Inverse treatment planning for spinal robotic radiosurgery: an international multi-institutional benchmark trial.

Stereotactic radiosurgery (SRS) is the accurate, conformal delivery of high-dose radiation to well-defined targets while minimizing normal structure doses via steep dose gradients. While inverse treatment planning (ITP) with computerized optimization algorithms are routine, many aspects of the planning process remain user-dependent. We performed an international, multi-institutional benchmark trial to study planning variability and to analyze preferable ITP practice for spinal robotic radiosurgery. 10 SRS treatment plans were generated for a complex-shaped spinal metastasis with 21 Gy in 3 fractions and tight constraints for spinal cord (V14Gy < 2 cc, V18Gy < 0.1 cc) and target (coverage > 95%). The resulting plans were rated on a scale from 1 to 4 (excellent-poor) in five categories (constraint compliance, optimization goals, low-dose regions, ITP complexity, and clinical acceptability) by a blinded review panel. Additionally, the plans were mathemati-cally rated based on plan indices (critical structure and target doses, conformity, monitor units, normal tissue complication probability, and treatment time) and compared to the human rankings. The treatment plans and the reviewers' rankings varied substantially among the participating centers. The average mean overall rank was 2.4 (1.2-4.0) and 8/10 plans were rated excellent in at least one category by at least one reviewer. The mathematical rankings agreed with the mean overall human rankings in 9/10 cases pointing toward the possibility for sole mathematical plan quality comparison. The final rankings revealed that a plan with a well-balanced trade-off among all planning objectives was preferred for treatment by most par-ticipants, reviewers, and the mathematical ranking system. Furthermore, this plan was generated with simple planning techniques. Our multi-institutional planning study found wide variability in ITP approaches for spinal robotic radiosurgery. The participants', reviewers', and mathematical match on preferable treatment plans and ITP techniques indicate that agreement on treatment planning and plan quality can be reached for spinal robotic radiosurgery.

Impact of Cochlear Dose on Hearing Preservation Following Stereotactic Radiosurgery in Treatment of Vestibular Schwannomas: A Multi-Center Study.

OBJECTIVE: Stereotactic radiosurgery (SRS) is a well-established treatment for vestibular schwannomas (VS). Hearing loss remains a main morbidity of VS and its treatments, including SRS. The effects of radiation parameters of SRS on hearing remain unknown. The goal of this study is to determine the effect of tumor volume, patient demographics, pretreatment hearing status, cochlear radiation dose, total tumor radiation dose, fractionation, and other radiotherapy parameters on hearing deterioration. METHODS: Multicenter retrospective analysis of 611 patients who underwent SRS for VS from 1990-2020 and had pre- and post-treatment audiograms. RESULTS: Pure tone averages (PTAs) increased and word recognition scores (WRSs) decreased in treated ears at 12-60 months while remaining stable in untreated ears. Higher baseline PTA, higher tumor radiation dose, higher maximum cochlear dose, and usage of single fraction resulted in higher post radiation PTA; WRS was only predicted by baseline WRS and age. Higher baseline PTA, single fraction treatment, higher tumor radiation dose, and higher maximum cochlear dose resulted in a faster deterioration in PTA. Below a maximum cochlear dose of 3 Gy, there were no statistically significant changes in PTA or WRS. CONCLUSIONS: Decline of hearing at one year in VS patients after SRS is directly related to maximum cochlear dose, single versus 3-fraction treatment, total tumor radiation dose, and baseline hearing level. The maximum safe cochlear dose for hearingtbrowd preservation at one year is 3 Gy, and the use of 3 fractions instead of one fraction was better at preserving hearing.

The gelastic seizures-hypothalamic hamartoma syndrome: facts, hypotheses, and perspectives.

