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.

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.

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.

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.

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.

Outcomes associated with brain tissue oxygen monitoring in patients with severe traumatic brain injury undergoing intracranial pressure monitoring.

OBJECTIVE: Brain tissue oxygen monitoring combined with intracranial pressure (ICP) monitoring in patients with severe traumatic brain injury (sTBI) may confer better outcomes than ICP monitoring alone. The authors sought to investigate this using a national database. METHODS: The National Trauma Data Bank from 2013 to 2017 was queried to identify patients with sTBI who had an external ventricular drain or intraparenchymal ICP monitor placed. Patients were stratified according to the placement of an intraparenchymal brain tissue oxygen tension (PbtO2) monitor, and a 2:1 propensity score matching pair was used to compare outcomes in patients with and those without PbtO2 monitoring. Sensitivity analyses were performed using the entire cohort, and each model was adjusted for age, sex, Glasgow Coma Scale score, Injury Severity Score, presence of hypotension, insurance, race, and hospital teaching status. The primary outcome of interest was in-hospital mortality, and secondary outcomes included ICU length of stay (LOS) and overall LOS. RESULTS: A total of 3421 patients with sTBI who underwent ICP monitoring were identified. Of these, 155 (4.5%) patients had a PbtO2 monitor placed. Among the propensity score-matched patients, mortality occurred in 35.4% of patients without oxygen monitoring and 23.4% of patients with oxygen monitoring (OR 0.53, 95% CI 0.33-0.85; p = 0.007). The unfavorable discharge rates were 56.3% and 47.4%, respectively, in patients with and those without oxygen monitoring (OR 1.41, 95% CI 0.87-2.30; p = 0.168). There was no difference in overall LOS, but patients with PbtO2 monitoring had a significantly longer ICU LOS and duration of mechanical ventilation. In the sensitivity analysis, PbtO2 monitoring was associated with decreased odds of mortality (OR 0.56, 95% CI 0.37-0.84) but higher odds of unfavorable discharge (OR 1.59, 95% CI 1.06-2.40). CONCLUSIONS: When combined with ICP monitoring, PbtO2 monitoring was associated with lower inpatient mortality for patients with sTBI. This supports the findings of the recent Brain Oxygen Optimization in Severe Traumatic Brain Injury phase 2 (BOOST 2) trial and highlights the importance of the ongoing BOOST3 trial.

Spatial progression and molecular heterogeneity of IDH-mutant glioblastoma determined by DNA methylation-based mapping.

Glioblastoma (GBM) is the most common malignant primary central nervous system (CNS) neoplasm in adults, and has an almost universally poor prognosis. Recently, an emphasis on genetic and epigenetic profiling has revealed a number of molecular features useful in the diagnostic and prognostic classification of GBM, advancing our understanding of the underlying features that make these tumors so aggressive and providing the rationale for the creation of better targeted therapeutics. One such method, DNA methylation profiling, has recently emerged as an important technique for the classification of CNS tumors, with diagnostic accuracy in some cases surpassing traditional methods. However, how DNA methylation profiles change with the course of the disease remains less understood. Here, we present a case of a 30-year-old male with primary IDH-mutant GBM with widespread recurrence and death two years later. Using unsupervised hierarchical clustering of methylation probes, we created a phylogenetic map to trace the tumor path as it spread from the initial biopsy site throughout the right hemisphere, across the corpus callosum to the contralateral hemisphere, and into the brainstem. We identified molecular divergence between the right and left hemisphere GBM samples marked by distinct copy number profile alterations, alterations in specific methylation sites, and regional loss of MGMT promoter methylation, providing a potential mechanism for treatment resistance in this case. In summary, this case both highlights the molecular diversity in GBM, and illustrates a novel use for methylation profiling in establishing a phylogenetic profile to allow for spatial mapping of tumor progression.

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.

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.

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.

Clinical, Pathologic, and Radiologic Features of Orbital Solitary Fibrous Tumors and Meningiomas.

