Ectopic Cavernous Sinus Microprolactinoma Treated Medically.

Ectopic prolactin-secreting microadenomas are rare and management is often surgical in contrast to intrasellar pituitary prolactin-secreting microadenomas. We present a case of ectopic dopamine-resistant microprolactinoma treated with cabergoline which led to symptom resolution, hormonal remission, and cystic degeneration of the tumor. A 30-year-old active duty male presented with a chief complaint of inability to maintain an erection for 6 months. Initial workup revealed suppressed serum testosterone of 128.60 ng/ml with an elevated prolactin level at 275.10 ng/ml. Pituitary magnetic resonance imaging showed a small mass measuring 9 mm in the left cavernous sinus. Medical management was initiated with cabergoline, which was titrated over the course of a year from 0.5 mg a week to 3.5 mg a week at its peak before being weaned off completely at 54 months. After treatment, the patient's symptoms resolved, his prolactin decreased to 29.5 ng/ml, near-normal, and his tumor had decreased size with cystic degeneration. Management for any prolactinoma has three primary goals: remittance of symptoms, decrease in prolactin levels, and decrease in tumor size. These are achieved through primarily medical management or surgery. Even though ectopic microprolactinomas are still frequently addressed surgically, this case shows that medical therapy can successfully treat ectopic prolactin-secreting pituitary microadenomas even in cases of dopamine resistance.

Unique Presentation of Thyrotoxic Periodic Paralysis With Urticarial Dermographia.

Thyrotoxic periodic paralysis (TPP) is an acute complication of hyperthyroidism. Thyrotoxic periodic paralysis is treatable, and the management consists of potassium correction, beta-blockers, and antithyroid drug (ATD) therapy. While TPP is well described in the literature, we describe a case of TPP with urticarial dermographia (UD) that resolved with a short course of antihistamines while continuing ATD therapy. To the best of our knowledge, this is the first reported case of UD after methimazole (MMI) therapy in a TPP patient. A 25-year-old Cambodian active duty male with no significant past medical history presented to the emergency department with acute loss of lower extremity muscle tone with hypokalemia in the setting of previously undiagnosed Graves' disease (GD). He was started on MMI but within 2 weeks developed a rash consistent with UD. This was successfully treated with a second-generation antihistamine while continuing his MMI. Thyrotoxic periodic paralysis is primarily treated by controlling the underlying thyroid disease causing paralysis. Methimazole is commonly chosen as a treatment due to its rapid efficacy and long duration of action. However, adverse effects like UD can occur. Current recommendations are that minor cutaneous reactions can be treated with antihistamines for the management of Graves' disease. However, this case and others show that even moderate reactions can be managed in this manner. In a patient with TPP with UD after treatment with MMI, it is reasonable to attempt a trial of antihistamine before changing to another ATD.

Case Report: COVID Associated Pancytopenia Unmasking Previously Undiagnosed Pernicious Anemia.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated pancytopenia is a known but rare complication of COVID-19 syndrome that is not well described in literature. Severe acute respiratory syndrome coronavirus 2 has shown the potential to affect any organ including the bone marrow, which then results in a decrease in all three blood cell lines. These cases usually resolve with the passage of time and treatment of underlying risk factors. As COVID pneumonia rates continue to increase worldwide, it is crucial to be able to recognize this complication. Additionally, deeper investigation into patient's response to COVID infection can be complicated by unexpected underlying disease. We report a case of a symptomatic 24-year-old active duty male in Hawaii with post-COVID pancytopenia that was found to have previously undiagnosed pernicious anemia and his response to standard treatment.

The Assessment of Visual Fields in Infants Using Saccadic Vector Optokinetic Perimetry (SVOP): A Feasibility Study.

Purpose: To examine the feasibility of saccadic vector optokinetic perimetry (SVOP), an automated eye tracking perimeter, as a tool for visual field (VF) assessment in infants. Methods: Thirteen healthy infants aged between 3.5 and 12.0 months were tested binocularly using an adapted SVOP protocol. SVOP uses eye tracking technology to measure gaze responses to stimuli presented on a computer screen. Modifications of SVOP for testing infants included adjusting the fixation target to display a short animation, increasing the stimulus size to equivalent to Goldmann V, and introducing a tiered test pattern strategy. Binocular, single-quadrant confrontation VF testing and Keeler preferential looking cards visual acuity testing was also performed. Results: Using multiple test attempts when required, all but the youngest infant (12 of 13 [92.3%]) successfully completed a 4-point screening test. Seven infants (53.8%) successfully completed the 12-point test, four (30.8%) successfully completed the 20-point test, and three (23.1%) successfully completed the 40-point test. The effect of multiple test attempts and the complexity of the test pattern (number of test points) on performance was investigated, including test completion rate, percentage of correctly seen stimuli, and average time per tested stimulus. Conclusions: The modified SVOP test strategy allowed successful assessment of binocular VFs in healthy infants. Future data collection from larger cohorts of infants is needed to derive normative limits of detection and assess accuracy in detecting and monitoring infant VF abnormalities. Translational Relevance: Eye tracking perimetry may provide a useful method of automated VF assessment in infants.

