Methotrexate administration directly into the fourth ventricle in children with malignant fourth ventricular brain tumors: a pilot clinical trial.

We hypothesize that chemotherapy can be safely administered directly into the fourth ventricle to treat recurrent malignant brain tumors in children. For the first time in humans, methotrexate was infused into the fourth ventricle in children with recurrent, malignant brain tumors. A catheter was surgically placed into the fourth ventricle and attached to a ventricular access device. Cerebrospinal fluid (CSF) flow was confirmed by CINE MRI postoperatively. Each cycle consisted of 4 consecutive daily methotrexate infusions (2 milligrams). Disease response was monitored with serial MRI scans and CSF cytologic analysis. Trough CSF methotrexate levels were sampled. Five patients (3 with medulloblastoma and 2 with ependymoma) received 18, 18, 12, 9, and 3 cycles, respectively. There were no serious adverse events or new neurological deficits attributed to methotrexate. Two additional enrolled patients were withdrawn prior to planned infusions due to rapid disease progression. Median serum methotrexate level 4 h after infusion was 0.04 µmol/L. Range was 0.02-0.13 µmol/L. Median trough CSF methotrexate level 24 h after infusion was 3.18 µmol/L (range 0.53-212.36 µmol/L). All three patients with medulloblastoma had partial response or stable disease until one patient had progressive disease after cycle 18. Both patients with ependymoma had progressive disease after 9 and 3 cycles, respectively. Low-dose methotrexate can be infused into the fourth ventricle without causing neurological toxicity. Some patients with recurrent medulloblastoma experience a beneficial anti-tumor effect both within the fourth ventricle and at distant sites.

Persistent communicating hydrocephalus in adult tuberous sclerosis patients: a possible therapeutic role for everolimus.

Subependymal giant cell tumor (SGCT) is a benign intraventricular tumor, usually located near the foramen of Monro. It is almost always associated with tuberous sclerosis complex (TSC). SGCTs may obstruct cerebrospinal fluid (CSF) pathways. Rarely, they may secrete a protein-rich exudate, causing communicating hydrocephalus. Surgery is indicated for symptomatic lesions or growing asymptomatic lesions. The operative approach to SGCT has shifted from simple shunt placement to a more aggressive approach, leading to early attempts at gross total resection. Recently, the mTOR inhibitor everolimus has been approved for treating SGCT. In this article, we present two cases of recurrent shunt malfunctions in adult TSC patients with protein-secreting SGCTs. We describe the complexity of treating such patients with an emphasis on the role mTOR inhibitors may have in their management. We also review the literature on surgical management of SGCT-related hydrocephalus.

[A case of intraventricular dissemination arising from hepatocelullar carcinoma effectively treated with intrathecal administration of methotrexate].

A 78-year-old man with hepatocellular carcinoma was admitted to our hospital for vertigo after transcatheter arterial chemoembolization. Contrast-enhanced magnetic resonance imaging revealed metastasis in the cerebellar vermis. Although the cerebellar metastasis decreased in size after cyberknife radiotherapy, multiple enhancing nodules appeared in the cerebral ventricles. A diagnosis of intraventricular dissemination from the cerebellar metastatic lesion originating from the hepatocellular carcinoma was made. Six intrathecal administrations of 20 mg of methotrexate through lumbar puncture resulted in a dramatic decrease in the intraventricular dissemination. Although intraventricular dissemination recurred 4 months later, these lesions disappeared after an additional 8 administrations of intrathecal methotrexate. Intraventricular dissemination arising from hepatocellular carcinoma is rare. Here we report a case that was successfully treated by intrathecal chemotherapy with methotrexate.

Occlusion of surgical opening of the ventricular system with fibrinogen-coated collagen fleece: a case collection study.

