Antonio Meola M.D. Ph.D graduated Summa cum Laude and Research Honors at the University of Pisa, Italy, in 2008, and completed his residency training in Neurosurgery at the same Institution in July 2015. Dr Meola attended a Ph.D. program at the University of Florence, Italy, where he discussed a doctoral thesis entitled "A New Head-Mounted Display-based Augmented Reality System in Neurosurgical Oncology: a study on phantom".
Since 2/2014 to 1/2015 Dr Meola completed a Research Fellowship in Neurosurgical anatomy at the University of Pittsburgh Medical Center (UPMC), under the Direction of Dr. Juan C. Fernandez-Miranda. The main focus of his research was the surgical neuroanatomy of the white matter tracts of the human brain.
Since 7/2015 to 6/2016 Dr Meola served as Clinical Fellow in Image-Guided Neurosurgery at the Brigham and Women's Hospital, Harvard Medical School, in Boston, MA (Director: Dr. Alexandra J. Golby M.D.). During the fellowship, he focused on the clinical application and integration of advanced imaging techniques, including intraoperative-MRI, intraoperative US, functional MRI, tractography.
Since 7/2016 to 6/2017 Dr Meola completed a Neurosurgical Oncology Fellowship at the Cleveland Clinic in Cleveland, OH, devoting his efforts to minimally-invasive neurosurgical techniques, such as Laser interstitial Thermal Therapy (LITT) and stereotactic radiosurgery (Gamma Knife), as well as to awake neurosurgery.
Starting 7/2017, Dr Meola joined the Department of Neurosurgery at Stanford. Dr. Meola mainly focuses on conventional and innovative treatments for brain and skull base tumors, including both surgery and stereotactic radiosurgery (CyberKnife).

Clinical Focus

  • Neurosurgery
  • Brain Tumors
  • Radiosurgery

Honors & Awards

  • Visiting Professor Guest Speaker, NIH Clinical Center, Bethesda, Washington, DC (10/2016)

Boards, Advisory Committees, Professional Organizations

  • Board Certified, European Association of Neurosurgical Societies (EANS) (2018 - Present)
  • Member, European Association of Neurosurgical Societies (EANS), Radiosurgery Section (2017 - Present)
  • Member, European Association of Neurosurgical Societies (EANS), Neuro-oncology Section (2017 - Present)

Program Affiliations

Professional Education

  • Board Certification: European Association of Neurological Sciences, Neurosurgery (2018)
  • Clinical Fellow, Cleveland Clinic Foundation, Cleveland, OH, Neurosurgical Oncology (2017)
  • Clinical Fellow, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, Image-guided Neurosurgery (2016)
  • Ph.D., University of Florence, Italy (2016)
  • Residency, University of Pisa, Italy, Neurosurgery (2015)
  • Research Fellow, University of Pittsburgh (UPMC), Pittsburgh, PA, Neurosurgical Anatomy (2015)
  • M.D., University of Pisa, Italy (2008)

All Publications

  • Impact of language barriers and use of interpreters on hope among patients with Central Nervous System Malignancies and Bone Metastases. International journal of radiation oncology, biology, physics Hui, C., Hall, J., Fang, Z., Lefebvre, S., Hayden-Gephart, M., Li, G., Meola, A., Nagpal, S., Soltys, S., Pollom, E. 2023


    PURPOSE: Hope is important in serious illnesses, as it has been linked to patient quality of life. We aimed to determine factors associated with lower hope scores among patients with central nervous system (CNS) disease or bone metastases.METHODS: The Adult Dispositional Hope Scale (AHS) is a 12-item questionnaire that measures hope through two qualities: agency (goal-directed energy) and pathways (plan to meet goals). Total scores range from 8 to 64, with higher scores reflecting higher agency and pathways thinking. We prospectively collected scores from patients seen in two radiation oncology clinics at our institution from 10/2022 to 4/2023. The method of least squares to fit general linear models and Pearson's correlation coefficients (PCC) was used to determine relationships between AHS score and socioeconomic and disease factors.RESULTS: Of the 197 patients who responded, median age was 60.5 years (range 16.9-92.5 years), most patients were male (60.9%), white (59.4%), and had malignant disease (59.4%). Median overall AHS score was 54 (range 8-64), and median pathway and agency thinking scores were 27 (range 4-32) and 27 (range 4-32), respectively. Patients who needed an interpreter compared to those who did not had significantly lower overall AHS scores (mean score 45.4 versus 51.2, respectively; p=0.0493) and pathway thinking scores (mean score 21.5 versus 25.7, respectively; p=0.0085), and patients with poorer performance status had significantly worse overall AHS scores (PCC=-0.2703, p=0.0003).CONCLUSION: Patients with CNS disease or bone metastases requiring the use of an interpreter had lower AHS scores, highlighting the possible association of language barriers to hope. Addressing patient language barriers and further studies on the possible association of language barriers to hope may improve hope, quality of life and outcomes among these patients.

    View details for DOI 10.1016/j.ijrobp.2023.11.056

    View details for PubMedID 38056777

  • The outcome of central nervous system hemangioblastomas in Von Hippel-Lindau (VHL) disease treated with belzutifan: a single-institution retrospective experience. Journal of neuro-oncology Zamarud, A., Marianayagam, N. J., Park, D. J., Yener, U., Yoo, K. H., Meola, A., Chang, S. D. 2023


    Belzutifan is a Hypoxia Inducible Factor 2-alpha inhibitor approved in 2021 by the FDA for the treatment of renal cell carcinoma (RCC) in patients with Von-Hippel Landau (VHL) disease. These patients can also present with central nervous system (CNS) hemangioblastomas (HBs). We aim to study the effectiveness and adverse effects of belzutifan for CNS HBs, by reporting our preliminary institutional experience.We present a series of VHL patients with CNS HBs undergoing treatment with belzutifan for RCC. All the included patients met the RECIST inclusion criteria. The clinical and radiological outcome measures included: Objective response rate (ORR), time-to-response (TTR), adverse events (AE), and patient response. Patient response was classified as partial response (PR), complete response (CR), progressive disease (PD), or stable disease (SD).Seven patients with 25 HBs were included in our study. A belzutifan dose of 120 mg/day PO was administered for a median of 13 months (range 10-17). Median follow up time was 15 months (range 10-24). An ORR of 71% was observed. The median TTR was 5 months (range: 1-10). None of the patients showed CR, while 5 patients (71.4%) showed PR and 2 (28.5%) showed SD. Among patients with SD the maximum tumor response was 20% [increase/decrease] of the lesion diameter. All the patients experienced decreased hemoglobin concentration, fatigue, and dizziness. None of the patients experienced severe anemia (grade 3-4 CTCAE).Belzutifan appears to be an effective and safe treatment for CNS hemangioblastoma in VHL patients. Further clinical trials to assess the long-term effectiveness of the medication are required.

    View details for DOI 10.1007/s11060-023-04496-z

    View details for PubMedID 37955759

    View details for PubMedCentralID 5573741

  • Stereotactic Radiosurgery for Cranial and Spinal Hemangioblastomas: A Single-Institution Retrospective Series. Neurosurgery Yoo, K. H., Park, D. J., Marianayagam, N. J., Gu, X., Pollom, E. L., Soltys, S. G., Chang, S. D., Meola, A. 2023


    Stereotactic radiosurgery (SRS) has been an attractive treatment modality for both cranial and spinal hemangioblastomas, especially for multiple lesions commonly associated with von Hippel-Lindau (VHL) disease. This study aims to provide the largest long-term analysis of treatment efficacy and adverse effects of SRS for cranial and spinal hemangioblastomas at a single institution.We evaluated the clinical and radiological outcomes of patients with hemangioblastomas treated with CyberKnife SRS at our institute from 1998 to 2022. The follow-up data were available for 135 hemangioblastomas in 35 patients. Twenty-eight patients had 123 hemangioblastomas associated with VHL, and 7 had 12 sporadic hemangioblastomas. The median age was 36 years, and the median tumor volume accounted for 0.4 cc. The SRS was administered with the median single-fraction equivalent dose of 18 Gy to the 77% median isodose line.At a median follow-up of 57 months (range: 3-260), only 20 (16.2%) of the VHL-associated and 1 (8.3%) sporadic hemangioblastomas progressed. The 5-year local tumor control rate was 91.3% for all hemangioblastomas, 91.7% among the sporadic lesions, and 92.9% in patients with VHL. SRS improved tumor-associated symptoms of 98 (74.8%) of 131 symptomatic hemangioblastomas, including headache, neck pain, dizziness, visual disturbances, dysesthesia, ataxia, motor impairment, seizures, and dysphagia. Two patients developed radiation necrosis (5.7%), and 1 of them required surgical resection.SRS is a safe and effective treatment option for patients with hemangioblastomas in critical locations, such as the brainstem, cervicomedullary junction, and spinal cord, and in patients with multiple hemangioblastomas associated with VHL disease.

    View details for DOI 10.1227/neu.0000000000002728

    View details for PubMedID 37967154

  • Practical Guideline for Prevention of Patchy Hair Loss following CyberKnife Stereotactic Radiosurgery for Calvarial or Scalp Tumors: Retrospective Analysis of a Single Institution Experience. Stereotactic and functional neurosurgery Park, D. J., Marianayagam, N. J., Yener, U., Tayag, A., Ustrzynski, L., Emrich, S. C., Pollom, E., Soltys, S., Meola, A., Chang, S. D. 2023: 1-7


    Patchy alopecia is a common adverse effect of stereotactic radiosurgery (SRS) on the calvarium and/or scalp, yet no guidelines exist for its prevention. This study aims to investigate the incidence and outcomes of patchy alopecia following SRS for patients with calvarial or scalp lesions and establish preventive guidelines.The study included 20 patients who underwent CyberKnife SRS for calvarial or scalp lesions, resulting in a total of 30 treated lesions. SRS was administered as a single fraction for 8 lesions and hypofractionated for 22 lesions. The median SRS target volume was 9.85 cc (range: 0.81-110.7 cc), and the median prescription dose was 27 Gy (range: 16-40 Gy), delivered in 1-5 fractions (median: 3). The median follow-up was 15 months.Among the 30 treated lesions, 11 led to patchy alopecia, while 19 did not. All cases of alopecia resolved within 12 months, and no patients experienced other adverse radiation effects. Lesions resulting in alopecia exhibited significantly higher biologically effective dose (BED) and single-fraction equivalent dose (SFED) on the overlying scalp compared to those without alopecia. Patients with BED and SFED exceeding 60 Gy and 20 Gy, respectively, were 9.3 times more likely to experience patchy alopecia than those with lower doses. The 1-year local tumor control rate for the treated lesions was 93.3%. Chemotherapy was administered for 26 lesions, with 11 lesions receiving radiosensitizing agents. However, no statistically significant difference was found.In summary, SRS is a safe and effective treatment for patients with calvarial/scalp masses regarding patchy alopecia near the treated area. Limiting the BED under 60 Gy and SFED under 20 Gy for the overlying scalp can help prevent patchy alopecia during SRS treatment of the calvarial/scalp mass. Clinicians can use this information to inform patients about the risk of alopecia and the contributing factors.

    View details for DOI 10.1159/000533555

    View details for PubMedID 37699370

  • Stereotactic Radiosurgery for Medically Refractory Trigeminal Neuralgia Secondary to Stroke: A Systematic Review and Clinical Case Presentation. World neurosurgery Zamarud, A., Park, D. J., Ung, T. H., McCleary, T. L., Yoo, K. H., Soltys, S. G., Lim, M., Chang, S. D., Meola, A. 2023

    View details for DOI 10.1016/j.wneu.2023.08.092

    View details for PubMedID 37640262

  • Optimizing the synergy between stereotactic radiosurgery and immunotherapy for brain metastases. Frontiers in oncology Yoo, K. H., Park, D. J., Choi, J. H., Marianayagam, N. J., Lim, M., Meola, A., Chang, S. D. 2023; 13: 1223599


    Solid tumors metastasizing to the brain are a frequent occurrence with an estimated incidence of approximately 30% of all cases. The longstanding conventional standard of care comprises surgical resection and whole-brain radiotherapy (WBRT); however, this approach is associated with limited long-term survival and local control outcomes. Consequently, stereotactic radiosurgery (SRS) has emerged as a potential alternative approach. The primary aim of SRS has been to improve long-term control rates. Nevertheless, rare observations of abscopal or out-of-field effects have sparked interest in the potential to elicit antitumor immunity via the administration of high-dose radiation. The blood-brain barrier (BBB) has traditionally posed a significant challenge to the efficacy of systemic therapy in managing intracranial metastasis. However, recent insights into the immune-brain interface and the development of immunotherapeutic agents have shown promise in preclinical and early-phase clinical trials. Researchers have investigated combining immunotherapy with SRS to enhance treatment outcomes in patients with brain metastasis. The combination approach aims to optimize long-term control and overall survival (OS) outcomes by leveraging the synergistic effects of both therapies. Initial findings have been encouraging in the management of various intracranial metastases, while further studies are required to determine the optimal order of administration, radiation doses, and fractionation regimens that have the potential for the best tumor response. Currently, several clinical trials are underway to assess the safety and efficacy of administering immunotherapeutic agents concurrently or consecutively with SRS. In this review, we conduct a comprehensive analysis of the advantages and drawbacks of integrating immunotherapy into conventional SRS protocols for the treatment of intracranial metastasis.

