Dr. Thomas J. Wilson was born in Omaha, Nebraska. He attended the University of Nebraska College of Medicine, earning his MD with highest distinction. While a medical student, he was awarded a Howard Hughes Medical Institute Research Training Fellowship and spent a year in the lab of Dr. Rakesh Singh at the University of Nebraska. He was also elected to the prestigious Alpha Omega Alpha Honor Medical Society. He completed his residency training in neurological surgery at the University of Michigan and was mentored by Dr. Lynda Yang and Dr. John McGillicuddy in peripheral nerve surgery. Following his residency, he completed a fellowship in peripheral nerve surgery at the Mayo Clinic in Rochester, Minnesota, working with Dr. Robert Spinner. He is now Clinical Associate Professor and Co-Director of the Center for Peripheral Nerve Surgery at Stanford University. He also holds a Master of Public Health (MPH) degree from the Bloomberg School of Public Health at Johns Hopkins University, with focused certificates in Clinical Trials and Health Finance and Management. His research interests include peripheral nerve outcomes research, clinical trials advancing options for patients with peripheral nerve pathologies and spinal cord injuries, and translational research focused on improved imaging techniques to assist in diagnosing nerve pain and other peripheral nerve conditions. His clinical practice encompasses the treatment of all peripheral nerve pathologies, including entrapment neuropathies, nerve tumors, nerve injuries (including brachial plexus injuries, upper and lower extremity nerve injuries), and nerve pain. Dr. Wilson enjoys working in multi-disciplinary teams to solve complex problems of the peripheral nervous system. His wife, Dr. Monique Wilson, is a practicing dermatologist in the Bay Area.

Clinical Focus

  • Neurosurgery
  • Peripheral Nerve Surgery

Academic Appointments

Administrative Appointments

  • Co-Director, Center for Peripheral Nerve Surgery (2017 - Present)

Honors & Awards

  • Kline Peripheral Nerve Award, AANS/CNS Section on Disorders of the Spine and Peripheral Nerves (2017)
  • Chandler Clinical Research Award, University of Michigan Medical School (2016)
  • McGillicuddy Leadership Award, University of Michigan Medical School (2016)
  • Crosby Basic Science Research Award, University of Michigan Medical School (2014)
  • Senior Thesis Award, Alpha Omega Alpha (2009)
  • Research Training Fellowship, Howard Hughes Medical Institute (2006)

Professional Education

  • Board Certification: American Board of Neurological Surgery, Neurosurgery (2021)
  • MPH, Johns Hopkins University, Clinical Trials, Health Care Finance and Management (2020)
  • Fellowship, Mayo Clinic, Peripheral Nerve Surgery (2017)
  • Residency, University of Michigan, Neurological Surgery (2016)
  • M.D., University of Nebraska College of Medicine, Medicine (2009)
  • Research Training Fellowship, Howard Hughes Medical Institute, Research Fellowship (2007)
  • B.S., Creighton University, Biology (2004)

Clinical Trials

  • Nerve Transfer After Spinal Cord Injury- Multi-center Recruiting

    Current treatment strategies of acute cervical spinal cord injuries remain limited. Treatment options that provide meaningful improvements in patient quality of like and long-term functional independence will provide a significant public health impact. Specific aim: Measure the efficacy of nerve transfer surgery in the treatment of patients with complete spinal cord injuries with no hand function. Optimize the efficiency of nerve transfer surgery by evaluating patient outcomes in relation to patient selection and quality of life and functional independence.

    View full details

All Publications

  • Machine Learning Approach to Differentiation of Peripheral Schwannomas and Neurofibromas: A Multi-Center Study. Neuro-oncology Zhang, M., Tong, E., Wong, S., Hamrick, F., Mohammadzadeh, M., Rao, V., Pendleton, C., Smith, B. W., Hug, N. F., Biswal, S., Seekins, J., Napel, S., Spinner, R. J., Mahan, M. A., Yeom, K. W., Wilson, T. J. 2021


    BACKGROUND: Non-invasive differentiation between schwannomas and neurofibromas is important for appropriate management, preoperative counseling, and surgical planning, but has proven difficult using conventional imaging. The objective of this study was to develop and evaluate machine learning approaches for differentiating peripheral schwannomas from neurofibromas.METHODS: We assembled a cohort of schwannomas and neurofibromas from 3 independent institutions and extracted high-dimensional radiomic features from gadolinium-enhanced, T1-weighted MRI using the PyRadiomics package on Quantitative Imaging Feature Pipeline. Age, sex, neurogenetic syndrome, spontaneous pain, and motor deficit were recorded. We evaluated the performance of 6 radiomics-based classifier models with and without clinical features and compared model performance against human expert evaluators.RESULTS: 107 schwannomas and 59 neurofibroma were included. The primary models included both clinical and imaging data. The accuracy of the human evaluators (0.765) did not significantly exceed the no-information rate (NIR), whereas the Support Vector Machine (0.929), Logistic Regression (0.929), and Random Forest (0.905) classifiers exceeded the NIR. Using the method of DeLong, the AUC for the Logistic Regression (AUC=0.923) and K Nearest Neighbor (AUC=0.923) classifiers was significantly greater than the human evaluators (AUC=0.766; p = 0.041).CONCLUSIONS: The radiomics-based classifiers developed here proved to be more accurate and had a higher AUC on the ROC curve than expert human evaluators. This demonstrates that radiomics using routine MRI sequences and clinical features can aid in differentiation of peripheral schwannomas and neurofibromas.

    View details for DOI 10.1093/neuonc/noab211

    View details for PubMedID 34487172

  • Machine-Learning Approach to Differentiation of Benign and Malignant Peripheral Nerve Sheath Tumors: A Multicenter Study. Neurosurgery Zhang, M., Tong, E., Hamrick, F., Lee, E. H., Tam, L. T., Pendleton, C., Smith, B. W., Hug, N. F., Biswal, S., Seekins, J., Mattonen, S. A., Napel, S., Campen, C. J., Spinner, R. J., Yeom, K. W., Wilson, T. J., Mahan, M. A. 2021


    BACKGROUND: Clinicoradiologic differentiation between benign and malignant peripheral nerve sheath tumors (PNSTs) has important management implications.OBJECTIVE: To develop and evaluate machine-learning approaches to differentiate benign from malignant PNSTs.METHODS: We identified PNSTs treated at 3 institutions and extracted high-dimensional radiomics features from gadolinium-enhanced, T1-weighted magnetic resonance imaging (MRI) sequences. Training and test sets were selected randomly in a 70:30 ratio. A total of 900 image features were automatically extracted using the PyRadiomics package from Quantitative Imaging Feature Pipeline. Clinical data including age, sex, neurogenetic syndrome presence, spontaneous pain, and motor deficit were also incorporated. Features were selected using sparse regression analysis and retained features were further refined by gradient boost modeling to optimize the area under the curve (AUC) for diagnosis. We evaluated the performance of radiomics-based classifiers with and without clinical features and compared performance against human readers.RESULTS: A total of 95 malignant and 171 benign PNSTs were included. The final classifier model included 21 imaging and clinical features. Sensitivity, specificity, and AUC of 0.676, 0.882, and 0.845, respectively, were achieved on the test set. Using imaging and clinical features, human experts collectively achieved sensitivity, specificity, and AUC of 0.786, 0.431, and 0.624, respectively. The AUC of the classifier was statistically better than expert humans (P=.002). Expert humans were not statistically better than the no-information rate, whereas the classifier was (P=.001).CONCLUSION: Radiomics-based machine learning using routine MRI sequences and clinical features can aid in evaluation of PNSTs. Further improvement may be achieved by incorporating additional imaging sequences and clinical variables into future models.

    View details for DOI 10.1093/neuros/nyab212

    View details for PubMedID 34131749

  • An Update on the Management of Adult Traumatic Nerve Injuries-Replacing Old Paradigms: A Review. The journal of trauma and acute care surgery Smith, B. W., Sakamuri, S., Spain, D. A., Joseph, J. R., Yang, L. J., Wilson, T. J. 2018


    Acute nerve injuries are routinely encountered in multisystem trauma patients. Advances in surgical treatment of nerve injuries now mean that good outcomes can be achieved. Despite this, old mantras associated with management of nerve injuries, including "wait a year to see if recovery occurs" and "there's nothing we can do", persist. Practicing by these mantras places these patients at a disadvantage.Changes begin to occur in the nerve, neuromuscular junction, and muscle from the moment a nerve injury occurs. These changes can become irreversible approximately 18-24 months following denervation. Thus, it is a race to reestablish a functional nerve-muscle connection prior to these irreversible changes. Good outcomes rely on appropriate acute management and avoiding delays in care. Primary nerve surgery options include direct primary repair, nerve graft repair, and nerve transfer. Acute management of nerve injuries proceeds according to the rule of 3s and requires early cooperation between trauma surgeons who recognize the nerve injury and consultant nerve surgeons.Care of patients with acute, traumatic nerve injuries should not be delayed. Awareness of current management paradigms among trauma surgeons will help facilitate optimal upfront management. With the ever-expanding surgical options for management of these injuries and the associated improvement of outcomes, early multidisciplinary approaches to these injuries has never been more important. Old mantras must be replaced with new paradigms in order to continue to see improvements in outcomes for these patients. The importance of this review is to raise awareness among trauma surgeons of new paradigms for management of traumatic nerve injuries.

    View details for PubMedID 30278019

  • Novel Uses of Nerve Transfers. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics Wilson, T. J. 2018


    Nerve transfer surgery involves using a working, functional nerve with an expendable or duplicated function as a donor to supply axons and restore function to an injured recipient nerve. Nerve transfers were originally popularized for the restoration of motor function in patients with peripheral nerve injuries. However, more recently, novel uses of nerve transfers have been described, including nerve transfers for sensory reinnervation, nerve transfers for spinal cord injury and stroke patients, supercharge end-to-side nerve transfers, and targeted muscle reinnervation for the prevention and treatment of postamputation neuroma pain. The uses for nerve transfers and the patient populations that can benefit from nerve transfer surgery continue to expand. Awareness about these novel uses of nerve transfers among the medical community is important in order to facilitate evaluation and treatment of these patients by peripheral nerve specialists. A lack of knowledge of these techniques continues to be a major barrier to more widespread implementation.

    View details for PubMedID 30267204

  • Technique for Primary and Redo Surgery for Peroneal Intraneural Ganglion Cysts. Operative neurosurgery Wilson, T. J., Rock, M. G., Spinner, R. J. 2017

    View details for DOI 10.1093/ons/opx114

    View details for PubMedID 28520989

  • Clinicoradiological features of intraneural perineuriomas obviate the need for tissue diagnosis. Journal of neurosurgery Wilson, T. J., Howe, B. M., Stewart, S. A., Spinner, R. J., Amrami, K. K. 2017: 1–7


    OBJECTIVE This study aimed to define a set of clinicoradiological parameters with a high specificity for the diagnosis of intraneural perineurioma, obviating the need for operative tissue diagnosis. METHODS The authors retrospectively reviewed MR images obtained in a large cohort of patients who underwent targeted fascicular biopsy and included only those patients for whom the biopsy yielded a diagnosis. Clinical and radiological findings were then tested for their ability to predict a tissue diagnosis of intraneural perineurioma. The authors propose a new set of diagnostic criteria, referred to as the Perineurioma Diagnostic Criteria. The sensitivity, specificity, positive predictive value, and negative predictive value of several clinicoradiological methods of diagnosis were compared. RESULTS A total of 195 patients who underwent targeted fascicular biopsy were included in the cohort, of whom 51 had a tissue diagnosis of intraneural perineurioma. When the clinicoradiological methods used in this study were compared, the highest sensitivity (0.86), negative predictive value (0.95), and F1 score (0.88) were observed for the decision trees generated in C5.0 and rPart, whereas the highest specificity (1.0) and positive predictive value (1.0) were observed for the Perineurioma Diagnostic Criteria. CONCLUSIONS This study identified clinical and radiological features that are associated with a diagnosis of perineurioma. The Perineurioma Diagnostic Criteria were determined to be the following: 1) no cancer history, 2) unifocal disease, 3) moderate to severe hyperintensity on T2-weighted MR images, 4) moderate to severe contrast enhancement, 5) homogeneous contrast enhancement, 6) fusiform shape, 7) enlargement of the involved nerves, and 8) age ≤ 40 years. Use of the Perineurioma Diagnostic Criteria obviates the need for tissue diagnosis when all of the criteria are satisfied.