Hypothalamic hamartoma (HH) can be associated with a wide spectrum of epileptic conditions, ranging from a mild form with seizures characterized by urge to laugh and no cognitive involvement up to a catastrophic encephalopathy with early onset gelastic seizures (GS), precocious puberty, and mental retardation. Moreover, a refractory, either focal or generalized, epilepsy develops during the clinical course in nearly all the cases. Neurophysiologic and neuroimaging studies have demonstrated that HH itself generates GS and starts a process of secondary epileptogenesis responsible for refractory focal or generalized epilepsy. The intrinsic epileptogenicity of HH may be explained by the neurophysiological properties of small GABAergic, spontaneously firing HH neurons. Surgical ablation of HH can reverse epilepsy and encephalopathy. Gamma-knife radiosurgery and image-guided robotic radiosurgery seem to be useful and safe approaches for treatment, in particular of small HH. Here, we review this topic, based on literature reports and our personal observations. In addition, we discuss pathogenetic hypotheses and suggest new approaches to this intriguing issue.

Efficacy and toxicity of CyberKnife re-irradiation and "dose dense" temozolomide for recurrent gliomas.

BACKGROUND: Stereotactic radiosurgery (SRS) can be a useful adjunct to the treatment of recurrent glioblastoma multiforme (GBM). Its combination with chemotherapy is attractive for the possible radiosensitization effect and cytotoxicity on tumor cells in distant areas. The aim of this study was to evaluate the efficacy and toxicity of CyberKnife SRS alone and combined with a "dose-dense" administration of temozolomide (TMZ) for recurrent GBM. METHODS: Between July 2007 and July 2010, 23 patients underwent CyberKnife SRS. In 12 patients irradiation was combined with TMZ at 75 mg/m(2)/day for 21 days every 28 days. The median prescription dose in this group was 20 Gy (mean 20.7 ± 4 Gy) with a median number of fractions of 2. The median dose for the 11 patients who underwent SRS alone was 20 Gy (mean 19.9 ± 4.4 Gy; p = NS). RESULTS: The median survival was 12 months for patients who underwent SRS/TMZ and 7 months for those who received SRS alone (p < 0.01). The 6-month progression-free survival (PFS) of the SRS/TMZ group was 66.7% vs. 18% for those who underwent SRS alone (p = 0.03). The median time to progression (TTP) was 7 months for patients who underwent SRS/TMZ and 4 months for those who underwent SRS alone (p = 0.01). Corticosteroid dependency was developed by most patients; radionecrosis was evident in one patient (4.3%) receiving TMZ. Grade 3 hematological toxicity was recorded in >40% of patients receiving chemotherapy. CONCLUSIONS: The results suggest that Cyberknife re-treatments are relatively safe using selected dose/fraction schemes. The combination with TMZ improved patients' outcomes with OS and 6-month PFS that favorably compares with alternative treatments, but the incidence of major adverse effects was >40%. Further studies are warranted.

Image-Guided Stereotactic Radiosurgery for the Treatment of Spasticity and Pain: A Preliminary Experience.

Background Spasticity is a major health problem worldwide. Response to current medical and rehabilitation treatments is often poor. Surgical treatment is available only for a very limited number of patients. Aim We recently reported the application of stereotactic radiosurgery as a treatment option for spasticity and related pain. This paper describes a larger experience using image-guided stereotactic radiosurgery targeting the cervical or lumbar spinal roots to relieve spasticity and pain in four patients. Methods All the patients had refractory spasticity and related pain, one patient had additional paroxystic neuralgic pain. The cause of spasticity and pain was a traumatic brain and/or spinal cord injury, brain and/or spinal cord surgery, and stroke. Symptoms affected the right superior limb in one patient, and the inferior limbs in three patients (unilaterally in two, bilaterally in one). According to the symptoms, one patient was treated at the cervical level (C7 right sensory root) and three patients at lumbar level (right L4, left S1, and L2 roots bilaterally). The target was selected on constructive interference in steady-state (CISS) MR, focusing the irradiation on the postganglionic sensory segment of the cervical root or the intra-foraminal dorsolateral sensory portion of the lumbar roots. Appropriate spasticity and pain scales were used to assess the patient's status after the treatment. Results The treatments were tolerated well. Marked symptomatic relief was found in all the treated patients. Improvements in spasticity and pain scales were observed up to the latest follow-up. After 2 years, the mean reduction of the visual analog scale (VAS) and Modified Ashworth Scale (MAS) was 64.3% and 43.7%, respectively, while the median reduction of MAS score was 50%. Conclusions Except for a previous case report, this is the first study describing a novel noninvasive technique based on image-guided radiosurgery to treat severe spasticity and pain due to brain and spinal cord injury. This novel technique appears to be safe and effective and deserves to be studied further.

