Jeffrey Wisoff - Academia.edu (original) (raw)

Papers by Jeffrey Wisoff

Research paper thumbnail of Endoscopic third ventriculostomy for hydrocephalus: early and late efficacy in relation to aetiology

Acta Neurochirurgica, 2003

Summary. Objectives: The aim of the study was to analyse the effectiveness and usefulness of t... more Summary. Objectives: The aim of the study was to analyse the effectiveness and usefulness of treatment of hydrocephalus by Endoscopic Third Ventriculostomy (ETV). We sought to relate rates of failure to the cause of hydrocephalus, distinguishing between early and late outcome. Patients and methods: Between September 1999 and April 2001, 30 patients underwent ETV. In 23 patients hydrocephalus was caused

Research paper thumbnail of Handbook of Bleeding and Coagulation for Neurosurgery

This book, including all parts thereof, is legally protected by copyright. Any use, exploitation,... more This book, including all parts thereof, is legally protected by copyright. Any use, exploitation, or commercialization outside the narrow limits set by copyright legislation without the publisher's consent is illegal and liable to prosecution. This applies in particular to photostat reproduction, copying, mimeographing or duplication of any kind, translating, preparation of microfilms, and electronic data processing and storage. We dedicate this book to our wives and children in recognition of the hours stolen and to our patients who entrust us with their care. Contents Foreword .

Research paper thumbnail of Hypothalamic Hamartoma and the Pallister-Hall Syndrome

Pediatric Neurosurgery, 1995

The Pallister-Hall syndrome (PHS) was initially described as the congenital hypothalamic &amp... more The Pallister-Hall syndrome (PHS) was initially described as the congenital hypothalamic 'hamartoblastoma' syndrome in 1980. Cardinal manifestations of the syndrome consist of a hypothalamic hamartoma and extracranial abnormalities, initially thought to be fatal in the perinatal period. The original pathologic description of these hypothalamic lesions were from infants who died in the perinatal period and revealed small cells of variable density which resembled primitive undifferentiated germinal cells and appeared to invade the hypothalamic nuclei, suggesting a neoplastic potential. Hypothalamic lesions have now been removed from older infants and children with this syndrome and reveal a more mature histologic appearance typical of a hypothalamic hamartoma. We present 2 new cases of PHS who underwent surgery and demonstrate the maturational nature of the hypothalamic lesion and the phenotypic variability of the syndrome.

Research paper thumbnail of Familial X-Linked Acrogigantism: Postnatal Outcomes and Tumor Pathology in a Prenatally Diagnosed Infant and His Mother

The Journal of Clinical Endocrinology & Metabolism, 2019

ContextX-linked acrogigantism (X-LAG), a condition of infant-onset acrogigantism marked by elevat... more ContextX-linked acrogigantism (X-LAG), a condition of infant-onset acrogigantism marked by elevated GH, IGF-1, and prolactin (PRL), is extremely rare. Thirty-three cases, including three kindreds, have been reported. These patients have pituitary adenomas that are thought to be mixed lactotrophs and somatotrophs.Case DescriptionThe patient’s mother, diagnosed with acrogigantism at 21 months, underwent pituitary tumor excision at 24 months. For more than 30 years, stable PRL, GH, and IGF-1 concentrations and serial imaging studies indicated no tumor recurrence. During preconception planning, X-LAG was diagnosed: single-nucleotide polymorphism microarray showed chromosome Xq26.3 microduplication. After conception, single-nucleotide polymorphism microarray on a chorionic villus sample showed the same microduplication in the fetus, confirming familial X-LAG. The infant grew rapidly with rising PRL, GH, and IGF-1 concentrations and an enlarging suprasellar pituitary mass, despite treatme...

Research paper thumbnail of Pilocytic astrocytoma and glioneuronal tumor with histone H3 K27M mutation

Acta Neuropathologica Communications, 2016

Research paper thumbnail of Shunt malfunction causing acute neurological deterioration in 2 patients with previously asymptomatic Chiari malformation Type I. Report of two cases

Journal of neurosurgery. Pediatrics, 2009

Patients with symptomatic Chiari malformation Type I (CM-I) typically exhibit a chronic, slowly p... more Patients with symptomatic Chiari malformation Type I (CM-I) typically exhibit a chronic, slowly progressive disease course with evolution of symptoms. However, some authors have reported acute neurological deterioration in the setting of CM-I and acquired Chiari malformations. Although brainstem dysfunction has been documented in patients with CM-II and hydrocephalus or shunt malfunction, to the authors' knowledge only 1 report describing ventriculoperitoneal (VP) shunt malfunction causing neurological deterioration in a patient with CM-I exists. The authors report on their experience with the treatment of previously asymptomatic CM-I in 2 children who experienced quite different manifestations of acute neurological deterioration secondary to VP shunt malfunction. Presumably, VP shunt malfunction created a positive rostral pressure gradient across a stenotic foramen magnum, resulting in tetraparesis from foramen magnum syndrome in 1 patient and acute ataxia and cranial nerve def...

