Verbal and General IQ Associate with Supragranular Layer Thickness and Cell Properties of the Left Temporal Cortex.

The left temporal lobe is an integral part of the language system and its cortical structure and function associate with general intelligence. However, whether cortical laminar architecture and cellular properties of this brain area relate to verbal intelligence is unknown. Here, we addressed this using histological analysis and cellular recordings of neurosurgically resected temporal cortex in combination with presurgical IQ scores. We find that subjects with higher general and verbal IQ scores have thicker left (but not right) temporal cortex (Brodmann area 21, BA21). The increased thickness is due to the selective increase in layers 2 and 3 thickness, accompanied by lower neuron densities, and larger dendrites and cell body size of pyramidal neurons in these layers. Furthermore, these neurons sustain faster action potential kinetics, which improves information processing. Our results indicate that verbal mental ability associates with selective adaptations of supragranular layers and their cellular micro-architecture and function in left, but not right temporal cortex.

Chronic activation of anti-oxidant pathways and iron accumulation in epileptogenic malformations.

AIMS: Oxidative stress is evident in resected epileptogenic brain tissue of patients with developmental brain malformations related to mammalian target of rapamycin activation: tuberous sclerosis complex (TSC) and focal cortical dysplasia type IIb (FCD IIb). Whether chronic activation of anti-oxidant pathways is beneficial or contributes to pathology is not clear. METHODS: We investigated oxidative stress markers, including haem oxygenase 1, ferritin and the inflammation associated microRNA-155 in surgically resected epileptogenic brain tissue of TSC (n = 10) and FCD IIb (n = 8) patients and in a TSC model (Tsc1GFAP-/- mice) using immunohistochemistry, in situ hybridization, real-time quantitative PCR and immunoblotting. Using human foetal astrocytes we performed an in vitro characterization of the anti-oxidant response to acute and chronic oxidative stress and evaluated overexpression of the disease-relevant pro-inflammatory microRNA-155. RESULTS: Resected TSC or FCD IIb tissue displayed higher expression of oxidative stress markers and microRNA-155. Tsc1GFAP-/- mice expressed more microRNA-155 and haem oxygenase 1 in the brain compared to wild-type, preceding the typical development of spontaneous seizures in these animals. In vitro, chronic microRNA-155 overexpression induced haem oxygenase 1, iron regulatory elements and increased susceptibility to oxidative stress. Overexpression of iron regulatory genes was also detected in patients with TSC, FCD IIb and Tsc1GFAP-/- mice. CONCLUSION: Our results demonstrate that early and sustained activation of anti-oxidant signalling and dysregulation of iron metabolism are a pathological hallmark of FCD IIb and TSC. Our findings suggest novel therapeutic strategies aimed at controlling the pathological link between both processes.

Third harmonic generation imaging for fast, label-free pathology of human brain tumors.

In brain tumor surgery, recognition of tumor boundaries is key. However, intraoperative assessment of tumor boundaries by the neurosurgeon is difficult. Therefore, there is an urgent need for tools that provide the neurosurgeon with pathological information during the operation. We show that third harmonic generation (THG) microscopy provides label-free, real-time images of histopathological quality; increased cellularity, nuclear pleomorphism, and rarefaction of neuropil in fresh, unstained human brain tissue could be clearly recognized. We further demonstrate THG images taken with a GRIN objective, as a step toward in situ THG microendoscopy of tumor boundaries. THG imaging is thus a promising tool for optical biopsies.

Immunohistochemical characterization of the out-of frame splice variants GFAP Delta164/Deltaexon 6 in focal lesions associated with chronic epilepsy.

