Maciej S. Lesniak

Surgical Outcome following Resection of Contrast-Enhanced Pediatric Brainstem Gliomas

Background: The role of surgery in the management of gadolinium-enhancing pediatric brainstem lesions on magnetic resonance imaging (MRI) has been a matter of open debate. This clinical series correlates radiological and pathological findings to assess the role of contrast enhancement as an indication for surgery with respect to clinical outcome. Methods: We retrospectively reviewed the charts of all pediatric patients admitted to the Johns Hopkins Hospital with a diagnosis of a brainstem tumor between January 1985 and December 2000. Results: There were a total of 89 patients who met the inclusion criteria. Fifty-seven patients (64.0%) underwent surgical resection while 32 (36%) were treated with radiation and/or chemotherapy. Of the surgical candidates, 57 (100%) had an accompanying MRI scan significant for an enhancing lesion in the midbrain, pons or the medulla. The pathology was consistent with juvenile pilocytic astrocytoma in 30 patients (52.6%) and glioblastoma multiforme in 12 patients (21.1%). The remaining cases consisted of 10 patients (17.5%) with fibrillary astrocytomas, 3 (5.3%) with gangliogliomas, 1 (1.8%) with an oligodendroglioma and 1 (1.8%) with a primitive neuroectodermal tumor. A total of 29 patients had a total surgical resection, 8 a near total resection (>90%), 15 a subtotal resection (50–90%) and 5 a partial resection (<50%). The progression-free survival of all patients was 71.9% at 3 years and 45.6% at 5 years. Conclusions: This case series illustrates that contrast-enhanced MRI has positive prognostic value in the management of pediatric brainstem gliomas. In our study, the majority of enhancing tumors were low grade and amenable to surgical intervention. Consequently, we recommend surgical resection and pathological diagnosis of all enhancing brainstem tumors with adjuvant therapy reserved for recurrent or unresectable cases.

Multicentric parenchymal xanthogranuloma in a child: Case report and review of the literature

OBJECTIVE AND IMPORTANCE Xanthogranulomas of the central nervous system are rare, and asymptomatic lesions are often identified in autopsies. We report the first case of a multicentric, cystic, intraparenchymal xanthogranuloma, involving both the supra- and infratentorial compartments, in a 16-month-old girl. CLINICAL PRESENTATION The clinical presentation consisted of a focal motor seizure in an otherwise healthy infant. INTERVENTION Gross total removal of the infratentorial lesion was accomplished via a midline suboccipital craniotomy. CONCLUSION Intracranial xanthogranulomas are rare, and limited experience with the diagnosis of these lesions has been reported. Although most cases are asymptomatic, this case involves a symptomatic, multicentric, intraparenchymal xanthoma in a pediatric patient. Our review of the literature provides further insights regarding the clinical, radiological, and pathological behavior of these lesions and examines the available treatment strategies.

Gene Therapy for Experimental Brain Tumors Using a Xenogenic Cell Line Engineered to Secrete hIL-2

Local delivery of cytokines has been shown to have a potent anti-tumor activity against a wide range of malignant brain tumors. In this study, we examined the feasibility and efficacy of using a rat endothelial cell line (NTC-121) transfected with the human interleukin-2 (IL-2) gene in treating experimental murine CNS tumors. The NTC-121 cells were injected intracranially in C57BL/6 mice (N = 10/group) along with non-irradiated, non-transfected B16/F10 (wild type) melanoma cells. Sixty percent of mice treated with IL-2 (p < 0.001 vs. control) were long-term survivors (LTS) of >120 days. Control animals that received only wild type cells had a median survival of 18 days (range 15–20). Histopathological examination of brains from animals sacrificed at different times showed no tumor growth in the non-irradiated NTC-121 group, moderate (1–2mm) tumor growth in the irradiated group, and gross tumor invasion (>2mm) and tissue necrosis in the control group. Moreover, animals treated with IL-2 showed an accumulation of CD8+ T cells around the site of the injected tumor. The use of a xenogenic cell line to deliver hIL-2 stimulates a strong immunologic cytotoxic anti-tumor response that leads to significant prolongation of survival in mice challenged with the B16/F10 intracranial melanoma tumor. Our findings demonstrate that the use of a xenogenic cell line can provide a potent vehicle for the delivery of gene therapy and may therefore represent a new approach for brain tumor therapy.

Targeting Drugs to Tumors of the Central Nervous System

Central nervous system (CNS) tumors represent one of the most devastating forms of human illness. In the United States, approx 16,800 people are diagnosed with primary brain tumors each year (33). Of these, half are glial cell neoplasms and more than three quarters of all gliomas are astrocytomas. Astrocytomas represent a heterogeneous group of tumors that can vary from lowgrade to the most aggressive-glioblastoma multiforme-based on histopathological classification. Conventional therapy for glioblastomas consists primarily of surgical debulking followed by radiation therapy. Unfortunately, the median survival after surgical intervention alone is 6 mo with only 7.5% of patients surviving for 2 yr. While systemic chemotherapy has been minimally effective, the addition of radiation therapy has extended the median survival to 9 mo (2,44). In spite of these efforts, little progress has been made in extending long-term patient survival, and new therapies and novel approaches are urgently needed to treat this disease.

