The authors present the case of a patient that demonstrates the long-standing use of megestrol acetate, a progesterone agonist, and its association with multiple intracranial meningioma presentation. Discontinuation of megestrol acetate led to shrinkage of multiple tumors and to the complete resolution of one tumor. Histological examination demonstrated that the largest tumor had high (by > 25% of tumor cell nuclei) progesterone-positive expression, including progesterone receptor (PR) isoform B, compared with low expression of PR isoform A; there was no evidence of estrogen receptor expression and only unaccentuated collagen expression. This is the first clinical report illustrating a causal relationship between exogenous hormones and modulation of meningioma biology in situ.
Sudhakar Vadivelu, Leroy Sharer and Michael Schulder
Sudhakar Vadivelu, Daniel Becker and John W. McDonald
To identify and evaluate stem cell–derived oligodendrocytes obtained for cell transplantation therapies, the authors developed a novel model to examine single, adult oligodendrocytes in situ.
Green fluorescent protein–expressing, mouse embryonic stem cells (ESCs) were neural induced and additionally staged in an oligosphere preparatory step for high-yield derivation of oligodendrocyte progenitors. These transplantable, induced progenitors were injected into postnatal Day 2 rat pups, in which spinal cord sections were then examined at 3 and 9 weeks posttransplantation.
Transplanted oligosphere ESCs survived and integrated anatomically into postnatal and adult white matter, generating targeted regions of chimeric spinal cord. A simple model for identifying adult oligodendrocytes in situ is presented, which is suitable for use in further studies examining functional myelination and derivation of oligodendrocytes from genetically engineered ESC lines, including human ESCs. Results from the model presented here demonstrate a unique method for examining transplantable oligodendrocyte progenitors derived from ESCs for repair of white matter disease.
Akash J. Patel, Sudhakar Vadivelu, Sohum K. Desai and Andrew Jea
The authors describe rare cases of congenital hypoplasia of the L-5 pedicles and the congenital absence of the left S-1 pedicle in 2 young girls, respectively, including the presentation, diagnosis, and treatment. Moreover, they review the literature on this clinical entity. The patients presented with intractable chronic low-back pain. Plain radiographs and 2D CT scanning revealed the presence of the aforementioned anomalies. Degenerative changes to adjacent level and contralateral facet joints were thought to be the result of overload and instability and seemed to have led to spondylolisthesis, micromotion at L-5 and S-1, and subsequent low-back pain. The pediatric patients were treated with posterior instrumented fusion with good functional outcomes at a minimum 3-month follow-up. To the best of the authors' knowledge, these are the first reports of intractable low-back pain and spondylolisthesis accompanied by hypoplastic-aplastic pedicles at the lumbosacral junction in children.
Sudhakar Vadivelu, Morris Edelman, Steven J. Schneider and Mark A. Mittler
The authors describe the case of a child who presented with hydrocephalus and phenotypic features characteristic of a multiple congenital anomalies/mental retardation syndrome. Dysmorphic facies, medial plantar lipomatosis, and developmental delay were observed in this case and are identical to documented findings of Pierpont syndrome diagnosed in 3 boys. This is the fourth case reported to date and is the first documented case of an oncological process— an intraventricular atypical choroid plexus papilloma tumor—found in association with Pierpont syndrome. Syndromes associated with choroid plexus papilloma are reviewed.
Loyola V. Gressot, Sudhakar Vadivelu, Steven W. Hwang, Daniel H. Fulkerson, Thomas G. Luerssen and Andrew Jea
Cervical spondylolysis is a rare condition that results from a pars interarticularis defect. The C-6 level is the most frequently involved site in the cervical spine. Its clinical presentations range from incidental radiographic findings to neck pain and, rarely, neurological deficits. Although 150 patients with subaxial cervical spondylolysis have been reported, a mere 24 adult and pediatric patients with C-2 spondylolysis have been described. The long-term outcomes of very young children with bilateral C-2 spondylolysis are of great interest, yet only a few longitudinal studies exist.
The authors retrospectively reviewed 5 cases of bilateral C-2 spondylolysis at Texas Children's Hospital and Riley Children's Hospital; these were combined with 5 other cases in the literature, yielding a total of 10 patients. Data regarding the patients' age, sex, C2–3 angulation and displacement, associated spine anomalies, neurological deficits, treatment, and most recent follow-up were recorded.
The patients' ages ranged from 3 to 36 months (mean 12.9 months). There were 6 boys and 4 girls. The C2–3 angulation, displacement, and width of pars defect were measured when available. The mean C2–3 angulation was 9.5° (range 1–34°), the mean C2–3 displacement was 4.78 mm (range 1.1–10.8 mm), and the mean width of the pars defect was 4.16 mm (range 0.9–7 mm). One patient developed myelopathy and spinal cord injury. All 10 of the patients were treated initially with conservative therapy: 3 with close observation alone, 1 with a rigid cervical collar, 4 with a Minerva jacket, 1 with a sternal-occipital-mandibular immobilizer, and 1 with a halo vest. Three patients ultimately underwent surgery for internal fixation due to progressive instability or development of neurological symptoms. All patients were neurologically intact at the last follow-up (mean 44.3 months, range 14–120 months).
Based on the literature and the authors' own experience, they conclude that most very young children with C-2 spondylolysis remain neurologically intact and maintain stability in long-term follow-up despite the bony defect. This defect is often an asymptomatic incidental finding and may be managed conservatively. More aggressive therapy including surgery is indicated for those patients with a neurological deficit from spinal cord compromise secondary to stenosis and local C-2 kyphosis, progressive deformity, or worsening C2–3 instability.
