Spinal cord pilocytic astrocytoma with cranial meningeal metastases.

Dissemination of tumour cells along the cerebrospinal fluid (CSF) pathway has been reported mostly in medulloblastomas, germ cell tumours or high grade gliomas. Juvenile pilocytic astrocytoma (JPA) is usually a benign astrocytoma. However, drop metastases of indolent nature from intracranial tumours to the spinal cord are documented. All of the previously reported cases represent metastases of cerebellar or hypothalamic tumours spreading to the spinal cord. We document in this paper the first report of a spinal cord pilocytic astrocytoma spreading via the CSF to the cerebral meninges. A 9 year old girl had a JPA of C5 to C7 subtotally resected. Two and a half years later she presented with hydrocephalus with radiologically meningeal enhancement. The meninges were biopsied which showed metastatic JPA. The girl was relatively well 4 years after initial surgery with residual tumour. Spinal cord JPA can rarely metastasize to the cranial meninges. Similar to intracranial tumours which spread to the spinal cord, such metastatic lesions are indolent.     

Malignant transformation in pediatric spinal intramedullary tumors: case-based update

BACKGROUND: In children, intramedullary spinal cord neoplasms are rare. These are typically low-grade neuroepithelial tumors, most commonly astrocytomas, ependymomas, and gangliogliomas. Malignant transformation, while common in recurrent adult low-grade gliomas, is an unusual event in pediatric low-grade neoplasms, specifically in intramedullary spinal cord tumors. ILLUSTRATIVE CASES: We report two cases of malignant transformation in low-grade neuroepithelial tumors of the pediatric intramedullary spinal cord. Two children with intramedullary tumors, one with a WHO grade I ganglioglioma and one with a low-grade astrocytoma, were treated surgically, diagnosed histologically, and followed through the course of their disease. Both patients' tumors transformed to higher grades without prior irradiation or chemotherapy, and without a genetic predisposition to tumorigenesis. DISCUSSION: Malignant transformation can occur in low-grade intramedullary neoplasms in children. This is a novel documented event for pediatric intramedullary spinal cord tumors and a rare event for all pediatric low-grade neuroepithelial tumors without induction by irradiation. A survey of the relevant literature reveals an underwhelming number of studies focusing on malignant transformation in children's CNS tumors relative to adults. Further investigation into molecular mechanisms of pediatric low-grade neoplasms may reveal more aggressive tumor sub-variants predisposed to malignant degeneration.     

Chemotherapy for spinal cord astrocytoma: can natural history be modified?

Standard treatment of spinal cord astrocytomas is based upon surgery, followed by radiotherapy when resection is incomplete or when histology is of high grade. Owing to the major consequences of radiotherapy on the spine in childhood, alternative therapies must be explored. The potential role of chemotherapy in the management of spinal cord astrocytoma remains to be defined. Two patients are described. The first was a 19-month-old child with an anaplastic astrocytoma of the cervical spinal cord that progressed rapidly after initial partial resection. Chemotherapy was begun according to the UKCCSG Baby Brain Protocol, with marked clinical improvement. Reassessment by MRI at 4 months showed improvement, and at the end of treatment no evaluable disease remained. The second was a 4-year-old child with a recurrent low-grade astrocytoma. Chemotherapy according to the SIOP Protocol for Low Grade Gliomas was administered for 3 months, after which marked tumour regression was seen, with neurological recovery. These patients demonstrate the potential value and low morbidity of chemotherapy in spinal cord astrocytoma. The management of this rare tumour is discussed.     

Spinal cord gliomas: management and outcome with reference to adjuvant therapy.

The authors review their experience with 19 consecutive cases with either astrocytic tumour (glioblastoma multiforme one, anaplastic astrocytoma one, astrocytoma 4, pilocytic astrocytoma 4) or ependymoma (10 tumours in 9 patients) of the spinal cord who were treated during the period from 1982 to 1996. The patients included 10 male and 9 female patients with a median age of 38 years. The main tumour locations included the cervicomedullary region 5 the cervical cord (8), the thoracic cord (5) and one each in the thoracolumbar region and conus medullaris. While a total removal of the tumour was achieved in 8 out of 10 ependymomas, the initial treatment for astrocytic tumours was a partial resection in 5, and biopsy in the remaining 5. As adjuvant treatment, 8 patients received radiation therapy and 2 received chemotherapy. Two patients with an astrocytic tumour received chemotherapy only, while the remaining 9 received neither radiation therapy nor chemotherapy initially. After these treatments, 6 out of the 8 patients with low grade astrocytoma have remained alive for 1.3-12.6 years, while 2 patients with high grade astrocytic tumours died within 15 months following surgery. Eight out of 9 patients with an ependymoma have remained alive for 3.0-12.3 years, while one committed suicide 2 years after surgery. As a result, 14 patients are still alive; half of them are accompanied by a mild neurological dysfunction, while the remaining one has a moderate deficit. The postoperative results and the rationale for surgery is discussed, and an approach for utilising adjuvant therapy for high grade tumours is also suggested.     