Image-guided LINAC radiosurgery in hypothalamic hamartomas.

Introduction: Hypothalamic hamartomas (HH) are developmental malformations that are associated with mild to severe drug-refractory epilepsy. Stereotactic radiosurgery (SRS) is an emerging non-invasive option for the treatment of small and medium-sized HH, providing good seizure outcomes without neurological complications. Here, we report our experience treating HH with frameless LINAC SRS. Materials and methods: We retrospectively collected clinical and neuroradiological data of ten subjects with HH-related epilepsy that underwent frameless image-guided SRS. Results: All patients underwent single-fraction SRS using a mean prescribed dose of 16.27 Gy (range 16-18 Gy). The median prescription isodose was 79% (range 65-81 Gy). The mean target volume was 0.64 cc (range 0.26-1.16 cc). Eight patients experienced complete or near complete seizure freedom (Engel class I and II). Five patients achieved complete seizure control within 4 to 18 months after the treatment. Four patients achieved Engel class II outcome, with stable results. One patient had a reduction of seizure burden superior to 50% (Engel class III). One patient had no benefit at all (Engel class IV) and refused further treatments. Overall, at the last follow-up, three patients experience class I, five class II, one class III and one class IV outcome. No neurological complications were reported. Conclusions: Frameless LINAC SRS provides good seizure and long-term neuropsychosocial outcome, without the risks of neurological complications inherently associated with microsurgical resection.

Non-conventional Ultra-High Dose Rate (FLASH) Microbeam Radiotherapy Provides Superior Normal Tissue Sparing in Rat Lung Compared to Non-conventional Ultra-High Dose Rate (FLASH) Radiotherapy.

Conventional radiotherapy is a widely used non-invasive form of treatment for many types of cancer. However, due to a low threshold in the lung for radiation-induced normal tissue damage, it is of less utility in treating lung cancer. For this reason, surgery is the preferred treatment for lung cancer, which has the detriment of being highly invasive. Non-conventional ultra-high dose rate (FLASH) radiotherapy is currently of great interest in the radiotherapy community due to demonstrations of reduced normal tissue toxicity in lung and other anatomy. This study investigates the effects of FLASH microbeam radiotherapy, which in addition to ultra-high dose rate incorporates a spatial segmentation of the radiation field, on the normal lung tissue of rats. With a focus on fibrotic damage, this work demonstrates that FLASH microbeam radiotherapy provides an order of magnitude increase in normal tissue radio-resistance compared to FLASH radiotherapy. This result suggests FLASH microbeam radiotherapy holds promise for much improved non-invasive control of lung cancer.

Microbeam radiosurgery using synchrotron-generated submillimetric beams: a new tool for the treatment of brain disorders.

Since its advent during the mid-twentieth century, radiosurgery has undergone a steady evolution. Gamma Knife and linear accelerator based systems using rigid frames preceded the development of frameless devices. The present report describes the development of microbeam radiosurgery, a technique which uses submillimetric beams of radiation to treat disease. Typically, the technique is employed using parallel arrays of beams delivered via a high-fluence synchrotron source. Beam widths between 20 and 950 µm have been used with the majority of studies utilizing beam widths less than 100 µm. In addition to its high precision, the technique allows users to take advantage of two unique properties of microbeams. The first is a remarkable tolerance of healthy tissue to microbeams delivered at doses up to several hundred grays, while at the same time, tumors are highly susceptible to the lethal effects of microbeams. Together, these findings allow for a "preferential tumoricidal effect" beyond the typical dose-volume relationship. Although only used in animal experiments so far, we explore the hypothetical clinical role of microbeam radiosurgery which may be feasible in the near future. In addition to the treatment of traditional radiosurgery targets such as malignancies and vascular malformations, microbeams may allow the non-invasive treatment of functional disease such as movement disorders, epilepsy, and mental illness.

