Radiosurgery for cerebral cavernomas.

The role of stereotactic radiosurgery (SRS) in the management of cerebral cavernomas (CCMs) remains controversial. However, during the last decade the increasing knowledge on natural history and numerous publications from SRS centers using modern treatment protocols has been changing the initial resistance of the neurosurgical community. Unfortunately, the quality of publications on CCM SRS remains heterogeneous. Controversies arise from the lack of control groups, the different definition of hemorrhage, heterogeneous patient populations, and poor definition of treatment protocols. The key for proper interpretation of results is the understanding of the natural history of CCMs, which is varied both according to anatomical location and the presence or absence of previous hemorrhage. Hemispheric lesions appear to be more benign with lower annual bleed rate and risk of persisting disability, whereas those found in the thalamus, basal ganglia and brainstem typically have higher rebleed risk resulting in higher cumulative morbidity following subsequent hemorrhages. However, we are still unable at presentation to predict the future behavior of an individual lesion. In the present paper we critically review and analyze the modern SRS literature on CCMs. The expanding number of available data with current treatment protocols strongly supports the initial intuition that SRS is an effective treatment alternative for deep-seated CCMs with multiple hemorrhages reducing pretreatment annual rebleed rates from 32% pre-treatment to 1.5% within 2 years after treatment (N.=197). Moreover, it appears to stabilize lesions with no more than one bleed, and it is also effective for CCMs causing therapy resistant epilepsy especially if applied within 3 years after presentation. In modern SRS series the rate of persisting adverse radiation effects is low, resulting only in mild morbidity even in deep-seated lesions (4.16%, N.=376), and morbidity caused by post-treatment hemorrhages is also low (5.3%, N.=132). Admittedly, there is no high quality evidence to define the relative roles of microsurgery, SRS and wait-and-see policy in the management of detected CCMs at present. However, based on increasing positive experience, we recommend early SRS soon after presentation in neurologically intact or minimally disabled patients harboring deep-seated CCMs, because waiting for the cumulative morbidity of the natural history to justify an otherwise low-risk intervention does not serve the patient well.

Vagus nerve stimulation in children with intractable epilepsy: indications, complications and outcome.

PURPOSE: To analyze the indication, complications and outcome of vagus nerve stimulation in intractable childhood epilepsy. MATERIALS AND METHODS: We retrospectively reviewed the data of 69 children who had insertion of vagal nerve stimulator (VNS) between June 1995 and August 2006 for medically intractable epilepsy. Outcome was based on the Engel's classification. Statistical analysis of the data was also done to see if any of the parameters significantly influenced the outcome. RESULT: Thirty-eight patients (55.08 %) had a satisfactory outcome (Engel class I, II or III), and in 31 patients (44.92 %), there was no worthwhile improvement of seizures (Engel class IV). There was no statistical significance between the type of seizure and outcome (Fisher's exact test, p = 0.351). Statistical analysis also showed that the following parameters did not significantly influence the outcome (p > 0.05): age at insertion of VNS, age of first fit, duration between first fit and insertion of VNS and the length of follow-up. Complications included infection, lead fracture, fluid collection around the stimulator, neck pain and difficulty swallowing. CONCLUSION: Vagus nerve stimulation is a relatively safe and potentially effective treatment for children with medically intractable epilepsy.

Embolization of residual fistula following stereotactic radiosurgery in cerebral arteriovenous malformations.

Treatment of brain arteriovenous malformations (BAVMs) often requires a multitechnique approach. We present 2 cases of BAVM, in which initial stereotactic radiosurgery (SRS) was successful in obliterating a significant volume of the nidus. At follow-up angiography, residual fistulas were identified and selectively embolized; this procedure cured the lesions. Many series describe initial embolization to reduce the nidal volume followed by SRS to the remnant. The described cases highlight the value of primary radiosurgery followed by selective fistula embolization.

Stereotactic radiosurgery for brain arteriovenous malformations: quantitative MR assessment of nidal response at 1 year and angiographic factors predicting early obliteration.