Neurocutaneous Melanosis in Association with Dandy-Walker Complex with Extensive Intracerebral and Spinal Cord Involvement

Neurocutaneous melanosis (NCM) is a rare congenital syndrome consisting of benign or malignant melanotic tumors of the central nervous system with large or numerous cutaneous melanocytic nevi. The Dandy-Walker complex (DWC) is characterized by an enlarged posterior fossa with high insertion of the tentorium, hypoplasia or aplasia of the cerebellar vermis, and cystic dilatation of the fourth ventricle. These each two conditions are rare, but NCM associated with DWC is even more rare. Most patients of NCM with DWC present neurological symptoms early in life such as intracranial hemorrhage, hydrocephalus, and malignant transformation of the melanocytes. We report a 14-year-old male patient who was finally diagnosed as NCM in association with DWC with extensive intracerebral and spinal cord involvement.     

Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing

Patients with cerebellar damage often present with the cerebellar motor syndrome of dysmetria, dysarthria and ataxia, yet cerebellar lesions can also result in the cerebellar cognitive affective syndrome (CCAS), including executive, visual spatial, and linguistic impairments, and affective dysregulation. We have hypothesized that there is topographic organization in the human cerebellum such that the anterior lobe and lobule VIII contain the representation of the sensorimotor cerebellum; lobules VI and VII of the posterior lobe comprise the cognitive cerebellum; and the posterior vermis is the anatomical substrate of the limbic cerebellum. Here we analyze anatomical, functional neuroimaging, and clinical data to test this hypothesis. We find converging lines of evidence supporting regional organization of motor, cognitive, and limbic behaviors in the cerebellum. The cerebellar motor syndrome results when lesions involve the anterior lobe and parts of lobule VI, interrupting cerebellar communication with cerebral and spinal motor systems. Cognitive impairments occur when posterior lobe lesions affect lobules VI and VII (including Crus I, Crus II, and lobule VIIB), disrupting cerebellar modulation of cognitive loops with cerebral association cortices. Neuropsychiatric disorders manifest when vermis lesions deprive cerebro-cerebellar-limbic loops of cerebellar input. We consider this functional topography to be a consequence of the differential arrangement of connections of the cerebellum with the spinal cord, brainstem, and cerebral hemispheres, reflecting cerebellar incorporation into the distributed neural circuits subserving movement, cognition, and emotion. These observations provide testable hypotheses for future investigations.     

MR characteristics of malignant spinal cord astrocytomas in children

OBJECTIVE: Malignant spinal cord astrocytomas are rare tumors and their specific MR characteristics have not been previously described. We present a detailed MR analysis of four children with malignant astrocytoma. METHODS: A review of the clinical database at the Hospital for Sick Children, Toronto revealed four patients with histologically-verified malignant spinal cord astrocytomas (WHO Grade 3 or 4) with pre-operative MR available for retrospective review. RESULTS: There were three boys and one girl with a mean age at presentation of four years (range 7 months-12 years). Mean duration of symptoms prior to presentation was six weeks (range 3 days-5 months). Pre-operative MR analysis revealed that all tumors were located in the cervical or cervico-thoracic regions and expanded the cord over an average of 6.5 vertebral levels. The signal was usually hypointense on T1-weighted and hyperintense or mixed intensity on T2-weighted images. In the three cases where gadolinium was given, all demonstrated enhancement (one rim enhancement with a discrete border and two with inhomogeneous central enhancement). One tumor appeared to be exophytic, one had a significant cystic component, and none showed evidence of hemorrhage. Pre-operative leptomeningeal spread of tumor was documented in two of four cases and involved intracranial spread in both cases. CONCLUSIONS: There did not appear to be any specific MR characteristics to help differentiate a malignant astrocytoma from a low-grade tumor, except for the high rate of leptomeningeal spread at presentation. It is recommended that full neuraxis MR imaging be performed pre-operatively in children in whom a rapidly progressive clinical course suggests a malignant lesion. This will likely have a high positive yield and provide valuable information prior to surgical intervention.     

