Venous Injury in Patients with Blunt Traumatic Brain Injury: Retrospective Analysis of a National Cohort.

BACKGROUND: Cerebral venous injury (CVI) includes injury to a dural venous sinus or major vein and leads to poorer outcomes for patients with blunt traumatic brain injury (TBI). We sought to identify the incidence, associated factors, and outcomes associated with CVI in a large national cohort. METHODS: Adult patients with blunt TBI were identified from the National Trauma Databank (2013-2017). Outcomes included inpatient mortality, discharge disposition, stroke, length of stay (LOS), intensive care unit LOS, and duration of mechanical ventilation. Multivariate regression models were used to identify the association between exposure variables and CVI, as well as each outcome. RESULTS: There were 619,659 patients with blunt TBI who met the inclusion criteria. CVI occurred in 1792 (0.3%) patients. Mixed intracranial injury type had the strongest association with CVI (odds ratio [OR] 2.89, 95% confidence interval [CI] 2.38-3.50), followed by isolated TBI (OR 1.76, 95% CI 1.54-2.02) and skull fracture (OR 1.72, 95% CI 1.55-1.91). CVI was associated with increased odds of mortality (OR 1.38, 95% CI 1.19-1.60), nonroutine discharge (OR 1.26, 95% CI 1.12-1.40), and stroke (OR 1.95, 95% CI 1.33-2.86). It was also associated with longer LOS (ß 2.02, 95% CI 1.55-2.50) and intensive care unit LOS (ß 0.14, 95% CI 0.13-0.16). Among locations of venous injury, superior sagittal sinus injury had significant associations with mortality (OR 2.93, 95% CI 1.62-5.30) and nonroutine discharge disposition (OR 1.94, 95% CI 1.12-3.35), whereas the others did not. CONCLUSIONS: We identified a 0.3% incidence of CVI in all-comers with blunt TBI as well as several injury-related variables that may be used to guide investigation for dural venous sinus injury. CVI was associated with poorer outcomes, with superior sagittal sinus injury having the strongest association.

Risk Factors and Outcomes Associated with Blunt Cerebrovascular Injury in Patients with Mild or Moderate Traumatic Brain Injury.

BACKGROUND: Blunt cerebrovascular injury (BCVI) represents a spectrum of traumatic injuries to the carotid and vertebral arteries that is an often-overlooked source of morbidity and mortality. Its incidence, risk factors, and effect on outcomes in patients with mild or moderate traumatic brain injury (mTBI) have not been studied independently. METHODS: The National Trauma Data Bank from 2013 to 2017 was queried to identify patients with mTBI who suffered blunt injuries. BCVI was identified using abbreviated injury scores and included blunt carotid artery injury (BCAI) and blunt vertebral artery injury (BVAI). A binary logistic regression was used to identify patient-related and injury-related factors associated with BCVI. Binary logistic regressions were also performed to evaluate the effect of BCVI on stroke, in-hospital mortality, nonroutine discharge disposition, total length of stay (LOS), intensive care unit LOS, and number of days mechanically ventilated. RESULTS: Of 485,880 patients with mTBI, there were 4,382 (0.9%) with BCVI. Cervical spine fracture was the strongest factor associated with BCAI (odds ratio [OR], 1.97; 95% confidence interval [95% CI], 1.77-2.19), followed by mandible fracture and basilar skull fracture. Cervical spine fracture also had the strongest association with BVAI (OR, 18.28; 95% CI, 16.47-20.28), followed by spinal cord injury and neck contusion. Stroke was more common in patients with BCAI (OR, 5.50; 95% CI, 4.19-7.21) and BVAI (OR, 7.238; 95% CI, 5.929-8.836). BVAI increased the odds of mortality, but BCAI did not. Both were associated with nonroutine discharge and increased LOS, intensive care unit LOS, and number of days mechanically ventilated. CONCLUSIONS: The incidence of BCVI in patients with mTBI is low, and it usually does not require invasive treatment. However, it is associated with greater odds of stroke and negative outcomes. Knowledge of risk factors for BCVI may tailor further investigation to aid prompt diagnosis.

