Langerhans cell histiocytosis and human herpes virus 6 (HHV-6), an analysis by real-time polymerase chain reaction.

Patients with Langerhans cell histiocytosis (LCH) usually present to orthopedic surgeons because this disease most commonly affects bone. The pathogenesis of LCH is unknown, although roles for environmental, infectious, immunologic, and genetic causes have been postulated. More specifically, there is limited data suggesting that human herpes virus 6 (HHV-6) may be a potential etiologic agent. Frozen biopsy material was obtained from 13 patients with LCH and 20 patients without the disease. After ensuring histologic adequacy of the material, the tissue was tested for HHV-6 by qualitative and quantitative real-time TaqMan PCR. Four of 13 patients with LCH had evidence of HHV-6 DNA in their tissue while 7 of 20 control patients tested positive for HHV-6 genome. Viral loads are reported for the positive patients; no statistical difference was observed in the presence or quantity of HHV-6 DNA found in either population, suggesting that the prevalence of HHV-6 in the tissue of LCH patients is the same as that found in tissue from individuals without disease.

Primary non-Hodgkin's lymphoma of bone in children.

BACKGROUND: Primary non-Hodgkin's lymphoma of bone, often more simply referred to as primary lymphoma of bone, is a rare subset of non-Hodgkin's lymphoma in children. There are only a few small series of primary lymphoma of bone in children with long-term follow-up, and none have appeared in the orthopaedic literature. METHODS: A review of our institution's Pediatric Tumor Registry identified fifteen cases of primary lymphoma of bone among 306 cases of diagnosed non-Hodgkin's lymphoma between 1970 and 2003. Retrospective evaluation included collection of demographic, clinical, radiographic, treatment, and follow-up data. A univariate analysis was used to assess the prognostic significance of risk factors with respect to survival of patients from this series and in a summary analysis of data collected from similar series in the literature. RESULTS: The patients included ten male and five female patients with a mean age of 11.6 years. Most patients had a presenting complaint of pain and had swelling and/or tenderness on physical examination. Eight children had a solitary bone lesion, and seven had multiple bone lesions. Overall, the mean number of bones involved was 3.1 per patient. The femur and the pelvis were the most frequently involved bones. The ten surviving patients were followed for a mean of 13.6 years. Five patients died: three of disease progression, one of treatment-related complications, and one of an unrelated cause. The mean time from diagnosis to death was 2.1 years. Nine patients received chemotherapy only, whereas six patients received a combination of chemotherapy and radiation therapy. In the present study, an age of nine years or less was predictive of poor survival (p < 0.05). In the summary analysis of cases collected from the literature, advanced stage, young age, non-large-cell histology, and multiple-bone involvement were predictive of poor survival (p < 0.05). CONCLUSIONS: On the basis of the present series and a comprehensive review of similar series in the literature involving patients with primary lymphoma of bone, it appears that younger age, advanced-stage disease, multiple-bone involvement, and non-large-cell histology are associated with decreased survival as compared with older age, localized disease, single-bone involvement, and large-cell histology, respectively.

Nontraumatic upper cervical spine instability in children.

The upper cervical spine begins at the base of the occiput, continues caudally to the C2-C3 disk space, and includes the occipitoatlantal and atlantoaxial joints. Nontraumatic upper cervical spine instability can result from abnormal development of osseous or ligamentous structures or from gradually increasing ligamentous laxity associated with connective tissue disorders. Such instability can lead to compression of the spinal cord during movement of the cervical spine. Establishing a correct diagnosis includes performing a thorough physical examination as well as evaluating radiographic relationships and measurements. Appropriate management of syndromes associated with instability of the upper cervical spine includes preventive care and recommendations for sports participation. Surgical treatment for the upper cervical spine includes a posterior surgical approach, used for instability, and the use of rigid plate implants, wiring, and bone graft materials to achieve a solid spinal fusion.

