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ABSTRACT: Though radiation therapy is generally considered the most effective treatment for unresectable pilocytic astrocytomas in children, there are few data to support this claim. To examine the efficacy of radiation therapy for pediatric pilocytic astrocytomas, we retrospectively reviewed the experience at our institution.
Thirty-five patients 18 years old or younger with unresectable tumors and without evidence of neurofibromatosis have been treated since 1982. Patients were treated with local radiation fields to a median dose of 54 Gy. Six patients were treated with radiosurgery to a median dose of 15.5 Gy. Five patients were treated with initial chemotherapy and irradiated after progression.
All patients were alive after a median follow-up of 5.0 years. However, progression-free survival was 68.7%. None of 11 infratentorial tumors progressed compared with 6 of 20 supratentorial tumors. A trend toward improved progression-free survival was seen with radiosurgery (80%) compared with external beam alone (66%), but this difference did not reach statistical significance. Eight of the 9 patients progressing after therapy did so within the irradiated volume.
Although the survival of these children is excellent, almost one third of patients have progressive disease after definitive radiotherapy. Improvements in tumor control are needed in this patient population, and the optimal therapy has not been fully defined. Prospective trials comparing initial chemotherapy to radiation therapy are warranted.
International journal of radiation oncology, biology, physics 03/2011; 79(3):829-34. · 4.59 Impact Factor
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ABSTRACT: Children may be more vulnerable to diagnostic radiation exposure because of the increased dose-volume ratio and the increased lifetime risk per unit dose of radiation from early exposure. Moreover, recent radiological literature suggests that exposure to ionizing radiation from imaging studies may play a role in the later development of malignancies.
We review the literature and present two illustrative clinical examples of children (each child developed head and neck malignancies during their late teen years) with hydrocephalus requiring multiple cerebrospinal fluid (CSF) shunt revisions and diagnostic computerized tomography (CT) scans throughout their life.
The literature reviewed suggests that children are more prone to diagnostic radiation exposure. Although it is not possible to prove that the multiple diagnostic studies result in malignancies, our review of the literature and illustrative cases describing malignancy risk and radiation exposure should give clinicians pause when considering requesting multiple diagnostic CT studies in children during the evaluation of possible CSF shunt dysfunction. Alternative tests such as "shunt MRI" protocols should be considered for patients and used whenever possible to minimize exposure to ionizing radiation.
Child s Nervous System 05/2008; 24(4):493-7. · 1.54 Impact Factor
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ABSTRACT: Dysembryoplastic neuroepithelial tumours (DNETs) were incorporated into the new World Health Organization classification of brain tumours as part of the group of glioneuronal tumours in 1993. Large series of patients with DNETs and pharmaco-resistant epilepsy have been reported. DNETs are most often located in the temporal lobe, occurring in both mesial and lateral temporal locations. DNETs have also been reported in the insular cortex, brain stem, cerebellum, occipital lobe and striatum. Approximately 40% of DNETs are cystic, and solitary nodular, multinodular or diffuse forms have been recognized. Approximately 30% of DNETs are associated with subtle cortical dysplastic changes in the adjacent cortex. DNET nodules usually look like oligodendroglioma, whilst between the nodules it may be possible to recognize vertical columns of neurons surrounded by oligodendrocyte-like cells. Cytologically, oligodendroglial-like cells of DNETs are distinguished from oligodendroglioma by larger nuclei with frequent nuclear indentations and multiple, small nucleoli, whilst oligodendrogliomas consistently show nuclear roundness with one or two occasional nucleoli. Very rare cases of malignant transformation have been reported. DNETs are hypodense on CT and demonstrate decreased signal on the T1-weighted images and a hyper-intense signal on T2-weighted MRI. DNETs associated with pharmaco-resistant epilepsy should be removed early to achieve seizure freedom and prevent tumour progression. The surgical approach should be that of an extended lesionectomy, i.e. excision of the lesion and the abnormal dysplastic cortex around it. Use of MRI-based image guidance (neuronavigation) as a surgical tool to identify this area of abnormal cortex is very helpful to ensure that the extended lesionectomy includes any visibly dysplastic cortex. It is not advocated to use a stereotactic biopsy only, as this may generate an unrepresentative tissue sample consisting of an oligodendroglial component only and may lead to an incorrect diagnosis.
