Biomedical subjects

Corey Raffel

Publications and source records attributed to Corey Raffel.

15 recordsLinked to original sources

PubMed2006

Imaging characteristics and growth of subependymal giant cell astrocytomas.

OBJECT: Subependymal giant cell astrocytomas (SEGAs) are a common manifestation of tuberous sclerosis (TS). These evolving tumors have a propensity to cause obstructive hydrocephalus, usually due to obstruction at the level of the foramen of Monro. Differentiating SEGAs from subependymal nodules (SENs) before obstruction occurs may improve the morbidity associated with these tumors. In this study the authors' aim was to determine imaging characteristics of proven tumors in a single-center pediatric population. METHODS: The authors retrospectively reviewed all records and images obtained in patients with TS in whom results of biopsy sampling had proven that their tumors were SEGAs. Time to presentation, signs and symptoms at presentation, and imaging characteristics of the evolving tumors were noted. Twelve patients with 14 SEGAs proven by the results of biopsy sampling were reviewed. Resection was recommended for symptomatic and neuroimaging evidence of hydrocephalus (41%), tumor growth without evidence of hydrocephalus (33%), and for poorly controlled seizures (25%). The mean diameter of the tumors at the time of resection was 1.9 cm (range 0.3-4 cm), and no tumor recurred. Because of the pathological and radiographic continuum of SENs and SEGAs, it remains difficult to predict whether and when a given lesion will progress. Tumor growth and contrast enhancement are the most common signs of progression on neuroimages, and may be seen prior to the development of obstructive hydrocephalus. CONCLUSIONS: Patients with SENs and SEGAs should undergo follow-up neuroimaging at yearly intervals, and if lesions show signs of progression (contrast enhancement or growth), these intervals should be shortened and consideration given to early resection.

Adolescent↗

PubMed2006

Pediatric neurosurgery.

Randomized controlled trials of neurosurgical procedures involving children have been organized infrequently; as a consequence, the majority of pediatric neurosurgical practice is not supported by class I data. Furthermore, many trials that have been reported suffer from serious methodological shortcomings such as insufficient power and poor statistical analysis. Finally, several trials of neurosurgical techniques that are frequently performed on children have either excluded children from participation or include an insufficient number of children to draw strong conclusions. Despite these shortcomings, pediatric neurosurgery, like all fields in medicine, is gradually moving towards a more stringent evidence-based medicine standard. This chapter will attempt to summarize the recent progress that has been made in this area.

Clinical Trials as Topic↗

PubMed2004

Neurosurgical treatment of brain tumors in children.

Primary brain tumors are the most common solid neoplasms of childhood. The diagnosis of brain tumors in the general pediatric population remains challenging. Nevertheless, it is clear that refinements in imaging, surgical technique, and adjunctive therapies have led to longer survival and an improving quality of life in children with brain tumors.

Brain Neoplasms↗

PubMed2003

Confirmation of research publications reported by neurological surgery residency applicants.

OBJECTIVE: Previous studies have reported that as many as 30% of resident and fellow applicants misrepresent their publication record on their residency and fellowship applications. To determine if neurologic surgery residency applicants were guilty of similar rates of misrepresentation, we reviewed the applications submitted to our institution in the year 2001-2002. METHODS: There were 102 applications submitted to our neurologic surgery residency program for the 2001-2002 academic year. All publications listed by applicants on the Central Application Service for Neurologic Surgery were verified using various online bibliographic databases including MEDLINE and an interlibrary search. Manuscripts listed as being "in press" were authenticated by contacting the journals' editorial office while those listed as either "in preparation" or "submitted for publication" were excluded. RESULTS: Seventy-three (71.6%) candidates reported 212 published citations, including 129 (61%) journal articles, 13 (6%) book chapters, and 70 (33%) printed abstracts. Twelve of these applicants also listed 13 papers as being "in press." Overall, among the entire applicant pool, there were nine examples of possible misrepresentation in six applicants (6%). One applicant provided inadequate information to verify a book chapter. Another candidate cited four journal articles with the authors' names, even though his name was not listed among them. Two applicants included one citation each without listing any of the authors' names. Verification of these citations revealed that neither of them was a coauthor, although one was acknowledged. Among the articles listed as "in press," one was still under consideration for publication, and one could not be verified because of the journal's discontinuation. CONCLUSIONS: We confirmed that applicants who reported their names along with their published citations did so honestly and accurately. In our study, misrepresentation of published manuscripts among neurologic surgery residency applicants was rare when compared to candidates in other specialties.