    View details for DOI 10.3389/fonc.2023.1223599

    View details for PubMedID 37637032

    View details for PubMedCentralID PMC10456862

  • Stereotactic Radiosurgery for Contrast-Enhancing Satellite Nodules in Recurrent Glioblastoma: A Rare Case Series From a Single Institution. Cureus Park, D. J., Persad, A. R., Yoo, K. H., Marianayagam, N. J., Yener, U., Tayag, A., Ustrzynski, L., Emrich, S. C., Chuang, C., Pollom, E., Soltys, S. G., Meola, A., Chang, S. D. 2023; 15 (8): e44455


    Introduction Glioblastoma (GBM) is the most common malignant adult brain tumor and is invariably fatal. The standard treatment for GBM involves resection where possible, followed by chemoradiation per Stupp's protocol. We frequently use stereotactic radiosurgery (SRS) as a single-fraction treatment for small (volume ≤ 1cc) nodular recurrent GBM to the contrast-enhancing target on T1 MRI scan. In this paper, we aimed to evaluate the safety and efficacy of SRS for patients with contrast-enhancing satellite nodules in recurrent GBM. Methods This retrospective study analyzed the clinical and radiological outcomes of five patients who underwent CyberKnife (Accuray Inc., Sunnyvale, California) SRS at the institute between 2013 and 2022. Results From 96 patients receiving SRS for GBM, five (four males, one female; median age 53) had nine distinct new satellite lesions on MRI, separate from their primary tumor beds. Those nine lesions were treated with a median margin dose of 20 Gy in a single fraction. The three-, six, and 12-month local tumor control rates were 77.8%, 66.7%, and 26.7%, respectively. Median progression-free survival (PFS) was seven months, median overall survival following SRS was 10 months, and median overall survival (OS) was 35 months. Interestingly, the only lesion that did not show radiological progression was separate from the T2-fluid attenuated inversion recovery (FLAIR) signal of the main tumor. Conclusion Our SRS treatment outcomes for recurrent GBM satellite lesions are consistent with existing findings. However, in a unique case, a satellite nodule distinct from the primary tumor's T2-FLAIR signal and treated with an enlarged target volume showed promising control until the patient's demise. This observation suggests potential research avenues, given the limited strategies for 'multicentric' GBM lesions.

    View details for DOI 10.7759/cureus.44455

    View details for PubMedID 37664337

    View details for PubMedCentralID PMC10470661

  • Stereotactic radiosurgery for distant brain metastases secondary to esthesioneuroblastoma: a single-institution series. Neurosurgical focus Zamarud, A., Yener, U., Yoo, K. H., Park, D. J., Marianayagam, N. J., Ho, Q. A., Pollom, E., Soltys, S., Wang, L., Chang, S. D., Meola, A. 2023; 55 (2): E6


    Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare, malignant tumor of neuroectodermal origin that arises from the olfactory neuroepithelium. In this study the authors present the first series in the literature on distant brain metastases (BMs) secondary to ENB that were treated with stereotactic radiosurgery (SRS), to evaluate the safety and effectiveness of SRS for this indication.A retrospective analysis of clinical and radiological outcomes of patients with ENB who underwent CyberKnife (CK) SRS at a single center was conducted. The clinical and radiological outcomes of patients, including progression-free survival, overall survival, and local tumor control (LTC) were reported.Between 2003 and 2022, 32 distant BMs in 8 patients were treated with CK SRS at Stanford University. The median patient age at BM diagnosis was 62 years (range 47-75 years). Among 32 lesions, 2 (6%) had previously been treated with surgery, whereas for all other lesions (30 [94%]), CK SRS was used as their primary treatment modality. The median target volume was 1.5 cm3 (range 0.09-21.54 cm3). CK SRS was delivered by a median marginal dose of 23 Gy (range 15-30 Gy) and a median of 3 fractions (range 1-5 fractions) to a median isodose line of 77% (range 70%-88%). The median biologically effective dose was 48 Gy (range 21-99.9 Gy) and the median follow-up was 30 months (range 3-95 months). The LTC at 1-, 2-, and 3-year follow-up was 86%, 65%, and 50%, respectively. The median progression-free survival and overall survival were 29 months (range 11-79 months) and 51 months (range 15-79 months), respectively. None of the patients presented adverse radiation effects.In the authors' experience, SRS provided excellent LTC without any adverse radiation effects for BMs secondary to ENB.

    View details for DOI 10.3171/2023.5.FOCUS23216

    View details for PubMedID 37527675

  • Stereotactic radiosurgery for sarcoma metastases to the brain: a single-institution experience. Neurosurgical focus Zamarud, A., Park, D. J., Dadey, D. Y., Yoo, K. H., Marianayagam, N. J., Yener, U., Szalkowski, G. A., Pollom, E., Soltys, S., Chang, S. D., Meola, A. 2023; 55 (2): E7


    Brain metastases (BMs) secondary to sarcoma are rare, and their incidence ranges from 1% to 8% of all bone and soft tissue sarcomas. Although stereotactic radiosurgery (SRS) is widely used for BMs, only a few papers have reported on SRS for sarcoma metastasizing to the brain. The purpose of this study was to evaluate the safety and effectiveness of SRS for sarcoma BM.The authors retrospectively reviewed the clinical and radiological outcomes of patients with BM secondary to histopathologically confirmed sarcoma treated with SRS, either as primary treatment or as adjuvant therapy after surgery, at their institution between January 2005 and September 2022. They also compared the outcomes of patients with hemorrhagic lesions and of those without.Twenty-three patients (9 females) with 150 BMs secondary to sarcoma were treated with CyberKnife SRS. Median age at the time of treatment was 48.22 years (range 4-76 years). The most common primary tumor sites were the heart, lungs, uterus, upper extremities, chest wall, and head and neck. The median Karnofsky Performance Status on presentation was 73.28 (range 40-100). Eight patients underwent SRS as a primary treatment and 15 as adjuvant therapy to the resection cavity. The median tumor volume was 24.1 cm3 (range 0.1-150.3 cm3), the median marginal dose was 24 Gy (range 18-30 Gy) delivered in a median of 1 fraction (range 1-5) to a median isodose line of 76%. The median follow-up was 8 months (range 2-40 months). Median progression-free survival and overall survival were 5.3 months (range 0.4-32 months) and 8.2 months (range 0.1-40), respectively. The 3-, 6-, and 12-month local tumor control (LTC) rates for all lesions were respectively 78%, 52%, and 30%. There were no radiation-induced adverse effects. LTC at the 3-, 6-, and 12-month follow-ups was better in patients without hemorrhagic lesions (100%, 70%, and 40%, respectively) than in those with hemorrhagic lesions (68%, 38%, and 23%, respectively).SRS, both as a primary treatment and as adjuvant therapy to the resection cavity after surgery, is a safe and relatively effective treatment modality for sarcoma BMs. Nonhemorrhagic lesions show better LTC than hemorrhagic lesions. Larger studies aiming to validate these results are encouraged.

    View details for DOI 10.3171/2023.5.FOCUS23168

    View details for PubMedID 37527671

  • Metastatic Lesions of the Brain and Spine. Advances in experimental medicine and biology Ung, T. H., Meola, A., Chang, S. D. 2023; 1405: 545-564


    Brain and spinal metastases are common in cancer patients and are associated with significant morbidity and mortality. Continued advancement in the systemic care of cancer has increased the life expectancy of patients, and consequently, the incidence of brain and spine metastasis has increased. There has been an increase in the understanding of oncogenic mutations, and research has also demonstrated spatial and temporal mutations in patients that may drive overall treatment resistance and failure. Combinatory treatments with radiation, surgery, and newer systemic therapies have continued to increase the life expectancy of patients with brain and spine metastases. Given the overall complexity of brain and spine metastases, this chapter aims to give a comprehensive overview and cover important topics concerning brain and spine metastases. This will include the molecular, genetic, radiographic, surgical, and non-surgical treatments of brain and spinal metastases.

    View details for DOI 10.1007/978-3-031-23705-8_21

    View details for PubMedID 37452953

    View details for PubMedCentralID 4916970

  • CyberKnife radiosurgery for treatment of residual or recurrent Grade 1 choroid plexus papilloma: A single institution experience. World neurosurgery Zhang, M., Park, D. J., Marianayagam, N. J., Yener, U., Soltys, S. G., Pollom, E., Chang, S. D., Meola, A. 2023


    Choroid plexus papillomas (CPP) are rare intraventricular brain tumors derived from the epithelium of the choroid plexus. Gross total resection has traditionally been considered curative, but residual tumor or recurrence remains possible. SRS has become particularly more important strategy for subtotally resectied and recurrent tumors. The evidence-based rationale of SRS treatment for residual or recurrent CPP in adult patients is still lacking due to its rarity.We retrospectively reviewed histopathologically confirmed cases of residual or recurrent CPP treated with SRS at our institute in the adult population between 2005 and 2022. Three patients, with five lesions, were identified with a median age of 63 years. Patients presented initially with hydrocephalus-related symptoms, although ventriculomegaly was noted only in one patient radiographically. The tumor locations were most common in 4th ventricle or along foramen of Luschka. Treatment was delivered in a single fraction in 4 lesions and in 3 fractions in 1 patient. The median follow-up was 26 months.The local tumor control rate for the lesions was 80%. One patient developed a new lesion outside the SRS field, and one lesion developed progression without need for subsequent treatment. There were no significant shrinkage of the lesions radiographically. None of the patients revealed radiation-related adverse events. No patients required surgical management after SRS treatment at our institution. Based on the literature review, our case series was the second largest retrospective series from a single institution on SRS for recurrent or residual CPP.SRS for patients with recurrent or residual CPP was a safe and effective treatment modality in this case series. Larger studies are encouraged to validate the role of SRS in the treatment of recurrent or residual CPP.

    View details for DOI 10.1016/j.wneu.2023.07.003

    View details for PubMedID 37423336

  • Impact of Cochlear Dose on Hearing Preservation Following Stereotactic Radiosurgery in Treatment of Vestibular Schwannomas: A Multi-center Study. World neurosurgery Chang, S. D., Muacevic, A., Klein, A. L., Sherman, J. H., Romanelli, P., Santa Maria, P. L., Fuerweger, C., Bossi Zanetti, I., Beltramo, G., Vaisbush, Y., Tran, E., Feng, A., Teng, H., Meola, A., Gibbs, I., Tolisano, A. M., Kutz, J. W., Wardak, Z., Nedzi, L. A., Hong, R., MacRae, D., Sohal, P., Kapoor, E., Sabet-Rasekh, P., Maghami, S., Moncada, P. X., Zaleski-King, A., Amdur, R., Monfared, A. 2023


    BACKGROUND: 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. Effects of radiation parameters of SRS on hearing remain unknown.OBJECTIVES: The goal of this study is to determine the effect of tumor volume, patient demographics, pre-treatment 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 (PTA)s increased and word recognition scores (WRS)s 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.CONCLUSION: Decline of hearing at 1 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 hearing preservation at 1 year is 3 Gy, and the use of 3 fractions instead of 1 fraction was better at preserving hearing.

    View details for DOI 10.1016/j.wneu.2023.05.098

    View details for PubMedID 37268187

  • Efficacy of Stereotactic Radiosurgery as Single or Combined Therapy for Brain Metastasis: A Systematic Review and Meta-Analysis. Critical reviews in oncology/hematology Rostampour, N., Rezaeian, S., Sarbakhsh, P., Meola, A., Choupani, J., Doosti-Irani, A., Nemati, H., Almasi, T., Badrigilan, S., Chang, S. D. 2023: 104015


    To determine the efficacy of stereotactic radiosurgery (SRS) in treating patients with brain metastases (BMs), a network meta-analysis (NMA) of randomized controlled trials (RCTs) and a direct comparison of cohort studies were performed. Relevant literature regarding the effectiveness of SRS alone and in combination with whole-brain radiotherapy (WBRT) and surgery was retrieved using systematic database searches up to April 2019. The patterns of overall survival (OS), one-year OS, progression-free survival (PFS), one-year local brain control (LBC), one-year distant brain control (DBC), neurological death (ND), and complication rate were analyzed. A total of 18 RCTs and 37 cohorts were included in the meta-analysis. Our data revealed that SRS carried a better OS than SRS+WBRT (p= 0.048) and WBRT (p= 0.041). Also, SRS+WBRT demonstrated a significantly improved PFS, LBC, and DBC compared to WBRT alone and SRS alone. Finally, SRS achieved the same LBC as high as surgery, but intracranial relapse occurred considerably more frequently in the absence of WBRT. However, there were not any significant differences in ND and toxicities between SRS and other groups. Therefore, SRS alone may be a better alternative since increased patient survival may outweigh the increased risk of brain tumor recurrence associated with it.

    View details for DOI 10.1016/j.critrevonc.2023.104015

    View details for PubMedID 37146702

  • CyberKnife Radiosurgery for Spinal Leptomeningeal Metastases Secondary to Esthesioneuroblastoma: A Clinical Case Report. Cureus Zamarud, A., Yener, U., Sayed, R., Chang, S. D., Meola, A. 2023; 15 (5): e39791


    Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare malignant tumor of neuroectodermal origin that arises from the olfactory epithelium. We present a case of ENB metastasizing through the leptomeningeal route to the spinal dura, which was treated with CyberKnife (CK) stereotactic radiosurgery (SRS), and aim to assess the safety and effectiveness of SRS in such cases. To the best of our knowledge, this is the first case report in the literature that discusses ENB spinal leptomeningeal metastases treated with CK radiosurgery. We retrospectively reviewthe clinical and radiological outcomes in a 70-year-old female with ENB metastasis to the spine. Progression-free survival (PFS), overall survival (OS), and local tumor control (LTC) are investigated. In our patient, ENB had been diagnosedat the age of 58 yearsand spinal metastases had been first noted at the age of 65 years. A total of six spinal lesions received CK SRS. Lesions were present at the level of C1, C2, C3, C6-C7, T5, and T10-11.The median target volume was 0.72 cc (range: 0.32-2.54). A median marginal dose of 24 Gy was delivered to the tumors with a median of three fractions to a median isodose line of 80% (range: 78-81). LTC at the 24-monthfollow-up was 100%. PFS and OS were 27 months and 40 months, respectively. No adverse radiation effects were reported. Even though the treated spinal lesions remained stable, the number of new metastatic lesions had increased with progressive osseous and dural metastatic lesions within the cervical, thoracic, and lumbar spine at the last follow-up. SRS provides relatively good LTC for patients with ENB metastasizing to the spine, with no radiation-induced adverse events.

