An uncommon presentation of a multifocal spinal osseous sarcoidosis: A case report on the diagnosis and exclusion with literature review.

Sarcoidosis is a granulomatous disease of indeterminate etiology. Women are more commonly affected than men at nearly twice the incidence with black women most commonly afflicted in the United States. Osseous spinal sarcoidosis (SS) is thought to be uncommon. Such lesions are often mistaken for metastatic disease, multiple myeloma, or disseminated fungal/granulomatous infection complicating the diagnosis, clinical course, and treatment. Patients presenting with clinical and imaging features of sarcoidosis may have normal serum laboratory values further complicating diagnosis. We present the case of a 61-year-old African American female with a diagnosis of osseous spinal sarcoidosis and normal calcium and ACE levels. Her initial presentation began with an incidentally discovered pulmonary nodule and was subsequently discovered to have multiple enlarging pulmonary nodules and widespread sclerotic lesions throughout her spine. This imaging presentation occurred before development of hilar adenopathy and cutaneous manifestations of sarcoidosis. Here, we describe her clinical course, exclusion of metastatic disease, and other confounders to arrive at the correct diagnosis.

Effective Use of Ketamine-Dexmedetomidine Following Propofol-Induced Hyperlactatemia: A Case Report.

There are limited options for intravenous anesthetics and a lack of available information on the use of ketamine infusion during intracranial surgeries. We present a patient case report of hyperlactatemia during a craniotomy with neuromonitoring while on a propofol infusion with arterial lactate rising from 2.1 mmol/L to a peak of 5.0 mmol/L before reducing to 3.9 mmol/L after the transition to a mixed ketamine and dexmedetomidine infusion in order to maintain neuromonitoring quality and an appropriate depth of anesthesia. No complications were caused by the use of ketamine during this extended neurosurgery case.

Longitudinal Course of Traumatic Brain Injury Biomarkers for the Prediction of Clinical Outcomes: A Review.

Protein biomarkers are often measured at hospital presentation to diagnose traumatic brain injury (TBI) and predict patient outcomes. However, a biomarker measurement at this single time point is no more accurate at predicting patient outcomes than less invasive and more cost-effective methods. Here, we review evidence that TBI biomarkers provide greater prognostic value when measured repeatedly over time, such that a trajectory of biomarker concentrations can be evaluated. PubMed, Google Scholar, and Cochrane Central Register were searched to identify studies from the last decade in which established TBI biomarkers had been measured at more than one time point following acute TBI, and which related their findings to patient outcomes. Twenty-two studies were identified, 18 of which focused on adults and 4 of which focused on children. Three general biomarker trajectories were identified: persistently high, persistently low, and reversal of decreasing concentrations. Downtrend reversal was highly specific to predicting poor patient outcomes. Four studies demonstrated that biomarker trajectories can be affected by therapeutic interventions. Additional studies demonstrated that biomarkers measured at a later time point offered superior prognostic value than a single measurement obtained at initial hospital presentation. Among other details, longitudinal biomarker trajectory assessments may identify ongoing injury and predict patient deterioration before clinical symptoms develop and thus help guide therapeutic interventions.

Decompressive Surgery for Patients with Traumatic Brain Injury.

Traumatic brain injury, which is a clinical spectrum, requires a thorough evaluation and strict monitoring for clinical deterioration owing to ongoing secondary injury and raised intracranial pressure. Once the intracranial pressure has been treated with maximal medical therapy, surgical decompression is necessary and must be initiated rapidly. Anesthetic management of surgical decompression must balance reduction of the intracranial pressure, maintenance of cerebral perfusion pressures, avoidance of secondary injuries, and optimization of surgical conditions.

Diazepam Inhibits Post-Traumatic Neurogenesis and Blocks Aberrant Dendritic Development.

