Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) in mainland China: an investigation of reliability, validity, and responsiveness.

BACKGROUND: The aim of this study is to investigate the reliability, validity, and responsiveness of JOACMEQ for CSM patients in mainland China. METHODS: A retrospective review was performed on 91 patients with CSM in our hospital from March 2015 to June 2015. Patients completed the JOACMEQ, the mJOA and the SF-36 questionnaires during the process. Cronbach's α was used to evaluate the internal consistency reliability, and test-retest reliability was checked. An exploratory factor analysis was used to determine the correlations among the JOACMEQ questions and the construct validity. The concurrent validity was assessed by Spearman correlation coefficient. The internal responsiveness was determined by effect sizes and standardized response means. External responsiveness was determined by the area under the receiver operating characteristic curve on the basis of the Youden Index. RESULTS: The mean age of patients was 57.61 years old. The mean follow-up was 24 months. JOACMEQ showed a good internal consistency (Cronbach's α, 0.897). Test-retest reliability showing good result (Pearson's correlation, 0.695-0.905). Our data were amenable to factor analysis (KMO = 0.816, Bartlett's test, χ2(45) = 1199.99, p < 0.001), and five factors above 1 were strongly loaded and clustered for each of the five factors. Comparing the scales preoperative to those 2 years postoperative, the average scores of the subscales all increased, and both the ES and SRM showing satisfied responsiveness. In external responsiveness analysis, the recovery rate a appeared to be most responsive to post-operative improvement. CONCLUSIONS: The Simplified Chinese version of JOACMEQ was well-developed with great reliability and sensitive responsiveness. Our study demonstrated that JOACMEQ has content psychometric properties to identify postoperative improvements in CSM patients.

Quantitative analysis of the correlation between preoperative cervical degeneration and postoperative heterotopic ossification after cervical disc replacement: minimum 10-year follow-up data.

OBJECTIVE: The authors aimed to identify factors that may be useful for quantifying the amount of degenerative change in preoperative patients to identify ideal candidates for cervical disc replacement (CDR) in patients with a minimum of 10 years of follow-up data. METHODS: During the period from December 2003 to August 2008, 54 patients underwent CDR with a Bryan cervical disc prosthesis performed by the same group of surgeons, and all of the patients in this group with at least 10 years of follow-up data were enrolled in this retrospective analysis of cases. Postoperative bone formation was graded in radiographic images by using the McAfee classification for heterotopic ossification. Preoperative degeneration was evaluated in radiographs based on a quantitative scoring system. After univariate analysis, the authors performed multifactor logistic regression analysis to identify significant factors. To determine the cutoff points for the significant factors, a receiver operating characteristic (ROC) curve analysis was conducted. RESULTS: Study patients had a mean age of 43.6 years and an average follow-up period of 120.3 months. The patients as a group had a 68.2% overall incidence of bone formation. Based on univariate analysis results, data for patient sex, disc height, and the presence of anterior osteophytes and endplate sclerosis were included in the multivariate analysis. According to the analysis results, the identified independent risk factors for postoperative bone formation included disc height, the presence of anterior osteophytes, and endplate sclerosis, and according to a quantitative scoring system for degeneration of the cervical spine based on these variables, the ROC curve indicated that the optimal cutoff scores for these risk factors were 0.5, 1.5, and 1.5, respectively. CONCLUSIONS: Among the patients who were followed up for at least 10 years after CDR, the incidence of postoperative bone formation was relatively high. The study results indicate that the degree of degeneration in the target level before surgery has a positive correlation with the incidence of postoperative ossification. Rigorous indication criteria for postoperative ossification should be applied in patients for whom CDR may be a treatment option.

The Effect of Surgical Decompression on Functional Balance Testing in Patients With Cervical Spondylotic Myelopathy.