Down syndrome in children: the role of the orthopaedic surgeon.

Down syndrome, the result of trisomy of chromosome 21, is one of the most common chromosomal abnormalities. Patients have a characteristic facial appearance, variable levels of intelligence and self-care skills, and a variety of associated medical conditions. Orthopaedic manifestations occur frequently; most are related to hypotonia, joint hypermobility, and ligamentous laxity. Atlanto-occipital and atlantoaxial hypermobility, as well as bony anomalies of the cervical spine, can produce atlanto-occipital and cervical instability. Methods of screening for this instability, particularly with regard to participation in sports, are a subject of controversy. Scoliosis, hip instability, slipped capital femoral epiphysis, patellar instability, and foot deformities are other musculoskeletal conditions found in patients with Down syndrome that can be challenging for the orthopaedic surgeon to treat.

Congenital osseous anomalies of the upper cervical spine.

BACKGROUND: The developmental anatomy and biomechanics of the upper cervical spine are unique in children. Congenital osseous anomalies in this region may be associated with an increased risk for subsequent neurological compromise from instability and/or spinal cord encroachment. We performed a double-cohort study evaluating congenital osseous anomalies of the upper cervical spine in children who presented with one or more clinical problems, and we attempted to outline the risk of possible neurological compromise. METHODS: We reviewed the medical records and imaging studies of all children seen and treated for osseous anomalies of the upper cervical spine at our institution between 1988 and 2003. Patients were divided into two cohorts on the basis of the presence or absence of associated syndromes. Parameters reviewed included demographic data, clinical presentation, and imaging features. All anomalies involving the central nervous system, the occipitocervical junction, and the upper cervical osseous canal were included. Complicating sequelae such as canal stenosis, segmental instability, and other anomalies of the central nervous system and spine were identified. RESULTS: Sixty-eight consecutive children were identified. Twenty-one patients had an underlying described syndrome. There were 234 osseous anomalies (average, 3.4 per patient). Three or more anomalies were noted in 79% of the patients. There was no significant difference in the mean number of anomalies (p = 0.80) or in the frequency of any specific anomaly (p > 0.20 for all) between syndromic and nonsyndromic patients. The variety of clinical presentations included neck pain (twenty-six patients), neurological changes (twenty-one patients), and torticollis and/or stiffness (twenty-one patients). Twenty-three patients had more than one complaint. Six patients had isolated spinal instability, twenty-eight had isolated spinal cord encroachment, and six had a combination of both. Forty-four (65%) of the sixty-eight patients underwent surgical decompression and/or arthrodesis principally focused from the foramen magnum to the second cervical vertebra. CONCLUSIONS: As a result of these findings, we recommend a thorough evaluation and advanced imaging of the upper cervical spine in all children who present with symptoms related to the upper cervical spine, to identify associated anomalies and further define the nature of canal encroachment including any potential for neurologic compromise.

