Confounding factors impacting the Glasgow coma score: a literature review.

BACKGROUND: The Glasgow coma score (GCS) is a clinical tool used to measure level of consciousness in traumatic brain injury and other settings. Despite its widespread use, there are many inaccuracies in its reporting. One source of inaccuracy is confounding factors which affect consciousness as well as each sub-score of the GCS. The purpose of this article was to create a comprehensive list of confounding factors in order to improve the accuracy of the GCS and ultimately improve decision-making. METHODS: An English language literature search was conducted discussing GCS and multiple other keywords. Ultimately, 64 out of 3972 articles were included for further analysis. RESULTS: A multitude of confounding factors were identified which may affect consciousness or GCS sub-scores including the eye exam, motor exam and the verbal response. CONCLUSIONS: An up-to-date comprehensive list of confounding factors has been created that may be used to aide in GCS recording in hopes of improving its accuracy and utility.

A Retrospective Analysis of Intracranial Pressure Monitoring and Outcomes in Adults after Severe Traumatic Brain Injury at Kaiser Permanente Trauma Centers.

BACKGROUND: The role of intracranial pressure (ICP) monitoring in improving outcomes after severe traumatic brain injury especially at level II trauma centers remains controversial. A retrospective analysis was undertaken to assess the impact of ICP monitoring on mortality and long-term functional outcome in adults after severe traumatic brain injury at level II trauma centers. METHODS: The data were extracted from the Kaiser Permanente trauma database. Inclusion criteria were adults (≥ 18 years) with severe traumatic brain injury (Glasgow Coma Scale score, < 9) admitted to 2 level II trauma centers in Northern California from 2014 to 2019. RESULTS: Of 199 patients, 58 (29.1%) underwent ICP monitoring. The monitored subgroup was significantly younger (< 65 years), had lower Glasgow Coma Scale scores (3-5), underwent cranial procedures (craniotomy or decompressive craniectomy) more often, and had greater injury severity scores (≥ 15). Despite monitored patients being more severely injured, there was no significant difference in mortality or 6-month favorable outcomes between monitored and nonmonitored patients, including patients who underwent cranial procedures. Increased monitoring frequency and reduction in overall mortality was seen throughout the study period yet with a parallel reduction in both groups. CONCLUSION: ICP monitoring may not impact in-patient mortality or long-term outcomes at level II trauma centers. Improved outcomes may be more related to identifying patients who may benefit from ICP-guided therapy rather than simply increasing the overall use of it. Last, our pattern of care and outcomes are comparable to level I trauma centers and our findings may serve as a benchmark for future studies.

Diagnosis, Classification, and Management of Fourth Ventriculomegaly in Adults: Report of 9 Cases and Literature Review.

OBJECTIVE: An enlarged fourth ventricle, otherwise known as fourth ventriculomegaly (4th VM), has been reported previously in the pediatric population, yet literature on adults is scant. We report our experience with 4th VM in adults over an 11-year period and review the literature. MATERIALS AND METHODS: This was a retrospective chart review of adult patients with the diagnosis of 4th VM admitted to the intensive care unit in a tertiary care center. RESULTS: Nine patients were identified with 4th VM. Most presented with symptoms in the posterior fossa. Five cases were related to previous shunting and the underlying neurosurgical diseases, and average time interval to develop symptoms was 5.3 years. We divided our cases into primary, acquired, and degenerative based on the pathophysiology involved. Treatments included extended subzero cerebrospinal fluid diversion using a frontal external ventricular drain followed by low-pressure shunt revision, endoscopic third ventriculostomy, suboccipital decompression, and fourth ventricular catheter placement. Literature review identified additional published cases, and there were no reports of a formal classification scheme or treatment algorithm. CONCLUSIONS: This case series illustrates a narrow spectrum of etiologies associated with 4th VM in adults. We propose a simple classification scheme dividing 4th VM into 3 categories: primary, acquired, and degenerative. We recommend a stepwise treatment approach starting with extended subzero cerebrospinal fluid diversion followed by shunting for symptomatic primary and acquired 4th VM. Lower success rates and greater morbidity are associated with rescue procedures such as fourth ventricle drainage catheters, endoscopic third ventriculostomies, and skull base decompression.

Type 2 Diabetes Mellitus and Glioblastoma Multiforme-Assessing Risk and Survival: Results of a Large Retrospective Study and Systematic Review of the Literature.

