Identifying at diagnosis the vestibular schwannomas at low risk of growth in a long-term retrospective cohort.

OBJECTIVES: Identification at time of diagnosis of those vestibular schwannomas that will not grow. DESIGN: Retrospective cohort study of consecutive patients diagnosed with a sporadic vestibular schwannoma that were entered in the wait-and-scan protocol. SETTING: Academic referral centre. PARTICIPANTS: The study group contained 155 patients with a sporadic vestibular schwannoma first seen in the full 8-year period 2000-2007: continual wait-and-scan (n = 89) and initial wait-and-scan until intervention (n = 66). MAIN OUTCOME MEASURES: Tumour growth, defined as more than 2 mm linear difference in any plane between the diagnostic MRI-scan and the last available scan, was related to clinical parameters at diagnosis: localisation of the tumour (solely intracanalicular versus cisternal extension), sudden sensorineural hearing loss, sensorineural hearing loss longer than 2 years and vertigo/instability. RESULTS: Hearing loss longer than 2 years and an entirely intracanalicular localisation were associated with no tumour growth by univariate and multivariate Cox analysis. Combining both factors at time of diagnosis resulted in a group with low risk of growth (n = 36, median follow-up of 6.2 years) with a Hazard Ratio for growth of 0.37 (95% CI, 0.19-0.69). This subgroup is about 25% of the wait-and-scan population. Thirty-one percent showed growth, while in the remaining higher risk group of 119 patients 62% showed growth. For the growing schwannomas, the median time for growth becoming manifest is 1.9 years after diagnostic MRI. CONCLUSIONS: In this study on vestibular schwannoma patients that start in a wait-and-scan protocol, about a quarter may be set apart having a low risk for growth. These patients at diagnosis combine a history of hearing loss longer than 2 years and a fully intracanalicular schwannoma. They seem to be not needed yearly MRI checks.

Fractionated stereotactic radiation therapy and single high-dose radiosurgery for acoustic neuroma: early results of a prospective clinical study.

PURPOSE: To prospectively assess the local control and toxicity rate in acoustic neuroma patients treated with linear accelerator-based radiosurgery and fractionated stereotactic radiation therapy. METHODS AND MATERIALS: We evaluated 37 consecutive patients treated with stereotactic radiation therapy for acoustic neuroma. All patients had progressive tumors, progressive symptoms, or both. Mean tumor diameter was 2.3 cm (range 0.8-3.3) on magnetic resonance (MR) scan. Dentate patients were given a dose of 5x4 Gy or 5x5 Gy and edentate patients were given a dose of 1x10 Gy or 1x12.50 Gy prescribed to the 80% isodose. All patients were treated with a single isocenter. RESULTS: With a mean follow-up period of 25 months (range 12-61), the actuarial local control rate at 5 years was 91% (only 1 patient failed). The actuarial rate of hearing preservation at 5 years was 66% in previously-hearing patients. The actuarial rate of freedom from trigeminal nerve toxicity was 97% at 5 years. No patient developed facial nerve toxicity or other complications. CONCLUSION: In this unselected series, fractionated stereotactic radiation therapy and linear accelerator-based radiosurgery give excellent local control in acoustic neuroma. It combines a high rate of preservation of hearing with a very low rate of other toxicity, although follow-up is relatively short.

Additive cytotoxic effect of cisplatin and X-irradiation on human glioma cell cultures derived from biopsy-tissue.

PURPOSE: Investigation of the in vitro cytotoxic effect of X-rays, either alone or combined with cisplatin on early passage cell cultures derived from human glioblastoma multiforme biopsy tissue. MATERIALS AND METHODS: Fresh tumour specimens from four patients were processed to cell cultures. The U373 glioma cell line was used as a reference. Early passage cell cultures were X-irradiated (0-8 Gy) either alone or in combination with cisplatin (0.5-1 microgram/ml). Cell survival was determined by either clonogenic assay or the colorimetric MTT assay. Survival curves were generated and mathematically analysed using the linear quadratic model, to obtain the radiosensitivity parameters alpha, beta, and SF2, i.e., the Surviving Fraction after 2 Gy. RESULTS: Two patient-derived glioma cell cultures and the U373 cell line showed rather high SF2 values of 0.61-0.72 in the clonogenic assay, indicating relative high radiation resistance. Cisplatin alone (1 microgram/ml) reduced cell survival by 10-30% (n = 4). When combined with irradiation, a clear additive cytotoxic effect of cisplatin was demonstrated by the unaltered value of the alpha-parameter for reproductive cell death. CONCLUSION: Cisplatin exerted an additive rather than radiosensitising cytotoxic effect in uncharacterised patient derived glioma cell cultures.