    View details for PubMedID 29192862

  • Depression and Anxiety in Traumatic Brachial Plexus Injury Patients Are Associated With Reduced Motor Outcome After Surgical Intervention for Restoration of Elbow Flexion NEUROSURGERY Wilson, T. J., Chang, K. W., Yang, L. J. 2016; 78 (6): 844-849


    Depression has been associated with poor outcomes in neurosurgical patients, including increased pain, poorer functional recovery, delayed return to work, and decreased patient satisfaction. No reports exist regarding an association of psychiatric diagnoses with outcomes after brachial plexus reconstruction. As outcomes and patient satisfaction become increasingly important to payers and physician reimbursement, assessing modifiable preoperative risk factors for their association with poor outcome and patient satisfaction is imperative.To analyze patients undergoing brachial plexus reconstruction to assess the relationship of depression/anxiety with functional outcome.Data were collected retrospectively on all patients who underwent brachial plexus reconstruction to restore elbow flexion between 2005 and 2013. Elbow flexion, graded via the Medical Research Council scale, was assessed at latest follow-up. Multiple variables, including the presence of Axis I psychiatric diagnoses, were assessed for their association with the dichotomous outcome of Medical Research Council scale score ≥3 (antigravity) vs <3 elbow flexion. Standard statistical methods were used.Thirty-seven patients met inclusion criteria. The median postsurgical follow-up time was 21 months. Operations included neurolysis (n = 3), nerve graft repair (n = 6), and nerve transfer (n = 28). Depression was present in 10 of 37 patients (27%). Of variables tested, only depression was associated with poor elbow flexion outcome (odds ratio: 6.038; P = .04).Preoperative depression is common after brachial plexus injury. The presence of depression is associated with reduced elbow flexion recovery after reconstruction. Our data suggest assessment and treatment of preoperative mental health is important in designing a comprehensive postoperative management plan to optimize outcomes and patient satisfaction.MRC, Medical Research CouncilTBI, traumatic brain injury.

    View details for DOI 10.1227/NEU.0000000000001086

    View details for Web of Science ID 000376882300033

    View details for PubMedID 26516821

  • Peripartum and neonatal factors associated with the persistence of neonatal brachial plexus palsy at 1 year: a review of 382 cases JOURNAL OF NEUROSURGERY-PEDIATRICS Wilson, T. J., Chang, K. W., Chauhan, S. P., Yang, L. J. 2016; 17 (5): 618-624


    OBJECTIVE Neonatal brachial plexus palsy (NBPP) occurs due to the stretching of the nerves of the brachial plexus before, during, or after delivery. NBPP can resolve spontaneously or become persistent. To determine if nerve surgery is indicated, predicting recovery is necessary but difficult. Historical attempts explored the association of recovery with only clinical and electrodiagnostic examinations. However, no data exist regarding the neonatal and peripartum factors associated with NBPP persistence. METHODS This retrospective cohort study involved all NBPP patients at the University of Michigan between 2005 and 2015. Peripartum and neonatal factors were assessed for their association with persistent NBPP at 1 year, as defined as the presence of musculoskeletal contractures or an active range of motion that deviated from normal by > 10° (shoulder, elbow, hand, and finger ranges of motion were recorded). Standard statistical methods were used. RESULTS Of 382 children with NBPP, 85% had persistent NBPP at 1 year. A wide range of neonatal and peripartum factors was explored. We found that cephalic presentation, induction or augmentation of labor, birth weight > 9 lbs, and the presence of Horner syndrome all significantly increased the odds of persistence at 1 year, while cesarean delivery and Narakas Grade I to II injury significantly reduced the odds of persistence. CONCLUSIONS Peripartum/neonatal factors were identified that significantly altered the odds of having persistent NBPP at 1 year. Combining these peripartum/neonatal factors with previously published clinical examination findings associated with persistence should allow the development of a prediction algorithm. The implementation of this algorithm may allow the earlier recognition of those cases likely to persist and thus enable earlier intervention, which may improve surgical outcomes.

    View details for DOI 10.3171/2015.10.PEDS15543

    View details for PubMedID 26799409

  • Motor Nerve Transfers: A Comprehensive Review NEUROSURGERY Ray, W. Z., Chang, J., Hawasli, A., Wilson, T. J., Yang, L. 2016; 78 (1): 1-25


    Brachial plexus and peripheral nerve injuries are exceedingly common. Traditional nerve grafting reconstruction strategies and techniques have not changed significantly over the last 3 decades. Increased experience and wider adoption of nerve transfers as part of the reconstructive strategy have resulted in a marked improvement in clinical outcomes. We review the options, outcomes, and indications for nerve transfers to treat brachial plexus and upper- and lower-extremity peripheral nerve injuries, and we explore the increasing use of nerve transfers for facial nerve and spinal cord injuries. Each section provides an overview of donor and recipient options for nerve transfer and of the relevant anatomy specific to the desired function.

    View details for DOI 10.1227/NEU.0000000000001029

    View details for Web of Science ID 000366814800001

    View details for PubMedID 26397751

  • Machine-learning Approach to Differentiation of Benign and Malignant Peripheral Nerve Sheath Tumors: A Multicenter Study Zhang, M., Tong, E., Hamrick, F., Pendleton, C., Smith, B., Hug, N., Mattonen, S., Napel, S., Spinner, R., Yeom, K., Wilson, T., Mahan, M. AMER ASSOC NEUROLOGICAL SURGEONS. 2021
  • Assessment of variability in motor grading and patient-reported outcome reporting: a multi-specialty, multi-national survey. Acta neurochirurgica Smith, B. W., Sakamuri, S., Flavin, K. E., Jensen, M., Purger, D. A., Yang, L. J., Spinner, R. J., Wilson, T. J. 2021


    BACKGROUND: The goal of this survey-based study was to evaluate the current practice patterns of clinicians who assess patients with peripheral nerve pathologies and to assess variance in motor grading on the Medical Research Council (MRC) scale using example case vignettes.METHODS: An electronic survey was distributed to clinicians who regularly assess patients with peripheral nerve pathology. Survey sections included (1) demographic data, (2) vignettes where respondents were asked to assess on the MRC scale, and (3) assessment of practice patterns regarding the use of patient-reported outcome measures. Inter-rater reliability statistics were calculated for the application of the MRC scale on example vignettes.RESULTS: There were 109 respondents. There was significant dispersion in motor grading seen on the example vignettes. For the raw responses grading the example vignettes on the MRC scale, Krippendorff's alpha was 0.788 (95% CI 0.604, 0.991); Gwet's AC2 was 0.808 (95% CI 0.683, 0.932); Fleiss' kappa was 0.416 (95% CI 0.413, 0.419). Most respondents reported not utilizing any patient-reported outcome measures across peripheral nerve pathologies.DISCUSSION: Our data show that there is significant disagreement among providers when applying the MRC scale. It is important for us to reassess our current tools for patient evaluation in order to improve upon both clinical evaluation and outcomes reporting. Consensus guidelines for outcomes reporting are needed, and domains outside of manual muscle testing should be included.

    View details for DOI 10.1007/s00701-021-04861-9

    View details for PubMedID 33990886

  • In Reply: Allograft Nerve Repair Reduces Postoperative Neuropathic Pain Following Nerve Biopsy. Neurosurgery Wilson, T. J. 2021

    View details for DOI 10.1093/neuros/nyab070

    View details for PubMedID 33763693

  • Characteristics of Patients With Complex Limb Pain Evaluated Through an Interdisciplinary Approach Utilizing Magnetic Resonance Neurography Frontiers in Pain Research Johnson, E. M., Yoon, D., Biswal, S., Curtin, C., Fox, P., Wilson, T. J., Carroll, I., Lutz, A., Tawfik, V. 2021
  • Clinical Features, Natural History and Outcomes of Intraneural Perineuriomas: A Systematic Review of the Literature. World neurosurgery Lenartowicz, K. A., Goyal, A., Mauermann, M. L., Wilson, T. J., Spinner, R. J. 2021


    Intraneural perineurioma is a rare peripheral nerve sheath tumor characterized by localized proliferation of perineurial cells. Current literature consists predominantly of case reports and institutional series, with inconsistent and confusing nomenclature. Herein, we present a pooled analysis of all of the current reported cases of intraneural perineurioma in the literature.A systematic search of Pubmed, Medline, Embase and Scopus was performed according to PRISMA guidelines to identify all reported cases of intraneural perineurioma in the literature. Individual cases were pooled and analyzed for demographics, clinical features and outcomes.A total of 172 cases were identified across 72 studies, of which 149 were found in major peripheral nerves and their branches. Median age(IQR) at diagnosis and onset of symptoms was 18(12-34) years and 13.5(8-26) years respectively, with 54.4% (81/149) being female. The most common sites were the sciatic nerve or its branches(41.9%), median nerve(13.5%), radial nerve(12.2%), and brachial plexus(12.2%). Most patients were managed conservatively (52.9%, 72/136). Among those managed conservatively with available follow up (n=31), median follow up was 11 months, and the majority (67.7%, n=21) reported no change in neurologic status, while worsening was noted in 29.0% (9/31). Among surgically managed cases(n=64), the most common intervention was resection with or without repair (62.5%, 40/64), neurolysis(25%, 16/64) or tendon transfers without resection (12.5%, 8/64). No lesion recurred following surgical resection.Intraneural perineurioma represents a benign, focal lesion presenting with weakness and atrophy affecting adolescents and young adults. Most cases are managed nonoperatively and surgical treatment strategies are varied.

    View details for DOI 10.1016/j.wneu.2021.07.042

    View details for PubMedID 34284162

  • Analysis of the effect of intraoperative neuromonitoring during resection of benign nerve sheath tumors on gross-total resection and neurological complications. Journal of neurosurgery Wilson, T. J., Hamrick, F. n., Alzahrani, S. n., Dibble, C. F., Koduri, S. n., Pendleton, C. n., Saleh, S. n., Ali, Z. S., Mahan, M. A., Midha, R. n., Ray, W. Z., Yang, L. J., Zager, E. L., Spinner, R. J. 2021: 1–10


    The aim of this study was to examine the role of intraoperative neuromonitoring (IONM) during resection of benign peripheral nerve sheath tumors in achieving gross-total resection (GTR) and in reducing postoperative neurological complications.Data from consecutive adult patients who underwent resection of a benign peripheral nerve sheath tumor at 7 participating institutions were combined. Propensity score matching was used to balance covariates. The primary outcomes of interest were the association between IONM and GTR and the association of IONM and the development of a permanent postoperative neurological complication. The secondary outcomes of interest were the association between IONM and GTR and the association between IONM and the development of a permanent postoperative neurological complication in the subgroup of patients with tumors involving a motor or mixed nerve. Univariate and multivariate logistic regression were then performed on the propensity score-matched samples to assess the ability of the independent variables to predict the outcomes of interest.A total of 337 patients who underwent resection of benign nerve sheath tumors were included. In multivariate analysis, the use of IONM (OR 0.460, 95% CI 0.199-0.978; p = 0.047) was a significant negative predictor of GTR, whereas none of the variables, including IONM, were associated with the occurrence of a permanent postoperative neurological complication. Within the subgroup of motor/mixed nerve tumors, in the multivariate analysis, IONM (OR 0.263, 95% CI 0.096-0.723; p = 0.010) was a significant negative predictor of a GTR, whereas IONM (OR 3.800, 95% CI 1.925-7.502; p < 0.001) was a significant positive predictor of a permanent postoperative motor deficit.Overall, 12% of the cohort had a permanent neurological complication, with new or worsened paresthesias most common, followed by pain and then weakness. The authors found that formal IONM was associated with a reduced likelihood of GTR and had no association with neurological complications. The authors believe that these data argue against IONM being considered standard of care but do not believe that these data should be used to universally argue against IONM during resection of benign nerve sheath tumors.

    View details for DOI 10.3171/2020.8.JNS202885

    View details for PubMedID 33578389

  • Allograft Nerve Repair Reduces Postoperative Neuropathic Pain Following Nerve Biopsy. Neurosurgery Sakamuri, S., Wilson, T. J. 2020


    BACKGROUND: New or worsened neuropathic pain is common following nerve biopsy and significantly impacts quality of life.OBJECTIVE: To examine the impact of allograft nerve repair on the likelihood of postoperative worsened neuropathic pain following nerve biopsy.METHODS: A retrospective cohort study was performed comparing standard nerve biopsy to nerve biopsy with allograft repair. Consecutive patients (N=51) who underwent whole nerve biopsy between August 1, 2017, and August 1, 2019, by a single surgeon were evaluated for inclusion. The primary outcome was significant worsening of visual analog scale (VAS) score in the nerve distribution 6-mo postbiopsy. Secondary outcomes included significant worsening of VAS in the nerve distribution 3-wk postbiopsy and significant change in Zung Self-Rating Depression Scale 6-mo postbiopsy.RESULTS: In a multivariate model, allograft nerve repair significantly reduced the likelihood of increased neuropathic pain at 6-mo postbiopsy (odds ratio 0.02, P=.03). Worsened neuropathic pain occurred in 28% of the standard nerve biopsy cohort compared to 4% of the allograft nerve repair cohort. In a multivariate model, an increase in neuropathic pain was strongly associated with an increased likelihood of self-reported depression (odds ratio 57.4, P=.01).CONCLUSION: Allograft nerve repair significantly reduces the likelihood of postbiopsy worsened neuropathic pain compared to standard techniques. Neuropathic pain significantly impacts quality of life after nerve biopsy, and this is the first technique to demonstrate a significant reduction in neuropathic pain while maintaining the ability to harvest an adequate nerve specimen.