STUDY DESIGN: A prospective cohort study. OBJECTIVE: Quantify the extent of change in dynamic balance and stability in a group of patients with cervical spondylotic myelopathy (CSM) after cervical decompression surgery and to compare them with matched healthy controls. SUMMARY OF BACKGROUND DATA: CSM is a naturally progressive degenerative condition that commonly results in loss of fine motor control in the hands and upper extremities and in gait imbalance. Whereas this was previously thought of as an irreversible condition, more recent studies are demonstrating postoperative improvements in balance and stability. MATERIALS AND METHODS: Thirty subjects with symptomatic CSM and 25 matched asymptomatic controls between the ages of 45 and 75 years underwent functional balance testing using a 3D motion capture system to gather kinematic and spatiotemporal parameters. CSM subjects underwent testing 1 week before surgery and again 3 months postoperatively. RESULTS: Patients with CSM exhibited markedly diminished balance as indicated by increased sway on a Romberg test and requiring significantly more time and a wider stance to complete tandem gait tests. The surgical intervention resulted in improved balance at the 3-month postoperative time point; however, kinematic and spatiotemporal parameters did not completely normalize to the levels observed in asymptomatic controls. CONCLUSIONS: Human motion video capture can be used to robustly quantify balance parameters in the setting of CSM. Compared with healthy controls, such patients exhibited increased standing sway and poorer performance on a tandem gait task. The surgical intervention resulted in significant improvement in many of the measures of functional balance, but overall profiles had not completely returned to normal when measured 3 months after surgery. These data reinforce the importance of operative intervention in the treatment of symptomatic CSM with the goal of halting disease progress but the expectation that balance may actually improve postoperatively.

Characterizing gait abnormalities in patients with cervical spondylotic myelopathy: a neuromuscular analysis.

BACKGROUND CONTEXT: Gait impairment is a hallmark of cervical spondylotic myelopathy (CSM). It has been shown to affect quality of life but has not been well defined. Further electromyographic (EMG) characterization of the gait cycle may help elucidate the true neuromuscular pathology with implications on prognosis and rehabilitation techniques. PURPOSE: This study compares neuromuscular activity in patients with CSM to that of healthy age-matched controls. STUDY DESIGN: Nonrandomized, prospective, concurrent control cohort study. METHODS: Neuromuscular activity was measured in 40 patients with symptomatic CSM during a series of over-ground gait trials at a self-selected speed before surgical intervention. External oblique, multifidus, erector spinae, rectus femoris, semitendinosus, tibialis anterior, medial gastrocnemius, and medial deltoid were assessed. Identical measurements were taken in 25 healthy control patients. Differences in time of muscle onset, peak EMG, time to peak EMG, and integrated electromyography (iEMG) were assessed using one-way ANOVA. RESULTS: There were no significant differences between patients with CSM and healthy controls with respect to time of muscle contraction onset. Peak EMG muscle activity was significantly higher in the medial deltoid of patients with CSM (39.3% vs. 23.3% sMVC, p=.042), but no other differences were seen in the remaining muscles tested. They also demonstrated significantly longer time to peak EMG muscle activity compared with controls in 5 of the 8 muscles tested, including the multifidus (20.2 vs. 16.8 ms, p=.050), erector spinae (18.2 vs. 8.9 ms, p<.001), semitendinosis (26.3 vs. 22.4 ms, p=.037), tibialis anterior (14.7 vs. 11.0 ms, p=.050), and medial deltoid (24.2 vs. 9.2 ms, p<.001). Compared with controls, patients with CSM demonstrated significantly higher iEMG activity in the semitendinosis (586.5% vs. 272.5 sMVC, p=.047) and medial deltoid (87.62% vs. 22.5% sMVC, p=.008). CONCLUSIONS: The onset of muscle activity is not delayed in CSM patients, but many key muscles take longer to fully contract. This produces a situation in which patients with CSM are unable to fully fire their muscles with sufficient speed to maintain a normal gait. The core and lower extremity muscles do not contract with increased peak amplitude in response, but the deltoid and hamstring muscles are more active, suggesting compensatory activity as patients attempt to maintain balance. The end result is less efficient ambulation. These findings provide a more nuanced understanding of gait in individuals suffering from CSM and may have implications on rehabilitation protocols.