The Effect of Timing of Intracranial Pressure Monitor Placement in Patients with Severe Traumatic Brain Injury.

BACKGROUND/OBJECTIVE: Intracranial pressure (ICP) monitor placement is indicated for patients with severe traumatic brain injury (sTBI) to minimize secondary brain injury. There is little evidence to guide the optimal timing of ICP monitor placement. METHODS: A retrospective cohort study using the National Trauma Data Bank (NTDB) from 2013 to 2017 was performed. The NTDB was queried to identify patients with sTBI who underwent external ventricular drain or intraparenchymal ICP monitor placement. Propensity score matching was used to create matched pairs of patients who underwent early compared to late ICP monitor placement using 6-h and 12-h cutoffs. The outcomes of interest were in-hospital mortality, non-routine discharge disposition, total length of stay (LOS), intensive care unit (ICU) LOS, and number of days mechanically ventilated. RESULTS: A total of 5057 patients with sTBI were included in the study. In-hospital mortality for patients with early compared to late ICP monitor placement was 33.6% and 30.4%, respectively (p = 0.049). The incidence of non-routine disposition was 92.6% in the within 6 h group and 94.4% in the late placement group (p = 0.037). Hospital LOS, ICU LOS, and number of days mechanically ventilated were significantly greater in the late ICP monitoring group. Similar results were seen when using a 12-h cutoff for late ICP monitor placement. In the Cox proportional hazards model, craniotomy (HR 1.097, 95% CI 1.037-1.160) and isolated intracranial injury (HR 1.128, 95% CI 1.055-1.207) were associated with early ICP monitor placement. Hypotension was negatively associated with early ICP monitor placement (HR 0.801, 95% CI 0.725-0.884). CONCLUSION: Despite a statistically marginal association between mortality and early ICP monitor placement, most outcomes were superior when ICP monitors were placed within 6 or 12 h of arrival. This may be due to earlier identification and treatment of intracranial hypertension.

The Obesity Paradox in Spontaneous Intracerebral Hemorrhage: Results from a Retrospective Analysis of the Nationwide Inpatient Sample.

BACKGROUND/OBJECTIVE: Mild obesity is associated with a survival benefit in cardiovascular and cerebrovascular disease. Only a few studies have analyzed the effect of obesity on outcomes after spontaneous intracerebral hemorrhage (ICH), and none have used a national US database. We sought to determine whether or not obesity was associated with outcomes and in-hospital complications following ICH. METHODS: The Nationwide Inpatient Sample was used to identify patients with ICH in the USA who were discharged between 2002 and 2011. The presence of obesity (body mass index [BMI] 30-39.9) or morbid obesity (BMI ≥ 40) was noted. The primary outcome of interest was in-hospital mortality, and secondary outcomes included non-routine discharge disposition, tracheostomy or gastrostomy placement, length of stay (LOS), inflation-adjusted hospital charges, and in-hospital complications. RESULTS: A total of 123,415 patients with ICH met the inclusion criteria, and the 10-year overall incidence of obesity was 4.5%. Between 2002 and 2011, the incidence of obesity increased from 1.9 to 4.4% and the incidence of morbid obesity increased from 0.7 to 3.2%. Both obese (OR 0.62, 95% CI 0.56-0.69) and morbidly obese (OR 0.76, 95% CI 0.66-0.88) patients had lower odds of inpatient mortality. Obese (OR 0.85, 95% CI 0.78-0.93) but not morbidly obese patients had lower odds of non-routine discharge. Morbidly obese patients were twice as likely to require a tracheostomy than non-obese patients (OR 2.07, 95% CI 1.62-2.66). Both obese and morbidly obese patients had higher total hospital charges and rates of pulmonary, renal, and venous thromboembolic complications. There was no difference in LOS according to body habitus. CONCLUSIONS: In patients with spontaneous ICH, obesity is associated with decreased in-hospital mortality but higher rates of in-hospital complications and greater total hospital charges. Non-morbid obesity carries lower odds of non-routine hospital discharge.

A Propensity Score-Matched Comparison of Readmission Rates Associated With Microsurgical Clipping and Endovascular Treatment of Ruptured Intracranial Aneurysms.

