John F. Sarwark

Relationships among musculoskeletal impairments and functional health status in ambulatory cerebral palsy.

Orthopedic surgery for patients with cerebral palsy addresses motion impairments, assuming that this will improve motor function. This study evaluates the relationships among clinical impairment measures with standardized assessments of function and disability as an initial step in testing this assumption. A total of 129 ambulatory children and adolescents across six institutions participated in a prospective evaluation that consisted of passive motion and spasticity examination of the lower extremities, three-dimensional gait temporal-spatial and kinematic analysis, and administration of the Gross Motor Function Measure (GMFM) and the Pediatric Outcomes Data Collection Instrument (PODCI). The analysis found that isolated impairment measures of motion and spasticity were only weakly related to motor function in cerebral palsy and even when averaged across multiple joints yielded no more than a fair correlation with functional scores, nor did a combination of impairments emerge that could predict substantial variance in motor function. These findings suggest that caution should be exercised when anticipating functional change through the treatment of isolated impairment and that addressing multiple impairments may be needed to produce appreciable effects.

Femoral shaft fractures in children treated with early spica cast.

We retrospectively reviewed 51 patients aged 3–11 years with femoral shaft fractures selected for treatment with early spica cast immobilization. Shortening > 20 mm was the most common complication, occurring in 22 (43%) of the 51 patients. Factors associated with unacceptable shortening were shortening at the time of spica cast application > 10 mm, shortening > 20 mm at initial examination, and increasing age. Achieving < 1 cm shortening at the time of cast application and close follow-up during the first 2 weeks after cast application are advised in order to achieve an acceptable final outcome.

Management of pediatric trauma

Injury is the number 1 killer of children in the United States. In 2004, injury accounted for 59.5% of all deaths in children younger than 18 years. The financial burden to society of children who survive childhood injury with disability continues to be enormous. The entire process of managing childhood injury is complex and varies by region. Only the comprehensive cooperation of a broadly diverse group of people will have a significant effect on improving the care and outcome of injured children. This statement has been endorsed by the American Association of Critical-Care Nurses, American College of Emergency Physicians, American College of Surgeons, American Pediatric Surgical Association, National Association of Childrens Hospitals and Related Institutions, National Association of State EMS Officials, and Society of Critical Care Medicine.

Evaluating congenital spine deformities for intraspinal anomalies with magnetic resonance imaging.

The incidence of intraspinal abnormalities associated with congenital spinal anomalies as detected by magnetic resonance imaging (MRI) is becoming better defined. In this study, 41 nonrandomized children with congenital spinal deformities (excluding myelomeningocele) who underwent complete MR evaluation were reviewed. Of the 41 congenital spinal deformities, 37 demonstrated congenital scoliosis, with failure of formation in 19, failure of segmentation in 4, and mixed defects in 14. The remaining four deformities were cases of congenital kyphosis. Thirteen patients with congenital spine anomalies were noted to have intraspinal abnormalities identified by MRI: tethered cord in 12 patients, syringomyelia in 3 patients, and diastematomyelia in 5 patients. Of the 12 patients with tethered cord, 2 patients had neurologic deficits. Urorectal anomaly was one of the most common associated findings (15%). Considering an incidence of intraspinal anomalies of 31% and as clinical manifestations may not be initially detectable, MRI is recommended in patients with congenital spinal deformity as part of the initial evaluation even in the absence of clinical findings.

Quantitative assessment with SPECT imaging of stress injuries of the pars interarticularis and response to bracing.

The evaluation and management of acute spondylolysis remains unclear in part because of outcome data that are primarily subjective. The aim of this study was to evaluate and monitor these patients objectively using quantitative single-photon emission computed tomography (SPECT). Thirty-four patients were so observed clinically between 1987 and 1996 and were studied with an initial and at least one follow-up SPECT scintigram. Initial radiographs and planar bone scans failed to demonstrate the pars lesion in 53 and 19% of the patients, respectively. The average SPECT ratio before brace treatment was 1.45. After treatment, this ratio significantly decreased to 1.27 (p = 0.03). A subset of patients remained symptomatic at follow-up. Their reduction in SPECT ratio averaged only 2.8% as compared with 13% for the remainder of the patients (p = 0.01). Patients diagnosed and braced in the early, more active stage of the condition (with greater intensity on SPECT) had more predictable symptom relief. An initial SPECT ratio of >1.5 was associated with complete symptom resolution after brace treatment. Patients treated with activity restriction only (>3 months) before bracing were more likely to have persistent symptoms and more modest improvement on SPECT (p = 0.01). These data, which use SPECT scintigraphy, support prompt treatment with brace immobilization for acute spondylolysis in children and adolescents.