Research paper thumbnail of Hypothalamic Hamartoma and the Pallister-Hall Syndrome

Pediatric Neurosurgery, 1995

The Pallister-Hall syndrome (PHS) was initially described as the congenital hypothalamic &amp... more The Pallister-Hall syndrome (PHS) was initially described as the congenital hypothalamic 'hamartoblastoma' syndrome in 1980. Cardinal manifestations of the syndrome consist of a hypothalamic hamartoma and extracranial abnormalities, initially thought to be fatal in the perinatal period. The original pathologic description of these hypothalamic lesions were from infants who died in the perinatal period and revealed small cells of variable density which resembled primitive undifferentiated germinal cells and appeared to invade the hypothalamic nuclei, suggesting a neoplastic potential. Hypothalamic lesions have now been removed from older infants and children with this syndrome and reveal a more mature histologic appearance typical of a hypothalamic hamartoma. We present 2 new cases of PHS who underwent surgery and demonstrate the maturational nature of the hypothalamic lesion and the phenotypic variability of the syndrome.

Research paper thumbnail of Deferring adjuvant therapy for totally resected intracranial ependymoma

Pediatric Neurology, 1996

Radical surgery is the most important treatment modality for ependymoma. The benefit of adjuvant ... more Radical surgery is the most important treatment modality for ependymoma. The benefit of adjuvant radiotherapy and/or chemotherapy following a gross total resection of a low grade intracranial ependymoma is uncertain. Since 1990 we elected to defer adjuvant therapy in 7 pediatric patients with a median age of 7 years (range 3-16 years) who had a radical resection of an intracranial ependymoma and no evidence of central nervous system metastases. The primary tumor site was the cerebral hemisphere (6) and the cerebellum (1). A gross total resection was radiologically confirmed in 5 of the 7 patients. Two of the patients had a blood clot in the resection site on the postoperative magnetic resonance imaging scan. All patients are alive after a median follow-up of 44 months and the median progression-free survival is 38+ months. Five of the patients remain in continuous remission. The 2 patients with postoperative blood clots developed subclinical local recurrences, 10 and 11 months, respectively, after diagnosis. They remain in remission for 13+ and 27+ months after subsequent radical surgical procedures. Involved field radiotherapy was administered to 1 patient. After a limited period of follow-up, radical surgery alone appears to be sufficient for the majority of children with low grade ependymomas diagnosed at >3 years of age when postoperative imaging confirms a gross total resection. This is more likely to occur in supratentorial ependymomas arising in older children.

Research paper thumbnail of Complications of Ventriculoperitoneal Shunt Procedures or Hydrocephalus Associated with Vein of Galen Malformations in Childhood

Neurosurgery, 1992

Twenty children with vein of Galen malformations and hydrocephalus required a ventriculoperitonea... more Twenty children with vein of Galen malformations and hydrocephalus required a ventriculoperitoneal shunt. Shunt placement was associated with a 70% incidence of complications that included status epilepticus in 3 patients, intraventricular hemorrhage in 7 patients, and subdural hematoma or hygroma in 5 patients. Based upon this experience, the authors recommend the use of preoperative prophylactic anticonvulsants and the placement of medium pressure frontal ventriculoperitoneal shunts. This report will address the overall experience with and the basis on which these therapeutic recommendations were made.

Research paper thumbnail of Phase II study of sorafenib in children with recurrent or progressive low-grade astrocytomas

Neuro-Oncology, 2014

Background. Activation of the RAS-RAF-MEK-ERK signaling pathway is thought to be the key driver o... more Background. Activation of the RAS-RAF-MEK-ERK signaling pathway is thought to be the key driver of pediatric low-grade astrocytoma (PLGA) growth. Sorafenib is a multikinase inhibitor targeting BRAF, VEGFR, PDGFR, and c-kit. This multicenter phase II study was conducted to determine the response rate to sorafenib in patients with recurrent or progressive PLGA. Methods. Key eligibility criteria included age ≥2 years, progressive PLGA evaluable on MRI, and at least one prior chemotherapy treatment. Sorafenib was administered twice daily at 200 mg/m 2 /dose (maximum of 400 mg/dose) in continuous 28-day cycles. MRI, including 3-dimensional volumetric tumor analysis, was performed every 12 weeks. BRAF molecular testing was performed on tumor tissue when available. Results. Eleven patients, including 3 with neurofibromatosis type 1 (NF1), were evaluable for response; 5 tested positive for BRAF duplication. Nine patients (82%) came off trial due to radiological tumor progression after 2 or 3 cycles, including 3 patients with confirmed BRAF duplication. Median time to progression was 2.8 months (95% CI, 2.1-31.0 months). Enrollment was terminated early due to this rapid and unexpectedly high progression rate. Tumor tissue obtained from 4 patients after termination of the study showed viable pilocytic or pilomyxoid astrocytoma. Conclusions. Sorafenib produced unexpected and unprecedented acceleration of tumor growth in children with PLGA, irrespective of NF1 or tumor BRAF status. In vitro studies with sorafenib indicate that this effect is likely related to paradoxical ERK activation. Close monitoring for early tumor progression should be included in trials of novel agents that modulate signal transduction.

