Gamma Knife Irradiation Research Articles

Acute embolization of ruptured brain arteriovenous malformations

BackgroundRuptured brain arteriovenous malformations (bAVMs) are at increased risk of re-hemorrhage but management has historically been conservative. This is because: (1) ruptured bAVMs have not been considered as catastrophic as...

Alveolar Soft Part Sarcoma: A Single-Center 26-Patient Case Series and Review of the Literature

Background. Alveolar soft part sarcoma (ASPS) is a rare tumor, and little information is available regarding its clinical features and appropriate treatments. Methods. A retrospective review of 26 consecutive ASPS patients (12 male, 14 female; mean age of 27 years) treated at our institution over 30 years (mean followup; 71 months) was performed. Results. The primary tumor developed in the lower extremity (12), trunk (8), and upper extremity (6), with an average size of 7.2 cm (range, 2–14 cm). The AJCC stage at presentation was IIA (7), III (3), and IV (16). Surgical excision was performed in 20 patients (R0 18, R1 plus radiotherapy 2) without local recurrence. Six patients (stage IIA 3/7, stage III 3/3) later developed metastases after an average period of 28.7 months. The median survival of the 26 patients was 90 months, with overall 5/10-year survival rates of 64%/48%. AJCC stage and tumor size were significant prognostic factors. Significant palliation and slowing of metastasis progression were achieved with gamma knife radiotherapy. Nine patients receiving chemotherapy showed no objective response. Conclusions. ASPS is indolent but has a high propensity for metastasis. Early diagnosis and complete excision of the small primary tumor are essential in the treatment of ASPS.

Pancytopenia Associated with Hypopituitarism in an Acromegaly Patient: A Case Report and a Review of the Literature

We present the case of a patient with acromegaly who had pancytopenia with hypopituitarism secondary to the excision of a pituitary macroadenoma and radiation therapy. A 28-year-old man presented with pancytopenia and serum electrolyte abnormalities. He was diagnosed with acromegaly and underwent surgery and gamma-knife radiotherapy for a pituitary macroadenoma at the age of 22 years. A recent brain magnetic reso nance imaging showed an empty sella, and the basal hormonal profile demonstrated deficiencies of pituitary hormones except thyrotropin. As presenting pancytopenia, his bone marrow biopsy showed hypocellular marrow. The total number of hemocytes increased after hydrocortisone replacement. Hypopituitarism was a possible cause of pan cytopenia, and glucocorticoids had crucial effects on converting pancytopenia to normal in this case. ( Endocrinol Metab 27:308313, 2012)

