Diagnosis and Therapeutic Management of Ventricular Gangliogliomas: An Illustrated Review.

BACKGROUND: Gangliogliomas (GGs) are extremely rare benign neoplasms frequently located within the temporal lobe that usually present with seizures. GGs growing predominantly within the ventricular system (VGGs) are even more infrequent, so definite conclusions concerning their diagnosis and therapeutic management are lacking. METHODS: A retrospective review of case reports of VGGs was performed from the introduction of modern imaging techniques, including 4 new illustrative cases treated in our department. RESULTS: Thirty-four cases were collected. Ages ranged from 10 to 71 years (mean, 26.62 years), and 55.9% were male. Most patients developed symptoms related to high intracranial pressure. The lateral ventricles were predominantly involved (58.8%). Obstructive hydrocephalus was observed in 54.5% of patients. Cystic degeneration and calcification were frequently observed. Surgical treatment was carried out in all cases. Morbidity and mortality were 17.6% and 2.9%, respectively. Gross total tumor resection was achieved in 64.5% of patients. Four patients experienced tumor dissemination along the neural axis. More than 90% of patients maintained a good functional status at last follow-up. CONCLUSIONS: Despite their low incidence, a diagnosis of VGGs should be considered in young male adults who progressively develop intracranial hypertension, caused by a ventricular mass showing signs of cystic degeneration and calcification. Maximal and safe surgical resection represents the gold standard for the treatment of symptomatic VGGs, although total removal is frequently precluded by difficulties in defining appropriate tumor boundaries. Adjuvant radiotherapy should be considered if an incomplete resection was carried out, especially in World Health Organization grade III neoplasms.

BRAF somatic mutation contributes to intrinsic epileptogenicity in pediatric brain tumors.

Pediatric brain tumors are highly associated with epileptic seizures1. However, their epileptogenic mechanisms remain unclear. Here, we show that the oncogenic BRAF somatic mutation p.Val600Glu (V600E) in developing neurons underlies intrinsic epileptogenicity in ganglioglioma, one of the leading causes of intractable epilepsy2. To do so, we developed a mouse model harboring the BRAFV600E somatic mutation during early brain development to reflect the most frequent mutation, as well as the origin and timing thereof. Therein, the BRAFV600E mutation arising in progenitor cells during brain development led to the acquisition of intrinsic epileptogenic properties in neuronal lineage cells, whereas tumorigenic properties were attributed to high proliferation of glial lineage cells. RNA sequencing analysis of patient brain tissues with the mutation revealed that BRAFV600E-induced epileptogenesis is mediated by RE1-silencing transcription factor (REST), which is a regulator of ion channels and neurotransmitter receptors associated with epilepsy. Moreover, we found that seizures in mice were significantly alleviated by an FDA-approved BRAFV600E inhibitor, vemurafenib, as well as various genetic inhibitions of Rest. Accordingly, this study provides direct evidence of a BRAF somatic mutation contributing to the intrinsic epileptogenicity in pediatric brain tumors and suggests that BRAF and REST could be treatment targets for intractable epilepsy.

Ganglioglioma of the adenohypophysis mimicking pituitary adenoma: A case report and review of the literature.

INTRODUCTION: Ganglioglioma is a generally benign tumor, mostly occurring in patients <30 years old. Temporal lobe is most frequently involved. Up to now, only 3 cases were reported of ganglioglioma in the pituitary gland, all being confined to the neurohypophysis. Here, we are the first to report an adenohypophysis ganglioglioma. CASE PRESENTATION: A 43-year-old woman presented with chronic headache was referred to our hospital. Magnetic resonance imaging (MRI) indicated pituitary adenoma. Endoscopic transnasal transsphenoidal surgery was performed. The tumor was rich in blood supply, with tough texture, therefore only subtotal resection was conducted. Pathology analysis revealed an adenohypophysial tumor composed of dysplastic ganglion cells and neoplastic glial cells collided with nonspecific hyperplasia of pituitary cells. Immunohistochemistry revealed positive staining of synaptophysin, glial-fibrillary acidic protein, and CD34. The results were consistent with the diagnosis of ganglioglioma. After the surgery the patient recovered well except developing cerebrospinal fluid rhinorrhea, which was controlled by lumbar drainage. MRI 6 months later did not show any sign of progression. CONCLUSION: According to the findings of our case, concerns should be raised considering ganglioglioma as a differential diagnosis of mass located in the sellar region. Furthermore, an ideal management strategy for pituitary ganglioglioma is not known; therefore, more cases and long-term follow-up are needed to enrich our knowledge of the diagnosis, treatment, and prognosis of this rare intracranial lesion.