British Journal of Neurosurgery 01/2008; 21(6):539-49. · 0.88 Impact Factor
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ABSTRACT: Cerebrovascular inflammation contributes to secondary brain injury following ischemia. Recent in vitro studies of cell migration and molecular guidance mechanisms have indicated that the Slit family of secreted proteins can exert repellant effects on leukocyte recruitment in response to chemoattractants. Utilizing intravital microscopy, we addressed the role of Slit in modulating leukocyte dynamics in the mouse cortical venular microcirculation in vivo following TNFalpha application or global cerebral ischemia. We also studied whether Slit affected neuronal survival in the mouse global ischemia model as well as in mixed neuronal-glial cultures subjected to oxygen-glucose deprivation. We found that systemically administered Slit significantly attenuated cerebral microvessel leukocyte-endothelial adherence occurring 4 h after TNFalpha and 24 h after global cerebral ischemia. Administration of RoboN, the soluble receptor for Slit, exacerbated the acute chemotactic response to TNFalpha. These findings are indicative of a tonic repellant effect of endogenous Slit in brain under acute proinflammatory conditions. Three days of continuous systemic administration of Slit following global ischemia significantly attenuated the delayed neuronal death of hippocampal CA1 pyramidal cells. Moreover, Slit abrogated neuronal death in mixed neuronal-glial cultures exposed to oxygen-glucose deprivation. The ability of Slit to reduce the recruitment of immune cells to ischemic brain and to provide cytoprotective effects suggests that this protein may serve as a novel anti-inflammatory and neuroprotective target for stroke therapy.
Experimental Neurology 11/2007; 207(2):186-94. · 4.70 Impact Factor
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ABSTRACT: The indications for surgical repair of congenital brachial plexus palsy are controversial. Our objective was to determine the results of early brachial plexus surgery following obstetric-induced brachial plexus palsy.
We performed a retrospective analysis of the outcome of 58 cases of brachial plexus surgery. The indication for operation consisted of the presence of less than antigravity strength in the biceps, triceps, and deltoid muscle groups at 6 months of age. Data gathered prospectively, previously, showed the likelihood of improvement with less than antigravity strength in these cases to be poor.
Follow-up data were obtained on 52 of the 58 cases. Overall mean follow-up was 2 years. Twelve patients had more than 3 years follow-up (mean 5.5 years, range 3-11.5 years). Significant improvement was seen in all injury patterns i.e., C5-C6, C5-C7, and C5-C8, T1. Greater than antigravity strength in the biceps, triceps, and deltoid muscle groups was seen in the majority of cases at follow-up.
Repair of obstetrical brachial plexus palsy in children at 6 months of age that is based on less than antigravity strength in the biceps, triceps, and deltoid muscle groups produces improvement in functional capabilities. Children with obstetrical brachial plexus palsy should be referred soon after birth to a center that specializes in the treatment of this type of palsy.
Child s Nervous System 03/2006; 22(2):103-12. · 1.54 Impact Factor
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ABSTRACT: IntroductionThe indications for surgical repair of congenital brachial plexus palsy are controversial. Our objective was to determine the results of early brachial plexus surgery following obstetric-induced brachial plexus palsy.MethodsWe performed a retrospective analysis of the outcome of 58 cases of brachial plexus surgery. The indication for operation consisted of the presence of less than antigravity strength in the biceps, triceps, and deltoid muscle groups at 6 months of age. Data gathered prospectively, previously, showed the likelihood of improvement with less than antigravity strength in these cases to be poor.ResultsFollow-up data were obtained on 52 of the 58 cases. Overall mean follow-up was 2 years. Twelve patients had more than 3 years follow-up (mean 5.5 years, range 3–11.5 years). Significant improvement was seen in all injury patterns i.e., C5-C6, C5-C7, and C5-C8, T1. Greater than antigravity strength in the biceps, triceps, and deltoid muscle groups was seen in the majority of cases at follow-up.ConclusionsRepair of obstetrical brachial plexus palsy in children at 6 months of age that is based on less than antigravity strength in the biceps, triceps, and deltoid muscle groups produces improvement in functional capabilities. Children with obstetrical brachial plexus palsy should be referred soon after birth to a center that specializes in the treatment of this type of palsy.