A case control study examining the feasibility of using eye tracking perimetry to differentiate patients with glaucoma from healthy controls.

To explore the feasibility of using Saccadic Vector Optokinetic Perimetry (SVOP) to differentiate glaucomatous and healthy eyes. A prospective case-control study was performed using a convenience sample recruited from a single university glaucoma clinic and a group of healthy controls. SVOP and standard automated perimetry (SAP) was performed with testing order randomised. The reference standard was a diagnosis of glaucoma based a comprehensive ophthalmic examination and abnormality on standard automated perimetry (SAP). The index test was SVOP. 31 patients with glaucoma and 24 healthy subjects were included. Mean SAP mean deviation (MD) in those with glaucoma was - 8.7 ± 7.4 dB, with mean SAP and SVOP sensitivities of 23.3 ± 0.9 dB and 22.1 ± 4.3 dB respectively. Participants with glaucoma were significantly older. On average, SAP sensitivity was 1.2 ± 1.4 dB higher than SVOP (95% limits of agreement = - 1.6 to 4.0 dB). SVOP sensitivity had good ability to differentiate healthy and glaucomatous eyes with a 95% CI for area under the curve (AUC) of 0.84 to 0.96, similar to the performance of SAP sensitivity (95% CI 0.86 to 0.97, P = 0.60). For 80% specificity, SVOP had a 95% CI sensitivity of 75.7% to 94.8% compared to 77.8% to 96.0% for SAP. SVOP took considerably longer to perform (514 ± 54 s compared to 267 ± 76 s for SAP). Eye tracking perimetry may be useful for detection of glaucoma but further studies are needed to evaluate SVOP within its intended sphere of use, using an appropriate design and independent reference standard.

Development of an Age-corrected Normative Database for Saccadic Vector Optokinetic Perimetry (SVOP).

PRECIS: Normal age-corrected threshold sensitivity values were determined for a new eye tracking perimeter and compared with standard automated perimetry (SAP). PURPOSE: The purpose of this study was to determine threshold visual field sensitivities in normal subjects performing saccadic vector optokinetic perimetry (SVOP), a new eye tracking perimeter. PATIENTS AND METHODS: A total of 113 healthy participants performed SVOP and SAP in both eyes with the order of testing randomized. The relationship between SAP and SVOP sensitivity was examined using Bland-Altman plots and 95% limits of agreement. The relationship between sensitivity and age was examined by pointwise linear regression and age-corrected normal threshold sensitivities were calculated. RESULTS: After excluding unreliable tests, 97 participants with a mean age of 65.9±10.1 years were included. Average SAP mean deviation was -0.87±1.56 dB, SAP sensitivity was 29.20±1.68 dB and SVOP sensitivity was 32.18±1.96 dB. SVOP had a longer test duration (431±110 compared with 307±42 seconds for SAP, P<0.001). On average, the mean sensitivity obtained using SVOP was 2.98 dB higher than average SAP sensitivity, with 95% limits of agreement of -0.11 to 6.15 dB. For each decade older, SAP sensitivity decreased by 0.93 dB (95% confidence interval: 1.21 to 0.64) and SVOP sensitivity decreased by 1.15 dB (95% confidence interval: 1.47 to 0.84). CONCLUSIONS: The results provide age-corrected normative values for threshold sensitivities from SVOP. Overall, SVOP provided a similar shaped hill of vision as SAP however threshold sensitivities were higher, meaning results are not interchangeable.

Speed and accuracy of saccades in patients with glaucoma evaluated using an eye tracking perimeter.