Molecular Analysis of Tumor Cell Components in Pilocytic Astrocytomas, Gangliogliomas, and Oligodendrogliomas.

Gliomas and glioneuronal tumors are histologically polymorphous tumors. They can harbor a clear cell "oligodendroglial-like" component that can be difficult to distinguish from tumor cells of oligodendrogliomas or neurons, particularly on small samples. Thus, knowledge of the pattern of molecular markers in different tumor cell components is essential to ensure reliable diagnosis. Here, we screened 14 pilocytic astrocytomas (PA), 12 gangliogliomas, and 13 oligodendrogliomas for the KIAA1549-BRAF fusion gene, IDH1/2 mutations, and 1p19q losses in various areas of interest representative of the different tumor cell components. Molecular patterns were analyzed according to histologic type, tumor cell components, and clinical data. The KIAA1549-BRAF fusion gene was detected only in 8 out of 11 PAs (73%) and in 3 out of 9 gangliogliomas (33%) (P=0.003). Interestingly, all of the studied areas of interest within the same tumor exhibited the same KIAA1549-BRAF fusion gene status. IDH1-R132H and 1p19q loss were found only in 12 out of the 13 oligodendrogliomas (P<0.0001). Our study shows that cellular polymorphism in PAs and gangliogliomas does not affect the results of molecular analysis investigating the status of the KIAA1549-BRAF fusion gene. Thus, this molecular analysis can be reliably used even if the sample size is limited and the selection of different tumor areas is not possible.

Dysplastic Cerebellar Epilepsy: Complete Seizure Control Following Resection of a Ganglioglioma.

Subcortical epilepsy has been a controversial issue, partially settled by evidence showing seizure generation in hypothalamic hamartomas and also by reports of seizures caused by cerebellar lesions. We report 4-year-old girl with right hemifacial seizures and autonomic phenomena, in whom MRI showed an irregular mass in the right cerebellar peduncle. Despite several unremarkable video-EEG recordings, seizure origin in the lesion was hypothesized. Complete resection was feasible, histopathology showed a ganglioglioma, and she has been seizure free for 3 years. A fine line separates these developmental tumors from focal cortical dysplasia, and the homogeneous presentation of this entity led us to propose the terminology dysplastic cerebellar epilepsy.

Pediatric posterior fossa ganglioglioma: unique MRI features and correlation with BRAF V600E mutation status.

Ganglioglioma (GG) is a rare pediatric brain tumor (1-4 %) with neoplastic glial and neuronal cells. Posterior fossa GGs (PF GGs) occur less frequently than supratentorial GGs (ST GGs). The BRAF V600E mutation has been reported in GGs and carries therapeutic implications. We compare the presenting symptoms, magnetic resonance imaging, BRAF V600E mutation status, treatment, and prognosis in children with ST and PF GGs. The neuro-oncology database at a tertiary care Children's Hospital was retrospectively reviewed from 1995 to 2010 for patients with ST and PF GG. All available imaging was reviewed. Symptoms, BRAF V600E mutation status, treatment, and survival data were collected from the electronic medical record and analyzed. Our series consisted of 11 PF GG and 20 ST GG. Children with PF GG presented with ataxia, cranial nerve deficits and long tract signs whereas the majority with ST GGs presented with seizures. On imaging, PF GGs were infiltrative and expansile solid masses with dorsal predominant "paintbrush" enhancement whereas ST GGs were well circumscribed mixed solid and cystic masses with heterogeneous enhancement. Five of 11 (45%) PF GGs and 6 of 9 (67%) ST GGs expressed the BRAF V600E mutation. No unique imaging features were identified in BRAF V600E mutation positive tumors. The majority of ST GGs were treated with surgery alone, whereas the majority of PF GGs required multimodality therapy. PF GGs had worse progression-free survival and a higher mortality rate compared with ST GGs. Unlike ST GGs, PF GGs are expansile, infiltrative, show dorsal predominant "paintbrush" enhancement, are not amenable to gross total resection, and have worse progression-free survival and mortality.