INTRODUCTION: We investigated the role of magnetic resonance angiography (MRA) in the early follow-up of patients after stereotactic radiosurgery (STRS) for cerebral arteriovenous malformations (AVMs) and determined the influence of individual morphological factors of AVMs in early response to treatment. METHODS: A group of 40 patients (41 AVMs) consented to a dedicated 1.5-T MR protocol 12 months after receiving STRS for a brain AVM. In addition to standard spin echo sequences, 3-D contrast-enhanced sliding interleaved Ky MRA (CE-SLINKY) and dynamic time-resolved subtraction angiography (MR-DSA) were performed. Nidal volumes were calculated using CE-SLINKY data in patients with a persisting arteriovenous shunt. Planning angiographic data was investigated in all 40 patients. The following AVM factors were used in the statistical analysis to determine their role in nidus obliteration: (1) maximum linear dimension, (2) nidal volume, (3) AVM location (4) nidal morphology, (5) venous drainage, (6) "high-flow angiographic change", (7) prior embolization, and (8) dose reduction. RESULTS: Complete nidal obliteration was found in 9 patients, 26 showed greater than 50% nidal reduction and 6 had less than 50%. Two AVM factors, venous drainage and AVM location, were found to significantly correlate with rate of obliteration. CONCLUSION: We successfully demonstrated the use of MRA to quantitatively assess the response of AVMs to STRS. Two AVM factors, venous drainage and AVM location were found to correlate with rate of obliteration prior to the application of the Bonferroni correction, but if this more rigorous statistical test was applied then none of the factors was found to be significant.

The use of stereotactic radiosurgery in the management of meningiomas.

This is a systematic review of a consecutive series of 309 meningiomas treated with gamma knife stereotactic radiosurgery between 1994 and 2000. There was an extreme selection bias towards lesions unfavourable for surgery, determined by the patients referred for treatment: 70% of tumours involved the skull base, 47% specifically the cavernous sinus: 15% of patients had multiple meningiomatosis or type 2 neurofibromatosis. Tumour histology was the main determinant of growth control (p < 0.001), the 5-year actuarial control rates being 87% for typical meningiomas, 49% for atypical tumours and 0% for malignant lesions. Complications from radiosurgery were rare, occurring in 3% of tumours, and were most frequently trigeminal and eye movement disturbances treating cavernous sinus meningiomas. Given the problems inherent in managing these tumours, radiosurgery is a valuable strategy and adjuvant treatment for these meningiomas.

Brain arteriovenous malformations: measurement of nidal volume using a combination of static and dynamic magnetic resonance angiography techniques.

Arteriovenous malformations of the brain are complex vascular lesions that are an important cause of death and long-term disability. Currently, catheter angiography (CA) is the reference standard procedure for the diagnosis and follow-up of treated arteriovenous malformations (AVMs). This is an invasive procedure with potential risks. Magnetic resonance angiography (MRA) is commonly used in neurovascular imaging as a non-invasive alternative. Various MRA techniques have been used in the diagnosis and follow-up of AVMs but these have suffered from lack of temporal or spatial resolution. In this 60-patient study we describe the combination of two techniques: dynamic magnetic resonance digital subtraction angiography with a high temporal resolution, and a non-dynamic contrast-enhanced time-of-flight sequence with a high spatial resolution technique, in the assessment of AVM. The results showed an excellent correlation between MRA and CA measurement of both maximum linear dimension and AVM nidus volume.

Treatment options for von Hippel-Lindau's haemangioblastomatosis: the role of gamma knife stereotactic radiosurgery.

Haemangioblastomas secondary to von Hippel-Lindau (VHL) disease can be difficult to manage surgically, which has lead to an interest in the use of stereotactic radiosurgery. Retrospectively reviewed here are 30 tumours treated in 14 patients with a mean +/- SD follow-up of 34 +/- 24 months. During this time, three of the 14 patients (21%) died, two of generalized progressive disease. Before radiosurgery, the median time between interventions for cranial haemangioblastomas was 3 years (mean 3.9 +/- 5.0 years). After radiosurgery, the tendency for cranial disease progression was similar, 50% of patients developing further disease by 5 years. Local tumour control was achieved in the majority of cases and estimates of this are included. Radiosurgery is a useful palliative measure controlling the majority of haemangioblastomas, although its efficacy in these patients is limited by the tendency of further disease to develop or progress intracranially.

Gamma knife radiosurgery for cerebral arteriovenous malformations.

Since its introduction, gamma knife radiosurgery has become an important treatment modality for cerebral arteriovenous malformations. This paper is a brief overview of the technique used, of the clinical results achieved and of the experience gained in Sheffield.

Gamma knife stereotactic radiosurgery for unilateral acoustic neuromas.

