Diffuse midline gliomas, H3 K27M-mutant are associated with less peritumoral edema and contrast enhancement in comparison to glioblastomas, H3 K27M-wildtype of midline structures.

PURPOSE: The entity 'diffuse midline glioma, H3 K27M-mutant (DMG)' was introduced in the revised 4th edition of the 2016 WHO classification of brain tumors. However, there are only a few reports on magnetic resonance imaging (MRI) of these tumors. Thus, we conducted a retrospective survey focused on MRI features of DMG compared to midline glioblastomas H3 K27M-wildtype (mGBM-H3wt). METHODS: We identified 24 DMG cases and 19 mGBM-H3wt patients as controls. After being retrospectively evaluated for microscopic evidence of microvascular proliferations (MVP) and tumor necrosis by two experienced neuropathologists to identify the defining histological criteria of mGBM-H3wt, the samples were further analyzed by two experienced readers regarding imaging features such as shape, peritumoral edema and contrast enhancement. RESULTS: The DMG were found in the thalamus in 37.5% of cases (controls 63%), in the brainstem in 50% (vs. 32%) and spinal cord in 12.5% (vs. 5%). In MRI and considering MVP, DMG were found to be by far less likely to develop peritumoral edema (OR: 0.13; 95%-CL: 0.02-0.62) (p = 0.010). They, similarly, were associated with a significantly lower probability of developing strong contrast enhancement compared to mGBM-H3wt (OR: 0.10; 95%-CL: 0.02-0.47) (P = 0.003). CONCLUSION: Despite having highly variable imaging features, DMG exhibited markedly less edema and lower contrast enhancement in MRI compared to mGBM-H3wt. Of these features, the enhancement level was associated with evidence of MVP.

Robot-assisted stereotactic biopsy of pediatric brainstem and thalamic lesions.

OBJECTIVE: Biopsies of tumors located in deep midline structures require highly accurate stereotaxy to safely obtain lesional tissue suitable for molecular and histological analysis. Versatile platforms are needed to meet a broad range of technical requirements and surgeon preferences. The authors present their institutional experience with the robotic stereotactic assistance (ROSA) system in a series of robot-assisted biopsies of pediatric brainstem and thalamic tumors. METHODS: A retrospective analysis was performed of 22 consecutive patients who underwent 23 stereotactic biopsies of brainstem or thalamic lesions using the ROSA platform at Rady Children's Hospital in San Diego between December 2015 and January 2020. RESULTS: The ROSA platform enabled rapid acquisition of lesional tissue across various combinations of approaches, registration techniques, and positioning. No permanent deficits, major adverse outcomes, or deaths were encountered. One patient experienced temporary cranial neuropathy, and 3 developed small asymptomatic hematomas. The diagnostic success rate of the ROSA system was 91.3%. CONCLUSIONS: Robot-assisted stereotactic biopsy of these lesions may be safely performed using the ROSA platform. This experience comprises the largest clinical series to date dedicated to robot-assisted biopsies of brainstem and diencephalic tumors.

ALK2 inhibitors display beneficial effects in preclinical models of ACVR1 mutant diffuse intrinsic pontine glioma.

Diffuse intrinsic pontine glioma (DIPG) is a lethal childhood brainstem tumour, with a quarter of patients harbouring somatic mutations in ACVR1, encoding the serine/threonine kinase ALK2. Despite being an amenable drug target, little has been done to-date to systematically evaluate the role of ACVR1 in DIPG, nor to screen currently available inhibitors in patient-derived tumour models. Here we show the dependence of DIPG cells on the mutant receptor, and the preclinical efficacy of two distinct chemotypes of ALK2 inhibitor in vitro and in vivo. We demonstrate the pyrazolo[1,5-a]pyrimidine LDN-193189 and the pyridine LDN-214117 to be orally bioavailable and well-tolerated, with good brain penetration. Treatment of immunodeprived mice bearing orthotopic xenografts of H3.3K27M, ACVR1R206H mutant HSJD-DIPG-007 cells with 25 mg/kg LDN-193189 or LDN-214117 for 28 days extended survival compared with vehicle controls. Development of ALK2 inhibitors with improved potency, selectivity and advantageous pharmacokinetic properties may play an important role in therapy for DIPG patients.

