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Vin Shen Ban, Christopher J. Madden, Julian E. Bailes, H. Hunt Batjer and Russell R. Lonser

Recently, the pathobiology, causes, associated factors, incidence and prevalence, and natural history of chronic traumatic encephalopathy (CTE) have been debated. Data from retrospective case series and high-profile media reports have fueled public fear and affected the medical community's understanding of the role of sports-related traumatic brain injury (TBI) in the development of CTE. There are a number of limitations posed by the current evidence that can lead to confusion within the public and scientific community. In this paper, the authors address common questions surrounding the science of CTE and propose future research directions.

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Ravi Sarode, Karén Matevosyan, Ramesh Bhagat, Cynthia Rutherford, Christopher Madden and Joseph E. Beshay

Object

Intracerebral hemorrhage (ICH) is the most serious bleeding complication of vitamin K antagonist (VKA) therapy, carrying a high mortality. Rapid reversal of VKA in ICH is critical. Plasma therapy, the standard of care in the US, is not optimal. The ideal prothrombin complex concentrate (PCC) containing all vitamin K–dependent factors (VKDFs) is not available in the US. Therefore, the authors developed a Trauma Coumadin Protocol (TCP) consisting of a 3-factor PCC available in the US (which contains insufficient factor VII [FVII]) with a low-dose recombinant FVIIa to rapidly reverse VKA.

Methods

Forty-six patients treated with the TCP were retrospectively analyzed. Fourteen patients had pre- and post-TCP plasma samples collected to assess their VKDF increment. Eleven patients had measurable intraparenchymal hematomas, which were evaluated for expansion.

Results

The mean pre- and post-TCP international normalized ratios (INRs) were 3.4 (median 2.9) and 1.0 (median 0.9), respectively. Once corrected, INR was maintained at < 1.3 during a patient's hospital stay. The pre-TCP median values of FII, FVII, FIX, and FX were 28%, 21%, 45%, and 20%, respectively; post-TCP median values increased to 144%, 417%, 102%, and 143%, respectively. Four of the 11 patients with measurable intraparenchymal hemorrhage had expansion at 24 hours after TCP. One patient probably (8 hours post-TCP) and 1 patient possibly (3 days post-TCP) had thrombotic complications.

Conclusions

The TCP was very effective in rapidly reversing VKA-associated coagulopathy; however, this protocol should be used cautiously in patients at high risk for thrombosis.

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Karén Matevosyan, Christopher Madden, Samuel L. Barnett, Joseph E. Beshay, Cynthia Rutherford and Ravindra Sarode

Object

Neurosurgical patients often have mildly prolonged prothrombin time (PT) or international normalized ratio (INR). In the absence of liver disease this mild prolongation appears to be due to the use of very sensitive PT reagents. Therefore, the authors performed relevant coagulation factor assays to assess coagulopathy in such patients. They also compared plasma transfusion practices in their hospital before and after the study.

Methods

The authors tested 30 plasma specimens from 25 patients with an INR of 1.3–1.7 for coagulation factors II, VII, and VIII. They also evaluated plasma orders during the 5-month study period and compared them with similar poststudy periods following changes in plasma transfusion guidelines based on the study results.

Results

At the time of plasma orders the median INR was 1.35 (range 1.3–1.7, normal reference range 0.9–1.2) with a corresponding median PT of 13.6 seconds (range 12.8–17.6 seconds). All partial thromboplastin times were normal (median 29.0 seconds, range 19.3–33.7 seconds). The median factor VII level was 57% (range 25%–124%), whereas the hemostatic levels recommended for major surgery are 15%–25%. Factors II and VIII levels were also within the hemostatic range (median 72% and 118%, respectively). Based on these scientific data, plasma transfusion guidelines were modified and resulted in a 75%–85% reduction in plasma orders for mildly prolonged INR over the next 2 years.

Conclusions

Neurosurgical patients with a mild prolongation of INR (up to 1.7) have hemostatically normal levels of important coagulation factors, and the authors recommend that plasma not be transfused to simply correct this abnormal laboratory value.

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William W. Scott, Steven Sharp, Stephen A. Figueroa, Alexander L. Eastman, Charles V. Hatchette, Christopher J. Madden and Kim L. Rickert

OBJECT

Screening, management, and follow-up of Grade 3 and 4 blunt carotid artery injuries (BCAIs) remain controversial. These high-grade BCAIs were analyzed to define their natural history and establish a rational management plan based on lesion progression and cerebral infarction.