OBJECTIVE: To evaluate the clinical results achievable using current techniques of gamma knife stereotactic radiosurgery to treat sporadic unilateral acoustic neuromas. METHODS: A retrospective review of 234 consecutive patients treated for unilateral acoustic neuromas between 1996 and 1999, with a mean (SD) follow up of 35 (16) months. Tumour control was assessed with serial radiological imaging and by the need for surgical intervention. Hearing preservation was assessed using Gardner-Robertson grades. Details of complications including cranial neuropathies and non-specific vestibulo-cochlear symptoms are included. RESULTS: A tumour control rate in excess of 92% was achieved, with only 3% of patients undergoing surgery after radiosurgery. Results were less good for larger tumours, but control rates of 75% were achieved for 35-45 mm diameter lesions. Of patients with discernible hearing, Gardner-Robertson grades were unchanged in 75%. Facial nerve function was adversely affected in 4.5%, but fewer than 1% of patients had persistent weakness. Trigeminal symptoms improved in 3%, but developed in 5% of patients, being persistent in less than 1.5%. Transient non-specific vestibulo-cochlear symptoms were reported by 13% of patients. CONCLUSIONS: Tumour control rates, while difficult to define, are comparable after radiosurgery with those experienced after surgery. The complications and morbidity after radiosurgery are far less frequent than those encountered after surgery. This, combined with its minimally invasive nature, may make radiosurgery increasingly the treatment of choice for small and medium sized acoustic neuromas.

Clinical experience with gamma knife stereotactic radiosurgery in the management of vestibular schwannomas secondary to type 2 neurofibromatosis.

OBJECTIVE: To evaluate the results of stereotactic radiosurgery treating vestibular schwannomas secondary to type 2 neurofibromatosis. METHODS: A retrospective review of 122 type 2 neurofibromatosis vestibular schwannomas consecutively treated in 96 patients. Tumour control was assessed by recourse to surgical intervention, by serial radiological imaging, and by the calculation of relative growth ratios in patients (n=29) habouring untreated contralateral tumours to act as internal controls. Hearing function was assessed with Gardner-Robertson grades and with averaged pure tone audiogram thresholds. Other complications are detailed. RESULTS: Applying current techniques, eight years after radiosurgery it was estimated that 20% of patients will have undergone surgery for their tumour, 50% will have radiologically controlled tumours, and in 30% there will be some variable concern about tumour control, but up to that time they will have been managed conservatively. Relative growth ratios one and two years after treatment indicate that radiosurgery confers a significant (p=0.01) advantage over the natural history of the disease. Analysis of these ratios beyond two years was precluded by the need to intervene and radiosurgically treat the contralateral control tumours in more than 50% of the cases. This growth control was achieved with 40% of patients retaining their Gardner-Robertson hearing grades three years after treatment, (40% having some deterioration in grade, 20% becoming deaf). Pure tone audiogram results suggest some progressive long term hearing loss, although interpretation of this is difficult. Facial and trigeminal neuropathy occurred in 5% and 2%. CONCLUSIONS: Radiosurgery is a valuable minimally invasive alternative treatment for these tumours. For most patients, it controls growth or defers the need for surgery, or both. There is a price in terms of hearing function, although this may compare favourably with the deafness associated with the natural history of the disease, and with surgery. In deciding on therapy, patients should be aware of this treatment option.

Radiosurgery for the control of glomus jugulare tumours.

OBJECTIVE: To ascertain the efficacy of stereotactic radiosurgery (gamma knife) for the control of glomus jugulare tumours. METHOD: Between March 1994 and December 1997 we treated eight patients of glomus jugulare tumour with radiosurgery. These patients have been followed for more than four years (range 52 to 97 months). The age of the patients ranged between 32-64 years (mean 53 years). The male: female ratio was 3:5. Three patients had previously undergone surgery and one had unsuccessful embolization. The dose applied to tumour margin ranged between 16-25 Gy (median 25 Gy). Patients were followed up with yearly MRI scans and where possible with cerebral angiography. RESULTS: All patients showed stabilisation of their symptoms following radiosurgery and six improved clinically. Five of these patients showed decrease in the size of lesion seen objectively on radiology, either slight to moderate decrease seen on the MRI scan or reduction in size and vascularity seen on cerebral angiography. The procedure is minimally invasive and none of the patients showed any adverse effect to radiosurgery. CONCLUSION: These results are encouraging but because of its naturally slow growth rate, up to 10 years of follow up will be necessary to establish a cure rate after radiosurgery for these lesions.

