Clinical Outcomes After Ultra-Early Cranioplasty Using Craniectomy Contour Classification as a Patient Selection Criterion.

BACKGROUND: Although not a technically difficult operation, cranioplasty is associated with high rates of complications. The optimal timing of cranioplasty to mitigate complications remains the subject of debate. OBJECTIVE: To report outcomes between patients undergoing cranioplasty at ultra-early (0-6 weeks), intermediate (6 weeks to 6 months), and late (>6 months) time frames. We report a novel craniectomy contour classification (CCC) as a radiographic parameter to assess readiness for cranioplasty. METHODS: A single-institution retrospective analysis of patients undergoing cranioplasty was performed. Patients were stratified into ultra-early (within 6 weeks of index craniectomy), intermediate (6 weeks to 6 months), and late (>6 months) cranioplasty cohorts. We have devised CCC scores, A, B, and C, based on radiographic criteria, where A represents those with a sunken brain/flap, B with a normal parenchymal contour, and C with "full" parenchyma. RESULTS: A total of 119 patients were included. There was no significant difference in postcranioplasty complications, including return to operating room ( P = .212), seizures ( P = .556), infection ( P = .140), need for shunting ( P = .204), and deep venous thrombosis ( P = .066), between the cohorts. Univariate logistic regression revealed that ultra-early cranioplasty was significantly associated with higher rate of functional independence at >6 months (odds ratio 4.32, 95% CI 1.39-15.13, P = .015) although this did not persist when adjusting for patient selection features (odds ratio 2.90, 95% CI 0.53-19.03, P = .234). CONCLUSION: In appropriately selected patients, ultra-early cranioplasty is not associated with increased rate of postoperative complications and is a viable option. The CCC may help guide decision-making on timing of cranioplasty.

Clinical Outcomes at One-year Follow-up for Patients With Surgical Site Infection After Spinal Fusion.

STUDY DESIGN: Retrospective case-control study. OBJECTIVE: To compare health-related quality of life outcomes at one-year follow-up between patients who did and did not develop surgical site infection (SSI) after thoracolumbar spinal fusion. SUMMARY OF BACKGROUND DATA: SSI is among the most common healthcare-associated complications. As healthcare systems increasingly emphasize the value of delivered care, there is an increased need to understand the clinical impact of SSIs. MATERIALS AND METHODS: A retrospective 3:1 (control:SSI) propensity-matched case-control study was conducted for adult patients who underwent thoracolumbar fusion from March 2014 to January 2020 at a single academic institution. Exclusion criteria included less than 18 years of age, incomplete preoperative and one-year postoperative patient-reported outcome measures, and revision surgery. Continuous and categorical data were compared via independent t tests and χ 2 tests, respectively. Intragroup analysis was performed using paired t tests. Regression analysis for ∆ patient-reported outcome measures (postoperative minus preoperative scores) controlled for demographics. The α was set at 0.05. RESULTS: A total of 140 patients (105 control, 35 SSI) were included in final analysis. The infections group had a higher rate of readmission (100% vs. 0.95%, P <0.001) and revision surgery (28.6% vs. 12.4%, P =0.048). Both groups improved significantly in Physical Component Score (control: P =0.013, SSI: P =0.039), Oswestry Disability Index (control: P <0.001, SSI: P =0.001), Visual Analog Scale (VAS) Back (both, P <0.001), and VAS Leg (control: P <0.001, SSI: P =0.030). Only the control group improved in Mental Component Score ( P <0.001 vs. SSI: P =0.228), but history of a SSI did not affect one-year improvement in ∆MCS-12 ( P =0.455) on regression analysis. VAS Leg improved significantly less in the infection group (-1.87 vs. -3.59, P =0.039), which was not significant after regression analysis (ß=1.75, P =0.050). CONCLUSION: Development of SSI after thoracolumbar fusion resulted in increased revision rates but did not influence patient improvement in one-year pain, functional disability, or physical and mental health status.

Fixed Positioning for Decompressive Hemicraniectomy Provides a Larger Diameter Flap than Nonfixed Positioning: A Single-Institution Experience.