BACKGROUND: To examine the speed and accuracy of saccadic eye movements during a novel eye tracking threshold visual field assessment and determine whether eye movement parameters may improve ability to detect glaucoma. METHODS: A prospective study including both eyes of 31 patients with glaucoma and 23 controls. Standard automated perimetry (SAP) and eye tracking perimetry (saccadic vector optokinetic perimetry, SVOP) was performed. SVOP provided data on threshold sensitivity, saccade latency, and two measures of accuracy of saccades (direction bias and amplitude bias). The relationship between eye movement parameters and severity of glaucoma was examined and Receiver Operating Characteristic curves were used to assess ability to detect glaucoma. RESULTS: Patients with glaucoma had significantly slower saccades (602.9 ± 50.0 ms versus 578.3 ± 44.6 ms for controls, P = 0.009) and reduced saccade accuracy (direction bias = 7.4 ± 1.8 versus 6.5 ± 1.5 degrees, P = 0.006). There was a significant slowing of saccades and saccades became less accurate with worsening SAP sensitivity. Slower saccades were associated with increased odds of glaucoma; however, the AUC for saccade latency was only 0.635 compared to 0.914 for SVOP sensitivity. CONCLUSION: Patients with glaucoma had significant differences in eye movements compared to healthy subjects, with a relationship between slower and less accurate eye movements and worse glaucoma severity. However, in a multivariable model, eye movement parameters were not of additional benefit in differentiating eyes with glaucoma from healthy controls.

Resolution patterns and duration of retinal haemorrhages measured by two-dimensional retinal area pixel counts from sequential retinal imaging in childhood encephalopathies: a morphometric study.

OBJECTIVE: To determine the time to resolution of different-layered retinal haemorrhages (RHs), and to describe the main patterns of their resolution in a group of children with encephalopathies. METHODS AND ANALYSIS: From a prospective study of 114 children with traumatic and non-traumatic encephalopathies, 429 selected individual RHs (iRHs) from 18 children were serially imaged from admission using a RetCam. Photoshop and Scion Imaging software allowed calculation of RH area in pixels. RESULTS: Two patterns of the resolution were recognised on the basis of area measurements: a progressive decrease (pattern A, 60% of iRHs), and a form of asymmetrical decay in which iRHs first increased in size before then progressively decreasing (pattern B, 35% of iRHs). Within the pattern A group, the Kaplan-Meier median survival time (MST) (95% CI) was 10 (9.3 to 10.7) days for intra-RHs (IRHs) and 38 (10.8 to 65.2) days for pre-RHs (PRHs), log rank (Mantel-Cox) p=0.001. The mean percentage reduction in area per day was 12.5% for all iRHs, 14.5% for IRHs and 6.3% for PRHs. CONCLUSION: Serial area measurements of iRHs revealed that 35% haemorrhages became temporarily larger before decreasing to resolution. Serially imaged selected RHs showed a longer MST for PRHs than for IRHs.

Detection and characterisation of visual field defects using Saccadic Vector Optokinetic Perimetry in children with brain tumours.

PURPOSE: To determine the ability of Saccadic Vector Optokinetic Perimetry (SVOP) to detect and characterise visual field defects in children with brain tumours using eye-tracking technology, as current techniques for assessment of visual fields in young children can be subjective and lack useful detail. METHODS: Case-series study of children receiving treatment and follow-up for brain tumours at the Royal Hospital for Sick Children in Edinburgh from April 2008 to August 2013. Patients underwent SVOP testing and the results were compared with clinically expected visual field patterns determined by a consensus panel after review of clinical findings, neuroimaging, and where possible other forms of visual field assessment. RESULTS: Sixteen patients participated in this study (mean age of 7.2 years; range 2.9-15 years; 7 male, 9 female). Twelve children (75%) successfully performed SVOP testing. SVOP had a sensitivity of 100% and a specificity of 50% (positive predictive value of 80% and negative predictive value of 100%). In the true positive and true negative SVOP results, the characteristics of the SVOP plots showed agreement with the expected visual field. Six patients were able to perform both SVOP and Goldmann perimetry, these demonstrated similar visual fields in every case. CONCLUSION: SVOP is a highly sensitive test that may prove to be extremely useful for assessing the visual field in young children with brain tumours, as it is able to characterise the central 30° of visual field in greater detail than previously possible with older techniques.

Comparison of Saccadic Vector Optokinetic Perimetry and Standard Automated Perimetry in Glaucoma. Part I: Threshold Values and Repeatability.