Spinal cord dimensions in children with Klippel-Feil syndrome: a controlled, blinded radiographic analysis with implications for neurologic outcomes.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To evaluate the axial cross-sectional dimensions of the spinal cord and cerebrospinal fluid (CSF) column in children with Klippel-Feil Syndrome (KFS) versus an age-matched cohort of control subjects. SUMMARY OF BACKGROUND DATA: Neurologic sequelae and chronic pain are known to occur in KFS and factors implicated include spinal cord compression from canal stenosis, segmental instability, vascular disruption, and central nervous system abnormalities including tethered cord, syrinx, and diastomyelia. No study to date, however, has examined the role of spinal cord size as a contributing factor to neurologic sequelae in KFS. METHODS: We retrospectively reviewed the plain radiographic, magnetic resonance imaging (MRI), and clinical records of 12 consecutive patients between 2 and 18 years with KFS (average age 9.5 +/- 5.3 years) and 14 age-matched controls (average age 8.3 +/- 5.1 year). For each patient, plain film radiography was reviewed to compare Torg ratios at each cervical level, and axial T1-weighted MRI was used to compare spinal cord and CSF column cross-sectional area calculations. RESULTS: The Torg-Pavlov ratios were identical between the 2 groups (0.77 +/- 0.15 vs. 0.77 +/- 0.19). Analysis of axial T1-weighted MRI cross-sectional spinal cord area revealed that the cord was smaller in KFS patients at each level from C2-C7 compared with controls. These differences were statistically significant at C4 (P = 0.016), C5 (P = 0.035), and C6 (P = 0.032). Subset analysis of abnormal (fused) levels compared with controls revealed the same findings, although these differences were not significant due to the limited numbers available at each level. Analysis of the CSF column, however, revealed that overall the canal was slightly larger in KFS patients compared with controls, although this difference was not statistically significant. Four of the 12 KFS patients presented with neurologic symptoms, all of which improved after posterior cervical stabilization. CONCLUSION: In our cohort of patients we have noted statistically significant differences in axial cord dimensions, with no differences in CSF column, suggesting that the cord size is smaller in KFS children compared with age-matched controls.

Evaluation of spinal kinematics following lumbar total disc replacement and circumferential fusion using in vivo fluoroscopy.

STUDY DESIGN: In vivo fluoroscopic analysis of lumbar spinal motion with total disc replacement (TDR), fusions, and controls. OBJECTIVES: Compare and contrast lumbar spinal motion profiles in TDR, circumferential fusion, and controls. SUMMARY OF BACKGROUND DATA: TDR has been shown to preserve motion and possibly prevent abnormal loading at the adjacent level. Although in vitro cadaveric studies have provided invaluable information, they are not capable of assessing the physiologic motion profile of the lumbar spine that is initiated and stabilized by in vivo trunk muscular contractions. METHODS: Cross-sectional evaluation using high-frequency low-dose pulsated video fluoroscopy to evaluate lumbar spinal motion in subjects who underwent TDR (n = 8), circumferential fusion (n = 5), and controls (n = 4). Angulation and translation were recorded at 20 time points during the extension-flexion arc. Motion gradients, or slopes of the motion curves, were generated to allow for comparison of lumbar spinal motion profiles. RESULTS: Circumferential fusions exhibited significantly steeper motion gradients at the proximal adjacent level compared with TDR during flexion. TDR had more physiologic motion profiles at the proximal adjacent level than fusions during flexion and extension. At operative levels L4/5 and L5/S1, TDR and controls exhibited similar motion profiles in flexion, while fusions exhibited significantly less motion. In extension, however, TDR had a steeper slope than controls at the L4/5 operative level. Between L3 and S1, the total range of motion accounted for by the L4/5 proximal adjacent level was 59% in 1-level fusions, 38% in 1-level TDR, and 29% in controls. While no control or TDR subjects underwent sagittal plane translation >3 mm during flexion-extension, 80% of fusions did (average 3.7 mm), most notably during the latter phase of extension. CONCLUSIONS: TDR produces physiologic lumbar spinal motion profiles in flexion and extension at the operative and proximal adjacent levels. Fusions, however, produced steeper motion gradients at the proximal adjacent level, while undergoing significantly greater sagittal plane translation during flexion-extension.

Comparison of Cobb angle measurement of scoliosis radiographs with preselected end vertebrae: traditional versus digital acquisition.