    View details for DOI 10.1093/neuros/nyaa250

    View details for PubMedID 32542326

  • Sigma-1 receptor PET/MRI for identifying nociceptive sources of radiating low back pain Yoon, D., Cipriano, P., Carroll, I., Curtin, C., Roh, E., Wilson, T., Biswal, S. SOC NUCLEAR MEDICINE INC. 2020
  • Imaging of Damaged Nerves. Clinics in plastic surgery Purger, D. A., Sakamuri, S., Hug, N. F., Biswal, S., Wilson, T. J. 2020; 47 (2): 245–59


    Nerve imaging is an important component in the assessment of patients presenting with suspected peripheral nerve pathology. Although magnetic resonance neurography and ultrasound are the most commonly utilized techniques, several promising new modalities are on the horizon. Nerve imaging is useful in localizing the nerve injury, determining the severity, providing prognostic information, helping establish the diagnosis, and helping guide surgical decision making. The focus of this article is imaging of damaged nerves, focusing on nerve injuries and entrapment neuropathies.

    View details for DOI 10.1016/j.cps.2019.12.003

    View details for PubMedID 32115050

  • The anatomic location and importance of the tibialis posterior fascicular bundle at the sciatic nerve bifurcation: report of 3 cases JOURNAL OF NEUROSURGERY Wilson, T. J., Maldonado, A. A., Amrami, K. K., Glazebrook, K. N., Moynagh, M. R., Spinner, R. J. 2019; 131 (6): 1869–75
  • Clinical and Radiological Follow-up of Intraneural Perineuriomas NEUROSURGERY Wilson, T. J., Amrami, K. K., Howe, B., Spinner, R. J. 2019; 85 (6): 786–91
  • Gastrostomy tube placement increases the risk of ventriculoperitoneal shunt infection: a multiinstitutional study JOURNAL OF NEUROSURGERY Al-Holou, W. N., Wilson, T. J., Ad, Z. S., Brennan, R. P., Bridges, K. J., Guivatchian, T., Habboub, G., Krishnaney, A. A., Lanzino, G., Snyder, K. A., Flanders, T. M., Than, K. D., Pandey, A. S. 2019; 131 (4): 1062–67
  • Peripheral Nerve OPERATIVE NEUROSURGERY Spinner, R. J., Hanna, A. S., Maldonado, A. A., Wilson, T. J. 2019; 17: S229–S255

    View details for DOI 10.1093/ons/opz072

    View details for Web of Science ID 000486941700010

  • Joint Outcomes Following Surgery for Superior Tibiofibular Joint-Associated Peroneal Intraneural Ganglion Cysts. Neurosurgery Wilson, T. J., Stone, J. J., Howe, B. M., Rock, M. G., Spinner, R. J. 2019


    BACKGROUND: Intraneural ganglion cysts are joint-connected, with the primary pathology residing in the associated joint. For peroneal intraneural ganglion cysts, the surgical strategy can include resection of the synovial surface of the superior tibiofibular joint (STFJ). However, the rate of instability postoperatively is unclear.OBJECTIVE: To evaluate the rate of STFJ instability, following surgery for peroneal intraneural ganglion cysts. The second goal of the study was to assess the relationship between volume of resection of the STFJ and risk of extraneural recurrence.METHODS: We performed a retrospective analysis of a cohort of patients with peroneal intraneural ganglion cysts. We analyzed clinical factors, including recurrence, and assessed the rate of postoperative STFJ instability. We created 3-dimensional models of the STFJ pre- and postoperatively to compare the volume of resection in recurrent cases and nonrecurrent cases using a case-control design.RESULTS: The total cohort consisted of 65 subjects. No patient had evidence of radiological or clinical instability of the STFJ postoperatively. Extraneural radiological recurrence occurred in 6 (9%) patients. No intraneural recurrences were observed. The average volume of resection for patients with recurrence was 1349 mm3 (SD=1027 mm3) vs 3018 mm3 (SD=1433 mm3) in controls that did not have a recurrence (P=.018).CONCLUSION: This study supports performing an aggressive STFJ resection to minimize the risk of extraneural recurrence. Superior tibiofibular joint resection is not associated with postoperative joint instability. A smaller volume resection is correlated with recurrence risk.

    View details for DOI 10.1093/neuros/nyz205

    View details for PubMedID 31215635

  • An 11-year analysis of peripheral nerve injuries in high school sports PHYSICIAN AND SPORTSMEDICINE Zuckerman, S. L., Kerr, Z. Y., Pierpoint, L., Kirby, P., Than, K. D., Wilson, T. J. 2019; 47 (2): 167–73
  • An update on the management of adult traumatic nerve injuries-replacing old paradigms: A review JOURNAL OF TRAUMA AND ACUTE CARE SURGERY Smith, B. W., Sakamuri, S., Spain, D. A., Joseph, J. R., Yang, L., Wilson, T. J. 2019; 86 (2): 299–306
  • Deep Brain Stimulation Versus Peripheral Denervation for Cervical Dystonia: A Systematic Review and Meta-Analysis WORLD NEUROSURGERY Ravindran, K., Kumar, N., Englot, D. J., Wilson, T. J., Zuckerman, S. L. 2019; 122: E940–E946
  • Nerve transfers in the upper extremity following cervical spinal cord injury. Part 2: Preliminary results of a prospective clinical trial. Journal of neurosurgery. Spine Khalifeh, J. M., Dibble, C. F., Van Voorhis, A. n., Doering, M. n., Boyer, M. I., Mahan, M. A., Wilson, T. J., Midha, R. n., Yang, L. J., Ray, W. Z. 2019: 1–13


    Patients with cervical spinal cord injury (SCI)/tetraplegia consistently rank restoring arm and hand function as their top functional priority to improve quality of life. Motor nerve transfers traditionally used to treat peripheral nerve injuries are increasingly used to treat patients with cervical SCIs. In this article, the authors present early results of a prospective clinical trial using nerve transfers to restore upper-extremity function in tetraplegia.Participants with American Spinal Injury Association (ASIA) grade A-C cervical SCI/tetraplegia were prospectively enrolled at a single institution, and nerve transfer(s) was performed to improve upper-extremity function. Functional recovery and strength outcomes were independently assessed and prospectively tracked.Seventeen participants (94.1% males) with a median age of 28.4 years (range 18.2-76.3 years) who underwent nerve transfers at a median of 18.2 months (range 5.2-130.8 months) after injury were included in the analysis. Preoperative SCI levels ranged from C2 to C7, most commonly at C4 (35.3%). The median postoperative follow-up duration was 24.9 months (range 12.0-29.1 months). Patients who underwent transfers to median nerve motor branches and completed 18- and 24-month follow-ups achieved finger flexion strength Medical Research Council (MRC) grade ≥ 3/5 in 4 of 15 (26.7%) and 3 of 12 (25.0%) treated upper limbs, respectively. Similarly, patients achieved MRC grade ≥ 3/5 wrist flexion strength in 5 of 15 (33.3%) and 3 of 12 (25.0%) upper limbs. Among patients who underwent transfers to the posterior interosseous nerve (PIN) for wrist/finger extension, MRC grade ≥ 3/5 strength was demonstrated in 5 of 9 (55.6%) and 4 of 7 (57.1%) upper limbs 18 and 24 months postoperatively, respectively. Similarly, grade ≥ 3/5 strength was demonstrated in 5 of 9 (55.6%) and 4 of 7 (57.1%) cases for thumb extension. No meaningful donor site deficits were observed. Patients reported significant postoperative improvements from baseline on upper-extremity-specific self-reported outcome measures.Motor nerve transfers are a promising treatment option to restore upper-extremity function after SCI. In the authors' experience, nerve transfers for the reinnervation of hand and finger flexors showed variable functional recovery; however, transfers for the reinnervation of arm, hand, and finger extensors showed a more consistent and meaningful return of strength and function.

    View details for DOI 10.3171/2019.4.SPINE19399

    View details for PubMedID 31299645

  • Peripheral Nerve. Operative neurosurgery (Hagerstown, Md.) Spinner, R. J., Hanna, A. S., Maldonado, A. A., Wilson, T. J. 2019

    View details for PubMedID 31099839

  • Novel Uses of Nerve Transfers NEUROTHERAPEUTICS Wilson, T. J. 2019; 16 (1): 26–35
  • Deep Learning-Assisted Diagnosis of Cerebral Aneurysms Using the HeadXNet Model. JAMA network open Park, A. n., Chute, C. n., Rajpurkar, P. n., Lou, J. n., Ball, R. L., Shpanskaya, K. n., Jabarkheel, R. n., Kim, L. H., McKenna, E. n., Tseng, J. n., Ni, J. n., Wishah, F. n., Wittber, F. n., Hong, D. S., Wilson, T. J., Halabi, S. n., Basu, S. n., Patel, B. N., Lungren, M. P., Ng, A. Y., Yeom, K. W. 2019; 2 (6): e195600


    Deep learning has the potential to augment clinician performance in medical imaging interpretation and reduce time to diagnosis through automated segmentation. Few studies to date have explored this topic.To develop and apply a neural network segmentation model (the HeadXNet model) capable of generating precise voxel-by-voxel predictions of intracranial aneurysms on head computed tomographic angiography (CTA) imaging to augment clinicians' intracranial aneurysm diagnostic performance.In this diagnostic study, a 3-dimensional convolutional neural network architecture was developed using a training set of 611 head CTA examinations to generate aneurysm segmentations. Segmentation outputs from this support model on a test set of 115 examinations were provided to clinicians. Between August 13, 2018, and October 4, 2018, 8 clinicians diagnosed the presence of aneurysm on the test set, both with and without model augmentation, in a crossover design using randomized order and a 14-day washout period. Head and neck examinations performed between January 3, 2003, and May 31, 2017, at a single academic medical center were used to train, validate, and test the model. Examinations positive for aneurysm had at least 1 clinically significant, nonruptured intracranial aneurysm. Examinations with hemorrhage, ruptured aneurysm, posttraumatic or infectious pseudoaneurysm, arteriovenous malformation, surgical clips, coils, catheters, or other surgical hardware were excluded. All other CTA examinations were considered controls.Sensitivity, specificity, accuracy, time, and interrater agreement were measured. Metrics for clinician performance with and without model augmentation were compared.The data set contained 818 examinations from 662 unique patients with 328 CTA examinations (40.1%) containing at least 1 intracranial aneurysm and 490 examinations (59.9%) without intracranial aneurysms. The 8 clinicians reading the test set ranged in experience from 2 to 12 years. Augmenting clinicians with artificial intelligence-produced segmentation predictions resulted in clinicians achieving statistically significant improvements in sensitivity, accuracy, and interrater agreement when compared with no augmentation. The clinicians' mean sensitivity increased by 0.059 (95% CI, 0.028-0.091; adjusted P = .01), mean accuracy increased by 0.038 (95% CI, 0.014-0.062; adjusted P = .02), and mean interrater agreement (Fleiss κ) increased by 0.060, from 0.799 to 0.859 (adjusted P = .05). There was no statistically significant change in mean specificity (0.016; 95% CI, -0.010 to 0.041; adjusted P = .16) and time to diagnosis (5.71 seconds; 95% CI, 7.22-18.63 seconds; adjusted P = .19).The deep learning model developed successfully detected clinically significant intracranial aneurysms on CTA. This suggests that integration of an artificial intelligence-assisted diagnostic model may augment clinician performance with dependable and accurate predictions and thereby optimize patient care.