[Clinicopathological characteristics and prognosis of diffuse midline gliomas with histone H3K27M mutation: an analysis of 30 cases].

Objective: To analyze the clinicopathological characteristics and prognosis of diffuse midline glioma (DMG) with H3K27M mutation. Methods: Thirty cases of DMG were collected in Guangdong Sanjiu Brain Hospital from October 2016 to May 2018. The patients' clinicopathological data including age, tumor site and histological grade, treatment and follow-up data were collected and analyzed. Results: There were 21 males and 9 females, with a mean age of 26 years (range 5-53 years). Fourteen tumors were located in thalamus, 12 in brainstem (one involved both thalamus and brainstem), and one each in hypothalamus, fourth ventricle, and sellar region, respectively. Two cases presented as diffuse intracranial lesions. Three cases (10.0%) were of WHO grade Ⅰ, 10 cases (33.3%) were grade Ⅱ, eight cases (26.7%) were grade Ⅲ, and nine cases (30.0%) were grade Ⅳ.All patients with gradeⅠ tumors were older than 20 years. Histologically, all were pilocytic astrocytoma-like. Immunohistochemical staining demonstrated that all tumors were IDH1 negative. Twenty-eight tumors showed diffuse expression of H3K27M, and two showed focal expression. Twenty-one tumors(100.0%, 21/21) showed absent expression of H3K27me3. Sixteen tumors (57.1%, 16/28) showed strongly positive expression of p53, and ATRX was negative in eight tumors (38.1%, 8/21). The Ki-67 proliferation index ranged from 5% to 40%. Eight cases (including two cases of H3K27M expression of individual cells) showed K27M mutation in H3F3A gene. Intracranial and spinal cord dissemination occurred in six cases (20.0%, 6/30). Median progression-free survival (PFS) was 9.5 months and median overall survival (OS) was 34 months. Mean PFS was 11.2 months and mean OS was 24.3 months. Compared with adults (>20 years old), children/adolescents (no more than 20 years old) had significantly shorter median OS (8 months vs. 34 months, P=0.013). There was no significant difference in PFS and OS between DMGs located in the brain stem/thalamus and other sites within midline (P>0.05). There was no significant difference in PFS and OS between WHO grade ⅠDMGs and WHO grade Ⅱ-Ⅳ DMGs (P>0.05). Conclusions: DMGs occur more commonly in children and adolescents with male predominance. DMGs present with WHO Ⅰ-Ⅳ tumors morphologically, and pilocytic astrocytoma-like lesions with WHO Ⅰ are more common in adults. Expression of H3K27M but not H3K27me3 is helpful for diagnosis of DMG. The prognosis of children/adolescents is significantly worse than that of adults, whereas histological grade and tumor location do not affect prognosis.

Diffuse intrinsic pontine glioma cells are vulnerable to low intensity electric fields delivered by intratumoral modulation therapy.

INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) is a high fatality pediatric brain cancer without effective treatment. The field of electrotherapeutics offers new potential for other forms of glioma but the efficacy of this strategy has not been reported for DIPG. This pilot study evaluated the susceptibility of patient-derived DIPG cells to low intensity electric fields delivered using a developing technology called intratumoral modulation therapy (IMT). METHODS: DIPG cells from autopsy specimens were treated with a custom-designed, in vitro IMT system. Computer-generated electric field simulation was performed to quantify IMT amplitude and distribution using continuous, low intensity, intermediate frequency stimulation parameters. Treatment groups included sham, IMT, temozolomide (TMZ) chemotherapy and radiation therapy (RT). The impact of single and multi-modality therapy was compared using spectrophotometric and flow cytometry viability analyses. RESULTS: DIPG cells exhibited robust, consistent susceptibility to IMT fields that significantly reduced cell viability compared to untreated control levels. The ratio of viable:non-viable DIPG cells transformed from ~ 6:1 in sham-treated to ~ 1.5:1 in IMT-treated conditions. The impact of IMT was similar to that of dual modality TMZ-RT therapy and the addition of IMT to this treatment combination dramatically reduced DIPG cell viability to ~ 20% of control values. CONCLUSIONS: This proof-of-concept study provides a novel demonstration of marked DIPG cell susceptibility to low intensity electric fields delivered using IMT. The potent impact as a monotherapy and when integrated into multi-modality treatment platforms justifies further investigations into the potential of IMT as a critically needed biomedical innovation for DIPG.

Biopsies of pediatric brainstem lesions display low morbidity but strong impact on further treatment decisions.

OBJECTIVE: The course of malignant brain stem gliomas in childhood is rarely positive. Because of limited therapeutic options and potentially hazardous biopsies oncologist often relay on MRI diagnoses only for further therapy decisions. In this study we show that brain stem biopsies display a low morbidity rate and neuropathological assessment has a considerable impact on further treatment decision. METHODS: Within 18-months five children with brainstem symptoms and the radiological diagnosis of a malignant brainstem glioma, were identified. From this time point it was possible to analyze all samples with the 450K methylome analysis. Other neuropathological techniques included classical histology with immunohistochemistry. Surgery was performed as biopsy, either microsurgical, frame-guided (Leksell), robot-assisted (ROSA) or navigated (BrainLab, two children). RESULTS: Mean age of the children was 7.5years (range: newborn to 12years). There was no biopsy-related morbidity or mortality. The mean number of taken samples was 12 (range: 1-25). Histologic diagnosis could be established in all children, however, 450K methylome diagnosis was positive in only two out of five patients. CONCLUSION: Despite the technically difficult biopsies, all specimens were sufficient for immunohistochemical diagnosis, however, 450K methylome analysis could only be better established where multiple small samples were taken, instead of few larger ones. Based on the preoperative radiological diagnosis suggesting malignant brainstem glioma, all children would have been treated with combined radiation and temozolomid chemotherapy. Nevertheless, due to the availability of histology and molecular diagnostics, individualized therapy could be performed, preventing in two out of five children from unnecessary radiation and chemotherapy.

Preclinical evaluation of convection-enhanced delivery of liposomal doxorubicin to treat pediatric diffuse intrinsic pontine glioma and thalamic high-grade glioma.

OBJECTIVE Pediatric high-grade gliomas (pHGGs) including diffuse intrinsic pontine gliomas (DIPGs) are primary brain tumors with high mortality and morbidity. Because of their poor brain penetrance, systemic chemotherapy regimens have failed to deliver satisfactory results; however, convection-enhanced delivery (CED) may be an alternative mode of drug delivery. Anthracyclines are potent chemotherapeutics that have been successfully delivered via CED in preclinical supratentorial glioma models. This study aims to assess the potency of anthracyclines against DIPG and pHGG cell lines in vitro and to evaluate the efficacy of CED with anthracyclines in orthotopic pontine and thalamic tumor models. METHODS The sensitivity of primary pHGG cell lines to a range of anthracyclines was tested in vitro. Preclinical CED of free doxorubicin and pegylated liposomal doxorubicin (PLD) to the brainstem and thalamus of naïve nude mice was performed. The maximum tolerated dose (MTD) was determined based on the observation of clinical symptoms, and brains were analyzed after H & E staining. Efficacy of the MTD was tested in adult glioma E98-FM-DIPG and E98-FM-thalamus models and in the HSJD-DIPG-007-Fluc primary DIPG model. RESULTS Both pHGG and DIPG cells were sensitive to anthracyclines in vitro. Doxorubicin was selected for further preclinical evaluation. Convection-enhanced delivery of the MTD of free doxorubicin and PLD in the pons was 0.02 mg/ml, and the dose tolerated in the thalamus was 10 times higher (0.2 mg/ml). Free doxorubicin or PLD via CED was ineffective against E98-FM-DIPG or HSJD-DIPG-007-Fluc in the brainstem; however, when applied in the thalamus, 0.2 mg/ml of PLD slowed down tumor growth and increased survival in a subset of animals with small tumors. CONCLUSIONS Local delivery of doxorubicin to the brainstem causes severe toxicity, even at doxorubicin concentrations that are safe in the thalamus. As a consequence, the authors could not establish a therapeutic window for treating orthotopic brainstem tumors in mice. For tumors in the thalamus, therapeutic concentrations to slow down tumor growth could be reached. These data suggest that anatomical location determines the severity of toxicity after local delivery of therapeutic agents and that caution should be used when translating data from supratentorial CED studies to treat infratentorial tumors.

