David F. Bauer

Oncolytic viral therapy of malignant glioma.

SummaryNovel approaches to treatment of malignant glioma, the most frequently occurring primary brain tumor, have included the use of a wide range of oncolytic viral vectors. These vectors, either naturally tumor-selective, or engineered as such, have shown promise in the handful of phase I and phase II clinical trials conducted in recent years. The strategies developed for each of the different viruses currently being studied and the history of their development are summarized here. In addition, the results of clinical trials in patients and their implication for future trials are also discussed.

Meta-analysis of hemorrhagic complications from ventriculostomy placement by neurosurgeons.

BACKGROUND:Ventriculostomy placement is an important diagnostic and therapeutic tool for neurosurgeons. Multiple authors have presented retrospective series of patients evaluating periprocedure hemorrhage. OBJECTIVE:We performed a meta-analysis of existing studies to determine a more accurate rate of hemorrhage. METHODS:A MEDLINE and PubMed search was performed to find all studies of 25 or more patients conducted since 1970 that found a hemorrhagic complication rate from placement of a ventriculostomy. Studies in which a non-neurosurgeon placed the ventriculostomy and studies involving premature infants were excluded. RESULTS:Sixteen studies were used to obtain data from 2428 ventriculostomy procedures. Hemorrhage was found after 203 procedures, and 52 of these hemorrhages were deemed significant by the authors. The cumulative rate of hemorrhage was 7.0% (95% confidence interval: 4.5%-9.4%), with P < .05. The cumulative rate of significant hemorrhage was 0.8% (95% confidence interval: 0.2%-1.4%) with P < .05. CONCLUSION:Based on our meta-analysis, the overall hemorrhagic complication rate from ventriculostomy placement by neurosurgeons is approximately 7%. The rate of significant hemorrhage from ventriculostomy placement is approximately 0.8%. Further prospective studies are warranted to better address this question.

The Relationship Between INR and Development of Hemorrhage With Placement of Ventriculostomy

BACKGROUND This study seeks to evaluate the relationship between the risk of symptomatic hemorrhage from ventriculostomy placement and International Normalized Ratio (INR) in patients who received a ventriculostomy after traumatic brain injury. METHODS Patients who received a ventriculostomy after traumatic brain injury between June 2007 and July 2008 were identified and their medical records were abstracted for information. RESULTS At the time of ventriculostomy placement, 32 patients had an INR<1.2, 26 patients had an INR 1.2 to 1.4, 12 patients had an INR 1.4 to 1.6, and one patient had an INR>1.6 (INR=1.61). No significant difference in the risk of hemorrhage between the groups was observed: 9.4%, 3.9%, 8.3%, and 0%, respectively (p=0.73). In a subgroup analysis of patients who received ventriculostomy in the Neurosurgical Intensive Care Unit within 24 hours of admission (n=54), the average time between admission and ventriculostomy placement in patients who did not receive fresh frozen plasma was 6.8 hours compared with 9.3 hours (p=0.03) for those who did. CONCLUSIONS In this retrospective study, INRs between 1.2 and 1.6 appeared to be acceptable for a neurosurgeon to place an emergent ventriculostomy in a patient with traumatic brain injury.

Postoperative Mycoplasma hominis infections after neurosurgical intervention

OBJECT Mycoplasma hominis is a rare cause of infection after neurosurgical procedures. The Mycoplasma genus contains the smallest bacteria discovered to date. Mycoplasma are atypical bacteria that lack a cell wall, a feature that complicates both diagnosis and treatment. The Gram stain and some types of culture media fail to identify these organisms, and typical broad-spectrum antibiotic regimens are ineffective because they act on cell wall metabolism. Mycoplasma hominis commonly colonizes the genitourinary tract in a nonvirulent manner, but it has caused postoperative, postpartum, and posttraumatic infections in various organ systems. The authors present the case of a 17-year-old male with a postoperative intramedullary spinal cord abscess due to M. hominis and report the results of a literature review of M. hominis infections after neurosurgical procedures. Attention is given to time to diagnosis, risk factors for infection, ineffective antibiotic regimens, and final effective antibiotic regimens to provide pertinent information for the practicing neurosurgeon to diagnose and treat this rare occurrence. METHODS A PubMed search was performed to identify reports of M. hominis infections after neurosurgical procedures. RESULTS Eleven cases of postneurosurgical M. hominis infection were found. No other cases of intramedullary spinal cord abscess were found. Initial antibiotic coverage was inadequate in all cases, and diagnosis was delayed in all cases. Multiple surgical interventions were often needed. Once appropriate antibiotics were started, patients typically experienced rapid resolution of their neurological symptoms. In 27% of cases, a suspicious genitourinary source other than urinary catheterization was identified. CONCLUSIONS Postoperative M. hominis infections are rarely seen after neurosurgical procedures. They are typically responsive to appropriate antibiotic therapy. Mycoplasma infection may cause prolonged hospitalization and multiple returns to the operating room due to delay in diagnosis. Early clinical suspicion with appropriate antibiotic coverage could help prevent these significant complications.