    View details for DOI 10.7759/cureus.39791

    View details for PubMedID 37398775

  • Cyberknife Radiosurgery for Synovial Sarcoma Metastasizing to the Spine: Illustrative Case Reports. Cureus Zamarud, A., Park, D. J., Haider, G., Chang, S. D., Meola, A. 2023; 15 (4): e37087


    Synovial sarcoma (SS) is a rare and aggressive type of soft tissue sarcoma that commonly affects young adults. Metastasis in the spine is a rare complication, and the management of these lesions is challenging. Radiosurgery is an increasingly popular treatment option for spinal metastasis due to its ability to deliver high doses of radiation to the target volume with minimal exposure to surrounding healthy tissues. In this paper, we present two cases of SS with spinal metastasis that were treated with CyberKnife radiosurgery (CKRS). The first case was a 52-year-old female with a history of multiple thoracotomies and lobectomies for lung metastases, who was diagnosed with T6-T8 and T4 spinal metastasis. The second case was a 53-year-old female with Down syndrome, who was diagnosed with T12-L1 spinal metastasis. Both patients experienced an improvement in their symptoms following CKRS treatment and showed stable or decreasing lesion sizes on follow-up imaging. The progression-free survival (PFS) in the first case was 37 months and overall survival (OS) was 79 months. In the second case, the PFS was 12 months and OS was 18 months. These cases highlight the potential benefits of CKRS as a treatment option for SS with spinal metastasis and support its use in the management of this challenging condition.

    View details for DOI 10.7759/cureus.37087

    View details for PubMedID 37168194

    View details for PubMedCentralID PMC10166278

  • Treatment Outcomes of Leiomyosarcoma Metastasis Affecting the Brachial Plexus: A Comparative Case Report Using Chat Generative Pre-trained Transformer (ChatGPT). Cureus Zamarud, A., Marianayagam, N., Sekar, V., Chang, S. D., Meola, A. 2023; 15 (3): e36715


    Sarcomas are a rare type of cancer that can develop in various parts of the body, including the brachial plexus. Leiomyosarcomas (LMs) are a subtype of sarcoma that develops in smooth muscle tissue and can metastasize to different parts of the body. In this case report, we present two patients with LM metastasized to the brachial plexus, one treated with CyberKnife (Accuray, Sunnyvale, CA) stereotactic radiosurgery (CK SRS) and the other with surgical resection. The aim of this case report is to present the treatment outcomes and adverse effects of CK SRS and surgical resection in brachial plexus LM metastasis. Patient 1 was a 39-year-old female who received CK SRS, and at three months of follow-up, the lesion was smaller, and she reported symptomatic improvement. At 15 months, the lesion was stable in size, and there was no evidence of local invasion of the adjacent vascular structures or nerves. Patient 2 was a 52-year-old male who underwent surgical resection, and at one-month follow-up, the patient was asymptomatic with no recurrence of his symptoms. The size of the residual axillary tumor was stable at three months and showed a slight interval decrease in size at five months of follow-up. He was followed for over 12 months, with no recurrence of his symptoms. Both treatments appear to have been effective in controlling LM growth and relieving symptoms. CK SRS provides a non-invasive option. However, more research is needed to fully understand the effectiveness and safety of these treatments for brachial plexus sarcoma. This case report highlights the importance of considering different treatment options for brachial plexus sarcoma and the need for further studies to understand the best approach for these rare cases.

    View details for DOI 10.7759/cureus.36715

    View details for PubMedID 37113342

    View details for PubMedCentralID PMC10129366

  • Stereotactic radiosurgery for localized cranial Langerhans cell histiocytosis: A single institution experience and review of literature. World neurosurgery Park, D. J., Marianayagam, N. J., Yener, U., Wang, L., Soltys, S. G., Pollom, E., Chang, S. D., Meola, A. 2023


    Langerhans cell histiocytosis (LCH) is a rare idiopathic disease characterized by the clonal proliferation of Langerhans histiocytes in various parts of the body and capable of leading to organ damage and tumor formation. Reports of cranial LCH in the adult population are extremely rare. Although surgery remains the preferred option for localized LCH lesions, the role of stereotactic radiosurgery (SRS) is emerging as well.To retrospectively review a rare case series to determine the safety and effectiveness of SRS for patients with localized cranial LCH.We retrospectively reviewed histopathologically confirmed cases of localized cranial LCH treated with SRS at our institute in the adult population between January 2005 and September 2022. Five patients were identified with a median age of 34 years (19-54 years). The tumor location was in the pituitary stalk in three patients, the orbit in one patient, and the parietal skull in one patient. The median target volume was 2.8 cc (range: 0.37-6.11). Treatment was delivered in a single fraction in 4 patients (median margin dose of 8 Gy (range: 7-10 Gy) and in 3 fractions (22.5 Gy) in 1 patient. The median follow-up was 12 years (range: 4-17). None of the patients required craniotomy for tumor debulking before or after SRS.The local tumor control rate for the lesions was 100%. All three patients with LCH in the pituitary stalk had diabetes insipidus at the initial presentation and developed panhypopituitarism after SRS. Diabetes insipidus was not improved after SRS. The other two patients presented no adverse radiation effects. Based on the literature review, our case series was the largest retrospective series on SRS for localized cranial LCH, with the longest median follow-up.SRS for patients with localized cranial LCH was a safe and effective treatment modality in this case series. Larger studies are encouraged to validate the role of SRS in the treatment of localized cranial LCH.

    View details for DOI 10.1016/j.wneu.2023.01.053

    View details for PubMedID 36681322

  • Cyberknife Radiosurgery for Synovial Sarcoma Metastasizing to the Spine Cureus Zamarud, A., Park, D. J., Haider, G., Chang, S. D., Meola, A. 2023; 15 (4)

    View details for DOI 10.7759/cureus.37087

  • Stereotactic radiosurgery for trigeminal neuralgia secondary to tumor: a single-institution retrospective series. Neurosurgical focus Hall, J. C., Ung, T. H., McCleary, T. L., Chuang, C., Gibbs, I. C., Soltys, S. G., Hayden Gephart, M., Li, G., Pollom, E. L., Chang, S. D., Meola, A. 2022; 53 (5): E3


    Trigeminal neuralgia (TN) secondary to tumor represents a rare and diverse entity, and treatment for secondary TN remains controversial. This report reviews a single institution's experience in treating secondary TN with stereotactic radiosurgery (SRS) and focuses on the durability of pain relief with respect to various treatment targets, i.e., the trigeminal nerve, offending tumor, or both.Between the years 2009 and 2021, 21 patients with TN secondary to benign (n = 13) or malignant (n = 8) tumors underwent SRS. Barrow Neurological Institute (BNI) pain intensity scale scores were collected from patient electronic medical records at baseline, initial follow-up, and 1 and 3 years post-SRS. The interval change in BNI scale score (ΔBNI) at the various follow-up time points was also calculated to assess the durability of pain relief following SRS.The median follow-up period was 24 (range 0.5-155) months. Five patients (24%) received treatment to the trigeminal nerve only, 10 (48%) received treatment to the tumor only, and 6 (29%) had treatment to both the nerve and tumor. The overall radiation dosage ranged from 14 to 60 Gy delivered in 1-5 fractions, with a median overall dose of 26 Gy. The median dose to the tumor was 22.5 (range 14-35) Gy, delivered in 1-5 fractions. Of the treatments targeting the tumor, 25% were delivered in a single fraction with doses ranging from 14 to 20 Gy, 60% were delivered in 3 fractions with doses ranging from 18 to 27 Gy, and 15% were delivered in 5 fractions with doses ranging from 25 to 35 Gy. The most common dose regimen for tumor treatment was 24 Gy in 3 fractions. The median biologically effective dose (with an assumed alpha/beta ratio of 10 [BED10]) for tumor treatments was 43.1 (range 13.3-60.0) Gy. There was a significant difference in the proportion of patients with recurrent pain (ΔBNI score ≥ 0) at the time of last follow-up across the differing SRS treatment targets: trigeminal nerve only, tumor only, or both (p = 0.04). At the time of last follow-up, the median ΔBNI score after SRS to the nerve only was -1, 0 after SRS to tumor only, and -2 after SRS to both targets.SRS offers clinical symptomatic benefit to patients with TN secondary to tumor. For optimal pain relief and response durability, treatment targeting both the tumor and the trigeminal nerve appears to be most advantageous.

    View details for DOI 10.3171/2022.8.FOCUS22381

    View details for PubMedID 36321284

  • Synchronous glioblastoma and brain metastases: illustrative case. Journal of neurosurgery. Case lessons Shahsavari, N., Ahmad, M., Sekar, V., Meola, A., Hancock, S. L., Chang, S. D., Chiang, V. L. 2022; 3 (12)


    BACKGROUND: Radiosurgical treatment of brain metastases is usually performed without brain tissue confirmation. While it is extremely rare for glioblastoma to develop concurrently in patients with brain metastases, they can look radiographically similar, and recognition is important because it alters management and prognosis. The synchronous presence of brain metastases and glioblastoma has not been published to date in the literature, making this a rare illustrative case.OBSERVATIONS: A 70-year-old female had lung biopsy-proven metastatic lung adenocarcinoma and multiple brain metastases. Her treatment course included initial carboplatin, pemetrexed, and bevacizumab followed by maintenance nivolumab, and she underwent stereotactic radiosurgery to the multiple brain metastases. During interval radiological surveillance, one lesion in the right temporal lobe was noted to slowly progress associated with development of significant perilesional edema causing midline shift despite repeated stereotactic radiosurgical treatments. Biopsy of this lesion revealed glioblastoma, IDH wildtype.LESSONS: Glioblastomas and brain metastases have similar radiological features, so the possibility of incorrect diagnosis needs to be considered for all lesions with interval growth poststereotactic radiosurgery. Biopsy and/or resection/laser ablation should be considered prior to reirradiation.

    View details for DOI 10.3171/CASE21714

    View details for PubMedID 36273867

  • Radiotherapy for brain metastases from thyroid cancer: an institutional and national retrospective cohort study. Thyroid : official journal of the American Thyroid Association Blomain, E. S., Berta, S., Hug, N. F., Giao, D. M., Meola, A., Binkley, M. S., Hui, C., Churilla, T., Shahsavari, N., Desai, K., Chang, S. D., Soltys, S., Pollom, E. L. 2022


    BACKGROUND: Stereotactic radiosurgery (SRS) is the standard of care for patients with a limited number of brain metastases. Despite the fact that the seminal studies regarding SRS for brain metastases were largely tissue agnostic, several current national guidelines do not uniformly recommend SRS in thyroid cancer. We therefore investigated oncologic outcomes in a cohort of patients with brain metastases from thyroid cancer who received radiotherapy at our institution as well as those in a nationally representative cancer cohort, the national cancer database (NCDB).METHODS: We identified patients with thyroid cancer and brain metastases treated with radiotherapy at our institution from 2002 through 2020. For the NCDB cohort, the national database of patients with thyroid cancer was screened on the basis of brain-directed radiotherapy or brain metastases. For the institutional cohort, the cumulative risk of local failure, distant intracranial failure and radiation necrosis were calculated, adjusted for the competing risk of death. Overall survival (OS) in both cohorts was analyzed using Kaplan-Meier method. Univariate analysis was accomplished via clustered competing risks regression.RESULTS: For the institutional cohort, we identified 33 patients with 212 treated brain metastases. Overall survival was 6.6 months. The 1-year cumulative incidences of local failure and distant intracranial failures were 7.0% and 38%, respectively. The 1-year risk of radiation necrosis was 3.3%. In the NCDB cohort, there were 289 patients and median survival was 10.2 months. NCDB national practice patterns analysis showed an increasing use of SRS over time in both the entire cohort and the subset of anaplastic patients. Univariate analysis was performed for overall survival, risk of local failure, risk of regional intracranial failure and risk of radiation necrosis.CONCLUSIONS: SRS is a safe, effective and increasingly-utilized treatment for thyroid cancer brain metastases of any histology and should be the standard of care treatment.