Lesional and nonlesional skin from patients with untreated juvenile dermatomyositis displays increased numbers of mast cells and mature plasmacytoid dendritic cells

OBJECTIVE To investigate the distribution of mast cells and dendritic cell (DC) subsets in paired muscle and skin (lesional/nonlesional) from untreated children with juvenile dermatomyositis (DM). METHODS Muscle and skin biopsy samples (4 skin biopsy samples with active rash) from 7 patients with probable/definite juvenile DM were compared with muscle and skin samples from 10 healthy pediatric controls. Mast cell distribution and number were assessed by toluidine blue staining and analyzed by Students t-test. Immunohistochemical analysis was performed to identify mature DCs, myeloid DCs (MDCs), and plasmacytoid DCs (PDCs) by using antibodies against DC-LAMP, blood dendritic cell antigen 1 (BDCA-1), and BDCA-2, respectively. Myxovirus resistance protein A (MxA) staining indicated active type I interferon (IFN) signaling; positive staining was scored semiquantitatively and analyzed using the Mann-Whitney U test. RESULTS Both inflamed and nonlesional skin from patients with juvenile DM contained more mast cells than did skin from pediatric controls (P = 0.029), and comparable numbers of mast cells were present in lesional and nonlesional skin. Interestingly, mast cell numbers were greater in skin than in paired muscle tissue from patients with juvenile DM (P = 0.014) and were not increased in muscle from patients with juvenile DM compared with control muscle. Both muscle and skin from patients with juvenile DM showed more mature PDCs and MxA staining than did their corresponding control tissues (P < 0.05). In both muscle and skin from patients with juvenile DM and in pediatric control muscle, there were fewer MDCs than PDCs, and the distributions of MDCs and PDCs were similar in pediatric control skin samples. CONCLUSION The identification of mast cells in skin (irrespective of rash) from patients with juvenile DM, but not in paired muscle tissue, suggests that they have a specific role in juvenile DM skin pathophysiology. In skin from patients with juvenile DM, increased numbers of PDCs and increased expression of type I IFN-induced protein suggest a selective influence on T cell differentiation and subsequent effector function.

Association of apolipoprotein E genotype and cerebral palsy in children

OBJECTIVES. We tested the hypotheses that apolipoprotein E genotype, in particular carriage of the ε4 allele, is more likely to be associated with cerebral palsy and that children with more severe neurologic impairment are more likely to carry this allele. METHODS. In this cross-sectional study, 209 children with cerebral palsy were matched with healthy control subjects according to gender and race. Diagnosis of cerebral palsy was confirmed through physician consultation, medical chart review, and parent interview. Apolipoprotein E genotyping was performed with DNA obtained with buccal swabs. Severity of motor impairment was rated by physical therapists, and occipitofrontal circumference was measured. RESULTS. Compared with gender- and race-matched control subjects, overall risk for cerebral palsy was elevated 3.4-fold among children carrying an ε4 allele and was particularly elevated for children with quadriplegia/triplegia. This finding was independent of birth weight. Carriage of the ε4 allele was also associated with increased severity of cerebral palsy and with a trend toward increased likelihood for microcephaly. Moreover, children carrying an ε2 allele were at greater risk for cerebral palsy. CONCLUSIONS. These data implicate the apolipoprotein E ε4 and ε2 genotypes as susceptibility factors in determining neurologic outcomes after perinatal brain injury. Additional studies are warranted to establish the role of apolipoprotein E in specific pathogenetic pathways leading to cerebral palsy or poor neurologic outcomes after perinatal brain injury.