METHODS

A retrospective review of a prospectively maintained database of all blunt traumatic carotid and vertebral artery injuries from August 2003 to April 2013 was performed, and Grade 3 and 4 BCAIs were identified. The authors define Grade 3 injuries as stenosis of the vessel greater than 50%, or the development of a pseudoaneurysm, and Grade 4 injuries as complete vessel occlusion. Demographic information, imaging findings, number of images obtained per individual, length of radiographic follow-up examination, radiographic outcome at end of follow-up period, treatment(s), and documentation of ischemic stroke or transient ischemic attack (TIA) were recorded.

RESULTS

Fifty-three Grade 3 BCAIs in 44 patients and 5 Grade 4 BCAIs in 5 patients were identified and had available follow-up information. The mean follow-up duration for Grade 3 BCAIs was 113 days, and the mean follow-up for Grade 4 BCAIs was 78 days. Final imaging of Grade 3 BCAIs showed that 53% of cases were radiographically stable, 11% had resolved, and 11% were improved, whereas 25% had radiographically worsened. In terms of treatment, 75% of patients received aspirin (ASA) alone, 5% received various medications, and 2% received no treatment. Eighteen percent of the patients in the Grade 3 BCAI group underwent endovascular intervention, and in all of these cases, treatment with ASA was continued after the procedure. Final imaging of the Grade 4 BCAIs showed that 60% remained stable (with persistent occlusion), whereas the remaining arteries improved (with recanalization of the vessel). All patients in the Grade 4 BCAI follow-up group were treated with ASA, although in 1 patient treatment was transitioned to Coumadin. There were 3 cases of cerebral infarction that appeared to be related to Grade 3 BCAIs (7% of 44 patients in the Grade 3 group), and 1 case of stroke that appeared to be related to a Grade 4 BCAI. All identified cases of stroke developed soon after hospital admission.

CONCLUSIONS

Although the posttraumatic cerebral infarction rate may be overestimated, the results of this study suggest that the Grade 3 and 4 BCAIs carry the highest stroke risk of the blunt cerebrovascular injuries, and those infarctions were identified on or shortly after hospital admission. Despite a 40% recanalization rate in the Grade 4 BCAI group and an 89% rate of persistent pseudoaneurysm in the Grade 3 BCAI group, follow-up imaging showed progressive worsening without radiographic improvement in only a small number of patients, and these findings alone did not correlate with adverse clinical outcome. Follow-up protocols may require amending; however, further prospective studies are needed to make conclusive changes as they relate to management.

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Joseph E. Beshay, Howard Morgan, Christopher Madden, Wengui Yu and Ravindra Sarode

Intracranial hemorrhage (ICH) is a common problem encountered by neurosurgeons. Patient outcomes are influenced by hematoma size, growth, location, and the timing of evacuation, when indicated. Patients may have abnormal coagulation due to pharmacological anticoagulation or coagulopathy due to underlying systemic disease or blood transfusions. Strategies to reestablish the integrity of the clotting cascade and platelet function assume a familiarity with these processes. As patients are increasingly treated with anticoagulants and antiplatelet agents, it is essential that the physicians who care for patients with ICH understand these pathways and recognize how they can be manipulated to restore hemostasis.

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Joshua W. Gatson, Cari Stebbins, Dana Mathews, Thomas S. Harris, Christopher Madden, Hunt Batjer, Ramon Diaz-Arrastia and Joseph P. Minei

Traumatic brain injury (TBI) is a major risk factor for Alzheimer’s disease. With respect to amyloid deposition, there are no published serial data regarding the deposition rate of amyloid throughout the brain after TBI. The authors conducted serial 18F-AV-45 (florbetapir F18) positron emission tomography (PET) imaging in 2 patients with severe TBI at 1, 12, and 24 months after injury. A total of 12 brain regions were surveyed for changes in amyloid levels.