    View details for DOI 10.1089/thy.2021.0628

    View details for PubMedID 35229625

  • Stereotactic radiosurgery with immune checkpoint inhibitors for brain metastases: a meta-analysis study. British journal of neurosurgery Badrigilan, S., Meola, A., Chang, S. D., Rezaeian, S., Nemati, H., Almasi, T., Rostampour, N. 1800: 1-11


    BACKGROUND: Immune checkpoint inhibitors (ICIs) are an emerging tool in the treatment of brain metastases (BMs), Stereotactic radiosurgery (SRS), traditionally used for BMs, elicits an immune brain response and can act synergistically with ICIs. We aim to investigate the efficacy of ICI administered with SRS and determine the impact of timing on BM response.METHODS: A systematical search was performed to identify potential studies concerning BMs managed with SRS alone or with SRS+ICI with relative timing administration (ICI concurrent with SRS, ICI nonconcurrent with SRS, SRS before ICI, SRS after ICI). The overall survival (OS), 12-month OS, local progression-free survival (LPFS), 12-month local brain control (LBC), distant progression-free survival (DPFS), 12-month distant brain control (DBC), and adverse events (intracranial hemorrhage, radionecrosis) were analyzed using the random-effects model.RESULTS: A total of 16 retrospective studies with 1356 BM patients were included. Compared to nonconcurrent therapy, concurrent therapy revealed a significantly longer OS (HR= 1.43; p=0.008) and 12-months LBC (HR = 1.91; p=0.04), a similar 12-months DBC (HR = 1.12; p=0.547) and higher complication rate (R=0.77; p=0.346). Concurrent therapy leads to a significantly higher OS compared to ICI before SRS (HR = 2.55; p=0.0003).CONCLUSION: The combination of SRS with ICI improves patients' clinical and radiological outcomes. The effectiveness of the combination is subject to the identification of an optimal therapeutic window.

    View details for DOI 10.1080/02688697.2021.2022098

    View details for PubMedID 34979828

  • Editorial: Atypical and malignant meningioma: Advances in pathophysiology, imaging and treatment. Frontiers in neurology Ahmad, M., Meola, A., Pollom, E. 2022; 13: 970394

    View details for DOI 10.3389/fneur.2022.970394

    View details for PubMedID 36051220

  • Microenvironment changes in arteriovenous malformations after stereotactic radiation. Frontiers in human neuroscience Ung, T. H., Belanger, K., Hashmi, A., Sekar, V., Meola, A., Chang, S. D. 2022; 16: 982190


    Cerebral arteriovenous malformations are dysplastic vascular tangles with aberrant vascular dynamics and can result significant morbidity and mortality. A myriad of challenges are encountered when treating these lesions and are largely based on nidal size, location, and prior hemorrhage. Currently, stereotactic radiosurgery is an accepted form of treatment for small to medium sized lesions and is especially useful in the treatment of lesions in non-surgically assessable eloquent areas of the brain. Despite overall high rates of nidal obliteration, there is relatively limited understand on the mechanisms that drive the inflammatory and obliterative pathways observed after treatment with stereotactic radiosurgery. This review provides an overview of arteriovenous malformations with respect to stereotactic radiosurgery and the current understanding of the mechanisms that lead to nidal obliteration.

    View details for DOI 10.3389/fnhum.2022.982190

    View details for PubMedID 36590065

  • RADIOTHERAPY FOR BRAIN METASTASES FROM THYROID CANCER: A RETROSPECTIVE COHORT STUDY Blomain, E., Berta, S., Hug, N., Giao, D., Meola, A., Binkley, M., Shahsavari, N., Desai, K., Chang, S., Soltys, S., Pollom, E. OXFORD UNIV PRESS INC. 2021: 42
  • Microsurgical resection of foramen magnum meningioma: multi-institutional retrospective case series and proposed surgical risk scoring system. Journal of neuro-oncology Fatima, N., Shin, J. H., Curry, W. T., Chang, S. D., Meola, A. 2021


    PURPOSE: Foramen magnum meningiomas (FMMs) are a major surgical challenge, due to relevant surgical morbidity and mortality. The paper aims to review the clinical (symptomatic improvement, complication rate, length of hospital stay) and radiological outcome (completeness of resection) of microsurgical resection of FMMs, and to identify predictors of complications.METHODS: A multi-institutional retrospective review of prospectively maintained database of FMMs included 51 patients (74.5% females) with a median tumor volume of 8.18cm3 (range, 1.77-57.9cm3) and median follow-up of 36months (range, 0.30-180.0months). Tumors were resected though suboccipital approach (58.8%) or posterior-lateral approaches (39.3%), including far-lateral, extreme lateral and transcondylar approaches.RESULTS: Gross-total resection (GTR) was achieved in 80.4% and 98% of cases did not present tumor regrowth or recurrence. Clinical symptoms improved in 34 patients (66.7%) and worsened in 5 (9.8%). The median length of hospital stay was 5days. Mortality was null. Postoperative complications developed in 15 patients (29.4%), with cerebrospinal fluid leak (7.8%) and lower cranial nerves deficits (7.8%) as the most frequent. Craniospinal location (p=0.03), location anterior to the dentate ligament (DL) (p=0.02), involvement of vertebral artery (VA) (p=0.03) were significantly associated with complication rate. These three elements allow calculating the Foramen Magnum Meningioma Risk Score (FRMMRS), to estimate the risk of post-operative complications.CONCLUSION: Microsurgical resection allows for high GTR rate and low rate of tumor regrowth or recurrence, despite complications in one third of the patients. The FMMRS allows classifying FMMs and estimating the risk of post-operative complications.

    View details for DOI 10.1007/s11060-021-03773-z

    View details for PubMedID 33973146

  • The Stanford stereotactic radiosurgery experience on 7000 patients over 2 decades (1999-2018): looking far beyond the scalpel. Journal of neurosurgery Fatima, N., Meola, A., Ding, V. Y., Pollom, E., Soltys, S. G., Chuang, C. F., Shahsavari, N., Hancock, S. L., Gibbs, I. C., Adler, J. R., Chang, S. D. 2021: 1–17


    OBJECTIVE: The CyberKnife (CK) has emerged as an effective frameless and noninvasive method for treating a myriad of neurosurgical conditions. Here, the authors conducted an extensive retrospective analysis and review of the literature to elucidate the trend for CK use in the management paradigm for common neurosurgical diseases at their institution.METHODS: A literature review (January 1990-June 2019) and clinical review (January 1999-December 2018) were performed using, respectively, online research databases and the Stanford Research Repository of patients with intracranial and spinal lesions treated with CK at Stanford. For each disease considered, the coefficient of determination (r2) was estimated as a measure of CK utilization over time. A change in treatment modality was assessed using a t-test, with statistical significance assessed at the 0.05 alpha level.RESULTS: In over 7000 patients treated with CK for various brain and spinal lesions over the past 20 years, a positive linear trend (r2 = 0.80) in the system's use was observed. CK gained prominence in the management of intracranial and spinal arteriovenous malformations (AVMs; r2 = 0.89 and 0.95, respectively); brain and spine metastases (r2 = 0.97 and 0.79, respectively); benign tumors such as meningioma (r2 = 0.85), vestibular schwannoma (r2 = 0.76), and glomus jugulare tumor (r2 = 0.89); glioblastoma (r2 = 0.54); and trigeminal neuralgia (r2 = 0.81). A statistically significant difference in the change in treatment modality to CK was observed in the management of intracranial and spinal AVMs (p < 0.05), and while the treatment of brain and spine metastases, meningioma, and glioblastoma trended toward the use of CK, the change in treatment modality for these lesions was not statistically significant.CONCLUSIONS: Evidence suggests the robust use of CK for treating a wide range of neurological conditions.

    View details for DOI 10.3171/2020.9.JNS201484

    View details for PubMedID 33799297

  • ZAP-X: A Novel Radiosurgical Device for the Treatment of Trigeminal Neuralgia. Cureus Romanelli, P., Chuang, C., Meola, A., Bodduluri, R. M., Adler, J. R. 2020; 12 (5): e8324


    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.

    View details for DOI 10.7759/cureus.8324

    View details for PubMedID 32617203

    View details for PubMedCentralID PMC7325335

  • ZAP-X: A Novel Radiosurgical Device for the Treatment of Trigeminal Neuralgia CUREUS Romanelli, P., Chuang, C., Meola, A., Bodduluri, R. M., Adler, J. R. 2020; 12 (5)
  • Stereotactic radiosurgery for head and neck paragangliomas: a systematic review and meta-analysis. Neurosurgical review Fatima, N., Pollom, E., Soltys, S., Chang, S. D., Meola, A. 2020


    Head and neck paragangliomas (HNPs) are rare, usually benign hyper vascularized neuroendocrine tumors that traditionally have been treated by surgery, with or without endovascular embolization, or, more recently stereotactic radiosurgery (SRS). The aim of our study is to determine the clinical and radiographic effectiveness of SRS for treatment of HNPs. A systematic search of electronic databases was performed, and 37 articles reporting 11,174 patients (1144 tumors) with glomus jugulare (GJT: 993, 86.9%), glomus tympanicum (GTT: 94, 8.2%), carotid body tumors (CBTs: 28, 2.4%), and glomus vagale (GVT: 16, 1.4%) treated with SRS definitively or adjuvantly were included. The local control (LC) was estimated from the pooled analysis of the series, and its association with SRS technique as well as demographic and clinical factors was analyzed. The median age was 56years (44-69years). With a median clinical and radiological follow-up of 44months (9-161months), LC was 94.2%. Majority of the patients (61.0%) underwent Gamma Knife Radiosurgery (GKS), but there was no statistically significant difference in LC depending upon the SRS technique (p=0.9). Spearmen's correlation showed that LC was strongly and negatively correlated with multiple parameters, which included female gender (r=-0.4, p=0.001), right-sided tumor (r=-0.3, p=0.03), primary SRS (r=-0.5, p≤0.001), and initial clinical presentation of hearing loss (r=-0.4, p=0.001). To achieve a LC ≥90%, a median marginal dose (Gy) of 15 (range, 12-30Gy) was required. The results corroborate that SRS in HNPs is associated with good clinical and radiological outcome.

    View details for DOI 10.1007/s10143-020-01292-5

    View details for PubMedID 32318920

  • Stereotactic Radiosurgery for Benign Spinal Tumors. Neurosurgery clinics of North America Meola, A., Soltys, S., Schmitt, A., Gerszten, P. C., Chang, S. D. 2020; 31 (2): 231–35


    Benign spinal tumors are rare clinical conditions, including meningiomas, schwannomas, and neurofibromas. Although these tumors are usually treated with open surgical resection, spinal stereotactic radiosurgery may be a safe and effective alternative to surgery in selected patients.

    View details for DOI 10.1016/

    View details for PubMedID 32147014

  • Local control and toxicity outcomes of stereotactic radiosurgery for spinal metastases of gastrointestinal origin. Journal of neurosurgery. Spine Sandhu, N. n., Benson, K. R., Kumar, K. A., Eyben, R. V., Chang, D. T., Gibbs, I. C., Hancock, S. L., Meola, A. n., Chang, S. D., Li, G. n., Hayden-Gephart, M. n., Soltys, S. G., Pollom, E. L. 2020: 1–8


    Colorectal cancer (CRC) and other gastrointestinal (GI) cancers are believed to have greater radioresistance than other histologies. The authors report local control and toxicity outcomes of stereotactic radiosurgery (SRS) to spinal metastases from GI primary cancers.A retrospective single-center review was conducted of patients with spinal metastases from GI primary cancers treated with SRS from 2004 to 2017. Patient demographics and lesion characteristics were summarized using medians, interquartile ranges (IQRs), and proportions. Local failure (LF) was estimated using the cumulative incidence function adjusted for the competing risk of death and compared using Gray's test for equality. Multivariable analyses were conducted using Cox proportional hazard models, adjusting for death as a competing risk, on a per-lesion basis. Patients were stratified in the Cox model to account for repeated measures for clustered outcomes. Median survival was calculated using the Kaplan-Meier method.A total of 74 patients with 114 spine lesions were included in our analysis. The median age of the cohort was 62 years (IQR 53-70 years). Histologies included CRC (46%), hepatocellular carcinoma (19%), neuroendocrine carcinoma (13%), pancreatic carcinoma (12%), and other (10%). The 1- and 2-year cumulative incidence rates of LF were 24% (95% confidence interval [CI] 16%-33%) and 32% (95% CI 23%-42%), respectively. Univariable analysis revealed that older age (p = 0.015), right-sided primary CRCs (p = 0.038), and single fraction equivalent dose (SFED; α/β = 10) < 20 Gy (p = 0.004) were associated with higher rates of LF. The 1-year cumulative incidence rates of LF for SFED < 20 Gy10 versus SFED ≥ 20 Gy10 were 35% and 7%, respectively. After controlling for gross tumor volume and prior radiation therapy to the lesion, SFED < 20 Gy10 remained independently associated with worse LF (hazard ratio 2.92, 95% CI 1.24-6.89, p = 0.014). Toxicities were minimal, with pain flare observed in 6 patients (8%) and 15 vertebral compression fractures (13%).Spinal metastases from GI primary cancers have high rates of LF with SRS at a lower dose. This study found that SRS dose is a significant predictor of failure and that prescribed SFED ≥ 20 Gy10 (biological equivalent dose ≥ 60 Gy10) is associated with superior local control.

