Sudhakar Vadivelu

Repair of the Injured Spinal Cord and the Potential of Embryonic Stem Cell Transplantation

Traditionally, treatment of spinal cord injury seemed frustrating and hopeless because of the remarkable morbidity and mortality, and restricted therapeutic options. Recent advances in neural injury and repair, and the progress towards development of neuroprotective and regenerative interventions are basis for increased optimism. Neural stem cells have opened a new arena of discovery for the field of regenerative science and medicine. Embryonic stem (ES) cells can give rise to all neural progenitors and they represent an important scientific tool for approaching neural repair. The growing number of dedicated regeneration centers worldwide exemplifies the changing perception towards the do-ability of spinal cord repair and this review was born from a presentation at one such leading center, the Kentucky Spinal Cord Injury Research Center. Current concepts of the pathophysiology, repair, and restoration of function in the damaged spinal cord are presented with an overlay of how neural stem cells, particularly ES cells, fit into the picture as important scientific tools and therapeutic targets. We focus on the use of genetically tagged and selectable ES cell lines for neural induction and transplantation. Unique features of ES cells, including indefinite replication, pluripotency, and genetic flexibility, provide strong tools to address questions of neural repair. Selective marker expression in transplanted ES cell derived neural cells is providing new insights into transplantation and repair not possible previously. These features of ES cells will produce a predictable and explosive growth in scientific tools that will translate into discoveries and rapid progress in neural repair.

Regression of multiple intracranial meningiomas after cessation of long-term progesterone agonist therapy

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.

A Review of the Neurological and Neurosurgical Implications of Tuberculosis in Children

Tuberculous involvement of the central nervous system (CNS) and vertebral column is the most lethal and disabling form of tuberculosis (TB). Several factors contribute to poor outcome, including cerebrovascular involvement with ischemia, hydrocephalus, direct parenchymal injury and formation of abscess and inflammation in the brain and spinal cord, hyponatremia, seizures, and delayed diagnosis. Spinal spondylitis from TB and associated spinal deformity is the leading cause of paraplegia in developing countries. The evidence for supportive treatment of TB infection of the CNS is limited, leading to substantial differences in management protocols. Many of the treatment approaches used in TB infection of the CNS have been extrapolated from treatment of other acute neurological disorders such as bacterial meningitis and traumatic brain injury. We review data from the available literature and highlight questions relating to the neurological and neurosurgical care of children with TB infection of the CNS and vertebral column.

Infected lumbar dermoid cyst mimicking intramedullary spinal cord tumor: Observations and outcomes.

We report two unusual cases of a 17-month-old boy with a previously undiagnosed lumbar dermal sinus tract terminating in an intradural dermoid cyst and holocord edema or syrinx, presenting with paraparesis and sphincter dysfunction secondary to an intramedullary abscess and a 26-month-old boy with a previously undiagnosed lumbar dermal sinus tract terminating in an infected dermoid cyst and intramedullary abscess, presenting with recurrent episodes of meningitis and hydrocephalus. Pre-operative magnetic resonance imaging (MRI) studies in these patients were initially confused for an intramedullary spinal cord tumor; however, the presence of an associated dermal sinus tract made this diagnosis of neoplasm less likely. Total excision of the dermal sinus tract, debulking of the dermoid cyst and drainage of the intramedullary abscess through an L1-L5 osteoplastic laminoplasty and midline myelotomy, followed by long-term antibiotic therapy resulted in a good functional recovery. Post-operative MRI of the spine showed removal of the dermoid cyst, decreased inflammatory granulation tissue and resolution of the holocord edema or syrinx. We also performed a literature review to determine the cumulative experience of management of intramedullary abscess in this rare clinical setting.

Resting-State Functional MRI in Pediatric Epilepsy Surgery

Resting-state functional MRI (rs-fMRI) identifies resting-state networks (RSN) in the human brain by analyzing the connectivity of anatomically remote neuronal populations with synchronous low-frequency fluctuation in blood oxygen level-dependent (BOLD) signal. Network analysis has informed the understanding of functional brain organization and is beginning to reveal the impact that neurological disorders such as epilepsy may have on the developing cerebral cortex. Among children undergoing epilepsy surgery, mapping the brain networks supporting language, sensorimotor and visual function is a critical part of the preoperative evaluation. However, task-based functional mapping techniques are particularly difficult in immature patients and those with severe impairment. Functional mapping of RSN is a promising tool that may help circumvent the challenges of adequate cooperation and limited abilities of developmentally disabled children to perform age-appropriate functions. We discuss the current methodology of rs-fMRI in the pediatric population, review the literature of rs-fMRI in pediatric epilepsy and present our experience of using rs-fMRI for functional network mapping in children undergoing epilepsy surgery.