Humans↗

PubMed2003

Neuro-oncology research opportunities in North America: results of a survey by the AANS/CNS section on tumors.

OBJECTIVE: A primary goal of the AANS/CNS Section on Tumors is to foster neuro-oncology research. The Research Committee was charged with the responsibility of assessing the neuro-oncology research opportunities currently available within neurosurgery residency programs and proposing strategies to enhance these activities. METHODS: Two separate surveys were mailed to all neurosurgery program directors (112) and neurosurgery residents (872) in North America. The initial mailing was in December 1997 and a follow-up mailing was sent in June 1998 to those who did not respond. RESULTS: Seventy-seven (69%) program directors and 279 (32%) neurosurgery residents responded to the survey. Neuro-oncology research rotations of varying duration (usually <12 months) were available at most residency programs (87%). Research mentors included equal numbers of neurosurgeons and outside faculty. Funding sources were well distributed among departmental (27%), federal (24%), institutional (22%), and private (19%) sources. Common basic science research areas included molecular biology, gene therapy, and pathology, whereas image-guided surgery was the most frequent area of clinical research. Approximately one-third of the responding residents had completed a neuro-oncology research rotation, mainly in an area of basic science, which resulted in an average of two publications and three presentations at national meetings. The most significant challenges for residents pursuing neuro-oncology research were concurrent clinical responsibilities, lack of faculty mentors, and insufficient research funding. CONCLUSIONS: Neuro-oncology research opportunities are available within most neurosurgery residency programs and appear to attract a reasonable number of productive trainees. The results of this survey have identified several important ways in which the AANS/CNS Section on Tumors can enhance neuro-oncology research opportunities and a comprehensive strategy for accomplishing these goals is presented.

Data Collection↗

PubMed2003

Congenital and childhood plexiform (multinodular) cellular schwannoma: a troublesome mimic of malignant peripheral nerve sheath tumor.

We present six cases of a plexiform nerve sheath tumor of childhood that previously had been designated a form of malignant peripheral nerve sheath tumor (MPNST), and we provide evidence that such tumors are in fact benign plexiform cellular schwannomas. At presentation, the four girls and two boys ranged in age from 2 to 15 months with tumors of the leg (four), deep groin and upper thigh (one), and pelvis (one). Of the six lesions, five were congenital and none was associated with type 1 neurofibromatosis. Tumor sizes ranged from 2.0 to 9 cm, with three larger than 5 cm. Three tumors were well circumscribed, two were purely infiltrative, and one had a mixed circumscribed and infiltrative growth pattern. Peripheral nerve involvement was evident in two cases. Grossly, the tumors were multinodular or plexiform in configuration and, on sectioning, lobulated and homogeneously tan without necrosis. Characteristic histologic features included hypercellularity, composition of cells spindle in shape with elongate hyperchromatic nuclei, and indistinct cellular outlines. Their nuclei varied minimally in size and shape but were at least three times the size of typical neurofibroma nuclei. Mitoses were seen in every tumor and in the areas of greatest proliferative activity ranged from 4 to 31/10 high power fields. MIB-1 staining of at least 30% of the cells was noted in three cases. In five cases in which p53 immunoreactions were performed, no nuclear staining was evident. That the tumors are schwannomas was evident from their uniform strong staining for S-100 protein and an ultrastructure in all five cases showing only differentiated neoplastic Schwann cells. Architecturally, the tumors differed from conventional schwannoma and nonplexiform cellular schwannomas by their lack of both well-formed capsules and degenerative changes. Follow-up was available in all cases and ranged from 2 to 13.6 years. All tumors recurred locally and were treated by local resections. With the exception of one child lost to follow-up at 25 months, all the children are alive and free of disease. Our data combined with cases previously reported by Meis-Kindblom and Enzinger show a childhood peripheral nerve tumor unassociated with type 1 neurofibromatosis, occurring most commonly in infants, often presenting as a congenital tumor and, though prone to local recurrence, having no metastatic potential. The behavior is that of a benign tumor, although its often rapid growth, hypercellularity and increased mitotic activity, sometimes locally aggressive behavior, and difficulties encountered in obtaining tumor-free margins are unsettling to pathologist and clinician alike. These features may lead to a misdiagnosis of malignancy, which could result in harmful overtreatment.