OBJECTIVE: Despite studies showing a positive correlation between type 2 diabetes mellitus (DM2), a modifiable risk factor, and various cancer types, the link remains controversial in the setting of glioblastoma multiforme (GBM). In this study, we assessed whether DM2 and DM2-associated factors were associated with a higher risk of developing GBM and also determined if DM2 affected the survival of patients with GBM. METHODS: A cross-sectional case-control study of 1144 GBM cases diagnosed between 2000 and 2013 of which 969 patients matched for age and sex was performed to assess the association between DM2, hyperlipidemia, and obesity with the incidence of GBM. A longitudinal study of the patients with GBM was also performed to assess the association between the effect of DM2 and GBM survival. RESULTS: No association was seen between DM2, hyperlipidemia, obesity, and GBM. DM2 was associated with poorer survival in univariate testing yet not in multivariate testing. Diabetic patients with GBM had good glycemic control. Older patients had poorer survival and overall survival improved over years of study. CONCLUSIONS: DM2, hyperlipidemia, and obesity were not associated with increased risk of developing GBM, and DM2 itself does not seem to influence survival among these patients. This finding might be related to good glycemic control in this cohort. Survey of the literature consistently shows that hyperglycemia is associated with poorer survival. Our findings suggest that rather than the presence or absence of DM2, glycemic control seems to be more important in the survival of patients with GBM, which warrants future investigation.

Cerebral venous overdrainage: an under-recognized complication of cerebrospinal fluid diversion.

Understanding the altered physiology following cerebrospinal fluid (CSF) diversion in the setting of adult hydrocephalus is important for optimizing patient care and avoiding complications. There is mounting evidence that the cerebral venous system plays a major role in intracranial pressure (ICP) dynamics especially when one takes into account the effects of postural changes, atmospheric pressure, and gravity on the craniospinal axis as a whole. An evolved mechanism acting at the cortical bridging veins, known as the "Starling resistor," prevents overdrainage of cranial venous blood with upright positioning. This protective mechanism can become nonfunctional after CSF diversion, which can result in posture-related cerebral venous overdrainage through the cranial venous outflow tracts, leading to pathological states. This review article summarizes the relevant anatomical and physiological bases of the relationship between the craniospinal venous and CSF compartments and surveys complications that may be explained by the cerebral venous overdrainage phenomenon. It is hoped that this article adds a new dimension to our therapeutic methods, stimulates further research into this field, and ultimately improves our care of these patients.

The cerebral venous system and the postural regulation of intracranial pressure: implications in the management of patients with cerebrospinal fluid diversion.

Loss of cerebrospinal fluid (CSF) occurs commonly in daily neurosurgical practice. Understanding the altered physiology following CSF loss is important for optimization of patient care and avoidance of complications. There is overwhelming evidence now that the cerebral venous system plays a major role in intracranial pressure (ICP) dynamics especially when one takes into account the effects of postural changes, atmospheric pressure, and gravity on the craniospinal axis as a whole. The CSF and cerebral venous compartments are tightly coupled in two important ways. CSF is resorbed into the venous system, and there is also an evolved mechanism that prevents overdrainage of venous blood with upright positioning known as the Starling resistor. With loss of CSF pressure, this protective mechanism could become nonfunctional which may result in posture-related venous overdrainage through the cranial venous outflow tracts leading to pathologic states. This review article summarizes the relevant anatomic and physiologic basis of the relationship between the craniospinal venous and CSF compartments in the setting of CSF diversion. It is hoped that this article improves our understanding of ICP dynamics after CSF loss, adds a new dimension to our therapeutic methods, stimulates further research into this field, and ultimately improves our care of these patients.

Experience with transforaminal interbody fusion in corrective surgery for adolescent idiopathic scoliosis.

One of the surgical goals during the treatment of adolescent idiopathic scoliosis (AIS) is to preserve segments and thus mobility while achieving a well-balanced spine on all planes. The transforaminal interbody fusion (TLIF) technique allows for a significant degree of rotational correction and thus may allow for preservation of more mobile segments. This retrospective study analyzed the use of TLIF in AIS patients who underwent surgery between 2006 and 2009 at a single center, and discusses the degree of curve correction, complications and outcomes. All curves were classified using the Lenke classification system. Standing posterior-anterior Cobb angle, sagittal and coronal balance, percent correction, and end/stable/neutral/apical vertebra were determined on preoperative, postoperative and follow-up radiographs. Nine patients were identified (eight women and one man) ranging in age from 11.6-18 years. All TLIF procedures were performed at the L2/3 level. Lenke curves included 5CN (n=5), 5BN (n=2), and 6CN (n=2). Average follow-up was 27.4 months (range, 12-57 months). Average postoperative curve correction was 79%. One patient underwent revision surgery. All patients remained stable from a clinical and radiographic standpoint on their last follow-up visit. TLIF is an important adjunct in the surgical management of select AIS patients. By allowing for greater rotational correction, it may be possible to preserve one more mobile segment without decompensation or overcorrection. To our knowledge, this is the first report on the role of TLIF in AIS. Future studies are warranted in determining those who will maximally benefit from this technique.