Traumatic brain injury (TBI) triggers a robust increase in neurogenesis within the dentate gyrus of the hippocampus, but these new neurons undergo aberrant maturation and dendritic outgrowth. Because gamma-aminobutyric acid (GABA)A receptors (GABAARs) modulate dendritic outgrowth during constitutive neurogenesis and GABAAR-modulating sedatives are often administered to human patients after TBI, we investigated whether the benzodiazepine, diazepam (DZP), alters post-injury hippocampal neurogenesis. We used a controlled cortical impact (CCI) model of TBI in adult mice, and administered DZP or vehicle continuously for 1 week after injury via osmotic pump. Although DZP did not affect the neurogenesis rate in control mice, it almost completely prevented the TBI-induced increase in hippocampal neurogenesis as well as the aberrant dendritic growth of neurons born after TBI. DZP did not reduce cortical injury, reactive gliosis, or cell proliferation early after injury, but decreased c-Fos activation in the dentate gyrus at both early and late time-points after TBI, suggesting an association between neuronal activity and post-injury neurogenesis. Because DZP blocks post-injury neurogenesis, further studies are warranted to assess whether benzodiazepines alter cognitive recovery or the development of complications after TBI.

Ketamine Alters Hippocampal Cell Proliferation and Improves Learning in Mice after Traumatic Brain Injury.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Traumatic brain injury induces cellular proliferation in the hippocampus, which generates new neurons and glial cells during recovery. This process is regulated by N-methyl-D-aspartate-type glutamate receptors, which are inhibited by ketamine. The authors hypothesized that ketamine treatment after traumatic brain injury would reduce hippocampal cell proliferation, leading to worse behavioral outcomes in mice. METHODS: Traumatic brain injury was induced in mice using a controlled cortical impact injury, after which mice (N = 118) received either ketamine or vehicle systemically for 1 week. The authors utilized immunohistochemical assays to evaluate neuronal, astroglial, and microglial cell proliferation and survival 3 days, 2 weeks, and 6 weeks postintervention. The Morris water maze reversal task was used to assess cognitive recovery. RESULTS: Ketamine dramatically increased microglial proliferation in the granule cell layer of the hippocampus 3 days after injury (injury + vehicle, 2,800 ± 2,700 cells/mm, n = 4; injury + ketamine, 11,200 ± 6,600 cells/mm, n = 6; P = 0.012). Ketamine treatment also prevented the production of astrocytes 2 weeks after injury (sham + vehicle, 2,400 ± 3,200 cells/mm, n = 13; injury + vehicle, 10,500 ± 11,300 cells/mm, n = 12; P = 0.013 vs. sham + vehicle; sham + ketamine, 3,500 ± 4,900 cells/mm, n = 14; injury + ketamine, 4,800 ± 3,000 cells/mm, n = 13; P = 0.955 vs. sham + ketamine). Independent of injury, ketamine temporarily reduced neurogenesis (vehicle-exposed, 105,100 ± 66,700, cells/mm, n = 25; ketamine-exposed, 74,300 ± 29,200 cells/mm, n = 27; P = 0.031). Ketamine administration improved performance in the Morris water maze reversal test after injury, but had no effect on performance in sham-treated mice. CONCLUSIONS: Ketamine alters hippocampal cell proliferation after traumatic brain injury. Surprisingly, these changes were associated with improvement in a neurogenesis-related behavioral recall task, suggesting a possible benefit from ketamine administration after traumatic brain injury in mice. Future studies are needed to determine generalizability and mechanism.

A Unique Case of Muscle-Invasive Metastatic Breast Cancer Mimicking Myositis.

Breast cancer rarely metastasizes to the muscles, and it is even more unusual for this phenomenon to result in airway compromise. We present a unique case of an 84-year-old female who presented with neck swelling and upper airway obstruction due to metastatic breast cancer invading the sternocleidomastoid muscles. After establishing the diagnosis and discussing possible treatment options, the patient elected for antiestrogen therapy, palliative tracheostomy, radiation therapy, and hospice services.

Cost-Effectiveness of Lumbar Spondylolisthesis Surgery at 2-Year Follow-up.