TU‐G‐214‐01: Imaging of Necrosis and PET Imaging

Purpose: Molecular targeted radiation protecting drugs can reduce the risk of injury to normal tissues in patients treated with radiotherapy. Inhibitors of enzyme GSK3β markedly attenuate radiation induced apoptosis in normal tissues but not in cancer. These drugs prevented radiation induced injury in brain, intestine, bone marrow and skin. We found that specific inhibitors of GSK3B prevent radiation induced apoptosis and necrosis without reducing cytotoxicity in cancer. Here we develop noninvasive imaging as a means to monitor radioprotection by GSK3 inhibitors for planned clinical trials. MRI imaging of necrosis and PET imaging of radiation‐induced apoptosis are needed to monitor the protective effects of these drugs in our planned clinical trials. Methods: The inhibitors of GSK3, SB415286 or lithium were administered to mice by IP injection prior to irradiation. Single‐treatment Gamma Knife doses of 15–60Gy were given to the 50% isodose volume (33.5mm3) in one mouse brain hemisphere. T2‐weighted, microMRI of the brain was performed weekly. Whole abdominal doses of 7–8Gy were used to treat intestine. F18‐labeled apoptosis radiotracer was manufactured in the radiochemistry laboratory and was injected by tail vein in mice at 24 hours after irradiation. MicroPET imaging was performed to monitor uptake of the apoptosis detector following irradiation. Brain necrosis was compared histologically with imaging following 15–60Gy and was first detected 3–7 weeks after irradiation. Results: To determine whether GSK‐3h inhibitors regulate cell survival and apoptosis in the subgranular zone of the hippocampus in comparison with lithium, we pretreated 1‐week‐old mice with a single dose of 0.6 mg/kg SB216763, 1.0 mg/kg SB415286, or 40 mg/kg lithium and treated them with a single dose of 7 Gy of cranial irradiation. Hippocampal sections were analyzed for apoptosis within the subgranular zone by TUNEL staining. Mice pretreated with SB216763 and SB415286 showed significantly less TUNEL‐positive neurons (<15 TPC) as compared with control. This protective effect of the GSK3 inhibitors was comparable to that of lithium. Similar results were obtained in a stereologic approach when TUNEL‐positive cells were counted in five tissue sections prepared throughout the hippocampus of treated mice at the various cutting deepness (<25 TPC for SB216763 pretreatment and <35 TPC for SB415286 and lithium pretreatment, as compared with <205 TPC for radiation alone). Prophylaxis with GSK‐3B inhibitors also improved cognitive function in irradiated mice. The apoptosis radiotracer has a short half life which is sufficient because apoptosis is transiently detected when tracer is injected at 24 hours after irradiation. Renal excretion of the radiotracer allows imaging of radiation induced apoptosis in intestinal crypts after abdominal irradiation. Radiation induced apoptosis in the brain and intestine occurred after 24 hours in a dose dependent manner with doses as low as 2Gy. GSK3 inhibition prevented radiation induced apoptosis and preserved organ function in irradiated mice. To study the radioprotective effects of GSK3 inhibitors in the brain necrosis model, cohorts of mice were administered either the GSK‐3D inhibitor SB415286 (prior to irradiation) or DMSO (control) and treated with a single 60‐Gy dose (50% isodose) of Gamma Knife radiation. Mice were imaged weekly, beginning 5 weeks post‐irradiation. A region of hyperintensity associated with radiation necrosis was visible in the irradiated control mouse, but was much less evident in the inhibitor‐treated, irradiated mouse. For each mouse, regions of interest were drawn around the entire brain in 5 contiguous image slices, chosen to include the irradiated region. MRI detected brain necrosis in mice treated with Gamma Knife. To determine whether GSK‐3b inhibition protects intestinal crypt cells from radiation‐induced apoptosis, we studied abdominal—irradiated mice that developed radiation‐ induced apoptosis in small intestine cells results in animal death. To determine whether GSK‐3b inhibition could affect radiation‐induced apoptosis in intestinal crypt cells, we treated 10‐week‐old mice with 1.0 mg/kg of SB415286 followed by a single dose of 4 or 8 Gy of radiation. At 4 h and 12 h later, the proximal jejunum was analyzed by TUNEL staining. At 12 h after irradiation, mice pretreated with SB415286 showed significantly fewer TPC per crypt at both 4 Gy (1.5 and 1.7 TPC, respectively) and 8 Gy (2.7 and 2.4 TPC, respectively) as compared with radiation alone (5 and 6.7 TPC for 4 and 8 Gy, respectively). Similar results were observed at the earlier time after irradiation. PET imaging of apoptosis showed uptake in irradiated intestine which was attenuated by SB216763. Conclusion: Radioprotection of the brain and intestine by GSK3β inhibitors can be monitored by MRI and PET imaging. Radiotracers with a high sensitivity for apoptosis are needed to monitor apoptosis. These imaging modalities are needed for the planned clinical trials of GSK3 inhibitors as radioprotectors.

Dosimetric and Clinical Analysis of Spatial Distribution of the Radiation Dose in Gamma Knife Radiosurgery for Vestibular Schwannoma