Research paper thumbnail of Bevacizumab in recurrent high-grade pediatric gliomas

Neuro-Oncology, 2010

Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown promise ... more Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown promise in treating recurrent adult high-grade glioma (HGG). However, there is very little data on recurrent or progressive pediatric HGG treated with bevacizumab. We report the results of a single institution experience using bevacizumab and irinotecan in children who relapsed or progressed following standard therapy. Twelve pediatric patients with recurrent or progressive HGG received bevacizumab at 10 mg/kg every 2 weeks with irinotecan at 125 mg/m 2. Magnetic resonance imaging (MRI) was performed prior to therapy and every 8 weeks subsequently. Ten patients had supratentorial HGG; 2 had DIPG. Radiological responses were defined according to MacDonald's criteria. Progression-free survival (PFS), overall survival (OS), and toxicities were analyzed. Ten (83.3%) patients tolerated bevacizumab without serious toxicity. Therapy was discontinued in 1 patient because of anaphylaxis. Another patient developed grade III delayed wound healing and deep vein thrombosis. Two patients (16.7%) experienced a partial response after the first MRI. No complete radiographic responses were seen. Stable disease was noted in 4 (33.3%) patients. The median PFS and OS were 2.25 and 6.25 months, respectively. A diffuse invasive recurrence pattern was noted in 5 (45.5%) patients. Treatment tolerance, toxicity, and recurrence profiles were comparable to adult HGG patients treated with bevacizumab. However, the radiological response rate, response duration, and survival appeared inferior in pediatric patients. Genetic differences in pediatric gliomas might account for this difference.

Research paper thumbnail of Temozolomide is Active in Childhood, Progressive, Unresectable, Low-Grade Gliomas

Journal of Pediatric Hematology/Oncology, 2003

To assess the activity and tolerability of temozolomide in children with progressive low-grade gl... more To assess the activity and tolerability of temozolomide in children with progressive low-grade gliomas (LGGs). Patients and Methods: The authors reviewed the records of 13 children (6 months to 19 years old) with progressive LGGs and magnetic resonance imaging evidence of unresectable tumors who were treated with temozolomide at the authors' institution since 1999. Results: Four patients received a 5-day regimen of temozolomide (150 mg/m 2 per day) repeated every 28 days, and nine patients received a 42-day regimen (75 mg/m 2 per day) repeated every 56 days. Three patients demonstrated partial responses to temozolomide, with a median time to maximal response of 5 months (range 4-12 months), and one had a minor response at 9 months. Four patients developed progression while on temozolomide, with a median time to progression of 7 months (range 1-12 months). Five patients had disease stabilization. Among the five patients with prior chemotherapy and/or radiation therapy, temozolomide was associated with disease stabilization in three and tumor response in one. In the three patients with neurofibromatosis type 1, two patients experienced tumor responses and one disease stabilization. Thrombocytopenia, nausea, emesis, and fatigue were the most common toxicities. Four patients discontinued therapy because of the side effects. Conclusions: Temozolomide is active in children with LGGs. It is effective in previously treated patients and in patients with neurofibromatosis type 1. The 42-day regimen appears less toxic than the 5-day regimen. Any impact on survival for these patients remains to be demonstrated.

Research paper thumbnail of Recurrent Central Nervous System Medulloepithelioma

Journal of Pediatric Hematology/Oncology, 2005

Medulloepithelioma is a rare primitive neuroectodermal tumor of the central nervous system usuall... more Medulloepithelioma is a rare primitive neuroectodermal tumor of the central nervous system usually developing in childhood, displaying highly malignant behavior, with early progression or recurrence. Once a recurrence develops, death reportedly follows with invariable rapidity. The purpose of this study was to evaluate the efficacy of high-dose, marrow-ablative chemotherapy with autologous hemopoietic stem cell rescue in the treatment of recurrent central nervous system medulloepithelioma. Three young children with recurrent central nervous system medulloepithelioma received high-dose marrow-ablative chemotherapy with thiotepa and etoposide either alone (one patient) or with the addition of carboplatin (two patients). This was followed by irradiation only in one patient. One child with residual radiographic tumor at the time of treatment could be evaluated for response and showed complete resolution of leptomeningeal disease after receiving marrow-ablative chemotherapy. Two children developed tumor recurrence at 2.0 and 5.5 months after receiving marrow-ablative chemotherapy. The third child continues free of tumor beyond 12 years from treatment. The authors' experience with marrow-ablative chemotherapy and autologous hemopoietic stem cell rescue suggests that this treatment strategy might be beneficially incorporated into the initial treatment approach for young children with medulloepithelioma.

Research paper thumbnail of Endoscopic third ventriculostomy in patients with cerebrospinal fluid infection and/or hemorrhage

Journal of Neurosurgery, 2002

Object. In this study the authors evaluate the safety, efficacy, and indications for endoscopic t... more Object. In this study the authors evaluate the safety, efficacy, and indications for endoscopic third ventriculostomy (ETV) in patients with a history of subarachnoid hemorrhage or intraventricular hemorrhage (IVH) and/or cerebrospinal fluid (CSF) infection. Methods. The charts of 101 patients from seven international medical centers were retrospectively reviewed; 46 patients had a history of hemorrhage, 42 had a history of CSF infection, and 13 had a history of both disorders. All patients experienced third ventricular hydrocephalus before endoscopy. The success rate for treatment in these three groups was 60.9, 64.3, and 23.1%, respectively. The follow-up period in successfully treated patients ranged from 0.6 to 10 years. Relatively minor complications were observed in 15 patients (14.9%), and there were no deaths. A higher rate of treatment failure was associated with three factors: classification in the combined infection/hemorrhage group, premature birth in the posthemorrhage ...