Progression of atypical extraventricular neurocytoma to anaplastic ganglioglioma.

We report a childhood case of thalamic atypical extraventricular neurocytoma that progressed to highly anaplastic ganglioglioma after 8 years of dormancy after subtotal resection and chemotherapy. The neurocytoma displayed immunoreactivity only for synaptophysin, ß-catenin, S100, and CD56. The ganglioglioma acquired strong immunoreactivity for chromogranin, glial fibrillary acidic protein, neuron-specific enolase, and p53 and showed a very high proliferation rate approaching 50% in some areas. Tumor transformation was associated with overexpression of components of the sonic hedgehog and Wnt developmental signaling pathways, which are known to regulate tumor-initiating cells in malignant brain neoplasms.

The H3.3 K27M mutation results in a poorer prognosis in brainstem gliomas than thalamic gliomas in adults.

Brainstem and thalamic gliomas are rare, and they are poorly understood in adults. Genetic aberrations that occur in these tumors are still unknown. In this study, we investigated whether thalamic gliomas have different genetic aberrations and clinical outcomes compared with brainstem gliomas in adults. Forty-three glioma samples were selected, including 28 brainstem and 15 thalamic gliomas. The frequency of the K27M mutation in adult midline gliomas was 58.1%. High-grade gliomas in the thalamus were statistically significantly more numerous than brainstem gliomas. Patients with K27M mutant brainstem gliomas had a significantly shorter overall survival than patients with wild-type tumors (P = .020) by Cox regression after adjustment for other independent risk factors. However, there was no statistical tendency toward a poorer overall survival in thalamic gliomas containing the K27M mutation compared with wild-type tumors. The presence of the K27M mutation significantly corresponded with mutations in TP53 in thalamic gliomas. Interestingly, the K27M mutation was mutually exclusive with mutations in IDH1, which was detected only in brainstem gliomas. The microarray data identified 86 differentially expressed genes between brainstem and thalamic gliomas with the K27M mutation. The cyclin-dependent kinase 6 (CDK6) gene, which plays an important role in cancer pathways, was found to be differentially expressed between brainstem and thalamic gliomas with K27M mutations. Although the K27M mutation was frequently observed in adult brainstem and thalamic gliomas, this mutation tended to be associated with a poorer prognosis in brainstem gliomas but not in thalamic gliomas. Brainstem gliomas may present different genetic aberrations from thalamic gliomas. These differences may provide guidance for therapeutic decisions for the treatment of adult brainstem and thalamic gliomas, which may have different molecular targets.

Imaging of adult brainstem gliomas.