Stereotactic Dorsolateral Irradiation of Spinal Nerve Roots: A Novel Technique for the Treatment of Spasticity and Pain.

Selective dorsal rhizotomy is an established surgical treatment to improve the neurological and functional status of children with spastic cerebral palsy and adults with spasticity and pain caused by a variety of brain and spinal injuries. This procedure requires a dorsolumbar laminectomy to expose the appropriate dorsal rootlets, which are sectioned according to the presence of sustained electromiographic discharges. Image-guided robotic radiosurgery targeting the intracisternal sensory root of the trigeminal nerve has been described as a safe and effective non-invasive treatment for trigeminal neuralgia, a paroxystic pain disorder which often responds poorly to medical therapy. Image-guided radiosurgery requires no frame placement and can treat brain or spinal targets with submillimetric precision. This technique can be used to treat cervical or lumbar dorsal roots. A 44-year-old patient with von Hippel-Lindau disease developed severe spastic tetraparesis following multiple brain and spinal procedures. Spasticity and related pain mostly affected the right leg, with sustained electromiographic discharges originating from the right L4 nerve root. Response to medical therapy with baclofen and cannabinoids was poor. Due to geographical and logistical issues, the patient declined the placement of an intrathecal baclofen pump. Considering the poor general condition of the patient and his decision to avoid invasive procedures, a novel treatment option was offered to provide relief from spasticity and pain: stereotactic image-guided irradiation delivered to the sensory root. The patient underwent a right intraforaminal dorsolateral L4 root stereotactic irradiation with a delivered dose of 45 Gy prescribed to the 82% isodose. The treatment was well tolerated, without side effects. Resolution of spasticity and related pain in the right leg was found six months after the procedure. A marked reduction of spasticity and pain was also evident in the contralateral leg. These improvements have been stable over the last 18 months. So far, two additional patients underwent stereotactic dorsolateral spinal root irradiation (one delivered to a cervical, the other to a lumbar), with similar positive outcomes. These preliminary results suggest that spinal root stereotactic image-guided irradiation, a novel treatment option in the neurosurgical armamentarium, is a safe and effective procedure and deserves further investigation.

ZAP-X: A Novel Radiosurgical Device for the Treatment of Trigeminal Neuralgia.

Introduction The treatment of trigeminal neuralgia (TN) is one of the most demanding of all radiosurgery procedures, requiring accurate delivery and sharp dose fall off. ZAP-X®, a new, innovative frameless radiosurgical device, maybe an attractive platform for the treatment of TN and other functional brain disorders. Here, we compared the dosimetry of ZAP-X plans for a single patient to that generated by a well-established dedicated radiosurgery device, the CyberKnife. Methods Radiosurgery plans that delineated the cranial nerve from a single patient's fused computed tomography and magnetic resonance imaging (CT-MR) data set were planned on both the ZAP-X and CyberKnife, with the latter serving as a validated benchmark. The same target and treatment planning constraints were applied. Plans were evaluated by a physician with experience treating TN and a medical physicist. The ZAP-X treatment plan used two isocenters delivered through 4-mm collimators based on a non-isocentric plan that delivered 29,441 MU through 81 beams. The CyberKnife plans used a 5-mm collimator for a non-isocentric plan that delivered 17,880 MU through 88 beams. Results Based on visual inspection, the isodose volumes covered by ZAP-X and CyberKnife were similar at the prescription isodose (70% and 80%, respectively, with a maximum dose (Dmax) of 7500 cGy. The conformality index was better for the CyberKnife as compared to ZAP-X. However, the irradiated volumes were smaller at the 50%, 20%, and 10% isodoses for ZAP-X (0.12 cc, 0.57 cc, and 1.69 for ZAP-X; 0.18 cc, 0.91 cc, and 3.41 cc for CyberKnife). In particular, the 20% and 10% isodose volumes were much smaller for ZAP-X, especially on the axial and sagittal planes. Conclusions ZAP-X treatment planning for TN compares favorably with equivalent planning on CyberKnife. The brain volumes containing the 20% and 10% isodoses are smaller using ZAP-X, thus relatively sparing critical structures close to the target, including the Gasserian ganglion and brainstem. This feature could be of clinical relevance by potentially reducing treatment-related complications.