Gait Alteration in Cervical Spondylotic Myelopathy Elucidated by Ground Reaction Forces.

STUDY DESIGN: .: Prospective cohort study. OBJECTIVE: .: Analyze GRF parameters in cervical spondylotic myelopathy (CSM) patients to elucidate gait alterations as compared with healthy controls. SUMMARY OF BACKGROUND DATA: .: During the human gait cycle, the magnitude and direction of the force each foot imparts on the ground varies in a controlled fashion to propel the body's center of mass forward. Alterations in GRF patterns can both point to subtle gait disturbances and explain altered gait patterns such as that seen in CSM. METHODS: .: Thirty-two patients with symptomatic CSM who have been scheduled for surgery, along with 30 healthy controls (HC), underwent clinical gait analysis a week before surgery. Vertical GRF parameters and force magnitude and timing at various points of the gait cycle (i.e., heel contact, maximum weight acceptance, mid-stance, and push off) were analyzed and compared between groups. RESULTS: .: Increased heel contact (CSM: 60.13% vs. HC: 27.82% of body weight, BW,P = 0.011), maximum weight acceptance (CSM: 120.13% vs. HC: 100.97% of BW, P = 0.016), and diminished push off (CSM: 91.35% vs. HC: 106.54% of BW, P = 0.001) forces were discovered in CSM patients compared with HC. Compared with controls CSM patients had delayed heel contact (CSM: 9.32% vs. HC: 5.12% of gait cycle, P = 0.050) and earlier push off (CSM: 54.96% vs. HC: 59.0% of gait cycle, P = 0.050), resulting in a shorter stance phase. CONCLUSION: .: This study reinforces how CSM patients commonly exhibit altered gait patterns, but also uniquely demonstrates the increased heel-contract and maximum weight acceptance forces, diminished toe-off forces, and the shorter stance phase to absorb the BW load. When examined from a global perspective, these altered GRF parameters reflect the difficulty CSM patients have with catching their center of mass during heel-contact to avoid falling and with subsequently propelling themselves forward. LEVEL OF EVIDENCE: 3.

Functional Balance Testing in Cervical Spondylotic Myelopathy Patients.

STUDY DESIGN: A prospective cohort study. OBJECTIVE: The aim of this study was to quantify the amount of sway associated with maintaining a balanced posture in a group of untreated cervical spondylotic myelopathy (CSM) patients. SUMMARY OF BACKGROUND DATA: Balance is defined as the ability of the human body to maintain its center of mass (COM) within the base of support with minimal postural sway. Sway is the movement of the COM in the horizontal plane when a person is standing in a static position. CSM patients have impaired body balance and proprioceptive loss. METHODS: Thirty-two CSM patients performed a series of functional balance tests a week before surgery. Sixteen healthy controls (HCs) performed a similar balance test. Patients are instructed to stand erect with feet together and eyes opened in their self-perceived balanced and natural position for a full minute. All test subjects were fitted to a full-body reflective markers set and surface electromyography (EMG). RESULTS: CSM patients had more COM sway in the anterior-posterior (CSM: 2.87 cm vs. C: 0.74 cm; P = 0.023), right-left (CSM: 5.16 cm vs. C: 2.51 cm; P = 0.003) directions as well as head sway (anterior-posterior - CSM: 2.17 cm vs. C: 0.82 cm; P = 0.010 and right-left - CSM: 3.66 cm vs. C: 1.69 cm; P = 0.044), more COM (CSM: 44.72 cm vs. HC: 19.26 cm, p = 0.001), and head (Pre: 37.87 cm vs. C: 19.93 cm, P = 0.001) total sway in comparison to controls. CSM patients utilized significantly more muscle activity to maintain static standing, evidenced by the increased trunk and lower extremity muscle activity (multifidus, erector spinae, rectus femoris, and tibialis anterior, P < 0.050) during 1-minute standing. CONCLUSION: In symptomatic CSM patients, COM and head total sway were significantly greater than controls. Individuals with CSM exhibit more trunk and lower extremity muscle activity, and thus expend more neuromuscular energy to maintain a balanced, static standing posture. This study is the first effort to evaluate global balance as a dynamic process in this patient population. LEVEL OF EVIDENCE: 3.