OBJECTIVES: The purpose of this study was to determine the cost/quality-adjusted life-year (QALY) of the operative treatment of lumbar spondylolisthesis and identify factors associated with cost-effectiveness at 2 years. METHODS: We evaluated patients who underwent surgery for spondylolisthesis. The QALY was determined from the EQ5D. Outcomes were also assessed using the Oswestry Disability Index (ODI). Surgical, neuromonitoring, and anesthesia Current Procedural Terminology (CPT) codes as well as hospital Diagnosis-Related Group codes were used to determine the Medicare direct care costs of surgery. Indirect costs were modeled based on existing literature. A discounting rate of 3% was applied. Analysis was performed to determine which factors were associated with a cost/QALY less than $100,000. RESULTS: There were 44 patients who underwent surgery for either degenerative (30) or isthmic spondylolisthesis (14). There were 27 women and 17 men, with an average age at surgery of 59.7 years (standard deviation [SD] = 14.69) and an average follow-up of 2 years (SD = 0.82). The average postoperative improvement in ODI was 24.77 (SD = 23.9), and change in QALY was 0.43 (SD = 0.30). The average cost/QALY at 2 years for direct care costs was $89,065. The average cost/QALY at 2 years for direct plus indirect costs was $112,588. Higher preoperative leg pain and greater leg pain change was associated with a cost/QALY <$100,000 (p < .005, p < .028). The cost-effective group had a higher proportion of patients with disease extent of two or more levels (p = .021). When comparing surgical techniques of anterior-posterior and posterior only, there was no difference in cost-effectiveness. CONCLUSIONS: Spondylolisthesis surgery is cost-effective at 2 years, with a QALY change of 0.43 and a direct cost/QALY of $89,065. Higher preoperative leg pain and larger extent of disease was associated with cost-effectiveness. LEVEL OF EVIDENCE: IV.

Pre-Operative Autologous Blood Donation Does Not Affect Pre-Incision Hematocrit in Adolescent Idiopathic Scoliosis Patients. A Retrospective Cohort of a Prospective Randomized Trial.

BACKGROUND: Pre-donation of autologous blood prior to spine fusion for adolescent idiopathic scoliosis (AIS) has been used in deformity surgery. The effect of pre-donation on pre-operative hematocrit (Hct) remains debated. Multiple factors may influence pre-operative Hct including intravascular volume status, patient factors, and timing of pre-operative blood donation. The purpose of this study was to determine if pre-donation significantly lowers pre-incision Hct in AIS patients. METHODS: A retrospective cohort study of a Level-1 prospective randomized trial was conducted. 125 patients from the homogeneous population were included. AIS patients undergoing a posterior only spinal fusion for AIS were separated into two groups based on their pre-operative blood donation history. Demographic variables, pre-incision Hct, and transfusion rates were compared between the two groups using the Student's T-test. RESULTS: Pre-donation and non pre-donation groups had 28 and 97 patients, respectively. Pre-donation group was 75% female (21F, 7M) and non pre-donation group was 78% female (76F, 21M). There was no difference between pre-donation and non pre-donation groups in mean age (15.6 ± 2.2 vs 14.8 ± 2.2, p = 0.081), BMI (23.1 ± 4.2 vs 21.7 ± 5.3, p = 0.219), and pre-incision Hct (32.8 ± 3.4 vs 33.8 ± 3.1, p = 0.628). The overall transfusion rates were equivalent (32.1± 48.0% vs 25.8 ± 44.0%, p = 0.509), however, the rate of allogenic transfusion for the pre-donation group was significantly lower (3.6 ± 18.9% vs 25.8 ± 44.0%, p = 0.011). CONCLUSIONS: This study supports the use of pre-donation for AIS, without a significant drop in pre-incision Hct. Patients that donate are also much less likely to be exposed to allogenic blood. There may be a surgeon bias to recommend pre-donation in patients with a larger BMI and older age. Future studies are needed from a larger population of patients including those with non-AIS pathology. LEVEL OF EVIDENCE: Level III.

Antifibrinolytics reduce blood loss in adult spinal deformity surgery: a prospective, randomized controlled trial.