Factors affecting outcome in frameless non-isocentric stereotactic radiosurgery for trigeminal neuralgia: a multicentric cohort study.

BACKGROUND: Stereotactic radiosurgery (SRS) is an effective treatment for trigeminal neuralgia (TN). Nevertheless, a proportion of patients will experience recurrence and treatment-related sensory disturbances. In order to evaluate the predictors of efficacy and safety of image-guided non-isocentric radiosurgery, we analyzed the impact of trigeminal nerve volume and the nerve dose/volume relationship, together with relevant clinical characteristics. METHODS: Two-hundred and ninety-six procedures were performed on 262 patients at three centers. In 17 patients the TN was secondary to multiple sclerosis (MS). Trigeminal pain and sensory disturbances were classified according to the Barrow Neurological Institute (BNI) scale. Pain-free-intervals were investigated using Kaplan Meier analyses. Univariate and multivariate Cox regression analyses were performed to identify predictors. RESULTS: The median follow-up period was 38 months, median maximal dose 72.4 Gy, median target nerve volume 25 mm3, and median prescription dose 60 Gy. Pain control rate (BNI I-III) at 6, 12, 24, 36, 48, and 60 months were 96.8, 90.9, 84.2, 81.4, 74.2, and 71.2%, respectively. Overall, 18% of patients developed sensory disturbances. Patients with volume ≥ 30 mm3 were more likely to maintain pain relief (p = 0.031), and low integral dose (< 1.4 mJ) tended to be associated with more pain recurrence than intermediate (1.4-2.7 mJ) or high integral dose (> 2.7 mJ; low vs. intermediate: log-rank test, χ2 = 5.02, p = 0.019; low vs. high: log-rank test, χ2 = 6.026, p = 0.014). MS, integral dose, and mean dose were the factors associated with pain recurrence, while re-irradiation and MS were predictors for sensory disturbance in the multivariate analysis. CONCLUSIONS: The dose to nerve volume ratio is predictive of pain recurrence in TN, and re-irradiation has a major impact on the development of sensory disturbances after non-isocentric SRS. Interestingly, the integral dose may differ significantly in treatments using apparently similar dose and volume constraints.

Understanding High-Dose, Ultra-High Dose Rate, and Spatially Fractionated Radiation Therapy.

The National Cancer Institute's Radiation Research Program, in collaboration with the Radiosurgery Society, hosted a workshop called Understanding High-Dose, Ultra-High Dose Rate and Spatially Fractionated Radiotherapy on August 20 and 21, 2018 to bring together experts in experimental and clinical experience in these and related fields. Critically, the overall aims were to understand the biological underpinning of these emerging techniques and the technical/physical parameters that must be further defined to drive clinical practice through innovative biologically based clinical trials.

Riluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins.