A 45-year-old woman with reversible bilateral hearing loss.

A 45-year-old woman complained of a progressive 2-month history of bilateral hearing impairment and diplopia on upward gaze. She had a history of a recurrent pineal region ganglioglioma with repeated tumor excision, adjuvant radiotherapy, and a ventriculo-peritoneal shunt performed 12 years prior. Subsequent imaging studies 6 years ago showed a pineal region cyst with progressive increase in size and a Rickham reservoir (Codman; Johnson & Johnson, Raynham, MA) was placed for percutaneous cyst fluid aspiration. The size of the cystic lesion remained static upon follow-up CT scans for several years.

Intraoperative visualisation of language fascicles by diffusion tensor imaging-based tractography in glioma surgery.

BACKGROUND: For gliomas, the goal of surgery is to maximise the extent of resection (EOR) while minimising the postoperative morbidity. The purpose of this study was to evaluate the benefits of a protocol developed for the surgical management of gliomas located in language areas, where tractography-integrated navigation was used in conjunction with direct electrical stimulations (DES). METHODS AND MATERIALS: The authors included ten patients suffering of gliomas located in language areas. The preoperative planning for multimodal navigation was done by integrating anatomical magnetic resonance images and subcortical pathway volumes generated by diffusion tensor imaging. Six white matter fascicles implicated in language functions were reconstructed in each patient, including fibres for phonological processing (i.e. the arcuate fasciculus), fibres for lexical-semantic processing (i.e. the inferior frontooccipital fasciculus, inferior longitudinal fasciculus and uncinate fasciculus), and two premotor fasciculi involved in the preparation of speech movements (the subcallosal medialis fasciculus and cortical fibres originating from the medial and lateral premotor areas). During surgery, language fascicles were identified by direct visualisation on tractography-integrated navigation images and by observing transient language inhibition after subcortical DES. Language deficits were evaluated preoperatively and postoperatively, and compared with the EOR. RESULTS: Tractography was successfully performed in all patients, preoperatively demonstrating the relationships between the tumours to resect and the language fascicles to preserve from injury. With the use of the tractography-integrated navigation system and intraoperative DES, language functions were preserved in all patients. The mean volumetric resection was 93.0 ± 10.4 % of the preoperative tumour volume, with a gross total resection in 60 % of patients. CONCLUSION: The intraoperative combination of tractography and DES contributed to maximum safe resection of gliomas located in language areas.

Multiple band frequency analysis in a child of medial temporal lobe ganglioglioma.

We report a 1-year 6-month-old girl with ganglioglioma in the right medial temporal lobe who showed epileptic spasms in clusters. Spasms occasionally followed a dazed and fearful gaze. Interictal electroencephalography (EEG) showed diffuse bursts of slightly irregular high-voltage spikes and slow waves without hypsarrhythmia. The findings on ictal EEG, single-photon emission computed tomography, and F-18 fluorodeoxyglucose positron emission tomography indicated focus on the right medial temporal lobe. Ictal fast rhythmic activity analysis of scalp EEG by multiple band frequency analysis showed gamma rhythms at 65-80 Hz with a high spectral power around the tumor area. Epileptic spasms completely disappeared after tumor resection. These findings suggest that the cerebral cortex may be a source of epileptic spasms and indicate the possibility of usefulness of fast activity analysis in this condition.