Spine and lower extremity kinematics during gait in patients with cervical spondylotic myelopathy.

BACKGROUND CONTEXT: Cervical spondylotic myelopathy (CSM) typically manifests with a slow, progressive stepwise decline in neurologic function, including hand clumsiness and balance difficulties. Gait disturbances are frequently seen in patients with CSM, with more advanced cases exhibiting a stiff, spastic gait. PURPOSE: To evaluate the spatiotemporal parameters and spine and lower extremity kinematics during the gait cycle of adult patients with CSM before surgical intervention. STUDY DESIGN: Prospective cohort study. PATIENT SAMPLE: Twenty-eight subjects with symptomatic CSM who have been scheduled for surgery and 30 healthy controls (HC). OUTCOME MEASURES: Spine and lower extremity kinematics and spatiotemporal parameters. METHODS: Clinical gait analysis was performed for patients with CSM and HC. The data were analyzed with a one-way analysis of variance. RESULTS: Patients with CSM have significantly more anterior pelvis tilt (CSM: 13.97°, HC: 5.56°), larger lumbar lordosis (CSM: 8.59°, HC: 2.7°), smaller cervical lordosis (CSM: 6.02°, HC: 11.35°), and less head flexion (CSM: 0.69°, HC: 8.66°) at the beginning of the gait cycle. There was a decrease in knee range of motion in patients with CSM compared with controls (CSM: 36.31°, HC: 50.17°). Furthermore, patients with CSM presented with slower walking speed (CSM: 0.81 m/s, HC: 1.05 m/s), decreased cadence (CSM: 95.57 step/m, HC: 107.64 step/m), increased double support time (CSM: 0.40 s, HC: 0.28 s) and stride time (CSM:1.28 s, HC: 1.13 s), shorter stride length (CSM: 1.04 m, HC: 1.18 m) and step length (CSM:0.51 m, HC: 0.58 m), and wider width (CSM: 0.14 m, HC:0.11 m). CONCLUSIONS: Our study shows that patients with CSM enter the gait cycle with a larger anterior pelvic tilt and lumbar lordosis as well as less cervical lordosis and head flexion. As a consequence of these abnormal spinal parameters at the onset of the gait cycle, lower extremity biomechanics are also altered. Our study is the first to demonstrate the relationship between aberrant spinal alignment and lower extremity function. Identification of this interrelationship as well as the specific gait and biomechanical disturbances seen in myelopathic patients can both inform our understanding of the disease and tailor rehabilitation protocols.

The use of gait analysis in the assessment of patients afflicted with spinal disorders.

PURPOSE: Use gait analysis to establish and detail the clinically relevant components of normal human gait, analyze the gait characteristics for those afflicted with spinal pathology, and identify those aspects of human gait that correlate with pre- and postoperative patient function and outcomes. METHODS: Twenty patients with adult degenerative scoliosis (ADS), 20 patients with cervical spondylotic myelopathy (CSM), and 15 healthy volunteers performed over-ground gait trials with a comfortable self-selected speed using video cameras to measure patient motion, surface electromyography (EMG) to record muscle activity, and force plates to record ground reaction force (GRF). Gait distance and temporal parameters, ankle, knee, hip, pelvic, and trunk range of motion (ROM), duration of lower extremity EMG activity and peak vertical GRF were measured. RESULTS: Patients with ADS and CSM exhibited a significantly slower gait speed, decrease in step length, cadence, longer stride time, stance time, double support time, and an increase in step width compared to those in the control group. These patients also exhibited a significantly different ankle, knee, pelvic, and trunk ROM. Moreover, spinal disorder patients exhibited a significantly longer duration of rectus femoris, semitendinosus, tibialis anterior and medial gastrocnemius muscle activity along with an altered vertical GRF pattern. CONCLUSIONS: Gait analysis provides an objective measure of functional gait in healthy controls as well as those with ADS and CSM. This study established and detailed some of the important kinematic and kinetic variables of gait in patients with spinal disorders. We recommend that spine care providers use gait analysis as part of their clinical evaluation to provide an objective measure of function. These slides can be retrieved under Electronic Supplementary Material.

