David M. Panczykowski

Comparative effectiveness of using computed tomography alone to exclude cervical spine injuries in obtunded or intubated patients: meta-analysis of 14,327 patients with blunt trauma

OBJECT The current standard of practice for clearance of the cervical spine in obtunded patients suffering blunt trauma is to use CT and an adjuvant imaging modality (such as MR imaging). The objective of this study was to determine the comparative effectiveness of multislice helical CT alone to diagnose acute unstable cervical spine injury following blunt trauma. METHODS The authors performed a meta-analysis of studies comparing modern CT with adjunctive imaging modalities and required that studies present acute traumatic findings as well as treatment for unstable injuries. Study quality, population characteristics, diagnostic protocols, and outcome data were extracted. Positive disease status included all injuries necessitating surgical or orthotic stabilization identified on imaging and/or clinical follow-up. RESULTS Seventeen studies encompassing 14,327 patients met the inclusion criteria. Overall, the sensitivity and specificity for modern CT were both > 99.9% (95% CI 0.99-1.00 and 0.99-1.00, respectively). The negative likelihood ratio of an unstable cervical injury after a CT scan negative for acute injury was < 0.001 (95% CI 0.00-0.01), while the negative predictive value of a normal CT scan was 100% (95% CI 0.96-1.00). Global severity of injury, CT slice thickness, and study quality did not significantly affect accuracy estimates. CONCLUSIONS Modern CT alone is sufficient to detect unstable cervical spine injuries in trauma patients. Adjuvant imaging is unnecessary when the CT scan is negative for acute injury. Results of this meta-analysis strongly show that the cervical collar may be removed from obtunded or intubated trauma patients if a modern CT scan is negative for acute injury.

Prospective Independent Validation of IMPACT Modeling as a Prognostic Tool in Severe Traumatic Brain Injury

Clinical trials in traumatic brain injury (TBI) have been fraught with failure due in part to heterogeneity in pathology and insensitive outcome measurements. The International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) prognostic model has been purposed as a means of risk adjustment and outcome prediction for use in trial design and analysis. The purpose of this study was to evaluate the performance of the IMPACT model in predicting 6-month functional outcome and mortality using prospectively collected data at a large, Level 1 neurotrauma center. This population-based cohort study included all TBI patients ≥14 years of age admitted with a Glasgow Coma Scale (GCS) score of ≤8 (severe TBI) to the University of Pittsburgh Medical Center between July 1994 and May 2009. Clinical data were prospectively collected and linked to 6-month functional outcome (Glasgow Outcome Scale [GOS]) and mortality. The discriminatory power and calibration of the three iterations of the IMPACT model (core, extended, and lab) were assessed using multiple regression analyses and indicated by the area under the receiver operating characteristic curve (AUC). A sample of 587 patients was available for analysis; the mean age was 37.8±17 years. The median 6-month GOS was 3 (IQR 3); 6-month mortality was 41%. The prognostic models were composed of age, motor score, and pupillary reactivity (core model), Marshall grade on head CT and secondary insults (extended), and laboratory values (lab); all of these displayed good prediction ability for unfavorable outcome and mortality (unfavorable outcome AUC=0.76, 0.79, 0.76; mortality AUC=0.78, 0.83, 0.83, respectively). All model iterations displayed adequate calibration for predicting unfavorable outcome and mortality. Prospective, independent validation supports the IMPACT prognostic models prediction of patient 6-month functional status and mortality after severe TBI. The IMPACT prognostic model is an effective instrument to assist TBI study design and analysis.

The use of a hybrid dynamic stabilization and fusion system in the lumbar spine: preliminary experience.