GFAP Delta164/Deltaexon 6 are two out-of frame splice variants of GFAP. The aim of this study was to investigate the distribution of GFAP Delta164/Deltaexon 6 expressing cells, in focal lesions associated with chronic intractable epilepsy, in light of the increasing interest in the role of specific astrocyte subtypes in epilepsy. Immunocytochemical analysis, using an antibody against Delta164 and Deltaexon6 (GFAP+1), was performed in surgical specimens of patients with hippocampal sclerosis (HS), focal cortical dysplasia type IIB (FCD), cortical tubers of tuberous sclerosis complex (TSC), glioneuronal and glial tumors. Expression of GFAP+1 was also evaluated in developing and adult human control cortex and hippocampus. GFAP+1 immunoreactivity was undetectable in developing human brain. In control human hippocampus and cortex (from young controls) only occasional GFAP+1 positive cells were observed. In contrast, GFAP+1 immunoreactivity was consistently detected in the glial component of the epileptogenic lesions. Balloon cells in FCD and giant cells in TSC, only rarely express GFAP+1. GFAP+1 co-localized with GFAPalpha, but not with GFAPdelta. Co-localization with aquaporin 4 was observed around blood vessels. GFAP+1 immunoreactivity in epilepsy-associated pathologies reveals a specific subpopulation of astrocytes in regions of astrogliosis. Further studies on GFAP+1 positive astrocytes are important to understand whether the expression of this isoform may affect the cytoskeletal integrity and the shape and function of glial cells under pathological conditions. However, while the staining is increased in epilepsy-associated pathologies, GFAP+1 is expressed in a small percentage of astrocytes. Thus, the possible role of this subpopulation of astrocytes in epilepsy is likely minor, compared to astrocytes expressing other GFAP isoforms.

Tissue plasminogen activator and urokinase plasminogen activator in human epileptogenic pathologies.

A growing body of evidence demonstrates the involvement of plasminogen activators (PAs) in a number of physiologic and pathologic events in the CNS. Induction of both tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) has been observed in different experimental models of epilepsy and tPA has been implicated in the mechanisms underlying seizure activity. We investigated the expression and the cellular distribution of tPA and uPA in several epileptogenic pathologies, including hippocampal sclerosis (HS; n=6), and developmental glioneuronal lesions, such as focal cortical dysplasia (FCD, n=6), cortical tubers in patients with the tuberous sclerosis complex (TSC; n=6) and in gangliogliomas (GG; n=6), using immuno-cytochemical, western blot and real-time quantitative PCR analysis. TPA and uPA immunostaining showed increased expression within the epileptogenic lesions compared to control specimens in both glial and neuronal cells (hippocampal neurons in HS and dysplastic neurons in FCD, TSC and GG specimens). Confocal laser scanning microscopy confirmed expression of both proteins in astrocytes and microglia, as well as in microvascular endothelium. Immunoblot demonstrated also up-regulation of the uPA receptor (uPAR; P<0.05). Increased expression of tPA, uPA, uPAR and tissue PA inhibitor type mRNA levels was also detected by PCR analysis in different epileptogenic pathologies (P<0.05). Our data support the role of PA system components in different human focal epileptogenic pathologies, which may critically influence neuronal activity, inflammatory response, as well as contributing to the complex remodeling of the neuronal networks occurring in epileptogenic lesions.

Expression pattern of miR-146a, an inflammation-associated microRNA, in experimental and human temporal lobe epilepsy.

Increasing evidence supports the involvement of inflammatory and immune processes in temporal lobe epilepsy (TLE). MicroRNAs (miRNA) represent small regulatory RNA molecules that have been shown to act as negative regulators of gene expression controlling different biological processes, including immune-system homeostasis and function. We investigated the expression and cellular distribution of miRNA-146a (miR-146a) in a rat model of TLE as well as in human TLE. miR-146a analysis in rat hippocampus was performed by polymerase chain reaction and immunocytochemistry at 1 week and 3-4 months after induction of status epilepticus (SE). Prominent upregulation of miR-146a activation was evident at 1 week after SE and persisted in the chronic phase. The miR-146a expression was confirmed to be present in reactive astrocytes. In human TLE with hippocampal sclerosis, increased astroglial expression of miR-146a was observed mainly in regions where neuronal cell loss and reactive gliosis occurred. The increased and persistent expression of miR-146a in reactive astrocytes supports the possible involvement of miRNAs in the modulation of the astroglial inflammatory response occurring in TLE and provides a target for future studies aimed at developing strategies against pro-epileptogenic inflammatory signalling.