BACKGROUND: Decompressive hemicraniectomy (DHC) is well established as an effective life-saving intervention. Although literature documents a correlation between mortality and hemicraniectomy flap size, no literature exists demonstrating whether a larger flap may be achieved with 3-pin fixation devices versus nonfixed positioning (e.g., occipital headrest, gel donut). Therefore, positioning for DHC remains the preference of the institution and attending physician. METHODS: Patients undergoing DHC during 2005-2016 were identified using Current Procedural Terminology codes. Inclusion criteria were: operative note available in the electronic medical record and postoperative head computed tomography (hCT). Exclusion criteria were: age <18 years, missing data in electronic medical record, no postoperative hCT performed, and craniectomy not done with intention of performing a hemicraniectomy (i.e., craniotomy converted to craniectomy). Anteroposterior diameter of the hemicraniectomy flap was measured in millimeters on the postoperative hCT. The average diameter was compared between the fixed positioning and nonfixed positioning groups. RESULTS: Analysis included 522 patients who met inclusion criteria; 363 were in the fixed positioning group, and 159 were in the nonfixed positioning group. The average hemicraniectomy diameter was 132.17 mm in the fixed positioning group, and 129.74 mm in the nonfixed positioning group, which was statistically significant (P = 0.027). CONCLUSIONS: This is the first large-scale single-institution study evaluating whether operative positioning for DHC affects the size of a hemicraniectomy flap. Positioning in 3-point fixation led to a statistically significant larger average diameter compared with nonfixed positioning. This indicates that the risks associated with pin fixation as well as additional time spent in positioning in this fashion are offset by the ability to obtain a larger hemicraniectomy flap, which is associated with decreased mortality.

Understanding the endocannabinoid system as a modulator of the trigeminal pain response to concussion.

Post-traumatic headache is the most common symptom of postconcussion syndrome and becomes a chronic neurological disorder in a substantial proportion of patients. This review provides a brief overview of the epidemiology of postconcussion headache, research models used to study this disorder, as well as the proposed mechanisms. An objective of this review is to enhance the understanding of how the endogenous cannabinoid system is essential for maintaining the balance of the CNS and regulating inflammation after injury, and in turn making the endocannabinoid system a potential modulator of the trigeminal response to concussion. The review describes the role of endocannabinoid modulation of pain and the potential for use of phytocannabinoids to treat pain, migraine and concussion.

Cannabinoid receptor type-2 stimulation, blockade, and deletion alter the vascular inflammatory responses to traumatic brain injury.

BACKGROUND: Immunomodulatory therapies have been identified as interventions for secondary injury after traumatic brain injury (TBI). The cannabinoid receptor type-2 (CB2R) is proposed to play an important, endogenous role in regulating inflammation. The effects of CB2R stimulation, blockade, and deletion on the neurovascular inflammatory responses to TBI were assessed. METHODS: Wild-type C57BL/6 or CB2R knockout mice were randomly assigned to controlled cortical impact (CCI) injury or to craniotomy control groups. The effects of treatment with synthetic, selective CB2R agonists (0-1966 and JWH-133), a selective CB2R antagonist, or vehicle solution administered to CCI groups were assessed at 1-day after injury. Changes in TNF-α, intracellular adhesion molecule (ICAM-1), inducible nitric oxide synthase (iNOS), macrophage/microglial ionized calcium-binding adaptor molecule, and blood-brain-barrier (BBB) permeability were assessed using ELISA, quantitative RT-PCR, immunohistochemistry, and fluorometric analysis of sodium fluorescein uptake. CB2R knockouts and wild-type mice with CCI injury were treated with a CB2R agonist or vehicle treatment. RESULTS: TNF-α mRNA increased at 6 hours and 1 to 3 days after CCI; a CB2R antagonist and genetic knockout of the CB2R exacerbated TNF-α mRNA expression. Treatment with a CB2R agonist attenuated TNF-α protein levels indicating post-transcriptional mechanisms. Intracellular adhesion molecule (ICAM-1) mRNA was increased at 6 hours, and at 1 to 2 days after CCI, reduced in mice treated with a CB2R agonist, and increased in CB2R knockout mice with CCI. Sodium fluorescein uptake was increased in CB2R knockouts after CCI, with and without a CB2R agonist. iNOS mRNA expression peaked early (6 hours) and remained increased from 1 to 3 days after injury. Treatment with a CB2R agonist attenuated increases in iNOS mRNA expression, while genetic deletion of the CB2R resulted in substantial increases in iNOS expression. Double label immunohistochemistry confirmed that iNOS was expressed by macrophage/microglia in the injured cortex. CONCLUSION: Findings demonstrate that the endogenous cannabinoid system and CB2R play an important role in regulating inflammation and neurovascular responses in the traumatically injured brain. CB2R stimulation with two agonists (0-1966 and JWH-133) dampened post-traumatic inflammation, while blockade or deletion of the CB2R worsened inflammation. Findings support previous evidence that modulating the CB2R alters infiltrating macrophages and activated resident microglia. Further investigation into the role of the CB2R on specific immune cell populations in the injured brain is warranted.