BACKGROUND: In the treatment of aneurysmal subarachnoid hemorrhage (aSAH), microsurgical clipping, and endovascular therapy (EVT) with coiling are modalities for securing the ruptured aneurysm. Little data is available regarding associated readmission rates. We sought to determine whether readmission rates differed according to treatment modality for ruptured intracranial aneurysms. METHODS: The Nationwide Readmissions Database (NRD) was used to identify adults who experienced aSAH and underwent clipping or EVT. Primary outcomes of interest were the incidences of 30- and 90-day readmissions (30dRA, 90dRA). Propensity score matching was used to generate matched pairs based on age, comorbidities, hospital volume, and hemorrhage severity. RESULTS: We identified 13,623 and 11,160 patients who were eligible for 30dRA and 90dRA analyses, respectively. Among the patients eligible for 30dRA and 90dRA, we created 4282 and 3518 propensity score-matched pairs, respectively. There was no difference in the incidence of 30dRA (12.4% for clipping versus 11.2% for EVT; P = .094). However, 90dRA occurred more frequently after clipping (22.5%) compared to EVT (19.7%; P = .003). Clipping was associated with poor outcome after 30dRA (odds ratio [OR] = 1.51, 95% confidence interval [CI] 1.21-1.88, P < .001) and after 90dRA (OR = 1.60, 95% CI 1.34-1.91, P = .001). Mean duration to readmission and cost of readmission did not vary, but clipping was associated with longer lengths of stay during readmission. CONCLUSIONS: Microsurgical clipping of ruptured aneurysms is associated with a greater incidence of 90dRA, but not 30dRA, compared to EVT. Poor outcomes after readmission are more common following clipping.

The risk factors, outcomes, and costs associated with venous thromboembolism after traumatic brain injury: a nationwide analysis.

Objective: We sought to identify risk factors for VTE following traumatic brain injury (TBI) and determine how venous thromboembolism (VTE) affects outcomes and costs using a national database.Methods: The Nationwide Inpatient Sample (NIS) was used to identify patients with TBI between 2002 and 2014. VTE was identified as any occurrence of deep venous thrombosis or pulmonary embolism. We investigated putative risk factors for VTE and determined the effect of VTE on outcomes including mortality and disposition.Results: 424,929 patients met the inclusion criteria. There were 16,690 (3.9%) patients who developed a VTE. The annual incidence of VTE increased from 2.2% in 2002 to 5.4% in 2014 (R2 = 0.992, p < .001). Older age, increasing number of comorbidities, craniotomy or craniectomy, and more severe injuries were associated with increased odds of developing VTE (p < .001 for all). Patients with VTE had decreased odds of in-hospital mortality (OR 0.53; 95% CI 0.50-0.57) and increased odds of non-routine disposition (OR 2.05; 95% CI 1.97-2.14), tracheostomy, and gastrostomy.Conclusion: To our knowledge, we provide the largest analysis of VTE in TBI. This entity appears to be increasing in frequency, which may merit new strategies for prevention.

The Incidence of Meningitis in Patients with Traumatic Brain Injury Undergoing External Ventricular Drain Placement: A Nationwide Inpatient Sample Analysis.

BACKGROUND/OBJECTIVE: Infection is the most common complication of external ventricular drain (EVD) placement. National trends in the annual incidence of meningitis among patients with traumatic brain injury (TBI) who have undergone EVD placement have not been reported. METHODS: The Nationwide Inpatient Sample was used to select adults with a primary diagnosis of TBI who underwent EVD placement between 2002 and 2011. Annual rates of meningitis among patients who underwent EVD placement were determined. We also calculated mortality rates and length of stay (LOS). Potential factors associated with meningitis were evaluated in a binary logistic regression analysis. RESULTS: Out of 1,571,927 adult discharges with a primary diagnosis of TBI between 2002 and 2011, 39,029 (2.5%) underwent EVD placement. Of these, 1544 (4.3%) patients developed meningitis. There was no significant trend in the annual incidence of meningitis (p = 0.88), mortality (p = 0.55), or mean LOS (p = 0.13) during the study period. Meningitis and mortality rates remained stable when stratifying patients by hospital volume. In the binary logistic regression, acquired immunodeficiency syndrome, sepsis, and cerebrospinal fluid leak were associated with meningitis. CONCLUSIONS: The incidence of meningitis in patients who underwent EVD placement remained stable between 2002 and 2011. Further prospective studies are needed to identify approaches for preventing these infections.