    View details for DOI 10.1001/jamanetworkopen.2019.5600

    View details for PubMedID 31173130

  • Nerve transfers in the upper extremity following cervical spinal cord injury. Part 1: Systematic review of the literature. Journal of neurosurgery. Spine Khalifeh, J. M., Dibble, C. F., Van Voorhis, A. n., Doering, M. n., Boyer, M. I., Mahan, M. A., Wilson, T. J., Midha, R. n., Yang, L. J., Ray, W. Z. 2019: 1–12


    Patients with cervical spinal cord injury (SCI)/tetraplegia consistently rank restoring arm and hand function as their top functional priority to improve quality of life. Motor nerve transfers traditionally used to treat peripheral nerve injuries are increasingly being used to treat patients with cervical SCIs. In this study, the authors performed a systematic review summarizing the published literature on nerve transfers to restore upper-extremity function in tetraplegia.A systematic literature search was conducted using Ovid MEDLINE 1946-, Embase 1947-, Scopus 1960-, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and to identify relevant literature published through January 2019. The authors included studies that provided original patient-level data and extracted information on clinical characteristics, operative details, and strength outcomes after nerve transfer procedures. Critical review and synthesis of the articles were performed.Twenty-two unique studies, reporting on 158 nerve transfers in 118 upper limbs of 92 patients (87 males, 94.6%) were included in the systematic review. The mean duration from SCI to nerve transfer surgery was 18.7 months (range 4 months-13 years) and mean postoperative follow-up duration was 19.5 months (range 1 month-4 years). The main goals of reinnervation were the restoration of thumb and finger flexion, elbow extension, and wrist and finger extension. Significant heterogeneity in transfer strategy and postoperative outcomes were noted among the reports. All but one case report demonstrated recovery of at least Medical Research Council grade 3/5 strength in recipient muscle groups; however, there was greater variation in the results of larger case series. The best, most consistent outcomes were demonstrated for restoration of wrist/finger extension and elbow extension.Motor nerve transfers are a promising treatment option to restore upper-extremity function after SCI. Flexor reinnervation strategies show variable treatment effect sizes; however, extensor reinnervation may provide more consistent, meaningful recovery. Despite numerous published case reports describing good patient outcomes with nerve transfers, there remains a paucity in the literature regarding optimal timing and long-term clinical outcomes with these procedures.

    View details for DOI 10.3171/2019.4.SPINE19173

    View details for PubMedID 31299644

  • The anatomic location and importance of the tibialis posterior fascicular bundle at the sciatic nerve bifurcation: report of 3 cases. Journal of neurosurgery Wilson, T. J., Maldonado, A. A., Amrami, K. K., Glazebrook, K. N., Moynagh, M. R., Spinner, R. J. 2018: 1–7


    The authors present the cases of 3 patients with severe injuries affecting the peroneal nerve combined with loss of tibialis posterior function (inversion) despite preservation of other tibial nerve function. Loss of tibialis posterior function is problematic, since transfer of the tibialis posterior tendon is arguably the best reconstructive option for foot drop, when available. Analysis of preoperative imaging studies correlated with operative findings and showed that the injuries, while predominantly to the common peroneal nerve, also affected the lateral portion of the tibial nerve/division near the sciatic nerve bifurcation. Sunderland's fascicular topographic maps demonstrate the localization of the fascicular bundle subserving the tibialis posterior to the area that corresponds to the injury. This has clinical significance in predicting injury patterns and potentially for treatment of these injuries. The lateral fibers of the tibial division/nerve may be vulnerable with long stretch injuries. Due to the importance of tibialis posterior function, it may be important to perform internal neurolysis of the tibial division/nerve in order to facilitate nerve action potential testing of these fascicles, ultimately performing split nerve graft repair when nerve action potentials are absent in this important portion of the tibial nerve.

    View details for PubMedID 30579281

  • Clinical and Radiological Follow-up of Intraneural Perineuriomas. Neurosurgery Wilson, T. J., Amrami, K. K., Howe, B. M., Spinner, R. J. 2018


    BACKGROUND: Management of intraneural perineuriomas remains controversial, largely due to the lack of knowledge regarding the natural history of these lesions.OBJECTIVE: To describe the typical radiological growth pattern of intraneural perineuriomas and to determine how the pattern of growth relates to clinical progression.METHODS: We performed a retrospective review of the magnetic resonance imaging (MRI) studies and serial clinical examinations of a cohort of patients with biopsy-proven intraneural perineuriomas who had 2 MRI studies at least 2 yr apart. The outcome of interest was radiological growth in length or width of the intraneural perineurioma. Radiological growth was tested for association with clinical progression.RESULTS: Twenty patients were included in the study. By width, the lesions were on average larger on repeat imaging (P=.009). By absolute length, the lesions were on average longer on repeat imaging (P=.02). By lesion:landmark ratio, there was no difference in length of the lesions between sequential images (P=.09), with 10 (50%) lesions being shorter and 7 (35%) showing no change. No lesions grew to involve a new nerve or division of a nerve on sequential imaging. None of the variables tested were associated with clinical progression.CONCLUSION: We found that intraneural perineuriomas only rarely grow in length, do not grow to involve new nerves or nerve divisions, and growth does not correlate with clinical progression. These findings have significant ramifications for management of these tumors.

    View details for PubMedID 30481319

  • Deep brain stimulation versus peripheral denervation for cervical dystonia: a systematic review and meta-analysis. World neurosurgery Ravindran, K., Kumar, N., Englot, D. J., Wilson, T. J., Zuckerman, S. L. 2018


    BACKGROUND: Cervical dystonia is a disabling medical condition that drastically decreases quality of life. Surgical treatment consists of peripheral nerve denervation procedures with or without myectomies or deep brain stimulation (DBS). The current objective was to compare the efficacy of peripheral denervation versus DBS in improving severity of cervical dystonia through a systematic review and meta-analysis.METHODS: A search of PubMed, MEDLINE, EMBASE and Web of Science electronic databases was conducted in accordance with PRISMA guidelines. Pre- and post-operative Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total scores were used to generate standardized mean differences and 95% confidence intervals, which were combined in a random-effects model. Both mean percentage and absolute reduction in TWSTRS scores were calculated. Absolute reduction was used for forest plots.RESULTS: Eighteen studies met inclusion criteria, comprising 870 patients with 180 (21%) undergoing DBS and 690 (79%) undergoing peripheral denervation procedures. Mean follow-up was 31.5 months (range 12-38 months). In assessing efficacy of each intervention, forest plots revealed significant absolute reduction in total post-operative TWSTRS scores for both peripheral denervation (standardized mean difference 1.54; 95% CI 1.42-1.66) and DBS (standardized mean difference 2.07; 95% CI 1.43-2.71). On subgroup analysis, DBS therapy was significantly associated with improvement in post-operative TWSTRS severity (standardized mean difference 2.08; 95% CI 1.66-2.50) and disability (standardized mean difference 2.12; 95% CI 1.57-2.68), but not pain (standardized mean difference 1.18; 95% CI 0.80-1.55).CONCLUSIONS: Both peripheral denervation and DBS are associated with a significant reduction in absolute TWSTRS total score, with no significant difference in the magnitude of reduction observed between the two treatments. Further comparative data are needed to better evaluate the long-term results of both interventions.

    View details for PubMedID 30419402

  • An 11-year analysis of peripheral nerve injuries in high school sports. The Physician and sportsmedicine Zuckerman, S. L., Kerr, Z. Y., Pierpoint, L., Kirby, P., Than, K. D., Wilson, T. J. 2018


    INTRODUCTION: Sports surveillance databases provide valuable information regarding common ailments, yet fewer studies have focused on more rare peripheral nerve injuries. Our objective was to characterize peripheral nerve injuries in high school athletics with respect to incidence, time loss, mechanism, and diagnoses.METHODS: Sport-related nerve injury data on high school athletes were collected during the 2005/2006 through 2015/2016 academic years via the High School Reporting Information Online (RIO) database. All injuries were reported by certified athletic trainers (ATs). Descriptive statistics were performed.RESULTS: A total of 588 peripheral nerve injuries were recorded during the 2005/06-2015/16 academic years, with an overall incidence of 1.46/100,000 athlete-exposures (AE; 95%CI: 1.34, 1.58). Boys' football had the majority of injuries (71.3%) and the highest injury rate (5.46/100,000AE; 95%CI: 4.93, 5.98), followed by boys' wrestling (7.1%) and boys' baseball (3.4%). Over half (50.3%) of peripheral nerve injuries resulted in time loss <1 week, while 9.4% resulting in the athletes prematurely ending their seasons. The most common mechanisms were player contact (67.3%), overuse (10.0%), and surface contact (9.7%). A specific diagnosis was available for 40 (6.8%) injuries, including upper extremity stinger (n=26), spinal cord neurapraxia (n=3), subacromial nerve impingement (n=2) neuroma (n=2), axillary nerve palsy (n=1), sciatic nerve impingement (n=1), femoral nerve impingement (n=1), tarsal tunnel syndrome (n=1), peroneal neuropathy (n=1), thoracic outlet syndrome (n=1), and ulnar nerve subluxation (n=1).DISCUSSION: Recognized peripheral nerve injuries are rare among high school athletes, occurring most commonly in boys' football. While most are minor, approximately 1:10 were season-ending. Specific diagnoses were available for 7% of injuries, with upper extremity stingers being the most commonly reported diagnosis. Working with ATs to identify and implement methods to obtain more specific diagnostic information via surveillance will help researchers better understand the epidemiology of peripheral nerve injuries.

    View details for PubMedID 30392428

  • Imaging Characteristics Predict Operative Difficulty Mobilizing the Sciatic Nerve for Proximal Hamstring Repair NEUROSURGERY Wilson, T. J., Howe, B., Spinner, R. J., Krych, A. J. 2018; 83 (5): 931–39
  • Gastrostomy tube placement increases the risk of ventriculoperitoneal shunt infection: a multiinstitutional study. Journal of neurosurgery Al-Holou, W. N., Wilson, T. J., Ali, Z. S., Brennan, R. P., Bridges, K. J., Guivatchian, T., Habboub, G., Krishnaney, A. A., Lanzino, G., Snyder, K. A., Flanders, T. M., Than, K. D., Pandey, A. S. 2018: 1–6


    OBJECTIVEGastrostomy tube placement can temporarily seed the peritoneal cavity with bacteria and thus theoretically increases the risk of shunt infection when the two procedures are performed contemporaneously. The authors hypothesized that gastrostomy tube placement would not increase the risk of ventriculoperitoneal shunt infection. The object of this study was to test this hypothesis by utilizing a large patient cohort combined from multiple institutions.METHODSA retrospective study of all adult patients admitted to five institutions with a diagnosis of aneurysmal subarachnoid hemorrhage between January 2005 and January 2015 was performed. The primary outcome of interest was ventriculoperitoneal shunt infection. Variables, including gastrostomy tube placement, were tested for their association with this outcome. Standard statistical methods were utilized.RESULTSThe overall cohort consisted of 432 patients, 47% of whom had undergone placement of a gastrostomy tube. The overall shunt infection rate was 9%. The only variable that predicted shunt infection was gastrostomy tube placement (p = 0.03, OR 2.09, 95% CI 1.07-4.08), which remained significant in the multivariate analysis (p = 0.04, OR 2.03, 95% CI 1.04-3.97). The greatest proportion of shunts that became infected had been placed more than 2 weeks (25%) and 1-2 weeks (18%) prior to gastrostomy tube placement, but the temporal relationship between shunt and gastrostomy was not a significant predictor of shunt infection.CONCLUSIONSGastrostomy tube placement significantly increases the risk of ventriculoperitoneal shunt infection.

    View details for PubMedID 30497165

  • Clinicoradiological features of intraneural perineuriomas obviate the need for tissue diagnosis JOURNAL OF NEUROSURGERY Wilson, T. J., Howe, B., Stewart, S. A., Spinner, R. J., Amrami, K. K. 2018; 129 (4): 1034–40
  • An Update on the Management of Neonatal Brachial Plexus Palsy-Replacing Old Paradigms A Review JAMA PEDIATRICS Smith, B. W., Daunter, A. K., Yang, L., Wilson, T. J. 2018; 172 (6): 585–91


    Neonatal brachial plexus palsy (NBPP) can result in persistent deficits for those who develop it. Advances in surgical technique have resulted in the availability of safe, reliable options for treatment. Prevailing paradigms include, "all neonatal brachial plexus palsy recovers," "wait a year to see if recovery occurs," and "don't move the arm." Practicing by these principles places these patients at a disadvantage. Thus, the importance of this review is to provide an update on the management of NBPP to replace old beliefs with new paradigms.Changes within denervated muscle begin at the moment of injury, but without reinnervation become irreversible 18 to 24 months following denervation. These time-sensitive, irreversible changes are the scientific basis for the recommendations herein for the early management of NBPP and put into question the old paradigms. Early referral has become increasingly important because improved outcomes can be achieved using new management algorithms that allow surgery to be offered to patients unlikely to recover sufficiently with conservative management. Mounting evidence supports improved outcomes for appropriately selected patients with surgical management compared with natural history. Primary nerve surgery options now include nerve graft repair and nerve transfer. Specific indications continue to be elucidated, but both techniques offer a significant chance of restoration of function.Mounting data support both the safety and effectiveness of surgery for patients with persistent NBPP. Despite this support, primary nerve surgery for NBPP continues to be underused. Surgery is but one part of the multidisciplinary care of NBPP. Early referral and implementation of multidisciplinary strategies give these children the best chance of functional recovery. Primary care physicians, nerve surgeons, physiatrists, and occupational and physical therapists must partner to continue to modify current treatment paradigms to provide improved quality care to neonates and children affected by NBPP.