[Intracranial gangliogliomas. A review of a series of 20 patients]. / Gangliogliomas intracraneales. Revisión de una serie de 20 pacientes.

INTRODUCTION: A ganglioglioma is a type of primary central nervous system low grade tumour composed of mixed populations of glial and neuroepithelial elements. They accounts for 0.4 to 2% of all intracranial tumours and appear more commonly in children and young adults. Seizures, which are the most important symptom in these tumours, improve significantly after surgical excision. METHODS: Between 1995 and 2008, 20 patients with (12 adults and 8 children) with intracranial ganglioglioma were treated at our hospital. Clinical information obtained by chart review included sex, age at onset of symptoms, clinical history, results of neurological examination, tumour location, CT and MRI appearance, surgical results and follow-up. All patients underwent tumour resection and the extent of surgery was determined from the surgical reports and postoperative imaging studies. RESULTS: The median age of patients was 26.4 years (range, 1-75 years), and the female to male ratio was 1.5:1. Except in one case, all patients had seizures with a median duration before diagnosis of 7.4 years (range 1-29). Seventeen tumours were located in the temporal lobe (9 right and 8 left). Macroscopically complete excision was performed in 17 patients and subtotal in the remaining 3. There were 4 cases of recurrence treated by surgery and radiotherapy being added in one case. The mean follow up was 8.5 years (range 22 months-14 years) and disease free survival at 5 years was 85% and an overall survival of 95%. CONCLUSIONS: The seizures, which are the most frequent symptoms, significantly improved after surgical removal. Surgery is the first choice of therapy in these tumours, and in the presence of subtotal resection or tumour recurrence the best indication for treatment is repeat surgery. Radiotherapy should be reserved only for malignant forms.

KIAA0510, the 3'-untranslated region of the tenascin-R gene, and tenascin-R are overexpressed in pilocytic astrocytomas.

AIMS: Studying the molecules and signalling pathways regulating glioma invasiveness is a major challenge because these processes determine malignancy, progression, relapse and prognosis. We took advantage of our previous study focused on genes that were critical in tumour invasion to further study here an unknown sequence, referred to as KIAA0510, the chromosomal location of which was 1q25, described as a 5596-bp long mRNA and that we found to be significantly overexpressed in pilocytic astrocytomas compared with glioblastomas. METHODS AND RESULTS: Using in silico analysis as well as Polymerase chain reaction techniques, we decipher the full genomic characterization of the KIAA0510 sequence and demonstrate that KIAA0510 constitutes the 3'-untranslated region of tenascin-R gene. We have clearly confirmed the overexpression of tenascin-R in pilocytic astrocytomas vs. glioblastomas at mRNA and protein levels. We also analysed a large series of various brain tumours and found that in the group of astrocytic tumours, tenascin-R expression decreased with malignancy, whereas oligodendrogliomas sometimes retained a high level of tenascin-R even in high-grade tumours. Gangliogliomas strongly expressed tenascin-R too. In contrast, ependymomas and meningiomas were negative. In normal brain, tenascin-R was exclusively expressed by normal oligodendrocytes and subsets of neurones during post-natal development and in adulthood, where it could differentially affect cellular adhesiveness and/or differentiation. CONCLUSION: KIAA0510, the 3'-untranslated region of the tenascin-R gene, and tenascin-R are overexpressed in pilocytic astrocytomas. Gangliogliomas shared with pilocytic astrocytomas strong tenascin-R expression. Whether tenascin-R overexpression negatively influences brain invasion remains to be determined.

Tissue plasminogen activator and urokinase plasminogen activator in human epileptogenic pathologies.