Biomarkers, Tumor↗

PubMed2003

Cortical resection for epilepsy in children with linear sebaceous nevus syndrome.

Linear sebaceous nevus syndrome (LSNS) is a rare neurocutaneous syndrome that is associated with seizures and mental retardation. The cortical abnormalities that are associated with this syndrome include focal cortical dysplasia, partial hemimegalencephaly and holohemispheric hemimegalencephaly. Few reports have addressed the utility of cortical resections for epilepsy treatment in the setting of LSNS. We report 3 children with this syndrome who underwent extensive cortical resections and experienced significant improvement in seizure frequency. Our results support the utility of extensive cortical resections for children with this condition.

Cerebral Cortex↗

PubMed2003

Advanced cancer genetics in neurosurgical research.

RAPID ADVANCES IN the technology used to study nucleic acids have revealed a great deal regarding the underlying biology of cancer. Most cancers arise as a result of chromosomal rearrangements and deoxyribonucleic acid mutations that lead to the activation of proto-oncogenes and loss of function of tumor suppressor genes. There are a number of different molecular routes that lead to these common goals, necessitating several different techniques of mutational analysis. Although many of these techniques can be difficult in practice, most are conceptually simple. We discuss several of the current techniques in cytogenetics and molecular genetics that are widely used in cancer biology laboratories. Understanding the molecular events that lead to cancer should allow the future development of targeted, nontoxic therapeutics similar to modern-day antibiotics. These technologies are being progressively applied in clinical neurosurgery, where they will be used to detect, diagnose, stratify, and treat cancers of the nervous system. High demand from an increasingly educated patient population means that neurosurgeons will need to be familiar with many of these techniques.

Cytogenetic Analysis↗

PubMed2003

Neurostimulation therapy for epilepsy: current modalities and future directions.

Neurostimulation is a recent development in the treatment of epilepsy. Vagus nerve stimulation (VNS), the only approved neurostimulation therapy for epilepsy to date, has proved to be a viable adjunctive treatment option. The exact mechanism of action of VNS is not fully understood. In 2 randomized double-blind trials, seizure frequency declined approximately 30% after 3 months of treatment. Long-term follow-up studies suggest that response improves over time, with approximately 35% of patients experiencing a 50% reduction and 20% experiencing a 75% reduction in seizure frequency after 18 months of treatment. Unfortunately, the number of patients rendered medication-free and seizure-free with VNS is low. Vagus nerve stimulation is best viewed as an option for patients who are not surgical candidates or who hesitate to take the risk of surgery yet continue to have seizures despite maximal medical therapy. Stimulation of other regions of the central nervous system for treating epilepsy, including the anterior and centromedian nuclei of the thalamus, the hippocampus, the subthalamic nucleus, and the cerebral neocortex, is currently under investigation. We review the history, proposed mechanisms of action, clinical trials, adverse effects, and future direction of VNS and other modalities of neurostimulation therapy for epilepsy.