Progressive Bone Formation After Cervical Disc Replacement: Minimum of 5-Year Follow-up.

STUDY DESIGN: Retrospective review. OBJECTIVE: Our objective was to examine the prevalence, clinical significance, ramifications, and possible etiology of postoperative bone formation at the index level after cervical disc replacement (CDR) with a minimum of 5 years of follow-up. SUMMARY OF BACKGROUND DATA: CDR can be complicated by postoperative ossification and unwanted ankylosis at the index level, which some authors have termed "heterotopic ossification." This terminology may be inaccurate as it assumes the postoperative bone formation is unnatural and a consequence of the CDR surgery. We advocate that this phenomenon has more to do with individual patient factors rather than the surgery. METHODS: Patients who underwent Bryan CDR for cervical myelopathy or radiculopathy between 12/2003 and 8/2008 with a minimum of 5-years follow-up were analyzed. They were divided into two groups, those with and without postoperative bone formation. Patient-reported outcomes (Japanese Orthopaedic Association score, Neck Disability Index, Visual Analogue Scale for neck and arm pain) and radiographic parameters were collected pre- and postoperatively and compared between groups. RESULTS: Sixty-one patients (76 levels) were identified (mean follow-up 94.2 mo). The overall incidence of postoperative ossification was 50%. Both groups had sustained significant improvements across all patient-reported outcome measures at final follow-up. Notably, patients with more severe preoperative cervical spondylosis had higher rates of postoperative ossification (P = 0.036) and adjacent segment degeneration (P = 0.010). CONCLUSION: Although the long-term incidence of postoperative bone formation after CDR was relatively high, this did not adversely affect patient outcomes. Patients with more severe preoperative spondylosis had higher rates of postoperative ossification, suggesting that postoperative ossification at the CDR segment is likely one of progressive bone formation in individuals already predisposed to forming bone rather than one of alleged heterotopic ossification as a consequence of the surgery. LEVEL OF EVIDENCE: 3.

Anterior Cervical Discectomy and Fusion.

Anterior cervical discectomy and fusion can be performed for a variety of pathologies but is most commonly used for the treatment of cervical radiculopathy or myelopathy. The procedure involves an anterior decompression of the disc space followed by interbody grafting and fusion. Supplemental anterior plating is commonly performed, and in certain circumstances, posterior instrumentation may provide additional fixation. The procedure includes the following steps: (1) The use of an anterior approach to the cervical spine, most commonly the Smith-Robinson approach medial to the sternocleidomastoid muscle and the carotid sheath. (2) Confirmation of the proper spinal level. (3) Elevation of the longus colli muscle, which acts as a cuff for the placement of retractors. (4) Removal of the involved disc and decompression of the spinal cord and nerve roots. This is facilitated by disc space distraction, most commonly via distraction pins. Osteophytes along the floor of the spinal canal impinging on the spinal cord are removed with a burr. Soft disc and anular material are also removed, usually with curets and rongeurs. Uncovertebral osteophyte resection and foraminotomies are completed to decompress the exiting nerve roots. (5) Carpentry and decortication of the end plates in preparation for fusion. (6) Sizing of the disc space followed by insertion of an interbody graft. (7) Anterior fixation, most commonly via application of a plate-and-screw construct. (8) Hemostasis and closure.

Predicting patients with concurrent noncontiguous spinal epidural abscess lesions.