Brainstem gliomas (BSGs) are uncommon in adults accounting for about 2% of all intracranial neoplasms. They are often phenotypically low-grade as compared to their more common paediatric counterparts. Since brainstem biopsies are rarely performed, these tumours are commonly classified according to their MR imaging characteristics into 4 subgroups: (a) diffuse intrinsic low-grade gliomas, (b) enhancing malignant gliomas, (c) focal tectal gliomas and (d) exophytic gliomas/other subtypes. The prognosis and treatment is variable for the different types and is almost similar to adult supratentorial gliomas. Radiotherapy (RT) with adjuvant chemotherapy is the standard treatment of diffuse low-grade and malignant BSGs, whereas, surgical resection is limited to the exophytic subtypes. Review of previous literature shows that the detailed imaging of adult BSGs has not received significant attention. This review illustrates in detail the imaging features of adult BSGs using conventional and advanced MR techniques like diffusion weighted imaging (DWI), diffusion tensor imaging (DTI), MR perfusion weighted imaging (PWI), MR spectroscopy (MRS), as well as 18F-fluoro-ethyl-tyrosine positron emission tomography (18F-FET/PET). We have discussed the pertinent differences between childhood and adult BSGs, imaging mimics, prognostic factors and briefly reviewed the treatment options of these tumours.

Management of diffuse pontine gliomas in children: recent developments.

The prognosis for children with diffuse intrinsic pontine gliomas (DIPGs) is dismal. Although DIPGs constitute only 10-15 % of all pediatric brain tumors, they are the main cause of death in this group with a median survival of less than 12 months. Standard therapy involves radiotherapy, which produces transient neurologic improvement. Despite several clinical trials having been conducted, including trials on targeted agents to assess their efficacy, there is no clear improvement in prognosis. However, knowledge of DIPG biology is increasing, mainly as a result of research using biopsy and autopsy samples. In this review, we discuss recent studies in which systemic therapy was administered prior to, concomitantly with, or after radiotherapy. The discussion also includes novel therapeutic options in DIPG. Continuing multimodal and multitargeted therapies might lead to an improvement in the dismal prognosis of the disease.

Transcerebellar stereotactic biopsy for lesions of the brainstem and peduncles under local anesthesia.

OBJECTIVE: For certain brainstem lesions, a diagnostic biopsy is required for treatment planning. We reviewed the indications, safety, and diagnostic effectiveness of a transcerebellar stereotactic biopsy using local anesthesia and sedation. METHODS: We retrospectively reviewed hospital records for all adult patients with symptomatic lesions of the pons and/or cerebellar peduncle who underwent an awake transcerebellar stereotactic biopsy at our institution over a 7-year period. Our technique features several modifications from the standard method and was performed under local anesthesia with patients in the semi-sitting position. RESULTS: Our rate of diagnostic success (92%) was comparable to those in other published reports. However, only 5 (42%) of 12 biopsy-derived diagnoses were consistent with those predicted from preoperative magnetic resonance imaging. There were no deaths, and the only neurological complication was a cranial nerve palsy. Diagnoses in the 13 cases included infiltrative glioma (), metastases (), lymphoma (), encephalitis (), and reactive astrogliosis (). CONCLUSION: Tissue diagnosis of lesions in the brainstem and cerebellar peduncles continues to be a significant challenge, with the potential for major morbidity. With appropriate patient selection, however, awake transcerebellar biopsy is a safe and effective procedure that can change clinical management and provide important prognostic information.

Targeted therapy with antineoplastons A10 and AS2-1 of high-grade, recurrent, and progressive brainstem glioma.