Correlation of posterior occipitocervical angle and surgical outcomes for occipitocervical fusion.

Study Type Retrospective cohort study. Introduction Craniocervical instability is a surgical disease, most commonly due to rheumatoid arthritis, trauma, erosive pathologies such as tumors and infection, and advanced degeneration. Treatment involves stabilization of the craniovertebral junction by occipitocervical instrumentation and fusion. However, the impact of the fixed occipitocervical angle on surgical outcomes, in particular the need for revision surgery and the incidence of dysphagia, remains unknown. Occipitocervical fusions (OCFs) at a single institution were reviewed to evaluate the relationships between postoperative neck alignment, the need for revision surgery, and dysphagia. Objective The objective of this study is to determine whether an increased posterior occipital cervical angle results in an increase in the need for revision surgery, and secondary, dysphagia. Methods A retrospective review of spinal surgery patients from January 2007 to June 2013 was conducted searching for patients who underwent an occipitocervical instrumented fusion utilizing diagnostic and procedural codes. Specifically, a current procedural code of 22590 (arthrodesis, posterior technique [craniocervical]) was queried, as well those with a description of "craniocervical" or "occipitocervical" arthrodesis. Ideal neck alignment before rod placement was judged by the attending surgeon. A review of all cases for revision surgery or evidence of dysphagia was then conducted. Results From January 2007 to June 2013, 107 patients were identified (31 male, 76 female, mean age 63). Rheumatoid arthritis causing myelopathy was the most common indication for OCF, followed by trauma. Twenty of the patients were lost to follow-up and seven died within the perioperative period. Average follow-up for the remaining 80 patients was 16.4 months. The mean posterior occipitocervical angle (POCA), defined as the angle formed by the intersection of a line drawn tangential to the posterior aspect of the occipital protuberance and a line determined by the posterior aspect of the facets of the third and fourth cervical vertebrae, calculated after stabilization, was 107.1 degrees (range, 72-140 degrees). Reoperation was required in 11 patients (11/107, 10.3%). The mean POCA for the reoperation group was 109.5 degrees (range, 72-123) and was not significantly different than patients not requiring reoperation (106.5, p > 0.05). However, for all pathologies excluding infection as a cause for reoperation, the mean POCA was significantly higher, 115.14 degrees (p = 0.039) (Table 1). Seven patients (6.5%) complained of dysphagia postoperatively with a significantly higher POCA of 115 degrees (p = 0.039). Of these seven patients, six underwent posterior-only procedures. One patient underwent anterior and posterior procedures for a severe kyphotic deformity. The dysphagia resolved in six patients over a mean of 3 weeks (range, 2-4 weeks). One patient, whose surgery was posterior only, required the insertion of a gastrostomy tube. Conclusions An elevated POCA may result in need for reoperation due to increased biomechanical stress upon adjacent segments or the construct itself due to flexion in an attempt to maintain forward gaze. Further, an elevated POCA seems to also correlate with a higher incidence of dysphagia. Further investigation is necessary to determine the ideal craniocervical angle which is likely individualized to a particular patient based on global and regional spinal alignments.

A cannabinoid type 2 receptor agonist attenuates blood-brain barrier damage and neurodegeneration in a murine model of traumatic brain injury.