Child s Nervous System 01/2006; 22(2):103-112. · 1.54 Impact Factor
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ABSTRACT: Results of recent studies reveal vascular and neuroprotective effects of matrix metalloproteinase-9 (MMP-9) inhibition and MMP-9 gene deletion in experimental stroke. However, the cellular source of MMP-9 produced in the ischemic brain and the mechanistic basis of MMP-9-mediated brain injury require elucidation. In the present study, we used MMP-9-/- mice and chimeric knockouts lacking either MMP-9 in leukocytes or in resident brain cells to test the hypothesis that MMP-9 released from leukocytes recruited to the brain during postischemic reperfusion contributes to this injury phenotype. We also tested the hypothesis that MMP-9 promotes leukocyte recruitment to the ischemic brain and thus is proinflammatory. The extent of blood-brain barrier (BBB) breakdown, the neurological deficit, and the volume of infarction resulting from transient focal stroke were abrogated to a similar extent in MMP-9-/- mice and in chimeras lacking leukocytic MMP-9 but not in chimeras with MMP-9-containing leukocytes. Zymography and Western blot analysis from these chimeras confirmed that the elevated MMP-9 expression in the brain at 24 h of reperfusion is derived largely from leukocytes. MMP-9-/- mice exhibited a reduction in leukocyte-endothelial adherence and a reduction in the number of neutrophils plugging capillaries and infiltrating the ischemic brain during reperfusion; microvessel immunopositivity for collagen IV was also preserved in these animals. These latter results document proinflammatory actions of MMP-9 in the ischemic brain. Overall, our findings implicate leukocytes, most likely neutrophils, as a key cellular source of MMP-9, which, in turn, promotes leukocyte recruitment, causes BBB breakdown secondary to microvascular basal lamina proteolysis, and ultimately contributes to neuronal injury after transient focal stroke.
AJP Heart and Circulatory Physiology 09/2005; 289(2):H558-68. · 3.71 Impact Factor
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David B Mansur,
Arie Perry,
Veena Rajaram,
Jeff M Michalski, T S Park,
Jeffrey R Leonard,
Lori Luchtman-Jones,
Keith M Rich,
Perry W Grigsby,
Mary Ann Lockett,
Sasha H Wahab,
Joseph R Simpson
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ABSTRACT: To retrospectively determine the long-term outcome of intracranial ependymoma patients treated with surgery and postoperative radiation therapy.
Sixty patients were treated at our institution between 1964 and 2000. Forty patients had World Health Organization Grade II ependymoma, and 20 patients had Grade III ependymoma. The median patient age was 10.7 years. The majority of patients were male (55%), had infratentorial tumors (80%), and had subtotal resections (72%). Postoperative radiation therapy was delivered to all patients to a median total dose of 50.4 Gy. Craniospinal radiation therapy was used in the earlier era in only 12 patients (20%).
The median follow-up of surviving patients was 12.5 years. The 5-year and 10-year disease-free survival rates for all patients were 58.4% and 49.5%, respectively. The 5-year and 10-year overall survival rates for all patients were 71.2% and 55.0%, respectively. Supratentorial tumor location was independently associated with a worse disease-free survival. Subtotal resection and supratentorial location predicted a worse overall survival, but this failed to reach statistical significance. No statistically significant effect on prognosis was observed with tumor grade, patient age, or radiation dose or volume.
Our long-term follow-up indicates that half of ependymoma patients will have disease recurrences, indicating the need for more effective treatments.
International Journal of Radiation OncologyBiologyPhysics 03/2005; 61(2):387-91. · 4.11 Impact Factor
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ABSTRACT: Selective dorsal rhizotomy (SDR) is an effective treatment for lower extremity spasticity in cerebral palsy. Cortical organization in sensory cortex may be abnormal in cerebral palsy, and deafferentation is known to lead to cortical reorganization in many situations.
We used functional magnetic resonance imaging (fMRI) of hand sensory stimulation to determine if the partial deafferentation of the lower extremity sensory system, associated with SDR, led to any alterations in the cortical somatosensory representation for the upper limbs. Three patients with spastic diplegia were studied with blood oxygen level-dependent (BOLD)-fMRI before and after SDR. fMRI during tactile stimulation of the digits of the right hand was used to map hand somatosensory cortex. Comparison of the cortical maps devoted to the hand before and after SDR assessed for cortical reorganization following partial deafferentation of the lower extremity.
In the one patient with upper extremity involvement, the hand sensory representation was markedly enhanced following SDR. In the other two patients, a normal pattern, but with diminished activity, was seen compared with preoperative findings. SDR for lower limb spastic diplegia does not lead to extensive reorganization of cortex dedicated to the representation of the upper limb. An essentially normal pattern of activation was seen both before and after SDR.
The relief of attention demands associated with spasticity may explain the modulation in intensity seen after SDR in the patients who exhibited no upper extremity involvement despite lower limb spasticity.