BACKGROUND: Brainstem glioma carries the worst prognosis of all malignancies of the brain. Most patients with brainstem glioma fail standard radiation therapy and chemotherapy and do not survive longer than 2 years. Treatment is even more challenging when an inoperable tumor is of high-grade pathology (HBSG). The objective of this report is to summarize the outcome of patients with HBSG treated with antineoplastons in 4 phase 2 trials. PATIENTS: The following group of 18 patients was evaluable: 4 patients with glioblastomas and 14 patients with anaplastic HBSG. Fourteen patients had diffuse intrinsic tumors. Twelve patients suffered from recurrence, and 6 patients did not have radiation therapy or chemotherapy. METHODS: Antineoplastons, which consist of antineoplaston A10 (A10I) and AS2-1 injections, were given in escalating doses by intravenous injections. The median duration of antineoplaston administration was 5 months, and the average dosage of A10I was 9.22 g/kg/d and of AS2-1 was 0.31 g/kg/d. Responses were assessed by gadolinium-enhanced magnetic resonance imaging and positron emission tomography. RESULTS: The overall survival at 2 and 5 years was 39% and 22%, respectively, and maximum survival was more than 17 years for a patient with anaplastic astrocytoma and more than 5 years for a patient with glioblastoma. Progression-free survival at 6 months was 39%. Complete response was achieved in 11%, partial response in 11%, stable disease in 39%, and progressive disease in 39% of patients. Antineoplastons were tolerated very well with 1 case of grade 4 toxicity (reversible anemia). CONCLUSION: Antineoplastons contributed to more than a 5-year survival in recurrent diffuse intrinsic glioblastomas and anaplastic astrocytomas of the brainstem in a small group of patients.

Brainstem auditory evoked potential monitoring: when is change in wave V significant?

BACKGROUND: The probability of hearing loss during cerebellopontine angle (CPA) surgery can be reduced by using brainstem auditory evoked potential (BAEP) intraoperative monitoring (IOM). A wave V latency prolongation of 1.0 milliseconds or amplitude decrement of greater than 50% is arbitrarily considered the point when damage to hearing occurs. OBJECTIVE: To determine the accuracy of wave V changes in predicting hearing impairment. METHODS: Patients undergoing BAEP IOM for surgery in the CPA region were evaluated. The greatest wave V latency and amplitude change was determined. Patients were divided into four groups depending on degree of change of wave V: Group 1 consisted of minimal change, whereas Group 4 was permanent loss of wave V. The frequency of hearing loss in each group was compared. RESULTS: Data from 156 patients were reviewed. When all patients were analyzed, the frequency of hearing loss was not significantly different between the groups. When patients with CPA tumor were excluded, a significantly higher number of patients in Group 4 had hearing loss. Analysis of the patients with CPA tumor showed no difference in the frequency of hearing loss in any of the groups; even a large number (50%) of Group 1 patients had hearing impairment. CONCLUSIONS: During brainstem auditory evoked potential intraoperative monitoring, the type of surgery is important when interpreting significance of changes of wave V. For non-cerebellopontine angle tumor surgery, hearing loss occurs usually only with permanent loss of wave V; much smaller changes may be important in cerebellopontine angle tumor surgery.

Radical resection for intrinsic midbrain pilocytic astrocytoma: report of two cases.

BACKGROUND: Intrinsic midbrain glioma has been one of the most challenging therapeutic tasks in neurosurgery due to its prognosis and risks associated with surgical procedures. It is known that the prognosis of pilocytic astrocytoma is relatively good if radical resection can be achieved without severe complications. In order to remove pilocytic astrocytoma within the midbrain radically, we used microsurgical techniques. METHOD: Two patients with intrinsic pilocytic astrocytomas located at the midbrain were operated on. The subtemporal approach was used with a point of entry on the lateral surface of the midbrain just behind the cerebral peduncle. Major vessels were preserved, followed by resection of the intrinsic tumor making the cleavage between tumour and midbrain. FINDINGS: In both patients, intrinsic pilocytic astrocytoma was grossly totally removed with minimal permanent morbidity. They have been able to maintain independent activities in their daily lives without tumor recurrance. CONCLUSIONS: Surgical cure can be accomplished in some cases of midbrain pilocytic astrocytoma, even if the lesions are intrinsic to the midbrain. To remove the tumor totally without further neurological deficits, it is necessary to select a safe access or entrance point to the tumor, and to demarcate the gliotic plane between tumour and midbrain. A long-term follow up with a larger number of patients is needed to establish the significance of radical resection for intrinsic midbrain pilocytic astrocytoma.