BACKGROUND CONTEXT: Spinal epidural abscess (SEA) is a serious condition that can lead to significant morbidity and mortality if not expeditiously diagnosed and appropriately treated. However, the nonspecific findings that accompany SEAs often make its diagnosis difficult. Concurrent noncontiguous SEAs are even more challenging to diagnose because whole-spine imaging is not routinely performed unless the patient demonstrates neurologic findings that are inconsistent with the identified lesion. Failure to recognize a separate SEA can subject patients to a second operation, continued sepsis, paralysis, or even death. PURPOSE: To formulate a set of clinical and laboratory predictors for identifying patients with concurrent noncontiguous SEAs. STUDY DESIGN: A retrospective, case-control study. PATIENT SAMPLE: Patients aged 18 years or older admitted to our institution during the study period who underwent entire spinal imaging and were diagnosed with one or more SEAs. OUTCOME MEASURES: The presence or absence of concurrent noncontiguous SEAs on magnetic resonance imaging or computed tomography (CT)-myelogram. METHODS: A retrospective review was performed on 233 adults with SEAs who presented to our health-care system from 1993 to 2011 and underwent entire spinal imaging. The clinical and radiographic features of patients with concurrent noncontiguous SEAs, defined as at least two lesions in different anatomical regions of the spine (ie, cervical, thoracic, or lumbar), were compared with those with a single SEA. Multivariate logistic regression identified independent predictors for the presence of a skip SEA, and a prediction algorithm based on these independent predictors was constructed. Institutional review board committee approval was obtained before initiating the study. RESULTS: Univariate and multivariate analyses comparing patients with skip SEA lesions (n=22) with those with single lesions (n=211) demonstrated significant differences in three factors: delay in presentation (defined as symptoms for ≥7 days), a concomitant area of infection outside the spine and paraspinal region, and an erythrocyte sedimentation rate of >95 mm/h at presentation. The predicted probability for the presence of a skip lesion was 73% for patients possessing all three predictors, 13% for two, 2% for one, and 0% for zero predictors. Receiver operating characteristic curve analysis, used to evaluate the predictive accuracy of the model, revealed a steep shoulder with an area under the curve of 0.936 (p<.001). CONCLUSIONS: The proposed set of three predictors may be a useful tool in predicting the risk of a skip SEA lesion and, consequently, which patients would benefit from entire spinal imaging.

Independent predictors of failure of nonoperative management of spinal epidural abscesses.

BACKGROUND CONTEXT: The notion that all patients with spinal epidural abscess (SEA) require surgical decompression has been recently challenged by reports of successful medical management of select patients with SEA. PURPOSE: The purpose of this study was to identify the independent variables that determine success or failure of medical management of SEA. STUDY DESIGN/SETTING: This was a retrospective, case-control study. PATIENT SAMPLE: Patients 18 years or older with diagnosis of SEA admitted to our institution during the study period were included in the sample. OUTCOME MEASURES: The outcome measure was successful management of SEA by eradication of the infection without worsening of neurologic deficits. METHODS: All patients admitted to our health-care system with a diagnosis of SEA from 1993 to 2011 were identified and the data were retrospectively collected. Patients 18 years or older diagnosed with SEA were included. Excluded were those with postsurgical SEA or phlegmon without an abscess and those with a complete spinal cord injury from SEA for longer than 48 hours. RESULTS: A total of 355 patients with average age of 60 years met our inclusion criteria. Of the patients who initially underwent nonoperative treatment, 54 patients failed medical management and 73 patients were successfully treated without surgery. Univariate and multivariate analysis identified incomplete or complete spinal cord deficits as the most significant risk factor for failure of medical management. Age older than 65 years, diabetes, and methicillin-resistant Staphylococcus aureus (MRSA) were also independent risk factors for failure. An algorithm for probability of failed antibiotic management of spinal epidural abscess predicted 99% probability of failure for patients with all four of these risk factors. CONCLUSIONS: SEA treated with medical management alone has a very high risk for failure if the patient is older than 65 years with diabetes, MRSA infection, or neurologic compromise. In the absence of these risk factors, nonoperative management of spinal epidural abscess may be considered as the initial line of treatment with close monitoring.

Differentiating between methicillin-resistant and methicillin-sensitive Staphylococcus aureus osteomyelitis in children: an evidence-based clinical prediction algorithm.