Risk factors for conversion to permanent ventricular shunt in patients receiving therapeutic ventriculostomy for traumatic brain injury.

BACKGROUND:Intracranial pressure is routinely monitored in patients with severe traumatic brain injury (TBI). Patients with TBI sometimes develop hydrocephalus, requiring permanent cerebrospinal fluid (CSF) diversion. OBJECTIVE:To quantify the need for permanent CSF diversion in patients with TBI. METHODS:Patients who received a ventriculostomy after TBI between June 2007 and July 2008 were identified, and their medical records were abstracted to a database. RESULTS:Sixteen of 71 patients (22.5%) receiving a ventriculostomy required a ventriculoperitoneal or ventriculoatrial shunt before discharge from the hospital. The average number of days between ventriculostomy and shunt was 18.3. Characteristics that predispose these patients to require permanent CSF diversion include the need for craniotomy within 48 hours of admission (odds ratio, 5.20; 95% confidence interval, 1.48-18.35) and history of culture-positive CSF (odds ratio, 5.52; 95% confidence interval, 1.19-25.52). Length of stay was increased in patients receiving permanent CSF diversion (average length of stay, 61 vs 31 days; P = .04). Patient discharge disposition was similar between shunted and nonshunted patients. CONCLUSION:In this retrospective study, 22% of TBI patients who required a ventriculostomy eventually needed permanent CSF diversion. Patients with TBI should be assessed for the need for permanent CSF diversion before discharge from the hospital. Care must be taken to prevent ventriculitis. Future studies are needed to evaluate more thoroughly the risk factors for the need for permanent CSF diversion in this patient population.

Surgical manifestations of thoracic arachnoid pathology: series of 28 cases

OBJECT Various pathologies involving the thoracic arachnoid mater uniformly manifest as thoracic myelopathy and may present a significant management dilemma. The authors undertook this study to assess outcome in cases of thoracic myelopathy due to thoracic arachnoid pathology. METHODS The authors have cared for and followed 28 patients with thoracic myelopathy from thoracic arachnoid pathology over the last 17 years. A chart review and contemporary follow-up of these patients was performed and outcomes were reported. RESULTS Patients with thoracic myelopathy from thoracic arachnoid pathology often have improvement in their condition after surgical decompression/detethering procedures. While not universal, patients in this series had improvement in mJOA scores at 1 year after surgery (p = 0.0001) and at last follow-up (p = 0.04). Results indicated that across a wide variety of pathologies the extent of thoracic spinal cord involvement is a predictor of the disease course and outcome. Comparison of the group of patients with cord involvement limited to 2 vertebral segments (short-segment pathology) versus the group with cord tethering of more than 2 segments (long-segment pathology) showed that patients in the short-segment group more frequently had ventral or dorsal arachnoid bands (p = 0.003), more frequently had signal change in the cord on MRI (p = 0.02), and less frequently presented with a syrinx (p = 0.02), and a smaller percentage of patients in this group underwent reoperation (p = 0.02). While patients with short-segment pathology typically improved after a single operative intervention, patients with long-segment pathology typically improved after multiple operations, frequently for CSF diversion. CONCLUSIONS Thoracic arachnoid pathology causing thoracic cord dysfunction and myelopathy is varied, has multiple etiologies, and can be difficult to treat over the long term. Surgical management, when indicated, is case specific. Serial long-term follow-up is essential to document enduring clinical and radiographic success.

Study of the effects of flexion on the position of the conus medullaris

BackgroundPrevious anatomic studies have shown the conus medullaris to terminate between T12 and L1 vertebral levels in adults with normal spinal anatomy. Prior anatomic and radiographic studies of conus position with flexion and extension of the spine have had conflicting results. We performed a cadaveric study with direct visualization of the conus during flexion and extension to further study this question and potentially determine if flexion and extension of the spine during magnetic resonance imaging may prove to be a diagnostic tool in such pathologies as occult tethered cord syndrome.Materials and methodsWe performed T12 to L3 laminectomies in five fresh adult cadavers and exposed the conus and cauda equina. Cadavers were fully flexed at the waist and neck and the conus position observed.ResultsIn all specimens, the conus terminated between T12 and L1 in the prone position. During flexion, the conus position remained stable with no ascent. However, flexion produced stretching and medial displacement of the cauda equina.ConclusionsFlexion of the spine does not cause the conus medullaris to change position in fresh human cadavers; however, flexion does cause the cauda equina to stretch and displace medially over the conus. Therefore, it is unlikely that the conus would change position during spine flexion during imaging or procedures such as lumbar puncture.