Long-term survival and complete response of a patient with recurrent diffuse intrinsic brain stem glioblastoma multiforme.

Recurrent diffuse intrinsic brain stem glioblastoma multiforme carries an extremely poor prognosis and a median survival of less than 7 months. In this article, the authors report good results in a 40-year-old man diagnosed with glioblastoma multiforme who received antineoplastons. The patient's brain tumor was diagnosed in May 1999, and he subsequently underwent subtotal tumor resection and standard radiation therapy. Magnetic resonance imaging and positron emission tomography scans documented his tumor recurrence. Approximately 2 months after completion of radiation therapy, he was admitted for administration of intravenous antineoplastons A10 and AS2-1 through a subclavian venous catheter by intermittent bolus injections 6 times per day using a portable pump. Administration of antineoplastons A10 and AS2-1 was over 655 consecutive days with the exception of a few short interruptions. The maximum dosage of A10 was 8.15 g/kg/d and AS2-1 0.35 g/kg/d. Antineoplastons A10 and AS2-1 administration was very well tolerated with only mild reversible side effects. Follow-up magnetic resonance imaging and positron emission tomography scans revealed decrease and eventually disappearance of the tumor. A complete response was documented after approximately 1 year of antineoplastons A10 and AS2-1 administration. More than 4 years later, off antineoplastons A10 and AS2-1, the patient is tumor free, able to carry on normal activities, and works full-time, and his Karnofsky Performance Status increased from 50 to 100. Extensive phase II trials with antineoplastons A10 and AS2-1 in patients with glioblastoma multiforme are nearing completion. These trials may provide more data regarding the efficacy of antineoplastons A10 and AS2-1 in the treatment of glioblastoma multiforme in untreated patients compared to the results in those patients with tumor recurrence after radiation therapy.

Stereotactic biopsy of brain tumours in the paediatric population.

OBJECTIVE: Our objective was to establish the role of stereotactic neurosurgical techniques in the management of brain tumours in children. MATERIALS AND METHODS: A retrospective analysis was conducted of all stereotactic procedures performed in a single centre between 1996 and 2001. The success rates of achieving histologic diagnosis and a correlation between radiologic and histologic diagnosis were examined. RESULTS: There were 7 boys and 7 girls with a mean age of 9.1 years (range: 4-15). Under general anaesthetic 15 procedures were performed in 14 patients: 12 diagnostic and 3 therapeutic; 10 with CT and 5 with MRI guidance; 10 lesions were supratentorial and 4 were in the pons. A definitive histologic diagnosis was established in 10 of the 12 cases (diagnostic yield 83%). The pre-operative radiological diagnosis was accurate for tumour type in only 75% of the cases. In 3 patients cyst aspiration was attempted: post-operatively the cyst size was decreased in 2 and unchanged in 1. Seizures and acute confusion following biopsy of a thalamic tumour occurred in 1 patient. Post-operative scans were performed in 7 patients and in 2 we noted small, clinically insignificant, haemorrhages at the biopsy site. There was no mortality and morbidity was 6.6%. CONCLUSIONS: This small series confirms that stereotactic procedures in children are safe, well tolerated, with a high diagnostic yield, which could be improved with the use of intraoperative histopathological examination.

Cerebellar mutism associated with a midbrain cavernous malformation. Case report and review of the literature.

The authors report a case of cerebellar mutism arising from a hemorrhagic midbrain cavernous malformation in a 14-year-old boy. No cerebellar lesion was identified; however, edema of the dorsal midbrain was noted on postoperative magnetic resonance images. Dysarthric speech spontaneously returned and then completely resolved to normal speech. This case provides further evidence for the theory that involvement of the dentatothalamic tracts, and not a cerebellar lesion per se, is the underlying cause of "cerebellar" mutism.