    View details for PubMedID 29710183

  • OUTCOMES FOLLOWING SURGERY FOR PERONEAL INTRANEURAL GANGLION CYSTS MUSCLE & NERVE Wilson, T. J., Mauermann, M. L., Rock, M. G., Spinner, R. J. 2018; 57 (6): 989–93


    The objective of this study was to answer the typical questions from patients regarding the likely neurologic outcome and likelihood of recurrence when discussing peroneal intraneural ganglion cysts preoperatively.Retrospective analysis of all patients who underwent surgery for a peroneal intraneural ganglion cyst between January 1, 2000, and April 1, 2017, was performed. Postoperative neurologic outcomes and radiologic recurrences are reported.There were 65 patients. Average clinical follow-up was 14 months. Median dorsiflexion and eversion preoperatively were 2/5 and 4/5, respectively. Median dorsiflexion and eversion at last follow-up postoperatively were 5/5. Radiologic recurrence occurred in 6 (9%) patients, all extraneural.The data support excellent postoperative motor outcomes, despite frequent dense weakness of peroneal-innervated musculature preoperatively. The surgical approach appears to eliminate risk of intraneural recurrence and minimizes risk of extraneural recurrence. Muscle Nerve 57: 989-993, 2018.

    View details for PubMedID 29315664

  • Distal peroneal nerve decompression after sciatic nerve injury secondary to total hip arthroplasty. Journal of neurosurgery Wilson, T. J., Kleiber, G. M., Nunley, R. M., Mackinnon, S. E., Spinner, R. J. 2018: 1–5


    OBJECTIVE The sciatic nerve, particularly its peroneal division, is at risk for injury during total hip arthroplasty (THA), especially when a posterior approach is used. The majority of the morbidity results from the loss of peroneal nerve-innervated muscle function. Approximately one-third of patients recover spontaneously. The objectives of this study were to report the outcomes of distal decompression of the peroneal nerve at the fibular tunnel following sciatic nerve injury secondary to THA and to attempt to identify predictors of a positive surgical outcome. METHODS A retrospective study of all patients who underwent peroneal decompression for the indication of sciatic nerve injury following THA at the Mayo Clinic or Washington University School of Medicine in St. Louis was performed. Patients with less than 6 months of postoperative follow-up were excluded. The primary outcome was dorsiflexion strength at latest follow-up. Univariate and multivariate logistic regression analyses were performed to assess the ability of the independent variables to predict a good surgical outcome. RESULTS The total included cohort consisted of 37 patients. The median preoperative dorsiflexion grade at the time of peroneal decompression was 0. Dorsiflexion at latest follow-up was Medical Research Council (MRC) ≥ 3 for 24 (65%) patients. Dorsiflexion recovered to MRC ≥ 4- for 15 (41%) patients. In multivariate logistic regression analysis, motor unit potentials in the tibialis anterior (OR 19.84, 95% CI 2.44-364.05; p = 0.004) and in the peroneus longus (OR 8.68, 95% CI 1.05-135.53; p = 0.04) on preoperative electromyography were significant predictors of a good surgical outcome. CONCLUSIONS After performing peroneal nerve decompression at the fibular tunnel, 65% of the patients in this study recovered dorsiflexion strength of MRC ≥ 3 at latest follow-up, potentially representing a significant improvement over the natural history.

    View details for DOI 10.3171/2017.8.JNS171260

    View details for PubMedID 29393761

  • Oberlin transfer compared with nerve grafting for improving early supination in neonatal brachial plexus palsy. Journal of neurosurgery. Pediatrics Chang, K. W., Wilson, T. J., Popadich, M., Brown, S. H., Chung, K. C., Yang, L. J. 2017: 1-7


    OBJECTIVE The use of nerve transfers versus nerve grafting for neonatal brachial plexus palsy (NBPP) remains controversial. In adult brachial plexus injury, transfer of an ulnar fascicle to the biceps branch of the musculocutaneous nerve (Oberlin transfer) is reportedly superior to nerve grafting for restoration of elbow flexion. In pediatric patients with NBPP, recovery of elbow flexion and forearm supination is an indicator of resolved NBPP. Currently, limited evidence exists of outcomes for flexion and supination when comparing nerve transfer and nerve grafting for NBPP. Therefore, the authors compared 1-year postoperative outcomes for infants with NBPP who underwent Oberlin transfer versus nerve grafting. METHODS This retrospective cohort study reviewed patients with NBPP who underwent Oberlin transfer (n = 19) and nerve grafting (n = 31) at a single institution between 2005 and 2015. A single surgeon conducted intraoperative exploration of the brachial plexus and determined the surgical nerve reconstruction strategy undertaken. Active range of motion was evaluated preoperatively and postoperatively at 1 year. RESULTS No significant difference between treatment groups was observed with respect to the mean change (pre- to postoperatively) in elbow flexion in adduction and abduction and biceps strength. The Oberlin transfer group gained significantly more supination (100° vs 19°; p < 0.0001). Forearm pronation was maintained at 90° in the Oberlin transfer group whereas it was slightly improved in the grafting group (0° vs 32°; p = 0.02). Shoulder, wrist, and hand functions were comparable between treatment groups. CONCLUSIONS The preliminary data from this study demonstrate that the Oberlin transfer confers an advantageous early recovery of forearm supination over grafting, with equivalent elbow flexion recovery. Further studies that monitor real-world arm usage will provide more insight into the most appropriate surgical strategy for NBPP.

    View details for DOI 10.3171/2017.8.PEDS17160

    View details for PubMedID 29219789

  • Intraoperative Ultrasound for Peripheral Nerve Applications. Neurosurgery clinics of North America Willsey, M., Wilson, T. J., Henning, P. T., Yang, L. J. 2017; 28 (4): 623-632


    Offering real-time, high-resolution images via intraoperative ultrasound is advantageous for a variety of peripheral nerve applications. To highlight the advantages of ultrasound, its extraoperative uses are reviewed. The current intraoperative uses, including nerve localization, real-time evaluation of peripheral nerve tumors, and implantation of leads for peripheral nerve stimulation, are reviewed. Although intraoperative peripheral nerve localization has been performed previously using guide wires and surgical dyes, the authors' approach using ultrasound-guided instrument clamps helps guide surgical dissection to the target nerve, which could lead to more timely operations and shorter incisions.

    View details for DOI 10.1016/

    View details for PubMedID 28917290

  • Delayed compression of the common peroneal nerve following rotational lateral gastrocnemius flap: case report. Journal of neurosurgery Himes, B. T., Wilson, T. J., Maldonado, A. A., Murthy, N. S., Spinner, R. J. 2017: 1-4


    The authors present a case of delayed peroneal neuropathy following a lateral gastrocnemius rotational flap reconstruction. The patient presented 1.5 years after surgery with a new partial foot drop, which progressed over 3 years. At operation, a fascial band on the deep side of the gastrocnemius flap was compressing the common peroneal nerve proximal to the fibular head, correlating with preoperative imaging. Release of this fascial band and selective muscle resection led to immediate improvement in symptoms postoperatively.

    View details for DOI 10.3171/2017.2.JNS162711

    View details for PubMedID 28753118

  • Selective Cervical Denervation for Cervical Dystonia: Modification of the Bertrand Procedure. Operative neurosurgery (Hagerstown, Md.) Wilson, T. J., Spinner, R. J. 2017


    Cervical dystonia, commonly referred to as spasmodic torticollis, is a neurological disorder characterized by aberrant, involuntary contraction of the muscles of the neck and shoulders. One surgical option that can be considered is selective cervical denervation.To report our modification of the Bertrand procedure for selective cervical denervation.Our modification of the Bertrand procedure for selective cervical denervation is reported with intraoperative photographs and schematic depictions of the operative steps.We report our modification of the Bertrand procedure for selective cervical denervation, which consists of a combination of C2-6 denervation, myectomy of the splenius capitis and/or semispinalis capitis, myotomy of the levator scapulae when indicated, and myotomy and selection denervation of the sternocleidomastoid. The combination of techniques utilized depends on the subtype and severity of cervical dystonia.Our modification of the original Bertrand procedure for selective cervical denervation represents an alternative surgical strategy for the treatment of cervical dystonia, with the potential advantages and disadvantages discussed.

    View details for DOI 10.1093/ons/opx147

    View details for PubMedID 29106650

  • Sciatic Nerve Injury After Proximal Hamstring Avulsion and Repair. Orthopaedic journal of sports medicine Wilson, T. J., Spinner, R. J., Mohan, R., Gibbs, C. M., Krych, A. J. 2017; 5 (7): 2325967117713685


    Muscle bellies of the hamstring muscles are intimately associated with the sciatic nerve, putting the sciatic nerve at risk of injury associated with proximal hamstring avulsion. There are few data informing the magnitude of this risk, identifying risk factors for neurologic injury, or determining neurologic outcomes in patients with distal sciatic symptoms after surgery.To characterize the frequency and nature of sciatic nerve injury and distal sciatic nerve-related symptoms after proximal hamstring avulsion and to characterize the influence of surgery on these symptoms.Cohort study; Level of evidence, 3.This was a retrospective review of patients with proximal partial or complete hamstring avulsion. The outcome of interest was neurologic symptoms referable to the sciatic nerve distribution below the knee. Neurologic symptoms in operative patients were compared pre- and postoperatively.The cohort consisted of 162 patients: 67 (41.4%) operative and 95 (58.6%) nonoperative. Sciatic nerve-related symptoms were present in 22 operative and 23 nonoperative patients, for a total of 45 (27.8%) patients (8 [4.9%] motor deficits, 11 [6.8%] sensory deficits, and 36 [22.2%] with neuropathic pain). Among the operative cohort, 3 of 3 (100.0%) patients showed improvement in their motor deficit postoperatively, 3 of 4 (75.0%) patients' sensory symptoms improved, and 17 of 19 (89.5%) patients had improvement in pain. A new or worsening deficit occurred in 5 (7.5%) patients postoperatively (2 [3.1%] motor deficits, 1 [1.5%] sensory deficit, and 3 [4.5%] with new pain). Predictors of operative intervention included lower age (odds ratio [OR], 0.952; 95% CI, 0.921-0.982; P = .001) and complete avulsion (OR, 10.292; 95% CI, 2.526-72.232; P < .001). Presence of neurologic deficit was not predictive.Sciatic nerve-related symptoms after proximal hamstring avulsion are underrecognized. Currently, neurologic symptoms are not considered when determining whether to pursue operative intervention. Given the high likelihood of improvement with surgical treatment, neurologic symptoms should be considered when making a decision regarding operative treatment.

    View details for DOI 10.1177/2325967117713685

    View details for PubMedID 28758137

    View details for PubMedCentralID PMC5513525

  • Patient-perceived surgical indication influences patient expectations of surgery for degenerative spinal disease. Clinical neurology and neurosurgery Wilson, T. J., Franz, E., Vollmer, C. F., Chang, K. W., Upadhyaya, C., Park, P., Yang, L. J. 2017; 157: 11-16


    Patients frequently have misconceptions regarding diagnosis, surgical indication, and expected outcome following spinal surgery for degenerative spinal disease. In this study, we sought to understand the relationship between patient-perceived surgical indications and patient expectations. We hypothesized that patients reporting appendicular symptoms as a primary surgical indication would report a higher rate of having expectations met by surgery compared to those patients reporting axial symptoms as a primary indication.Questionnaires were administered to patients who had undergone surgery for degenerative spinal disease at 2 tertiary care institutions. Questions assessed perception of the primary indication for undergoing surgery (radicular versus axial), whether the primary symptom improved after surgery, and whether patient expectations were met with surgery. Outcomes of interest included patient-reported symptomatic improvement following surgery and expectations met by surgery. Various factors were assessed for their relationship to these outcomes of interest.There were 151 unique survey respondents. Respondents were nearly split between having a patient-perceived indication for surgery as appendicular symptoms (55.6%) and axial symptoms (44.4%). Patient-perceived surgical indication being appendicular symptoms was the only factor predictive of patient-reported symptomatic improvement in our logistic regression model (OR 2.614; 95% CI 1.218-5.611). Patient-perceived surgical indication being appendicular symptoms (OR 3.300; 95% CI 1.575-6.944) and patient-reported symptomatic improvement (OR 33.297; 95% CI 12.186-90.979) were predictive of patients reporting their expectations met with surgery in both univariate and multivariate logistic regression modeling.We found that patient-reported appendicular symptoms as the primary indication for surgery were associated with a higher rate of both subjective improvement following surgery and having expectations met by surgery. Studies such as ours point to the fact that while performing technically superlative operations is paramount, it may be equally important to address other factors that help determine patient perception of the surgery experience.