Child s Nervous System 03/2005; 21(2):115-21. · 1.54 Impact Factor
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ABSTRACT: Obstructive sleep apnea, apnea of prematurity, and sudden infant death syndrome are associated with a high risk of morbidity and mortality secondary to the neuronal and cerebrovascular consequences of the associated intermittent hypoxia. We hypothesized that episodic hypoxia (EH) promotes inflammation in the cerebral microcirculation and that nitric oxide (NO) produced by the endothelial and neuronal isoforms of NO synthase (eNOS and nNOS, respectively) modulates this response. Anesthetized and ventilated Swiss-Webster ND4 mice, wild-type mice, and NO synthase knockout mice were subjected to a 1-h period of EH (twelve 30-s periods of hypoxia every 5 min). Four, 24, or 48 h later, mice were reanesthetized for imaging of leukocyte dynamics in the cortical venular microcirculation by epifluorescence videomicroscopy through closed cranial windows. In Swiss-Webster ND4 mice, leukocyte adherence increased 2.1-fold at 4 h, 3.4-fold at 24 h, and 1.8-fold at 48 h relative to time-matched, normoxic controls; there was no evidence of delayed hippocampal CA1 pyramidal cell death. A similar response was noted in wild-type mice. However, in eNOS knockouts, leukocyte-endothelial cell adherence was elevated to 4.4-fold over baseline 24 h after EH, and a significant fraction of these animals showed evidence of delayed CA1 cell death. Conversely, in nNOS knockouts, no increase in adherence was noted at 24 h and CA1 viability remained unaffected. We conclude that NO derived from nNOS promotes an inflammatory response in the cerebrovascular microcirculation after short-term EH and that NO produced by eNOS blunts the extent of this response and exerts neuroprotective effects.
Journal of Applied Physiology 04/2004; 96(3):1223-30; discussion 1196. · 3.75 Impact Factor
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ABSTRACT: Shuntograms are performed when patients present with symptoms suggestive of, but inconclusive for, shunt malfunction, without confirmatory radiological evidence.
Shuntograms over the past 3.5 years were reviewed. Patient records were reviewed for revision in proximity to a negative (normal) study.
One hundred and fifteen out of 149 tests were negative. Thirty-four surgeries (in 31 patients) occurred subsequent to a negative shuntogram. In 18 out of 34 revisions the shunt was functional: 13 surgeries were for overdrainage, 4 were for unrelated reasons with shunt function confirmed incidentally and 1 was an exploration for cognitive deterioration. In 16 cases (13 patients) the shunt was not functional: 12 had proximal catheter occlusion in which, on subsequent review, there was no ventricular reflux present and the remaining had distal malfunctions.
The false negative rate for shuntograms was 16 out of 115 (14%) with proximal occlusion most common. This estimate of the predictive value of a normal flow study may influence the decision to revise a shunt.
Child s Nervous System 07/2003; 19(5-6):337-41. · 1.54 Impact Factor
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ABSTRACT: Ventriculoperitoneal shunts have one of the highest complication rates of all neurosurgical procedures. The purpose of this study was to identify factors associated with malfunction of shunts placed in infants with neonatal hydrocephalus, with the goal of maximizing long-term shunt survival.
We performed a retrospective chart review of 200 consecutive patients less than 1 year old who underwent primary intracranial shunt placement for hydrocephalus by one of two experienced pediatric neurosurgeons at a single institution. A multivariate analysis was conducted to identify variables that were statistically independent predictors of a shunt malfunction or problem.
Adequate data were available for 158 patients, with a mean follow-up of 39.8 months (range 6-99 months). Variables tested for independent prediction of shunt revision included the etiology of the hydrocephalus, gestation period, age at shunt placement, surgeon, ventricular catheter entry site and valve opening pressure. Frontal versus occipital catheter entry site was not associated with a different revision rate. The only significant controllable factor associated with shunt malfunction was the valve opening pressure. The revision rate per year of follow-up was 4 times higher for patients with no valve or a low-pressure valve than for patients with a medium- or high-pressure valve.
This retrospective review demonstrated that the valve opening pressure is an important component of the shunt complication rate. A prospective multicenter randomized trial is warranted to further evaluate the conclusions of this study.
Pediatric Neurosurgery 01/2003; 37(6):287-94. · 0.70 Impact Factor
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ABSTRACT: Spasticity is an endpoint of a variety of neurologic disorders with upper motor neuron damage. There have been several studies demonstrating improvement in spasticity through administration of intrathecal baclofen. Withdrawal from oral baclofen has been well described. Intrathecal baclofen withdrawal has been less frequently reported. We present a case of withdrawal after intrathecal baclofen pump catheter failure.