We investigated variations in the distribution of radiation dose inside (dose inhomogeneity) and outside (dose falloff) the target volume during Gamma Knife (GK) irradiation of vestibular schwannoma (VS). We analyzed the relationship between some parameters of dose distribution and the clinical and radiological outcome of patients. Data from dose plans of 203 patients treated for a vestibular schwannoma by GK C using same prescription dose (12 Gy at the 50% isodose) were collected. Four different dosimetric indexes were defined and calculated retrospectively in all plannings on the basis of dose-volume histograms: Paddick conformity index (PI), gradient index (GI), homogeneity index (HI), and unit isocenter (UI). The different measures related to distribution of the radiation dose were compared with hearing and tumor outcome of 203 patients with clinical and radiological follow-up of minimum 2 years. Mean, median, SD, and ranges of the four indexes of dose distribution analyzed were calculated; large variations were found between dose plans. We found a high correlation between the target volume and PI, GI, and UI. No significant association was found between the indexes of dose distribution calculated in this study and tumor control, tumor volume shrinkage, hearing worsening, loss of functional hearing, or complete hearing loss at last follow-up. Parameters of distribution of the radiation dose during GK radiosurgery for VS can be highly variable between dose plans. The tumor and hearing outcome of patients treated is not significantly related to these global indexes of dose distribution inside and around target volume. In GK radiosurgery for VS, the outcome seems more to be influenced by local radiation dose delivered to specific structures or volumes than by global dose gradients.

Clinical Effects of Accelerator Linear Plus Gamma Knife Radiotherapy Combined with Concurrent DP Regimen Chemotherapy for Locally Advanced Non-small Cell Lung Cancer

Objective To investigate the short-term effects and adverse reactions of accelerator linear and gamma knife radiotherapy combined with concurrent DP chemotherapy for locally advanced non-small cell lung cancer(NSCLC).Methods Ninety six patients with locally advanced NSCLC were randomly assigned to three treatment arms.In group A,patients received accelerator linear and gamma knife radiotherapy combined with concurrent 4 cycles of DP chemotherapy.The treatment plans were accelerator linear using 6MV x-rays by 50Gy/25F,and then gamma knife radiotherapy by 20Gy/4F,once every other day.In group B,patients received accelerator linear radiotherapy by(60～66)Gy/(30～33)F with concurrent 4 cycles of DP chemotherapy.In group C,patients received accelerator linear radiotherapy using 6MV x-rays by(60～66)Gy/(30～33)F after 2 cycles of DP chemotherapy,and then received another 2 cycles of DP chemotherapy.Results Ninety patients finished the treatment.The overall response rates of the three groups were 87.1%,86.7% and 62.1%,respectively(PAB=1.000,PAC=0.025,PBC=0.030).The overall 1-year survival rates of the three groups were 77.4%,73.3% and 72.4%,respectively(PAB=0.711,PAC=0.655,PBC=0.937).The adverse reactions were radiation pneumonitis,radiation esophagitis,gastrointestinal effects and myelosuppression.The incidence rates of radiation pneumonitis more than gradel were 32.3%,60.0% and 20.7%,respectively(PAB=0.030,PAC=0.311,PBC=0.002).The incidence rates of myelosuppression over gradel were 61.3%,66.7% and 31.0%,respectively(PAB=0.662,PAC=0.019,PBC=0.006).Conclusion The combination of accelerator linear plus gamma knife radiotherapy with concurrent DP chemotherapy can improve the short-term effects in locally advanced NSCLC patients with acceptable toxicities although the long-term effects and toxicities need to be further researched.

Clinical outcome of gamma knife (GK) radiotherapy for central nervous system (CNS) metastases from renal cell carcinoma (RCC).

e15071 Background: Current treatment modalities for RCC CNS metastases include resection, GK and whole-brain radiotherapy. Existing series describing treatment outcomes include a mix of tumor types, and thus provide little insight into CNS metastasis response by tumor type. Although RCC has historically been considered radioresistant, GK is increasingly being applied to RCC CNS metastases. Methods: RCC pts with brain metastases treated with GK between 1996 and 2010 were retrospectively identified. Pt, GK and systemic therapy characteristics were recorded. Pts were followed radiographically at 30 days post GK and every 3-6 months thereafter with MRI scans. Local failure was defined as treated tumor progression after GK and distant failure was defined as new CNS metastases not in the GK field. Results: One hundred sixty-six patients were identified: 75% male, median age 60, 55% performance status 0, 21% received systemic therapy within 30 days of GK and 97% clear cell histology. Two hundred thirty-three GK procedures were performed on a total of 487 CNS lesions, most commonly in the frontal lobe (32%), parietal lobe (17%), cerebellum (12%), occipital lobe (11%) and temporal lobe (9%). The median interval from diagnosis of RCC to first GK was 20 months (range, 0.1-310). The majority of pts (65%) received a GK dose of 24 Gy with a mean of 1.8 targets per GK procedure. 76% of pts received 1 GK and 24% received multiple GK procedures. Considering all GK procedures, local control was 87%, with an additional 38% of patients having distant CNS failure. The median time to local or distant failure was 9.9 months (range, 5.9-12.9). Local control and failure-free interval of a second GK procedure was not different from the first GK procedure (p=.31, sign test). Potential predictors of CNS failure were examined, and only age >60 (p=.07) and number of targets > 2 (p=.09) approached significance. Prognostic variables, GK treatment characteristics or systemic targeted therapy within 30 days of GK did not predict for subsequent CNS relapse. Conclusions: GK is a common treatment modality for RCC CNS metastases, providing excellent local control and freedom from CNS relapse for several months.