STUDY DESIGN: This is a prospective, randomized, double-blinded comparison of tranexamic acid (TXA), epsilon aminocaproic acid (EACA), and placebo used intraoperatively in patients with adult spinal deformity. OBJECTIVE: The purpose of this study was to provide high-quality evidence regarding the comparative efficacies of TXA, EACA, and placebo in reducing blood loss and transfusion requirements in patients undergoing posterior spinal fusion surgery. SUMMARY OF BACKGROUND DATA: Spine deformity surgery usually involves substantial blood loss. The antifibrinolytics TXA and EACA have been shown to improve hemostasis in large blood loss surgical procedures. METHODS: Fifty-one patients undergoing posterior spinal fusion of at least 5 levels for correction of adult spinal deformity were randomized to 1 of 3 treatment groups. Primary outcome measures included intraoperative estimated blood loss, total loss, (estimated blood loss + postoperative blood loss), and transfusion rates. RESULTS: Patients received TXA (n = 19), EACA (n = 19), or placebo (n = 13) in the operating room (mean ages: 60, 47, and 43 yr, respectively); TXA patients were significantly older and had larger estimated blood volumes than both other groups. Total losses were significantly reduced for EACA versus control, and there was a demonstrable but nonsignificant trend toward reduced intraoperative blood loss in both antifibrinolytic arms versus control. EACA had significant reductions in postoperative blood transfusions versus TXA. CONCLUSION: The findings in this study support the use of antifibrinolytics to reduce blood loss in posterior adult spinal deformity surgery. LEVEL OF EVIDENCE: 1.

Night Activity Reduction is a Signature Physiological Biomarker for Duchenne Muscular Dystrophy Dogs.

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked lethal muscle disease. Dystrophic dogs are excellent models to test novel therapies for DMD. However, the use of the dog model has been hindered by the lack of an effective method to evaluate whole-body mobility. We recently showed that night activity is a good indicator of dog mobility. However, our published method relies on frame-by-frame manual processing of a 12-hour video for each dog. This labor-intensive and time-consuming approach makes it unrealistic to use this assay as a routine outcome measurement. OBJECTIVE: To solve this problem, we developed an automatic video-capturing/imaging processing system. The new system reduces the data analysis time over 1,000 fold and also provides a more detailed activity profile of the dog. METHODS: Using the new system, we analyzed more than 120 twelve-hour recordings from 12 normal and 22 affected dogs. RESULTS: We observed similar activity profiles during repeated recording of the same dog. Throughout the night, normal dogs were in motion 10.4 ± 0.9% of the time while affected dogs were in motion 4.6 ± 0.2% of the time (p < 0.0001). Further, normal dogs made significantly more movements (p < 0.0001) while affected dogs rested significantly longer (p < 0.0001) during the period of recording (from 6 pm to 6 am next day). Importantly, statistical significance persisted irrespective of the coat color, gender and mutation type. CONCLUSIONS: Our results suggest that night activity reduction is a robust, quantitative physiological biomarker for dystrophic dogs. The new system may be applicable to study mobility in other species.

Disease severity and treatment in adolescent idiopathic scoliosis: the impact of race and economic status.

