Blunt cerebrovascular injuries (BCVIs) are associated with significant morbidity and mortality. This guideline evaluates several aspects of BCVI diagnosis and management including the role of ...screening protocols, criteria for screening cervical spine injuries, and the use of antithrombotic therapy (ATT) and endovascular stents.
Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, a taskforce of the Practice Management Guidelines Committee of the Eastern Association for the Surgery of Trauma performed a systematic review and meta-analysis of currently available evidence. Four population, intervention, comparison, and outcome questions were developed to address diagnostic and therapeutic issues relevant to BCVI.
A total of 98 articles were identified. Of these, 23 articles were selected to construct the guidelines. In these studies, the detection of BCVI increased with the use of a screening protocol versus no screening protocol (odds ratio OR, 4.74; 95% confidence interval CI, 1.76-12.78; p = 0.002), as well as among patients with high-risk versus low-risk cervical spine injuries (OR, 12.7; 95% CI, 6.24-25.62; p = 0.003). The use of ATT versus no ATT resulted in a decreased risk of stroke (OR, 0.20; 95% CI, 0.06-0.65; p < 0.0001) and mortality (OR, 0.17; 95% CI, 0.08-0.34; p < 0.0001). There was no significant difference in the risk of stroke among patients with Grade II or III injuries who underwent stenting as an adjunct to ATT versus ATT alone (OR, 1.63; 95% CI, 0.2-12.14; p = 0.63).
We recommend using a screening protocol to detect BCVI in blunt polytrauma patients. Among patients with high-risk cervical spine injuries, we recommend screening computed tomography angiography to detect BCVI. For patients with low-risk risk cervical injuries, we conditionally recommend performing a computed tomography angiography to detect BCVI. We recommend the use of ATT in patients diagnosed with BCVI. Finally, we recommend against the routine use of endovascular stents as an adjunct to ATT in patients with Grade II or III BCVIs.
Guidelines, Level III.
Epidemiological studies have associated increased risk of Alzheimer's disease (AD)-related clinical symptoms with a medical history of head injury. Currently, little is known about pathophysiology ...mechanisms linked to this association. Persistent neuroinflammation is one outcome observed in patients after a single head injury. Neuroinflammation is also present early in relevant brain regions during AD pathology progression. In addition, previous mechanistic studies in animal models link neuroinflammation as a contributor to neuropathology and cognitive impairment in traumatic brain injury (TBI) or AD-related models. Therefore, we explored the potential interplay of neuroinflammatory responses in TBI and AD by analysis of the temporal neuroinflammatory changes after TBI in an AD model, the APP/PS1 knock-in (KI) mouse. Discrete temporal aspects of astrocyte, cytokine, and chemokine responses in the injured KI mice were delayed compared with the injured wild-type mice, with a peak neuroinflammatory response in the injured KI mice occurring at 7 d after injury. The neuroinflammatory responses were more persistent in the injured KI mice, leading to a chronic neuroinflammation. At late time points after injury, KI mice exhibited a significant impairment in radial arm water maze performance compared with sham KI mice or injured wild-type mice. Intervention with a small-molecule experimental therapeutic (MW151) that selectively attenuates proinflammatory cytokine production yielded improved cognitive behavior outcomes, consistent with a link between neuroinflammatory responses and altered risk for AD-associated pathology changes with head injury.
Platelet dysfunction (PD) is an independent predictor of mortality in patients with severe traumatic brain injury (sTBI). Platelet transfusions (PLTs) have been shown to be an effective treatment ...strategy to reverse platelet inhibition. Their use is contingent on availability and may be associated with increased cost and transfusion-related complications, making desmopressin (DDAVP) attractive. We hypothesized that DDAVP would correct PD similarly to PLTs in patients with sTBI.
This retrospective study evaluated all blunt trauma patients admitted to an urban, level 1 trauma center from July 2015 to October 2016 with sTBI (defined as head abbreviated injury scale AIS ≥3) and PD (defined as adenosine diphosphate ADP inhibition ≥60% on thromboelastography) and subsequently received treatment. Per our institutional practice, patients with sTBI and PD are transfused one unit of apheresis platelets to reverse inhibition. During a platelet shortage, we interchanged DDAVP for the initial treatment. Patients were classified as receiving DDAVP or PLT based on the initial treatment.
A total of 57 patients were included (DDAVP, n = 23; PLT, n = 34). Patients who received DDAVP were more severely injured (injury severity score, 29 vs. 23; p = 0.045), but there was no difference in head AIS (4 vs. 4, p = 0.16). There was no difference between the two groups in admission platelet count (244 ± 68 × 10/μL vs. 265 ± 66 × 10/μL, p = 0.24) or other coagulation parameters such as prothrombin time, partial thromboplastin time, or international normalized ratio. Before treatment, both groups had similar ADP inhibition as measured by thromboelastography (ADP, 86% vs. 89%, p = 0.34). After treatment, both the DDAVP and PLT groups had similar correction of platelet ADP inhibition (p = 0.28).
