Arthur J. DiPatri

Cellular injury and neuroinflammation in children with chronic intractable epilepsy

ObjectiveTo elucidate the presence and potential involvement of brain inflammation and cell death in neurological morbidity and intractable seizures in childhood epilepsy, we quantified cell death, astrocyte proliferation, microglial activation and cytokine release in brain tissue from patients who underwent epilepsy surgery.MethodsCortical tissue was collected from thirteen patients with intractable epilepsy due to focal cortical dysplasia (6), encephalomalacia (5), Rasmussens encephalitis (1) or mesial temporal lobe epilepsy (1). Sections were processed for immunohistochemistry using markers for neuron, astrocyte, microglia or cellular injury. Cytokine assay was performed on frozen cortices. Controls were autopsy brains from eight patients without history of neurological diseases.ResultsMarked activation of microglia and astrocytes and diffuse cell death were observed in epileptogenic tissue. Numerous fibrillary astrocytes and their processes covered the entire cortex and converged on to blood vessels, neurons and microglia. An overwhelming number of neurons and astrocytes showed DNA fragmentation and its magnitude significantly correlated with seizure frequency. Majority of our patients with abundant cell death in the cortex have mental retardation. IL-1beta, IL-8, IL-12p70 and MIP-1beta were significantly increased in the epileptogenic cortex; IL-6 and MCP-1 were significantly higher in patients with family history of epilepsy.ConclusionsOur results suggest that active neuroinflammation and marked cellular injury occur in pediatric epilepsy and may play a common pathogenic role or consequences in childhood epilepsy of diverse etiologies. Our findings support the concept that immunomodulation targeting activated microglia and astrocytes may be a novel therapeutic strategy to reduce neurological morbidity and prevent intractable epilepsy.

Infectious intracranial aneurysms in the pediatric population: Endovascular treatment with Onyx

ObjectsInfectious intracranial aneurysms present a treatment challenge in the pediatric population. Current endovascular strategies and tools have been developed, which make treatment of infectious intracranial aneurysms with liquid embolics safe and effective. This study reviews the use of the liquid embolic Onyx in the treatment of infectious intracranial aneurysms in the pediatric population.Materials and methodsWe used an endovascular approach to treat ruptured infectious intracranial aneurysms. We embolized the aneurysms with either Onyx alone or in combination with platinum coils.ConclusionEndovascular therapy with liquid embolics (Onyx) has been shown to be a safe and effectual treatment option in the case of pediatric infectious intracranial aneurysms. The combination of endovascular modalities can also be used to tailor the therapeutic goal of exclusion of infectious aneurysms with good results. Further studies are needed to assess the long-term effectiveness of this approach to pediatric infectious intracranial aneurysms.

Choroid plexus tumors in pediatric patients.

Abstract Objective. Choroid plexus tumors are rare intraventricular tumors, accounting for less than 1% of all intracranial tumors and 2–4% of brain tumors in children. The authors present their experience in the management of these lesions, and a review of the literature is performed. Methods. We retrospectively analyzed the outcome of pediatric patients with choroid plexus tumors treated with surgical resection. The patients’ charts were reviewed for demographic data, clinical presentation, surgical therapy and follow-up. Results. This study involves 18 consecutive choroid plexus tumors: 14 papillomas, 2 atypical papillomas and 2 carcinomas. The tumor was located in the lateral ventricles (12), the fourth ventricle (4) and the third ventricle (2). The mean age at presentation was 4.6 years. Surgical resection was performed in all cases and no patients died perioperatively. Survival rate of papilloma patients was 100% without evidence of recurrent disease (mean follow-up for 73 months). Survival rate of carcinoma patients was 50% (mean follow-up for 23.5 months). One carcinoma patient died of disseminated disease 13 months after surgery. The functional outcome in long-term survivors after papilloma surgery was excellent. Postoperative extraventricular drainage (EVD) was performed in 12 patients. Five patients (27.8%) had persistent hydrocephalus after tumor resection and required a ventriculoperitoneal shunt. Conclusion. Choroid plexus papilloma is a surgically curable disease. Postoperative EVD was considered effective in lowering the rate of shunt requirement through releasing the blood-tinged CSF and small particles of tumor residue.