BACKGROUND: Implantation of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafer for malignant glioma is not recommended in the case of surgical opening of the ventricular system during microsurgical tumor resection because the wafer material may dislocate from the resection cavity into the ventricular system and cause obstructive hydrocephalus. TachoSil is an adhesive collagen fleece used in different surgical disciplines that provides an air- and liquid-tight seal closing communications between the ventricular system and the resection cavity after tumor removal. METHODS: Occlusion of ventricular defects with TachoSil after microsurgical glioma resection was performed in two patients with newly diagnosed and seven patients with recurrent malignant glioma prior to BCNU wafer implantation into the resection cavity. Early postoperative cranial computed tomography (CCT)/MRI and follow-up MRI at 3 months' intervals were performed with a median follow-up of 10.4 months. RESULTS: The collagen fleece was identified as a linear structure hypodense/hypointense to white matter on postoperative CT/MRI separating the resection cavity from the ventricular lumen in all cases. In no case did early CCT/MRI or follow-up MRI reveal wafer material within the ventricular system. In no case did signs of obstructive hydrocephalus occur. CONCLUSION: Sealing of the ventricular system using a fibrinogen-coated collagen fleece effectively separates the resection cavity from the ventricular system and allows implantation of BCNU wafers into the resection cavity. No morphological evidence for wafer material dislocation into the ventricular system or obstruction of CSF pathways was found in nine patients who received 41 follow-up MRI over 10.4 months of follow-up.

Acute transient encephalopathy following paclitaxel treatment in an adolescent with a recurrent suprasellar germinoma.

Paclitaxel is an antineoplastic agent that is used in the treatment of a variety of solid tumors. Dose-limiting side effects of myelosuppression and peripheral neuropathy are well known. Paclitaxel has minimal penetration of the blood-brain barrier and central nervous system side effects are rare. However, transient encephalopathy following paclitaxel infusion has been described in adults but not in children. We present the case of a 14-year-old female with a recurrent suprasellar germinoma who developed an acute encephalopathy 4-6 hr following paclitaxel infusion.

Intrathecal chemotherapy delivered by a lumbar-thecal catheter in metastatic medulloblastoma: a case illustration.

BACKGROUND: Medulloblastoma is the most common malignant brain tumour in children. Despite recent advances, the prognosis in high risk patients remains poor. Further improvement in survival is dependent upon the development of strategies to attack the tumour more effectively, but with less toxicity. Intrathecal chemotherapy, is an ideal but currently underused method of directly targeting residual tumour within the area of resection and the leptomeningeal disease commonly associated with this tumour. METHOD: We describe the case of a 12 yr old child with metastatic medulloblastoma, who received intrathecal topotecan via a spinal catheter. CONCLUSION: This method represents a simple, safe and effective method of delivering an even and widespread distribution of drug within the cerebrospinal fluid (CSF) of the neuroaxis. With new agents being identified and others in the early stages of development, intrathecal chemotherapy may emerge as an important therapeutic option to consider when faced with such challenging cases.

Acquired amnesia in childhood: a single case study.

We report the case of C.L., an 8-year-old child who, following the surgical removal of an ependymoma from the left cerebral ventricle at the age of 4 years, developed significant difficulties in retaining day-to-day events and information. A thorough neuropsychological analysis documented in C.L. a severe anterograde amnesic syndrome, characterised by normal short-term memory, but poor performance on episodic long-term memory tests. In particular, C.L. demonstrated virtually no ability to recollect new verbal information several minutes after the presentation. As for semantic memory, C.L. demonstrated general semantic competencies, which, depending on the test, ranged from the level of a 6-year-old girl to a level corresponding to her actual chronological age. Finding a patient who, despite being severely impaired in the ability to recollect new episodic memories, still demonstrates at least partially preserved abilities to acquire new semantic knowledge suggests that neural circuits implicated in the memorisation of autobiographical events and factual information do not overlap completely. This case is examined in the light of growing literature concerned with the dissociation between episodic and semantic memory in childhood amnesia.

Recurrent intracranial germinoma along the endoscopic ventriculostomy tract. Case report.