Causes, Predictors, and Trends of Unplanned Readmissions after Elective Endovascular Embolization of Cerebral Aneurysms.

BACKGROUND: 30- and 90-day readmissions (dRA) are being increasingly scrutinized as quality metrics for hospital and provider performances. Little information regarding risk factors for readmission after elective endovascular treatment (EVT) of an unruptured cerebral aneurysm (UCA) is available. METHODS: The Nationwide Readmissions Database was used to identify patients who underwent elective endovascular embolization of an unruptured aneurysm between 2010 and 2014. The primary outcomes of interest were unplanned readmissions occurring within 30 or 90 days of discharge. Binary logistic regressions were used to identify variables related to patients' demographics, comorbidities, and index hospital admission that were associated with 30dRA and 90dRA. RESULTS: A total of 8588 patients met the inclusion criteria for 30dRA analysis and 7289 patients were eligible for 90dRA analysis. The 5-year 30dRA and 90dRA readmission rates were 7.1% and 13.5%, respectively. The annual incidences of 30dRAs and 90dRAs between 2010 and 2014 decreased significantly (pooled odds ratio (OR) for 30dRA: .874, 95% confidence interval (CI) .765-.998; pooled OR for 90dRA: .841, 95% CI .755-.938). Patients in higher income quartiles experienced decreased odds of 30dRA and 90dRA. Nonroutine disposition following the index admission and greater comorbidity burdens were associated with higher likelihoods of both 30dRA and 90dRA. The presence of pulmonary or cardiac complications was associated with increased odds of 90dRA. CONCLUSION: Readmission rates after elective EVT of UCAs decreased between 2010 and 2014. We identified several novel risk factors for both 30dRAs and 90dRAs that can be used to identify patients who are at highest risk of readmission.

Osteoblastomas of the spine: a comprehensive review.

Osteoblastomas are primary bone tumors with an affinity for the spine. They typically involve the posterior elements, although extension through the pedicles into the vertebral body is not uncommon. Histologically, they are usually indistinguishable from osteoid osteomas. However, there are different variants of osteoblastomas, with the more aggressive type causing more pronounced bone destruction, soft-tissue infiltration, and epidural extension. A bone scan is the most sensitive radiographic examination used to evaluate osteoblastomas. These osseous neoplasms usually present in the 2nd decade of life with dull aching pain, which is difficult to localize. At times, they can present with a painful scoliosis, which usually resolves if the osteoblastoma is resected in a timely fashion. Neurological manifestations such as radiculopathy or myelopathy do occur as well, most commonly when there is mass effect on nerve roots or the spinal cord itself. The mainstay of treatment involves surgical intervention. Curettage has been a surgical option, although marginal excision or wide en bloc resection are preferred options. Adjuvant radiotherapy and chemotherapy are generally not undertaken, although some have advocated their use after less aggressive surgical maneuvers or with residual tumor. In this manuscript, the authors have aimed to systematically review the literature and to put forth an extensive, comprehensive overview of this rare osseous tumor.

Controversies in the role of preoperative embolization in meningioma management.