PURPOSE: Huntington disease (HD) mutation increases gain-of-toxic functions contributing to glutamate-mediated excitotoxicity. Riluzole interferes with glutamatergic neurotransmission, thereby reducing excitotoxicity, enhancing neurite formation in damaged motoneurons and increasing serum concentrations of BDNF, a brain cortex neurotrophin protecting striatal neurons from degeneration. METHODS: We investigated metabolic and volumetric differences in distinct brain areas between 11 riluzole-treated and 12 placebo-treated patients by MRI and (18)F-fluoro-2-deoxy-D-glucose (FDG) PET scanning, according to fully automated protocols. We also investigated the influence of riluzole on peripheral growth factor blood levels. RESULTS: Placebo-treated patients showed significantly greater proportional volume loss of grey matter and decrease in metabolic FDG uptake than patients treated with riluzole in all cortical areas (p<0.05). The decreased rate of metabolic FDG uptake correlated with worsening clinical scores in placebo-treated patients, compared to those who were treated with riluzole. The progressive decrease in metabolic FDG uptake observed in the frontal, parietal and occipital cortex correlated linearly with the severity of motor scores calculated by Unified Huntington Disease Rating Scale (UHDRS-I) in placebo-treated patients. Similarly, the rate of metabolic changes in the frontal and temporal areas of the brain cortex correlated linearly with worsening behavioural scores calculated by UHDRS-III in the placebo-treated patients. Finally, BDNF and transforming growth factor beta-1 serum levels were significantly higher in patients treated with riluzole. CONCLUSION: The linear correlation between decreased metabolic FDG uptake and worsening clinical scores in the placebo-treated patients suggests that FDG-PET may be a valuable procedure to assess brain markers of HD.

The syndrome gelastic seizures-hypothalamic hamartoma: severe, potentially reversible encephalopathy.

Hypothalamic hamartoma (HH) is the pathologic hallmark of a spectrum of epileptic conditions, ranging from a mild form of epilepsy, whose seizures are an urge to laugh without cognitive defects, to the fully developed syndrome of early onset gelastic seizures (GS) associated with precocious puberty and the evolution to a catastrophic epilepsy syndrome. However, a refractory focal or generalized epilepsy develops during the clinical course in nearly all cases. Neurophysiologic and neuroimaging studies have assessed the role of HH in the generation of the GS as well as in the process of secondary epileptogenesis. Electrophysiologic properties of small gamma-aminobutyric acid (GABA)ergic, spontaneously firing neurons might explain the intrinsic epileptogenicity of HH. Surgical ablation of the HH can reverse both epilepsy and encephalopathy. Gamma-knife radiosurgery and image-guided robotic radiosurgery can be useful and safe approaches for treatment, in particular of small HH.

Survival following stereotactic radiosurgery for newly diagnosed and recurrent glioblastoma multiforme: a multicenter experience.

Despite decades of clinical trials investigating new treatment modalities for glioblastoma multiforme (GBM), there have been no significant treatment advances since the 1980s. Reported median survival times for patients with GBM treated with current modalities generally range from 9 to 19 months. The purpose of the current study is to retrospectively review the ability of CyberKnife (Accuray Incorporated, Sunnyvale, CA, USA) radiosurgery to provide local tumor control of newly diagnosed or recurrent GBM. Twenty patients (43.5%) underwent CyberKnife treatment at the time of the initial diagnosis and/or during the first 3 months of their initial clinical management. Twenty-six patients (56.5%) were treated at the time of tumor recurrence or progression. CyberKnife was performed in addition to the traditional therapy. The median survival from diagnosis for the patients treated with CyberKnife as an initial clinical therapy was 11.5 months (range, 2-33) compared to 21 months (range, 8-96) for the patients treated at the time of tumor recurrence/progression. This difference was statistically significant (Kaplan-Meier analysis, P = 0.0004). The median survival from the CyberKnife treatment was 9.5 months (range, 0.25-31 months) and 7 months (range, 1-34 months) for patients in the newly diagnosed and recurrent GBM groups (Kaplan-Meier analysis, P = 0.79), respectively. Cox proportional hazards survival regression analysis demonstrated that survival time did not correlate significantly with treatment parameters (Dmax, Dmin, number of fractions) or target volume. Survival time and recursive partitioning analysis class were not correlated (P = 0.07). Patients with more extensive surgical interventions survived longer (P = 0.008), especially those who underwent total tumor resection vs. biopsy (P = 0.004). There is no apparent survival advantage in using CyberKnife in initial management of glioblastoma patients, and it should be reserved for patients whose tumors recur or progress after conventional therapy.

