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Pradeep K. Narotam, James R. van Dellen and Keshavlal D. Bhoola

✓ There is frequently a need for dural grafts to cover defects resulting from retraction, shrinkage, or excision following neurosurgical procedures. Several materials have been evaluated both experimentally and clinically, and then discarded. Collagen, in its various forms, continues to be an area of intense interest. In this study the authors examined the suitability of collagen sponge to effect dural repair.

In a 5-year clinical study 102 collagen sponge implants were examined macroscopically and histologically. Graft encapsulation, neomembrane formation, delayed hemorrhage, and foreign body reactions were not found. The porous nature of the collagen sponge encouraged fibroblastic ingrowth and dural repair. Meningocerebral adhesions were present in 11 patients, all of whom had required significant cortical resection or had pia-arachnoid disruption during the initial surgery. Inflammatory cells were seen only in response to infection.

Postoperative cerebrospinal fluid leaks developed in only three of 67 patients who underwent an intradural posterior fossa procedure. In a prospective arm of the study involving 459 patients, the wound infection rate using collagen sponge was 6.1%, which compared favorably (p = 0.67) with the 5.7% rate in a similar group of 637 patients in whom collagen sponge had not been used.

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Pradeep K. Narotam, Sarah M. Pauley and Gregory J. McGinn

Object. Reconstruction after anterior cervical decompression has involved the use of tricortical iliac crest bone or fibular strut grafts, but has been associated with significant morbidity. In this study the authors evaluated the efficacy of titanium mesh cages (TMCs) for stability and fusion following anterior cervical corpectomy.

Methods. Thirty-seven patients were prospectively evaluated during a 4-year period. The majority presented with spinal cord compression (97%) often due to cervical spondylosis (87%). The TMC was filled with iliac crest bone chips or Surgibone and stabilized by anterior cervical plates (ACPs). The changes in settling ratio, coronal and sagittal angles, and sagittal displacement were determined at 3, 6, and 12 months; immediate postoperative radiographs were used as baseline. Flexion—extension radiographs and computerized tomography (CT) scans (obtained at 1 year) were examined to assess stability, fusion, and bone growth within the TMC.

Complications such as settling, telescoping, migration, and pseudarthrosis were not observed. Dynamic radiography revealed spinal stability in all patients. Cage-related complications occurred in 2.7% (TMC malplacement [one patient]), surgery-related complications in 10.8%, and graft-related complications in 21.6%. Evidence of bone growth into the TMC was documented in 16 (95%) of 17 patients on CT scans. The mean cage height—related settling rates were 4.46% at 3 months (31 patients [p = 0.066]), 3.89% at 6 months (28 patients [p = 0.028]), and 4.35% at 1 year (27 patients [p = 0.958]). The mean sagittal displacement changed by 3.9% (23 patients [p = 0.73]). The mean coronal and sagittal angles changed 2.89° (30 patients [p = 0.498]) and 2.09° (29 patients [p = 0.001]) at 1 year, respectively, or at last follow up from baseline. No significant differences in the radiological indices were seen when multilevel vertebrectomy cases were compared with single-level vertebrectomy (p = 0.221), smoking status, or age.

Conclusions. Titanium mesh cages, in combination with ACPs, are safe and effective for vertebral replacement in the cervical spine.

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Narendra Nathoo, Pradeep K. Narotam, Devendra K. Agrawal, Catherine A. Connolly, James R. van Dellen, Gene H. Barnett and Runjan Chetty

Object. Apoptosis has increasingly been implicated in the pathobiology of traumatic brain injury (TBI). The present study was undertaken to confirm the presence of apoptosis in the periischemic zone (PIZ) of traumatic cerebral contusions and to determine the role of apoptosis, if any, in neurological outcome.

Methods. Brain tissue harvested at Wentworth Hospital from the PIZ in 29 patients with traumatic supratentorial contusions was compared with brain tissue resected in patients with epilepsy. Immunohistochemical analyses were performed on the tissues to see if they contained the apoptosis-related proteins p53, bcl-2, bax, and caspase-3. The findings were then correlated to demographic, clinical, surgical, neuroimaging, and outcome data.

In the PIZ significant increases of bax (18-fold; p < 0.005) and caspase-3 (20-fold; p < 0.005) were recorded, whereas bcl-2 was upregulated in only 14 patients (48.3%; 2.9-fold increase) compared with control tissue. Patients in the bcl-2—positive group exhibited improved outcomes at the 18-month follow-up examination despite an older mean age and lower mean admission Glasgow Coma Scale score (p < 0.03). Caspase-3 immunostaining was increased in those patients who died (Glasgow Outcome Scale [GOS] Score 1, 12 patients) when compared with those who experienced a good outcome (GOS Score 4 or 5, 17 patients) (p < 0.005). Regression analysis identified bcl-2—negative status (p < 0.04, odds ratio [OR] 5.5; 95% confidence interval [CI] 1.1–28.4) and caspase-3—positive status (p < 0.01, OR 1.4, 95% CI 1.1—1.8) as independent predictors of poor outcome. No immunostaining for p53 was recorded in the TBI specimens.

