Chronic cognitive impairment is an enduring aspect of traumatic brain injury (TBI) in both humans and animals. Treating cognitive impairment in the post-traumatic stages of injury often involves the delivery of pharmacologic agents aimed at specific neurotransmitter systems. The current investigation examined the effects of the nootropoic drug aniracetam on cognitive recovery following TBI in rats. Three experiments were performed to determine (1) the optimal dose of aniracetam for treating cognitive impairment, (2) the effect of delaying drug treatment for a period of days following TBI, and (3) the effect of terminating drug treatment before cognitive assessment. In experiment 1, rats were administered moderate fluid percussion injury and treated with vehicle, 25, or 50 mg/kg aniracetam for 15 days. Both doses of aniracetam effectively reduced injury-induced deficits in the Morris water maze (MWM) as measured on postinjury days 11-15. In experiment 2, injured rats were treated with 50 mg/kg aniracetam or vehicle beginning on day 11 postinjury and continuing for 15 days. MWM performance, assessed on days 26-30, indicates that aniracetam-treated animals performed as well as sham-injured controls. In experiment 3, animals were injured and treated with aniracetam for 15 days. Drug treatment was terminated during MWM testing on postinjury days 16-20. In this experiment, aniracetam-treated rats did not perform better than vehicle-treated rats. The results of these experiments indicate that aniracetam is an effective treatment for cognitive impairment induced by TBI, even when treatment is delayed for a period of days following injury.

Assessment of Cognitive Function in the Water Maze Task: Maximizing Data Collection and Analysis in Animal Models of Brain Injury.

Animal models play a critical role in understanding the biomechanical, pathophysiological, and behavioral consequences of traumatic brain injury (TBI). In preclinical studies, cognitive impairment induced by TBI is often assessed using the Morris water maze (MWM). Frequently described as a hippocampally dependent spatial navigation task, the MWM is a highly integrative behavioral task that requires intact functioning in numerous brain regions and involves an interdependent set of mnemonic and non-mnemonic processes. In this chapter, we review the special considerations involved in using the MWM in animal models of TBI, with an emphasis on maximizing the degree of information extracted from performance data. We include a theoretical framework for examining deficits in discrete stages of cognitive function and offer suggestions for how to make inferences regarding the specific nature of TBI-induced cognitive impairment. The ultimate goal is more precise modeling of the animal equivalents of the cognitive deficits seen in human TBI.