Choroid plexus papilloma and Pierpont syndrome

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.

Iatrogenic dural arteriovenous fistula and aneurysmal subarachnoid hemorrhage

The authors present the case of a patient who presented acutely with aneurysmal subarachnoid hemorrhage (SAH) and a contralateral iatrogenic dural arteriovenous fistula (DAVF). Diagnostic angiography was performed, revealing a right-sided middle cerebral artery (MCA) aneurysm and a left-sided DAVF immediately adjacent to the entry of the ventriculostomy and bur hole site. A craniotomy was performed for clipping of the ruptured MCA aneurysm, and the patient subsequently underwent endovascular obliteration of the DAVF 3 days later. The authors present their treatment of an iatrogenic DAVF in a patient with an aneurysmal SAH, considerations in management options, and a literature review on the development of iatrogenic DAVFs.

Normal Development and Measurements of the Occipital Condyle-C1 Interval in Children and Young Adults

BACKGROUND AND PURPOSE: Widening of the occipital condyle-C1 interval is the most specific and sensitive means of detecting atlanto-occipital dislocation. Recent studies attempting to define normal measurements of the condyle-C1 interval in children have varied substantially. This study was performed to test the null hypothesis that condyle-C1 interval morphology and joint measurements do not change as a function of age. MATERIALS AND METHODS: Imaging review of subjects undergoing CT of the upper cervical spine for reasons unrelated to trauma or developmental abnormality was performed. Four equidistant measurements were obtained for each bilateral condyle-C1 interval on sagittal and coronal images. The cohort was divided into 7 age groups to calculate the mean, SD, and 95% CIs for the average condyle-C1 interval in both planes. The prevalence of a medial occipital condyle notch was calculated. RESULTS: Two hundred forty-eight joints were measured in 124 subjects with an age range of 2 days to 22 years. The condyle-C1 interval varies substantially by age. Average coronal measurements are larger and more variable than sagittal measurements. The medial occipital condyle notch is most prevalent from 1 to 12 years and is uncommon in older adolescents and young adults. CONCLUSIONS: The condyle-C1 interval increases during the first several years of life, is largest in the 2- to 4-year age range, and then decreases through late childhood and adolescence. A single threshold value to detect atlanto-occipital dissociation may not be sensitive and specific for all age groups. Application of this normative data to documented cases of atlanto-occipital injury is needed to determine clinical utility.

Giant invasive spinal schwannoma in children: a case report and review of the literature

IntroductionGiant invasive spinal schwannoma is defined as a tumor that extends over two or more vertebral levels, erodes vertebral bodies, and extends into the extraspinal space disrupting myofascial planes. Because of its rarity, there have been few published reports describing clinical features and surgical outcomes, especially in the pediatric patient population.Case presentationWe analyzed the medical record, pathologic findings, and radiographic studies of a 14-year-old Hispanic boy who presented to Texas Children’s Hospital with a three-month history of progressive spastic paraparesis. Preoperative computed tomography and magnetic resonance imaging reports showed a large mass lesion centered at the left T7-8 neural foramen with intra- and extraspinal extension, resulting in severe spinal cord compression and vertebral body erosion, and protrusion into the retropleural space and descending aorta. Our patient underwent a single-stage posterior approach for complete resection of the tumor with reconstruction and stabilization of the vertebral column. The pathological examination was consistent with schwannoma. At the six-month follow-up, our patient had resolution of preoperative symptoms and remains neurologically intact without any radiographic evidence of recurrent tumor.ConclusionTo the best of our knowledge, our case represents the fourth child with giant invasive spinal schwannoma reported in the literature. We describe our case and review the literature to discuss the aggregate clinical features, surgical strategies, and operative outcomes for giant invasive spinal schwannoma in the pediatric age group.

Potential role of stem cells for neuropathic pain disorders.

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.