Changing utilization of stereotactic radiosurgery in the UK: the Sheffield experience.

Recognizing a change in our workload and variabilities in referral patterns, we reviewed our previous activity from 1994 to 2000 retrospectively and examined prospectively formal referrals to the Unit in 2001. Arteriovenous malformations still constitute 30% of referrals and treatments, although as a proportion of our workload, this has declined. Radiosurgery is increasingly being chosen as a first line treatment for small and moderate-sized acoustic neuromas, although referral rates vary widely, some neuroscience units referring all and others none of their acoustic neuromas at least for a radiosurgical opinion. About 100 meningiomas, mainly skull-base and/or recurrent tumours after previous surgery, are now treated per year. Compared with other units world-wide, very few pituitary adenomas and cerebral metastases are treated. The implications of this are discussed.

Malignancy in a vestibular schwannoma. Report of a case with central neurofibromatosis, treated by both stereotactic radiosurgery and surgical excision, with a review of the literature.

Malignant change in schwannoma is rare. Malignant change in a vestibular schwannoma (acoustic neuroma) is even more rare. This paper presents a case of rapidly growing vestibular schwannoma first treated by radiosurgery whose histopathology after surgical excision 42 months later showed malignant changes. Up to now, eight cases of malignancy in eighth nerve tumours have been reported, four of which, including the present case, had previously been treated with radiosurgery and four cases that had not received radiation. Thus, it would seem, the overall incidence is extremely low. Nevertheless, extreme vigilance and careful reporting continues to be necessary.

Surgery for epilepsy.

While medical treatment remains the first line of treatment for epilepsy, surgery provides effective long-term control in suitable patients. Detailed investigations are necessary to prove suitability and in order to choose the appropriate procedure. This article gives an outline of the investigative programme and the various operative approaches. Novel methods and those under investigation are also discussed.

Cerebral arteriovenous malformations: comparison of novel magnetic resonance angiographic techniques and conventional catheter angiography.

OBJECTIVE: To investigate the potential of novel magnetic resonance (MR) angiographic techniques for the assessment of cerebral arteriovenous malformations. METHODS: Forty patients who were about to undergo stereotactic radiosurgery were prospectively recruited. Three-dimensional, sliding-slab interleaved ky (SLINKY), time-of-flight acquisition was performed, as was a dynamic MR digital subtraction angiography (DSA) procedure in which single thick slices (6-10 cm) were obtained using a radiofrequency spoiled Fourier-acquired steady-state sequence (1 image/s). Sixty images were acquired, in two or three projections, during passage of a 6- to 10-ml bolus of gadolinium chelate. Subtraction and postprocessing were performed, and images were viewed in an inverted cine mode. SLINKY time-of-flight acquisition was repeated after the administration of gadolinium. Routine stereotactic conventional catheter angiography was performed after MR imaging. All images were assessed (in a blinded randomized manner) for Spetzler-Martin grading and determination of associated vascular pathological features. RESULTS: Forty-one arteriovenous malformations were assessed in 40 patients. Contrast-enhanced (CE) SLINKY MR angiography was the most consistent MR imaging technique, yielding a 95% correlation with the Spetzler-Martin classification defined by conventional catheter angiography; MR DSA exhibited 90% agreement, and SLINKY MR angiography exhibited 81% agreement. CE SLINKY MR angiography provided improved nidus delineation, compared with non-CE SLINKY MR angiography. Dynamic information from MR DSA significantly improved the observation of early-draining veins and associated aneurysms. CONCLUSION: CE SLINKY MR angiographic assessment of cerebral arteriovenous malformations offers significant advantages, compared with the use of non-CE SLINKY MR angiography, including improved nidus demonstration. MR DSA shows promise as a noninvasive method for dynamic angiography but is presently restricted by limitations in both temporal and spatial resolution.

Spontaneous obliteration of pial arteriovenous malformations: a review of 27 cases.