    View details for DOI 10.3171/2020.1.SPINE191260

    View details for PubMedID 32114530

  • Tractographic Anatomy of White Matter PEDIATRIC EPILEPSY SURGERY: PREOPERATIVE ASSESSMENT AND SURGICAL TREATMENT, 2ND EDITION Panesar, S. S., Fernandes-Cabral, D. T., Meola, A., Yeh, F., Nunez, M., Fernandez-Mirand, J. C., Cataltepe, O., Jallo, G. 2020: 228–39
  • Predictors of visual functional outcome following treatment for cavernous sinus meningioma. Journal of neurosurgery Fatima, N. n., Ding, V. Y., Han, S. S., Chang, S. D., Meola, A. n. 2020: 1–12


    Cavernous sinus meningioma (CSM) can affect visual function and require expeditious treatment to prevent permanent visual loss. Authors of this retrospective study sought to determine the factors associated with visual functional outcomes in CSM patients treated with surgery, stereotactic radiosurgery (SRS), or stereotactic radiation therapy (SRT), alone or in combination.Consecutive patients with CSM who had presented at an academic tertiary care hospital from 2000 to 2018 were identified through retrospective chart review. Visual function-visual eye deficit (VED), optic disc (OD) appearance, intraocular pressure (IOP), and extraocular movement (EOM)-was assessed before and after treatment for CSM. VED with visual acuity (VA) ≤ 20/200 and visual field defect ≥ -11 dB, pale OD appearance in the ipsilateral or contralateral eye, increased ipsilateral IOP, and/or EOM restriction were defined as a poor visual functional outcome. Multivariable logistic regression was used to evaluate the associations between pretreatment visual functional assessment and posttreatment visual outcomes.The study cohort included 44 patients (73% female; median age 55 years), with a median clinical follow-up of 14 months. Ipsilateral VED improved, remained stable, or worsened, respectively, in 0%, 33.4%, and 66.6% of the patients after subtotal resection (STR) alone; in 52.6%, 31.6%, and 15.8% after STR plus radiation treatment; in 28.5%, 43.0%, and 28.5% after gross-total resection (GTR) alone; and in 56.3%, 43.7%, and 0% after radiation treatment (SRS or SRT) alone. Contralateral VED remained intact in all the patients after STR alone and those with radiation treatment (SRS or SRT) alone; however, it improved, remained stable, or worsened in 10.5%, 84.2%, and 5.3% after STR plus radiation treatment and in 43.0%, 28.5%, and 28.5% after GTR alone. EOM remained intact, fully recovered, remained stable, and worsened, respectively, in 0%, 50%, 50%, and 0% of the patients after STR alone; in 36.8%, 47.4%, 15.8%, and 0% of the patients after STR with radiation treatment; in 57.1%, 0%, 28.6%, and 14.3% of the patients after GTR alone; and in 56.2%, 37.5%, 6.3%, and 0% of the patients after radiation treatment (SRS or SRT) alone.In multivariable analyses adjusted for age, tumor volume, and treatment modality, initial ipsilateral poor VED (OR 10.1, 95% CI 1.05-97.2, p = 0.04) and initial ipsilateral pale OD appearance (OR 21.1, 95% CI 1.6-270.5, p = 0.02) were associated with poor ipsilateral VED posttreatment. Similarly, an initial pale OD appearance (OR 15.7, 95% CI 1.3-199.0, p = 0.03), initial poor VED (OR 21.7, 95% CI 1.2-398.6, p = 0.03), and a higher IOP in the ipsilateral eye (OR 55.3, 95% CI 1.7-173.9, p = 0.02) were associated with an ipsilateral pale OD appearance posttreatment. Furthermore, a higher initial ipsilateral IOP (OR 35.9, 95% CI 3.3-400.5, p = 0.004) was indicative of a higher IOP in the ipsilateral eye posttreatment. Finally, initial restricted EOM was indicative of restricted EOM posttreatment (OR 20.6, 95% CI 18.7-77.0, p = 0.02).Pretreatment visual functional assessment predicts visual outcomes in patients with CSM and can be used to identify patients at greater risk for vision loss.

    View details for DOI 10.3171/2020.2.JNS193009

    View details for PubMedID 32413851

  • Commentary: Peritumoral Edema/Tumor Volume Ratio: A Strong Survival Predictor for Posterior Fossa Metastases NEUROSURGERY Chow, K. H., Meola, A., Chang, S. D. 2019; 85 (1): E18–E19
  • Stereotactic radiosurgery in large intracranial meningiomas: a systematic review. World neurosurgery Fatima, N., Meola, A., Pollom, E., Chaudhary, N., Soltys, S., Chang, S. 2019


    Gross total resection (GTR) of large intracranial meningiomas (LIMs) can be challenging and cause significant morbidity and mortality. The aim of this systematic review is to determine the clinical effectiveness and safety of Stereotactic Radiosurgery (SRS) either as primary or adjuvant therapy for LIMs, with tumor ≥2.5 cm in maximum dimension (tumor volume ≥8.1 cm3). A total of 452 tumors in 496 patients [350 females (69.3%) and 146 males (30.6%)] with median age 60 years (48 to 65 years) were included. The median tumor volume at the time of diagnosis was 16.7 cm3 (10 to 53.3cm3). The tumors were typically located in the skull-base (77.2%), while only 14.6% were in the supratentorial space. The median follow-up after SRS was 54 months (18-90 months). 87.8% of patients were treated with single session gamma knife radiosurgery (SS GKS), while the remaining 12.1% patients received non-single session (non-SS) GKS. Of 452 LIMs assessed for clinical response, 45.1% showed improvement, and 15.7% deteriorated after SRS. Radiographic tumor control at last follow-up (2-7.5 years) ranged from 84% to 100%. Overall, radiation-induced toxicity occurred in 23% of patients; with the most common adverse effect being cranial nerve neuropathy (5.5%) and peritumoral edema (PTE) (5.3%). Sub-group analysis revealed that there is 2-fold higher likelihood of improvement in clinical symptoms in patients with non-SS GKS than SS GKS [OR: 2.47; 95% (1.38-4.44); p=0.002].SRS is safe and effective in the treatment of LIMs as primary or adjuvant treatment. Further prospective studies are required to validate our results.

    View details for DOI 10.1016/j.wneu.2019.06.064

    View details for PubMedID 31226450

  • Efficacy and toxicity of particle radiotherapy in WHO grade II and grade III meningiomas: a systematic review. Neurosurgical focus Wu, A., Jin, M. C., Meola, A., Wong, H., Chang, S. D. 2019; 46 (6): E12


    OBJECTIVEAdjuvant radiotherapy has become a common addition to the management of high-grade meningiomas, as immediate treatment with radiation following resection has been associated with significantly improved outcomes. Recent investigations into particle therapy have expanded into the management of high-risk meningiomas. Here, the authors systematically review studies on the efficacy and utility of particle-based radiotherapy in the management of high-grade meningioma.METHODSA literature search was developed by first defining the population, intervention, comparison, outcomes, and study design (PICOS). A search strategy was designed for each of three electronic databases: PubMed, Embase, and Scopus. Data extraction was conducted in accordance with the PRISMA guidelines. Outcomes of interest included local disease control, overall survival, and toxicity, which were compared with historical data on photon-based therapies.RESULTSEleven retrospective studies including 240 patients with atypical (WHO grade II) and anaplastic (WHO grade III) meningioma undergoing particle radiation therapy were identified. Five of the 11 studies included in this systematic review focused specifically on WHO grade II and III meningiomas; the others also included WHO grade I meningioma. Across all of the studies, the median follow-up ranged from 6 to 145 months. Local control rates for high-grade meningiomas ranged from 46.7% to 86% by the last follow-up or at 5 years. Overall survival rates ranged from 0% to 100% with better prognoses for atypical than for malignant meningiomas. Radiation necrosis was the most common adverse effect of treatment, occurring in 3.9% of specified cases.CONCLUSIONSDespite the lack of randomized prospective trials, this review of existing retrospective studies suggests that particle therapy, whether an adjuvant or a stand-alone treatment, confers survival benefit with a relatively low risk for severe treatment-derived toxicity compared to standard photon-based therapy. However, additional controlled studies are needed.

    View details for DOI 10.3171/2019.3.FOCUS1967

    View details for PubMedID 31153145

  • Magnetic Particle Imaging in Neurosurgery WORLD NEUROSURGERY Meola, A., Rao, J., Chaudhary, N., Song, G., Zheng, X., Chang, S. D. 2019; 125: 261–70
  • In Reply: Commentary: Peritumoral Edema/Tumor Volume Ratio: A Strong Survival Predictor for Posterior Fossa Metastases NEUROSURGERY Meola, A., Chow, K. H., Chang, S. D. 2019; 84 (3): E232
  • "Magnetic Particle Imaging (MPI) in Neurosurgery". World neurosurgery Meola, A., Rao, J., Chaudhary, N., Song, G., Zheng, X., Chang, S. D. 2019


    Magnetic particle imaging (MPI) is a novel radiation-free tomographic imaging method that provides a background-free, signal attenuation-free, direct quantification of the spatial distribution of superparamagnetic iron-oxide nanoparticles (SPIONs) with high temporal resolution (milliseconds), high spatial resolution (< 1 mm), and extreme sensitivity (mumol). The technique is based on non-linear magnetization of the SPIONs when exposed to an oscillating magnetic field. MPI was first described in 2001. Since then, the technique has been applied to experimental imaging of diseases affecting different organs in the human body. The aim of this paper is to review the potential applications of MPI in the field of neurosurgery. MPI has been used for the detection the loco-regional invasion of brain tumors, tracking and monitoring the viability of neural stem cells implanted for neuro-regenerative purposes, diagnosis of cerebral ischemia, and diagnosis and morpho-functional assessment of brain aneurysms. Currently, MPI is at a pre-clinical stage. In the future, human-sized MPI scanners, along with the optimal toxicity profile of SPIONs will allow diagnostic applications in neurosurgical diseases.

    View details for PubMedID 30738942

  • In Reply: Commentary: Peritumoral Edema to Tumor Volume Ratio: A Strong Survival Predictor for Posterior Fossa Metastases. Neurosurgery Meola, A., Chow, K. K., Chang, S. D. 2019

    View details for PubMedID 30629229

  • Stereotactic Radiosurgery for Large Benign Intracranial Tumors. World neurosurgery Fatima, N. n., Meola, A. n., Pollom, E. n., Chang, S. D., Soltys, S. n. 2019


    Historically, it is stated that large intracranial tumors, herein defined as a maximum dimension of > 3cm or tumor volume >14.2 cm3, are not candidates for Stereotactic Radiosurgery (SRS). We report outcomes of patients with large benign intracranial tumors treated with SRS.With IRB approval, we retrospectively identified 74 patients with large benign intracranial tumors (59 meningiomas, 9 vestibular schwannomas, and 6 glomus jugulare tumors) treated with robotic SRS (2007-2018). Patients received definitive SRS in 47.3% of the cases, adjuvant to surgical resection in 44.6%, and salvage following past radiation treatment in 8.1%. A median tumor volume of 16.0 cm3 (10.1-65.5 cm3) received a median dose of 24.0 Gy (14.0-30.0 Gy) in a median of 3 fractions (1-5), for a median single fraction equivalent dose (SFED) (with alpha/beta of 3) of 14.8 Gy (11.3-18.0 Gy). The Kaplan-Meier estimate of tumor local control (LC) was calculated from date of SRS.With a median clinical follow-up of 32.8 months (0.6-125.9 months) and median radiological follow-up of 28.5 months (0.6-121.4 months), LC was 96.5% (95%CI:92.4-100%) at 3-years and 91.7% (95%CI:87.6-95.7%) at 5-years. Adverse radiation effect (ARE) was seen in 10 patients (13.5%) at a median of 13.5 months (7.8-34.5 months). ARE occurred in 9% of those with prior treatment compared to 5% radiation-naïve (p=0.23). With 236.4 person-years of follow-up, no secondary malignancies were seen.Despite the historical adage, we find that SRS provides high rates of LC for these large tumors, with rates of ARE similar to historical reports of SRS for smaller benign tumors.

    View details for DOI 10.1016/j.wneu.2019.10.005

    View details for PubMedID 31605862

  • Automatic Removal of False Connections in Diffusion MRI Tractography Using Topology-Informed Pruning (TIP) NEUROTHERAPEUTICS Yeh, F., Panesar, S., Barrios, J., Fernandes, D., Abhinav, K., Meola, A., Fernandez-Miranda, J. C. 2019; 16 (1): 52–58
  • Stereotactic radiosurgery versus stereotactic radiotherapy in the management of intracranial meningiomas: a systematic review and meta-analysis. Neurosurgical focus Fatima, N. n., Meola, A. n., Pollom, E. L., Soltys, S. G., Chang, S. D. 2019; 46 (6): E2


    OBJECTIVEStereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) have been used as a primary treatment or adjuvant to resection in the management of intracranial meningiomas (ICMs). The aim of this analysis is to compare the safety and long-term efficacy of SRS and SRT in patients with primary or recurrent ICMs.METHODSA systematic review of the literature comparing SRT and SRS in the same study was conducted using PubMed, the Cochrane Library, Google Scholar, and EMBASE from January 1980 to December 2018. Randomized controlled trials, case-control studies, and cohort studies (prospective and retrospective) analyzing SRS versus SRT for the treatment of ICMs in adult patients (age > 16 years) were included. Pooled and subgroup analyses were based on the fixed-effect model.RESULTSA total of 1736 patients from 12 retrospective studies were included. The treatment modality used was: 1) SRS (n = 306), including Gamma Knife surgery (n = 36), linear accelerator (n = 261), and CyberKnife (n = 9); or 2) SRT (n = 1430), including hypofractionated SRT (hFSRT, n = 268) and full-fractionated SRT (FSRT, n = 1162). The median age of patients at the time of treatment was 59 years. The median follow-up duration after treatment was 35.5 months. The median tumor volumes at the time of treatment with SRS, hFSRT, and FSRT were 2.84 cm3, 5.45 cm3, and 12.75 cm3, respectively. The radiographic tumor control at last follow-up was significantly worse in patients who underwent SRS than SRT (odds ratio [OR] 0.47, 95% confidence interval [CI] 0.27-0.82, p = 0.007) with 7% less volume of tumor shrinkage (OR 0.93, 95% CI 0.61-1.40, p = 0.72). Compared to SRS, the radiographic tumor control was better achieved by FSRT (OR 0.46, 95% CI 0.26-0.80, p = 0.006) than by hFSRT (OR 0.81, 95% CI 0.21-3.17, p = 0.76). Moreover, SRS leads to a significantly higher risk of clinical neurological worsening during follow-up (OR 2.07, 95% CI 1.06-4.06, p = 0.03) and of immediate symptomatic edema (OR 4.58, 95% CI 1.67-12.56, p = 0.003) with respect to SRT. SRT could produce a better progression-free survival at 4-10 years compared to SRS, but this was not statistically significant (p = 0.29).CONCLUSIONSSRS and SRT are both safe options in the management of ICMs. However, SRT carries a better radiographic tumor control rate and a lower incidence of posttreatment symptomatic worsening and symptomatic edema, with respect to SRS. However, further prospective studies are still needed to validate these results.