BACKGROUND CONTEXT: Ethnic disparities have been documented in the incidence and treatment of many diseases. Additionally, race and socioeconomic status (SES) have been shown to affect disease severity and access to care in the recent orthopedic literature. PURPOSE: To assess the role, if any, that race, SES, and health insurance type play in disease severity and treatment decisions in patients with adolescent idiopathic scoliosis. STUDY DESIGN: Retrospective chart review. PATIENT SAMPLE: Pediatric patients seen in a single surgeon's practice over 6 years (2004-2009). OUTCOME MEASURES: Treatment modality (observation, bracing, or surgery). METHODS: Data were obtained from 403 patients seen over 6 years (2004-2009). A patient-reported questionnaire was used to collect race, age, family income, and parent marital status data. Race was self-reported as "Asian," "black or African American," "Hispanic or Latino," "white or Caucasian," or "Other." Socioeconomic status was determined using family income and type of health insurance as indicators. Major curve magnitude and prescribed initial treatment (observation, brace, or surgery) were assessed from physician records. An independent sample t test was used to detect differences in curve magnitude of the different racial groups. A Pearson chi-square analysis was used to detect group differences for curves in surgical patients, defined as curves greater than 40°, and their initial treatment. RESULTS: Patients self-identified with one of the following racial groups: white (N=219), black (N=86), Hispanic (N=44), Asian (N=37), or Other (N=17). Mean curve magnitude was greater in black than in white patients (33° vs. 28°, p<.05). Black patients were more likely to present with curves in the surgical range (34% vs. 24%, p<.05) and were more likely to have surgery as their initial treatment than white patients (34% vs. 19%, p<.05). Black patients had more limited health care plans and lower incomes compared with whites (p<.001). Patients with higher access insurance plans presented at a younger age than patients with more limited access plans, irrespective of race (13.6 vs. 14.1, p<.05). There was no difference in Cobb angle at presentation by income or type of insurance. CONCLUSIONS: Curve magnitude and percentage of patients with curves in the surgical range were greater in black than in white patients. There was no difference in age on presentation or treatment offered across all racial groups. Black patients were more likely to have surgery as their initial treatment than white patients. While race did have an impact on disease severity in this single surgeon's practice, SES did not.

Interpars - an anatomical examination of the lumbar pars interarticulares with significance for spinal decompression.

BACKGROUND: Spine procedures continue to increase significantly. As such, a more precise understanding of the anatomy, especially the pars interarticularis (PI) is critical. Current data characterizing the PI level-by-level is lacking. This study analyzed the average PI width at each level of the lumbar spine in order to elucidate statistically significant PI variations between lumbar levels. METHODS: The interpars distance, the narrowest distance between the lateral edges of the left and right PI, was measured directly with calipers on 53 complete lumbar specimens and digitally via Fastrack measurements of 30 sets of lumbar vertebrae. For both methods, the mean interpars distances were compared moving down the lumbar spine. RESULTS: For direct measurements, the average interpars distances increased from L2 to L5. Analysis revealed significant differences across all levels. A significant difference was noted between male and female vertebrae only at L1. For Fastrack measurements, the average interpars distances also increased from L2 to L5. An increase in spinal canal width was observed across all but L1-L2, and an increase in the interpars-to-spinal-canal-width ratio was noted at all levels except L1-L2 and L4-L5. CONCLUSIONS: The amount of bone in the PI available for surgical removal becomes smaller moving from L5 to L1. There is a larger "margin-for-error" at L4 and L5 when decompressing the spinal canal from one side to the other than there is in the upper lumbar spine. At L1 and L2, de- compressing the entire width of the spinal canal leaves only a millimeter of remaining pars on either side. Care should be taken to use "undercutting techniques" in upper lumbar decompressions to preserve the PI.

The relative efficacy of antifibrinolytics in adolescent idiopathic scoliosis: a prospective randomized trial.