Sohum K. Desai, Sudhakar Vadivelu, Akash J. Patel, Alison Brayton and Andrew Jea
Isolated cervical canal stenosis at the level of the atlas (C-1) is a rare cause of cervical myelopathy in the pediatric population. It has been associated with several genetic disorders including spondyloepiphysial dysplasia congenita, Down syndrome, and Klippel-Feil syndrome. The purpose of this study is to highlight the authors' experience with 4 additional pediatric cases, review the literature, and report a new association of this disease with Williams syndrome.
The medical records and radiological imaging studies of 4 patients treated at Texas Children's Hospital for symptomatic hypoplasia of the atlas were retrospectively reviewed. Pertinent patient demographic data, clinical presentation, imaging findings, and outcomes after surgery were recorded. A thorough literature review was performed, allowing the authors to compare and contrast their 4 cases to surgical cases already published in the literature.
There were 11 boys and 1 girl in the aggregate series. The average age of the patients was 7 years (range 13 months–14 years), and the duration of symptoms prior to presentation was 6 months (range 0–36 months). The mean sagittal diameter of the spinal canal at the level of the atlas measured from the posterior aspect of the dens to the anterior aspect of the arch of C-1 was 11.9 mm (range 8.3–16 mm) in the aggregate series. In 2 new pediatric patients with hypoplasia of the atlas the disease was associated with Williams syndrome, which has not been previously described. Patients in the aggregate series were followed for an average of 18 months (range 3–50 months). Laminectomy of C-1 provided neurological improvement in all patients who presented.
Isolated cervical spinal canal stenosis at the level of the atlas is a rare cause of cervical myelopathy. The authors hope that this report will prompt clinicians to consider it when searching for the origin of signs and symptoms of cervical myelopathy, especially in children.
Sudhakar Vadivelu, Matthew Willsey, Daniel J. Curry and John W. McDonald III
Chronic neuropathic pain is a debilitating disease process associated with several medical disorders. Different from pain caused by inflammation, neuropathic pain is a diffuse pain disorder often found to be recalcitrant to the limited medical treatments available. Intractable nerve pain may benefit from other therapies capable of longer-lasting pain coverage or greater efficacy. A growing number of reports have emerged suggesting a role for stem cells as a cellular delivery source with neuroprotective agents opposing the effects of nerve damage. Here, the authors review the current experimental therapies examining the use of stem cells for the treatment of neuropathic pain disorders.
Sudhakar Vadivelu, Harold L. Rekate, Debra Esernio-Jenssen, Mark A. Mittler and Steven J. Schneider
The incidence of posttraumatic ventriculomegaly (PTV) and shunt-dependent hydrocephalus after nonaccidental head trauma (NAHT) is unknown. In the present study, the authors assessed the timing of PTV development, the relationship between PTV and decompressive craniectomy (DC), and whether PTV necessitated placement of a permanent shunt. Also, NAHT/PTV cases were categorized into a temporal profile of delay in admission and evaluated for association with outcomes at discharge.
The authors retrospectively reviewed the cases of patients diagnosed with NAHT throughout a 10-year period. Cases in which sequential CT scans had been obtained (n = 28) were evaluated for Evans' index to determine the earliest time ventricular dilation was observed. Discharge outcomes were assessed using the King's Outcome Scale for Childhood Head Injury score.
Thirty-nine percent (11 of 28) of the patients developed PTV. A low admission Glasgow Coma Scale (GCS) score predicted early PTV presentation (within < 3 days) versus a high GCS score (> 1 week). A majority of PTV/NAHT patients presented with a subdural hematoma (both convexity and interhemispheric) and ischemic stroke, but subarachnoid hemorrhage was significantly associated with PTV/NAHT (p = 0.011). Of 6 patients undergoing a DC for intractable intracranial pressure, 4 (67%) developed PTV (p = 0.0366). These patients tended to present with lower GCS scores and develop ventriculomegaly early. Only 2 patients developed hydrocephalus requiring shunt placement.
PTV presents early after NAHT, particularly after a DC has been performed. However, the authors found that only a few PTV/NAHT patients developed shunt-dependent hydrocephalus.
Christina Sayama, Sudhakar Vadivelu, Andrew Livingston, Allen Ho, Shayan A. Izaddoost, Valentina Briceño, Thomas G. Luerssen and Andrew Jea
Wound-related complications following complex posterior spine procedures in children may result in the need for serial debridements and may place spinal instrumentation at risk. In this study, the authors review their experience with the management of soft-tissue defects from spinal instrumentation in 5 high-risk pediatric patients. The use of various rotational and transpositional flaps in the management of these complicated cases is discussed, as well as their outcomes.
The authors retrospectively reviewed the medical records of 5 patients who returned to the Neuro-Spine service at Texas Children's Hospital for erosion of spinal instrumentation through the skin between September 1, 2007, and October 31, 2012. Patient demographics and clinical and operative data were recorded.
Risk factors such as young age (1 case), poor nutritional status (1 case), multiple previous surgeries (3 cases), severe neurological deficits (2 cases), and history of radiation therapy for malignancy (2 cases) were noted in the 5 patients. The paraspinous flap (4 cases) was the mainstay of the treatment. Follow-up ranged from 7.5 to 17.5 months (mean 11 ± 4.2 months). One of the patients required more than 1 procedure for revision of the wound. Cultures were positive in 2 of the 5 cases. Spinal instrumentation was removed in 3 of the 5 cases; however, in all 3 of the cases there was evidence of delayed instability that developed after the removal of spinal instrumentation.
The use of local tissue flaps is safe and efficacious for treatment of posterior wound complications due to spinal instrumentation in children. Removal of spinal instrumentation should be avoided due to the development of delayed instability. Highly vascularized tissue is used to speed healing, clear bacteria, and eliminate dead space, obviating the need to remove contaminated spinal instrumentation.