A 14-year-old boy presented with fevers, which were thought to be related to recent spine surgery and possible pneumonia. Eventual workup revealed evidence of intrathecal baclofen withdrawal owing to pump catheter failure. His fevers, with temperatures of up to 40 degrees C, and painful muscle spasms resolved and his clinical condition improved after pump exploration and resumption of intrathecal delivery.
Intrathecal baclofen withdrawal can be life threatening. Prompt recognition and restoration of an adequate intrathecal baclofen dose is essential for recovery.
Child s Nervous System 11/2002; 18(9-10):522-5. · 1.54 Impact Factor
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Pediatric Neurosurgery 06/2002; 36(5):275-6. · 0.70 Impact Factor
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ABSTRACT: Infantile myofibromatosis is the most common fibrous disorder of infancy and early childhood. Intracranial involvement is rare, with the majority of lesions being localized to the skull or dura with variable intracranial extension. We present the case of a 19-month-old girl with infantile myofibromatosis and an incidentally discovered, enlarging, calcified, posterior fossa mass. The patient underwent suboccipital craniotomy and resection of the lesion. This is the first report of the surgical removal of an intraparenchymal infantile myofibroma.
Pediatric Neurosurgery 05/2002; 36(4):214-7. · 0.70 Impact Factor
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Pediatric Neurosurgery 03/2002; 36(2):111-2. · 0.70 Impact Factor
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Pediatric Neurosurgery 08/2001; 35(1):51. · 0.70 Impact Factor
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Pediatric Neurosurgery 08/2001; 35(1):53-5. · 0.70 Impact Factor
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ABSTRACT: The prognosis for recovery from brachial plexus injury sustained at or before birth is generally favorable. However, roughly 10% of these infants remain profoundly weak and later exhibit functional disability in the affected arm. Early identification of these at-risk infants would be helpful in selecting patients for surgical management. In our prospective study, 80 infants with brachial plexus injury were examined on a monthly basis. Complete recovery occurred in 53 (66%); in 9 (11%), mild weakness persisted. In each child, recovery to antigravity strength in the biceps, triceps, and deltoid was noted by 6 months of age. Moderate arm weakness persisted in 7 children (9%); none had antigravity strength in the deltoid at age 6 months. Eleven children (14%) had severe permanent weakness (mean follow-up: 4.4 years). At age 6 months, these individuals exhibited at best 2/5 strength proximally and typically 0-1/5 strength in the wrist and finger extensors. Our results demonstrate that detailed strength testing up to 6 months of age predicts not only complete recovery of neonatal brachial plexus injury but also those children destined for long-term severe disability.
Journal of Child Neurology 08/2001; 16(7):488-92. · 1.75 Impact Factor
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ABSTRACT: Medulloblastoma is the most common malignant central nervous system neoplasm found in children. A distinct variant designated large cell/anaplastic (LC/A) medulloblastoma is characterized by frequent dissemination of cerebrospinal fluid (CSF) at presentation and a more aggressive clinical course. The authors report on their examination of the clinicopathological and genetic features of seven such cases encountered at their institution.
Eighty cases of medulloblastomas were reviewed and seven (8.8%) of these were believed to fit the histological and immunohistochemical criteria for LC/A medulloblastoma. In three cases (43%) either desmoplastic or classic medulloblastoma was the underlying subtype, and in two cases (28%) the LC/A tumor was found within the setting of medullomyoblastoma. Fluorescence in situ hybridization was used in six of the seven cases to characterize the presence of isochromosome 17q, deletion of chromosome 22q (a deletion characteristically found in atypical teratoid/rhabdoid tumors), and c-myc amplification. The patients' clinical histories revealed CSF dissemination in all cases and lymph node metastasis in one case. Isochromosome 17q was found in five (83%) of six cases. Evidence of chromosomal gains indicated aneuploidy in three tumors (50%), and amplification of c-myc was found in three tumors (50%). No 22q deletions were encountered.
A high percentage of LC/A medulloblastomas arise within a background of typical medulloblastomas or medullomyoblastomas. As is the case in conventional medulloblastomas, the presence of 17q is a common early tumorigenic event; however, in a significant percentage of specimens there is also evidence of aneuploidy and/or amplification of c-myc. These findings indicate that LC/A morphological characteristics reflect a more advanced tumor stage than that found in pure medulloblastomas or in typical medullomyoblastomas.
Journal of Neurosurgery 08/2001; 95(1):82-8. · 2.96 Impact Factor