OBJECT The authors report the use and preliminary results of a novel hybrid dynamic stabilization and fusion construct for the surgical treatment of degenerative lumbar spine pathology. METHODS The authors performed a retrospective chart review of all patients who underwent posterior lumbar instrumentation with the Dynesys-to-Optima (DTO) hybrid dynamic stabilization and fusion system. Preoperative symptoms, visual analog scale (VAS) pain scores, perioperative complications, and the need for subsequent revision surgery were recorded. Each patient was then contacted via telephone to determine current symptoms and VAS score. Follow-up was available for 22 of 24 patients, and the follow-up period ranged from 1 to 22 months. Clinical outcome was gauged by comparing VAS scores prior to surgery and at the time of telephone interview. RESULTS A total of 24 consecutive patients underwent lumbar arthrodesis surgery in which the hybrid system was used for adjacent-level dynamic stabilization. The mean preoperative VAS score was 8.8, whereas the mean postoperative VAS score was 5.3. There were five perioperative complications that included 2 durotomies and 2 wound infections. In addition, 1 patient had a symptomatic medially placed pedicle screw that required revision. These complications were not thought to be specific to the DTO system itself. In 3 patients treatment failed, with treatment failure being defined as persistent preoperative symptoms requiring reoperation. CONCLUSIONS The DTO system represents a novel hybrid dynamic stabilization and fusion construct. The technique holds promise as an alternative to multilevel lumbar arthrodesis while potentially decreasing the risk of adjacent-segment disease following lumbar arthrodesis. The technology is still in its infancy and therefore follow-up, when available, remains short. The authors report their preliminary experience using a hybrid system in 24 patients, along with short-interval clinical and radiographic follow-up.

Measurement of the glial fibrillary acidic protein and its breakdown products GFAP-BDP biomarker for the detection of traumatic brain injury compared to computed tomography and magnetic resonance imaging

Glial fibrillary acidic protein and its breakdown products (GFAP-BDP) are brain-specific proteins released into serum as part of the pathophysiological response after traumatic brain injury (TBI). We performed a multi-center trial to validate and characterize the use of GFAP-BDP levels in the diagnosis of intracranial injury in a broad population of patients with a positive clinical screen for head injury. This multi-center, prospective, cohort study included patients 16-93 years of age presenting to three level 1 trauma centers with suspected TBI (loss of consciousness, post-trauma amnesia, and so on). Serum GFAP-BDP levels were drawn within 24 h and analyzed, in a blinded fashion, using sandwich enzyme-linked immunosorbent assay. The ability of GFAP-BDP to predict intracranial injury on admission computed tomography (CT) as well as delayed magnetic resonance imaging was analyzed by multiple regression and assessed by the area under the receiver operating characteristic curve (AUC). Utility of GFAP-BDP to predict injury and reduce unnecessary CT scans was assessed utilizing decision curve analysis. A total of 215 patients were included, of which 83% suffered mild TBI, 4% moderate, and 12% severe; mean age was 42.1±18 years. Evidence of intracranial injury was present in 51% of the sample (median Rotterdam Score, 2; interquartile range, 2). GFAP-BDP demonstrated very good predictive ability (AUC=0.87) and demonstrated significant discrimination of injury severity (odds ratio, 1.45; 95% confidence interval, 1.29-1.64). Use of GFAP-BDP yielded a net benefit above clinical screening alone and a net reduction in unnecessary scans by 12-30%. Used in conjunction with other clinical information, rapid measurement of GFAP-BDP is useful in establishing or excluding the diagnosis of radiographically apparent intracranial injury throughout the spectrum of TBI. As an adjunct to current screening practices, GFAP-BDP may help avoid unnecessary CT scans without sacrificing sensitivity (Registry: ClinicalTrials.gov Identifier: NCT01565551).

Premorbid oral antithrombotic therapy and risk for reaccumulation, reoperation, and mortality in acute subdural hematomas.