Light propagation in the brain depends on nerve fiber orientation.

In this study, the penetration of red laser light (632.8 nm) in fresh bovine brain was measured parallel, oblique, and perpendicular to the axis of white matter tracts. The measurements were performed in eight samples with an isotropic light source and detector and were obtained by advancing the detector tip toward the light source in the tissue. A statistically significant difference in the effective attenuation coefficient of the light (mueff) was found between the parallel and perpendicular directions, 0.47 +/- 0.06 mm -1 and 0.63 +/- 0.13 mm-1, respectively (P = 0.005). The measurements taken at an angle of 45 degrees in the same sample resulted in an intermediate mueff of 0.58 +/- 0.09 mm-1. These results suggest a preferential guidance of light along the axis of the white matter tracts of the brain.

Local neurotoxicity of hematoporphyrin derivative following intracerebral injection.

The present study reports on toxicity of hematoporphyrin derivative (HpD) for normal brain tissue in vivo without the addition of light. Hematoporphyrin derivative was injected by slow infusion in rat brains. Histological examination was carried out for intervals after HpD administration, ranging from 0 h to 15 days. Ultrastructural changes were examined with transmission electron microscopy. The extent of the necrosis was determined for different HpD concentrations and compared with control animals infused with 0.9% saline. Leukocytic infiltration was observed at day 5. Transmission electron microscopy showed that nuclei of neurons were completely disintegrated 4 h after HpD administration. Furthermore disruption of myelin sheaths was observed. The extent of the necrosis decreased with lower HpD doses. Injection of 2 micrograms HpD in a volume of 4 microL (0.5 mg/mL) resulted in a virtually equal extension of the tissue damage, as compared to the mechanical damage in the control animals caused by the infusion procedure.

Malignant optic glioma in adults. Case report.

Malignant optic glioma in adulthood is a rare tumor that causes early loss of vision and nearly always leads to death within a year. A case history is presented illustrating the clinical and neuroradiological characteristics of the malignant optic glioma in adults. A review of the literature is given.

Bleeding risk of cerebrovascular malformations in hereditary hemorrhagic telangiectasia.

OBJECT: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal-dominant vascular dysplasia with a high prevalence of cerebrovascular malformations (CVMs), mostly manifested as arteriovenous malformations (AVMs). The natural history and bleeding risk of these CVMs is unknown. The authors investigated the risk of bleeding in conjunction with clinical and radiological features in patients with HHT and proven CVMs. METHODS: Intravenous digital subtraction (DS) angiography was used to screen 196 patients with HHT for the presence of CVMs. Patients with abnormal results on DS angiography were asked to undergo a conventional cerebral angiographic study. All patients with a proven CVM were assessed by a neurologist. The bleeding risk was retrospectively and prospectively calculated for patients with AVMs only, as well as for the whole cohort of patients with CVMs. Twenty-four patients (12.2%; 16 female and eight male), aged 14 to 66 years (mean 35.4 years) with one or more CVMs were identified. Fifteen patients (62.5%) had a CVM and a pulmonary AVM. Eleven patients (45.8%) exhibited no neurological signs of their CVM; six (25%) had headache or migraine; four (16.7%) had seizures; and three (12.5%) had an intracranial hemorrhage. Twenty-two patients had at least one AVM (with a total of 28 AVMs), whereas two patients only had telangiectases. Twenty-seven AVMs were small (96%), 36% were located in eloquent areas of the brain, and 82% had superficial venous drainage. One third of the patients had multiple CVMs. The bleeding risk for patients with at least one AVM ranged from 0.41 to 0.72% per year, and for the whole cohort the range was 0.38 to 0.69% per year. Calculation of the bleeding risk as determined by lesion-years ranged from 0.36 to 0.56% per year for patients with AVMs and from 0.27 to 0.46% per year for all patients with CVMs. CONCLUSIONS: Patients with HHT have a high risk of harboring a CVM, especially in the presence of a pulmonary AVM. These CVMs are mostly low-grade AVMs (Spetzler-Martin Grade I or II), are frequently multiple, and have a lower risk of bleeding than that associated with sporadic AVMs. Female patients are more often affected than male patients. The inherent low sensitivity of DS angiography screening for CVMs may yield false negative results.

