Bio

Clinical Focus


  • Neurosurgery

Academic Appointments


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)

Professional Education


  • Fellowship:Brigham and Women's Hospital Anesthesiology Residency (2016) MA
  • PhD Training:University of Florence (2016) Italy
  • Fellowship:Cleveland Clinic Foundation (2017) OH
  • Residency:University of Pisa (2015) Italy
  • Internship:University of Pisa (2009) Italy
  • Medical Education:University of Pisa (2008) Italy
  • 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)

Publications

All Publications


  • 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 DOI 10.1056/NEJMicm1804944

    View details for PubMedID 30304657

  • 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

    Abstract

    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 DOI 10.1007/s13311-018-0663-y

    View details for PubMedID 30218214

  • 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 DOI 10.1093/neuros/nyy281

    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 DOI 10.1093/ons/opy048

    View details for PubMedID 29590481

  • 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

    Abstract

    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 DOI 10.1016/j.neuroimage.2018.05.027

    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

    Abstract

    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 DOI 10.3389/fneur.2018.00328

    View details for Web of Science ID 000431972100001

    View details for PubMedID 29867737

    View details for PubMedCentralID PMC5960696

  • 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): 928–36

    Abstract

    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

  • 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): 173–82

    Abstract

    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

  • 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

    Abstract

    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

  • 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): 1007–14

    Abstract

    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

  • 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

    Abstract

    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

  • Augmented reality in neurosurgery: a systematic review. Neurosurgical review Meola, A., Cutolo, F., Carbone, M., Cagnazzo, F., Ferrari, M., Ferrari, V. 2017; 40 (4): 537–48

    Abstract

    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

  • 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): 525–33

    Abstract

    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/j.nec.2017.05.015

    View details for PubMedID 28917281

  • 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

    Abstract

    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

  • 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): 744–54

    Abstract

    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

    Abstract

    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

  • 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: 138–53

    Abstract

    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

  • 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

    Abstract

    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 DOI 10.1227/NEU.0000000000001224

    View details for Web of Science ID 000383274400028

    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

    Abstract

    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 DOI 10.3171/2015.4.JNS142741

    View details for Web of Science ID 000374723000022

    View details for PubMedID 26452117

  • 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): 1515–16

    View details for DOI 10.1080/02699052.2016.1199912

    View details for PubMedID 27740866

  • 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

    Abstract

    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 DOI 10.1002/hbm.22990

    View details for Web of Science ID 000368283100017

    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): 136–38

    Abstract

    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

    Abstract

    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

    Abstract

    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