Conclusions. The present findings confirm apoptosis in the PIZ of traumatic cerebral contusions and indicate that this form of cell death can influence neurological outcome following a TBI.

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Pradeep K. Narotam, Kesava Reddy, Derek Fewer, Fan Qiao and Narendra Nathoo

Object

The repair of dural defects is controversial in contemporary neurosurgery. To date, collagen-based products remain a continued area of interest in the development of dural grafts. The authors conducted a prospective case–control study in which they evaluated collagen matrix in the repair of dural defects following cranial and spinal surgery by using specific clinical and magnetic resonance (MR) imaging outcome measures.

Methods

Enrolled in the study were 79 patients, 36 male (45.6%) and 43 female (54.4%), with a mean age of 53 ± 15.8 years. The pathological diagnosis was brain tumor in 49 cases (62%), vascular conditions in 16 (20.2%), degenerative spine in 10 (12.7%), trauma in two (2.5%), and other in two (2.5%). Most of the patients underwent supratentorial craniotomy (57; 72.2%), whereas 11 patients (13.9%) each underwent posterior fossa and spinal surgery. Sixty-three patients (79.7%) completed the study, which included clinical and MR imaging evaluations at 3 months postsurgery. There were no cerebrospinal fluid (CSF) leaks or delayed hemorrhages. The neurosurgical wound infection rate was 3.8%: superficial wound infection in two cases and deep infection and brain abscess in one case (recurrent brain tumor following radiation therapy).

Among the 63 patients in whom 3-month postsurgery imaging data were available, asymptomatic small pseudomeningoceles were detected on MR imaging in two (3.2%); a minor subgaleal fluid collection, which resolved spontaneously, was apparent in another patient (1.6%). Nonspecific dural enhancement was demonstrated on images obtained in seven patients (11.1%), and asymptomatic spinal epidural enhancement was observed on images obtained in two of three patients who had undergone lumbar laminectomy for spinal stenosis.

Conclusions

When used as a dural onlay graft, collagen matrix had a 100% CSF containment rate but might be associated with occult radiological abnormalities.

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Pradeep K. Narotam, Varun Puri, John M. Roberts Jr., Charles Taylon, Yashail Vora and Narendra Nathoo

Object

Inappropriate sudden blood pressure (BP) reductions may adversely affect cerebral perfusion. This study explores the effect of nicardipine on regional brain tissue O2 (PbtO2) during treatment of acute hypertensive emergencies.

Methods

A prospective case–control study was performed in 30 patients with neurological conditions and clinically elevated BP. All patients had a parenchymal PbtO2 and intracranial pressure bolt inserted following resuscitation. Using a critical care guide, PbtO2 was optimized. Intravenous nicardipine (5–15 mg/hour) was titrated to systolic BP < 160 mm Hg, diastolic BP < 90 mm Hg, mean arterial BP (MABP) 90–110 mm Hg, and PbtO2 > 20 mm Hg. Physiological parameters—intracranial pressure, PbtO2, central venous pressure, systolic BP, diastolic BP, MABP, fraction of inspired O2, and cerebral perfusion pressure (CPP)—were compared before infusion, at 4 hours, and at 8 hours using a t-test.

Results

Sixty episodes of hypertension were reported in 30 patients (traumatic brain injury in 13 patients; aneurysmal subarachnoid hemorrhage in 11; intracerebral and intraventricular hemorrhage in 3 and 1, respectively; arteriovenous malformation in 1; and hypoxic brain injury in 1). Nicardipine was effective in 87% of the patients (with intravenous β blockers in 4 patients), with a 19.7% reduction in mean 4-hour MABP (115.3 ± 13.1 mm Hg preinfusion vs 92.9 ± 11.40 mm Hg after 4 hours of therapy, p < 0.001). No deleterious effect on mean PbtO2 was recorded (26.74 ± 15.42 mm Hg preinfusion vs 27.68 ± 12.51 mm Hg after 4 hours of therapy, p = 0.883) despite significant reduction in CPP. Less dependence on normobaric hyperoxia was achieved at 8 hours (0.72 ± 0.289 mm Hg preinfusion vs 0.626 ± 0.286 mm Hg after 8 hours of therapy, p < 0.01). Subgroup analysis revealed that 12 patients had low pretreatment PbtO2 (10.30 ± 6.49 mm Hg), with higher CPP (p < 0.001) requiring hyperoxia (p = 0.02). In this group, intravenous nicardipine resulted in an 83% improvement in 4- and 8-hour PbtO2 levels (18.1 ± 11.33 and 19.59 ± 23.68 mm Hg, respectively; p < 0.01) despite significant reductions in both mean MABP (120.6 ± 16.65 vs 95.8 ± 8.3 mm Hg, p < 0.001) and CPP (105.00 ± 20.7 vs 81.2 ± 15.4 mm Hg, p < 0.001).

Conclusions

Intravenous nicardipine is effective for the treatment of hypertensive neurological emergencies and has no adverse effect on PbtO2.