Electric Stimulation Therapy↗

PubMed2002

Mutations in SUFU predispose to medulloblastoma.

The sonic hedgehog (SHH) signaling pathway directs the embryonic development of diverse organisms and is disrupted in a variety of malignancies. Pathway activation is triggered by binding of hedgehog proteins to the multipass Patched-1 (PTCH) receptor, which in the absence of hedgehog suppresses the activity of the seven-pass membrane protein Smoothened (SMOH). De-repression of SMOH culminates in the activation of one or more of the GLI transcription factors that regulate the transcription of downstream targets. Individuals with germline mutations of the SHH receptor gene PTCH are at high risk of developmental anomalies and of basal-cell carcinomas, medulloblastomas and other cancers (a pattern consistent with nevoid basal-cell carcinoma syndrome, NBCCS). In keeping with the role of PTCH as a tumor-suppressor gene, somatic mutations of this gene occur in sporadic basal-cell carcinomas and medulloblastomas. We report here that a subset of children with medulloblastoma carry germline and somatic mutations in SUFU (encoding the human suppressor of fused) of the SHH pathway, accompanied by loss of heterozygosity of the wildtype allele. Several of these mutations encode truncated proteins that are unable to export the GLI transcription factor from nucleus to cytoplasm, resulting in the activation of SHH signaling. SUFU is a newly identified tumor-suppressor gene that predisposes individuals to medulloblastoma by modulating the SHH signaling pathway through a newly identified mechanism.

Base Sequence↗

PubMed2002

Frequency and significance of acute postoperative seizures following epilepsy surgery in children and adolescents.

PURPOSE: To determine the frequency and prognostic features of acute postoperative seizures (APOSs), within the first postoperative week, in a group of children undergoing surgery for the treatment of medically refractory epilepsy. METHODS: Patients younger than 18 years who underwent surgery for the relief of medically intractable epilepsy at the Mayo Clinic between 1985 and 1998 with a minimum of 12 months of follow-up were eligible. A retrospective chart review was conducted to abstract information regarding demographics, epilepsy history, and preoperative, intraoperative, and postoperative risk factors, APOSs, and outcome. A multivariate analysis was conducted to control for confounding variables. RESULTS: The study group was composed of 148 patients (mean age at surgery, 13 years; range, 5 months to 18 years). Twenty-five percent of patients experienced APOSs. Risk factors associated with a statistically significant (p < 0.05) greater likelihood of experiencing APOS were non-complex partial seizure type, extratemporal surgery, postoperative fever, non-temporal lobe epilepsy, and postoperative interictal epileptiform activity. At last follow-up, patients who did not experience APOSs had a significantly greater chance of being seizure free (80 vs. 51%; p < 0.001). With a multivariate analysis, APOS was found to be an independent predictor of outcome. CONCLUSIONS: This study indicates that APOSs are predictive of a less favorable outcome in the pediatric postsurgical patient; however, 51% remained seizure free at last follow-up. Finally, the effects of APOSs on outcome were shown to be stable over a 12-month follow-up period.

Acute Disease↗

PubMed2002

Oligodendrogliomas with neurocytic differentiation. A report of 4 cases with diagnostic and histogenetic implications.