Endovascular Treatment of Intracranial Ruptured Aneurysms Associated with Arteriovenous Malformations: A Clinical Analysis of 14 Hemorrhagic Cases

This study investigated and summarized endovascular therapeutic strategies for intracranial ruptured aneurysms associated with arteriovenous malformations (AVMs). Between June 2005 and June 2009, we identified 16 aneurysms in 14 hemorrhagic cases of intracranial AVM using digital subtraction angiography (DSA). Of the 16 aneurysms, 14 were ruptured and two were unruptured. Aneurysms were classified as types I to IV, and were treated. Aneurysm treatment was followed by AVM treatment via various therapies, including embolization, gamma knife radiotherapy, or follow-up and observation to reduce the risk of aneurysm rupture or intracranial hemorrhage. Over a follow-up period ranging from six months to one year, none of the patients had aneurysm ruptures or intracranial hemorrhage. Most (13/14) patients had a Glasgow Outcome Scale (GOS) score of 5, and one patient had a score of 4. Sixteen aneurysms were treated successfully, as confirmed by DSA examination, and no AVMs re-grew. Clinical therapeutic strategies for intracranial ruptured aneurysms associated with AVMs should include aneurysm treatment first to reduce the risk of rupture and intracranial hemorrhage, eventually leading to a better prognosis.

Association of high metabolic activity measured by positron emission tomography imaging with poor prognosis of choroidal melanoma

AimsTo evaluate the prognostic value of positron emission tomography (PET) imaging in patients with choroidal melanoma.MethodsWe undertook a retrospective review of 40 consecutive patients with choroidal melanoma who underwent pretreatment...

Treatment Strategy Based on Multimodal Management Outcome of Cavernous Sinus Dural Arteriovenous Fistula (CSDAVF)

PurposeAngiographic finding including venous drainage pattern should be correlated to the presenting symptom pattern (SxP) in CSDAVF. We present outcome of CSDAVF management and suggest a strategy according to SxP and type of treatment based on our experience.Materials and MethodsWe evaluated SxP, angiographic type (proliferative, restrictive or late restrictive), mode of treatment (embolization, Gamma Knife Radiation (GKR) or conservative management), mode of embolization (transarterial or transvenous), and final clinical status (cure, improvement, aggravation or no change). Ninety consecutive patients were included from a prospective database. The mean follow-up was 17 months. We compared the outcomes according to SxP, angiographic type, mode of treatment, and embolization using the chi-square or Fisher's exact test.ResultsNinety patients with 34 proliferative, 40 restrictive, and 16 late restrictive types of CSDAVF were treated by embolization (n = 63), GKR (n = 7), and conservative management (n = 20). Cure or improvement was 91% after embolization, 88% after conservative management, and 72% after GKR. Following embolization, 100% of 24 proliferative types, 87% of 30 restrictive types, and 90% of 10 late restrictive types were cured or improved. Cure or improvement after transvenous embolization was 98% (43/44) compared with 88% (15/17) after transarterial embolization (p = 0.003).ConclusionVarious factors of SxP, angiographic type, and mode of treatment should be considered in order to obtain a more favorable outcome for patients with CSDAVF. Embolization via venous approach tended to result in a more complete cure than that via arterial approach.