BACKGROUND AND PURPOSE: Brain arteriovenous malformations (AVMs) occur in approximately 0.14% of the population. The most common presentations are hemorrhage (50%) and seizures (25%). Although they are congenital abnormalities, their angioarchitecture may vary over time. A rare but well-recognized phenomenon of AVMs is that of spontaneous obliteration. It is not known what factors predispose to spontaneous obliteration. The purpose of our study was to determine whether spontaneous thrombosis of AVMs can be predicted by their angioarchitecture and whether there is any risk of recurrence once obliteration has occurred. METHODS: We retrospectively reviewed the angiographic and cross-sectional imaging data amassed over an 18-year period, including follow-up imaging studies and mail surveys of referring and family physicians. A control group was obtained from contemporaneous AVMs of a similar size. RESULTS: We identified 28 cases of spontaneous obliteration in a series of 2162 patients. The mean time between initial diagnostic angiography and angiographic obliteration was 10 months, during which time there was no intervention and no history of repeat hemorrhage; nor had hemorrhage recurred during the follow-up period (mean, 53 months). Most of the AVMs were deep (22/27) with only one draining vein (21/27) and few feeding arteries. In more than half the cases (15/27) drainage was exclusively into the superficial venous system. CONCLUSION: Spontaneous obliteration is rare (1.3%). Common features include hemorrhagic presentation and few arterial feeding vessels. Although we found no instance of repeat hemorrhage during the follow-up period, AVMs can recanalize, and follow-up is therefore recommended.

Slow hyperpolarization in cortical neurons: a possible mechanism behind vagus nerve simulation therapy for refractory epilepsy?

PURPOSE: Recent studies have shown that chronic, intermittent stimulation of the left vagus nerve (VNS) decreases the frequency, duration, and/or intensity of seizures in some patients with medically refractory focal seizures. Although VNS is being used in an increasing number of patients, the neuronal mechanism behind VNS therapy of refractory epileptic seizures is yet unclear. METHODS: In vivo intracellular recordings were used to study responses elicited by the VNS in pyramidal neurons of the parietal association cortex in anesthetized rats. RESULTS: Low-intensity trains of VNS, which activated predominantly myelinated fibers (100 microA, 30 Hz, 0.5 millisecond, 20 seconds), elicited a slow hyperpolarization (onset latency 17.4 +/- 2.0 seconds, amplitude -4. 7 +/- 0.6 mV, duration 35 +/- 3.2 seconds; n = 19). Increasing the intensity of VNS to recruit nonmyelinated vagal fibers (200 microA) led to an increase in the magnitude of the response in some neurons while failed to evoke a response in others. On increasing the stimulus intensity to 500 microA, only one in nine neurons exhibited a visible response. All recorded and visualised neurons were pyramidal cells in cortical layer V. CONCLUSIONS: Stimulus intensities that activate predominantly myelinated fibers (less than 200 microA) were most effective to induce slow vagal hyperpolarization. It is suggested that slow hyperpolarization may be one of the mechanisms that underlie the seizure-reducing effect of VNS, by means of reducing the excitability in neurons that would be involved in propagation of seizure activity. As the balance of activity in myelinated and nonmyelinated primary vagal afferents influenced the effect of VNS stimulation, it is likely that the effect of VNS is modulated as changes occur in the underlying vagal tone.

Stereotactic radiosurgery and the risk of haemorrhage from cavernous malformations.

Eighteen patients with cerebral cavernous malformations were treated with single dose of cobalt 60 source stereotactic radiosurgery. All had suffered at least one haemorrhage prior to treatment with six suffering 2, four suffering 3 and one suffering 4. Mean follow-up was 4.5 years. A total of 36 pretreatment haemorrhages occurred in 139 patient years. The first haemorrhage each patient suffered was taken as the start of observation and not included in the rehaemorrhage rate calculation. Three posttreatment haemorrhages occurred in 81 patient years of observation. The annual haemorrhage rate thus fell from 13% before to 3.7% after treatment. The odds ratio was thus 0.29 with a 95% confidence interval of (0.08-0.97), but this must be interpreted with caution because of the prereferral selection of this group of patients. Three patients developed complications of radiosurgery, two of them recovered fully.

Distortion in magnetic resonance images obtained for stereotactic localization. Case report.

The purpose of this paper was to note a potential source of error in magnetic resonance (MR) imaging. Magnetic resonance images were acquired for stereotactic planning for GKS of a vestibular schwannoma in a female patient. The images were acquired using three-dimensional sequence, which has been shown to produce minimal distortion effects. The images were transferred to the planning workstation, but the coronal images were rejected. By examination of the raw data and reconstruction of sagittal images through the localizer side plate, it was clearly seen that the image of the square localizer system was grossly distorted. The patient was returned to the MR imager for further studies and a metal clasp on her brassiere was identified as the cause of the distortion.