After traumatic brain injury (TBI), inflammation participates in both the secondary injury cascades and the repair of the CNS, both of which are influenced by the endocannabinoid system. This study determined the effects of repeated treatment with a cannabinoid type 2 receptor (CB(2) R) agonist on blood-brain barrier integrity, neuronal degeneration, and behavioral outcome in mice with TBI. We also looked for the presence of a prolonged treatment effect on the macrophage/microglial response to injury. C57BL/6 mice underwent controlled cortical impact (CCI) and received repeated treatments with a CB(2) R agonist, 0-1966, or vehicle. After euthanasia at 6 hr or 1, 2, 3, or 7 days postinjury, brains were removed for histochemical analysis. Blood-brain barrier permeability changes were evaluated by using sodium fluorescein (NaF). Perilesional degenerating neurons, injury volumes, and macrophage/microglia cells were quantified by stereological methods. Rota-rod and open-field testing were performed to evaluate motor function and natural exploratory behavior in mice. 0-1966 Treatment resulted in a significant reduction in NaF uptake and number of degenerating neurons compared with the vehicle-treated group. 0-1966-Treated mice demonstrated improvement on rota-rod and open-field testing compared with vehicle-treated mice. These changes in CCI mice treated with 0-1966 were associated with a prolonged reduction in macrophage/microglia cell counts. In conclusion, repeated treatments with a CB(2) R agonist, 0-1966, result in attenuated blood-brain barrier disruption and neuronal degeneration. In addition, repeated treatment with 0-1966 shows prolonged treatment effects on behavior and the macrophage/microglia cell response over several days.

Nociceptive neuropeptide increases and periorbital allodynia in a model of traumatic brain injury.

OBJECTIVE: This study tests the hypothesis that injury to the somatosensory cortex is associated with periorbital allodynia and increases in nociceptive neuropeptides in the brainstem in a mouse model of controlled cortical impact (CCI) injury. METHODS: Male C57BL/6 mice received either CCI or craniotomy-only followed by weekly periorbital von Frey (mechanical) sensory testing for up to 28 days post-injury. Mice receiving an incision only and naïve mice were included as control groups. Changes in calcitonin gene-related peptide (CGRP) and substance P (SP) within the brainstem were determined using enzyme-linked immunosorbent assay and immunohistochemistry, respectively. Activation of ionized calcium-binding adaptor molecule-1-labeled macrophages/microglia and glial fibrillary acidic protein (GFAP)-positive astrocytes were evaluated using immunohistochemistry because of their potential involvement in nociceptor sensitization. RESULTS: Incision-only control mice showed no changes from baseline periorbital von Frey mechanical thresholds. CCI significantly reduced mean periorbital von Frey thresholds (periorbital allodynia) compared with baseline and craniotomy-only at each endpoint, analysis of variance P < .0001. Craniotomy significantly reduced periorbital threshold at 14 days but not 7, 21, or 28 days compared with baseline threshold, P < .01. CCI significantly increased SP immunoreactivity in the brainstem at 7 and 14 days but not 28 days compared with craniotomy-only and controls, P < .001. CGRP levels in brainstem tissues were significantly increased in CCI groups compared with controls (incision-only and naïve mice) or craniotomy-only mice at each endpoint examined, P < .0001. There was a significant correlation between CGRP and periorbital allodynia (P < .0001, r = -0.65) but not for SP (r = 0.20). CCI significantly increased the number of macrophage/microglia in the injured cortex at each endpoint up to 28 days, although cell numbers declined over weeks post-injury, P < .001. GFAP(+) immunoreactivity was significantly increased at 7 but not 14 or 28 days after CCI, P < .001. Craniotomy resulted in transient periorbital allodynia accompanied by transient increases in SP, CGRP, and GFAP immunoreactivity compared with control mice. There was no increase in the number of macrophage/microglia cells compared with controls after craniotomy. CONCLUSION: Injury to the somatosensory cortex results in persistent periorbital allodynia and increases in brainstem nociceptive neuropeptides. Findings suggest that persistent allodynia and increased neuropeptides are maintained by mechanisms other than activation of macrophage/microglia or astrocyte in the injured somatosensory cortex.

Analysis of nonmodifiable risk factors for intracranial aneurysm rupture in a large, retrospective cohort.