Case 1 involved a 50-year-old man who experienced a severe TBI. Compared with the 1-month time point, of the 12 brain regions that were surveyed, a decrease in amyloid (as indicated by standard uptake value ratios) was only observed in the hippocampus (−16%, left; −12%, right) and caudate nucleus (−18%, left; −18%, right), suggesting that initial amyloid accumulation in the brain was cleared between time points 1 and 12 months after injury. Compared to the scan at 1 year, a greater increase in amyloid (+15%) was observed in the right hippocampus at the 24-month time point. The patient in Case 2 was a 37-year-old man who suffered severe trauma to the head and a subsequent stroke; he had poor cognitive/functional outcomes and underwent 1.5 years of rehabilitation. Due to a large infarct area on the injured side of the brain (right side), the authors focused primarily on brain regions affected within the left hemisphere. Compared with the 1-month scan, they only found an increase in brain amyloid within the left anterior putamen (+11%) at 12 months after injury. In contrast, decreased amyloid burden was detected in the left caudate nucleus (−48%), occipital cortex (−21%), and precuneus (−19%) brain regions at the 12-month time point, which is indicative of early accumulation and subsequent clearance. In comparison with 12-month values, more clearance was observed, since a reduction in amyloid was found at 24 months after trauma within the left anterior putamen (−12%) and occipital cortex (−15%). Also, by 24 months, most of the amyloid had been cleared and the patient demonstrated improved results on the Rivermead symptom questionnaire, Glasgow Outcome Scale-Extended, and Disability Rating Scale. With respect to APOE status, the patient in Case 1 had two ε3 alleles and the patient in Case 2 had one ε2 and one ε3 allele.

In comparison to the findings of the initial scan at 1 month after TBI, by 12 and 24 months after injury amyloid was cleared in some brain regions and increased in others. Serial imaging conducted here suggests that florbetapir F18 PET imaging may be useful in monitoring amyloid dynamics within specific brain regions following severe TBI and may be predictive of cognitive deficits.

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William W. Scott, Steven Sharp, Stephen A. Figueroa, Alexander L. Eastman, Charles V. Hatchette, Christopher J. Madden and Kim L. Rickert

OBJECT

Proper screening, management, and follow-up of Grade 1 and 2 blunt carotid artery injuries (BCIs) remains controversial. These low-grade BCIs were analyzed to define their natural history and establish a rational management plan based on lesion progression and cerebral infarction.

METHODS

A retrospective review of a prospectively maintained database of all blunt traumatic carotid and vertebral artery injuries treated between August 2003 and April 2013 was performed and Grade 1 and 2 BCIs were identified. Grade 1 injuries are defined as a vessel lumen stenosis of less than 25%, and Grade 2 injuries are defined as a stenosis of the vessel lumen between 25% and 50%. Demographic information, radiographic imaging, number of imaging sessions performed per individual, length of radiographic follow-up, radiographic outcome at end of follow-up, treatment(s) provided, and documentation of ischemic stroke or transient ischemic attack were recorded.

RESULTS

One hundred seventeen Grade 1 and 2 BCIs in 100 patients were identified and available for follow-up. The mean follow-up duration was 60 days. Final imaging of Grade 1 and 2 BCIs demonstrated that 64% of cases had resolved, 13% of cases were radiographically stable, and 9% were improved, whereas 14% radiographically worsened. Of the treatments received, 54% of cases were treated with acetylsalicylic acid (ASA), 31% received no treatment, and 15% received various medications and treatments, including endovascular stenting. There was 1 cerebral infarction that was thought to be related to bilateral Grade 2 BCI, which developed soon after hospital admission.

CONCLUSIONS

The majority of Grade 1 and 2 BCIs remained stable or improved at final follow-up. Despite a 14% rate of radiographic worsening in the Grade 1 and 2 BCIs cohort, there were no adverse clinical outcomes associated with these radiographic changes. The stroke rate was 1% in this low-grade BCIs cohort, which may be an overestimate. The use of ASA or other antiplatelet or anticoagulant medications in these low-grade BCIs did not appear to correlate with radiographic injury stability, nor with a decreased rate of cerebral infarction. Although these data suggest that these Grade 1 and 2 BCIs may require less intensive radiographic follow-up, future prospective studies are needed to make conclusive changes related to treatment and management.

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William W. Scott, Steven Sharp, Stephen A. Figueroa, Alexander L. Eastman, Charles V. Hatchette, Christopher J. Madden and Kim L. Rickert

OBJECT

Grade 3 and 4 blunt vertebral artery (VA) injuries may carry a different natural course from that of lower-grade blunt VA injuries. Proper screening, management, and follow-up of these injuries remain controversial. Grade 3 and 4 blunt VA injuries were analyzed to define their natural history and establish a rational management plan based on lesion progression and cerebral infarction.

METHODS

A retrospective review of a prospectively maintained database of all blunt traumatic carotid and vertebral artery injuries from August 2003 to April 2013 was performed, and Grade 3 and 4 blunt VA injuries were identified. Grade 3 injuries were defined as stenosis of the vessel greater than 50% or the development of a pseudoaneurysm, and Grade 4 injuries were defined as complete vessel occlusion. Demographic information, radiographic imaging findings, number of imaging sessions performed per individual, length of radiographic follow-up, radiographic outcome at end of follow-up, treatment(s) provided, and documentation of ischemic stroke or transient ischemic attack were recorded.