BACKGROUND: Although osteomyelitis was once commonly due to methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA)--which causes more virulent and invasive infections--has emerged as an increasingly important cause. Differentiating clinically between MRSA and MSSA can be challenging, but is necessary in order to promptly administer appropriate antibiotics and maintain vigilance against possible sequelae of MRSA osteomyelitis. The purpose of our study was to develop a clinical prediction algorithm to distinguish between MRSA and MSSA osteomyelitis in children. METHODS: A retrospective review of 129 children presenting with culture-proven Staphylococcus aureus osteomyelitis between 2000 and 2009 was performed. The demographics, symptoms, vital signs, and laboratory test values in the MSSA group (n = 118) and the MRSA group (n = 11) were compared with use of univariate analysis. Multivariate logistic regression with backward stepwise selection was then used to identify independent multivariate predictors of MRSA osteomyelitis, and each of these predictors was subjected to receiver operating characteristic curve analysis to determine the optimal cutoff value. Finally, a prediction algorithm for differentiating between MRSA and MSSA osteomyelitis on the basis of these independent predictors was constructed. RESULTS: Patients with MRSA osteomyelitis differed significantly from those with MSSA osteomyelitis with regard to non-weight-bearing status, antibiotic use at presentation, body temperature, hematocrit value, heart rate, white blood-cell count, platelet count, C-reactive protein level, and erythrocyte sedimentation rate. Four significant independent multivariate predictors were identified: a temperature of >38°C, a hematocrit value of <34%, a white blood-cell count of >12,000 cells/µL, and a C-reactive protein level of >13 mg/L. The predicted probability of MRSA osteomyelitis, determined on the basis of the number of these predictors that a child satisfied, was 92% for all four predictors, 45% for three, 10% for two, 1% for one, and 0% for zero predictors. Receiver operating characteristic curve analysis was used to evaluate the predictive accuracy of the number of multivariate predictors, and this analysis revealed a steep shoulder and an area under the curve of 0.94 (95% confidence interval, 0.88 to 1.00). CONCLUSIONS: Our proposed set of four predictors provided excellent diagnostic performance in differentiating between MRSA and MSSA osteomyelitis in children, and thus would be able to guide patient management and facilitate timely antibiotic selection.

Genomewide linkage in a large Caucasian family maps a new locus for intracranial aneurysms to chromosome 13q.

BACKGROUND AND PURPOSE: Familial aggregation of intracranial aneurysms (IAs) indicates a genetic role in the pathogenesis of this disease. Despite a number of reported susceptibility loci, no disease-causing gene variants have been identified. In this study, we used a parametric genomewide linkage approach to search for new IA susceptibility loci in a large Caucasian family. METHODS: The affection status of family members with clinical signs of IA was confirmed with medical records or through radiological or surgical examinations. All other relatives were screened using MR angiography. Genomewide linkage analysis was performed on 35 subjects using approximately 250 000 single nucleotide polymorphic markers. RESULTS: Ten individuals had an IA. Linkage analysis using a dominant model showed significant linkage to a 7-cM region in 13q14.12-21.1 with a maximum logarithm of odds score of 4.56. CONCLUSIONS: A new IA susceptibility locus on 13q was identified, adding to the number of IA loci already reported. Given that no coding variants have been reported to date, it is possible that alternative genetic variants such as regulatory elements or copy number variation are important in IA pathogenesis. We are proceeding with attempts to identify such variants in our locus.

Anti-apoptotic therapy with a Tat fusion protein protects against excitotoxic insults in vitro and in vivo.

A number of gene therapy approaches have been developed for protecting neurons from necrotic neurological insults. Such therapies are limited by the need for transcription and translation of the protective protein, delaying therapeutic impact. As an alternative, we explore the neuroprotective potential of protein therapy, using a fusion protein comprised of the death-suppressing BH4 domain of the Bcl-xL protein and the protein transduction domain of the human immunodeficiency virus Tat protein. This fusion protein decreased neurotoxicity caused by the excitotoxins glutamate and kainic acid in primary hippocampal cultures, and decreased hippocampal damage in vivo in an excitotoxic seizure model.