Endovascular Treatment of Aneurysms Arising from the Basilar Artery Trunk and Branches

This study reports our experience with the endovascular treatment of basilar artery (BA) trunk and branch aneurysms. Subjects included 16 patients with BA trunk and branch aneurysms who underwent endovascular treatment in our hospital from October 2000 to October 2009, including four patients with associated arteriovenous malformation (AVM), two with associated moyamoya disease, one with multiple aneurysms at adjacent sites, and one with a distant aneurysm. Endovascular coil embolization, together with stent or balloon assistance when necessary, or while occluding the parent artery was performed. Associated diseases were managed intraoperatively or in the second stage, or treated with gamma knife radiotherapy, or followed up. Two patients with unsuccessful embolization died of re-rupture at the fourth month and fifth month follow-up. The remaining 14 patients reported good outcomes and experienced no re-rupture of either the aneurysm or associated disease. Angiographic follow-ups were conducted for the 14 patients for six to 12 months. Digital subtraction angiography (DSA) examination at the last follow-up showed no recurrence of the BA trunk and branch aneurysms. Together, BA trunk and branch aneurysms should be actively managed via endovascular techniques to prevent serious consequences due to aneurysm rupture and bleeding. Favorable outcomes can be obtained by the proper selection of endovascular treatment regimens.

Is it possible to avoid hypopituitarism after irradiation of pituitary adenomas by the Leksell gamma knife?

Radiation therapy is one of the treatment options for pituitary adenomas. The most common side effect associated with Leksell gamma knife (LGK) irradiation is the development of hypopituitarism. The aim of this study was to verify that hypopituitarism does not develop if the maximum mean dose to pituitary is kept under 15 Gy and to evaluate the influence of maximum distal infundibulum dose on the development of hypopituitarism. We followed the incidence of hypopituitarism in 85 patients irradiated with LGK in 1993-2003. The patients were divided in two subgroups: the first subgroup followed prospectively (45 patients), irradiated with a mean dose to pituitary <15 Gy; the second subgroup followed retrospectively 1993-2001 and prospectively 2001-2009 (40 patients), irradiated with a mean dose to pituitary >15 Gy. Serum TSH, free thyroxine, testosterone or 17β-oestradiol, IGF1, prolactin and cortisol levels were evaluated before and every 6 months after LGK irradiation. Hypopituitarism after LGK irradiation developed only in 1 out of 45 (2.2%) patients irradiated with a mean dose to pituitary <15 Gy, in contrast to 72.5% patients irradiated with a mean dose to pituitary >15 Gy. The radiation dose to the distal infundibulum was found as an independent factor of hypopituitarism with calculated maximum safe dose of 17 Gy. Keeping the mean radiation dose to pituitary under 15 Gy and the dose to the distal infundibulum under 17 Gy prevents the development of hypopituitarism following LGK irradiation.

Outcomes of Patients with Resected Metastatic Brain Lesions Treated with Gamma Knife or Whole Brain Irradiation

Outcomes of Patients with Resected Metastatic Brain Lesions Treated with Gamma Knife or Whole Brain Irradiation

Gamma knife irradiation - induced histopathological changes in the trigeminal nerves of Rhesus monkeys

Objective The authors sought to observe histopathological changes in the trigeminal nerve(TN)after Gamma knife treatment in rhesus monkeys and to investigate the radiobiological mechanism of Gamma knife treatment for primary trigeminal neuralgia. The nerve length dose effect of irradiation was discussed. Method One of five rhesus monkeys randomly served as control and the other four monkeys were randomly administered a target dose of 60,70,80, and 100 Gy respectively. The size of the collimator was 4 mm and the target point was the TN root. In each experimental monkey, one side was exposed to single - target point irradiation and the contralateral side to two - target point irradiation. After 6 months, the TN root was examined by light microscopy, transmission electron microscopy, and immunohistochemistry.Results At the same dose of radiation, the damage to the nervous tissue by single - target point irradiation was identical to that caused by two - target point irradiation. In the trigeminal nerve tissues of the monkeys irradiated with 60 and 70 Gy,there was scant nerve demyelination and degeneration, fragmentation, or loss of axons. In the trigeminal nerve tissue of the monkey irradiated with 80 Gy, the nervous tissue showed a disordered structure. In the trigeminal nerve tissue of the monkey irradiated with 100 Gy, there were severe derangement in the structure of the nervous tissue and extensive demyelination, fragmentation, and loss of axons. Conclusions The target doses of 60 and 70 Gy have very little impact on the structure of the TN. Irradiation at 80 Gy can cause partial degeneration and loss of axons and demyelination. A 100 Gy dose can cause some necrosis of neurons. Comparing the single - target irradiation with the two - target point irradiation,the extent of damage to the nervous tissue is identical and no difference in the nerve length dose effect was found. Key words: Gamma knife; Macaque; Trigeminal neuralgia; Pathology; Stereotactic radiosurgery