PURPOSE: We evaluated threshold saccadic vector optokinetic perimetry (SVOP) and compared results to standard automated perimetry (SAP). METHODS: A cross-sectional study was done including 162 subjects (103 with glaucoma and 59 healthy subjects) recruited at a university hospital. All subjects underwent SAP and threshold SVOP. SVOP uses an eye tracker to monitor eye movement responses to stimuli and determines if stimuli have been perceived based on the vector of the gaze response. The test pattern used was equivalent to SAP 24-2 and stimuli were presented at Goldmann III. Average and pointwise sensitivity values obtained from both tests were compared using Pearson's correlation coefficient. Two versions of SVOP were evaluated. RESULTS: A total of 124 tests were performed with SAP and SVOP version 2. There was excellent agreement between mean threshold values obtained using SVOP and SAP (r = 0.95, P < 0.001). Excluding the blind spot, correlation between SVOP and SAP individual test point sensitivity ranged from 0.61 to 0.90, with 48 of 54 (89%) test points > 0.70. Overall SVOP showed good repeatability with a Pearson correlation of 0.88. The repeatability on a point-by-point basis ranged from 0.66 to 0.98, with 45 of 54 points (83%) > 0.80. Repeatability of SAP was 0.87, ranging from 0.69 to 0.96, with 47 of 54 (87%) points > 0.80. CONCLUSION: Eye-tracking perimetry is repeatable and compares well with the current gold standard of SAP. The technique has advantages over conventional perimetry and could be useful for evaluating glaucomatous visual field loss, particularly in patients who may struggle with conventional perimetry. TRANSLATIONAL RELEVANCE: Suprathreshold SVOP already is in the field. To our knowledge, this is the first report of threshold SVOP and provides a benchmark for future iterations.

Comparison of Threshold Saccadic Vector Optokinetic Perimetry (SVOP) and Standard Automated Perimetry (SAP) in Glaucoma. Part II: Patterns of Visual Field Loss and Acceptability.

PURPOSE: We compared patterns of visual field loss detected by standard automated perimetry (SAP) to saccadic vector optokinetic perimetry (SVOP) and examined patient perceptions of each test. METHODS: A cross-sectional study was done of 58 healthy subjects and 103 with glaucoma who were tested using SAP and two versions of SVOP (v1 and v2). Visual fields from both devices were categorized by masked graders as: 0, normal; 1, paracentral defect; 2, nasal step; 3, arcuate defect; 4, altitudinal; 5, biarcuate; and 6, end-stage field loss. SVOP and SAP classifications were cross-tabulated. Subjects completed a questionnaire on their opinions of each test. RESULTS: We analyzed 142 (v1) and 111 (v2) SVOP and SAP test pairs. SVOP v2 had a sensitivity of 97.7% and specificity of 77.9% for identifying normal versus abnormal visual fields. SAP and SVOP v2 classifications showed complete agreement in 54% of glaucoma patients, with a further 23% disagreeing by one category. On repeat testing, 86% of SVOP v2 classifications agreed with the previous test, compared to 91% of SAP classifications; 71% of subjects preferred SVOP compared to 20% who preferred SAP. CONCLUSIONS: Eye-tracking perimetry can be used to obtain threshold visual field sensitivity values in patients with glaucoma and produce maps of visual field defects, with patterns exhibiting close agreement to SAP. Patients preferred eye-tracking perimetry compared to SAP. TRANSLATIONAL RELEVANCE: This first report of threshold eye tracking perimetry shows good agreement with conventional automated perimetry and provides a benchmark for future iterations.

Raised intracranial pressure and retinal haemorrhages in childhood encephalopathies.

AIM: To explore the relationship between raised intracranial pressure (RICP) and retinal haemorrhages in traumatic and non-traumatic childhood encephalopathies. METHOD: A prospective study of 112 children (35 females and 77 males, age range 0.01mo-17y 8.3mo; mean 5y 8.6mo, median 4y 5.6mo) included 57 accidental traumatic brain injuries (ATBIs), 21 inflicted traumatic brain injuries (ITBIs), and 34 non-traumatic encephalopathy cases. Measurements included intracranial pressure (ICP), cerebral perfusion pressure, pressure-time index of ICP, and number, zone, and layer of retinal haemorrhages on retinal imaging. RESULTS: Group I had measured elevated ICP (n=42), Group II had clinical and/or radiological signs of RICP (n=21), and Group III had normal ICP (n=49). In the combined Groups I and II, 38% had retinal haemorrhages. Multiple logistic regression confirmed that the presence of retinal haemorrhages was significantly related to the presence of RICP independent of age and aetiology; however, the occurrence and overall numbers were not significantly related to the specific ICP level. The numbers of intraretinal (nerve-fibre layer and dot blot) retinal haemorrhages were significantly greater in those with RICP. The ITBI population was significantly different from the other combined aetiological categories. INTERPRETATION: The study results indicate a complex RICP/retinal haemorrhage relationship. There was no evidence of existing retinal haemorrhages being exacerbated or new retinal haemorrhages developing during periods of confirmed RICP.