OBJECT Acute subdural hematomas (SDHs) impart serious morbidity and mortality on the elderly population, with only 5% of those older than 65 years of age attaining functional independence. Despite its widespread use, oral antithrombotic therapy (OAT) in the context of acute SDH has not been extensively studied. The authors sought to evaluate the impact of premorbid OAT on recurrence of SDH, radiographic outcome, and mortality in patients undergoing surgical evacuation of an acute SDH. METHODS The authors conducted a retrospective comparative cohort study reviewing all surgically treated cases of acute SDH at their institution between September 2005 and December 2008. They assessed baseline demographics, coagulation parameters, surgical management, and clinical course. Study end points included additional craniotomy for SDH reaccumulation, follow-up Rotterdam score, recurrent SDH volumetric analysis, Glasgow Outcome Score, and death. RESULTS A total of 300 patients with acute SDH treated by craniotomy were assessed. Of these patients, 49% (148 patients) were receiving OAT. Of those who were on a regimen of OAT, 49% were taking warfarin (mean international normalized ratio 3.1 ± 1.8), 31% were receiving antiplatelet therapy, and 20% were on a regimen of a combination of agents. On presentation, 72% of those using OAT received reversal agents. Recurrence of SDH necessitating additional evacuation was not significantly different with respect to premorbid OAT status (13% vs 14%). Patients with a history of OAT did not demonstrate a significant difference in Rotterdam score (2 vs 2), recurrent SDH volume (24.1 vs 19.6 cm(3)), GOS score (4 vs 3), or mortality (21% vs 24%). These findings remained stable after controlling for age, injury mechanism, and injury severity. CONCLUSIONS Premorbid OAT was not a significant risk factor for recurrence of SDH necessitating additional evacuation following acute SDH. Additionally, postoperative Rotterdam score, volume of SDH reaccumulation, and overall mortality were not predicted by antithrombotic history. While premorbid use may predispose the patient to an SDH, OAT does not increase the risk of morbidity or mortality following surgical intervention.

Prealbumin as a Serum Biomarker of Impaired Perioperative Nutritional Status and Risk for Surgical Site Infection after Spine Surgery

INTRODUCTION Impaired perioperative nutritional status has been shown to be an important predictor of surgical morbidity and is the earliest marker of nutritional deficiency. No study, however, has examined serum prealbumin as a surrogate marker of nutritional status in patients undergoing spine surgery. METHODS We performed a retrospective review of all patients who developed a postoperative deep wound infection after undergoing spine surgery at the University of Pittsburgh Medical Center from January 2008 through December 2011. Demographics, preoperative diagnosis, type of surgery, perioperative serum prealbumin level, time to infection, number and type of debridement procedures, and length of hospital stay were recorded. RESULTS A total of 83 patients had prealbumin levels available at the time of presentation of infection. Mean patient age was 56 years, and 71% were women. Surgical treatment for the infection required between 1 and 13 debridements, and 21 (25%) of the 83 patients who had instrumentation placed at the time of the initial surgery required removal of their instrumentation. Inpatient hospitalizations were extended by an average of 13 days. Prealbumin levels were below normal in 82 (99%) of the 83 patients; levels were < 7 mg/dL in 24 patients, between 7 and 11 mg/dL in 32 patients, and between 11 and 19 mg/dL in 26 patients. CONCLUSIONS All patients except one who developed postoperative deep wound infection after spine surgery had serum prealbumin levels in the malnutrition range at the time of presentation. The current study suggests serum prealbumin levels may be an inexpensive screening biomarker for nutritional status and risk stratification for postoperative infection after spine surgery.

Lifetime Attributable Risk of Cancer From CT Among Patients Surviving Severe Traumatic Brain Injury