A wide variety of benign and malignant tumors can arise from different structures in the orbital and peri-orbital area, affecting the eye and the optic nerve. This spectrum of tumors includes primary and metastatic carcinomas, lymphomas, melanomas, soft tissue tumors, and primary tumors of the retina, optic disc, and optic nerve. These also extend to relatively rare entities such as solitary fibrous tumor and meningioma of the orbit and optic nerve, which can present with very similar clinical and radiologic features, although the tumor grades, treatment plans, and outcomes can vary widely. In this report, we present two clinical cases of solitary fibrous tumor [central nervous system (CNS) World Health Organization (WHO) grade 2 and 3) and compare their clinical presentation, radiologic and histologic features, treatment, and clinical outcomes to a group of three orbital meningiomas (CNS WHO grade 1 and 2). In the context of these five cases of orbital lesions, we review the current clinical, pathologic, and radiologic literature on orbital tumors, focusing primarily on solitary fibrous tumors and meningiomas, along with an expanded discussion on the diagnostic criteria of both entities, as well as the treatment and prognosis of these lesions.

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.

Molecular Correlates of Long Survival in IDH-Wildtype Glioblastoma Cohorts.

IDH-wildtype glioblastoma is a relatively common malignant brain tumor in adults. These patients generally have dismal prognoses, although outliers with long survival have been noted in the literature. Recently, it has been reported that many histologically lower-grade IDH-wildtype astrocytomas have a similar clinical outcome to grade IV tumors, suggesting they may represent early or undersampled glioblastomas. cIMPACT-NOW 3 guidelines now recommend upgrading IDH-wildtype astrocytomas with certain molecular criteria (EGFR amplifications, chromosome 7 gain/10 loss, and/or TERT promoter mutations), establishing the concept of a "molecular grade IV" astrocytoma. In this report, we apply these cIMPACT-NOW 3 criteria to 2 independent glioblastoma cohorts, totaling 393 public database and institutional glioblastoma cases: 89 cases without any of the cIMPACT-NOW 3 criteria (GBM-C0) and 304 cases with one or more criteria (GBM-C1-3). In the GBM-C0 groups, there was a trend toward longer recurrence-free survival (median 12-17 vs 6-10 months), significantly longer overall survival (median 32-41 vs 15-18 months), younger age at initial diagnosis, and lower overall mutation burden compared to the GBM-C1-3 cohorts. These data suggest that while histologic features may not be ideal indicators of patient survival in IDH-wildtype astrocytomas, these 3 molecular features may also be important prognostic factors in IDH-wildtype glioblastoma.

Use of Intracranial Pressure Monitoring in Patients with Severe Traumatic Brain Injury.

OBJECTIVE: The Brain Trauma Foundation (BTF) recommends intracranial pressure (ICP) monitoring for all salvageable patients with an abnormal computed tomography (CT) scan and a Glasgow Coma Scale <9. Studies have shown that compliance with this recommendation is low. We sought to obtain contemporary national rates of ICP monitor placement in patients with severe traumatic brain injury (TBI). METHODS: Patients from the National Trauma Data Bank from 2013 to 2017 who met BTF criteria for ICP monitoring were included. Placement of an intraparenchymal ICP monitor or an external ventricular drain was queried. Binary logistic regression was used to determine factors that influenced the placement of an ICP monitor. RESULTS: A total of 21,374 patients with severe TBI and an abnormal CT scan were included in the study. An ICP monitor was placed in 6543 patients (30.6%). ICP monitor placement increased modestly from 28.6% in 2013 to 32.8% in 2017. The pooled odds of ICP monitor placement between 2014 and 2017 were not different from 2013 (odds ratio, 1.04; 95% confidence interval, 0.99-1.09), but the adjusted odds of ICP monitor placement in 2017 were significantly greater (odds ratio, 1.18; 95% confidence interval, 1.06-1.30). Treatment at a teaching hospital, subdural hematoma, multiple intracranial abnormalities on CT, and greater Injury Severity Score were associated with ICP monitor placement, whereas older age was negatively associated with ICP monitor placement. CONCLUSIONS: The rate of ICP monitoring in patients with severe TBI who meet BTF criteria is low and increased only slightly from 2013 to 2017.