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Pradeep K. Narotam, Fan Qiao and Narendra Nathoo

Object

Complete dural closure is not always possible following posterior fossa surgery, often requiring a graft to secure complete closure. The authors report their experience of using a collagen matrix as an onlay dural graft for repair of a posterior fossa dural defect.

Methods

A retrospective analysis was performed in 52 adult patients who had undergone collagen matrix duraplasty for the posterior fossa. Complications directly related to the dural graft, the presence or absence of hydrocephalus, and the role of closed suction wound drainage in relation to postsurgical pseudomeningoceles were analyzed.

Results

The indication for posterior fossa surgery was tumors in 32 patients, vascular abnormalities in 9 patients, and spontaneous cerebellar hemorrhage in 11 patients. Closed suction wound drainage was used in 23 patients (44.2%). Forty-eight (92.3%) of 52 patients had a dural defect > 2 cm. Nine (81.8%) of 11 patients with hydrocephalus required ventriculoperitoneal shunts. Complications of the surgery included pseudomeningoceles in 2 patients (3.8%; no closed suction wound drainage); superficial wound infections in 1 patient (1.9%; with closed suction wound drainage); and unexplained eosinophilia in 1 patient.

Conclusions

Duraplasty using a collagen matrix is safe and effective in the posterior fossa, and is easy to use and time efficient. Meticulous layered wound closure, the detection and effective control of hydrocephalus, and the use of closed suction wound drainage reduces complications related to collagen matrix duraplasty for the posterior fossa.

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Pradeep K. Narotam, John F. Morrison and Narendra Nathoo

Object

Cerebral ischemia is the leading cause of preventable death in cases of major trauma with severe traumatic brain injury (TBI). Intracranial pressure (ICP) control and cerebral perfusion pressure (CPP) manipulation have significantly reduced the mortality but not the morbidity rate in these patients. In this study, the authors describe their 5-year experience with brain tissue oxygen (PbtO2) monitoring, and the effect of a brain tissue oxygen–directed critical care guide (PbtO2-CCG) on the 6-month clinical outcome (based on the 6-month Glasgow Outcome Scale score) in patients with TBIs.

Methods

One hundred thirty-nine patients admitted to Creighton University Medical Center with major traumatic injuries (Injury Severity Scale [ISS] scores ≥ 16) and TBI underwent prospective evaluation. All patients were treated with a PbtO2-CCG to maintain a brain oxygen level > 20 mm Hg, and control ICP < 20 mm Hg. The role of demographic, clinical, and imaging parameters in the identification of patients at risk for cerebral hypooxygenation and the influence of hypooxygenation on clinical outcome were recorded. Outcomes were compared with those in a historical ICP/CPP patient cohort. Subgroup analysis of severe TBI was performed and compared to data reported in the Traumatic Coma Data Bank.

Results

The majority of injuries were sustained in motor vehicle crashes (63%), and diffuse brain injury was the most common abnormality (58%). Mechanism of injury, severity of TBI, pathological entity, neuroimaging results, and trauma indices were not predictive of ischemia. Factors affecting death included gunshot injury, poor trauma indices, subarachnoid hemorrhage, and coma. After standard resuscitation, 65% of patients had an initially low PbtO2. Data are presented as means ± SDs. Treatment with the PbtO2-CCG resulted in a 44% improvement in mean PbtO2 (16.21 ± 12.30 vs 23.65 ± 14.40 mm Hg; p < 0.001), control of ICP (mean 12.76 ± 6.42 mm Hg), and the maintenance of CPP (mean 76.13 ± 15.37 mm Hg). Persistently low cerebral oxygenation was seen in 37% of patients at 2 hours, 31% at 24 hours, and 18% at 48 hours of treatment. Thus elevated ICP and a persistent low PbtO2 after 2 hours represented increasing odds of death (OR 14.3 at 48 hours). Survivors and patients with good outcomes generally had significantly higher mean daily PbtO2 and CPP values compared to nonsurvivors. Polytrauma, associated with higher ISS scores, presented an increased risk of vegetative outcome (OR 9.0). Compared to the ICP/CPP cohort, the mean Glasgow Outcome Scale score at 6 months in patients treated with PbtO2-CCG was higher (3.55 ± 1.75 vs 2.71 ± 1.65, p < 0.01; OR for good outcome 2.09, 95% CI 1.031–4.24) as was the reduction in mortality rate (25.9 vs 41.50%; relative risk reduction 37%), despite higher ISS scores in the PbtO2 group (31.6 ± 13.4 vs 27.1 ± 8.9; p < 0.05). Subgroup analysis of severe closed TBI revealed a significant relative risk reduction in mortality rate of 37–51% compared with the Traumatic Coma Data Bank data, and an increased OR for good outcome especially in patients with diffuse brain injury without mass lesions (OR 4.9, 95% CI 2.9–8.4).

Conclusions

The prevention and aggressive treatment of cerebral hypooxygenation and control of ICP with a PbtO2-directed protocol reduced the mortality rate after TBI in major trauma, but more importantly, resulted in improved 6-month clinical outcomes over the standard ICP/CPP-directed therapy at the authors' institution.

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Narendra Nathoo, Pradeep K. Narotam, Sameer S. Nadvi and James R. van Dellen