Feasibility, Accuracy, and Repeatability of Suprathreshold Saccadic Vector Optokinetic Perimetry.

PURPOSE: To evaluate feasibility, accuracy, and repeatability of suprathreshold Saccadic Vector Optokinetic Perimetry (SVOP) by comparison with Humphrey Field Analyzer (HFA) perimetry. METHODS: The subjects included children with suspected field defects (n = 10, age 5-15 years), adults with field defects (n = 33, age 39-78 years), healthy children (n = 12, age 6-14 years), and healthy adults (n = 30, age 16-61 years). The test protocol comprised repeat suprathreshold SVOP and HFA testing with the C-40 test pattern. Feasibility was assessed by protocol completeness. Sensitivity, specificity, and accuracy of SVOP was established by comparison with reliable HFA tests in two ways: (1) visual field pattern results (normal/abnormal), and (2) individual test point outcomes (seen/unseen). Repeatability of each test type was assessed using Cohen's kappa coefficient. RESULTS: Of subjects, 82% completed a full protocol. Poor reliability of HFA testing in child patients limited the robustness of comparisons in this group. Sensitivity, specificity, and accuracy across all groups when analyzing the visual field pattern results was 90.9%, 88.5%, and 89.0%, respectively, and was 69.1%, 96.9%, and 95.0%, respectively, when analyzing the individual test points. Cohen's kappa coefficient for repeatability of SVOP and HFA was excellent (0.87 and 0.88, respectively) when assessing visual field pattern results, and substantial (0.62 and 0.74, respectively) when assessing test point outcomes. CONCLUSIONS: SVOP was accurate in this group of adults. Further studies are required to assess SVOP in child patient groups. TRANSLATIONAL RELEVANCE: SVOP technology is still in its infancy but is used in a number of centers. It will undergo iterative improvements and this study provides a benchmark for future iterations.

Correcting LCD luminance non-uniformity for threshold Saccadic Vector Optokinetic Perimetry (SVOP).

The accurate assessment of visual field function can provide valuable information on a range of visual disorders. Saccadic Vector Optokinetic Perimetry (SVOP) is a novel instrument for measuring supra-threshold visual fields in young children who are otherwise unable to perform Automated Static Perimetry (ASP). However, limitations in Liquid Crystal Display (LCD) technology restrict the ability of SVOP to determine threshold values at various points in the visual field, often required in detailed perimetry examinations. This paper introduces a purpose-specific LCD luminance non-uniformity compensation approach to address this limitation. Thorough quantitative evaluation identifies the effectiveness of the proposed approach in (i) compensating for luminance non-uniformities across an LCD, and (ii) enabling SVOP to perform accurate and precise threshold visual field tests. The findings demonstrate that SVOP provides a promising alternative to the current threshold ASP standard (Humphrey Field Analyser).

Saccadic Vector Optokinetic Perimetry (SVOP): a novel technique for automated static perimetry in children using eye tracking.

Perimetry is essential for identifying visual field defects due to disorders of the eye and brain. However, young children are often unable to reliably perform the preferred method of visual field assessment known as automated static perimetry (ASP). This paper introduces a novel method of ASP specifically developed for children called Saccadic Vector Optokinetic Perimetry (SVOP). SVOP uses eye tracking to detect the natural saccadic eye response of gaze orientation towards visual field stimuli if they are seen. In this paper, the direction and magnitude of a sample of subject gaze responses to visual field stimuli is used to construct a software decision algorithm for use in SVOP. SVOP was clinically evaluated in a group of 24 subjects, comprising children and adults, with and without visual field defects, by comparison with an equivalent test on the Humphrey Field Analyser (HFA). SVOP provides promising visual field test results when compared with the reference HFA test, and has proven extremely useful in detecting visual field defects in children unable to perform traditional ASP.

Prediction of inflicted brain injury in infants and children using retinal imaging.