The contribution of stem cell factor and granulocyte colony-stimulating factor in reducing neurodegeneration and promoting neurostructure network reorganization after traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of death and disability in young adults worldwide. TBI-induced long-term cognitive deficits represent a growing clinical problem. Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) are involved in neuroprotection and neuronal plasticity. However, the knowledge concerning reparative efficacy of SCF + G-CSF treatment in post-acute TBI recovery remains incomplete. This study aims to determine the efficacy of SCF + G-CSF on post-acute TBI recovery in young adult mice. The controlled cortical impact model of TBI was used for inducing a severe damage in the motor cortex of the right hemisphere in 8-week-old male C57BL mice. SCF + G-CSF treatment was initiated 3 weeks after induction of TBI. Severe TBI led to persistent motor functional deficits (Rota-Rod test) and impaired spatial learning function (water maze test). SCF + G-CSF treatment significantly improved the severe TBI-impaired spatial learning function 6 weeks after treatment. TBI also caused significant increases of Fluoro-Jade C positive degenerating neurons in bilateral frontal cortex, striatum and hippocampus, and significant reductions in MAP2+ apical dendrites and overgrowth of SMI312+ axons in peri-TBI cavity frontal cortex and in the ipsilateral hippocampal CA1 at 24 weeks post-TBI. SCF + G-CSF treatment significantly reduced TBI-induced neurodegeneration in the contralateral frontal cortex and hippocampal CA1, increased MAP2+ apical dendrites in the peri-TBI cavity frontal cortex, and prevented TBI-induced axonal overgrowth in both the peri-TBI cavity frontal cortex and ipsilateral hippocampal CA1.These findings reveal a novel pathology of axonal overgrowth after severe TBI and demonstrate a therapeutic potential of SCF + G-CSF in ameliorating severe TBI-induced long-term neuronal pathology, neurostructural network malformation, and impairments in spatial learning.

Long-term beneficial effects of hematopoietic growth factors on brain repair in the chronic phase of severe traumatic brain injury.

Severe traumatic brain injury (TBI) is the major cause of long-term, even life-long disability and cognitive impairments in young adults. The lack of therapeutic approaches to improve recovery in the chronic phase of severe TBI is a big challenge to the medical research field. Using a single severe TBI model in young adult mice, this study examined the restorative efficacy of two hematopoietic growth factors, stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF), on brain repair in the chronic phase of TBI. SCF and G-CSF alone or combination (SCF + G-CSF) treatment was administered at 3 months post-TBI. Functional recovery was evaluated by neurobehavioral tests during the period of 21 weeks after treatment. Neuropathology was examined 22 weeks after treatment. We observed that severe TBI caused persistent impairments in spatial learning/memory and somatosensory-motor function, long-term and widespread neuropathology, including dendritic reduction, decrease and overgrowth of axons, over-generated excitatory synapses, and demyelination in the cortex, hippocampus and striatum. SCF, G-CSF, and SCF + G-CSF treatments ameliorated severe TBI-induced widespread neuropathology. SCF + G-CSF treatment showed superior efficacy in improving long-term functional outcome, enhancing neural plasticity, rebalancing neural structure networks disturbed by severe TBI, and promoting remyelination. These novel findings demonstrate the therapeutic potential of SCF and G-CSF in enhancing recovery in the chronic phase of severe TBI .

Prediction of mortality after evacuation of supratentorial intracerebral hemorrhage using NSQIP data.

Spontaneous intracerebral hemorrhage (sICH) is associated with high rates of morbidity and mortality. Neurosurgical clot evacuation is controversial but often a life saving maneuver in the setting of severe mass effect and cerebral herniation. Outcomes from large multicenter databases are sparsely reported. Patients who underwent craniotomy for evacuation of a supratentorial sICH between 2006 and 2017 were systematically extracted from the American College of Surgeons National Surgical Quality Improvement Program Participant Use Files. Our primary outcomes of interest were 30-day mortality, non-routine discharge disposition, and extended length of stay ([eLOS], defined as the top quartile for the cohort). Individual binary logistic regression models were constructed to query the associations between pre- and perioperative variables and each outcome. A total of 751 patients met the inclusion criteria. The 30-day mortality rate was 23.3% and increased from 2011 to 2017 (pooled OR 2.060 [95% CI 1.437 - 2.953]). Older age, morbid obesity, preoperative mechanical ventilation, preoperative systemic inflammatory response syndrome (SIRS) or septic shock, and thrombocytopenia were associated with mortality. Older age, race, and preoperative mechanical ventilation were associated with non-routine discharge. Patients who were mechanically ventilated or were insulin-dependent diabetics had greater odds of experiencing eLOS. A formula for estimating 30-day mortality was developed and found to have a strong linear association with actual mortality rates (R2 = 0.777, p = 0.002). Preoperative mechanical ventilation is a consistent predictor of poor outcomes following surgery for supratentorial sICH. Mortality is also influenced by older age, body habitus, SIRS, septic shock, and thrombocytopenia.