The role of preoperative embolization in meningioma management remains controversial, even though 4 decades have passed since it was first described. It has been shown to offer benefits such as decreased blood loss and "softening of the tumor" during subsequent resection. However, the actual benefits remain unclear, and the potential harm of an additional procedure along with the cost of embolization have limited its use to a small proportion of the meningiomas treated. In this article the authors retrospectively reviewed their experience with preoperative embolization of meningiomas over the previous 6 years (March 2007-March 2013). In addition, they performed a MEDLINE search using a combination of the terms "meningioma," "preoperative," and "embolization" to analyze the indications, embolizing agents, timing, and complications reported during preoperative embolization of meningiomas. In this retrospective review, 18 cases (female/male ratio 12:6) were identified in which endovascular embolization was used prior to resection of an intracranial meningioma. Craniotomy for tumor resection was performed within 4 days after endovascular embolization in all cases, with an average time to surgery of 1.9 days. The average duration of surgery was 4 hours and 18 minutes, and the average blood loss was 574 ml, with a range of 300-1000 ml. Complications following endovascular therapy were identified in 3 (16.7%) of 18 cases, including one each of transient hemiparesis, permanent hemiparesis, and tumor swelling. The literature review returned 15 articles consisting of a study population greater than 25 patients. No randomized controlled study was found. The use of small polyvinyl alcohol particles (45-150 µm) is more effective in preoperative devascularization than larger particles (150-250 µm), but is criticized due to the higher risk of complications such as cranial nerve palsies and postprocedural hemorrhage. Time to surgery after embolization is inconsistently reported across the articles, and conclusions on the appropriate timing of surgery could not be drawn. The overall complication rate reported after treatment with preoperative meningioma embolization ranges from as high as 21% in some of the older literature to approximately 6% in recent literature describing treatment with newer embolization techniques. The evidence in the literature supporting the use of preoperative meningioma embolization is mainly from case series, and represents Level III evidence. Due to the lack of randomized controlled clinical trials, it is difficult to draw any significant conclusions on the overall usefulness of preoperative embolization during the management of meningiomas to consider it a standard practice.

Return to play after cervical spine injury in sports.

Spinal cord injuries (SCIs) resulting from sports now represent 8.9% of the total causes of SCI. Regardless of cause, there are bound to be return-to-play decisions to be made for athletes. Since catastrophic cervical spine injuries are among the most devastating injuries in all of sports, returning from a cervical spine injury is one of the most difficult decisions in sports medicine. Axial loading is the primary mechanism for catastrophic cervical spine injuries. Axial loading occurs as a result of intentional or unintentional head-down contact and spearing. Most would agree that the athlete returning to a contact or collision sport after a cervical spine injury must be asymptomatic, have full strength, and have full active range of motion; however, each situation is unique. The following review discusses the pathophysiology of these conditions and suggests guidelines for return to contact sports after traumatic cervical SCI.

Chronic traumatic encephalopathy.

Sports-related concussion has gained increased prominence, in part due to media coverage of several well-known athletes who have died from consequences of chronic traumatic encephalopathy (CTE). CTE was first described by Martland in 1928 as a syndrome seen in boxers who had experienced significant head trauma from repeated blows. The classic symptoms of impaired cognition, mood, behavior, and motor skills also have been reported in professional football players, and in 2005, the histopathological findings of CTE were first reported in a former National Football League (NFL) player. These finding were similar to Alzheimer's disease in some ways but differed in critical areas such as a predominance of tau protein deposition over amyloid. The pathophysiology is still unknown but involves a history of repeated concussive and subconcussive blows and then a lag period before CTE symptoms become evident. The involvement of excitotoxic amino acids and abnormal microglial activation remain speculative. Early identification and prevention of this disease by reducing repeated blows to the head has become a critical focus of current research.

Stem cell factor and granulocyte colony-stimulating factor promote remyelination in the chronic phase of severe traumatic brain injury.

Severe traumatic brain injury (TBI) causes long-term disability and death in young adults. White matter is vulnerable to TBI damage. Demyelination is a major pathological change of white matter injury after TBI. Demyelination which is characterized by myelin sheath disruption and oligodendrocyte cell death leads to long-term neurological function deficits. Stem cell factor (SCF) and granulocyte colonyâ€"stimulating factor (G-CSF) treatments have shown neuroprotective and neurorestorative effects in the subacute and chronic phases of experimental TBI. Our previous study has revealed that combined SCF and G-CSF treatment (SCF+G-CSF) enhances myelin repair in the chronic phase of TBI. However, the long-term effect and mechanism of SCF+G-CSF-enhanced myelin repair remain unclear. In this study, we uncovered persistent and progressive myelin loss in the chronic phase of severe TBI. SCF+G-CSF treatment in the chronic phase of severe TBI enhanced remyelination in the ipsilateral external capsule and striatum. The SCF+G-CSF-enhanced myelin repair is positively correlated with the proliferation of oligodendrocyte progenitor cells in the subventricular zone. These findings reveal the therapeutic potential of SCF+G-CSF in myelin repair in the chronic phase of severe TBI and shed light on the mechanism underlying SCF+G-CSF-enhanced remyelination in chronic TBI.