A growing body of evidence demonstrates the involvement of plasminogen activators (PAs) in a number of physiologic and pathologic events in the CNS. Induction of both tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) has been observed in different experimental models of epilepsy and tPA has been implicated in the mechanisms underlying seizure activity. We investigated the expression and the cellular distribution of tPA and uPA in several epileptogenic pathologies, including hippocampal sclerosis (HS; n=6), and developmental glioneuronal lesions, such as focal cortical dysplasia (FCD, n=6), cortical tubers in patients with the tuberous sclerosis complex (TSC; n=6) and in gangliogliomas (GG; n=6), using immuno-cytochemical, western blot and real-time quantitative PCR analysis. TPA and uPA immunostaining showed increased expression within the epileptogenic lesions compared to control specimens in both glial and neuronal cells (hippocampal neurons in HS and dysplastic neurons in FCD, TSC and GG specimens). Confocal laser scanning microscopy confirmed expression of both proteins in astrocytes and microglia, as well as in microvascular endothelium. Immunoblot demonstrated also up-regulation of the uPA receptor (uPAR; P<0.05). Increased expression of tPA, uPA, uPAR and tissue PA inhibitor type mRNA levels was also detected by PCR analysis in different epileptogenic pathologies (P<0.05). Our data support the role of PA system components in different human focal epileptogenic pathologies, which may critically influence neuronal activity, inflammatory response, as well as contributing to the complex remodeling of the neuronal networks occurring in epileptogenic lesions.

Pediatric epileptogenic gangliogliomas: seizure outcome and surgical results.

OBJECT: Ganglioglioma is the most common neoplasm causing focal epilepsy, accounting for approximately 40% of all epileptogenic tumors and for 1-4% of all pediatric CNS tumors. The optimal surgical treatment for pediatric epileptogenic ganglioglioma has not been fully established. The authors present their experience in the surgical management of these lesions. METHODS: The authors retrospectively analyzed seizure outcome and surgical results of pediatric patients with ganglioglioma treated with resection. The patients' charts were reviewed for demographic data, clinical presentation, surgical therapy, and follow-up. RESULTS: The 30 patients (17 boys, 13 girls) had a history of medically intractable epilepsy. Total resection of tumor was achieved with or without adjacent epileptogenic tissue resection in all patients except 1, who underwent cyst fenestration and biopsy. Intraoperative electrocorticography (ECoG) was used in 21 patients. If an active spike focus or profound attenuation was observed in adjacent tissues, resection of those tissues was performed in addition to complete tumor resection (lesionectomy). The interval between onset of seizures and surgery ranged from 1 month to 9 years (mean 1.6 years). Patient age at the time of surgery ranged from 9 months to 16.3 years (mean 8.6 years). Twenty-five patients (83.3%) had complex partial seizures and 5 (16.7%) had simple partial seizures. Eighteen tumors (60%) were temporal (14 temporomesial, 4 temporolateral), and 12 (40%) were extratemporal. The mean follow-up period was 3.4 years (range 1 month-8.16 years). In 2 cases (6.7%), tumor recurrence was observed. Outcome was Engel Class I in 27 cases (90.0%; 14 temporomesial, 4 temporolateral, 9 extratemporal) and Engel Class II in 3 (10.0%; all extratemporal). Tumor resection allowed good seizure control, especially in the 18 cases of temporal ganglioglioma (all Engel Class I postoperatively). Eleven patients underwent removal of extratumoral epileptogenic tissue (anterior temporal neocortex resection in 10, anterior temporal neocortex resection with anterior hippocampectomy in 1) in addition to lesionectomy using intraoperative ECoG. CONCLUSIONS: Lesionectomy with adjacent temporal neocortex resection using intraoperative ECoG provided good seizure control of pediatric temporal ganglioglioma. For extratemporal ganglioglioma, lesionectomy alone can provide fairly good seizure control. Considering the memory function of the hippocampus, lesionectomy with adjacent temporal neocortical resection can be a safe, feasible, and effective treatment option for epileptogenic gangliogliomas in pediatric patients.