In patients with severe traumatic brain injury and PD, DDAVP may be an alternative to PLTs to correct PD.
Therapeutic, level IV.
Objective Despite recent progress, prognosis for the elderly (defined as aged ≥70 years) afflicted by traumatic brain injury (TBI) is unfavorable and surgical intervention remains controversial. ...Research during the past decade on the mortality rates or prognostic factors for survival in the elderly is limited. Methods We analyzed 97 patients aged ≥70 years who were treated surgically for closed TBI at our neurosurgical unit between January 1, 2003 and December 31, 2012. In addition, we analyzed 22 patients aged ≥70 years who had sustained a closed TBI and on whom no neurosurgical intervention was performed. Outcome in both groups was measured as 30-, 90- and 180-day mortality. Results Surgically treated patients: median age, 76 years' 30-day overall mortality rate, 36%. Higher mortality was seen with lower level of consciousness, high energy trauma, one pupil fixed and dilated, and more extensive intracranial pathology. Presence of warfarin, more advanced age, or degree of midline shift were not associated with worsened outcome. Patients not treated neurosurgically: median age. 81.5 years; 30-day overall mortality rate, 23%. Mortality for patients with Glasgow coma scale (GCS) 10–15 was 6%, GCS 6–9 67%, and GCS 3–5 100%. Conclusions Selected patients aged ≥70 years can benefit from surgical intervention for closed TBI. Level of consciousness, radiologic type of injury, mechanism of injury, and pupil abnormalities should be carefully evaluated. There also seems to exist a group of patients in whom surgical intervention offers little benefit, as mortality rate is low without surgical intervention.
Few injuries have produced as much debate with respect to management as have blunt cerebrovascular injuries (BCVIs). Recent work (American Association for the Surgery of Trauma 2013) from our ...institution suggested that 64-channel multidetector computed tomographic angiography (CTA) could be the primary screening tool for BCVI. Consequently, our screening algorithm changed from digital subtraction angiography (DSA) to CTA, with DSA reserved for definitive diagnosis of BCVI following CTA-positive study results or unexplained neurologic findings. The current study was performed to evaluate outcomes, including the potential for missed clinically significant BCVI, since this new management algorithm was adopted.
Patients who underwent DSA (positive CTA finding or unexplained neurologic finding) over an 18-month period subsequent to the previous study were identified. Screening and confirmatory test results, complications, and BCVI-related strokes were reviewed and compared.
A total of 228 patients underwent DSA: 64% were male, with mean age and Injury Severity Score (ISS) of 43 years and 22, respectively. A total of 189 patients (83%) had a positive screening CTA result. Of these, DSA confirmed injury in 104 patients (55%); the remaining 85 patients (45%) (false-positive results) were found to have no injury on DSA. Five patients (4.8%) experienced BCVI-related strokes, unchanged from the previous study (3.9%, p = 0.756); two were symptomatic at trauma center presentation, and three occurred while receiving appropriate therapy. No patient with a negative screening CTA result experienced a stroke.
This management scheme using 64-channel CTA for screening coupled with DSA for definitive diagnosis was proven to be safe and effective in identifying clinically significant BCVIs and maintaining a low stroke rate. Definitive diagnosis by DSA led to avoidance of potentially harmful anticoagulation in 45% of CTA-positive patients (false-positive results). No strokes resulted from injuries missed by CTA.
Diagnostic study, level III.
Concussion, caused by a rotational acceleration/deceleration injury mild enough to avoid structural brain damage, is insufficiently captured in recent preclinical models, hampering the relation of ...pathophysiological findings on the cellular level to functional and behavioral deficits. We here describe a novel model of unrestrained, single vs. repetitive concussive brain injury (CBI) in male C56Bl/6j mice. Longitudinal behavioral assessments were conducted for up to seven days afterward, alongside the evaluation of structural cerebral integrity by in vivo magnetic resonance imaging (MRI, 9.4 T), and validated ex vivo by histology. Blood-brain barrier (BBB) integrity was analyzed by means of fluorescent dextran- as well as immunoglobulin G (IgG) extravasation, and neuroinflammatory processes were characterized both in vivo by positron emission tomography (PET) using
FDPA-714 and ex vivo using immunohistochemistry. While a single CBI resulted in a defined, subacute neuropsychiatric phenotype, longitudinal cognitive testing revealed a marked decrease in spatial cognition, most pronounced in mice subjected to CBI at high frequency (every 48 h). Functional deficits were correlated to a parallel disruption of the BBB, (R
= 0.29,
< 0.01), even detectable by a significant increase in hippocampal uptake of
FDPA-714, which was not due to activation of microglia, as confirmed immunohistochemically. Featuring a mild but widespread disruption of the BBB without evidence of macroscopic damage, this model induces a characteristic neuro-psychiatric phenotype that correlates to the degree of BBB disruption. Based on these findings, the BBB may function as both a biomarker of CBI severity and as a potential treatment target to improve recovery from concussion.