RESULTS

A total of 79 high-grade (Grade 3 and 4) blunt VA injuries in 67 patients were identified. Fifty-nine patients with 66 high-grade blunt VA injuries were available for follow-up. There were 17 patients with 23 Grade 3 injuries and 42 patients with 43 Grade 4 injuries. The mean follow-up duration was 58 days for Grade 3 and 67 days for Grade 4 blunt VA injuries. Repeat imaging of Grade 3 blunt VA injuries showed that 39% of injuries were radiographically stable, 43% resolved, and 13% improved, while 1 injury radiographically worsened. Repeat imaging of the Grade 4 blunt VA injuries showed that 65% of injuries were radiographically stable (persistent occlusion), 30% improved (recanalization of the vessel), and in 2 cases (5%) the injury resolved. All Grade 3 injuries that were treated were managed with aspirin or clopidogrel alone, as were the majority of Grade 4 injuries. There were 3 cerebral infarctions thought to be related to Grade 4 blunt VA injuries, which were likely present on admission. All 3 of these patients died at a mean of 13.7 days after hospital admission. No cerebral infarctions directly related to Grade 3 blunt VA injuries were identified.

CONCLUSIONS

The majority of high-grade blunt VA injuries remain stable or are improved at final follow-up. Despite a 4% rate of radiographic worsening in the Grade 3 blunt VA injury group and a 35% recanalization rate in the Grade 4 blunt VA injury group, there were no adverse clinical outcomes associated with these radiographic changes. No cerebral infarctions were noted in the Grade 3 group. A 7% stroke rate was identified in the Grade 4 blunt VA injury group; however, this was confined to the immediate postinjury period and was associated with 100% mortality. While these data suggest that these high-grade vertebral artery injuries may require less intensive radiographic follow-up, future prospective studies are needed to make conclusive changes related to treatment and management.

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William W. Scott, Steven Sharp, Stephen A. Figueroa, Christopher J. Madden and Kim L. Rickert

Object

Screening of blunt vertebral artery (VA) injuries has increased since research has shown that they occur at a higher incidence than originally reported. Grade 1 and 2 injuries are the most common form of blunt VA injury. Proper screening, management, and follow-up of these injuries remain controversial. In this report, imaging, progression, treatment, and outcomes of Grade 1 and 2 blunt VA injuries were analyzed to better define their natural history and to establish a rational management plan based upon their risk of progression and cerebral infarct.

Methods

A retrospective review of all blunt traumatic carotid artery and VA injuries from December 2003 to April 2013 was performed. For the purposes of this report, focus was given to Grade 1 and 2 VA injuries. Grade 1 injuries were defined as a vessel lumen stenosis of less than 25%, and Grade 2 injuries were defined as vessel lumen stenosis between 25% and 50%. Demographic information, radiological imaging, number of images performed per individual, length of radiological follow-up, radiological outcome at the end of follow-up, treatment provided, and documentation of stroke or transient ischemic attack were recorded.

Results

One hundred eighty-seven Grade 1 and 2 VA injuries in 143 patients were identified. Of these 143 patients, 120 with 152 Grade 1 or 2 blunt VA injuries were available for follow-up. The mean duration of follow-up was 40 days. Repeat imaging showed that 148 (97.4%) Grade 1 or 2 blunt VA injuries were stable, improved, or resolved on final follow-up imaging. Seventy-nine patients (66%) were treated with aspirin, whereas 35 patients (29%) received no treatment. The remaining patients were treated with other antiplatelet agents or anticoagulant medication. Neuroimaging demonstrated 2 cases (1.7%) with posterior circulation infarcts that were believed to be related to their blunt VA injuries, both of which occurred during the initial hospitalization and within the first 4 days after injury.

Conclusions

Although follow-up imaging showed progressive worsening without radiological improvement in only a small number of patients with low-grade blunt VA injuries, these findings did not correlate with adverse clinical outcome. The posttraumatic cerebral infarction rate of 1.7% may be overestimated, and the use of acetylsalicylic acid or other antiplatelet or anticoagulant medication did not correlate with radiological changes or rate of cerebral infarction. While these data suggest the possibility that these low-grade VA injuries may not require treatment or follow-up, future prospective studies are needed to make conclusive changes related to management.

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Alan Hoffer and Warren Selman