    View details for DOI 10.3171/2019.3.FOCUS1970

    View details for PubMedID 31153149

  • Long-Term Outcome Following Stereotactic Radiosurgery for Glomus Jugulare Tumors: A Single Institution Experience of 20 Years. Neurosurgery Sharma, M., Meola, A., Bellamkonda, S., Jia, X., Montgomery, J., Chao, S. T., Suh, J. H., Angelov, L., Barnett, G. H. 2018; 83 (5): 1007-1014


    Glomus jugulare tumors (GJTs) are rare benign tumors, which pose significant treatment challenges due to proximity to critical structures.To evaluate the long-term clinical and radiological outcome in patients undergoing stereotactic radiosurgery (SRS) for GJTs through retrospective study.Forty-two patients with 43 GJTs were treated using Gamma Knife radiosurgery (GKRS; Elekta AB, Stockholm, Sweden) at our institute from 1997 to 2016. Clinical, imaging, and radiosurgery data were collected from an institutional review board approved database.Most patients were females (n = 35, 83.3%) and median age was 61 yr (range 23-88 yr). Median tumor volume and diameter were 5 cc and 3 cm, respectively, with a median follow-up of 62.3 mo (3.4-218.6 mo). Overall, 20 patients (47.6%) improved clinically and 14 (33.3%) remained unchanged at last follow-up. New onset or worsening of hearing loss was noted in 6 patients (17.2%) after SRS. The median prescription dose to the tumor margin was 15 Gy (12-18 Gy). Median reduction in tumor volume and maximum tumor diameter at last follow-up was 33.3% and 11.54%, respectively. The 5-yr and 10-yr tumor control rates were 87% ± 6% and 69% ± 13%, respectively. There was no correlation between maximum or mean dose to the internal acoustic canal and post-GK hearing loss (P > .05).SRS is safe and effective in patients with GJTs and results in durable, long-term control. SRS has lower morbidity than that associated with surgical resection, particularly lower cranial nerve dysfunction, and can be a first-line management option in these patients.

    View details for DOI 10.1093/neuros/nyx566

    View details for PubMedID 29228343

  • Bilateral Vestibular Schwannomas in Neurofibromatosis Type 2. The New England journal of medicine Meola, A., Chang, S. D. 2018; 379 (15): 1463

    View details for PubMedID 30304657

  • Bilateral Vestibular Schwannomas in Neurofibromatosis Type 2 NEW ENGLAND JOURNAL OF MEDICINE Meola, A., Chang, S. D. 2018; 379 (15): 1463
  • Stereotactic radiosurgery for jugular foramen schwannomas: an international multicenter study. Journal of neurosurgery Kano, H., Meola, A., Yang, H. C., Guo, W. Y., Martínez-Alvarez, R., Martínez-Moreno, N., Urgosik, D., Liscak, R., Cohen-Inbar, O., Sheehan, J., Lee, J. Y., Abbassy, M., Barnett, G. H., Mathieu, D., Kondziolka, D., Lunsford, L. D. 2018; 129 (4): 928-936


    For some jugular foramen schwannomas (JFSs), complete resection is possible but may be associated with significant morbidity. Stereotactic radiosurgery (SRS) is a minimally invasive alternative or adjunct to microsurgery for JFSs. The authors reviewed clinical and imaging outcomes of SRS for patients with these tumors.Nine participating centers of the International Gamma Knife Research Foundation identified 92 patients who underwent SRS between 1990 and 2013. Forty-one patients had prior subtotal microsurgical resection. The median interval between previous surgery and SRS was 15 months (range 0.5-144 months). Eighty-four patients had preexisting cranial nerve (CN) symptoms and signs. The median tumor volume was 4.1 cm3 (range 0.8-22.6 cm3), and the median margin dose was 12.5 Gy (range 10-18 Gy). Patients with neurofibromatosis were excluded from this study.The median follow-up was 51 months (range 6-266 months). Tumors regressed in 47 patients, remained stable in 33, and progressed in 12. The progression-free survival (PFS) was 93% at 3 years, 87% at 5 years, and 82% at 10 years. In the entire series, only a dumbbell shape (extension extracranially via the jugular foramen) was significantly associated with worse PFS. In the group of patients without prior microsurgery (n = 51), factors associated with better PFS included tumor volume < 6 cm3 (p = 0.037) and non-dumbbell-shaped tumors (p = 0.015). Preexisting cranial neuropathies improved in 27 patients, remained stable in 51, and worsened in 14. The CN function improved after SRS in 12% of patients at 1 year, 24% at 2 years, 27% at 3 years, and 32% at 5 years. Symptomatic adverse radiation effects occurred in 7 patients at a median of 7 months after SRS (range 5-38 months). Six patients underwent repeat SRS at a median of 64 months (range 44-134 months). Four patients underwent resection at a median of 14 months after SRS (range 8-30 months).Stereotactic radiosurgery proved to be a safe and effective primary or adjuvant management approach for JFSs. Long-term tumor control rates and stability or improvement in CN function were confirmed.

    View details for DOI 10.3171/2017.5.JNS162894

    View details for PubMedID 29125412

  • Automatic Removal of False Connections in Diffusion MRI Tractography Using Topology-Informed Pruning (TIP). Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics Yeh, F., Panesar, S., Barrios, J., Fernandes, D., Abhinav, K., Meola, A., Fernandez-Miranda, J. C. 2018


    Diffusion MRI fiber tracking provides a non-invasive method for mapping the trajectories of human brain connections, but its false connection problem has been a major challenge. This study introduces topology-informed pruning (TIP), a method that automatically identifies singular tracts and eliminates them to improve the tracking accuracy. The accuracy of the tractography with and without TIP was evaluated by a team of 6 neuroanatomists in a blinded setting to examine whether TIP could improve the accuracy. The results showed that TIP improved the tracking accuracy by 11.93% in the single-shell scheme and by 3.47% in the grid scheme. The improvement is significantly different from a random pruning (p value <0.001). The diagnostic agreement between TIP and neuroanatomists was comparable to the agreement between neuroanatomists. The proposed TIP algorithm can be used to automatically clean-up noisy fibers in deterministic tractography, with a potential to confirm the existence of a fiber connection in basic neuroanatomical studies or clinical neurosurgical planning.

    View details for PubMedID 30218214

  • Population-averaged atlas of the macroscale human structural connectome and its network topology NEUROIMAGE Yeh, F., Panesar, S., Fernandes, D., Meola, A., Yoshino, M., Fernandez-Miranda, J. C., Vettel, J. M., Verstynen, T. 2018; 178: 57–68
  • Correlation Between the Residual Tumor Volume, Extent of Tumor Resection, and O6-Methylguanine DNA Methyltransferase Status in Patients with Glioblastoma. World neurosurgery Sharma, M., Bellamkonda, S., Mohapatra, S., Meola, A., Jia, X., Mohammadi, A., Angelov, L., Barnett, G. H., Vogelbaum, M., Ahluwalia, M. S. 2018; 116: e147-e161


    There is limited information on O6-methylguanine DNA methyltransferase (MGMT) status, extent of surgical resection, and its impact on overall outcomes in patients with glioblastoma (GBM).After institutional review board approval, 233 newly diagnosed patients with GBM with known MGMT status (2009-2015) were included in our analysis. Clinical, imaging, and follow-up data were collected from the database. Overall survival (OS) and progression-free survival (PFS) were the primary and secondary end points, respectively.Of patients, 51.9% were younger than 65 years and 44.2% were noted to have promoter methylation of MGMT. Median residual tumor volume was 1.1 cm3 and extent of complete resection of enhancing tumor on imaging was 96%. Estimated median OS and PFS were 10.9 months and 5.4 months, respectively. MGMT status was an independent predictor of PFS (hazard ratio [HR], 0.52; P = 0.005) but only marginally associated with OS (P = 0.059). In MGMT methylated patients, extent of resection (≥86%) and good performance status (Karnofsky Performance Status ≥70) were independently associated with PFS and OS, respectively (PFS: HR, 0.21; P = 0.015; OS: HR, 0.05; P = 0.002). In MGMT promoter unmethylated patients, extent of resection (≥86%) was independently associated with OS (P = 0.039). Concurrent chemoradiotherapy was associated with OS/PFS irrespective of age and MGMT status.Greater extent of resection of enhancing tumor was associated with improved PFS in MGMT promoter methylated patients, OS regardless of MGMT status. Elderly patients with methylated MGMT promoter were found to have improved PFS whereas younger patients had improved OS with MGMT promoter methylated status.

    View details for DOI 10.1016/j.wneu.2018.04.134

    View details for PubMedID 29709748

  • Commentary: Peritumoral Edema/Tumor Volume Ratio: A Strong Survival Predictor for Posterior Fossa Metastases. Neurosurgery Chow, K. K., Meola, A., Chang, S. D. 2018

    View details for PubMedID 29982666

  • Letter: Navigation-Linked Heads-Up Display in Intracranial Surgery: Early Experience. Operative neurosurgery (Hagerstown, Md.) Meola, A., Chang, S. D. 2018; 14 (6): E71–E72

    View details for PubMedID 29590481

  • Letter: Navigation-Linked Heads-Up Display in Intracranial Surgery: Early Experience OPERATIVE NEUROSURGERY Meola, A., Chang, S. D. 2018; 14 (6): E71–E72

    View details for DOI 10.1093/ons/opy048

    View details for Web of Science ID 000449371500004

  • Population-averaged atlas of the macroscale human structural connectome and its network topology. NeuroImage Yeh, F., Panesar, S., Fernandes, D., Meola, A., Yoshino, M., Fernandez-Miranda, J. C., Vettel, J. M., Verstynen, T. 2018; 178: 57–68


    A comprehensive map of the structural connectome in the human brain has been a coveted resource for understanding macroscopic brain networks. Here we report an expert-vetted, population-averaged atlas of the structural connectome derived from diffusion MRI data (N = 842). This was achieved by creating a high-resolution template of diffusion patterns averaged across individual subjects and using tractography to generate 550,000 trajectories of representative white matter fascicles annotated by 80 anatomical labels. The trajectories were subsequently clustered and labeled by a team of experienced neuroanatomists in order to conform to prior neuroanatomical knowledge. A multi-level network topology was then described using whole-brain connectograms, with subdivisions of the association pathways showing small-worldness in intra-hemisphere connections, projection pathways showing hub structures at thalamus, putamen, and brainstem, and commissural pathways showing bridges connecting cerebral hemispheres to provide global efficiency. This atlas of the structural connectome provides representative organization of human brain white matter, complementary to traditional histologically-derived and voxel-based white matter atlases, allowing for better modeling and simulation of brain connectivity for future connectome studies.

    View details for PubMedID 29758339

  • Gold Nanoparticles for Brain tumor imaging: a Systematic Review FRONTIERS IN NEUROLOGY Meola, A., Rao, J., Chaudhary, N., Sharma, M., Chang, S. D. 2018; 9: 328


    Demarcation of malignant brain tumor boundaries is critical to achieve complete resection and to improve patient survival. Contrast-enhanced brain magnetic resonance imaging (MRI) is the gold standard for diagnosis and pre-surgical planning, despite limitations of gadolinium (Gd)-based contrast agents to depict tumor margins. Recently, solid metal-based nanoparticles (NPs) have shown potential as diagnostic probes for brain tumors. Gold nanoparticles (GNPs) emerged among those, because of their unique physical and chemical properties and biocompatibility. The aim of the present study is to review the application of GNPs for in vitro and in vivo brain tumor diagnosis.We performed a PubMed search of reports exploring the application of GNPs in the diagnosis of brain tumors in biological models including cells, animals, primates, and humans. The search words were "gold" AND "NP" AND "brain tumor." Two reviewers performed eligibility assessment independently in an unblinded standardized manner. The following data were extracted from each paper: first author, year of publication, animal/cellular model, GNP geometry, GNP size, GNP coating [i.e., polyethylene glycol (PEG) and Gd], blood-brain barrier (BBB) crossing aids, imaging modalities, and therapeutic agents conjugated to the GNPs.The PubMed search provided 100 items. A total of 16 studies, published between the 2011 and 2017, were included in our review. No studies on humans were found. Thirteen studies were conducted in vivo on rodent models. The most common shape was a nanosphere (12 studies). The size of GNPs ranged between 20 and 120 nm. In eight studies, the GNPs were covered in PEG. The BBB penetration was increased by surface molecules (nine studies) or by means of external energy sources (in two studies). The most commonly used imaging modalities were MRI (four studies), surface-enhanced Raman scattering (three studies), and fluorescent microscopy (three studies). In two studies, the GNPs were conjugated with therapeutic agents.Experimental studies demonstrated that GNPs might be versatile, persistent, and safe contrast agents for multimodality imaging, thus enhancing the tumor edges pre-, intra-, and post-operatively improving microscopic precision. The diagnostic GNPs might also be used for multiple therapeutic approaches, namely as "theranostic" NPs.