Research paper thumbnail of Current neurosurgical management and the impact of the extent of resection in the treatment of malignant gliomas of childhood: a report of the Children's Cancer Group Trial No. CCG-945

Journal of Neurosurgery, 1998

Object. One hundred seventy-two children with high-grade astrocytomas were treated by members of ... more Object. One hundred seventy-two children with high-grade astrocytomas were treated by members of the Children's Cancer Group in a prospective randomized trial designed to evaluate the role of two chemotherapy regimens. Seventy-six percent of the patients (131 children) in whom a diagnosis of either anaplastic astrocytoma or glioblastoma multiforme was confirmed by central pathological review are the subject of this report. Methods. Patients were stratified according to the extent of tumor resection (biopsy [< 10%], partial resection [10–50%], subtotal resection [51–90%], near-total resection [> 90%], and total resection) as determined by surgical observation and postoperative computerized tomography scanning. Information on contemporary neurosurgical management was obtained from the patient's operative records and standardized neurosurgical report forms. The vast majority of tumors were supratentorial: 63% (83 tumors) in the superficial cerebral hemisphere, 28% (37 tum...

Research paper thumbnail of Intra-axial tumors of the cervicomedullary junction

Journal of Neurosurgery, 1987

The authors present their experience with the operative management of 20 intra-axial tumors of th... more The authors present their experience with the operative management of 20 intra-axial tumors of the cervicomedullary junction. There were two distinct modes of clinical presentation: lower cranial nerve dysfunction and spinal cord dysfunction. Both groups of patients had indolent courses: in 75% of the patients the symptoms had been present for 6 months to 2 years. Radical excision was carried out in all patients. There was no surgical mortality. Postoperative neurological recovery was directly related to the preoperative status; one patient had a significant new deficit. The authors conclude that intrinsic gliomas of the cervicomedullary junction are amenable to radical excision and that an aggressive surgical approach offers the potential for both neurological recovery and long-term survival. The neuroradiological evaluation and operative technique are discussed.

Research paper thumbnail of Central nervous system gangliogliomas

Journal of Neurosurgery, 1993

The records of 58 patients with gangliogliomas surgically treated between January 1, 1980, and Ju... more The records of 58 patients with gangliogliomas surgically treated between January 1, 1980, and June 30, 1990, were retrospectively reviewed in order to determine long-term survival, event-free survival, and functional outcome resulting after radical resection and to assess the impact of histological grading on outcome. Tumors were located in the cerebral hemisphere in 19 cases, the spinal cord in 30, and the brain stem in nine. Forty-four patients had gross total resection and 14 had radical subtotal resection. Only six patients underwent postoperative irradiation or chemotherapy and, therefore, the outcome was generally related to surgery alone. Of the 58 gangliogliomas, 40 were classified as histological grade I, 16 were grade II, and two were grade III. The median follow-up period was 56 months. There were no operative deaths, and the operative morbidity rate was 5%, 37%, and 33% for cerebral hemisphere, spinal cord, and brain-stem gangliogliomas, respectively. The 5-year actuari...

Research paper thumbnail of Surgical management of exophytic chiasmatic-hypothalamic tumors of childhood

Journal of Neurosurgery, 1990

✓ Sixteen children underwent 18 operations for radical resection of chiasmatic-hypothalamic tumor... more ✓ Sixteen children underwent 18 operations for radical resection of chiasmatic-hypothalamic tumors. The clinical presentation correlated with age: infants under 1 year of age presented with macrocephaly, failure to thrive, and severe visual failure; children aged 1 to 5 years predominantly had precocious puberty with mild visual deficits; and older children (> 5 years old) had slowly progressive loss of vision. All three infants had biologically aggressive tumors in spite of low-grade histology, and died from progressive tumor growth. Eleven of the 13 children aged 1 year or over are alive and well, without clinical or radiographic evidence of disease progression, 4 months to 4½ years following surgery. Six of these patients, with a follow-up period of 10 months to 4½ years (mean 27 months), have had no adjuvant therapy following radical surgical resection. The authors conclude that: 1) radical surgical resection of chiasmatic-hypothalamic tumors can be performed with minimal mor...

Research paper thumbnail of Tumor antigen precursor protein profiles of adult and pediatric brain tumors identify potential targets for immunotherapy

Journal of Neuro-Oncology, 2008

Research paper thumbnail of Alzheimer's disease comorbidity in normal pressure hydrocephalus: prevalence and shunt response

Journal of Neurology, Neurosurgery & Psychiatry, 2000

The clinical impact of Alzheimer's disease pathology at biopsy was investigated in 56 cognitively... more The clinical impact of Alzheimer's disease pathology at biopsy was investigated in 56 cognitively impaired patients undergoing shunt surgery for idiopathic normal pressure hydrocephalus (NPH). Cognition was measured by means of the global deterioration scale (GDS), the mini mental status examination (MMSE) and a battery of six psychometric tests. Gait was assessed using objective measurements of velocity and the ambulatory index (AI). The prevalence of cases exhibiting neuritic plaques (positive biopsies) increased in parallel with dementia severity from 18% for patients with GDS 3 to 75% for patients with GDS scores>6. Patients with positive biopsies were more cognitively impaired (higher GDS and lower MMSE scores) as well as more gait impaired (higher AI scores and slower velocities) than patients with negative biopsies. After surgery, gait velocity and AI scores improved significantly and to a comparable degree for patients with and without positive biopsies. Similar proportions of positive and negative biopsy patients also had improved gait as assessed by means of subjective video tape comparisons. There were no significant diVerences between the biopsy groups in the magnitude of postoperative psychometric change or in the proportion of cases exhibiting improved urinary control. Alzheimer's disease pathology is a common source of comorbidity in older patients with idiopathic NPH where it contributes to the clinical impairment associated with this disorder. For patients accurately diagnosed with NPH, concomitant Alzheimer's disease pathology does not strongly influence the clinical response to shunt surgery.