Fluorescence localization in tumour and normal brain after intratumoral injection of haematoporphyrin derivative into rat brain tumour.

In the intracerebral 9L rat gliosarcoma, the spatial distribution of the photosensitizer haematoporphyrin derivative (HpD) was studied after intratumoral injection. The fluorescence volume was measured in histological sections from 10 min up to 5 days after injection. Complete sensitization of the tumours could not be achieved by slow stereotactical injection of 4 mm3 HpD (mean HpD fluorescence volume, 13 +/- 11 mm3). Larger parts of the tumour could be loaded with HpD (39 +/- 23 mm3, p = 0.0001) by increasing the injection velocity and the volume to 50 mm3. Again, complete sensitization of the tumours was not achieved during a time scale of 5 days after intratumoral injection. Although the fluorescence volume did not change significantly with time, it was influenced by the injection site within the tumour. Injection of HpD within 1 mm from the tumour border resulted in significantly smaller fluorescence volumes in the tumour than injection into the tumour centre. Large injection volumes caused an increased leakage of HpD to normal brain, leading to the loss of selectivity of photosensitizer content and the occurrence of dark toxicity of normal brain while the tumours still appeared vital.

Hemangioblastoma of the cauda equina.

A very rare hemangioblastoma of the filum terminale with sciatic pain and partial cauda syndrome in a 36-year-old man is presented. The difference between solitary hemangioblastoma, hemangioblastomatosis and von Hippel-Lindau disease is stressed. The literature is reviewed and the diagnosis of cauda equina neoplasms is discussed. Even nowadays often the final diagnosis is made late and only after operation and microscopical tissue examination.

Ventriculo-peritoneal shunt procedure complicated by liver capsule perforation. A case report.

A 29-year-old woman in childbed, presented with obstruction hydrocephalus due to a cerebellar spongioblastoma, was treated by ventriculo-peritoneal shunting. The peritoneal spring catheter used in this procedure caused a perforation of the liver capsule. The type and length of a catheter appropriate to such a case are discussed.

Photodynamic therapy of malignant glioma. A review of literature.

Photodynamic therapy is a new form of cancer treatment which can serve as an adjuvant therapy for malignant glioma. It is based on the selective retention of a photosensitive dye in tumour tissue. Subsequent exposure of the tumour to light of an appropriate wavelength causes selective destruction of tumour tissue. Experimental data indicates that the blood-brain barrier plays an important role in the delivery of the photosensitizer to a brain tumour and that intratumoral injection of the photosensitizer may be advantageous as compared to intravenous administration. A limited group of patients have entered clinical trials. Treatment protocols varied too much and the number of patients was too small to draw any conclusions on the efficiency of PDT of gliomas.

Spinal subarachnoid hemorrhage due to a filum terminale ependymoma.

We present a case of spinal subarachnoid hemorrhage due to an ependymoma of the filum terminale in a 23-year-old male. Clinical signs indicating a spinal origin of the subarachnoid hemorrhage are discussed. Subarachnoid hemorrhages are only rarely caused by an intraspinal tumor, most of which are located in the cauda equina. Our findings in this case proved the value of MRI examination in tumors of the cauda equina.

Rhinorrhoea as the presenting symptom of pituitary adenoma.

A case, in which rhinorrhoea was caused by a pituitary adenoma, is presented. Leakage of CSF or metrizamide could be observed on CT.

Treatment of leptomeningeal carcinomatosis with continuous intraventricular infusion of recombinant interleukin-2.