    View details for DOI 10.1016/j.clineuro.2017.03.007

    View details for PubMedID 28359906

  • Commentary: Cubital tunnel syndrome caused by intraneural or extraneural ganglion cysts-case report and review of the literature: Ulnar nerve ganglion cysts: Drawing closer to shore. Journal of plastic, reconstructive & aesthetic surgery : JPRAS Wilson, T. J., Spinner, R. J. 2017

    View details for DOI 10.1016/j.bjps.2017.05.022

    View details for PubMedID 28579179

  • Recognition of peroneal intraneural ganglia in an historical cohort with "negative" MRIs ACTA NEUROCHIRURGICA Wilson, T. J., Hebert-Blouin, M., Murthy, N. S., Amrami, K. K., Spinner, R. J. 2017; 159 (5): 925-930


    The objective of this study was to review an historical cohort of patients with peroneal neuropathy and magnetic resonance imaging (MRI) read as negative for mass or cyst to determine if occult peroneal intraneural ganglion cysts can be identified on subsequent imaging review and to use this as an estimation of how under-recognized this pathologic entity is.The patient cohort utilized in this study was a previously published control cohort of 11 patients with peroneal neuropathy and MRI read as negative for mass or cyst. Clinical history, neurologic examination, and MRI studies of the knee were reviewed for each of the included patients. The primary outcome of interest was the presence of peroneal intraneural ganglion cyst on MRI.Overall, 7 of 11 (64%) patients in this historical "normal" cohort had evidence of a peroneal intraneural ganglion cyst on subsequent review of imaging. Deep peroneal-predominant weakness, knee pain, and tibialis anterior-predominant denervation/atrophy were seen more commonly in patients in whom an intraneural cyst was identified.This retrospective cohort study provides evidence that peroneal intraneural ganglion cysts are an historically under-recognized cause of peroneal neuropathy, with 64% of this historical "negative" cohort having evidence of a cyst on subsequent imaging review. Larger studies are needed to determine the treatment ramifications of identifying small cysts and to determine the clinical features suggestive of an intraneural ganglion cyst.

    View details for DOI 10.1007/s00701-017-3130-3

    View details for Web of Science ID 000399177300028

    View details for PubMedID 28258311

  • Prediction Algorithm for Surgical Intervention in Neonatal Brachial Plexus Palsy. Neurosurgery Wilson, T. J., Chang, K. W., Yang, L. J. 2017


    Neonatal brachial plexus palsy (NBPP) results in reduced function of the affected arm with profound ramifications on quality of life. Advances in surgical technique have shown improvements in outcomes for appropriately selected patients. Patient selection, however, remains difficult.To develop a decision algorithm that could be applied at the individual patient level, early in life, to reliably predict persistent NBPP that would benefit from surgery.Retrospective review of NBPP patients was undertaken. Maternal and neonatal factors were entered into the C5.0 statistical package in R (The R Foundation). A 60/40 model was employed, whereby 60% of randomized data were used to train the decision tree, while the remaining 40% were used to test the decision tree. The outcome of interest for the decision tree was a severe lesion meeting requirements for surgical candidacy.A decision tree prediction algorithm was generated from the entered variables. Variables utilized in the final decision tree included presence of Horner's syndrome, presence of a pseudomeningocele, Narakas grade, clavicle fracture at birth, birth weight >9 lbs, and induction or augmentation of labor. Sensitivity of the decision tree was 0.71, specificity 0.96, positive predictive value 0.94, negative predictive value 0.79, and F1 score 0.81.We developed a decision tree prediction algorithm that can be applied shortly after birth to determine surgical candidacy of patients with NBPP, the first of its kind utilizing only maternal and neonatal factors. This conservative decision tree can be used to offer early surgical intervention for appropriate candidates.

    View details for DOI 10.1093/neuros/nyx190

    View details for PubMedID 28419287

  • Frontal Sinus Breach During Routine Frontal Craniotomy Significantly Increases Risk of Surgical Site Infection: 10-Year Retrospective Analysis. Neurosurgery Linzey, J. R., Wilson, T. J., Sullivan, S. E., Thompson, B. G., Pandey, A. S. 2017


    Frontotemporal craniotomies are commonly performed for a variety of neurosurgical pathologies. Infections related to craniotomies cause significant morbidity. We hypothesized that the risk of cranial surgical site infections (SSIs) may be increased in patients whose frontal sinuses are breached during craniotomy.To compare the rate of cranial SSIs in patients undergoing frontotemporal craniotomies with and without frontal sinus breach (FSB).We performed a retrospective analysis of all patients undergoing frontotemporal craniotomies for the management of cerebral aneurysms from 2005 to 2014. This study included 862 patients undergoing 910 craniotomies. Primary outcome of interest was occurrence of a cranial SSI. Standard statistical methods were utilized to explore associations between a variety of variables including FSB, cranial SSI, and infections requiring reoperation.Of the 910 craniotomies, 141 (15.5%) involved FSB. Of those involving FSB, 22 (15.6%) developed a cranial SSI, compared to only 56 of the 769 without FSB (7.3%; P = .001). Cranial SSI requiring reoperation was much more likely in patients with FSB compared to those without a breach (7.8% vs 1.6%; P < .001). In those presenting with cranial SSIs, epidural abscess formation was more common with FSB compared to no FSB (27.3% vs 5.4%; P = .006). In multivariate analysis, breach of the frontal sinus was significantly associated with cranial SSI (OR 2.16; 95% CI 1.24-3.78; P = .01) and reoperation (OR 4.20; 95% CI 1.66-10.65; P = .003).Patients undergoing frontotemporal craniotomies are at significantly greater risk of serious cranial SSIs if the frontal sinus has been breached.

    View details for DOI 10.1093/neuros/nyx046

    View details for PubMedID 28327980

  • Osborne's Ligament: A Review of its History, Anatomy, and Surgical Importance. Cureus Granger, A., Sardi, J. P., Iwanaga, J., Wilson, T. J., Yang, L., Loukas, M., Oskouian, R. J., Tubbs, R. S. 2017; 9 (3)


    When discussing the pathophysiology of ulnar neuropathy, Geoffrey Vaughan Osborne described a fibrous band that can be responsible for the symptoms seen in this disorder. In this paper, we take a glimpse at the life of Osborne and review the anatomy and surgical significance of Osborne's ligament. This band of tissue connects the two heads of the flexor carpi ulnaris and thus forms the roof of the cubital tunnel. To our knowledge, no prior publication has reviewed the history of this ligament, and very few authors have studied its anatomy in any detail. Therefore, the aim of the present paper is to elucidate this structure that is often implicated and surgically transected to decompress the ulnar nerve at the elbow.

    View details for DOI 10.7759/cureus.1080

    View details for PubMedID 28405530

    View details for PubMedCentralID PMC5383373

  • Superficial ulnar nerve articular branch: More than arcane trivia. Clinical anatomy Wilson, T. J., Amrami, K. K., Spinner, R. J. 2017

    View details for DOI 10.1002/ca.22863

    View details for PubMedID 28247942

  • Pilot study of intraoperative ultrasound-guided instrument placement in nerve transection surgery for peripheral nerve pain syndromes NEUROSURGICAL FOCUS Henning, P. T., Wilson, T. J., Willsey, M., John, J. K., Popadich, M., Yang, L. J. 2017; 42 (3)


    Surgical transection of sensory nerves in the treatment of intractable neuropathic pain is a commonly performed procedure. At times these cases can be particularly challenging when encountering obese patients, when targeting deeper nerves or those with a variable branching pattern, or in the case of repeat operations. In this case series, the authors describe their experience with ultrasound-guided surgical instrument placement during transection of a saphenous nerve in the region of prior vascular surgery in 1 patient and in the lateral femoral cutaneous nerve in 2 obese patients. The authors also describe this novel technique and provide pilot data that suggests ultrasound-assisted surgery may allow for complex cases to be completed in an expedited fashion through smaller incisions.

    View details for DOI 10.3171/2017.1.FOCUS16438

    View details for Web of Science ID 000395837500006

    View details for PubMedID 28245671

  • The nearly invisible intraneural cyst: a new and emerging part of the spectrum NEUROSURGICAL FOCUS Wilson, T. J., Hebert-Blouin, M., Murthy, N. S., Garcia, J. J., Amrami, K. K., Spinner, R. J. 2017; 42 (3)


    OBJECTIVE The authors have observed that a subset of patients referred for evaluation of peroneal neuropathy with "negative" findings on MRI of the knee have subtle evidence of a peroneal intraneural ganglion cyst on subsequent closer inspection. The objective of this study was to introduce the nearly invisible peroneal intraneural ganglion cyst and provide illustrative cases. The authors further wanted to identify clues to the presence of a nearly invisible cyst. METHODS Illustrative cases demonstrating nearly invisible peroneal intraneural ganglion cysts were retrospectively reviewed and are presented. Case history and physical examination, imaging, and intraoperative findings were reviewed for each case. The outcomes of interest were the size and configuration of peroneal intraneural ganglion cysts over time, relative to various interventions that were performed, and in relation to physical examination and electrodiagnostic findings. RESULTS The authors present a series of cases that highlight the dynamic nature of peroneal intraneural ganglion cysts and introduce the nearly invisible cyst as a new and emerging part of the spectrum. The cases demonstrate changes in size and morphology over time of both the intraneural and extraneural compartments of these cysts. Despite "negative" MR imaging findings, nearly invisible cysts can be identified in a subset of patients. CONCLUSIONS The authors demonstrate here that peroneal intraneural ganglion cysts ride a roller coaster of change in both size and morphology over time, and they describe the nearly invisible cyst as one end of the spectrum. They identified clues to the presence of a nearly invisible cyst, including deep peroneal predominant symptoms, fluctuating symptoms, denervation changes in the tibialis anterior muscle, and abnormalities of the superior tibiofibular joint, and they correlate the subtle imaging findings to the internal fascicular topography of the common peroneal nerve. The description of the nearly invisible cyst may allow for increased recognition of this pathological entity that occurs with a spectrum of findings.

    View details for DOI 10.3171/2016.12.FOCUS16439

    View details for Web of Science ID 000395837500010

    View details for PubMedID 28245669

  • Imaging Characteristics Predict Operative Difficulty Mobilizing the Sciatic Nerve for Proximal Hamstring Repair. Neurosurgery Wilson, T. J., Howe, B. M., Spinner, R. J., Krych, A. J. 2017


    Repair of proximal hamstring avulsions requires mobilization of the sciatic nerve away from the tendon stump, which can be achieved with varying difficulty depending on the degree of scar formation and adherence. Predicting when a scarred, adherent, difficult-to-mobilize nerve will be encountered has been difficult.To identify clinical and/or radiological factors predictive of a difficult intraoperative dissection of the sciatic nerve during proximal hamstring repair.We retrospectively reviewed the medical records and preoperative magnetic resonance imaging of consecutive patients undergoing proximal hamstring repair. We compared the groups with and without a difficult sciatic nerve dissection.The total cohort consisted of 67 patients. Factors found to increase the likelihood of a difficult sciatic nerve dissection included complete conjoint tendon avulsion, higher maximal amount of tendon retraction, higher degree of imaging abnormality in the sciatic nerve, and higher degree of circumferential relationship of hematoma to the sciatic nerve. At a threshold of 23 for the Sciatic Nerve Dissection Score, the positive and negative predictive values were 53% and 88%, respectively. For the decision tree, the positive and negative predictive values were 75% and 87%, respectively.We have identified imaging factors associated with a scarred, adherent sciatic nerve that predict a difficult dissection during proximal hamstring repair. We have developed 2 novel methods-the Sciatic Nerve Dissection Score and a decision tree-that can be applied to predict the probability of a difficult sciatic nerve dissection at the time of surgical repair.

