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PubMed1992

Treatment of children with progressive or recurrent brain tumors with carboplatin or iproplatin: a Pediatric Oncology Group randomized phase II study.

PURPOSE: The Pediatric Oncology Group (POG) conducted a randomized phase II study to evaluate the activity of carboplatin and iproplatin in children with progressive or recurrent brain tumors. PATIENTS AND METHODS: The study was designed to evaluate the activity of these agents and to compare the toxicities associated with their use. Treatment consisted of carboplatin 560 mg/m2 at 4-week intervals or iproplatin 270 mg/m2 at 3-week intervals. RESULTS: The major toxicity observed was myelosuppression, particularly thrombocytopenia, for both agents. Ototoxicity (grade 1 or 2) was seen in 2.5% of patients treated with carboplatin and 1.3% of patients treated with iproplatin. The majority of patients with low-grade astrocytic neoplasms treated with carboplatin (nine of 12 patients) or iproplatin (eight of 12 patients) demonstrated tumor response or prolonged stable disease that persisted off-therapy. The duration of stable disease produced by carboplatin was particularly striking, ranging from 2 months to 68 + months (median, 40 + months). Neither drug demonstrated appreciable activity in the treatment of medulloblastoma (two of 26 responses to carboplatin, one of 14 responses to iproplatin), ependymoma (two of 17 responses to carboplatin, none of seven responses to iproplatin), high-grade glioma (two of 19 responses to carboplatin, one of 14 responses to iproplatin), or brain-stem tumors (one of 23 responses to carboplatin, none of 14 responses to iproplatin). CONCLUSION: Carboplatin is active against low-grade gliomas. Further evaluation of the role of carboplatin in the preirradiation treatment of children with low-grade gliomas of the optic pathway is currently underway in a clinical trial.

Adolescent↗

PubMed2003

Study of the MIB-1 labeling index as a predictor of tumor progression in pilocytic astrocytomas in children and adolescents.

PURPOSE: The pilocytic astrocytoma (PA) is the most common childhood brain tumor. This report examines the MIB-1 labeling index (LI) as a predictor of progression-free survival (PFS) among childhood PAs. PATIENTS AND METHODS: Consecutive PAs were examined to determine whether the MIB-1 LI was associated with tumor progression. Other variables evaluated included tumor location, use of adjuvant therapy, extent of resection, and age at diagnosis. RESULTS: One hundred forty-one children were identified (mean +/- SD age, 7.6 +/- 4.7 years; range, 0.43 to 18.56 years); 118 children had adequate tissue for MIB-1 immunohistochemistry. The 5-year PFS was 61.25%. By log-rank analysis, an MIB-1 LI of more than 2.0 was associated with shortened PFS (P =.035). Patients with PAs who underwent complete surgical resection, had tumors located in the cerebellum, and were treated with surgery only also had more prolonged PFS (P =.001 for all). Tumors in the optic pathways were associated with a shorter PFS (P =.001). Restricting the evaluation of MIB-1 LI to only incompletely resected tumors revealed an insignificant trend of MIB-1 LI of more than 2.0 having a shortened PFS. Multivariate analysis demonstrated completely resected tumors and tumors located in the cerebellum as less likely to progress (P =.001 and.019, respectively). CONCLUSION: Children with PAs with an MIB-1 LI of more than 2.0 have a shortened PFS. PAs that are completely resected and are located in the cerebellum have a prolonged PFS. This initial study suggests that the MIB-1 LI identifies a more aggressive subset of PAs. Further work should focus on elucidating features of pilocytic astocytomas that will identify prospectively children at risk for progression.

Adolescent↗

PubMed2006

Changes in attentional performance of children and young adults with localized primary brain tumors after conformal radiation therapy.

PURPOSE: To prospectively assess the impact of conformal radiation therapy (CRT) and demographic and clinical variables on four measures of attention in pediatric and young adult patients with localized primary brain tumors. PATIENTS AND METHODS: We prospectively evaluated 120 patients with primary brain tumors, ages 2 to 24.4 years (median, 9.2 years). Evaluations were done using the computerized Conners' Continuous Performance Test (CCPT). We analyzed errors of omission (inattentiveness), errors of commission (impulsivity), reaction time, and an overall index of performance before CRT, weekly during CRT, and serially up to 60 months after the start of CRT. RESULTS: Before CRT, patients exhibited mild inattentiveness. During CRT, impulsivity decreased significantly (P = .002). After CRT, inattentiveness increased significantly (P = .03), and global attention disorders were associated with craniopharyngioma (P < .0001), supratentorial tumors (P = .008), optic pathway and diencephalic tumors (P = .012), and subtotal resection of the tumor (P = .010). CONCLUSION: Brain tumors and their treatment impair sustained attention and reaction time. A decline in impulsivity and relative stability of the other CCPT scores over the course of CRT demonstrated the absence of early radiation-related cognitive sequelae. Local tumor effects, initial surgical intervention, and focal irradiation of central structures contribute to long-lasting attentional problems in pediatric and young adult patients.