The authors report a case of a recurrent intracranial germinoma along the site of an endoscopic third ventriculostomy (ETV) after complete local tumor control using 3D conformal radiation therapy. A 13-year-old girl presented with sudden left upward gaze limitation for 4 days. A pineal region tumor and obstructive hydrocephalus were noted on magnetic resonance (MR) images. An ETV and tumor biopsy procedure were performed, which revealed the lesion to be a germinoma. The patient's visual symptoms and hydrocephalus disappeared postoperatively. Chemotherapy using cisplatin, etoposide, vincristine, and cyclophosphamide was initiated on postoperative Day 10. An MR image obtained 10 weeks after surgery and 2 weeks after chemotherapy revealed a significant (> 50%) reduction of the lesion. Radiation therapy was administered at 50.4 Gy to the target and 36 Gy to the periphery. Ten months after surgery, an MR image revealed further shrinkage of the tumor mass. One year after surgery, follow-up MR imaging demonstrated a small mass lesion at the entry site of the ETV, measuring 1.0 x 1.4 x 1.5 cm. An operation was performed to remove the small lesion, and pathological findings revealed it to be of the same histology as the primary tumor.

Rosette-Forming Glioneuronal Tumor of the Fourth Ventricle in Children: Case Report and Literature Review.

BACKGROUND: Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle is a rare World Health Organization (WHO) grade I neoplasm. Gross total resection (GTR) is the treatment of choice, and there is no firm evidence supporting other treatment options when GTR is not feasible. CASE DESCRIPTION: We report a 6-year-old boy who, following an initial subtotal resection of a fourth ventricular RGNT, received an individualized chemotherapy protocol with vincristine, etoposide, and carboplatin for 3 cycles. The tumor was stable for 2 years after the completion of chemotherapy but then began to progress, at which point GTR was successfully performed. In addition, we completed a comprehensive literature review of RGNT cases. To date, a total of 104 cases have been reported, 33 of which are pediatric cases. Recurrence has been reported in only 7 cases of all ages (4 in the pediatric population). Radiotherapy has been used in several cases, but adjuvant chemotherapy has been reported only once following a recurrence. CONCLUSIONS: We report a case of chemotherapy administration as a first-line treatment for a subtotally resected RGNT. Chemotherapy may be considered as an adjuvant therapy option for RGNT when GTR cannot be achieved. Furthermore, increased incidence of recurrence in the pediatric population may suggest that the tumor biology of RGNT in children differs from that in adults.

Pitfalls of Neuroendoscopic Biopsy of Intraventricular Germ Cell Tumors.

OBJECTIVE: A neuroendoscopic biopsy has become common for the diagnosis of ventricular tumors. However, its utility in patients with germ cell tumors (GCTs) has not been well discussed. We examined the usefulness and pitfalls of neuroendoscopic biopsies of intraventricular GCTs at a single institution. METHODS: We retrospectively studied 21 consecutive patients diagnosed with GCTs by a neuroendoscopic biopsy of the ventricular region via the lateral ventricle. We examined the localization of tumors, histologic diagnoses using biopsies, surgical complications, and consistency of the diagnosis at the latest follow-up. RESULTS: Tumor specimens were obtained from a pineal lesion (n = 20), neurohypophysial lesion (n = 5), and lateral ventricular wall lesion (n = 2). In 5 patients, the specimens were obtained from multiple areas. The initial diagnoses were pure germinoma (n = 16), immature teratoma (n = 1), yolk sac tumor (n = 1), and mixed GCT (n = 3). Six of 21 patients needed a second transcranial removal of enhanced residual lesions in the course of the treatment. A discrepancy in the histologic diagnosis between 2 surgeries occurred in 3 patients: All 3 patients had a new diagnosis of teratoma component following transcranial surgery. No postoperative mortality or permanent morbidity related to the neuroendoscopic procedures was noted. CONCLUSION: Neuroendoscopic biopsies are safe and useful for obtaining reliable histologic diagnoses in the management of GCTs. However, for GCTs with mixed histology, biopsies are susceptible to diagnostic errors, especially missing detecting a component of teratoma.

Intraventricular Gliosarcomas: Literature Review and a Case Description.