Research paper thumbnail of Endoscopic third ventriculostomy for hydrocephalus: early and late efficacy in relation to aetiology

Acta Neurochirurgica, 2003

Summary. Objectives: The aim of the study was to analyse the effectiveness and usefulness of t... more Summary. Objectives: The aim of the study was to analyse the effectiveness and usefulness of treatment of hydrocephalus by Endoscopic Third Ventriculostomy (ETV). We sought to relate rates of failure to the cause of hydrocephalus, distinguishing between early and late outcome. Patients and methods: Between September 1999 and April 2001, 30 patients underwent ETV. In 23 patients hydrocephalus was caused

Research paper thumbnail of Handbook of Bleeding and Coagulation for Neurosurgery

This book, including all parts thereof, is legally protected by copyright. Any use, exploitation,... more This book, including all parts thereof, is legally protected by copyright. Any use, exploitation, or commercialization outside the narrow limits set by copyright legislation without the publisher's consent is illegal and liable to prosecution. This applies in particular to photostat reproduction, copying, mimeographing or duplication of any kind, translating, preparation of microfilms, and electronic data processing and storage. We dedicate this book to our wives and children in recognition of the hours stolen and to our patients who entrust us with their care. Contents Foreword .

Research paper thumbnail of Hypothalamic Hamartoma and the Pallister-Hall Syndrome

Pediatric Neurosurgery, 1995

The Pallister-Hall syndrome (PHS) was initially described as the congenital hypothalamic &amp... more The Pallister-Hall syndrome (PHS) was initially described as the congenital hypothalamic &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;hamartoblastoma&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; syndrome in 1980. Cardinal manifestations of the syndrome consist of a hypothalamic hamartoma and extracranial abnormalities, initially thought to be fatal in the perinatal period. The original pathologic description of these hypothalamic lesions were from infants who died in the perinatal period and revealed small cells of variable density which resembled primitive undifferentiated germinal cells and appeared to invade the hypothalamic nuclei, suggesting a neoplastic potential. Hypothalamic lesions have now been removed from older infants and children with this syndrome and reveal a more mature histologic appearance typical of a hypothalamic hamartoma. We present 2 new cases of PHS who underwent surgery and demonstrate the maturational nature of the hypothalamic lesion and the phenotypic variability of the syndrome.

Research paper thumbnail of Familial X-Linked Acrogigantism: Postnatal Outcomes and Tumor Pathology in a Prenatally Diagnosed Infant and His Mother

The Journal of Clinical Endocrinology & Metabolism, 2019

ContextX-linked acrogigantism (X-LAG), a condition of infant-onset acrogigantism marked by elevat... more ContextX-linked acrogigantism (X-LAG), a condition of infant-onset acrogigantism marked by elevated GH, IGF-1, and prolactin (PRL), is extremely rare. Thirty-three cases, including three kindreds, have been reported. These patients have pituitary adenomas that are thought to be mixed lactotrophs and somatotrophs.Case DescriptionThe patient’s mother, diagnosed with acrogigantism at 21 months, underwent pituitary tumor excision at 24 months. For more than 30 years, stable PRL, GH, and IGF-1 concentrations and serial imaging studies indicated no tumor recurrence. During preconception planning, X-LAG was diagnosed: single-nucleotide polymorphism microarray showed chromosome Xq26.3 microduplication. After conception, single-nucleotide polymorphism microarray on a chorionic villus sample showed the same microduplication in the fetus, confirming familial X-LAG. The infant grew rapidly with rising PRL, GH, and IGF-1 concentrations and an enlarging suprasellar pituitary mass, despite treatme...

Research paper thumbnail of Pilocytic astrocytoma and glioneuronal tumor with histone H3 K27M mutation

Acta Neuropathologica Communications, 2016

Research paper thumbnail of Shunt malfunction causing acute neurological deterioration in 2 patients with previously asymptomatic Chiari malformation Type I. Report of two cases

Journal of neurosurgery. Pediatrics, 2009

Patients with symptomatic Chiari malformation Type I (CM-I) typically exhibit a chronic, slowly p... more Patients with symptomatic Chiari malformation Type I (CM-I) typically exhibit a chronic, slowly progressive disease course with evolution of symptoms. However, some authors have reported acute neurological deterioration in the setting of CM-I and acquired Chiari malformations. Although brainstem dysfunction has been documented in patients with CM-II and hydrocephalus or shunt malfunction, to the authors' knowledge only 1 report describing ventriculoperitoneal (VP) shunt malfunction causing neurological deterioration in a patient with CM-I exists. The authors report on their experience with the treatment of previously asymptomatic CM-I in 2 children who experienced quite different manifestations of acute neurological deterioration secondary to VP shunt malfunction. Presumably, VP shunt malfunction created a positive rostral pressure gradient across a stenotic foramen magnum, resulting in tetraparesis from foramen magnum syndrome in 1 patient and acute ataxia and cranial nerve def...