Adolescent↗

PubMed2006

The role of surgical biopsy in the diagnosis of glioma in individuals with neurofibromatosis-1.

Most gliomas in neurofibromatosis type 1 (NF1) are pilocytic astrocytomas (PAs) of the optic pathway occurring in young children. However, some individuals develop gliomas that lack the typical NF1-associated clinical features or radiographic appearance. We identified 17 atypical presentations from a review of 100 patients with NF1-associated gliomas. Biopsy showed that 9 were not classic PAs. These data highlight the value of biopsy in NF1-associated gliomas with unusual clinical or radiographic presentations.

Adolescent↗

PubMed1980

Surgical removal of craniopharyngiomas by the transcranial approach through the lamina terminalis and sphenoid sinus.

We describe a method of attempting total removal of a craniopharyngioma using a subfrontal approach; dissection of the tumor from the brain stem, hypothalamus, and optic chiasm through the lamina terminalis; and then piecemeal removal of the tumor through the sphenoid sinus. Eleven patients treated by this approach are reported. In these patients, prior subfrontal operation did not affect outcome, but a prior transventricular operation or prior high dose radiation therapy made complete tumor removal less likely. We believe that this operation is one way to remove a craniopharyngioma that affords satisfactory exposure and reduces the chances of injury to the frontal lobes, hypothalamus, and optic pathways.

Adolescent↗

PubMed1993

Mucoceles of the paranasal sinuses with intracranial and intraorbital extension: report of 28 cases.

Twenty-eight patients received surgical treatment for a paranasal sinus mucocele with intracranial and/or intraorbital extension. The lesions were classified by site and extension: anterior without intracranial extension (Type 1), 7 patients; anterior with intracranial extension (Type 2), 11 patients; posterior midline without intracranial extension (Type 3), 5 patients; and posterior with intracranial extension (Type 4), 5 patients. The surgical approaches were: transnaso-orbital, transfrontonaso-orbital, transsphenoidal, transmaxillosphenoidal, and subfrontal transbasal; the choice depended on the site and extension of the lesion, with the aim of securing maximum exposure to ensure total removal of the lesion with its capsule. A transcranial approach was reserved for mucoceles possessing an intracranial extension or causing distension of the bone structures with optic pathway neurological symptoms. With a coronal or transfacial skin incision along the lines of the forehead, nose, and orbital muscles of expression and careful reconstruction, the patients' natural cast of features was spared or restored in a single operation.

Adolescent↗

PubMed2004

Intensity-modulated radiation therapy for head and neck cancer.

In head and neck cancer, intensity-modulated radiation therapy (IMRT) makes the use of electron beams for irradiation of the posterior neck obsolete, inherently performs missing tissue compensation, and allows concave and intentionally nonhomogeneous dose distributions. By clinical use of these physical characteristics, salivary or lacrimal glands, optic pathway and auditory structures can be selectively underdosed and good evidence of decreased radiation toxicity is available. Evidence for increased local control is still lacking. Recurrences are mainly located in the high-dose-prescription regions, suggesting the need for even higher doses in these areas. Image-aided design of IMRT dose distribution is an area of intense research. New positron emission tomography and magnetic resonance imaging developments might allow definition of volumes inside the tumor where treatment failure is most likely to occur. If these volumes are small, focused dose escalation of large magnitude can be attempted and the hypothesis of improved local control by IMRT can be tested.

Dose Fractionation, Radiation↗

PubMed1995

[Brown-Vialleto-van Laere syndrome: report of 2 cases].

Brown-Vialetto-van Laere syndrome is a rare hereditary or sporadic degenerative disorder characterised by progressive sensoryneural deafness, followed or accompanied by cranial nerve palsies. The anterior horn cells and the optic pathways may be involved in some cases. We report two cases, and comment the differential diagnosis and the relationships of this syndrome to the muscle spinal atrophies and the hereditary deafness.