    View details for PubMedID 29145673

  • The anconeus epitrochlearis muscle may protect against the development of cubital tunnel syndrome: a preliminary study JOURNAL OF NEUROSURGERY Wilson, T. J., Tubbs, R. S., Yang, L. J. 2016; 125 (6): 1533-1538


    OBJECTIVE The authors hypothesized that when the anatomical variant of an anconeus epitrochlearis is present, the risk of developing cubital tunnel syndrome would be reduced by replacing the normal roof of the cubital tunnel (Osborne's ligament) with a more forgiving muscular structure, the anconeus epitrochlearis. The authors further hypothesized that when the presence of an anconeus epitrochlearis contributes to ulnar neuropathy, it would be secondary to muscular hypertrophy, thereby making it more likely to occur in the dominant arm. Therefore, the goal of the present study was to evaluate these hypotheses. METHODS This retrospective cohort study was performed by reviewing the records of all adult patients who underwent operative intervention for cubital tunnel syndrome between 2005 and 2014 as the experimental group and all asymptomatic patients in the medical literature who were part of a series reporting the prevalence of an anconeus epitrochlearis as the control group. The primary outcome of interest was the presence of an anconeus epitrochlearis in asymptomatic individuals versus patients with cubital tunnel syndrome. RESULTS During the study period, 168 patients underwent decompression of the ulnar nerve for cubital tunnel syndrome, and an anconeus epitrochlearis was found at surgery in 9 (5.4%) patients. The control group consisted of 634 asymptomatic patients from the medical literature, and an anconeus epitrochlearis was present in 98 (15.5%) of these patients. An anconeus epitrochlearis was present significantly less frequently in the symptomatic patients than in asymptomatic individuals (p < 0.001). Among patients undergoing surgical decompression, an anconeus epitrochlearis was associated with symptoms in the dominant arm (p = 0.037). CONCLUSIONS The authors found that an anconeus epitrochlearis was present significantly less often in patients with cubital tunnel syndrome than in asymptomatic controls. The mechanism of protection may be that this muscle decreases the rigidity of the entrance into the cubital tunnel. When an anconeus epitrochlearis does contribute to cubital tunnel syndrome, it is significantly more likely to occur in the dominant arm, possibly due to repetitive use and hypertrophy of the anconeus epitrochlearis. The presence of an anconeus epitrochlearis may be protective against the development of cubital tunnel syndrome, although this is a preliminary finding.

    View details for DOI 10.3171/2015.10.JNS151668

    View details for Web of Science ID 000388783000024

    View details for PubMedID 26871208

  • Reversibility of glioma stem cells' phenotypes explains their complex in vitro and in vivo behavior. Discovery of a novel neurosphere-specific enzyme, cGMP-dependent protein kinase 1, using the genomic landscape of human glioma stem cells as a discovery tool ONCOTARGET Wilson, T. J., Zamler, D. B., Doherty, R., Castro, M. G., Lowenstein, P. R. 2016; 7 (39): 63020-63041


    Glioma cells grow in two phenotypic forms, as adherent monolayers and as free floating "neurospheres/tumorspheres", using specific media supplements. Whether each phenotype is irreversible remains unknown. Herein we show that both states are reversible using patient derived glioblastoma cell cultures (i.e., HF2303, IN859, MGG8, IN2045). Both phenotypic states differ in proliferation rate, invasion, migration, chemotaxis and chemosensitivity. We used microarrays to characterize gene expression across the patient derived glioblastoma cell cultures, to find specific inhibitors of the sphere population. Traditional chemotherapeutics (i.e., doxorubicin or paclitaxel) inhibit rapidly dividing adherent cells; it has been more challenging to inhibit the growth of the sphere phenotype. PRKG1, known to induce apoptosis when activated, is increased in all patient derived glioblastoma spheres. Stimulation of PRKG1 activity preferentially reduced cell viability in the sphere phenotype. Computational network and gene ontology analysis identified novel potential target genes linked to the PRKG1 expression node.

    View details for DOI 10.18632/oncotarget.11589

    View details for Web of Science ID 000387167800017

    View details for PubMedID 27564115

    View details for PubMedCentralID PMC5325344

  • Changes in Therapeutic Intensity Level Following Airway Pressure Release Ventilation in Severe Traumatic Brain Injury. Journal of intensive care medicine Fletcher, J. J., Wilson, T. J., Rajajee, V., Davidson, S. B., Walsh, J. C. 2016


    Airway pressure release ventilation (APRV) utilizes high levels of airway pressure coupled with brief expiratory release to facilitate open lung ventilation. The aim of our study was to evaluate the effects of APRV-induced elevated airway pressure mean in patients with severe traumatic brain injury.This was a retrospective cohort study at a 424-bed Level I trauma center. Linear mixed effects models were developed to assess the difference in therapeutic intensity level (TIL), intracranial pressure (ICP), and cerebral perfusion pressure (CPP) over time following the application of APRV.The study included 21 epochs of APRV in 21 patients. In the 6-hour epoch following the application of APRV, the TIL was significantly increased (P = .002) and the ICP significantly decreased (P = .041) compared to that before 6 hours. There was no significant change in CPP (P = .42) over time. The baseline static compliance and time interaction was not significant for TIL (χ2 = 0.2 [df 1], P = .655), CPP (χ2 = 0 [df 1], P = 1), or ICP (χ2 = 0.1 [df 1], P = .752).Application of APRV in patients with severe traumatic brain injury was associated with significantly, but not clinically meaningful, increased TIL and decreased ICP. No significant change in CPP was observed. No difference was observed based on the baseline pulmonary static compliance.

    View details for PubMedID 27651443

  • Morphometric analysis of the developing pediatric cervical spine JOURNAL OF NEUROSURGERY-PEDIATRICS Johnson, K. T., Al-Holou, W. N., Anderson, R. C., Wilson, T. J., Karnati, T., Ibrahim, M., Garton, H. J., Maher, C. O. 2016; 18 (3): 377-389


    OBJECTIVE Our understanding of pediatric cervical spine development remains incomplete. The purpose of this analysis was to quantitatively define cervical spine growth in a population of children with normal CT scans. METHODS A total of 1458 children older than 1 year and younger than 18 years of age who had undergone a cervical spine CT scan at the authors' institution were identified. Subjects were separated by sex and age (in years) into 34 groups. Following this assignment, subjects within each group were randomly selected for inclusion until a target of 15 subjects in each group had been measured. Linear measurements were performed on the midsagittal image of the cervical spine. Twenty-three unique measurements were obtained for each subject. RESULTS Data showed that normal vertical growth of the pediatric cervical spine continues up to 18 years of age in boys and 14 years of age in girls. Approximately 75% of the vertical growth occurs throughout the subaxial spine and 25% occurs across the craniovertebral region. The C-2 body is the largest single-segment contributor to vertical growth, but the subaxial vertebral bodies and disc spaces also contribute. Overall vertical growth of the cervical spine throughout childhood is dependent on individual vertebral body growth as well as vertical growth of the disc spaces. The majority of spinal canal diameter growth occurs by 4 years of age. CONCLUSIONS The authors' morphometric analyses establish parameters for normal pediatric cervical spine growth up to 18 years of age. These data should be considered when evaluating children for potential surgical intervention and provide a basis of comparison for studies investigating the effects of cervical spine instrumentation and fusion on subsequent growth.

    View details for DOI 10.3171/2016.3.PEDS1612

    View details for Web of Science ID 000381781300017

    View details for PubMedID 27231821

  • Comparison of the accuracy and proximal shunt failure rate of freehand placement versus intraoperative guidance in parietooccipital ventricular catheter placement NEUROSURGICAL FOCUS Wilson, T. J., Mccoy, K. E., Al-Holou, W. N., Molina, S. L., Smyth, M. D., Sullivan, S. E. 2016; 41 (3)


    OBJECTIVE The aim of this paper is to compare the accuracy of the freehand technique versus the use of intraoperative guidance (either ultrasound guidance or frameless stereotaxy) for placement of parietooccipital ventricular catheters and to determine factors associated with reduced proximal shunt failure. METHODS This retrospective cohort study included all patients from 2 institutions who underwent a ventricular cerebrospinal fluid (CSF) shunting procedure in which a new parietooccipital ventricular catheter was placed between January 2005 and December 2013. Data abstracted for each patient included age, sex, method of ventricular catheter placement, side of ventricular catheter placement, Evans ratio, and bifrontal ventricular span. Postoperative radiographic studies were reviewed for accuracy of ventricular catheter placement. Medical records were also reviewed for evidence of shunt failure requiring revision. Standard statistical methods were used for analysis. RESULTS A total of 257 patients were included in the study: 134 from the University of Michigan and 123 from Washington University in St. Louis. Accurate ventricular catheter placement was achieved in 81.2% of cases in which intraoperative guidance was used versus 67.3% when the freehand technique was used. Increasing age reduced the likelihood of accurate catheter placement (OR 0.983, 95% CI 0.971-0.995; p = 0.005), while the use of intraoperative guidance significantly increased the likelihood (OR 2.809, 95% CI 1.406-5.618; p = 0.016). During the study period, 108 patients (42.0%) experienced shunt failure, 79 patients (30.7%) had failure involving the proximal catheter, and 53 patients (20.6%) had distal failure (valve or distal catheter). Increasing age reduced the likelihood of being free from proximal shunt failure (OR 0.983, 95% CI 0.970-0.995; p = 0.008), while both the use of intraoperative guidance (OR 2.385, 95% CI 1.227-5.032; p = 0.011), and accurate ventricular catheter placement (OR 3.424, 95% CI 1.796-6.524; p = 0.009) increased the likelihood. CONCLUSIONS The use of intraoperative guidance during parietooccipital ventricular catheter placement as part of a CSF shunt system significantly increases the likelihood of accurate catheter placement and subsequently reduces the rate of proximal shunt failure.

    View details for DOI 10.3171/2016.5.FOCUS16159

    View details for Web of Science ID 000383442500010

    View details for PubMedID 27581306

  • The current role of diagnostic imaging in the preoperative workup for refractory neonatal brachial plexus palsy CHILDS NERVOUS SYSTEM Somashekar, D. K., Wilson, T. J., DiPietro, M. A., Joseph, J. R., Ibrahim, M., Yang, L. J., Parmar, H. A. 2016; 32 (8): 1393-1397


    Despite recent improvements in perinatal care, the incidence of neonatal brachial plexus palsy (NBPP) remains relatively common. CT myelography is currently considered to be the optimal imaging modality for evaluating nerve root integrity. Recent improvements in MRI techniques have made it an attractive alternative to evaluate nerve root avulsions (preganglionic injuries).We demonstrate the utility of MRI for the evaluation of normal and avulsed spinal nerve roots. We also show the utility of ultrasound in providing useful preoperative evaluation of the postganglionic brachial plexus in patients with NBPP.

    View details for DOI 10.1007/s00381-016-3106-2

    View details for Web of Science ID 000380667400010

    View details for PubMedID 27179536

  • A Randomized Trial of Central Venous Catheter Type and Thrombosis in Critically Ill Neurologic Patients NEUROCRITICAL CARE Fletcher, J. J., Wilson, T. J., Rajajee, V., Stetler, W. R., Jacobs, T. L., Sheehan, K. M., Brown, D. L. 2016; 25 (1): 20-28


    Observational studies suggest peripherally inserted central venous catheters (PICCs) are associated with a high risk of catheter-related large vein thrombosis (CRLVT) in critically ill neurologic patients. We evaluated the difference in thrombosis risk between PICCs and centrally inserted central venous catheters (CICVCs).We conducted a pragmatic, randomized controlled trial of critically ill adult neurologic patients admitted to neurological and trauma critical care units at two level I trauma centers. Patients were randomized to receive either a PICC or CICVC and undergo active surveillance for CRLVT or death within 15 days of catheter placement.In total, 39 subjects received a PICC and 41 received a CICVC between February 2012 and July 2015. The trial was stopped after enrollment of 80 subjects due to feasibility affected by slow enrollment and funding. In the primary intention-to-treat analysis, 17 (43.6 %) subjects that received a PICC compared to 9 (22.0 %) that received a CICVC experienced the composite of CRLVT or death, with a risk difference of 21.6 % (95 % CI 1.57-41.71 %). Adjusted common odds ratio of CRLVT/death was significantly higher among subjects randomized to receive a PICC (adjusted OR 3.08; 95 % CI 1.1-8.65). The higher adjusted odds ratio was driven by risk of CRLVT, which was higher in those randomized to PICC compared to CICVC (adjusted OR 4.66; 95 % CI 1.3-16.76) due to increased large vein thrombosis without a reduction in proximal deep venous thrombosis.Our trial demonstrates that critically ill neurologic patients who require a central venous catheter have significantly lower odds of ultrasound-diagnosed CRLVT with placement of a CICVC as compared to a PICC.