Stem Cell Factor and Granulocyte Colony-Stimulating Factor Promote Remyelination in the Chronic Phase of Severe Traumatic Brain Injury.

Severe traumatic brain injury (TBI) causes long-term disability and death in young adults. White matter is vulnerable to TBI damage. Demyelination is a major pathological change of white matter injury after TBI. Demyelination, which is characterized by myelin sheath disruption and oligodendrocyte cell death, leads to long-term neurological function deficits. Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) treatments have shown neuroprotective and neurorestorative effects in the subacute and chronic phases of experimental TBI. Our previous study has revealed that combined SCF and G-CSF treatment (SCF + G-CSF) enhances myelin repair in the chronic phase of TBI. However, the long-term effect and mechanism of SCF + G-CSF-enhanced myelin repair remain unclear. In this study, we uncovered persistent and progressive myelin loss in the chronic phase of severe TBI. SCF + G-CSF treatment in the chronic phase of severe TBI enhanced remyelination in the ipsilateral external capsule and striatum. The SCF + G-CSF-enhanced myelin repair is positively correlated with the proliferation of oligodendrocyte progenitor cells in the subventricular zone. These findings reveal the therapeutic potential of SCF + G-CSF in myelin repair in the chronic phase of severe TBI and shed light on the mechanism underlying SCF + G-CSF-enhanced remyelination in chronic TBI.

Recurrent Spontaneous Intracranial Hypotension (SIH) and the Durability of Repeat Epidural Blood Patch (EBP).

OBJECTIVE: Spontaneous intracranial hypotension (SIH) remains a rare and difficult clinical entity to diagnose and treat. Epidural blood patch (EBP) of the dural sac is the mainstay definitive treatment for refractory cases and has mixed efficacy. We sought to evaluate the recent efficacy and outcomes of EBP for SIH at our institution. METHODS: Twenty-three patients (14 women, 9 men, mean age 49) were seen and treated for SIH between Summer 2009 and Spring 2018 at the same institution. All patients underwent brain MRI with and without gadolinium contrast and T2-weighted spine MRI. Targeted EBP was placed one or two vertebral levels below areas of suspected leak, while the patient was positioned in the lateral decubitus position. Patients were seen in the outpatient setting within a week following initial EBP and repeat EBP was offered to patients with persistent symptoms. Patients were followed if symptoms persisted or for 6 months following clinical relief of symptoms. RESULTS: 22/23 (95.7%) patients presented with complaints of orthostatic headache, and 3 (13%) patients presented with altered mental status (AMS) or focal neurologic deficit. Brain MRI demonstrated pachymeningeal enhancement in 16/23 (69.6%) patients, and 5/23 (21.7%) patients had a subdural hematoma (SDH) present. Dural leaks were successfully identified in 18/23 (78.3%) patients. 12/23 (52.2%) patients had symptomatic relief with initial EBP, and 5/23 (21.7%) patients received further EBPs for persistent disease with all achieving relief after repeat EBP. 5/12 (41.7%) of patients had recurrent symptoms after initial relief with EBP, and 4/5 (80%) were successfully treated with a second EBP. The mean initial EBP volume and number of EBPs per patient were 21.7 mL (median 20 mL, 7-40 mL) and 3.54 (median 1, 1-13) respectively. There was one complication from initial EBP (cervical dural tear requiring operative closure) treated with open surgical management successfully. In total, 18/23 (78.2%) patients are currently asymptomatic with regard to their SIH. The mean follow-up in this cohort was 2.6 years (median 1.8 years, 1.8 months-9.27 years). CONCLUSIONS: EBP is a viable and effective option for the treatment of recurrent SIH caused by cerebrospinal fluid (CSF) leaks.