Expression and localization of voltage dependent potassium channel Kv4.2 in epilepsy associated focal lesions.

An increasing number of observations suggest an important role for voltage-gated potassium (Kv) channels in epilepsy. We studied the cell-specific distribution of Kv4.2, phosphorylated (p) Kv4.2 and the Kv4.2 interacting protein NCS-1 using immunocytochemistry in different epilepsy-associated focal lesions. In hippocampal sclerosis (HS), Kv4.2 and pKv4.2 immunoreactivity (IR) was reduced in the neuropil in regions with prominent neuronal cell loss. In both HS and malformations of cortical development (MCD), intense labeling was found in neuronal somata, but not in dendrites. Strong NCS-1 IR was observed in neurons in all lesion types. Western blot analysis demonstrated an increase of total Kv4.2 in all lesions and activation of the ERK pathway in HS and ganglioglioma. These findings indicate that Kv4.2 is expressed in both neuronal and glial cells and its regulation may involve potassium channel interacting proteins, alterations in the subcellular localization of the channel, as well as phosphorylation-mediated posttranslational modifications.

Gemcitabine uptake in glioblastoma multiforme: potential as a radiosensitizer.

Glioblastoma multiforme (GBM), the most frequent malignant brain tumor, has a poor prognosis, but is relatively sensitive to radiation. Both gemcitabine and its metabolite difluorodeoxyuridine (dFdU) are potent radiosensitizers. The aim of this phase 0 study was to investigate whether gemcitabine passes the blood-tumor barrier, and is phosphorylated in the tumor by deoxycytidine kinase (dCK) to gemcitabine nucleotides in order to enable radiosensitization, and whether it is deaminated by deoxycytidine deaminase (dCDA) to dFdU. Gemcitabine was administered at 500 or 1000 mg/m(2) just before surgery to 10 GBM patients, who were biopsied after 1-4 h. Plasma gemcitabine and dFdU levels varied between 0.9 and 9.2 microM and 24.9 and 72.6 microM, respectively. Tumor gemcitabine and dFdU levels varied from 60 to 3580 pmol/g tissue and from 29 to 72 nmol/g tissue, respectively. The gene expression of dCK (beta-actin ratio) varied between 0.44 and 2.56. The dCK and dCDA activities varied from 1.06 to 2.32 nmol/h/mg protein and from 1.51 to 5.50 nmol/h/mg protein, respectively. These enzyme levels were sufficient to enable gemcitabine phosphorylation, leading to 130-3083 pmol gemcitabine nucleotides/g tissue. These data demonstrate for the first time that gemcitabine passes the blood-tumor barrier in GBM patients. In tumor samples, both gemcitabine and dFdU concentrations are high enough to enable radiosensitization, which warrants clinical studies using gemcitabine in combination with radiation.

Radiosurgery of brain arteriovenous malformations in children.

OBJECTIVE: The authors describe their experience in treating 22 children with a single brain arteriovenous malformation (bAVM) using a dedicated LINAC stereotactic radiosurgery unit. METHODS: The findings of 22 consecutive patients < or = 18 years of age who underwent radiosurgery for a single bAVM and with at least 24 months of follow-up, or earlier proven obliteration,were reviewed. The median age at radiosurgery was 13.8 years,with a hemorrhagic presentation in 86%. Median bAVM-volume was 1.8 ml, with a median prescribed marginal dose of 19.0 Gy. RESULTS: The crude complete obliteration-rate was 68% (n = 15) after a median follow-up of 24 months. The actuarial obliteration- rate was 45 % after two years and 64 % after three years. Patients with a radiosurgery-based AVM score < or = 1 more frequently had an excellent outcome than patients with a bAVM score > 1 (71% vs. 20%, P = 0.12), as well as an increased obliteration rate (P = 0.03) One patient died from a bAVM-related hemorrhage 27 months after radiosurgery, representing a postradiosurgery hemorrhage rate of 1.3%/year for the complete followup interval. Overall outcome was good to excellent in 68% (n = 15). Radiation-induced changes on MR imaging were seen in 36% (n = 8) after a median interval of 12.5 months, resulting in deterioration of pre-existing neurological symptoms in one patient. CONCLUSIONS: Radiosurgery is a relatively effective, minimally invasive treatment for small bAVMs in children. The rebleeding rate is low, provided that known predilection places for bleeding had been endovascularly eliminated.Our overall results compare unfavourably to recent pediatric microsurgical series, although comparison between series remains imprecise. Nevertheless, when treatment is indicated in a child with a bAVM that is amenable to both microsurgery or radiosurgery, microsurgery should carefully be advocated over radiosurgery, because of its immediate risk reduction.