Gamma Knife irradiation–induced histopathological changes in the trigeminal nerves of rhesus monkeys

The authors' goal was to observe histopathological changes in the trigeminal nerve after Gamma Knife surgery (GKS) in rhesus monkeys, and to investigate the radiobiological mechanism of GKS for primary trigeminal neuralgia. The nerve length-dosage effect of irradiation is also discussed. One of 5 rhesus monkeys randomly served as a control, and the other 4 monkeys were randomly administered a target radiation dose of 60, 70, 80, or 100 Gy (a different dose in each animal). The size of the collimator was 4 mm, and the target point was the trigeminal nerve root. In each experimental monkey, one side was exposed to single-target-point irradiation, and the contralateral side was exposed to double-target-point irradiation. After 6 months, the trigeminal nerve root was examined using light microscopy, transmission electron microscopy, and immunohistochemistry. At each radiation dose, the damage to the nerve tissue by single-target-point irradiation was identical to that caused by double-target-point irradiation. In the trigeminal nerve tissues of the monkeys irradiated with 60 and 70 Gy, there was limited nerve demyelination and degeneration, fragmentation, or loss of axons. In the trigeminal nerve tissue of the monkey irradiated with 80 Gy, the nerve tissue showed a disordered structure. In the trigeminal nerve tissue of the monkey irradiated with 100 Gy, there was severe derangement in the structure of the nerve tissue, and extensive demyelination, fragmentation, and loss of axons. The target doses of 60 and 70 Gy have very little impact on the structure of the trigeminal nerve. Irradiation at 80 Gy can cause partial degeneration and loss of axons and demyelination. A 100-Gy dose can cause some necrosis of neurons. Comparing the single-target-point with the double-target-point irradiation, the extent of damage to the nerve tissue is identical, and no difference in the nerve length-dosage effect was found.

Re: Evaluation of cost effectiveness for conservative and active management strategies for acoustic neuroma

Objective: To determine whether economic costs associated with a conservative management strategy for unilateral acoustic neuroma offer an economic advantage over active management options. Design: Cost and sensitivity analysis on a prospective cohort. Setting: Single centre study within a tertiary referral centre in Toronto, Canada. Participants: 72 patients (32 males, 40 females) aged 36 to 78 years with unilateral acoustic neuroma were assigned initially to a conservative management strategy. Entry criteria were small tumour size (less than 15mm in the cerebellopontine angle), patient preference and/or significant co-morbidity. Interventions: MRI scanning was performed every 6 months for the first year, annually subsequently and then every 2-3 years as required. Clinical review occurred every 6 months. Failure of conservative management led to active treatment. Main outcome measures: Cost analysis was performed to determine the mean total cost per patient for continued conservative management over the follow up period compared to the mean upfront total cost per patient undergoing active intervention. Results: Cost analysis within the Canadian health care system determined the mean total cost per patient for microsurgical removal at CAD$22,402 (£12,545; 14,561€), for gamma knife radiotherapy at CAD$27659 (£15,489; 17,978€), for LINAC radiotherapy at CAD$9,003(£5,041; 5,852€) and for conservative management at CAD$9,651 (£5,405;6,273€) over the follow-up timeframe. Conclusion: An economic advantage can be demonstrated for the conservative management of acoustic neuromas compared to microsurgical removal and gamma knife radiotherapy on the proviso that no increase in active treatment complications arose from continued tumour growth during the period of observation.