OBJECTIVE The purpose of this study was to determine the lifetime attributable risk of cancer from CT among patients surviving severe traumatic brain injury. MATERIALS AND METHODS A retrospective cross-sectional study was conducted with prospectively collected data on patients 16 years old and older admitted with a Glasgow coma scale score of 8 or less to a single level 1 trauma center from 2007 to 2010. The effective dose of each CT examination the patients underwent was predicted with literature-accepted effective dose values of standard helical CT protocols. The lifetime attributable risk of cancer and related mortality incurred as a result of CT were estimated with the cumulative effective dose incurred from the time of injury to a 1-year follow-up evaluation and with the approach established by the Biologic Effects of Ionizing Radiation VII report. RESULTS The average patient was a 34-year-old man. The median number of CT examinations received during the first 12 months after injury was 20, and the average cumulative effective dose was 87 ± 45 mSv. This resulted in increases in the lifetime incidence of all cancer types from 45.5% to 46.3% and in the lifetime incidence of cancer-related mortality from 22.1% to 22.5%. CONCLUSION Radiation exposure from the use of CT in the evaluation and management of severe traumatic brain injury causes negligible increases in lifetime attributable risk of cancer and cancer-related mortality. Treating physicians should not allow the concern for future risk of radiation-induced cancer to influence decisions regarding radiographic evaluation in the acute treatment of traumatic brain injury.

Decompressive Hemicraniectomy, Strokectomy, or Both in the Treatment of Malignant Middle Cerebral Artery Syndrome

OBJECTIVE We sought to evaluate the impact of a craniotomy for strokectomy (CS) with bone replacement, decompressive hemicraniectomy (DHC), or DHC with a strokectomy (DHC+S) on outcome after malignant supratentorial infarction. METHODS We conducted a retrospective cohort study of cases of malignant supratentorial infarction treated by CS (n = 18), DHC (n = 17), or DHC+S (n = 33) at our institution from 2002 to 2008. End points included functional outcome measured by the modified Rankin Scale and incidence of mortality at 1 year. RESULTS Mean age, gender, side, vessel, and time from ictus to surgery were not statistically different between treatment groups. Stroke volume was significantly higher in the CS group. Operative time and blood loss were significantly higher in the DHC+S group. At 1 year, the median modified Rankin Scale score was 4 and overall survival was 71%. Functional outcomes and mortality for both the CS and DHC+S groups were not significantly different from the DHC group (P = 0.24). After adjusting for patient age, stroke volume, and time to surgery, there was no significant difference in outcome. CONCLUSION In patients with malignant supratentorial infarction, a strokectomy alone may be equivalent to a decompressive hemicraniectomy with or without brain resection.

Prophylactic Antiepileptics and Seizure Incidence Following Subarachnoid Hemorrhage A Propensity Score–Matched Analysis

Background and Purpose— The utility of prophylactic antiepileptic drug (AED) administration after spontaneous subarachnoid hemorrhage remains controversial. AEDs have not clearly been associated with a reduction in seizure incidence and have been associated with both neurological worsening and delayed functional recovery in this setting. Methods— We retrospectively analyzed a prospectively collected database of subarachnoid hemorrhage patients admitted to our institution between 2005 and 2010. Between 2005 and 2007, all patients received prophylactic AEDs upon admission. After 2007, no patients received prophylactic AEDs or had AEDs immediately discontinued if initiated at an outside hospital. A propensity score–matched analysis was then performed to compare the development of clinical and electrographic seizures in these 2 populations. Results— Three hundred and fifty three patients with spontaneous subarachnoid hemorrhage were analyzed, 43% of whom were treated with prophylactic AEDs upon admission. Overall, 10% of patients suffered clinical and electrographic seizures, most frequently occurring within 24 hours of ictus (47%). The incidence of seizures did not vary significantly based on the use of prophylactic AEDs (11 versus 8%; P=0.33). Propensity score–matched analyses suggest that patients receiving prophylactic AEDs had a similar likelihood of suffering seizures as those who did not (P=0.49). Conclusions— Propensity score–matched analysis suggests that prophylactic AEDs do not significantly reduce the risk of seizure occurrence in patients with spontaneous subarachnoid hemorrhage.

Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans.