    View details for PubMedID 29867737

  • Stereotactic Radiosurgery for Intracranial Ependymomas: An International Multicenter Study. Neurosurgery Kano, H., Su, Y. H., Wu, H. M., Simonova, G., Liscak, R., Cohen-Inbar, O., Sheehan, J. P., Meola, A., Sharma, M., Barnett, G. H., Mathieu, D., Vasas, L. T., Kaufmann, A. M., Jacobs, R. C., Lunsford, L. D. 2018


    Stereotactic radiosurgery (SRS) is a potentially important option for intracranial ependymoma patients.To analyze the outcomes of intracranial ependymoma patients who underwent SRS as a part of multimodality management.Seven centers participating in the International Gamma Knife Research Foundation identified 89 intracranial ependymoma patients who underwent SRS (113 tumors). The median patient age was 16.3 yr (2.9-80). All patients underwent previous surgical resection and radiation therapy (RT) of their ependymomas and 40 underwent previous chemotherapy. Grade 2 ependymomas were present in 42 patients (52 tumors) and grade 3 ependymomas in 48 patients (61 tumors). The median tumor volume was 2.2 cc (0.03-36.8) and the median margin dose was 15 Gy (9-24).Forty-seven (53%) patients were alive and 42 (47%) patients died at the last follow-up. The overall survival after SRS was 86% at 1 yr, 50% at 3 yr, and 44% at 5 yr. Smaller total tumor volume was associated with longer overall survival (P = .006). Twenty-two patients (grade 2: n = 9, grade 3: n = 13) developed additional recurrent ependymomas in the craniospinal axis. The progression-free survival after SRS was 71% at 1 yr, 56% at 3 yr, and 48% at 5 yr. Adult age, female sex, and smaller tumor volume indicated significantly better progression-free survival. Symptomatic adverse radiation effects were seen in 7 patients (8%).SRS provides another management option for residual or recurrent progressive intracranial ependymoma patients who have failed initial surgery and RT.

    View details for DOI 10.1093/neuros/nyy082

    View details for PubMedID 29608701

  • Image Registration to Compensate for EPI Distortion in Patients with Brain Tumors: An Evaluation of Tract-Specific Effects. Journal of neuroimaging : official journal of the American Society of Neuroimaging Albi, A., Meola, A., Zhang, F., Kahali, P., Rigolo, L., Tax, C. M., Ciris, P. A., Essayed, W. I., Unadkat, P., Norton, I., Rathi, Y., Olubiyi, O., Golby, A. J., O'Donnell, L. J. 2018; 28 (2): 173-182


    Diffusion magnetic resonance imaging (dMRI) provides preoperative maps of neurosurgical patients' white matter tracts, but these maps suffer from echo-planar imaging (EPI) distortions caused by magnetic field inhomogeneities. In clinical neurosurgical planning, these distortions are generally not corrected and thus contribute to the uncertainty of fiber tracking. Multiple image processing pipelines have been proposed for image-registration-based EPI distortion correction in healthy subjects. In this article, we perform the first comparison of such pipelines in neurosurgical patient data.Five pipelines were tested in a retrospective clinical dMRI dataset of 9 patients with brain tumors. Pipelines differed in the choice of fixed and moving images and the similarity metric for image registration. Distortions were measured in two important tracts for neurosurgery, the arcuate fasciculus and corticospinal tracts.Significant differences in distortion estimates were found across processing pipelines. The most successful pipeline used dMRI baseline and T2-weighted images as inputs for distortion correction. This pipeline gave the most consistent distortion estimates across image resolutions and brain hemispheres.Quantitative results of mean tract distortions on the order of 1-2 mm are in line with other recent studies, supporting the potential need for distortion correction in neurosurgical planning. Novel results include significantly higher distortion estimates in the tumor hemisphere and greater effect of image resolution choice on results in the tumor hemisphere. Overall, this study demonstrates possible pitfalls and indicates that care should be taken when implementing EPI distortion correction in clinical settings.

    View details for DOI 10.1111/jon.12485

    View details for PubMedID 29319208

    View details for PubMedCentralID PMC5844838

  • A new head-mounted display-based augmented reality system in neurosurgical oncology: a study on phantom. Computer assisted surgery (Abingdon, England) Cutolo, F., Meola, A., Carbone, M., Sinceri, S., Cagnazzo, F., Denaro, E., Esposito, N., Ferrari, M., Ferrari, V. 2017; 22 (1): 39-53


    Benefits of minimally invasive neurosurgery mandate the development of ergonomic paradigms for neuronavigation. Augmented Reality (AR) systems can overcome the shortcomings of commercial neuronavigators. The aim of this work is to apply a novel AR system, based on a head-mounted stereoscopic video see-through display, as an aid in complex neurological lesion targeting. Effectiveness was investigated on a newly designed patient-specific head mannequin featuring an anatomically realistic brain phantom with embedded synthetically created tumors and eloquent areas.A two-phase evaluation process was adopted in a simulated small tumor resection adjacent to Broca's area. Phase I involved nine subjects without neurosurgical training in performing spatial judgment tasks. In Phase II, three surgeons were involved in assessing the effectiveness of the AR-neuronavigator in performing brain tumor targeting on a patient-specific head phantom.Phase I revealed the ability of the AR scene to evoke depth perception under different visualization modalities. Phase II confirmed the potentialities of the AR-neuronavigator in aiding the determination of the optimal surgical access to the surgical target.The AR-neuronavigator is intuitive, easy-to-use, and provides three-dimensional augmented information in a perceptually-correct way. The system proved to be effective in guiding skin incision, craniotomy, and lesion targeting. The preliminary results encourage a structured study to prove clinical effectiveness. Moreover, our testing platform might be used to facilitate training in brain tumour resection procedures.

    View details for DOI 10.1080/24699322.2017.1358400

    View details for PubMedID 28754068

  • Automated white matter fiber tract identification in patients with brain tumors. NeuroImage. Clinical O'Donnell, L. J., Suter, Y., Rigolo, L., Kahali, P., Zhang, F., Norton, I., Albi, A., Olubiyi, O., Meola, A., Essayed, W. I., Unadkat, P., Ciris, P. A., Wells, W. M., Rathi, Y., Westin, C. F., Golby, A. J. 2017; 13: 138-153


    We propose a method for the automated identification of key white matter fiber tracts for neurosurgical planning, and we apply the method in a retrospective study of 18 consecutive neurosurgical patients with brain tumors. Our method is designed to be relatively robust to challenges in neurosurgical tractography, which include peritumoral edema, displacement, and mass effect caused by mass lesions. The proposed method has two parts. First, we learn a data-driven white matter parcellation or fiber cluster atlas using groupwise registration and spectral clustering of multi-fiber tractography from healthy controls. Key fiber tract clusters are identified in the atlas. Next, patient-specific fiber tracts are automatically identified using tractography-based registration to the atlas and spectral embedding of patient tractography. Results indicate good generalization of the data-driven atlas to patients: 80% of the 800 fiber clusters were identified in all 18 patients, and 94% of the 800 fiber clusters were found in 16 or more of the 18 patients. Automated subject-specific tract identification was evaluated by quantitative comparison to subject-specific motor and language functional MRI, focusing on the arcuate fasciculus (language) and corticospinal tracts (motor), which were identified in all patients. Results indicate good colocalization: 89 of 95, or 94%, of patient-specific language and motor activations were intersected by the corresponding identified tract. All patient-specific activations were within 3mm of the corresponding language or motor tract. Overall, our results indicate the potential of an automated method for identifying fiber tracts of interest for neurosurgical planning, even in patients with mass lesions.

    View details for DOI 10.1016/j.nicl.2016.11.023

    View details for PubMedID 27981029

    View details for PubMedCentralID PMC5144756

  • Magnetic Resonance Thermometry and Laser Interstitial Thermal Therapy for Brain Tumors. Neurosurgery clinics of North America Silva, D., Sharma, M., Juthani, R., Meola, A., Barnett, G. H. 2017; 28 (4): 525-533


    Recent technological advancements in intraoperative imaging are shaping the way for a new era in brain tumor surgery. Magnetic resonance thermometry has provided intraoperative real-time imaging feedback for safe and effective application of laser interstitial thermal therapy (LITT) in neuro-oncology. Thermal ablation has also established itself as a surgical option in epilepsy surgery and is currently used in spine oncology with promising results. This article reviews the principles and rationale as well as the clinical application of LITT for brain tumors. It also discusses the technical nuances of the current commercially available systems.

    View details for DOI 10.1016/

    View details for PubMedID 28917281

  • Augmented reality in neurosurgery: a systematic review. Neurosurgical review Meola, A., Cutolo, F., Carbone, M., Cagnazzo, F., Ferrari, M., Ferrari, V. 2017; 40 (4): 537-548


    Neuronavigation has become an essential neurosurgical tool in pursuing minimal invasiveness and maximal safety, even though it has several technical limitations. Augmented reality (AR) neuronavigation is a significant advance, providing a real-time updated 3D virtual model of anatomical details, overlaid on the real surgical field. Currently, only a few AR systems have been tested in a clinical setting. The aim is to review such devices. We performed a PubMed search of reports restricted to human studies of in vivo applications of AR in any neurosurgical procedure using the search terms "Augmented reality" and "Neurosurgery." Eligibility assessment was performed independently by two reviewers in an unblinded standardized manner. The systems were qualitatively evaluated on the basis of the following: neurosurgical subspecialty of application, pathology of treated lesions and lesion locations, real data source, virtual data source, tracking modality, registration technique, visualization processing, display type, and perception location. Eighteen studies were included during the period 1996 to September 30, 2015. The AR systems were grouped by the real data source: microscope (8), hand- or head-held cameras (4), direct patient view (2), endoscope (1), and X-ray fluoroscopy (1) head-mounted display (1). A total of 195 lesions were treated: 75 (38.46 %) were neoplastic, 77 (39.48 %) neurovascular, and 1 (0.51 %) hydrocephalus, and 42 (21.53 %) were undetermined. Current literature confirms that AR is a reliable and versatile tool when performing minimally invasive approaches in a wide range of neurosurgical diseases, although prospective randomized studies are not yet available and technical improvements are needed.

    View details for DOI 10.1007/s10143-016-0732-9

    View details for PubMedID 27154018

    View details for PubMedCentralID PMC6155988

  • Stereotactic radiosurgery for intracranial hemangiopericytomas: a multicenter study. Journal of neurosurgery Cohen-Inbar, O., Lee, C. C., Mousavi, S. H., Kano, H., Mathieu, D., Meola, A., Nakaji, P., Honea, N., Johnson, M., Abbassy, M., Mohammadi, A. M., Silva, D., Yang, H. C., Grills, I., Kondziolka, D., Barnett, G. H., Lunsford, L. D., Sheehan, J. 2017; 126 (3): 744-754


    OBJECTIVE Hemangiopericytomas (HPCs) are rare tumors widely recognized for their aggressive clinical behavior, high recurrence rates, and distant and extracranial metastases even after a gross-total resection. The authors report a large multicenter study, through the International Gamma Knife Research Foundation (IGKRF), reviewing management and outcome following stereotactic radiosurgery (SRS) for recurrent or newly discovered HPCs. METHODS Eight centers participating in the IGKRF participated in this study. A total of 90 patients harboring 133 tumors were identified. Patients were included if they had a histologically diagnosed HPC managed with SRS during the period 1988-2014 and had a minimum of 6 months' clinical and radiological follow-up. A de-identified database was created. The patients' median age was 48.5 years (range 13-80 years). Prior treatments included embolization (n = 8), chemotherapy (n = 2), and fractionated radiotherapy (n = 34). The median tumor volume at the time of SRS was 4.9 cm3 (range 0.2-42.4 cm3). WHO Grade II (typical) HPCs formed 78.9% of the cohort (n = 71). The median margin and maximum doses delivered were 15 Gy (range 2.8-24 Gy) and 32 Gy (range 8-51 Gy), respectively. The median clinical and radiographic follow-up periods were 59 months (range 6-190 months) and 59 months (range 6-183 months), respectively. Prognostic variables associated with local tumor control and post-SRS survival were evaluated using Cox univariate and multivariate analysis. Actuarial survival after SRS was analyzed using the Kaplan-Meier method. RESULTS Imaging studies performed at last follow-up demonstrated local tumor control in 55% of tumors and 62.2% of patients. New remote intracranial tumors were found in 27.8% of patients, and 24.4% of patients developed extracranial metastases. Adverse radiation effects were noted in 6.7% of patients. During the study period, 32.2% of the patients (n = 29) died. The actuarial overall survival was 91.5%, 82.1%, 73.9%, 56.7%, and 53.7% at 2, 4, 6, 8, and 10 years, respectively, after initial SRS. Local progression-free survival (PFS) was 81.7%, 66.3%, 54.5%, 37.2%, and 25.5% at 2, 4, 6, 8, and 10 years, respectively, after initial SRS. In our cohort, 32 patients underwent 48 repeat SRS procedures for 76 lesions. Review of these 76 treated tumors showed that 17 presented as an in-field recurrence and 59 were defined as an out-of-field recurrence. Margin dose greater than 16 Gy (p = 0.037) and tumor grade (p = 0.006) were shown to influence PFS. The development of extracranial metastases was shown to influence overall survival (p = 0.029) in terms of PFS; repeat (multiple) SRS showed additional benefit. CONCLUSIONS SRS provides a reasonable rate of local tumor control and a low risk of adverse effects. It also leads to neurological stability or improvement in the majority of patients. Long-term close clinical and imaging follow-up is necessary due to the high probability of local recurrence and distant metastases. Repeat SRS is often effective for treating new or recurrent HPCs.