OBJECTIVE: Gliosarcomas are rare, extremely high-grade, bimorphous malignant tumors of the central nervous system. Intraventricular location is extremely rare, and only a few case reports exist in the literature. The aim of our study is to review clinical, radiologic, and pathologic features of this unique oncological entity and report this rare case of primary cystic intraventricular gliosarcoma (IVGS) with a mural nodule. METHODS: A 23-year-old man had a 6-month history of headache and a single episode of generalized seizure. Examination revealed grade 1 papilledema. Brain magnetic resonance imaging revealed a cystic lesion with a mural nodule located within the occipital horn of the right lateral ventricle, which exhibited an intense enhancement of the nodule with patchy rim enhancement of the wall on gadolinium administration. The patient underwent right parietal craniotomy and gross total excision of the tumor. RESULTS: Postoperative computed tomography of the brain showed evidence of complete tumor excision. The postoperative course of the patient was uneventful. Histopathologic analysis revealed malignant tumor comprising both glial and mesenchymal components suggestive of gliosarcoma. CONCLUSION: Primary IVGS is an extremely rare malignancy, with only 9 cases reported in the literature, and it should be considered in the differential diagnosis of lateral ventricular tumors.

Multicentric atypical teratoid/rhabdoid tumors occurring in the eye and fourth ventricle of an infant: case report.

Atypical teratoid/rhabdoid tumors (AT/RTs) are aggressive malignant tumors found in infants and young children. The tumor is characterized by the presence of a rhabdoid cell component in all cases, but the histological origin is still unclear. Recently, germline mutation of the hSNF5/INI1 gene has been reported in association with AT/RTs. The authors report a rare case of an intraocular AT/RT followed by a fourth ventricular tumor. The results of immunohistochemical studies of the surgical specimens revealed the presence of an AT/RT and from this finding the neural origin was inferred. A novel missense mutation of the hSNF5/INI1 gene was demonstrated by DNA analysis. High-dose chemotherapy with stem cell rescue was effective in treating this patient. The immunohistochemical relationship between rhabdoid cells and the neurogenic zone, which has not been described in AT/RTs, is of great interest in view of the nature of rhabdoid cells.

Assessment of bone marrow function: microscopy versus the agar colony assay.

Changes in bone marrow status followig cytotoxic chemotherapy were measured by means of peripheral blood counts, bone marrow cytology and colony-formation in agar culture. A correlation is described between colony-forming ability and marrow differential count.

Use of mTOR inhibitor everolimus in three neonates for treatment of tumors associated with tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex is characterized by the growth of benign tumors in multiple organs, caused by the disinhibition of the mammalian target of rapamycin (mTOR) protein. mTOR inhibitors, such as everolimus, are used in patients with tuberous sclerosis complex, mainly to reduce the size of renal angiomyolipomas and subependymal giant cell astrocytomas. There are minimal data available regarding its use during the neonatal period. METHODS: We report clinical and pharmacological data of three neonates treated with the mTOR inhibitor everolimus (two hemodynamically significant cardiac rhabdomyomas and one voluminous subependymal giant cell astrocytoma). RESULTS: Beneficial clinical responses were observed in all three patients and the medication was generally well-tolerated. Optimal dose was 0.1 mg orally once daily and was confirmed with therapeutic drug monitoring. CONCLUSION: Everolimus is a promising pharmacological approach to treat clinically significant inoperable cardiac rhabdomyomas or subependymal giant cell astrocytoma associated with tuberous sclerosis complex during the neonatal period.

Recurrent germinoma in the optic nerve: report of two cases.