BACKGROUND: The risk factors predictive of intracranial aneurysm rupture remain incompletely defined. OBJECTIVE: To examine the association between various nonmodifiable risk factors and aneurysm rupture in a large cohort of patients evaluated at a single institution. METHODS: A retrospective analysis of patients admitted to a cerebrovascular facility between January 2006 and 2010 with a primary diagnosis of cerebral aneurysm. Aneurysms were divided into 2 groups: unruptured or ruptured. The dome diameter, aspect ratio (AR), location, sidedness, neck morphology, and multiplicity were entered into a central database. A full model was constructed, and a systematic removal of the least significant variables was performed in a sequential fashion until only those variables reaching significance remained. RESULTS: We identified 2347 patients harboring 5134 individual aneurysms, of which 34.90% were ruptured and 65.09% were unruptured. On admission, 25.89% of aneurysms with a dome diameter <10 mm and 58.33% of aneurysms with a dome >10 mm were ruptured (P < .001). Of aneurysms with an AR >1.6, 52.44% presented following a rupture (P < .001). The highest incidence of rupture (69.21%) was observed in aneurysms with an AR >1.6, dome diameter <10 mm, and a deviated neck. Deviated neck-type aneurysms had a significantly greater incidence of rupture than classical neck-type aneurysms (P < .001). CONCLUSION: An AR >1.6, dome diameter >10 mm, a deviated neck, and right-sidedness are independently associated with aneurysm rupture.

Acute effects of a selective cannabinoid-2 receptor agonist on neuroinflammation in a model of traumatic brain injury.

Proposed therapeutic strategies for attenuating secondary traumatic brain injury (TBI) include modulation of acute neuroimmune responses. The goal of this study was to examine the acute effects of cannabinoid-2 receptor (CB(2)R) modulation on behavioral deficits, cerebral edema, perivascular substance P, and macrophage/microglial activation in a murine model of TBI. Thirty male C57BL/6 mice underwent sham surgery, or cortical contusion impact injury (CCI). CCI mice received vehicle or the CB(2)R agonist 0-1966 at 1 and 24 h after injury. Performance on the rotarod, forelimb cylinder, and open-field tests were evaluated before and at 48 h after sham or CCI surgery. Cerebral edema was evaluated using the wet-dry weight technique. Immunohistochemical analysis was used to examine changes in substance P and macrophage/microglia-specific Iba1 protein immunoreactivity. Locomotor performance and exploratory behavior were significantly improved in mice receiving 0-1966 (CB(2)R agonist) compared to vehicle-treated mice. Significant reductions were found for cerebral edema, number of perivascular areas of substance P immunoreactivity, and number of activated macrophages/microglial cells in the injured brains of 0-1966-treated mice compared to vehicle-treated mice. The findings show that the effects of the CB(2)R agonist 0-1966 on edema, substance P immunoreactivity, and macrophage/microglial activation, were associated with recovery of acute motor and exploratory deficits. This study provides evidence of acute neuroprotective effects derived from selective CB(2)R activation that may represent an avenue for further development of novel therapeutic agents in the treatment of TBI.

A murine model of hypertonic saline as a treatment for acute spinal cord injury: effects on autonomic outcome.

OBJECT: spinal cord injury (SCI) continues to be a problem without a definitive cure. Research based on improved understanding of the immunological aspects of SCI has revealed targets for treating and ameliorating the extent of secondary injury. Hypertonic saline (HTS), a substance both easy to create and to transport, has been investigated as an immunologically active material that can be used in a clinically relevant interval after injury. In this pilot study, HTS was investigated in a murine model for its abilities to ameliorate secondary injury after a severe spinal cord contusion. METHODS: female C57Bl/6 mice with severe T8-10 contusion injuries were used as the model subjects. A group of 41 mice were studied in a blinded fashion. Mice received treatments with HTS (HTS, 7.5%) or normal saline solution (NSS, 0.9%) at 2 discreet time points (3 and 24 hours after injury.) A separate group of 9 untreated animals were also used as controls. Animals were assessed for autonomic outcome (bladder function). In a group of 33 mice, histological assessment (cellular infiltration) was also measured. RESULTS: bladder function was found to be improved significantly in those treated with HTS compared with those who received NSS and also at later treatment times (24 hours) than at earlier treatment times (3 hours). Decreased cellular infiltration in each group correlated with bladder recovery. CONCLUSIONS: the increased effectiveness of later administration time of the more osmotically active and immunomodulatory substance (HTS) suggests that interaction with events occurring around 24 hours after injury is critical. These events may be related to the invasion of leukocytes peaking at 8-24 hours postinjury and/or the peak benefit time of subject rehydration.