Onyx embolization of intracranial arteriovenous malformations in pediatric patients.

OBJECT The authors undertook this study to assess the safety and efficacy of Onyx embolization in the treatment of intracranial arteriovenous malformations (AVMs) in pediatric patients. METHODS All pediatric Onyx embolization of intracranial AVM cases performed consecutively at a single childrens hospital over a 5-year period were collected and evaluated. RESULTS Twenty-five patients (mean age 10.5 years) underwent a total of 38 procedures. An aggregate of 56 pedicles were embolized (mean 1.47 per session). The Spetzler-Martin grade was determined in all cases. Onyx embolization resulted in complete obliteration of the AVM in 3 cases (12%) and partial obliteration in 22 cases (88%). A total of 23 patients underwent surgical treatment. The mean preoperative AVM devascularization in these cases was 72%. One patient was treated with radiosurgery following Onyx embolization. Overall, 10 complications occurred in a total of 38 procedures (26.3%). None of the complications resulted in permanent neurological morbidity. The rate of transient neurological complications was 10.5% (4 of 38 procedures) and the rate of transient nonneurological complications was 5.3% (2 of 38 procedures). The remaining 4 complications were clinically silent (rate of 10.5%). There were no procedure-related deaths in this study population. There was no significant difference in patients with and without complications in terms of demographic characteristics, AVM grade, or embolization features (p ≥ 0.2). Deep venous drainage was associated with higher complication rates (p = 0.03). CONCLUSIONS Onyx utilization is feasible for preoperative or primary embolization in the treatment of pediatric intracranial AVMs; however, the spectrum of complications encountered is broad, and attention must be paid to the technical nuances of and indications for its use to avoid many potential dangerous effects. Although the overall complication rates were higher than expected, all were either clinically silent or had only transient clinical effects. Thus, this experience suggests that Onyx embolization can be performed safely with a low rate of permanent morbidity in pediatric patients harboring these difficult lesions.

A history of the treatment of craniopharyngiomas

RationaleNearly 100 years have passed since the first surgical attempt to remove a craniopharyngioma was undertaken, and the management of patients with these tumors continues to both challenge and frustrate those involved with their treatment.MethodsBy constructing a historical framework from past literature on the treatment of craniopharyngioma, the authors have attempted to document the early and important events in the treatment of these tumors in order to add a historical dimension to their current treatment and to engender a more comprehensive understanding of the modern treatment of craniopharyngioma.ConclusionThe application of radiotherapeutic techniques to the management of craniopharyngioma would begin to complement the role of surgery, but debate would soon emerge as to what constituted the most appropriate management for craniopharyngioma in children.

Hydro Coil embolization of a ruptured infectious aneurysm in a pediatric patient: case report and review of the literature

IntroductionIntracranial infectious aneurysms in the pediatric population are rare. Although surgery has been the traditional treatment of ruptured pediatric infectious aneurysms, endovascular coil embolization has become an attractive alternative due to its low rate of morbidity and mortality.Case reportA 9-year-old boy with a significant medical history of aortic valve replacement, antibiotic-treated infective endocarditis, and multiple embolic cerebral infarcts presented with a high-grade intraventricular hemorrhage due to the rupture of a large infectious proximal posterior circulation aneurysm. Computed tomography and cerebral angiogram demonstrated a right crural/ambient cistern hematoma and an associated infectious aneurysm of the right proximal posterior cerebral artery. The ruptured infectious aneurysm was coil-embolized with hydrogel-coated platinum coils without sacrifice of the distal parent artery. The aneurysm was completely occluded, and the patient regained all neurological function.ConclusionRuptured infectious aneurysms in the pediatric population occur despite aggressive medical therapy. Patients with infective endocarditis and embolic infarcts should be followed closely due to the risk of major hemorrhagic events, including aneurysm rupture. Hybrid coil embolization of ruptured infectious aneurysms with preservation of the distal parent artery is exceedingly rare and effective in the management of ruptured infectious aneurysms in the pediatric population.