Arrested growth and spontaneous tumor regression of partially resected low-grade cerebellar astrocytomas in children

Purpose

The prognosis of children with low-grade cerebellar astrocytoma who have partial resection of tumor is largely unpredictable. The purpose of this study was to review the long-term outcome of such patients.

Methods

The medical charts, imaging findings, operative notes, histopathological reports, and survival times of 12 patients with cerebellar astrocytoma were reviewed.

Results

Five patients had total resection and seven had partial resection. Nine patients had grade I histology and three patients had grade II. Follow-up duration ranged from 3 to 25 years. Among the seven patients with residual tumor, five had tumor progression, one had arrested tumor growth, and one had spontaneous tumor regression. Five patients with partial resection received radiotherapy and three had malignant transformation of tumor during follow-up. Six patients, including five who had partial resection, underwent a second operation. One patient with partial resection died of pneumonia 23 years after surgery.

Conclusions

Patients with complete tumor resection had a better prognosis than patients with partial resection. For patients with partial resection, we recommend a “wait and see” policy with surveillance using MRI. The phenomenon of arrested tumor growth and spontaneous tumor regression in patients with cerebellar astrocytoma who have subtotal resection warrants further study.     

小脑性缄默4例报告及文献复习

目的探讨后颅窝手术后小脑性缄默的临床特点及其形成的病理生理机制。方法回顾性总结分析我科4例和英文文献报告的137例共141例后颅窝手术后出现的小脑性缄默病例。结果儿童病例127例,占90.1%。手术病变位于小脑蚓部者125例(88.7%)。小脑性缄默均为暂时性,发生的平均潜伏期和持续时间分别为1.7d和56.2d。结论小脑性缄默多见于儿童小脑蚓部肿瘤手术后其发生机制可能与小脑齿状核丘脑腹外侧核运动区和辅助运动区之间的纤维联系的直接或间接损害有关。     

Sub-classification of low-grade cerebellar astrocytoma: is it clinically meaningful?

OBJECTIVES: The objectives were to identify prognostic factors for the survival of children with cerebellar astrocytoma, and to evaluate the reproducibility and prognostic value of histological sub-classification and grading. METHODS: Children aged 0-14 years treated in Denmark for a cerebellar astrocytoma in the period 1960-1984 were included and followed until January 2001 or until their death. The histological specimens from each patient were reviewed for revised grading and classification according to three different classification schemes: the WHO, the Kernohan and the Daumas-Duport grading systems. RESULTS: The overall survival rate was 81% after a follow-up time of 15-40 years. The significant positive prognostic factors for survival were "surgically gross-total removal" of the tumour at surgery and location of the tumour in the cerebellum proper as opposed to location in the fourth ventricle. No difference in survival time was demonstrated when we compared pilocytic astrocytoma and fibrillary astrocytoma. Moreover, we found that the Kernohan and the WHO classification systems had no predictive value and that the Daumas-Duport system is unsuitable as a prognostic tool for low-grade posterior fossa astrocytomas. CONCLUSION: Discordant observations due to interobserver variability make histological sub-classification of low-grade cerebellar astrocytomas in children insufficient for predicting prognosis and biological behaviour. Similar survival rates in a population of paediatric low-grade cerebellar astrocytomas of grades I and II indicate that tumour grade has no prognostic significance within this group of patients. "Surgically gross-total removal", especially if the tumour is located in the fourth ventricle is of the highest importance for long-term survival. Histological sub-classification of the tumours has no predictive value.     

Clinical aspects and long-term prognosis of infratentorial intracranial tumours in infancy and childhood

An unselected series of 185 children with intracranial tumours in the posterior fossa, aged from birth up to and including 14 years, was followed from 1 to 40 years after diagnosis. Follow-up was 100%. There were 102 boys and 83 girls, i.e. a male/female ratio of 1.22. the same sex ratio was found in all tumour localisations and in most of the histological groups, with the exception of ependymoma, where it was 2.0. All children with tumours in the fourth ventricle or in the cerebellar hemispheres had signs of increased intracranial pressure on admission to hospital, and the duration of these symptoms was less than 6 months in 77% of the children. 113 patients survived for more than 1 month after surgery or diagnosis, and 46 (41%) for at least 15 years. All 34 children with tumours in the brain stem died within the first 2 years of observation, apart from three who survived 4, 5, and 10 years. All but one of the children with medulloblastoma, and all but two with ependymoma died within 1–17 years. Five children with astrocytoma suffered tumour recurrence more than 10 years after primary surgery. One with astrocytoma in the fourth ventricle and 36 with cerebellar astrocytoma survived for at least 15 years. In the survivors the tumour was located in the fourth ventricle in three, in the cerebello-pontine angle in one, and in either the vermis or the cerebellar hemispheres in 42. 41 of these 46 survivors lead a normal life.     