Role of stereotactic radiosurgery and fractionated stereotactic radiotherapy for the treatment of recurrent glioblastoma multiforme.

Glioblastoma multiforme (GBM) is a devastating malignant brain tumor characterized by resistance to available therapeutic approaches and relentless malignant progression that includes widespread intracranial invasion, destruction of normal brain tissue, progressive disability, and death. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) are increasingly used in patients with recurrent GBM to complement traditional treatments such as resection, conventional external beam radiotherapy, and chemotherapy. Both SRS and fSRT are powerful noninvasive therapeutic modalities well suited to treat focal neoplastic lesions through the delivery of precise, highdose radiation. Although no randomized clinical trials have been performed, a variety of retrospective studies have been focused on the use of SRS and fSRT for recurrent GBMs. In addition, state-of-the-art neuroimaging techniques, such as MR spectroscopic imaging, diffusion tensor tractography, and nuclear medicine imaging, have enhanced treatment planning methods leading to potentially improved clinical outcomes. In this paper the authors reviewed the current applications and efficacy of SRS and fSRT in the treatment of GBM, highlighting the value of these therapies for recurrent focal disease.

Protecting venous structures during radiosurgery for parasagittal meningiomas.

Symptomatic edema is a potential complication of meningioma radiosurgery. Parasagittal meningiomas are at a particular risk for symptomatic edema, suggesting a role for a venous occlusive complication. The authors sought to develop a strategy to optimize CyberKnife stereotactic radiosurgical treatment parameters to reduce the irradiation of the peritumoral venous system. Multislice CT venography with 3D reconstructions was performed and coregistered with thin-section, contrast-enhanced, volumetric MR images. The tumor and critical volumes were contoured on the MR images. Venous anatomical details obtained from the CT venographic study were then exported onto the MR imaging and fused MR imaging-CT study. Target and critical structure volumes and dosimetric parameters obtained with this method were analyzed. The authors found that reducing the irradiation of veins that course along the surface of the meningioma, which may be at risk for radiation-induced occlusion, is feasible in parasagittal meningioma radiosurgery without compromising other treatment parameters including conformality, homogeneity, and target coverage. Long-term follow-up is needed to assess the clinical validity of this treatment strategy.

A Wireless Neuroprosthesis for Patients with Drug-refractory Epilepsy: A Proof-of-Concept Study.

Objective Acute or protracted cortical recording may be necessary for patients with drug-refractory epilepsy to identify the ictogenic regions before undergoing resection. Currently, these invasive recording techniques present certain limitations, one of which is the need for cables connecting the recording electrodes placed in the intracranial space with external devices displaying the recorded electrocorticographic signals. This equates to a direct connection between the sterile intracranial space with the non-sterile environment. Due to the increasing likelihood of infections with time, subdural grids are typically removed a few days after implantation, a limiting factor in localizing the epileptogenic zone if seizures are not frequent enough to be captured within this time-frame. Furthermore, patients are bound to stay in the hospital, connected by the wires to the recording device, thus increasing substantially the treatment costs. To address some of the current shortcomings of invasive monitoring, we developed a neuroprosthesis made of a subdural silicone grid connected to a wireless transmitter allowing prolonged electrocorticografic recording and direct cortical stimulation. This device consists of a silicone grid with 128-platinum/iridium contacts, connected to an implantable case providing wireless recording and stimulation. The case also houses a wirelessly rechargeable battery for chronic long-term implants. We report the results of the first human proof-of-concept trial for wireless transmission of electrocorticographic recordings using a device suited for long-term implantation in three patients with drug-refractory epilepsy.  Methods Three patients with medically refractory epilepsy underwent the temporary intraoperative placement of the subdural grid connected to the wireless device for recording and transmission of electrocorticographic signals for a duration of five minutes before the conventional recording electrodes were placed or the ictal foci were resected. Results Wireless transmission of brain signals was successfully achieved. The wireless electrocorticographic signal was judged of excellent quality by a blinded neurophysiologist. Conclusions This preliminary experience reports the first successful placement of a wireless electrocorticographic recording device in humans. Long-term placement for prolonged wireless electrocorticographic recording in epilepsy patients will be the next step.