OBJECTIVE AND IMPORTANCE: Intracranial germinomas often disseminate via the ventricular and subarachnoid pathways, but seeding to the perioptic arachnoid space is extremely unusual. We report two cases of recurrent germinoma seeding in the optic nerve. CLINICAL PRESENTATION: Two men with pure germinoma were initially treated with three cycles of a three-drug regimen of bleomycin, etoposide, and cisplatin, and a complete response was achieved. Patient 1 experienced ventricle wall dissemination 10 months after undergoing the initial treatment and was successfully treated with three cycles of carboplatin and etoposide and then by 24-Gy whole-ventricle radiation. Twelve months later, he complained of progressive visual acuity loss, and magnetic resonance imaging demonstrated bilateral enhancement of the optic nerves. Patient 2 also experienced ventricle wall dissemination 3 months after undergoing the initial chemotherapy, but he exhibited a complete response after undergoing 24-Gy whole-ventricle radiation. Two years later, he complained of progressive visual acuity loss. Magnetic resonance imaging demonstrated bilateral enhancement of the optic nerves and cerebellar hemispheres. INTERVENTION: None of the locations of recurrence were included in the irradiation field, whereas there was no recurrence within the radiation field. Complete responses were obtained with three cycles of a three-drug regimen of ifosfamide, cisplatin, and etoposide and then by 24-Gy whole-brain radiation that included the bilateral optic nerves. The visual acuity of each patient improved slightly. CONCLUSION: Delayed seeding in the optic nerve may result from germinoma cells that remain dormant, so they cannot be destroyed by chemotherapy regimens alone.

Second-look surgery for incompletely resected fourth ventricle ependymomas: technical case report.

OBJECTIVE AND IMPORTANCE: The prognosis for patients with ependymomas is related to the adequacy of surgical clearance. It is, however, often not possible to obtain a macroscopically complete resection of tumors arising in the posterior fossa. This may be because of the involvement of structures, the sacrifice of which would result in unacceptable morbidity, or because of metastatic lesions at diagnosis. For those patients in whom initial surgery was incomplete, elective second-look surgery may allow more complete clearance of tumor. INTERVENTION: We have performed second-look surgery for fourth ventricle ependymomas in five patients: two women, aged 26 and 27 years, and three male patients, aged 4 months, 19 months, and 18 years. The 19-month-old male patient underwent early second-look surgery without receiving any interim chemotherapy. Second-look surgery on the other four patients was performed after they had received chemotherapy. No additional major morbidity was associated with the subsequent surgery, which achieved macroscopically complete clearances in four of the five patients. Three of four patients who underwent macroscopically complete resections were well, without clinical or radiological evidence of recurrent tumor, at 23, 25, and 34 months after their second operations. The 10-month-old patient who underwent early second-look complete resection relapsed locally at 33 months after surgery. Complete resection was not possible in one patient who had progressive tumor 8 months after second-look surgery. CONCLUSION: For patients in whom complete excision of fourth ventricle ependymomas is not possible at initial surgery, second-look procedures may enable macroscopic clearance to be achieved with little morbidity. A larger study is needed to evaluate this approach to treatment.

Chemotherapeutic implications of growth fraction and cell cycle time in glioblastomas.

Four patients received 3H-thymidine 4 to 7 days and vinblastine 4 to 6 hours prior to operation for recurrent malignant gliomas (three glioblastomas and one anaplastic astrocytoma). Tumor biopsies obtained at operation were fixed for routine histological studies and radioautography. The tumors' growth fractions averaged 0.28 with a range of 0.14 to 0.39. The tumor cell cycle time calculated in three patients had a mean duration of 57 hours with a standard deviation of 6 hours. The authors concluded that: 1) single short-term courses of cell-cycle specific chemotherapeutic agents alone will probably fail to achieve either significant reduction in tumor mass or dramatic clinical improvement; 2) cell-cycle phase-specific drugs should be administered to maintain effective blood levels over 2 to 3 days for maximal tumor cell kill. Tumor growth rate appears to correlate with the fraction of proliferating cells rather than the length of the tumor cell cycle. The scientific basis for combination drug and multimodality therapy is discussed.

Craniospinal dissemination of central neurocytoma. Report of two cases.

Central neurocytoma was first described in the literature in 1982 and has been noted to be a benign neuronal tumor usually located in the ventricular system. Of the more than 100 reported cases, only seven recurrences have been reported, all of which have been local. The authors report two cases of recurrent central neurocytoma that disseminated through the ventricular system with seeding to the spine, as evidenced by magnetic resonance images and positive cerebrospinal fluid cytology. The histological appearance of these two tumors was typical for the lesion and lacked evidence of malignant change. Central neurocytoma may not be as benign as previously thought, and the recognition of this more malignant behavior has implications for patient follow up and therapy.