    View details for DOI 10.3171/2016.1.JNS152860

    View details for PubMedID 27104850

  • Impact of cervicothoracic region stereotactic spine radiosurgery on adjacent organs at risk. Neurosurgical focus Sharma, M., Bennett, E. E., Rahmathulla, G., Chao, S. T., Koech, H. K., Gregory, S. N., Emch, T., Magnelli, A., Meola, A., Suh, J. H., Angelov, L. 2017; 42 (1): E14


    OBJECTIVE Stereotactic radiosurgery (SRS) of the spine is a conformal method of delivering a high radiation dose to a target in a single or few (usually ≤ 5) fractions with a sharp fall-off outside the target volume. Although efforts have been focused on evaluating spinal cord tolerance when treating spinal column metastases, no study has formally evaluated toxicity to the surrounding organs at risk (OAR), such as the brachial plexus or the oropharynx, when performing SRS in the cervicothoracic region. The aim of this study was to evaluate the radiation dosimetry and the acute and delayed toxicities of SRS on OAR in such patients. METHODS Fifty-six consecutive patients (60 procedures) with a cervicothoracic spine tumor involving segments within C5-T1 who were treated using single-fraction SRS between February 2006 and July 2014 were included in the study. Each patient underwent CT simulation and high-definition MRI before treatment. The clinical target volume and OAR were contoured on BrainScan and iPlan software after image fusion. Radiation toxicity was evaluated using the common toxicity criteria for adverse events and correlated to the radiation doses delivered to these regions. The incidence of vertebral body compression fracture (VCF) before and after SRS was evaluated also. RESULTS Metastatic lesions constituted the majority (n = 52 [93%]) of tumors treated with SRS. Each patient was treated with a median single prescription dose of 16 Gy to the target. The median percentage of tumor covered by SRS was 93% (maximum target dose 18.21 Gy). The brachial plexus received the highest mean maximum dose of 17 Gy, followed by the esophagus (13.8 Gy) and spinal cord (13 Gy). A total of 14 toxicities were encountered in 56 patients (25%) during the study period. Overall, 14% (n = 8) of the patients had Grade 1 toxicity, 9% (n = 5) had Grade 2 toxicity, 2% (n = 1) had Grade 3 toxicity, and none of the patients had Grade 4 or 5 toxicity. The most common (12%) toxicity was dysphagia/odynophagia, followed by axial spine pain flare or painful radiculopathy (9%). The maximum radiation dose to the brachial plexus showed a trend toward significance (p = 0.066) in patients with worsening post-SRS pain. De novo and progressive VCFs after SRS were noted in 3% (3 of 98) and 4% (4 of 98) of vertebral segments, respectively. CONCLUSIONS From the analysis, the current SRS doses used at the Cleveland Clinic seem safe and well tolerated at the cervicothoracic junction. These preliminary data provide tolerance benchmarks for OAR in this region. Because the effect of dose-escalation SRS strategies aimed at improving local tumor control needs to be balanced carefully with associated treatment-related toxicity on adjacent OAR, larger prospective studies using such approaches are needed.

    View details for DOI 10.3171/2016.10.FOCUS16364

    View details for PubMedID 28041323

  • Teaching NeuroImages: Stroke mimicking thalamotomy: Cessation of tremor following ventrolateral thalamic ischemia. Neurology Horn, A., Kipp, L., Meola, A., Kühn, A. A., Leithner, C. 2016; 87 (17): e208-e209

    View details for DOI 10.1212/WNL.0000000000003263

    View details for PubMedID 27777349

  • Letter to the Editor. Brain injury Meola, A. 2016; 30 (13-14): 1515-1516

    View details for DOI 10.1080/02699052.2016.1199912

    View details for PubMedID 27740866

  • Human Connectome-Based Tractographic Atlas of the Brainstem Connections and Surgical Approaches NEUROSURGERY Meola, A., Yeh, F., Fellows-Mayle, W., Weed, J., Fernandez-Miranda, J. C. 2016; 79 (3): 437–54


    The brainstem is one of the most challenging areas for the neurosurgeon because of the limited space between gray matter nuclei and white matter pathways. Diffusion tensor imaging-based tractography has been used to study the brainstem structure, but the angular and spatial resolution could be improved further with advanced diffusion magnetic resonance imaging (MRI).To construct a high-angular/spatial resolution, wide-population-based, comprehensive tractography atlas that presents an anatomical review of the surgical approaches to the brainstem.We applied advanced diffusion MRI fiber tractography to a population-based atlas constructed with data from a total of 488 subjects from the Human Connectome Project-488. Five formalin-fixed brains were studied for surgical landmarks. Luxol Fast Blue-stained histological sections were used to validate the results of tractography.We acquired the tractography of the major brainstem pathways and validated them with histological analysis. The pathways included the cerebellar peduncles, corticospinal tract, corticopontine tracts, medial lemniscus, lateral lemniscus, spinothalamic tract, rubrospinal tract, central tegmental tract, medial longitudinal fasciculus, and dorsal longitudinal fasciculus. Then, the reconstructed 3-dimensional brainstem structure was sectioned at the level of classic surgical approaches, namely supracollicular, infracollicular, lateral mesencephalic, perioculomotor, peritrigeminal, anterolateral (to the medulla), and retro-olivary approaches.The advanced diffusion MRI fiber tracking is a powerful tool to explore the brainstem neuroanatomy and to achieve a better understanding of surgical approaches.CN, cranial nerveCPT, corticopontine tractCST, corticospinal tractCTT, central tegmental tractDLF, dorsal longitudinal fasciculusHCP, Human Connectome ProjectML, medial lemniscusMLF, medial longitudinal fasciculusRST, rubrospinal tractSTT, spinothalamic tract.

    View details for PubMedID 26914259

  • The nondecussating pathway of the dentatorubrothalamic tract in humans: human connectome-based tractographic study and microdissection validation JOURNAL OF NEUROSURGERY Meola, A., Comert, A., Yeh, F., Sivakanthan, S., Fernandez-Miranda, J. C. 2016; 124 (5): 1406–12


    OBJECT The dentatorubrothalamic tract (DRTT) is the major efferent cerebellar pathway arising from the dentate nucleus (DN) and decussating to the contralateral red nucleus (RN) and thalamus. Surprisingly, hemispheric cerebellar output influences bilateral limb movements. In animals, uncrossed projections from the DN to the ipsilateral RN and thalamus may explain this phenomenon. The aim of this study was to clarify the anatomy of the dentatorubrothalamic connections in humans. METHODS The authors applied advanced deterministic fiber tractography to a template of 488 subjects from the Human Connectome Project (Q1-Q3 release, WU-Minn HCP consortium) and validated the results with microsurgical dissection of cadaveric brains prepared according to Klingler's method. RESULTS The authors identified the "classic" decussating DRTT and a corresponding nondecussating path (the nondecussating DRTT, nd-DRTT). Within each of these 2 tracts some fibers stop at the level of the RN, forming the dentatorubro tract and the nondecussating dentatorubro tract. The left nd-DRTT encompasses 21.7% of the tracts and 24.9% of the volume of the left superior cerebellar peduncle, and the right nd-DRTT encompasses 20.2% of the tracts and 28.4% of the volume of the right superior cerebellar peduncle. CONCLUSIONS The connections of the DN with the RN and thalamus are bilateral, not ipsilateral only. This affords a potential anatomical substrate for bilateral limb motor effects originating in a single cerebellar hemisphere under physiological conditions, and for bilateral limb motor impairment in hemispheric cerebellar lesions such as ischemic stroke and hemorrhage, and after resection of hemispheric tumors and arteriovenous malformations. Furthermore, when a lesion is located on the course of the dentatorubrothalamic system, a careful preoperative tractographic analysis of the relationship of the DRTT, nd-DRTT, and the lesion should be performed in order to tailor the surgical approach properly and spare all bundles.

    View details for PubMedID 26452117

  • The Controversial Existence of the Human Superior Fronto-Occipital Fasciculus: Connectome-Based Tractographic Study With Microdissection Validation HUMAN BRAIN MAPPING Meola, A., Comert, A., Yeh, F., Stefaneanu, L., Fernandez-Miranda, J. C. 2015; 36 (12): 4964–71


    The superior fronto-occipital fasciculus (SFOF), a long association bundle that connects frontal and occipital lobes, is well-documented in monkeys but is controversial in human brain. Its assumed role is in visual processing and spatial awareness. To date, anatomical and neuroimaging studies on human and animal brains are not in agreement about the existence, course, and terminations of SFOF. To clarify the existence of the SFOF in human brains, we applied deterministic fiber tractography to a template of 488 healthy subjects and to 80 individual subjects from the Human Connectome Project (HCP) and validated the results with white matter microdissection of post-mortem human brains. The imaging results showed that previous reconstructions of the SFOF were generated by two false continuations, namely between superior thalamic peduncle (STP) and stria terminalis (ST), and ST and posterior thalamic peduncle. The anatomical microdissection confirmed this finding. No other fiber tracts in the previously described location of the SFOF were identified. Hence, our data suggest that the SFOF does not exist in the human brain.

    View details for PubMedID 26435158

    View details for PubMedCentralID PMC4715628

  • Peduncles Without Cerebellum: The Cerebellar Agenesis EUROPEAN NEUROLOGY Meola, A., Fernandez-Miranda, J. C. 2015; 74 (3-4): 162

    View details for DOI 10.1159/000441055

    View details for Web of Science ID 000366741200007

    View details for PubMedID 26452266

  • Hydrocephalus following bilateral dumbbell-shaped c2 spinal neurofibromas resection and postoperative cervical pseudomeningocele in a patient with neurofibromatosis type 1: a case report. Evidence-based spine-care journal Montemurro, N., Cocciaro, A., Meola, A., Lutzemberger, L., Vannozzi, R. 2014; 5 (2): 136-8


    Study Design Case report. Objective To present a rare case of hydrocephalus following bilateral dumbbell-shaped C2 spinal neurofibromas resection and postoperative cervical pseudomeningocele in a patient with neurofibromatosis type 1 (NF1). Methods The patient's clinical course is retrospectively reviewed. A 37-year-old man affected by NF1 referred to our department for progressive weakness of both lower extremities and gait disturbance. Radiological imaging showed bilateral dumbbell-shaped C2 spinal neurofibromas. After its resection, at the 1-month follow-up evaluation, the patient reported headache and nausea. A CT brain scan showed a postoperative cervical pseudomeningocele and an increase in the ventricular sizes, resulting in hydrocephalus. Results A ventriculoperitoneal shunting was performed using a programmable valve opening pressure set to 120 mmH20. After surgery, the patient's neurological status markedly improved. Conclusion Hydrocephalus must be considered a possible complication of cervical spine tumor resection.

    View details for DOI 10.1055/s-0034-1387805

    View details for PubMedID 25364327

    View details for PubMedCentralID PMC4212698

  • Management and outcome of high-grade multicentric gliomas: a contemporary single-institution series and review of the literature. Acta neurochirurgica di Russo, P., Perrini, P., Pasqualetti, F., Meola, A., Vannozzi, R. 2013; 155 (12): 2245-51


    Multicentric malignant gliomas are well-separated tumours in different lobes or hemispheres, without anatomical continuity between lesions. The purpose of this study was to explore the clinical features, the pathology and the outcome according to the management strategies in a consecutive series of patients treated at a single institution. In addition, an analysis of the existing literature is presented.For the institutional analysis, a retrospective review of all patients who underwent treatment for multicentric gliomas in the last 7 years was performed. For the analysis of the literature, a MEDLINE search with no date limitations was accomplished for surgical treatment of multicentric malignant gliomas.Two hundred and thirty-nine patients with glioma were treated in our department. Eighteen patients (7.5 %) with a mean age of 64 years (age range, 37-78 years) presented multicentric malignant gliomas. Thirteen patients (72 %) underwent surgical resection of at least one lesion that was followed by adjuvant treatment in all but one case. Five patients (28 %) underwent stereotactic biopsy and thereafter received chemotherapy. A survival advantage was associated with resection of at least one lesion followed by adjuvant treatment (median overall survival 12 months) compared with 4 months for stereotactic biopsy followed by chemotherapy. Similar results were obtained from the review of the literature.Resection of at least one lesion seems to play a significant role in the management of selected patients with multicentric malignant gliomas. Multi-institutional studies on larger series are warranted to define how aggressively the patients with malignant multicentric gliomas should be treated.

    View details for DOI 10.1007/s00701-013-1892-9

    View details for PubMedID 24105045

  • Primary dumbbell-shaped lymphoma of the thoracic spine: a case report. Case reports in neurological medicine Meola, A., Perrini, P., Montemurro, N., di Russo, P., Tiezzi, G. 2012; 2012: 647682


    Primary spinal non-Hodgkin's lymphoma is extremely rare, and the occurrence of spinal dumbbell-shaped lymphoma is exceptional. We present a case of primary spinal dumbbell-shaped lymphoma to clarify the diagnosis and the management of these lesions. A 45-year-old man presented with sensory symptoms for 8 months. Magnetic resonance imaging of the thoracic spine demonstrated a dumbbell-shaped lesion at the D4-D6 level with spinal cord compression and right foraminal extension at D4-D5 level. The patient underwent D4-D6 laminectomy, with a subtotal resection of the mass. Diffuse large B-cell lymphoma was diagnosed in the pathological examination. He underwent local spinal radiotherapy and chemotherapy. Follow-up evaluation at one year demonstrated no evidence of relapse. Although highly unusual, lymphoma should be included in the differential diagnosis for spinal dumbbell-shaped tumours. After surgery and adjuvant therapy a long-term clinical and neuroradiological followup is mandatory.

    View details for DOI 10.1155/2012/647682

    View details for PubMedID 23227379

    View details for PubMedCentralID PMC3514806