Anaplastic astrocytoma of the spinal cord presenting with features of raised intracranial pressure

Intramedullary tumors of the spinal cord in childhood are usually of low grades (grades I and II) and are most commonly seen in the cervical and cervicothoracic regions. They present with symptoms and signs of spinal cord tumor. It is uncommon to find an anaplastic astrocytoma situated in the thoracolumbar segment of the spinal cord. Whereas papilledema and raised intracranial symptoms have been reported in about 12.5% of cases of spinal cord tumors it is rare to find them presenting initially only with symptoms of raised intracranial pressure and only later followed by spinal cord symptoms. The case of an 11-year-old female child is reported here because of a combination of these two rare features.     

Leptomeningeal gliomatosis with spinal cord or cauda equina compression: a complication of supratentorial gliomas in adults

Seven patients with supratentorial gliomas developed leptomeningeal gliomatosis (LMG) without symptomatic recurrence at the primary tumor site. In all, severe back and radicular pain, often simulating disc disease, preceded the development of spinal cord or cauda equina dysfunction. In 4 instances, intracranial hypertension due to hydrocephalus developed prior to spinal involvement. Cytological examination of the CSF revealed malignant cells in only 2/7 but a myelogram was diagnostic in all 7. All patients received spinal irradiation (RT) and 5 received chemotherapy. Two patients with low-grade gliomas improved transiently; 5 with malignant gliomas responded poorly, became paraplegic over 4 months and eventually died of LMG. When fatal LMG occurs in young adults suffering from supratentorial glioma, the primary tumor is often quiescent. Hydrocephalus is often the first manifestation of LMG and, when it is detected, a myelogram and CSF cytology study should be performed in the hope that diagnosis and treatment of spinal cord lesion at a very early stage will prove beneficial. Irradiation of the entire spinal canal is probably required as there is a high risk of rapid development of new lesions in non irradiated segments of the spinal canal.     

Surgical management of long intramedullary spinal cord tumors

Object Spinal cord tumors represent approximately 10–20% of primary central nervous system tumors. Only 20–30% of primary intradural tumors are intramedullary. The incidence of longitudinally extensive tumors involving the cervical, thoracic, and lumbar spine is very low (<1% of intramedullary lesions); hence, little literature exists on the management of this entity. Materials and methods We retrospectively reviewed all patients undergoing surgical resection of longitudinally extensive intramedullary spinal cord tumors involving the majority of the spinal cord between 1990 and 2002. Clinical, radiographic, operative, and outcome variables were retrospectively recorded and reported. Results Thirteen patients (eight male, five female) were included in the study. Mean age was 15 years (range, 3–45) at the time of the initial resection. Gross total resection was achieved in eight cases and subtotal resection in five cases. Pathology revealed astrocytoma in six cases (two pilocytic, four grade II), gangliogliomas in four cases, oligodendroglioma in two cases (one anaplastic), and lipoma in one case. One (8%) patient died from progression of anaplastic oligodendroglioma, and two (15%) underwent reoperation for recurrent tumor (ganglioglioma, grade II astrocytoma). With a mean of 3.4 years (range, 1–12) after surgery, the modified McCormick score (MMS) had worsened in only two (15%) patients, improved in three (23%) patients, and remained stable in seven (54%) patients compared to preoperative MMS. Five (38%) patients required fusion for progressive spinal deformity. Conclusion Gross total resection of holocord and longitudinally extensive intramedullary spinal cord tumors can be achieved with preservation of long-term neurological function in many cases. Serial imaging is recommended to guide subsequent resection for tumor recurrence and stabilization of progressive spinal deformity.     

Precentral cerebellar vein in cystic astrocytomas of the vermis.