Mature astrocytes in the adult human neocortex express the early neuronal marker doublecortin.

Doublecortin (DCX) is a microtubule-associated protein expressed by migrating neuroblasts and is considered to be a reliable marker of neurogenesis. DCX has been used to study the relation between neurogenesis in adult human brain and neurological and neurodegenerative disease processes in the search for putative therapeutic strategies. Using autopsy and surgically resected tissue from a total of 60 patients, we present evidence that DCX is present in several cellular compartments of differentiated astrocytes in the adult human neocortex. One of these compartments consisted of peripheral processes forming punctate envelopes around mature neuronal cell bodies. Markers of glial activation, such as GFAP and HLA, were not associated with DCX immunoreactivity, however, the presence of cytoarchitectural alterations tended to correlate with reduced DCX staining of astrocytic somata. Interestingly, local Alzheimer pathology that showed no relation with cytoarchitectural abnormalities appeared to correlate negatively with the expression of DCX in the astrocytic somata. In combination with the literature our data support the view that DCX in the adult human neocortex may have a function in glia-to-neuron communication. Furthermore, our results indicate that in the adult human neocortex DCX is neither a reliable nor a selective marker of neurogenesis.

Complement activation in experimental and human temporal lobe epilepsy.

We investigated the involvement of the complement cascade during epileptogenesis in a rat model of temporal lobe epilepsy (TLE), and in the chronic epileptic phase in both experimental as well as human TLE. Previous rat gene expression analysis using microarrays indicated prominent activation of the classical complement pathway which peaked at 1 week after SE in CA3 and entorhinal cortex. Increased expression of C1q, C3 and C4 was confirmed in CA3 tissue using quantitative PCR at 1 day, 1 week and 3-4 months after status epilepticus (SE). Upregulation of C1q and C3d protein expression was confirmed mainly to be present in microglia and in a few hippocampal neurons. In human TLE with hippocampal sclerosis, astroglial, microglial and neuronal (5/8 cases) expression of C1q, C3c and C3d was observed particularly within regions where neuronal cell loss occurs. The membrane attack protein complex (C5b-C9) was predominantly detected in activated microglial cells. The persistence of complement activation could contribute to a sustained inflammatory response and could destabilize neuronal networks involved.

Serial analysis of gene expression in the hippocampus of patients with mesial temporal lobe epilepsy.

Hippocampal sclerosis constitutes the most frequent neuropathological finding in patients with medically intractable mesial temporal lobe epilepsy. Serial analysis of gene expression was used to get a global view of the gene profile in human hippocampus in control condition and in epileptic condition associated with hippocampal sclerosis. Libraries were generated from control hippocampus, obtained by rapid autopsy, and from hippocampal surgical specimens of patients with mesial temporal lobe epilepsy and the classical pattern of hippocampal sclerosis. More than 50,000 tags were analyzed (28,282, control hippocampus; 25,953, hippocampal sclerosis) resulting in 9206 (control hippocampus) and 9599 (hippocampal sclerosis) unique tags (genes), each representing a specific mRNA transcript. Comparison of the two libraries resulted in the identification of 143 transcripts that were differentially expressed. These genes belong to a variety of functional classes, including basic metabolism, transcription regulation, protein synthesis and degradation, signal transduction, structural proteins, regeneration and synaptic plasticity and genes of unknown identity of function. The database generated by this study provides an extensive inventory of genes expressed in human control hippocampus, identifies new high-abundant genes associated with altered hippocampal morphology in patients with mesial temporal lobe epilepsy and serves as a reference for future studies aimed at detecting hippocampal transcriptional responses under various pathological conditions.