Oligodendroglioma represents a distinct type of diffuse glioma with a relatively favorable prognosis. Although an O2A-like glial progenitor cell of origin has been suggested, a neuronal-oligodendroglial progenitor cell is also of interest, particularly because variable degrees of neuronal marker expression have been reported in typical oligodendrogliomas. We present 2 female and 2 male patients (ages 34-54) with frontal lobe oligodendrogliomas containing a) morphologically distinct collections of small round cells with hyperchromatic nuclei, b) well-formed Homer Wright-like and perivascular rosettes, and c) demonstrable neuronal differentiation by immunohistochemistry and/or electron microscopy in the rosette-associated regions. Unlike extraventricular neurocytomas, these cases featured an infiltrative growth pattern and a classic oligodendroglioma immunophenotype in non-rosette bearing portions of each tumor. FISH analysis demonstrated chromosome 1p and 19q codeletions in 3 (75%) cases, both in regions with and without rosettes. Recurrences were common, although all patients are currently alive 4 months to 13 yr from initial diagnosis. Based on clinicopathologic and genetic features, we diagnosed these tumors as oligodendrogliomas with neurocytic differentiation. However, it is unclear whether they represent a) gliomas with divergent neuronal differentiation, b) a distinctive form of glioneuronal neoplasm, or c) a reflection of glioneuronal histogenesis in oligodendrogliomas in general. In any case, their occurrence suggests a histogenetic overlap between oligodendroglioma and extraventricular neurocytoma not previously recognized.

Adult↗

PubMed2002

Natural history of tethered cord in patients with meningomyelocele.

OBJECTIVE: The purpose of this study was to describe the natural history of tethered cord in patients who have undergone meningomyelocele repair. METHODS: We performed a retrospective review of 45 patients with a history of neonatal meningomyelocele repair who subsequently developed symptoms of tethered cord. Symptoms of tethered cord in this cohort consisted of the development of bladder spasticity or orthopedic foot deformity. None of these patients were treated with cord untethering; instead, they were treated symptomatically. RESULTS: On follow-up, 40 (88.9%) of these patients subsequently required additional orthopedic or urological procedures because of further symptoms of tethered cord. The incidence of progression of tethered cord syndrome is 27.5, 40, and 60% at 1, 2, and 5 years, respectively. CONCLUSION: Although this study does not address the question whether cord untethering will prevent further symptom development, these results do provide a strong rationale for consideration of an untethering procedure in patients with repaired meningomyelocele at the time of the onset of symptoms of tethered cord.

Adolescent↗

PubMed2002

Surgical treatment of fibrous dysplasia of the skull in children.

INTRODUCTION: We evaluate the role of surgery in the treatment of fibrous dysplasia of the skull in children. METHODS: We identified 48 consecutive cases of fibrous dysplasia of the skull that were surgically treated at a single institution over a 23-year interval. The 28 patients that initially presented during the first two decades of life were selected for further analysis. Presenting symptoms, signs, surgical treatment, surgical outcome and the state of the disease at the extended follow-up interval were recorded. RESULTS: Fibrous dysplasia of the skull in children most often involved the frontal, sphenoid and ethmoid bones. Most patients presented with facial asymmetry or proptosis. A gross total resection was achieved in 7 patients, subtotal resection in 17 patients, and 4 patients underwent biopsy alone. Over the follow-up interval, 7 patients had symptomatic progression of subtotally resected fibrous dysplasia and 3 patients had asymptomatic progression. The extent of resection was correlated with recurrence risk. CONCLUSIONS: In order to prevent progression of disease, an attempt at gross total resection is indicated in cases of fibrous dysplasia of the skull in childhood where the risk of neurologic morbidity is low and cosmetic results will be acceptable.

Child↗

PubMedDate not supplied

Medulloblastoma: molecular genetics and animal models.

Medulloblastoma is a primary brain tumor found in the cerebellum of children. The tumor occurs in association with two inherited cancer syndromes: Turcot syndrome and Gorlin syndrome. Insights into the molecular biology of the tumor have come from looking at alterations in the genes altered in these syndromes, PTC and APC, respectively. Murine models of medulloblastoma have been constructed based on these alterations. Additional murine models that, while mimicking the appearance of the human tumor, seem unrelated to the human tumor's molecular alterations have been made. In this review, the clinical picture, origin, molecular biology, and murine models of medulloblastoma are discussed. Although a great deal has been discovered about this tumor, the genetic alterations responsible for tumor development in a majority of patients have yet to be described.

Animals↗