Relationships between brain tumor and optic tract or calcarine fissure are involved in visual field deficits after surgery for brain tumor.

PURPOSE: Diffusion tensor tractography provides useful information regarding the surgical strategy for brain tumors. The goal of the present study was to analyze relationships between visual field deficits and the locations of brain tumors compared with optic tracts as visualized by tractography, and compared with the calcarine fissure. METHODS: Subjects comprised 11 patients with brain tumor in the occipital lobe or atrium of the lateral ventricle who underwent surgery between October 2006 and February 2009. Tumors were categorized as Type A, with almost all the optic tract in the occipital lobe or atrium of the lateral ventricle running close to and stretched by the brain tumor; and Type B, with the optic tract running at least partially distant to the brain tumor and remaining unstretched. RESULTS: Those type A optic tracts that were laterally compressed by brain tumors (Cases 1-3) displayed hemianopsia after surgery. When the brain tumor was located rostro-medial to the calcarine fissure and optic tracts were compressed caudally by the tumor, lower quadrant hemianopsia remained after surgery (Cases 4, 5). In other cases, the visual field remained or improved to normal after surgery. CONCLUSION: The relationship between optic tracts or the calcarine fissure, and brain tumors in the occipital lobe or atrium of the lateral ventricle is related to visual field deficits after surgery. In particular, those Type A optic tracts that are compressed laterally show hemianopsia of the visual field after surgery.

Anaplastic ganglioglioma in children.

PURPOSE: Anaplastic gangliogliomas (AGG) are gangliogliomas with areas of pronounced hypercellularity, vascular proliferation, necrosis, and many mitotic figures. As very few pediatric patients have been studied, we analyzed the cases registered in the HIT-GBM database. PATIENTS AND METHODS: Patient data were obtained from the German HIT-GBM database. Inclusion criteria were diagnosis of AGG proven by a central neuropathological review and patient age 0 to 17 years. Eight patients (five male and three female) were identified. RESULTS: Patients' median age was 10 years. The median history of disease was 9 months (range, 1.0-43.0 months). Initial symptoms included signs of raised intracranial pressure, seizures, and, in the case of spinal cord tumor, bladder dysfunction. In five cases, AGGs were localized supratentorially with three patients having multiple lobes involved. The tumors affected the frontal (n = 3 cases), parietal (n = 2), temporal (n = 2), and occipital lobes (n = 1), as well as the brainstem (n = 1) and the spinal cord (n = 2). Gross total tumor resection was achieved in six patients. The estimated 5-year overall survival rate +/- standard error was 88 +/- 12%, and the event-free survival rate was 63 +/- 17%. While gender and tumor location did not affect survival rates, gross total tumor resection provided a better overall survival than non-total resection. CONCLUSION: The prognosis of pediatric patients with AGG is good, especially for those who undergo gross total tumor resection.

Rosette-forming glioneuronal tumor: pathology case report.

OBJECTIVE: Rosette-forming glioneuronal tumor is a newly described mixed glial and neuronal tumor. We describe two cases and review the literature to better characterize this entity. METHODS: Patients were surgically treated, and tumors were diagnosed by light microscopy and immunohistochemistry using the avidin-biotin complex method. PubMed was searched for previously reported cases. RESULTS: Patient 1 was a 38-year-old woman who presented with headaches and no neurological abnormality. Magnetic resonance imaging showed a solid mass in the fourth ventricle. Subtotal excision of the mass caused transient gait ataxia. Patient 2 was a 51-year-old woman with dizziness who fell and sustained head trauma. Magnetic resonance imaging revealed a right paramedian cerebellar cystic and nodular mass and a separate nodule in the vermis, which were excised gross totally with no morbidity. Microscopic examination showed neuroepithelial tumors composed of neurocytic cells focally forming well-defined rosettes that were immunopositive for neuronal markers and of elongated, glial fibrillary acidic protein-immunoreactive astrocytes. No histological anaplasia was present. Both patients were well 18 and 8 months after surgery, respectively. Eighteen rosette-forming glioneuronal tumors were identified with the literature search. CONCLUSION: These are tumors of young adulthood (range, 12-59 yr) usually in or close to the fourth ventricle. Histologically, they are low-grade, although multiple foci or local extension may prevent total excision and account for some recurrences. On imaging, they are cystic, solid, or both, with minimal perilesional edema or mass effect. They are composed of neurocytic and glial elements, probably arising from a common progenitor in the subependymal plate, and need to be differentiated from a variety of glioneuronal tumors.