Incidence, risk factors and management of delayed wound dehiscence after craniotomy for tumor resection.

Dehiscence after a wound has healed is a known complication of craniotomy for tumor resection. We conducted a retrospective analysis of 64 patients who underwent craniotomy for tumor resection followed by radiation or radiosurgery between 2006 and 2010. Five patients (7.8%) were identified who showed wound dehiscence from two to eight months after the craniotomy wound had healed. Four patients had previously undergone additional craniotomies, additional radiosurgery or had been treated with the anti-angiogenic factor, bevacizumab. These treatments may be risk factors for developing delayed dehiscence and, in combination, may potentiate local wound healing problems. Potential mechanisms and management strategies are discussed.

CyberKnife radiosurgery for management of intracranial perineural spread of cutaneous malignancies.

Intracranial perineural spread (PNS) is a rare complication of cutaneous malignancies and refers to access of the tumor to the intracranial space typically by tracking along cranial nerves. Patients are usually treated with palliative external-beam radiotherapy or with radiosurgery if there has been prior standard radiotherapy. Two patients are presented, both with cranial neuropathies occurring years after treatment for cutaneous malignancies. Radiographic workup showed recurrent tumor involving multiple cranial nerves. Both patients were treated with CyberKnife radiosurgery. To the author's knowledge, these are the first reported patients with intracranial PNS treated via CyberKnife radiosurgery.

Oncomodulatory mechanisms of human cytomegalovirus in gliomas.

Human cytomegalovirus (HCMV), a widespread beta-herpes virus, infects a high percentage of high grade gliomas. Although HCMV is not recognized as an oncogenic virus, it might increase the malignancy of the infected cell by disrupting cellular pathways involved in the cell cycle, apoptosis, angiogenesis, cell invasion and the host immune response. This article reviews the recent evidence of the modulatory effects of HCMV infection leading to the malignant progression of gliomas and explores novel therapeutic targets against such lethal tumors.

Lipopolysaccharide-induced inflammatory cytokine production by Schwann's cells dependent upon TLR4 expression.

Signaling of Toll-like receptor-4 (TLR4) through its cognate ligand endotoxin appears critical in tissue inflammation associated with bacterial infection. We found that anti-GM1 antibody (Ab) enhances TLR4 expression in Schwann's cells (SCs) in vivo and in vitro. The anti-GM1 Ab-treated SC also showed increased release of pro-inflammation cytokines IL-1beta and TNF-alpha after incubation with lipopolysaccharide (LPS). Furthermore, down-regulation of TLR4 expression using antisense oligonucleotides targeted to TLR4 mRNA suppressed cytokine production in LPS stimulated cultures. These findings suggest that elevation of TLR4 expression increases sensitivity of SC to LPS and production of inflammatory mediators that may be responsible for peripheral nerve dysfunction.

Relationship of gliomas to the ventricular walls.

The role of neural stem cells in gliomagenesis remains controversial. The aim of this study was to determine the anatomic relationship of human gliomas to the lining of the ventricular walls, known as the subventricular zone, an area replete with neural stem cells. We performed a retrospective radiographic analysis of 100 consecutive patients with gliomas and sought to determine the relationship of the lesions to the ventricular walls as seen on their MRI scans. Our results indicated that in 93% of cases the lesions contacted at least one region of the lateral ventricular wall. Contact with the ventricular wall was independent of the glioma size or mass effect. These findings were correlated to cytoarchitectural studies of the human subventricular zone. Our findings lend further support that there is an intimate association between gliomas and the subventricular zone.

Relationship of neural stem cells with their vascular niche: implications in the malignant progression of gliomas.

During embryogenesis and in regions of the adult brain undergoing post-natal neurogenesis, neural stem cells and endothelial precursors are found within a vascular niche, where the coordinated interactions between neurogenesis and vasculogenesis dictates development and responses to the environment. Moreover, recent evidence suggests that gliomas may arise from transformed neural stem cells and that angiogenesis is important in the malignant progression of these tumors. Taken together, these findings have led researchers to focus on the dynamic interaction between neural stem cells and their vascular niche so as to find new therapeutic strategies to halt the progression of gliomas. This review summarizes the cellular substrates responsible for the coordinated interactions between the nervous and vascular systems and how this relates to gliomagenesis.

Biology of the subventricular zone in relation to gliomagenesis.

There is recent compelling evidence that gliomas arise from neural stem cells residing in the lining of the lateral ventricles, known as the subventricular zone, that have undergone malignant transformation. This article reviews the operative elements, including cytoskeletal proteins, tumor suppressor genes, cell adhesion molecules, growth factors, transcription factors and developmental pathways that link the subventricular zone to gliomagenesis. It is hoped that with an improved understanding of the putative source of gliomas, new therapeutic strategies will be developed against such deadly tumors.