Isolated origin of the left internal carotid artery from the pulmonary artery: Case report

The authors describe what is, to their knowledge, the first reported case of the anomalous origin of an internal carotid artery from the pulmonary artery. An otherwise asymptomatic 6-year-old girl, who presented with headaches and hypertension, underwent a comprehensive workup that revealed extensive meningeal and cerebral artery anastomoses to the left internal carotid artery--itself arising from the origin of the left pulmonary artery. This unique anatomical anomaly, caused by a disturbed pattern of aortic arch regression, resulted in a right-to-left vascular shunt into the pulmonary artery and a disturbance of intracranial artery flow patterns, complicating the management options.

Juvenile Pilocytic Astrocytoma in Association with Arteriovenous Malformation

Pilocytic astrocytomas are highly vascular, relatively common primary brain tumors in the pediatric population, but their association with a true arteriovenous malformation (AVM) is extremely rare. We describe an eight-year-old girl with a right supratentorial juvenile pilocytic astrocytoma (WHO grade I) with an angiographically documented AVM entangled in the tumor mass who presented with intracranial hemorrhage due to a ruptured anterior choroidal artery pseudoaneurysm encased in the lesion. The AVM nidus as well as the hemorrhage site was embolized with Onyx. A literature review revealed only one previous report of a true intermixture of these two lesions. We hypothesize whether the association of vascular malformations and primary brain tumors are merely coincidental or if they point to the existence of a distinct entity and/or a common etiologic factor.

Diffuse postoperative cerebellar swelling in medulloblastoma: report of two cases

BackgroundWe report two cases of diffuse cerebellar swelling with upward transtentorial herniation following medulloblastoma resection. We present our insight for managing medulloblastoma with aggressive clinical behavior.Review summaryCase 1 is a 32-month-old boy. Magnetic resonance imaging (MRI) revealed fourth ventricular mass with diffuse leptomeningeal metastasis. He underwent gross total resectioning of the tumor and histopathology revealed a large cell medulloblastoma. A ventriculoperitoneal shunt was placed on the 25th postoperative day. Ten days after he developed lethargy, and MRI showed diffuse cerebellar swelling with upward herniation. He underwent emergent posterior fossa decompression; however, he remained unresponsive since then. Case 2 is a 31-month-old boy. MRI revealed a fourth ventricular mass with diffuse leptomeningeal metastasis. He underwent gross total resection and histopathology was a large cell medulloblastoma. Due to developing ventriculomegaly, extraventricular drainage was reinserted on the 11th postoperative day. Four days after, he developed lethargy and decerebrate posturing. MRI showed diffuse cerebellar swelling with upward herniation. He underwent aggressive posterior fossa decompression. Chemotherapy was started postoperatively. Gradually, his movement of extremities improved. On the 79th postoperative day, he started to follow commands and talk some words. He was discharged to a rehabilitation institute and has continued to improve since then.ConclusionDiffuse cerebellar swelling with upward herniation could occur in patients with aggressive medulloblastoma postoperatively. Our patients had diffuse leptomeningeal dissemination of the tumor at the initial presentation. Close monitoring and prompt diagnosis with earlier surgical posterior fossa decompression and administration of chemotherapy may prevent irreversible neurologic deterioration.

Late effects of neurosurgery

For most diagnoses in neuro-oncology, surgery plays a key role in the multidisciplinary patient management strategy. While the goals of surgery will vary between specific cases, most procedures are performed with the intention to procure tissue to establish the histological diagnosis, to alleviate mass effect on the surrounding structures, and to achieve maximal cytoreduction in anticipation of subsequent adjuvant therapy. Since many patients will go on to require other treatments such as chemotherapy and radiation therapy, the long-term effects of the surgery itself can be difficult to determine. In this chapter, we will provide a historical perspective on the specialty of neurosurgery and discuss the evolution of techniques and noteworthy innovations that have contributed to a reduction in morbidity and mortality and, ultimately, in an improvement in the incidence and severity of late effects. Since the neurological, cognitive and endocrinological late effects of treatment are discussed elsewhere in this text, we will limit our discussion to the late effects related to the surgical treatment of central nervous system tumors.