BACKGROUND: Retinal hemorrhages (RHs) occur in inflicted traumatic brain injury (ITBI), accidental traumatic brain injury (ATBI), and some medical conditions, although the reported number, distribution, type, and frequency vary greatly between these different etiologies. We hypothesize that these RH characteristics reliably help to distinguish ITBI from ATBI and nontraumatic etiologies. METHODS: A 6-year prospective observational study using wide-field retinal imaging (RetCam) was conducted within 24 hours of admission to PICU, on serially recruited children with traumatic and nontraumatic encephalopathies. "Definite" and "probable" ITBI cases were confirmed by multiagency child protection case conferences. Image analysis used digital color and grayscale images for retinal "zoning" and "layering" of hemorrhages. RESULTS: Significant differences were found between the mean numbers of hemorrhages in ATBI/ITBI, and ITBI/nontraumatic etiologies for the 3 retinal zones (range, P = .003-.009) and for the dot-blot hemorrhages (range P = .001-.002). The mean numbers of RHs per ITBI patient in the peripapillary, macula, and peripheral zones were 14, 28, and 31 respectively. RHs in ATBI were near the optic disc and more superficial than in ITBI, where hemorrhages involved deeper layers (range, P = .003-.039) and were more peripheral (P = .03). The positive predictive value for ITBI in children <3 years with >25 dot-blot (intraretinal) hemorrhages was 93%. CONCLUSIONS: This prospective study, which included all potential causes of RHs, with objective retinal methodology, has confirmed that a young age and a high dot-blot count are strong predictors of ITBI. This high predictive value may support medicolegal deliberations.

An inter-observer and intra-observer study of a classification of RetCam images of retinal haemorrhages in children.

BACKGROUND: There is currently no universally accepted classification of childhood retinal haemorrhages. AIM: To measure the inter- and intra-observer agreement of clinical classifications of retinal haemorrhages in children. METHODS: Four examiners (two consultant ophthalmologists and two other clinicians) were shown 142 retinal haemorrhages on 31 RetCam photographs. The retinal haemorrhages were from children with accidental or abusive head injury, or other encephalopathies, and included retinal haemorrhages of different ages. Specified haemorrhages were initially classified by each examiner according to their clinical understanding. Altogether, 26 haemorrhages were re-presented to test intra-observer consistency. Examiners then agreed a common description for each haemorrhage type and five categories were described (vitreous, pre-retinal, nerve fibre layer, intra-retinal/sub-retinal or indeterminate) and the study repeated. RESULTS: There was 'fair agreement' initially (Fleiss' unweighted κ=0.219) and, with the agreed classification, slight improvement (0.356). Intra-observer agreement marginally improved on re-test. The two consultant ophthalmologists showed 'fair' agreement on both occasions (paired κ statistic). The other rater pair improved from 'fair' to 'substantial' agreement with the new classification. CONCLUSIONS: The classification of retinal haemorrhage in children by appearance alone shows only fair agreement between examiners. Clinicians who are not consultant ophthalmologists appear to benefit from the new succinct classification.

Combining coma score and serum biomarker levels to predict unfavorable outcome following childhood brain trauma.

This study aims to determine if pairing the Glasgow Coma Scale (GCS) with serum biomarker levels may achieve higher outcome predictive values than using either the GCS or biomarker levels alone in childhood brain trauma. Twenty-eight critically ill children with isolated accidental brain trauma were studied in a prospective observational study. The GCS was recorded at various time points post injury. Enzyme-linked immunosorbent assay (ELISA) was used to quantify eight different serum biomarker levels (S100b, NSE, IL-6, IL-8, IL-10, L-selectin, SICAM, and endothelin) on day 1 post injury. The Glasgow Outcome Score (GOS) was used to assess global outcome at 6 months post injury. Outcome predictive values of the GCS, individual biomarker levels, and paired combinations of the GCS and biomarkers were compared using receiver operator characteristic (ROC) curve analysis and its multivariate extension, multivariate ROC curve (MultiROC). When using either the GCS or individual biomarker levels alone to predict unfavorable outcome, only the PICU discharge summated GCS achieved an area under the ROC curve (AUC) of more than 0.95. This high degree of outcome predictability was also achieved by pairing the GCS with a single biomarker level. The most pronounced improvement in outcome prediction was observed by pairing the post-resuscitation summated GCS with the day-1 serum IL-8 level, which increased the AUC from 0.78 to 0.98 and the sensitivity and specificity from 75% to 100% and 96% respectively. Paired combinations of the GCS and serum biomarker levels greatly enhanced the accuracy of post-traumatic unfavorable outcome prediction than may be achieved using either the GCS or individual biomarker levels alone.