Reversible deficit affecting the perception of tone of a human voice after tumour resection from the right auditory cortex.

We report on a young woman operated for a ganglioglioma involving the right auditory cortex (AC), presenting with auditory seizures. Despite a normal pre-operative examination, a specific post-operative disorder affecting the perception of a human voice occurred. The patient was unable to recognise the tone of familiar voices while she recognised the expressed content. A temporal lobectomy for recurrence was performed two years later. The patient recovered from the voice perception deficit. This report shows that (1) a discrete site within the AC is specifically involved in the perception of tone of the human voice (2) functional compensation is possible.

Mechanisms of epileptogenesis in tuberous sclerosis complex and related malformations of cortical development with abnormal glioneuronal proliferation.

Malformations of cortical development (MCDs) are increasingly recognized as causes of medically intractable epilepsy. In order to develop more effective, rational therapies for refractory epilepsy related to MCDs, it is important to achieve a better understanding of the underlying mechanisms of epileptogenesis, but this is complicated by the wide variety of different radiographic, histopathological, and molecular features of these disorders. A subset of MCDs share a number of characteristic cellular and molecular abnormalities due to early defects in neuronal and glial proliferation and differentiation and have a particularly high incidence of epilepsy, suggesting that this category of MCDs with abnormal glioneuronal proliferation may also share a common set of primary mechanisms of epileptogenesis. This review critically analyzes both clinical and basic science evidence for overlapping mechanisms of epileptogenesis in this group of disorders, focusing on tuberous sclerosis complex, focal cortical dysplasia with balloon cells, and gangliogliomas. Specifically, the role of lesional versus perilesional regions, circuit versus cellular/molecular defects, and nonneuronal factors, such as astrocytes, in contributing to epileptogenesis in these MCDs is examined. An improved understanding of these various factors involved in epileptogenesis has direct clinical implications for optimizing current treatments or developing novel therapeutic approaches for epilepsy in these disorders.

Pediatric infratentorial gangliogliomas: a retrospective series.

OBJECT: The aim of this study was to retrospectively review the clinical presentation, the roles of surgery and adjuvant therapy, and the treatment-related morbidity in children with a ganglioglioma in the posterior fossa and to try and determine the prognostic factors. METHODS: Between 1991 and 2006, 10 children were treated for a posterior fossa ganglioglioma at the authors' institution. The mean age of the children, the duration of symptoms prior to diagnosis, and the follow-up were 8.2, 2.4, and 3.9 years, respectively. Nine of the children presented with symptoms of raised intracranial pressure. Preoperative imaging showed enhancement in all patients; in eight it was in a patchy distribution. The operations consisted of radical resection (> 75%) in seven children, biopsy in two, and a total macroscopic excision in one. RESULTS: The surgical procedure did not cause deterioration in the neurological condition in any of the children. There was no recurrence in the child who underwent total macroscopic excision of the tumor, and there has been no tumor progression in three children, two of whom have had no evidence of enhancement of the postoperative residual tumor. The tumor has progressed in six children, requiring further surgery in three, chemotherapy in four, and radiotherapy and second-line chemotherapy in one child to control the tumor. CONCLUSIONS: The imaging of gangliogliomas in the posterior fossa showed patchy enhancement. The patients in whom it was possible to achieve a radical resection, aimed at removing at least the enhancing portion of the tumor, have not required further treatment. A second excision, for progressive tumors, is an effective adjuvant therapy.