BACKGROUND: Antifibrinolytics can reduce intraoperative blood loss. The primary aim of this study was to determine the efficacy of intraoperative tranexamic acid, epsilon-aminocaproic acid, and placebo at reducing perioperative blood loss and the transfusion rate in patients with adolescent idiopathic scoliosis undergoing posterior spinal arthrodesis. METHODS: This is a prospective, randomized, double-blind comparison of tranexamic acid, epsilon-aminocaproic acid, and placebo used intraoperatively in patients with adolescent idiopathic scoliosis. One hundred and twenty-five patients with adolescent idiopathic scoliosis were randomly assigned to the tranexamic acid, epsilon-aminocaproic acid, or control groups. Parameters recorded included estimated blood loss, hematocrit, blood product usage, drain output, and total blood losses. The primary outcomes were intraoperative blood loss and postoperative drainage. Secondary outcomes were transfusion requirements and hematocrit changes both intraoperatively and postoperatively. RESULTS: One hundred and twenty-five patients (ninety-seven female and twenty-eight male, with a mean age of fifteen years) were randomized to receive tranexamic acid (thirty-six patients), epsilon-aminocaproic acid (forty-two patients), or saline solution (forty-seven patients). The groups were similar at baseline, with one exception: the saline solution group had a higher estimated blood volume at baseline than the tranexamic acid group. Both tranexamic acid and epsilon-aminocaproic acid reduced the estimated blood loss per degree and estimated blood loss per pedicle screw. Epsilon-aminocaproic acid, but not tranexamic acid, reduced estimated blood loss and estimated blood loss per level. Tranexamic acid also reduced total blood losses compared with epsilon-aminocaproic acid or saline solution. In an analysis controlling for level, degree, and number of anchors, tranexamic acid reduced drain output and total blood losses. Tranexamic acid or epsilon-aminocaproic acid had a smaller decrease in hematocrit postoperatively. In an analysis controlling for the mean arterial pressure during surgical exposure, tranexamic acid reduced estimated blood loss and total blood losses. Overall, antifibrinolytics (tranexamic acid or epsilon-aminocaproic acid) reduced estimated blood loss, total blood losses, and the decline in hematocrit postoperatively compared with saline solution. There was no difference among the groups with respect to the transfusion rate, duration of surgery, levels fused, or pedicle screws placed. CONCLUSIONS: Tranexamic acid and epsilon-aminocaproic acid reduced operative blood loss but not transfusion rate. Tranexamic acid is more effective at reducing postoperative drainage and total blood losses compared with epsilon-aminocaproic acid. Maintenance of the mean arterial pressure at <75 mm Hg during surgical exposure appears to be critical for maximizing antifibrinolytic benefit. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Outcomes and complications of the midline anterior approach 3 years after lumbar spine surgery.

Objective. The purpose of this study was to evaluate a new questionnaire to assess outcomes related to the midline anterior lumbar approach and to identify risk factors for negative patient responses. Methods. A retrospective review of 58 patients who underwent anterior lumbar surgery at a single institution for either degenerative disc disease or spondylolisthesis in 2009 was performed. The outcome measures included our newly developed Anterior Lumbar Surgery Questionnaire (ALSQ), ODI, and EQ-5D. Results. There were 58 patients available for followup, 27 women and 31 men. The average age at surgery was 50.8 years, with an average followup of 2.92 years. The average change in ODI was 34.94 (22.7) and EQ-5D was 0.28 (0.29). The rate of complications with the anterior approach was 10.3% and there was one male patient (3.2%) with retrograde ejaculation. Determination of the effectiveness of the new ALSQ revealed that it significantly correlated to the EQ-5D and ODI (P < 0.05). Smoking was associated with a negative response on thirteen questions. BMP use was not associated with a negative response on any sexual function questions. Conclusions. Our new Anterior Lumbar Surgery Questionnaire determines patient perceived complications related to the midline anterior lumbar surgical approach.

Nutraceutical-mediated restoration of wild-type levels of IKBKAP-encoded IKAP protein in familial dysautonomia-derived cells.

SCOPE: The reported ability to modulate the production of the wild-type transcript in cells bearing the splice-altering familial dysautonomia (FD)-causing mutation in the IKBKAP gene prompted an evaluation of the impact of commonly consumed nutraceuticals on the splicing of this transcript. METHODS AND RESULTS: Screening efforts revealed the ability of the isoflavones, genistein, and daidzein, to impact splicing and increase the production of the wild-type, exon-20-containing, transcript, and the full-length IKBKAP-encoded IΚB kinase complex associated protein(IKAP) in FD-derived cells. Genistein was also found to impact splicing in neuronal cells, a cell type profoundly impacted by FD. The simultaneous exposure of FD-derived cells to genistein and epigallocatechin gallate (EGCG) resulted in the almost exclusive production of the exon-20-containing transcript and the production of wild-type amounts of IKAP protein. CONCLUSION: This study represents the first demonstration that the isoflavones, genistein and daidzein, possess splice-altering capabilities and that simultaneous treatment with genistein and EGCG reverses the splice-altering impact of the FD-causing mutation. These findings support the clinical evaluation of the therapeutic impact of the combined administration of these two commonly consumed nutraceuticals on this patient population and suggest a broader evaluation of the impact of these nutraceuticals on the in vivo RNA splicing process.