Neurotrophin receptor immunoreactivity in the hippocampus of patients with mesial temporal lobe epilepsy.

Recent evidence supports a critical role of neurotrophins in the regulation of both neuronal survival and synaptic transmission during epileptogenesis. We have examined the immunohistochemical expression of high- (tyrosine kinase receptors, trk) and low-affinity (p75) neurotrophin receptors (NTRs) in the hippocampal specimens from 18 patients with chronic temporal lobe epilepsy [TLE; 14 patients with hippocampal sclerosis (HS) and four with focal lesions (tumours) not involving the hippocampus proper]. Nonepileptic autopsy brains (n = 6) and surgical specimens from tumour patients without epilepsy (n = 3) were used as controls. Immunoreactivity (IR) for the trk receptors (trkA, trkB, trkC) was detected in normal human brain within the pyramidal neurones of hippocampal cornus ammoni (CA) regions and in the dentate gyrus. There were no detectable differences in the neuronal trk IR patterns in the hippocampus between control and TLE cases with HS, except for a decrease in neuronal density in regions where cell death had occurred (CA1, CA3 and CA4). In contrast, a consistent increase in trkA IR was observed in reactive astrocytes in CA1 and dentate gyrus. The low-affinity p75 neurotrophin receptor (p75(NTR)) was expressed in low levels in postnatal normal hippocampus. In contrast, neuronal p75(NTR) IR was detected in 10/14 cases of HS in spared neurones within the CA and hilar regions of the hippocampus. Double labelling revealed that p75(NTR)-positive neurones also contain trk receptor IR. In six cases with prominent glial activation strong p75(NTR) IR was observed in microglial cells within the sclerotic hippocampus. The present results indicate that changes in NTR expression are still detectable in the hippocampus of patients with chronic TLE and involve both glial and neuronal cells. Reactive astrocytes were immunoreactive for trkA, whereas activated microglia cells were reactive for p75(NTR), suggesting different functions for specific NTRs in the development of reactive gliosis. Moreover, the increased expression of p75(NTR) in hippocampal neurones of TLE patients may critically influence the neuronal survival during the epileptogenic process.

The influence of brain tumor treatment on pathological delta activity in MEG.

The goal of the MEG study was to investigate the influence of tumor treatment on pathological delta activity (1-4 Hz). The treatment consisted of neurosurgery, and in some of the patients, additional radiotherapy. MEG and MR recordings were made both before and after the treatment in 17 patients. The signal power in the delta frequency band was determined for each recording. The malignant tumors were associated with large tumor volumes. Furthermore, both malignant tumors and tumor volume were associated with high signal powers in the delta band, indicating a correlation of delta power with the severity of the lesions. In all patients with high grade tumors, the delta power was lower after the treatment. The sources underlying the delta signals were estimated with an automatic single dipole analysis method. Estimated sources were projected onto MR scans. Preoperatively 14 clusters of equivalent sources describing focal activity were found in 12 out of 17 patients. Thirteen of these clusters were located near the tumor, and one cluster near an edema border. The locations near tumors are plausible and suggest that in general the source estimation was reliable. After the operation, 13 such clusters were found in 12 patients. Eleven clusters were located near the lesion border and one cluster near the edema border. Furthermore a cluster contralateral to the lesion in the other hemisphere indicated that brain lesions can affect the functioning of more distant brain areas than just the peritumoral brain tissue. Of the 12 patients who had preoperatively peritumoral clusters, 11 patients had postoperatively perilesional sources. In these cases the shift in source locations was in general considerably smaller than the dimension of the preoperative tumors. This finding indicates that similar areas generate the pre- and postoperative delta activity. Furthermore, focal delta sources were found in a case without tumor recurrence, and also in cases that most tumor tissue was removed. These findings suggest that the pathology underlying the slow waves is not the presence of the tumor bulk but the structural damage done by the tumors on the surrounding white/gray matter.

Single-fraction vs. fractionated linac-based stereotactic radiosurgery for vestibular schwannoma: a single-institution study.