Cotransplantation with specific populations of spina bifida bone marrow stem/progenitor cells enhances urinary bladder regeneration

Spina bifida (SB) patients afflicted with myelomeningocele typically possess a neurogenic urinary bladder and exhibit varying degrees of bladder dysfunction. Although surgical intervention in the form of enterocystoplasty is the current standard of care in which to remedy the neurogenic bladder, it is still a stop-gap measure and is associated with many complications due to the use of bowel as a source of replacement tissue. Contemporary bladder tissue engineering strategies lack the ability to reform bladder smooth muscle, vasculature, and promote peripheral nerve tissue growth when using autologous populations of cells. Within the context of this study, we demonstrate the role of two specific populations of bone marrow (BM) stem/progenitor cells used in combination with a synthetic elastomeric scaffold that provides a unique and alternative means to current bladder regeneration approaches. In vitro differentiation, gene expression, and proliferation are similar among donor mesenchymal stem cells (MSCs), whereas poly(1,8-octanediol-cocitrate) scaffolds seeded with SB BM MSCs perform analogously to control counterparts with regard to bladder smooth muscle wall formation in vivo. SB CD34+ hematopoietic stem/progenitor cells cotransplanted with donor-matched MSCs cause a dramatic increase in tissue vascularization as well as an induction of peripheral nerve growth in grafted areas compared with samples not seeded with hematopoietic stem/progenitor cells. Finally, MSC/CD34+ grafts provided the impetus for rapid urothelium regeneration. Data suggest that autologous BM stem/progenitor cells may be used as alternate, nonpathogenic cell sources for SB patient-specific bladder tissue regeneration in lieu of current enterocystoplasty procedures and have implications for other bladder regenerative therapies.

A kyphectomy technique with reduced perioperative morbidity for myelomeningocele kyphosis.

Study Design. The lumbar sacropelvis in 11 patients with myelomeningocele and kyphosis was treated with a subtraction kyphectomy technique and posterior instrumentation. The results of this procedure in the 11 patients were evaluated and compared with previous results. Objective. To examine critically their experience using the subtraction (decancellation) vertebrectomy technique combined with posterior instrumentation for myelomeningocele kyphosis, the authors reviewed the charts of 18 myelomeningocele patients who underwent surgery for lumbar kyphosis between 1994 and 1998. Summary of Background. The benefits of restoring sagittal spinal alignment in myelomeningocele patients with severe lumbar kyphosis deformity to achieve postural stability and improved sitting balance generally are accepted. The optimal method of deformity correction, the extent of instrumentation, and the role of limited arthrodesis remain undefined. Methods. Of the 18 patients considered, 11 met the inclusion criteria of having undergone reconstruction using a subtraction (decancellation) vertebrectomy technique, preservation of the thecal sac, limited arthrodesis with posterior transpedicular lumbosacral instrumentation, and a minimum follow-up evaluation of 2 years. The study considered the age of the patient, number of levels fused, estimated blood loss, preoperative deformity, immediate postoperative correction, magnitude of correction, and maintenance of correction at latest follow-up assessment. Results. The average age at the time of the index procedure was 6 years (range, 3–12 years). The average preoperative kyphosis was 88° (range, 50–149°). Immediately after surgery, the average curve measurement was 3° lordosis (range, 50° to 50°). The average magnitude of postoperative sagittal plane deformity correction was 91° (range, 43–126°). Finally, the magnitude of correction maintained at the final follow-up assessment averaged 66° (range, 22–114°). This represented an average loss of correction at 2 years of 24° (range, 0–84°). There were no deaths, episodes of acute-onset hydrocephalus, vascular complications, or chronic deep wound infections. Conclusions. The subtraction (decancellation) vertebrectomy technique with preservation of the dural sac is a safe and efficacious technique for correction and stabilization of myelomeningocele kyphosis in young patients. Morbidity is reduced, as compared with that of excision techniques. Restoration of sagittal alignment at the time of initial correction and stabilization to achieve a balanced spine led to acceptable results.

Neural tube defects and the 13q deletion syndrome: Evidence for a critical region in 13q33‐34

Neural tube defects (NTD) are common findings in the 13q deletion syndrome, but the relationship between the 13q- syndrome and NTDs is poorly understood. We present a child with a 13q deletion and lumbosacral myelomeningocele. This was a boy with microcephaly, telecanthus, minor facial anomalies, and ambiguous genitalia. Cytogenetic and fluorescence in situ hybridization analysis showed a de novo 46,XY,del(13)(q33.2-->qter) with no visible translocation. By using microsatellite markers, the deletion breakpoint was mapped to a 350-kb region between D13S274 and D13S1311 and was paternal in origin. An analysis of 13q deletions with NTDs, including the present case, suggests that a deletion in 13q33-34 is sufficient to cause an NTD. The deletions associated with NTDs are distal to and nonoverlapping with the previously defined critical region in 13q32 for the major malformation syndrome [Brown et al., 1999: Am J Hum Genet 57: 859-866]. Our analysis also suggests that one or more genes in 13q33-34 produces NTDs by haploinsufficiency.