Abstract Background We implemented expanded screening criteria for blunt cerebrovascular injuries (BCVIs) in an attempt to capture the remaining 20% of patients not historically identified with ...earlier protocols. We hypothesized that these expanded criteria would capture the additional 20% of BCVI patients not previously identified. Methods Screening criteria for BCVI were expanded in 2011 after identifying new injury patterns. The study population included 4 years prior (2007 to 2010; classic) and following (2011 to 2014; expanded) implementation of expanded criteria. Results BCVIs were identified in 386 patients: 150 during the classic period (2.36% incidence) and 236 in the expanded period (2.99% incidence). In the expanded period, 155 patients were imaged based on classic screening criteria, 62 on expanded criteria (21 complex skull fractures, 20 upper rib fractures, 6 mandible fractures, 2 scalp degloving, 1 great vessel injury, and 12 combination), and 19 for other injuries and symptoms. Conclusions There was a significant increase in the identification of BCVI following the adoption of expanded screening criteria, resulting in a substantial reduction of missed injuries. Expanded criteria should be adopted when screening for BCVI.
A mild insult to the brain can sometimes trigger secondary brain injury, causing severe postconcussion syndrome, but the underlying mechanism is ill understood. We show here that secondary brain ...injury occurs consistently in mice lacking immediate early responsive gene X-1 (IEX-1), after a gentle impact to the head, which closely simulates mild traumatic brain injury in humans. The pathologic lesion was characterized by extensive cell death, widespread leukocyte infiltrates, and severe tissue loss. On the contrary, a similar insult did not induce any secondary injury in wild-type mice. Strikingly, noninvasive exposure of the injured head to a low-level laser at 4 hours after injury almost completely prevented the secondary brain injury in IEX-1 knockout mice. The low-level laser therapy (LLLT) suppressed proinflammatory cytokine expression like interleukin (IL)-1β and IL-6 but upregulated TNF-a. Moreover, although lack of IEX-1 compromised ATP synthesis, LLLT elevated its production in injured brain. The protective effect of LLLT may be ascribed to enhanced ATP production and selective modulation of proinflammatory mediators. This new closed head injury model provides an excellent tool to investigate the pathogenesis of secondary brain injury as well as the mechanism underlying the beneficial effect of LLLT.
A young miniature poodle was presented following blunt force trauma to the head. The dog initially responded well to medical management before developing clinical signs associated with increased ...intracranial pressure 48 h post-injury that became refractory to hyperosmolar therapy. A
computed tomography scan obtained 76 h post-injury showed a short, oblique, non-displaced, complete fissure in the right temporal bone and a second short, oblique, non-displaced, complete fissure in the ventral aspect of the temporal bone. A biconvex, moderately hyperattenuating, space-occupying
temporoparietal lesion was visualized immediately adjacent to the area of the temporal fractures. These findings were consistent with a diagnosis of intracranial extradural hematoma. Decompressive craniectomy successfully evacuated the extradural hematoma to alleviate increased intracranial
pressure. The dog's neurologic function recovered quickly postoperatively. At follow-up physical examinations at 14 and 437 d, excellent return to function was noted.Key clinical message:This report describes the diagnosis and surgical management of an intracranial extradural
hematoma in a dog with increased intracranial pressure refractory to medical management. Furthermore, this report describes the diagnostic imaging findings used to diagnose this particular form of primary brain injury.
Background. Cerebrolysin is a neuropeptide preparation with neuroprotective and neurotrophic properties. Our previous study demonstrates that cerebrolysin significantly improves functional recovery ...in rats after mild traumatic brain injury (mTBI). Objective. To determine histological outcomes associated with therapeutic effects of cerebrolysin on functional recovery after TBI. Methods. In this prospective, randomized, blinded, and placebo-controlled study, adult Wistar rats with mild TBI induced by a closed head impact were randomly assigned to one of the cerebrolysin dose groups (0.8, 2.5, 7.5 mL/kg) or placebo, which were administered 4 hours after TBI and then daily for 10 consecutive days. Functional tests assessed cognitive, behavioral, motor, and neurological performance. Study end point was day 90 after TBI. Brains were processed for histological tissue analyses of astrogliosis, axonal injury, and neurogenesis. Results. Compared with placebo, cerebrolysin significantly reduced amyloid precursor protein accumulation, astrogliosis, and axonal damage in various brain regions and increased the number of neuroblasts and neurogenesis in the dentate gyrus. There was a significant dose effect of cerebrolysin on functional outcomes at 3 months after injury compared with saline treatment. Cerebrolysin at a dose of ⩾0.8 mL/kg significantly improved cognitive function, whereas at a dose of ⩾2.5 mL/kg, cerebrolysin also significantly improved sensorimotor function at various time points. There were significant correlations between multiple histological and functional outcomes 90 days after mTBI. Conclusions. Our findings demonstrate that cerebrolysin reduces astrogliosis and axonal injury and promotes neurogenesis, which may contribute to improved functional recovery in rats with mTBI.