Trends in the Incidence of Spontaneous Subarachnoid Hemorrhages in the United States, 2007-2017.

BACKGROUND AND OBJECTIVE: To test the hypothesis that age-specific, sex-specific, and race-specific and ethnicity-specific incidence of nontraumatic subarachnoid hemorrhage (SAH) increased in the United States over the last decade. METHODS: In this retrospective cohort study, validated International Classification of Diseases codes were used to identify all new cases of SAH (n = 39,475) in the State Inpatients Databases of New York and Florida (2007-2017). SAH counts were combined with Census data to calculate incidence. Joinpoint regression was used to compute the annual percentage change (APC) in incidence and to compare trends over time between demographic subgroups. RESULTS: Across the study period, the average annual age-standardized/sex-standardized incidence of SAH in cases per 100,000 population was 11.4, but incidence was significantly higher in women (13.1) compared with that in men (9.6), p < 0.001. Incidence also increased with age in both sexes (men aged 20-44 years: 3.6; men aged 65 years or older: 22.0). Age-standardized and sex-standardized incidence was greater in Black patients (15.4) compared with that in non-Hispanic White (NHW) patients (9.9) and other races and ethnicities, p < 0.001. On joinpoint regression, incidence increased over time (APC 0.7%, p < 0.001), but most of this increase occurred in men aged 45-64 years (APC 1.1%, p = 0.006), men aged 65 years or older (APC 2.3%, p < 0.001), and women aged 65 years or older (APC 0.7%, p = 0.009). Incidence in women aged 20-44 years declined (APC -0.7%, p = 0.017), while those in other age/sex groups remained unchanged over time. Incidence increased in Black patients (APC 1.8%, p = 0.014), whereas that in Asian, Hispanic, and NHW patients did not change significantly over time. DISCUSSION: Nontraumatic SAH incidence in the United States increased over the last decade predominantly in middle-aged men and elderly men and women. Incidence is disproportionately higher and increasing in Black patients, whereas that in other races and ethnicities did not change significantly over time.

The scaffolding protein DLG5 promotes glioblastoma growth by controlling Sonic Hedgehog signaling in tumor stem cells.

BACKGROUND: Tumor invasion, a hallmark of malignant gliomas, involves reorganization of cell polarity and changes in the expression and distribution of scaffolding proteins associated with polarity complexes. The scaffolding proteins of the DLG family are usually downregulated in invasive tumors and regarded as tumor suppressors. Despite their important role in regulating neurodevelopmental signaling, the expression and functions of DLG proteins have remained almost entirely unexplored in malignant gliomas. METHODS: Western blot, immunohistochemistry, and analysis of gene expression were used to quantify DLG members in glioma specimens and cancer datasets. Over-expression and knockdown of DLG5, the highest-expressed DLG member in glioblastoma, were used to investigate its effects on tumor stem cells and tumor growth. qRT-PCR, Western blotting, and co-precipitation assays were used to investigate DLG5 signaling mechanisms. RESULTS: DLG5 was upregulated in malignant gliomas compared to other solid tumors, being the predominant DLG member in all glioblastoma molecular subtypes. DLG5 promoted glioblastoma stem cell invasion, viability, and self-renewal. Knockdown of this protein in vivo disrupted tumor formation and extended survival. At the molecular level, DLG5 regulated Sonic Hedgehog (Shh) signaling, making DLG5-deficient cells insensitive to Shh ligand. Loss of DLG5 increased the proteasomal degradation of Gli1, underlying the loss of Shh signaling and tumor stem cell sensitization. CONCLUSIONS: The high expression and pro-tumoral functions of DLG5 in glioblastoma, including its dominant regulation of Shh signaling in tumor stem cells, reveal a novel role for this protein that is strikingly different from its proposed tumor-suppressor role in other solid tumors.

Hypernatremia is associated with poorer outcomes following aneurysmal subarachnoid hemorrhage: a nationwide inpatient sample analysis.