Research paper thumbnail of Hypothalamic Hamartoma and the Pallister-Hall Syndrome

Pediatric Neurosurgery, 1995

The Pallister-Hall syndrome (PHS) was initially described as the congenital hypothalamic &amp... more The Pallister-Hall syndrome (PHS) was initially described as the congenital hypothalamic &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;hamartoblastoma&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; syndrome in 1980. Cardinal manifestations of the syndrome consist of a hypothalamic hamartoma and extracranial abnormalities, initially thought to be fatal in the perinatal period. The original pathologic description of these hypothalamic lesions were from infants who died in the perinatal period and revealed small cells of variable density which resembled primitive undifferentiated germinal cells and appeared to invade the hypothalamic nuclei, suggesting a neoplastic potential. Hypothalamic lesions have now been removed from older infants and children with this syndrome and reveal a more mature histologic appearance typical of a hypothalamic hamartoma. We present 2 new cases of PHS who underwent surgery and demonstrate the maturational nature of the hypothalamic lesion and the phenotypic variability of the syndrome.

Research paper thumbnail of Deferring adjuvant therapy for totally resected intracranial ependymoma

Pediatric Neurology, 1996

Radical surgery is the most important treatment modality for ependymoma. The benefit of adjuvant ... more Radical surgery is the most important treatment modality for ependymoma. The benefit of adjuvant radiotherapy and/or chemotherapy following a gross total resection of a low grade intracranial ependymoma is uncertain. Since 1990 we elected to defer adjuvant therapy in 7 pediatric patients with a median age of 7 years (range 3-16 years) who had a radical resection of an intracranial ependymoma and no evidence of central nervous system metastases. The primary tumor site was the cerebral hemisphere (6) and the cerebellum (1). A gross total resection was radiologically confirmed in 5 of the 7 patients. Two of the patients had a blood clot in the resection site on the postoperative magnetic resonance imaging scan. All patients are alive after a median follow-up of 44 months and the median progression-free survival is 38+ months. Five of the patients remain in continuous remission. The 2 patients with postoperative blood clots developed subclinical local recurrences, 10 and 11 months, respectively, after diagnosis. They remain in remission for 13+ and 27+ months after subsequent radical surgical procedures. Involved field radiotherapy was administered to 1 patient. After a limited period of follow-up, radical surgery alone appears to be sufficient for the majority of children with low grade ependymomas diagnosed at >3 years of age when postoperative imaging confirms a gross total resection. This is more likely to occur in supratentorial ependymomas arising in older children.

Research paper thumbnail of Complications of Ventriculoperitoneal Shunt Procedures or Hydrocephalus Associated with Vein of Galen Malformations in Childhood

Neurosurgery, 1992

Twenty children with vein of Galen malformations and hydrocephalus required a ventriculoperitonea... more Twenty children with vein of Galen malformations and hydrocephalus required a ventriculoperitoneal shunt. Shunt placement was associated with a 70% incidence of complications that included status epilepticus in 3 patients, intraventricular hemorrhage in 7 patients, and subdural hematoma or hygroma in 5 patients. Based upon this experience, the authors recommend the use of preoperative prophylactic anticonvulsants and the placement of medium pressure frontal ventriculoperitoneal shunts. This report will address the overall experience with and the basis on which these therapeutic recommendations were made.

Research paper thumbnail of Phase II study of sorafenib in children with recurrent or progressive low-grade astrocytomas

Neuro-Oncology, 2014

Background. Activation of the RAS-RAF-MEK-ERK signaling pathway is thought to be the key driver o... more Background. Activation of the RAS-RAF-MEK-ERK signaling pathway is thought to be the key driver of pediatric low-grade astrocytoma (PLGA) growth. Sorafenib is a multikinase inhibitor targeting BRAF, VEGFR, PDGFR, and c-kit. This multicenter phase II study was conducted to determine the response rate to sorafenib in patients with recurrent or progressive PLGA. Methods. Key eligibility criteria included age ≥2 years, progressive PLGA evaluable on MRI, and at least one prior chemotherapy treatment. Sorafenib was administered twice daily at 200 mg/m 2 /dose (maximum of 400 mg/dose) in continuous 28-day cycles. MRI, including 3-dimensional volumetric tumor analysis, was performed every 12 weeks. BRAF molecular testing was performed on tumor tissue when available. Results. Eleven patients, including 3 with neurofibromatosis type 1 (NF1), were evaluable for response; 5 tested positive for BRAF duplication. Nine patients (82%) came off trial due to radiological tumor progression after 2 or 3 cycles, including 3 patients with confirmed BRAF duplication. Median time to progression was 2.8 months (95% CI, 2.1-31.0 months). Enrollment was terminated early due to this rapid and unexpectedly high progression rate. Tumor tissue obtained from 4 patients after termination of the study showed viable pilocytic or pilomyxoid astrocytoma. Conclusions. Sorafenib produced unexpected and unprecedented acceleration of tumor growth in children with PLGA, irrespective of NF1 or tumor BRAF status. In vitro studies with sorafenib indicate that this effect is likely related to paradoxical ERK activation. Close monitoring for early tumor progression should be included in trials of novel agents that modulate signal transduction.