Small mammal MRI imaging in spinal cord injury: a novel practical technique for using a 1.5 T MRI.

The field of spinal cord injury research is an active one. The pathophysiology of SCI is not yet entirely revealed. As such, animal models are required for the exploration of new therapies and treatments. We present a novel technique using available hospital MRI machines to examine SCI in a mouse SCI model. The model is a 60 kdyne direct contusion injury in a mouse thoracic spine. No new electronic equipment is required. A 1.5T MRI machine with a human wrist coil is employed. A standard multisection 2D fast spin-echo (FSE) T2-weighted sequence is used for imaging the mouse. The contrast-to-noise ratio (CNR) between the injured and normal area of the spinal cord showed a three-fold increase in the contrast between these two regions. The MRI findings could be correlated with kinematic outcome scores of ambulation, such as BBB or BMS. The ability to follow a SCI in the same animal over time should improve the quality of data while reducing the quantity of animals required in SCI research. It is the aim of the authors to share this non-invasive technique and to make it available to the scientific research community.

Cannabinoid CB(2) receptor activation decreases cerebral infarction in a mouse focal ischemia/reperfusion model.

Cannabinoid CB(2) Receptor (CB(2)) activation has been shown to have immunomodulatory properties without psychotropic effects. The hypothesis of this study is that selective CB(2) agonist treatment can attenuate cerebral ischemia/reperfusion injury. Selective CB(2) agonists (O-3853, O-1966) were administered intravenously 1 h before transient middle cerebral artery occlusion (MCAO) or 10 mins after reperfusion in male mice. Leukocyte/endothelial interactions were evaluated before MCAO, 1 h after MCAO, and 24 h after MCAO via a closed cranial window. Cerebral infarct volume and motor function were determined 24 h after MCAO. Administration of the selective CB(2) agonists significantly decreased cerebral infarction (30%) and improved motor function (P<0.05) after 1 h MCAO followed by 23 h reperfusion in mice. Transient ischemia in untreated animals was associated with a significant increase in leukocyte rolling and adhesion on both venules and arterioles (P<0.05), whereas the enhanced rolling and adhesion were attenuated by both selective CB(2) agonists administered either at 1 h before or after MCAO (P<0.05). CB(2) activation is associated with a reduction in white blood cell rolling and adhesion along cerebral vascular endothelial cells, a reduction in infarct size, and improved motor function after transient focal ischemia.

Neuroendoscopy for spinal disorders: a brief review.

Neuroendoscopy has grown rapidly in the last 20 years as a therapeutic modality for treating a variety of spinal disorders. Spinal endoscopy has been widely used to treat patients with cervical, thoracic, and lumbosacral disorders safely and effectively. Although it is most commonly used with minimally invasive lumbar spine surgery, endoscopy has gained widespread acceptance for the treatment of thoracic disc herniations and for anterior release and rod implantation in the correction of thoracic spinal deformity. The authors review the use of endoscopy in spine surgery and in the treatment of spinal disorders as well as in the treatment of intrathoracic nonspinal lesions. Endoscopy has some significant advantages over open or other minimally invasive techniques in that it can allow for better visualization of the lesion, smaller incision sizes with reduced morbidity and mortality, reduced hospital stays, and ultimately lower cost. In addition, spinal endoscopy allows observers and operating room staff to be more involved in each case and fosters education. Spinal endoscopy, like any novel modality, carries with it additional risks and the surgeon must always be prepared to convert to an open procedure. The learning curve for spinal endoscopy is steep and the procedure should not be attempted alone by a novice surgeon. Nevertheless, with training and experience, the spine surgeon can achieve better outcomes, reduced morbidity, and better cosmesis with spinal endoscopy, and the operating times are comparable to open procedures. As technology evolves and more experience is obtained, neuroendoscopy will likely achieve further roles as a mainstay in spine surgery.