Vascular Malformations of the Posterior Fossa: Clinical Features, Treatment, and Outcomes

Vascular malformations affecting the cerebral hemispheres are a relatively common clinical entity. In contrast, vascular malformations of the posterior fossa are rare, and there are few documented series involving a large number of patients. Our experience with 93 patients encountered at The Johns Hopkins Hospital is reported. The records of all patients admitted with a radiologically verified diagnosis of posterior circulation vascular malformation from January 1986 through December 2000 were retrospectively reviewed. There were a total of 712 cases of vascular malformations. Of these, 93 cases localized to the posterior fossa (13%). The pathologic findings were consistent with an arteriovenous malformation in 38 patients (41%), cavernous malformation in 20 patients (22%), venous malformation (VM) in 17 patients (18%), and dural arteriovenous fistula in 18 patients (19%). All patients, except for those with VMs, were treated by means of surgery, radiosurgery, or neuroradiologic intervention. Sixty-six percent of patients showed excellent recovery, with 18% more exhibiting only mild neurologic deficits. The overall morbidity in this series was 10.5%, with a mortality rate of 5.3%. Management of vascular malformations in the posterior fossa can pose significant problems. In our experience, patients who are symptomatic, have a prior history of hemorrhage, and are at increased risk for future bleeds are best treated by surgery ± preoperative embolization. On the other hand, patients who are asymptomatic or who harbor small lesions in relatively inaccessible areas benefit the most from radiosurgery. This approach has led to excellent clinical outcomes, with the majority of patients remaining neurologically intact.

Surgical outcome following resection of contrast-enhanced pediatric brainstem gliomas (multiple letters)

Accessible online at: www.karger.com/pne To the Editor: I enjoyed this article from the Hopkins group regarding their experience with surgery for brainstem gliomas [1], but I believe that the authors need to refine their conclusions regarding surgical outcome following resection of contrast-enhanced pediatric brainstem gliomas. They indicate that contrast enhancement has a ‘positive prognostic value’ in the management of these tumors, yet they never clearly define ‘contrast enhancement’ – neither its location within in the tumor nor its intensity. In the single MRI illustration in their paper, the lesion shown is a well-circumscribed cystic lesion with an enhancing mural nodule. A brainstem tumor of this appearance is clearly benign and would not at all be confused with the usual diffuse ‘pediatric brainstem glioma’, many of which do enhance to a variable extent and which are not surgical cases as a rule. The authors need to be more specific about their definition of contrast enhancement and describe exactly what patterns they feel are associated with benign tumors. I suspect that they will inform us that the enhancement that they are talking about is well defined and uniform, and corresponds with a sharply defined lesion on the T2 and other sequences – typical for a pilocytic astrocytoma and not at all typical for the usual ‘brainstem glioma’ of their paper’s title.

The Role of Stereotactic Radiosurgery in the Management of Benign, Atypical, and Malignant Meningiomas

Stereotactic radiosurgery and fractionated Stereotactic radiotherapy (SR) offer precise localization of radiation dose (Gy) for the treatment of meningioma (M). For the multimodal treatment with preservation of function, SR is complementary to both microsurgery (S) and conventional external beam radiotherapy (XRT). The role of SR in the management of atypical and malignant meningiomas, however, remains unexplored. Fifty consecutive patients with meningioma: 18 males (60.1 +/− 2.3 years) and 32 females (56.9 +/− 2.2 years) (p = NS) received SR. Thirty-one patients had surgery 69.6 +/− 13.9 months (95% CI: 53.3–98.0) prior to SR. For patients having S, the incidence of atypical or malignant versus benign meningiomas (14 versus 17 patients) increased with age (p = 0.03). Twenty patients had XRT approximately 18 months prior to SR. For antecedent XRT, the range of doses was 3600–6400 cGy (median: 5040 cGy). Following failure of S and/or XRT, patients had SR. Compared to other series, the mean tumor volumes for SR were comparatively large: 9.8 +/− 1.3 cm3 (range 0.3–37.1 cm3). The median SR dose was 3500 cGy (range 540–5400 cGy) administered in seven fractions (range 1–30). Linear regression analysis showed a consistent method for fractionation: the number of administered fractions increased (p = 0.053) and the total dose increased (p = 0.054) with tumor size. During the interval for follow–up (17.9 +/− 2.9 months), one patient with malignant meningioma required surgery for progression 8 months after SR. In the remaining patients, post-SR MRIs showed control (unchanged or smaller tumor volume) regardless of histology. These results show that SR may provide control of M regardless of grade.