Adolescent↗

PubMed2006

Treatments for astrocytic tumors in children: current and emerging strategies.

Strategies for the treatment of childhood cancer have changed considerably during the last 50 years and have led to dramatic improvements in long-term survival. Despite these accomplishments, CNS tumors remain the leading cause of death in pediatric oncology. Astrocytic tumors form the most common histologic group among childhood brain tumors. They are a heterogeneous group that from a practical therapeutic point of view can be subdivided into low-grade astrocytomas (LGA), optic pathway gliomas (OPG), high-grade astrocytomas (HGA), and brainstem gliomas (BSG). This article focuses on the practical application of treatments that lead to long-term survival, improved quality of life, and reduced long-term complications. Improvement in therapy has led to better outcomes for patients with LGA and OPG. Careful follow-up without any treatment is indicated for a small percentage of patients diagnosed with LGA with an indolent course including children with neurofibromatosis type 1 (NF1). Surgery is the main recommended treatment for children with resectable LGA. Radiation therapy is generally recommended for children with progressive LGA, or after failure of chemotherapy, accomplishing tumor control at 10 years in over 60% of patients. Cytotoxic chemotherapy is usually reserved for children who have had treatment failure with surgery and radiation therapy. It is also offered for children who are too young to be treated with radiation or to defer or avoid radiotherapy. Carboplatin and vincristine achieve 5% complete and 28% partial responses but the use of vincristine is criticized due to poor penetration of the CNS. A regimen of tioguanine, procarbazine, mitolactol, lomustine, and vincristine is frequently administered as an alternative to carboplatin and vincristine in LGA. The introduction of temozolomide has allowed better responses, including a 24% complete response rate compared with 0-5% complete response rates with the previous regimens. OPG are usually histologically LGA, and are treated with similar chemotherapy regimens. OPG is the most common type of brain tumor associated with NF1. Tumor growth in some of these patients is slow with no treatment recommended for an extended period of time. The prognosis for children with the remaining types of astrocytomas remains poor. Surgical resection is typically the first step in the treatment of HGA followed in older children by radiation therapy. The data regarding chemotherapy are mixed. Combination chemotherapy before or after radiation, including cisplatin, carmustine, cyclophosphamide, and vincristine or carboplatin, ifosfamide, cyclophosphamide, and etoposide has provided disappointing results. Clinical trials with temozolomide and agents directed against single targets have not shown substantially better results, but it is hoped that currently conducted studies will provide better outcomes. Diffuse intrinsic BSG are among the most difficult-to-treat brain tumors. Surgical treatment is not recommended for diffuse intrinsic BSG and standard radiation therapy is typically given in children aged >3 years. None of the numerous chemotherapy regimens, including temozolomide, has provided a significant response rate or an improvement in survival. It is expected that newer agents affecting multiple targets such as AEE-788 and antineoplastons, and combinations of single-targeted agents with chemotherapy will provide better results. Careful evaluation of histology, location of the tumor, patient age, and consideration of treatment-related morbidity play an important part in selecting between clinical observation, surgery, radiation, chemotherapy, or investigational agents. The goals of treatment for astrocytic tumors should extend well beyond objective responses and increased survival. Improvement of quality of life is an equally important objective of treatment. Radiation therapy and chemotherapy result in serious late toxicities.

Astrocytoma↗

PubMed1992

Diaphragma sellae meningioma associated only with signs of hypopituitarism--case report.

A rare diaphragma sellae meningioma presenting only with signs of hypopituitarism occurred in a 54-year-old male. Preoperative magnetic resonance (MR) imaging clearly demonstrated a small lesion in the supradiaphragmatic area immediately beneath the optic chiasm, displacing the pituitary stalk laterally. Intraoperatively, the tumor was confirmed to be attached only to the posterior leaf of the diaphragma sellae. Histological examination revealed a transitional type meningioma. Such a small meningioma may be associated only with hypopituitarism, as compression is confined to the pituitary stalk, not affecting the optic pathways. MR imaging can demonstrate the clinicopathological features of this small but significant tumor.

Humans↗

PubMed2000

Terson syndrome caused by ventricular hemorrhage associated with moyamoya disease--case report.

A 24-year-old female presented with Terson syndrome secondary to bilateral ventricular hemorrhage as a complication of moyamoya disease. Ophthalmoscopy and magnetic resonance imaging clearly demonstrated vitreous hemorrhage in the left eye globe. Various visual symptoms are associated with moyamoya disease, almost all of which result from ischemic lesions in the visual cortex and optic pathways. In this case, the visual disturbance was caused by Terson syndrome secondary to ventricular hemorrhage. Close ophthalmological and radiological evaluation is mandatory even in patients with moyamoya disease and hemorrhagic manifestation located in the intracerebral, subarachnoid, or intraventricular space.