Research paper thumbnail of Bevacizumab in recurrent high-grade pediatric gliomas

Neuro-Oncology, 2010

Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown promise ... more Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown promise in treating recurrent adult high-grade glioma (HGG). However, there is very little data on recurrent or progressive pediatric HGG treated with bevacizumab. We report the results of a single institution experience using bevacizumab and irinotecan in children who relapsed or progressed following standard therapy. Twelve pediatric patients with recurrent or progressive HGG received bevacizumab at 10 mg/kg every 2 weeks with irinotecan at 125 mg/m 2. Magnetic resonance imaging (MRI) was performed prior to therapy and every 8 weeks subsequently. Ten patients had supratentorial HGG; 2 had DIPG. Radiological responses were defined according to MacDonald's criteria. Progression-free survival (PFS), overall survival (OS), and toxicities were analyzed. Ten (83.3%) patients tolerated bevacizumab without serious toxicity. Therapy was discontinued in 1 patient because of anaphylaxis. Another patient developed grade III delayed wound healing and deep vein thrombosis. Two patients (16.7%) experienced a partial response after the first MRI. No complete radiographic responses were seen. Stable disease was noted in 4 (33.3%) patients. The median PFS and OS were 2.25 and 6.25 months, respectively. A diffuse invasive recurrence pattern was noted in 5 (45.5%) patients. Treatment tolerance, toxicity, and recurrence profiles were comparable to adult HGG patients treated with bevacizumab. However, the radiological response rate, response duration, and survival appeared inferior in pediatric patients. Genetic differences in pediatric gliomas might account for this difference.

Research paper thumbnail of Temozolomide is Active in Childhood, Progressive, Unresectable, Low-Grade Gliomas

Journal of Pediatric Hematology/Oncology, 2003

To assess the activity and tolerability of temozolomide in children with progressive low-grade gl... more To assess the activity and tolerability of temozolomide in children with progressive low-grade gliomas (LGGs). Patients and Methods: The authors reviewed the records of 13 children (6 months to 19 years old) with progressive LGGs and magnetic resonance imaging evidence of unresectable tumors who were treated with temozolomide at the authors' institution since 1999. Results: Four patients received a 5-day regimen of temozolomide (150 mg/m 2 per day) repeated every 28 days, and nine patients received a 42-day regimen (75 mg/m 2 per day) repeated every 56 days. Three patients demonstrated partial responses to temozolomide, with a median time to maximal response of 5 months (range 4-12 months), and one had a minor response at 9 months. Four patients developed progression while on temozolomide, with a median time to progression of 7 months (range 1-12 months). Five patients had disease stabilization. Among the five patients with prior chemotherapy and/or radiation therapy, temozolomide was associated with disease stabilization in three and tumor response in one. In the three patients with neurofibromatosis type 1, two patients experienced tumor responses and one disease stabilization. Thrombocytopenia, nausea, emesis, and fatigue were the most common toxicities. Four patients discontinued therapy because of the side effects. Conclusions: Temozolomide is active in children with LGGs. It is effective in previously treated patients and in patients with neurofibromatosis type 1. The 42-day regimen appears less toxic than the 5-day regimen. Any impact on survival for these patients remains to be demonstrated.

Research paper thumbnail of Recurrent Central Nervous System Medulloepithelioma

Journal of Pediatric Hematology/Oncology, 2005

Medulloepithelioma is a rare primitive neuroectodermal tumor of the central nervous system usuall... more Medulloepithelioma is a rare primitive neuroectodermal tumor of the central nervous system usually developing in childhood, displaying highly malignant behavior, with early progression or recurrence. Once a recurrence develops, death reportedly follows with invariable rapidity. The purpose of this study was to evaluate the efficacy of high-dose, marrow-ablative chemotherapy with autologous hemopoietic stem cell rescue in the treatment of recurrent central nervous system medulloepithelioma. Three young children with recurrent central nervous system medulloepithelioma received high-dose marrow-ablative chemotherapy with thiotepa and etoposide either alone (one patient) or with the addition of carboplatin (two patients). This was followed by irradiation only in one patient. One child with residual radiographic tumor at the time of treatment could be evaluated for response and showed complete resolution of leptomeningeal disease after receiving marrow-ablative chemotherapy. Two children developed tumor recurrence at 2.0 and 5.5 months after receiving marrow-ablative chemotherapy. The third child continues free of tumor beyond 12 years from treatment. The authors' experience with marrow-ablative chemotherapy and autologous hemopoietic stem cell rescue suggests that this treatment strategy might be beneficially incorporated into the initial treatment approach for young children with medulloepithelioma.

Research paper thumbnail of Endoscopic third ventriculostomy in patients with cerebrospinal fluid infection and/or hemorrhage

Journal of Neurosurgery, 2002

Object. In this study the authors evaluate the safety, efficacy, and indications for endoscopic t... more Object. In this study the authors evaluate the safety, efficacy, and indications for endoscopic third ventriculostomy (ETV) in patients with a history of subarachnoid hemorrhage or intraventricular hemorrhage (IVH) and/or cerebrospinal fluid (CSF) infection. Methods. The charts of 101 patients from seven international medical centers were retrospectively reviewed; 46 patients had a history of hemorrhage, 42 had a history of CSF infection, and 13 had a history of both disorders. All patients experienced third ventricular hydrocephalus before endoscopy. The success rate for treatment in these three groups was 60.9, 64.3, and 23.1%, respectively. The follow-up period in successfully treated patients ranged from 0.6 to 10 years. Relatively minor complications were observed in 15 patients (14.9%), and there were no deaths. A higher rate of treatment failure was associated with three factors: classification in the combined infection/hemorrhage group, premature birth in the posthemorrhage ...