SMARCE1 mutations in pediatric clear cell meningioma: case report

Clear cell meningioma (CCM) is an uncommon variant of meningioma. The authors describe a case of a pediatric CCM localized to the lumbar spine. After resection, sequencing revealed an inactivating mutation in the SWI/SNF chromatin remodeling complex subunit SMARCE1, with loss of the second allele in the tumor. The authors present a literature review of this mutation that is associated with CCM and a family history of spine tumors.

CSF hydrothorax without intrathoracic catheter migration in children with ventriculoperitoneal shunt.

Background: Thoracic complications of ventriculoperitoneal (VP) shunts have been extensively reported in the literature. Cerebrospinal fluid (CSF) hydrothorax without catheter migration, however, has been rarely described and poorly understood. Case Description: We describe development of pleural effusion and respiratory distress in a 3-year-old boy with no evidence of VP shunt catheter displacement on plain radiograph and stable ventricle size on rapid sequence magnetic resonance imaging (MRI) brain. Chest X-ray revealed complete opacity of right hemithorax. Pleural effusion was consistent with transudate. Beta-2 transferrin returned positive. The patient underwent externalization of VP shunt, and upon resolution of effusion, re-internalization with new distal shunt catheter. A literature review of CSF hydrothorax in children without intrathoracic shunt migration was performed. Eleven cases were identified in the English literature. Age at VP shunt placement ranged from birth to 8 years of age. Interval from VP shunt placement to CSF hydrothorax ranged from 1.5 months to 5 years. History of shunt revision was reported in two cases. Presenting symptoms also included ascites and inguinal hernia or hydrocele. Reported diagnostic studies consist of CSF culture, radionuclide shuntogram, beta-2 transferrin, and beta-trace protein. Laterality of the VP shunt and development of pleural effusion were predominantly right sided. Definitive surgical treatment included VA shunt, repositioning of the peritoneal catheter, and endoscopic choroid plexus coagulation. Conclusion: CSF hydrothorax is a rare thoracic complication of VP shunt placement with no radiographic evidence of shunt migration or malfunction. Postulated mechanisms include limited peritoneal capacity to resorb CSF in children and microscopic communications present in congenital diaphragmatic hiatuses.

A prospective natural history study of nonoperatively managed Chiari I malformation: does follow-up MRI surveillance alter surgical decision making?

OBJECT Chiari malformation Type I (CM-I) in children is a common incidental finding. Resolution of cerebellar tonsil ectopia has been reported, but no studies have followed tonsil position over regular intervals throughout childhood. To better elucidate the clinical and radiological natural history of CM-I in children, the authors prospectively followed up children with nonoperatively managed CM-I for up to 7 years. METHODS The study included all children evaluated for CM-I over a period of 12 years for whom surgery was not initially recommended. The study excluded patients with associated conditions, including syringomyelia and hydrocephalus. For all patients, initial management was nonoperative, and follow-up management consisted of annual cervical spine or brain MRI and clinical examination. At each follow-up examination, the neurological examination findings, subjective symptoms, and the position of the cerebellar tonsils on MR images were recorded. An alteration in tonsillar descent of 2 mm or greater was considered a change. RESULTS Neurological examination findings did not change over the course of the study in the 52 children who met the inclusion criteria. Although radiological changes were common, no surgeries were performed solely because of radiological change. Overall, tonsil position on radiological images remained stable in 50% of patients, was reduced in 38%, and increased in 12%. Resolution was seen in 12% of patients. Radiological changes in tonsil position were seen during every year of follow-up. On average, in any given year, 24% of images showed some form of change in tonsil position. A total of 3 patients, for whom no changes were seen on MR images, ultimately underwent surgery for subjective clinical reasons. CONCLUSIONS CM-I in children is not a radiologically static entity but rather is a dynamic one. Radiological changes were seen throughout the 7 years of follow-up. A reduction in tonsillar descent was substantially more common than an increase. Radiological changes did not correlate with neurological examination finding changes, symptom development, or the need for future surgery. Follow-up imaging of asymptomatic children with CM-I did not alter treatment for any patient. It would be reasonable to follow these children with clinical examinations but without regular surveillance MRI.