Adult↗

PubMed2005

Multifocal pilocytic astrocytomas with ependymal differentiation in the bilateral medial temporal lobes: case report.

A 7-year-old boy presented with headache, visual disturbance, and psychomotor seizures persisting for 7 months. He had mild hemiparesis and homonymous hemianopia on the left. Neuroimaging showed bilateral temporal lobe masses with calcification and cysts. The right temporal mass was subtotally resected. The histological diagnosis was pilocytic astrocytoma with ependymal differentiation and a MIB-1 staining index of up to 8.0%. Postoperatively his hemiparesis and psychomotor seizures disappeared. Adjuvant chemotherapy consisting of carboplatin and vincristine was given followed by radiotherapy. Neuroimaging showed that the bilateral tumors had disappeared and showed no recurrence for 29 months after the diagnosis. Pilocytic astrocytoma usually presents as a solitary mass in the cerebellum or optic pathway with low proliferative activity, but should be included in the differential diagnosis of multifocal tumors arising in the bilateral temporal lobes. Ependymal differentiation with extremely high proliferative activity might be related to this unusual clinical presentation. Intensive treatment is recommended for patients with such specific neuroimaging and histological features.

Antibodies, Antinuclear↗

PubMedDate not supplied

Flash-induced nystagmus (FIN) and the vestibular system in the rabbit.

Flash-induced nystagmus (FIN) was found more often in albino than in pigmented rabbits. Incremental and decremental phase mainly showed exponential change in SPV, but linear change was seen as well with apparent time constant of 5-40 sec. FIN was unaltered by rendering the stimulated eye akinetic. Lesioning the nucleus of the optic tract (NOT) on one side abolished FIN and OKN responses from the other side. Bilateral labyrinthectomy led to a diminished response and after-responses were lost. Algebraic addition was shown if FIN was combined with vestibular reflex eye movements. The gain of these reflexes was enhanced. FIN may be specified as a type of nystagmus that is evoked by monocular essentially open-loop stimulation of the crossed ('subcortical') optic pathway. Direction-selective elements in the retina may play a specific role in that their predominant orientation gives rise to abduction nystagmus during on/off stimulation by flashes.

Animals↗

PubMed1989

Visuospatial disorders and related lesions of the brain.

Ten right-handed patients suffering from visuospatial impairment were examined. The impairment was ascertained by a test requiring visual organization (picture completion). The patients did not suffer from other neuropsychological disorders (e.g., aphasia, dementia). Furthermore, psychiatric symptoms and defective oculomotion (gaze paresis, ocular paresis) were controlled. CT scan data revealed that in 4 patients the impairment was associated with lesions of the posterior right hemisphere. All lesions involved the central optic pathways and were accompanied by visual field defects. On the other hand, 6 patients turned out as suffering from damage of the cerebellum or brainstem. The available electronystagmographical data revealed impaired visual fixation, an oculomotor defect characterizing gaze apraxia, the diagnostic marker of Balint's syndrome.

Brain↗

PubMed1995

Long term beneficial effects of weak electromagnetic fields in multiple sclerosis.

A 39 year-old severely disabled woman with a 19 year history of chronic relapsing-remitting multiple sclerosis (MS) began to experience improvement in symptoms within 24 hours after she received experimental treatment with picotesla electromagnetic fields (EMFs). Pattern reversal visual evoked potential (VEP) study obtained three weeks after the initiation of the first magnetic treatment showed a return to normal of the P100 latencies in each eye. The patient continued to receive 1-2 EMFs treatments per week and during the following 32 months she made a dramatic recovery with resolution of diplopia, blurring of vision, dysarthria, ataxia of gait, and bladder dysfunction as well as improvement in fatigue, heat tolerance, mood, sleep, libido, and cognitive functions. VEP studies, which were repeated in April of 1995 more than 2 1/2 years after the initiation of magnetic treatment, showed that P100 latencies remained normal in each eye providing objective documentation that continued application of these EMFs may sustain normal conduction in the damaged optic pathways over a long period of time. This is the first case report documenting the dramatic long term beneficial effects of treatment with picotesla range EMFs in a patient with MS.

Adult↗

PubMed1990

Red or rufous albinism in southern Africa.