Research paper thumbnail of Current neurosurgical management and the impact of the extent of resection in the treatment of malignant gliomas of childhood: a report of the Children's Cancer Group Trial No. CCG-945

Journal of Neurosurgery, 1998

Object. One hundred seventy-two children with high-grade astrocytomas were treated by members of ... more Object. One hundred seventy-two children with high-grade astrocytomas were treated by members of the Children's Cancer Group in a prospective randomized trial designed to evaluate the role of two chemotherapy regimens. Seventy-six percent of the patients (131 children) in whom a diagnosis of either anaplastic astrocytoma or glioblastoma multiforme was confirmed by central pathological review are the subject of this report. Methods. Patients were stratified according to the extent of tumor resection (biopsy [< 10%], partial resection [10–50%], subtotal resection [51–90%], near-total resection [> 90%], and total resection) as determined by surgical observation and postoperative computerized tomography scanning. Information on contemporary neurosurgical management was obtained from the patient's operative records and standardized neurosurgical report forms. The vast majority of tumors were supratentorial: 63% (83 tumors) in the superficial cerebral hemisphere, 28% (37 tum...

Research paper thumbnail of Intra-axial tumors of the cervicomedullary junction

Journal of Neurosurgery, 1987

The authors present their experience with the operative management of 20 intra-axial tumors of th... more The authors present their experience with the operative management of 20 intra-axial tumors of the cervicomedullary junction. There were two distinct modes of clinical presentation: lower cranial nerve dysfunction and spinal cord dysfunction. Both groups of patients had indolent courses: in 75% of the patients the symptoms had been present for 6 months to 2 years. Radical excision was carried out in all patients. There was no surgical mortality. Postoperative neurological recovery was directly related to the preoperative status; one patient had a significant new deficit. The authors conclude that intrinsic gliomas of the cervicomedullary junction are amenable to radical excision and that an aggressive surgical approach offers the potential for both neurological recovery and long-term survival. The neuroradiological evaluation and operative technique are discussed.

Research paper thumbnail of Central nervous system gangliogliomas

Journal of Neurosurgery, 1993

The records of 58 patients with gangliogliomas surgically treated between January 1, 1980, and Ju... more The records of 58 patients with gangliogliomas surgically treated between January 1, 1980, and June 30, 1990, were retrospectively reviewed in order to determine long-term survival, event-free survival, and functional outcome resulting after radical resection and to assess the impact of histological grading on outcome. Tumors were located in the cerebral hemisphere in 19 cases, the spinal cord in 30, and the brain stem in nine. Forty-four patients had gross total resection and 14 had radical subtotal resection. Only six patients underwent postoperative irradiation or chemotherapy and, therefore, the outcome was generally related to surgery alone. Of the 58 gangliogliomas, 40 were classified as histological grade I, 16 were grade II, and two were grade III. The median follow-up period was 56 months. There were no operative deaths, and the operative morbidity rate was 5%, 37%, and 33% for cerebral hemisphere, spinal cord, and brain-stem gangliogliomas, respectively. The 5-year actuari...

Research paper thumbnail of Surgical management of exophytic chiasmatic-hypothalamic tumors of childhood

Journal of Neurosurgery, 1990

✓ Sixteen children underwent 18 operations for radical resection of chiasmatic-hypothalamic tumor... more ✓ Sixteen children underwent 18 operations for radical resection of chiasmatic-hypothalamic tumors. The clinical presentation correlated with age: infants under 1 year of age presented with macrocephaly, failure to thrive, and severe visual failure; children aged 1 to 5 years predominantly had precocious puberty with mild visual deficits; and older children (> 5 years old) had slowly progressive loss of vision. All three infants had biologically aggressive tumors in spite of low-grade histology, and died from progressive tumor growth. Eleven of the 13 children aged 1 year or over are alive and well, without clinical or radiographic evidence of disease progression, 4 months to 4½ years following surgery. Six of these patients, with a follow-up period of 10 months to 4½ years (mean 27 months), have had no adjuvant therapy following radical surgical resection. The authors conclude that: 1) radical surgical resection of chiasmatic-hypothalamic tumors can be performed with minimal mor...

Research paper thumbnail of Tumor antigen precursor protein profiles of adult and pediatric brain tumors identify potential targets for immunotherapy

Journal of Neuro-Oncology, 2008

Research paper thumbnail of Alzheimer's disease comorbidity in normal pressure hydrocephalus: prevalence and shunt response

Journal of Neurology, Neurosurgery & Psychiatry, 2000

The clinical impact of Alzheimer's disease pathology at biopsy was investigated in 56 cognitively... more The clinical impact of Alzheimer's disease pathology at biopsy was investigated in 56 cognitively impaired patients undergoing shunt surgery for idiopathic normal pressure hydrocephalus (NPH). Cognition was measured by means of the global deterioration scale (GDS), the mini mental status examination (MMSE) and a battery of six psychometric tests. Gait was assessed using objective measurements of velocity and the ambulatory index (AI). The prevalence of cases exhibiting neuritic plaques (positive biopsies) increased in parallel with dementia severity from 18% for patients with GDS 3 to 75% for patients with GDS scores>6. Patients with positive biopsies were more cognitively impaired (higher GDS and lower MMSE scores) as well as more gait impaired (higher AI scores and slower velocities) than patients with negative biopsies. After surgery, gait velocity and AI scores improved significantly and to a comparable degree for patients with and without positive biopsies. Similar proportions of positive and negative biopsy patients also had improved gait as assessed by means of subjective video tape comparisons. There were no significant diVerences between the biopsy groups in the magnitude of postoperative psychometric change or in the proportion of cases exhibiting improved urinary control. Alzheimer's disease pathology is a common source of comorbidity in older patients with idiopathic NPH where it contributes to the clinical impairment associated with this disorder. For patients accurately diagnosed with NPH, concomitant Alzheimer's disease pathology does not strongly influence the clinical response to shunt surgery.