Gamma knife irradiation operates differentially on the neuronal subpopulations of the rat basal ganglia

Gamma knife irradiation operates differentially on the neuronal subpopulations of the rat basal ganglia

A porcine model of hydrocephalus induced by gamma knife irradiation

Background The Leksell Gamma Knife® has been used for several decades as a relatively non-invasive, highly effective and precise therapeutic tool for brain disorders ranging from tumors to vascular malformations. It has a very benign side effect profile. To date many animal hydrocephalus models have been surgically or chemically invasive. Our exploratory model uses gamma knife to induce a lesion with the aim of increasing CSF outflow resistance at the cerebral aqueduct.

Evaluation of cost effectiveness for conservative and active management strategies for acoustic neuroma

To determine whether economic costs associated with a conservative management strategy for unilateral acoustic neuroma offer an economic advantage over active management options. Cost and sensitivity analysis on a prospective cohort. Single centre study within a tertiary referral centre in Toronto, Canada. 72 patients (32 males, 40 females) aged 36 to 78 years with unilateral acoustic neuroma were assigned initially to a conservative management strategy. Entry criteria were small tumour size (less than 15 mm in the cerebellopontine angle), patient preference and/or significant co-morbidity. MRI scanning was performed every 6 months for the first year, annually subsequently and then every 2-3 years as required. Clinical review occurred every 6 months. Failure of conservative management led to active treatment. Cost analysis was performed to determine the mean total cost per patient for continued conservative management over the follow up period compared to the mean upfront total cost per patient undergoing active intervention. Cost analysis within the Canadian health care system determined the mean total cost per patient for microsurgical removal at CAD$22,402 (12,545 pounds; 14,561 euros), for gamma knife radiotherapy at CAD$27659 (15,489 pounds; 17,978 euros), for LINAC radiotherapy at CAD$9,003(5,041 pounds; 5,852 euros) and for conservative management at CAD$9,651 (5,405 pounds;6,273 euros) over the follow-up timeframe. An economic advantage can be demonstrated for the conservative management of acoustic neuromas compared to microsurgical removal and gamma knife radiotherapy on the proviso that no increase in active treatment complications arose from continued tumour growth during the period of observation.

Clinical Course and Prognosis of Trochlear Nerve Schwannomas

To delineate the disease course and prognosis of patients with mass lesions of the fourth nerve presumed to be schwannomas. Nonrandomized retrospective case series. Thirty-seven consecutive cases of presumed trochlear nerve schwannoma from 9 tertiary university neuro-ophthalmology centers. Cases were collected, and their clinical characteristics on presentation and follow-up are described. Inclusion criteria were brain magnetic resonance imaging (MRI) with a lesion suggestive of a schwannoma along the course of the fourth nerve. Exclusion criteria were other causes of fourth nerve palsy, such as congenital, traumatic or microvascular; normal (or lack of) initial brain MRI; lack of adequate clinical information; and disappearance of the lesion on subsequent follow-up brain MRI. Demographics of patients, presence of neurofibromatosis, symptoms on presentation, vertical deviation, lesion size (on presentation and follow-up), length of follow-up, and outcomes of treatment for lesions or diplopia. Seven patients were excluded and of the 30 patients included in our series, patients were predominantly male (77%) with a mean age of 51 years (range 9-102 years). In contrast with prior case reports, almost all of our cases had a fourth nerve palsy on presentation (29/30), often isolated. Mean follow-up was 3.1 years (range 0.2 months to 11.1 years). There was no significant difference between initial and follow-up lesion size (4.4 vs. 5 mm) for patients who did not receive treatment of lesions (P = 0.36). Only 3 patients underwent neurosurgical resection and an additional patient received gamma-knife radiotherapy. The majority of patients (24/30) did not pursue strabismus surgery for vertical diplopia. Patients with isolated fourth nerve palsy and small lesions of the fourth nerve have a good prognosis and should be followed with serial MRI scans without neurosurgical intervention unless they develop signs of brain stem compression. Most patients with diplopia and benign fourth nerve lesions typical of trochlear nerve schwannoma can adapt with either prism spectacles or no treatment at all, although strabismus surgery can be successful.