A 42-year-old man developed leptomeningeal carcinomatosis 6 years after treatment of a malignant melanoma. He was treated with two courses of recombinant interleukin-2, administered as a continuous intraventricular infusion (6 X 10E5 U/24 h) during 5 days. During the first day of the first course he also received 5 X 10E9 lymphokine-activated killer cells intraventricularly. This gave rise to a severe elevation of intracranial pressure, with headaches and meningismus. During the second course no LAK cells were administered. This course was tolerated much better. The neurological status did not change during the treatment. Recombinant interleukin-2 levels were maintained at about 300 U/mL during both courses.

[Meningiomas: prognostic relevance of histopathologic and genetic markers]. / Meningiomen: prognostische relevantie van histopathologische en genetische kenmerken.

The majority of meningiomas are histologically benign tumours. Location and invasion of tumour tissue in adjacent structures may hamper radical resections and give rise to recurrences. The rise in human life expectancy has prolonged the postoperative period and thus the risk of tumour recurrence has increased markedly. Infiltration in brain tissue and mitotic activity are important histologic features which negatively influence the disease-free duration of the postoperative period. Molecular studies of relevant genetic defects involved in meningioma are currently underway, but as yet these are of little clinical relevance.

[Stereotaxic irradiation of vestibular schwannoma (acoustic neuroma)]. / Stereotactische bestraling van het vestibulair schwannoom (acusticusneurinoom).

A vestibular schwannoma (acoustic neurinoma) is a benign tumour localized in the cerebellopontine angle; it can give rise to cranial nerve symptoms. In recent years stereotactic irradiation has become an alternative to radical surgery. Stereotactic irradiation is administered with a gamma knife unit or with an adapted linear accelerator, as a single fraction (radiosurgery) or fractionated (stereotactic radiation therapy). Stereotactic irradiation gives local control rates of over 90%. Post treatment hearing preservation rate is over 60% and treatment related toxicity is low. Comparable treatment results are also found in the Netherlands at the VU-Ziekenhuis in Amsterdam.

['Benign' meningioma]. / Een 'goedaardig' meningioom.

Meningioma was diagnosed in four women, aged 40, 24, 41 and almost 75 years, respectively. The first of these patients was treated with surgery, the second and third patients underwent surgery followed by conventional radiotherapy because of a tumour residue or dural tail, and the last patient was treated with stereotactic radiosurgery. They recovered well and were followed by means of regular outpatient check-ups. Twenty percent of all primary brain tumours are meningiomas, over 90% of which are benign. Nevertheless, a large hospital-based population study showed a 5-year survival rate of only 70%. Microsurgery is usually the treatment of first choice. However, in about 25% of cases, excision is incomplete and tumour growth almost always continues. Further surgery influences prognosis unfavourably. New sophisticated radiation techniques help to control tumour progression in about 80-90% of cases. This success, however, may be associated with new cranial nerve deficits or panhypopituitarism. Prospective, comparative studies are not available.

[Stereotactic radiosurgery with adjusted linear accelerator for cerebral arteriovenous malformations: preliminary results in the Netherlands]. / Stereotactische radiochirurgie met aangepaste lineaire versneller voor cerebrale arterioveneuze malformaties: eerste ervaringen in Nederland.

OBJECTIVE: To assess the effects of stereotactic radiosurgery of a cerebral arteriovenous malformation (AVM). DESIGN: Prospective. METHOD: In November 1991-December 1995 linear acceleration radiosurgery was performed on 29 patients for their 30 cerebral AVMs in the University Hospital Vrije Universiteit, Amsterdam, the Netherlands. There were 15 females and 14 males with a mean age of 37.1 years (range: 13-58). Generally one isocentre was used and 15 Gy was given to the margins of the AVM at the 80% isodose. The mean target volume was 2.4 ml (range; 0.5-8.2). After 6 months, one year and thereafter every year, neurological and MRI-controls took place, in the outpatient ward. Angiography was performed after an average of 35 months (range: 24-70) to check if the AVM had obliterated. RESULTS: Angiographic post-treatment results were available in 27 patients and MRI information in one. Angiographic obliteration occurred in 20 patients (71%). No permanent radiation-induced neurological deficit was seen, nor did any hemorrhage occur during the interval between irradiation and obliteration.