Cyberknife Radiosurgery for Trigeminal Neuralgia.

Introduction Image-guided robotic radiosurgery is an emerging minimally-invasive treatment option for trigeminal neuralgia (TN). Our group has treated 560 cases up to date, and report here the clinical outcomes of 387 treatments with three years follow-up. This study represents the largest single-center experience on CyberKnife radiosurgery for the treatment of TN so far reported. Methods CyberKnife radiosurgery treatment was offered to patients with drug-resistant TN, after the failure of other treatments or refusal of invasive procedures. A second treatment was offered to patients with a poor response after the first treatment or with recurrent pain. Treatment protocol required the non-isocentric delivery of 60 Gy prescribed to the 80% isodose to a 6 mm retrogasserian segment of the affected trigeminal nerve. Retreatments typically received 45 Gy, again prescribed to the 80% isodose. The final plan was developed accordingly to individual anatomy and dose distribution over the trigeminal nerve, gasserian ganglion, and brainstem. Clinical outcomes such as pain control and hypoesthesia/numbness have been evaluated after 6, 12, 24, and 36 months.  Results Our group has treated 527 patients with Cyberknife radiosurgery at Centro Diagnostico Italiano (CDI), Milan, Italy, during the last decade. A minimum follow-up of six months was available on 496 patients. These patients received 560 treatments: 435 patients (87.7%) had a single treatment, 60 patients (12.1%) had two treatments, and one patient (0.2%) had five treatments (two on the right side, three on the left side). Twenty four patients had multiple sclerosis (4.8%). Four hundred and forty-three patients (84%) received the treatment without previous procedures, while 84 patients (16%) underwent radiosurgery after the failure of other treatments. A neurovascular conflict was identified in 59% of the patients. Three hundred and forty-three patients (receiving a total of 387 treatments) had a minimum of 36 months follow up. Pain relief rate at 6, 12, 18, 24, 30 and 36 months was respectively 92, 87, 87, 82, 78 and 76%. Forty-four patients out of 343 (12.8%) required a second treatment during the observed period. At 36 months post-treatment, 21 patients (6,1%) reported the presence of bothering facial hypoesthesia. Eighteen patients out of 21 (85.7%) developed this complication after a repeated treatment.  Conclusions Frameless image-guided robotic radiosurgery in experienced hands is a safe and effective procedure for the treatment of TN, providing excellent pain control rates in the absence of major neurological complications. Repeated treatments due to recurrent pain are associated with restored pain control but at the price of a higher rate of sensory complications.

Technology Insight: image-guided robotic radiosurgery--a new approach for noninvasive ablation of spinal lesions.

The need for an effective noninvasive tool to ablate spinal lesions reflects the limitations of traditional surgical and radiotherapeutic approaches. Open surgery is invasive and carries a risk of neurological injury and vertebral column dysfunction. Conventional radiotherapy often has poor clinical efficacy and a risk of neurologic complications. Spinal radiosurgery has been developed to overcome these limitations. This technique consists of precise delivery of high-dose radiation to a spinal target. To spare the delicate and radiation-sensitive spinal cord and to avoid potentially devastating neurological complications, it is essential that the radiation dose decreases rapidly outside of the target. This is accomplished by use of advanced, image-guidance technology, treatment planning software, and robotics. Preliminary data indicate that this approach can achieve high rates of tumor control of spinal and paraspinal lesions and durable reduction of associated vertebral pain without neurological complications. Although spinal radiosurgery is not yet widely practiced, the benefits of this new therapeutic approach are likely to encourage its widespread adoption in coming years.