A peculiar abnormality of the precentral cerebellar vein seen only in cystic astrocytoma of the vermis is reported. Implications of this angiographic finding are discussed. The importance of posterior fossa angiography (especially venography) in the diagnosis of posterior fossa mass lesions is emphasized.     

Unusual dissemination patterns of low-grade astrocytomas in childhood

CONTEXT: Low-grade astrocytomas are intracerebral lesions of relatively high frequency in the under-18 pediatric population. They often present indolent behaviour, and complete surgical resection is the choice treatment. In cases where the surgery is not possible, chemotherapy and radiotherapy may be used. Medical reports do not recommend examination of the spinal cord at diagnosis or during treatment, since the risk of dissemination of the lesion to the spine is minimal according to medical experience. We describe here four cases of children with low-grade astrocytoma with aggressive dissemination to the neuroaxis.     

Late malignant recurrence of childhood cerebellar astrocytoma

Juvenile pilocytic astrocytoma of the cerebellum has a benign course and a good prognosis. We report a case of juvenile cerebellar astrocytoma in a 6-year-old girl that underwent surgical resection of the tumor and had two recurrences, 13 and 35 years after first removal. After surgery the patient did not receive any radiation therapy. The last relapse showed histological features of an anaplastic astrocytoma. Six months later the patient died with a diffuse leptomeningeal dissemination. Late malignant transformation of a benign cerebellar astrocytoma is very rare and it is thought to be favored by postsurgical irradiation. The possible pathogenetic mechanisms of this evolution are discussed. This case and the few others reported in the literature emphasize the risk of an unpredictable outcome with the low-grade cerebellar astrocytomas of childhood.     

Medulloblastoma with mandibular metastasis after complete remission of the central nervous system lesions]

A 6-year-old boy presented with headache and vomiting. Brain and spinal MRI demonstrated a large mass in the cerebellar vermis and 4th ventricle and showed thick spinal subarachnoid dissemination. Suboccipital craniotomy was performed and the tumor was totally removed. The histological diagnosis was medulloblastoma. The patient subsequently received craniospinal irradiation, and also received systemic and intrathecal perfusion chemotherapy. Then complete remission was achieved 10 months after operation. Three years later, however, a swelling at the left mandibular angle appeared. A CT scan revealed osteosclerotic lesion. After biopsy was performed, the specimen was detected infiltration of medulloblastoma cells. Bone scintigram showed a single lesion and MRI of brain and spinal cord revealed no recurrence of the central nervous system lesions. He underwent local irradiation and systemic chemotherapy with ICE regimen. This is the rare case of extracranial metastasis following remission of medulloblastoma in childhood.     

Recurrent spinal cord astrocytoma with intraventricular seeding

Patient We report on an unusual case of a recurrent and progressive spinal pilocytic astrocytoma with metastatic spreading to the hypothalamus in a 14-year-old boy.Treatment and results The patient underwent resection of an intramedullary atypical pilocytic astrocytoma classified as WHO grade II at the level of Th11/12 in 1997 and received local photon beam irradiation. Three years later, a second operation was necessary for a recurrent tumour at the same level. Seventeen months later, a second recurrent tumour with spinal seeding as well as an intracranial tumour in the third ventricle and hypothalamus was detected. He was shunted for an occlusive hydrocephalus and a stereotactic biopsy of the hypothalamic lesion was performed. The tumour was classified as anaplastic pilocytic astrocytoma (WHO grade III). He received chemotherapy with ifosfamide, cisplatin and etoposide (HIT-GBM-C-protocol), craniospinal radiation, and is still alive 60 months after the first operative intervention without neurological deficits.     

Multicentric anaplastic astrocytoma in a child.

We report a rare case of anaplastic astrocytoma with multicentric central nervous system lesions in a 10-year-old girl presenting with a 1-month history of progressive headache and paraparesis. Neurological examination upon admission revealed papilloedema of both eyes and grade 2/5 weakness of both legs. Cranial and spinal magnetic resonance imaging revealed multiple tumour foci within the suprasellar region, cerebellar hemisphere, cervical and thoracic cords. After an uneventful laminectomy and excision of the tumour at the T8-9 level, a significant improvement of motor function was observed. The histological diagnosis was anaplastic astrocytoma based on the WHO classification. The patient received postoperative radiotherapy and chemotherapy, and was able to walk with the aid of auxiliary crutches. Despite being an uncommon disease in children and being associated with an unfavourable long-term outcome, early diagnosis and appropriate management of this condition may contribute to reduced patient morbidity.