BACKGROUND: Hypernatremia is one of the most common electrolyte disturbances following aneurysmal subarachnoid hemorrhage (aSAH) and has been correlated with increased mortality in single institution studies. We investigated this association using a large nationwide healthcare database. METHODS: We performed a retrospective analysis of adults between 2002 and 2011 with a primary diagnosis of aSAH using the Nationwide Inpatient Sample (NIS). Patients were grouped according to whether or not an inpatient diagnosis of hypernatremia was present. The primary outcome was the NIS-SAH outcome measure. Secondary outcomes included in-hospital mortality, length of stay (LOS), and non-routine hospital discharge. Outcomes analyses adjusted for SAH severity using the NIS-SAH Severity Score, Charlson Comorbidity Index, and the presence of cerebral edema. RESULTS: A total of 18,377 patients were included in the study. The incidence of a poor outcome as defined by the NIS-SAH outcome measure was 65.9% in the hypernatremia group and 33.4% in the normonatremia group (OR=1.96, 95% CI: 1.68-2.27). There was higher mortality in the hypernatremia group (OR=1.60, 95% CI: 1.37-1.87). Patients with hypernatremia had a significantly higher rate of non-routine hospital discharge and gastrostomy. The incidences of poor outcome, in-hospital mortality, and non-routine disposition were higher in the hypernatremia group regardless of treatment type (clipping vs. endovascular embolization). Pulmonary complications and acute kidney injury were more common in the hypernatremia group as well. CONCLUSIONS: In patients with aSAH, hypernatremia is associated with poorer functional outcomes regardless of SAH severity.

SCF + G-CSF treatment in the chronic phase of severe TBI enhances axonal sprouting in the spinal cord and synaptic pruning in the hippocampus.

Traumatic brain injury (TBI) is a major cause of long-term disability in young adults. An evidence-based treatment for TBI recovery, especially in the chronic phase, is not yet available. Using a severe TBI mouse model, we demonstrate that the neurorestorative efficacy of repeated treatments with stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) (SCF + G-CSF) in the chronic phase is superior to SCF + G-CSF single treatment. SCF + G-CSF treatment initiated at 3 months post-TBI enhances contralesional corticospinal tract sprouting into the denervated side of the cervical spinal cord and re-balances the TBI-induced overgrown synapses in the hippocampus by enhancing microglial function of synaptic pruning. These neurorestorative changes are associated with SCF + G-CSF-improved somatosensory-motor function and spatial learning. In the chronic phase of TBI, severe TBI-caused microglial degeneration in the cortex and hippocampus is ameliorated by SCF + G-CSF treatment. These findings reveal the therapeutic potential and possible mechanism of SCF + G-CSF treatment in brain repair during the chronic phase of severe TBI.

Management of chronic subdural hematoma with the subdural evacuating port system: Systematic review and meta-analysis.

The subdural evacuating port system (SEPS) is a minimally invasive option for treating chronic subdural hematoma (cSDH). Individual case series have shown it to be safe and effective, but outcomes have not been systematically reviewed. We sought to review the literature in order to determine the safety and efficacy of SEPS as a first line treatment for cSDH. A comprehensive literature search for outcomes following SEPS placement as a primary treatment for cSDH was performed. The primary outcome was treatment success, which was defined as a composite of improvement in presenting symptoms and no need for further treatment in the operating room. Additional outcomes included discharge disposition, length of stay (LOS), hematoma recurrence, and complications. A total of 12 studies comprising 953 patients who underwent SEPS placement met the inclusion criteria. The pooled rate of a successful outcome was 0.79 (95% CI 0.75-0.83). Frequency of delayed hematoma recurrence was 0.15 (95% CI 0.10-0.21). The pooled inpatient mortality rate was 0.02 (95% CI 0.01-0.03). Complications rates included 0.02 (95% CI 0.00-0.03) for any acute hemorrhage, 0.01 (95% CI 0.00-0.01) for acute hemorrhage requiring surgery, and 0.02 (95% CI 0.01-0.03) for seizure. SEPS placement is associated with a success rate of 79% and very low rates of acute hemorrhage and seizure. This data supports its use as a first-line management strategy, although prospective randomized studies are needed.