STUDY DESIGN: Prospective study. OBJECTIVE: To compare variability in Cobb angle between digitally and traditionally acquired scoliosis radiographs. SUMMARY OF BACKGROUND DATA: Previous studies have shown that the 95% confidence interval for Cobb angle can vary from 2.6 degrees to 8.8 degrees. No study directly comparing Cobb angles measured from traditional and digitally acquired radiographs has been reported. METHODS: A spine model simulating 25 single right thoracic curves (range, 20 degrees-60 degrees) was imaged using traditional and digital techniques. Traditional films and miniaturized printed digital films were each measured twice manually. Digital films were also measured twice using computer imaging software. RESULTS: Overall mean angle and (95% confidence interval) were 41.7 degrees (39.1 degrees-44.3 degrees) for traditional, 40.6 degrees (37.4 degrees-43.8 degrees) for digital, and 39.7 degrees (36.3 degrees-43.1 degrees) for computer measurements. Overall correlation was 0.994 for traditional and digital, 0.987 for traditional and computer, and 0.993 for digital and computer. Fixed effect model analysis demonstrated that, although a statistically significant difference existed between the 3 methods of measuring the Cobb angle (P < 0.0001), the difference between methods was less than 2 degrees. CONCLUSIONS: Any of the 3 evaluated methods of measurement can be used to measure Cobb angles. Additionally, the methods can be used interchangeably.

Os odontoideum revisited: the case for a multifactorial etiology.

STUDY DESIGN: Retrospective analysis of our experience with os odontoideum at the Children's Hospital of Philadelphia. OBJECTIVE: To review the origin of os odontoideum and provide evidence for two separate etiologies. SUMMARY OF BACKGROUND DATA: The etiology of os odontoideum has been debated in the literature. Most authors support a post-traumatic etiology; however, some evidence exists to support a congenital origin. METHODS: We reviewed all 519 abnormal cervical spine radiographs performed from 1991 to 2004 to identify os odontoideum. Medical records and imaging studies were examined to determine: history of trauma, severity of injury, interval from injury to presentation, coexisting syndromes, and associated congenital cervical spine anomalies. RESULTS: Sixteen of 519 patients (3.1%) had os odontoideum. Only 8 of 16 patients reported previous trauma. Only 3 of these 8 injuries occurred with an interval remote enough to allow remodeling of the dens to an ossicle by the time of presentation. Six of 16 patients had associated congenital anomalies in the cervical spine. Three of 16 had a coexisting genetic syndrome. CONCLUSION: Our data supports two separate etiologies for the os odontoideum: post-traumatic and congenital. The data should raise awareness that some children with preexisting syndromes may develop os odontoideum without previous trauma.

Change in lordosis at the occipitocervical junction following posterior occipitocervical fusion in skeletally immature children.

STUDY DESIGN: Retrospective case series. OBJECTIVE: Evaluate the change in lordosis at the occipitocervical junction occurring during growth in skeletally immature children treated with posterior occipitocervical arthrodesis versus patients skeletally mature at arthrodesis. SUMMARY OF BACKGROUND DATA: Posterior occipitocervical arthrodesis is often indicated for children who have instability of the upper cervical spine develop. Theoretically, in skeletally immature children, this approach retards the growth of the posterior spinal elements but allows the anterior spinal column to continue to grow with the risk of excessive lordosis of the cervical spine developing. METHODS: There were 21 children, younger than 11 years (range 1.9-10.9) at surgery and expected to have normal spinal growth, followed radiographically for an average of 6.3 years (range 2.0-12.4). Postoperative lateral neutral radiographs were compared to those at most recent follow-up to measure the change in occipitocervical angle. These results were then compared to a series of control patients who were skeletally mature at surgery. RESULTS: Average overall change in lordosis at the occipitocervical junction was -4.6 degrees (range -12.8 degrees to +6.5 degrees). Average annualized change was -0.28 degrees per vertebral level per year (range -1.13 degrees to +0.67 degrees). This annualized change in angle was statistically significant compared to the average change of +0.01 degrees (range -0.09 degrees to +0.11 degrees) measured in the control series of patients skeletally mature at surgery (P = 0.01). CONCLUSIONS: Increasing lordosis occurs at the occipitocervical junction following fusion in skeletally immature children. If occipitocervical arthrodesis is indicated in a skeletally immature child, fusion in excessive extension and overtightening of posterior wires should be avoided.