E arly attempts at stimulation of the central nervous system to modulate function date back to ancient Rome, but it was Sir Victor Horsley who is credited with first utilizing intraoperative electrical stimulation for cortical mapping. Although noninvasive methods of stimulation have been developed, these suffer from poor spatial resolution. Consequently, attempts at neuromodulation often impact the activity of not only the intended target but also surrounding brain. The effects of focused ultrasound (FUS) on neuronal activity have been studied since the 1920s, and in animals have been shown to modulate activity of peripheral nerves, the retina, spinal reflexes, hippocampus, and motor cortex. Unlike high intensity, continuous ultrasound (US), FUS can exert nondestructive mechanical pressure effects on cellular membranes and ion channels without producing cavitation and thermal injury. Animal studies have demonstrated the ability of FUS to reversibly suppress visual evoked potentials, modulate activity of the frontal eye fields, and disrupt seizure activity, all in the absence of cellular damage. In a recent report, investigators sought to establish the ability of transcranial focused ultrasound (tFUS) to modulate brain activity in the human primary somatosensory cortex. Legon et al employed a single-element tFUS transducer to transmit a 0.5 MHz pulsed wave for 500 ms. The acoustic power of the tFUS waveform used was well below the maximum recommended limit for diagnostic imaging applications. The authors first characterized the acoustic pressure field emitted from the tFUS transducer in an acoustic test-tank. Next, a magnetic resonance imaging-based 3-D simulation model of a human head was created to estimate acoustic field distribution in the brain during tFUS.Ultimately the authors assessed the neuromodulating influence and spatial resolution of tFUS targeted to Brodmann area 3b (anterior bank of the postcentral gyrus facing the central sulcus) by examining effects on somatosensory evoked potentials (SEPs) and sensory detection thresholds via within-subjects, sham-controlled, blinded design study of 12 volunteers. Primary endpoints included amplitude of short-latency and late-onset evoked potentials by median nerve stimulation, as well as two-point and frequency discrimination tasks. The focal volume of the ellipsoid acoustic beam produced was 0.21cm3 at 50% maximum intensity line and demonstrated spatial resolution of 4.9mm laterally and 18mm axially when focused through the human skull. Electrophysiologic studies demonstrated that tFUS targeted to Brodmann area 3b significantly reduced the amplitude of short-latency and late-onset evoked cortical activity elicited by median-nerve SEPs. The effects of tFUS on SEP activity were abolished when targeted to brain regions 1 cm posterior or 1 cm anterior to the postcentral gyrus. Functional investigations revealed that tFUS targeted to somatosensory cortex significantly enhanced discrimination of pins at closer distances as well as frequency of air puffs, without affecting response bias or task attention. Additionally, the authors noted that volunteers did not report thermal or mechanical sensations due to tFUS transmission through the scalp. Similarly, there were no reports of perceptual differences between the sham and tFUS conditions. These data demonstrate that a pulsed acoustic beam created by a single-element 0.5-MHz tFUS transducer for 500 ms can be used to transiently and noninvasively modulate neuronal activity in the cortex of humans. tFUS may transiently shift the balance of neuronal activity in favor of local inhibition, perhaps through either dampening thalamocortical excitation or increasing interneuron inhibitory firing. One hypothesis for the paradoxical improvement in somatosensory discrimination provided by the authors is through filtering by local inhibition. In other words, the inhibition produced by tFUSmay reduce spatial spread of cortical excitation resulting in restricted neuronal population activation and a more precise cortical representation of tactile stimuli. Although this study provided evidence that the influence of tFUS can be restricted to discrete modules of cortex, it did not elucidate which cellular structures tFUS most affects. Further studies are needed to characterizewhether neurophysiologic effects vary according to anatomic location and/or cytoarchitectonic division. One of the most enticing applications of tFUS is the possibility of noninvasive, functional brain mapping of both cortical and sub-cortical structures and circuits. Subablative sonication targeting the ventral intermediate region of the thalamus has already been used to provide functional target confirmation prior to lesioning with MR guided high-intensity FUS. However, the current study highlights the nondestructive capabilities of tFUS and inspires exploration of potential applications in both the research and clinical settings.