Red or rufous albinism is a rare type of oculocutaneous albinism described, but not as yet fully investigated, in Africa and New Guinea. Twelve rufous albino subjects from 10 families participated in this preliminary study. The prevalence of rufous albinism was found to be approximately one in 8,580 among school children in the negroid population. The combination of the unusual red skin colour, ginger to reddish hair colour, low susceptibility to sun damage, and minimal visual problems, in affected individuals, suggested that they form a group which is distinct from the brown and other types of albinism. The mode of inheritance was found to be recessive. Tyrosinase assays showed that rufous albinos are tyrosinase positive and on electron microscopy studies normal melanosomes and melanocytes were observed in hair bulbs and skin. Visual evoked potential testing did not show the gross decussation abnormalities of the optic pathway detected in other types of albinism. Rufous albinism might be at one end of the spectrum of types of oculocutaneous albinism and, because affected people have such mild symptoms, their inclusion in this group might be debatable.

Adolescent↗

PubMed1998

Phase II study of carboplatin (CBDCA) in progressive low-grade gliomas.

In this study, the authors sought to investigate the response rate and toxicity of carboplatin in patients with progressive low-grade glioma (LGG). Thirty-two patients with progressive LGG were treated with carboplatin at a dosage of 560 mg/m(2). Treatment was given at 4-week intervals and continued until the disease progressed, unacceptable toxicity supervened, or for 12 additional courses after achieving maximal response. Patients with stable disease were treated with a total of 12 cycles. All patients were treated as outpatients. Patients were evaluated for response to treatment and toxicity. All patients received a minimum of two cycles of carboplatin, and were examined for response. A partial response was achieved in nine patients (28%) and a minimal response in two (6%), for an overall response rate of 34% (11 of 32 patients). Eighteen patients (56%) had stable disease. A partial response was achieved in the nine patients after a median of six cycles (range 4-11 cycles), a minimal response was achieved in the two patients after five cycles. Glioma progression was noted in three patients after three, five, and five cycles, respectively. The 11 patients in whom some response was achieved had either an optic pathway tumor or a juvenile pilocytic astrocytoma. Twenty-six of the 32 patients had those characteristics, making the response rate in that group 42% (11 of 26 patients). Thirty-two patients received a total of 387 cycles of chemotherapy. Hematological toxicity was moderate. Twenty-one patients developed thrombocytopenia (platelet count < 50,000/microl); three patients required one platelet transfusion each. Nine patients developed neutropenia (absolute neutrophil count < 500/microl); one developed fever and required administration of antibiotic agents. One dose adjustment in each of the patients prevented further thrombocytopenia and neutropenia. Two patients with stable disease died of respiratory complications. One patient developed Grade III ototoxicity after receiving five cycles, one patient developed hypersensitivity to carboplatin, and none developed nephrotoxicity. Carboplatin given at a dosage of 560 mg/m(2) every 4 weeks has activity in patients with progressive LGG. This drug regimen is relatively simple and well tolerated. Further investigation and longer follow-up study are warranted.

Journal Article↗

PubMed2003

A population-based study of the incidence and survival rates in patients with pilocytic astrocytoma.

OBJECT: The incidence of pilocytic astrocytomas and the rate of patient survival were analyzed in a population-based study in the canton of Zürich, Switzerland. METHODS: Between 1980 and 1994, 987 astrocytic and oligodendroglial tumors were diagnosed, of which 55 (5.5%) were pilocytic astrocytomas. The incidence rate, adjusted to the World Standard Population, was 4.8 per 1 million per year. The mean age at clinical diagnosis was 19.6 +/- 12.7 years, and the male/female ratio was 1.12. The most frequent tumor sites were the cerebellum (40%), followed by supratentorial locations (35%), the optic pathway and hypothalamus (11%), and the brainstem (9%). The mean follow-up period was 12 years. Observed survival rates were 100% at 5 years and 95.8% at 10 years after diagnosis (relative survival rate at 10 years: 96.8%). Seven patients (13%) received postoperative radiotherapy, but this did not significantly affect survival. In all patients the tumors were histologically classified as WHO Grade I, except in two patients who had anaplastic pilocytic astrocytoma (Grade III), one of whom died after 7 years, whereas the other was still alive after 10 years. CONCLUSIONS: This population-based study shows that, because of the benign biological behavior of pilocytic astrocytomas and advances in microneurosurgery, the survival rates for patients with these tumors are excellent, regardless of postoperative radiotherapy.

Adult↗