PURPOSE: In this single-institution trial, we investigated whether fractionated stereotactic radiation therapy is superior to single-fraction linac-based radiosurgery with respect to treatment-related toxicity and local control in patients with vestibular schwannoma. METHODS AND MATERIALS: All 129 vestibular schwannoma patients treated between 1992 and June 2000 at our linac-based radiosurgery facility were analyzed with respect to treatment schedule. Dentate patients were prospectively selected for a fractionated schedule of 5 x 4 Gy and later on 5 x 5 Gy at the 80% isodose in 1 week with a relocatable stereotactic frame. Edentate patients were prospectively selected for a nonfractionated treatment of 1 x 10 Gy and later on 1 x 12.5 Gy at 80% isodose with an invasive stereotactic frame. Both MRI and CT scans were made in all 129 patients within 1 week before treatment. All patients were followed yearly with MRI and physical examination. RESULTS: A fractionated schedule was given to 80 patients and a single fraction to 49 patients. Mean follow-up time was 33 months (range: 12-107 months). There was no statistically significant difference between the single-fraction group and the fractionated group with respect to mean tumor diameter (2.6 vs. 2.5 cm) or mean follow-up time (both 33 months). Only mean age (63 years vs. 49 years) was statistically significantly different (p = 0.001). Outcome differences between the single-fraction treatment group and the fractionated treatment group with respect to 5-year local control probability (100% vs. 94%), 5-year facial nerve preservation probability (93% vs. 97%), and 5-year hearing preservation probability (75% vs. 61%) were not statistically significant. The difference in 5-year trigeminal nerve preservation (92% vs. 98%) reached statistical significance (p = 0.048). CONCLUSION: Linac-based single-fraction radiosurgery seems to be as good as linac-based fractionated stereotactic radiation therapy in vestibular schwannoma patients, except for a small difference in trigeminal nerve preservation rate in favor of a fractionated schedule.

Localization of fast MEG waves in patients with brain tumors and epilepsy.

It was investigated if single dipole analysis of spontaneous fast waves (>8 Hz) can be used to determine the location of the epileptic focus. Automatic dipole analysis was applied to MEG data of 25 patients with intracranial tumors and epilepsy. The frequency range of 8-50 Hz was divided into standard EEG bands. MEG results were overlaid on the MRI scans of the patients. Dipoles describing fast wave fields were located in the parietal/occipital cortex, and not at tumor border zones. In the cases that the dipoles were lateralized there was no clear preference to be located ipsi or contralateral to the tumor. However the generators of epileptic activity in these patients are thought to be located in the border areas of the tumors. Therefore it seems unlikely that the dipole locations describing fast waves are related to the epileptic zones in patients with brain tumors and epilepsy. A remarkable finding is that lateralized dipoles tend to be located in the right hemisphere and not in the left hemisphere. This appears to reflect an asymmetry of possibly normal background activity.

The localization of spontaneous brain activity: first results in patients with cerebral tumors.

OBJECTIVE: From EEG studies, it is known that structural brain lesions are accompanied by abnormal rhythmic electric activity. With the better spatial resolution of MEG, MEG dipole analysis can extend the knowledge based on EEG power spectra. This study presents the first results of a completely automatic analysis method applied to spontaneous MEG. METHODS: Spontaneous MEG data of 5 patients with cerebral brain tumors and 4 controls were collected using a whole-head MEG system. Signals were bandpass-filtered with cut-off frequencies according to standard EEG bands. A moving dipole model was fitted to samples with at least twice the average sample power. Dipoles explaining 90% or more of the magnetic variance were projected onto a matched MR scan. RESULTS: In controls, dipole distributions are symmetrical with respect to the mid-sagittal plane whereas distributions in patients often are asymmetrical to it. Dipoles describing gamma activity were located contralateral, and dipoles describing delta and theta activity were located ipsilateral to lesions. CONCLUSIONS: The automatic method gives plausible 3-dimensional information about generator foci of abnormal slow waves and other rhythms with respect to lesion foci and thereby adds physiological knowledge to that derived from EEG power spectra.

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.

[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.