    View details for DOI 10.1007/s12028-016-0247-9

    View details for Web of Science ID 000380150700004

    View details for PubMedID 26842716

  • Is intensive care monitoring necessary after coil embolization of unruptured intracranial aneurysms? Journal of neurointerventional surgery Stetler, W. R., Griauzde, J., Saadeh, Y., Wilson, T. J., Al-Holou, W. N., Chaudhary, N., Thompson, B. G., Pandey, A. S., Gemmete, J. J. 2016


    Patients with an unruptured intracranial aneurysm treated with coil embolization are routinely admitted to the intensive care unit (ICU) after the procedure; however, this practice is questionable. The purpose of this study was to determine if routine admission to the ICU is necessary for patients undergoing coil embolization of an unruptured intracranial aneurysm.We conducted a retrospective cohort study of all patients undergoing elective endovascular treatment of an unruptured intracranial aneurysm between 2005 and 2012 at our institution. Multivariate regression analysis was performed to identify predictors of outcome. Cost savings analysis compared ICU admission to step-down or telemetry unit admission.311 unruptured intracranial aneurysms were treated by coil embolization (190), balloon remodeling (13), or stent-assisted coiling (108). Eleven (3.5%) neurologic complications were noted; 5 (1.6%) of these were permanent. Multivariate regression analysis identified female sex (p=0.028), hypercoagulability (p=0.021), aneurysm size >2 cm (p=0.003), and intraoperative rupture (p<0.001) as predictors of a post-procedural neurologic complication. Cost savings were 57% for admission to a step-down unit and 32% for admission to a telemetry unit compared with ICU admission.Neurologic complications are rare in the treatment of unruptured intracranial aneurysms, suggesting that routine ICU admission after treatment may not be necessary. Female sex, history of hypercoagulability, aneurysm size >2 cm, and an intraprocedural rupture were predictive of a postoperative complication. ICU monitoring in these subgroups may therefore be warranted.

    View details for DOI 10.1136/neurintsurg-2016-012511

    View details for PubMedID 27382122

  • Persistence of Neonatal Brachial Plexus Palsy Associated with Maternally Reported Route of Delivery: Review of 387 Cases AMERICAN JOURNAL OF PERINATOLOGY Chang, K. W., Ankumah, N. E., Wilson, T. J., Yang, L. J., Chauhan, S. P. 2016; 33 (8): 765-769


    Objective The factors associated with persistent neonatal brachial plexus palsy (PNBPP) are unknown. Our objectives are to compare PNBPP at 1 and 2 years in children delivered via vaginal delivery (VD) versus cesarean delivery (CD) and in children delivered via VD with or without reported shoulder dystocia (SD). Study Design Retrospective cohort of children diagnosed with neonatal brachial plexus palsy (NBPP). Maternally reported delivery history and presence of SD were recorded with Student t-test, chi-square test, and odds ratio (OR) with 95% confidence intervals (CI) calculated for comparisons. Results Of 387 cases of NBPP, 8% (30) delivered via CD. Rates of PNBPP were higher in the VD group at 1 and 2 years (60% of CD and 85% of VD; OR, 0.26; 95% CI, 0.11-0.62 at 1 year; 33% of CD and 73% of VD; OR, 0.15; 95% CI, 0.05-0.39 at 2 years). There was no difference in PNBPP in women with VD with or without maternally reported SD (87 vs. 85%, p = 0.68 at 1 year; 64 vs. 61%, p = 0.61 at 2 years). Conclusion PNBPP is possible with CD, and there is no difference in PNBPP in VD with or without maternally reported SD. A prospective study is warranted to ascertain associative factors.

    View details for DOI 10.1055/s-0036-1571351

    View details for PubMedID 26890435

  • Delayed Sciatic Nerve Injury Resulting From Myositis Ossificans Traumatica PM&R Guan, Z., Wilson, T. J., Jacobson, J. A., Hollon, T. C., Yang, L. J. 2016; 8 (5): 484-487


    A motorcyclist sustained multiple-system trauma, including a left buttock hematoma requiring decompression and evacuation. Presentation for severe hip pain and lower extremity weakness was delayed. Imaging revealed myositis ossificans traumatica compressing the sciatic nerve in the buttock. The patient underwent sciatic nerve decompression with resection of heterotopic calcification, resulting in improvement in pain and left lower extremity function. This case illustrates the contrast in differential diagnosis of peripheral nerve injury immediately posttrauma and that occurring in a slow, delayed fashion posttrauma. Myositis ossificans may be an underrecognized complication of trauma but should be considered in cases of delayed peripheral nerve injury after trauma.

    View details for DOI 10.1016/j.pmrj.2015.10.011

    View details for Web of Science ID 000375749500011

    View details for PubMedID 26548968

  • Sonography of Common Peripheral Nerve Disorders With Clinical Correlation JOURNAL OF ULTRASOUND IN MEDICINE Jacobson, J. A., Wilson, T. J., Yang, L. J. 2016; 35 (4): 683-693


    Sonography is now considered an effective method to evaluate peripheral nerves. Low cost, high resolution, the ability to image an entire limb in a short time, and dynamic assessment are several of the positive attributes of sonography. This article will review the normal appearance of peripheral nerves as shown with sonography. In addition, the most common applications for sonography of the peripheral nerves will be reviewed, which include entrapment neuropathies, intraneural ganglion cyst, nerve trauma, and peripheral nerve sheath tumors. Clinical information related to nerve disorders is also included, as it provides valuable information that can be obtained during sonographic examinations, increasing diagnostic accuracy.

    View details for DOI 10.7863/ultra.15.05061

    View details for Web of Science ID 000375333200002

    View details for PubMedID 26931790

  • Evaluation and management of fibrofatty tumors of the extremities: case report JOURNAL OF NEUROSURGERY-PEDIATRICS Wilson, T. J., Joseph, J. R., Dillman, J. R., Heider, A., Yang, L. J. 2016; 17 (1): 66-69


    Patients presenting with enlarging fibrofatty masses in the extremities pose an interesting dilemma to clinicians, as the differential diagnosis in such cases ranges from benign to malignant, and from lesions optimally managed operatively to those managed nonoperatively. The differential diagnosis includes benign lipoma, liposarcoma, lipoblastoma, and fibrolipomatous hamartoma (lipomatosis) of the nerves. The authors present the case of a 14-year-old girl with an enlarging fibrofatty mass of the forearm, initially thought, based on diagnostic imaging, to be a fibrolipomatous hamartoma of the median nerve, but found to be a lipoblastoma without direct nerve involvement based on histopathological examination of the operative specimen. This case serves to illustrate the diagnostic predicament that can exist with such masses. The authors advocate the need to establish a tissue diagnosis while having a contingency plan for each of the diagnostic possibilities because the management of each lesion is markedly different. In this report, the authors consider the differential diagnosis of fibrofatty masses of the extremities that the peripheral nerve surgeon may encounter, and they highlight the significant differences in management strategies for each possible diagnosis.

    View details for DOI 10.3171/2015.2.PEDS14570

    View details for Web of Science ID 000367027900011

    View details for PubMedID 26451716

  • Management of recurrent aneurysms following endovascular therapy JOURNAL OF CLINICAL NEUROSCIENCE Chen, K. S., Wilson, T. J., Stetler, W. R., Davis, M. C., Giles, D. A., Kahn, E. N., Chaudhary, N., Gemmete, J. J., Thompson, B. G., Pandey, A. S. 2015; 22 (12): 1901-1906


    The aim of the current study is to describe the complication rates and clinical outcomes in patients who either underwent repeat intervention or conservative management with radiographic surveillance when presenting with aneurysmal recurrence after endovascular treatment. Since publication of the international subarachnoid aneurysm trial (ISAT), an increasing number of patients are treated with endovascular therapy. However, recurrence after endovascular therapy continues to pose a challenge, and there is minimal evidence to guide its management. We performed a retrospective review of all patients who underwent endovascular treatment of an intracranial aneurysm from January 2005 to February 2013. The patients who had an aneurysmal recurrence following the initial endovascular treatment were identified and divided into two groups: those followed with conservative management (n=24), and those who underwent reintervention (n=65). The groups were compared for complications and clinical outcomes. When a reintervention was undertaken, microsurgical clip ligation was associated with a higher rate of occlusion than additional endovascular therapy (p<0.001). When comparing conservative treatment and reintervention, there was no statistically significant difference in complications or clinical outcomes. Reintervention was more common in patients who were younger, had presented with subarachnoid hemorrhage, or had a greater degree of recurrence. We conclude that clinical outcomes and repeat subarachnoid hemorrhage are similar in patients who underwent retreatment versus those who had conservative management for their recurrent cerebral aneurysms.

    View details for DOI 10.1016/j.jocn.2015.04.012

    View details for Web of Science ID 000365370600010

    View details for PubMedID 26256068

  • Intraoperative angiography does not lead to increased rates of surgical site infections JOURNAL OF NEUROINTERVENTIONAL SURGERY Stetler, W. R., Wilson, T. J., Al-Holou, W. N., Khan, A., Thompson, B. G., Pandey, A. S. 2015; 7 (10): 744-747


    Intraoperative angiography (IOA) is essential in evaluating residual aneurysm following clip ligation, but it does lead to an additional procedure which increases the duration of the procedure as well as increasing room traffic. We examined whether IOA during microsurgery is a risk factor for developing cranial surgical site infection.A retrospective cohort study was performed of all patients undergoing craniotomy for aneurysm treatment between 2005 and 2012 at the University of Michigan. IOA was used at the surgeons' discretion. The primary outcome of interest was occurrence of a surgical site infection and the secondary outcome of interest was clip repositioning following IOA. Variables including IOA were tested for their independent association with the occurrence of a surgical site infection.During the study period 676 intracranial aneurysms were treated by craniotomy; IOA was used in 104 of these cases. There were a total of 20 surgical site infections, 2 in the IOA group (1.9%) and 18 in the non-IOA group (3.1%), indicating that IOA was not a statistically significant variable for infection (p=0.50). No additional single variable measured could be shown to have a statistically significant increase in infection, and there were no direct complications related to the use of IOA (stroke, dissection, perforation).IOA does not increase the risk of developing a surgical site infection. It can be conducted without exposing patients to an undue risk of infection.

    View details for DOI 10.1136/neurintsurg-2014-011346

    View details for Web of Science ID 000361756100013

    View details for PubMedID 25155479

  • High Subarachnoid Hemorrhage Patient Volume Associated With Lower Mortality and Better Outcomes NEUROSURGERY Pandey, A. S., Gemmete, J. J., Wilson, T. J., Chaudhary, N., Thompson, B. G., Morgenstern, L. B., Burke, J. F. 2015; 77 (3): 462-470


    High-volume centers have better outcomes than low-volume centers when managing complex conditions including subarachnoid hemorrhage (SAH).To quantify SAH volume-outcome association and determine the extent to which this association is influenced by aggressiveness of care.A serial cross-sectional retrospective study using the Nationwide Inpatient Sample for 2002 to 2010 was performed. Included were all adult (older than 18 years of age) discharged patients with a primary diagnosis of SAH admitted from the emergency department or transferred to a discharging hospital; cases of trauma or arteriovenous malformation were excluded. Survey-weighted descriptive statistics estimated temporal trends. Multilevel logistic regression estimated volume-outcome associations for inpatient mortality and discharge home. Models were adjusted for demographic characteristics, year, transfer status, insurance status, all individual Charlson comorbidities, intubation, and all patient-refined, diagnosis-related group mortality. Analyses were repeated, excluding cases in which aggressive care was not pursued.A total of 32,336 discharges were included; 13,398 patients underwent clipping (59.1%) or coiling (40.9%). The inpatient mortality rate decreased from 32.2% in 2002 to 22.2% in 2010; discharge home increased from 28.5% to 40.8% during the same period. As SAH volume decreased from 100/year, the mortality rate increased from 18.7% to 19.8% at 80/year, 21.7% at 60/year, 24.5% at 40/year, and 28.4% at 20/year. As SAH patient volume decreased, the probability of discharge home decreased from 40.3% at 100/year to 38.7% at 60/year, and 35.3% at 20/year. Better outcomes persisted in patients receiving aggressive care and in those not receiving aggressive care.Short-term SAH outcomes have improved. High-volume hospitals have more favorable outcomes than low-volume hospitals. This effect is substantial, even for hospitals conventionally classified as high volume.

    View details for DOI 10.1227/NEU.0000000000000850

    View details for Web of Science ID 000359680700032

    View details for PubMedID 26110818

    View details for PubMedCentralID PMC4869982

  • Conventional endovascular treatment of small intracranial aneurysms is not associated with additional risks compared with treatment of larger aneurysms JOURNAL OF NEUROINTERVENTIONAL SURGERY Stetler, W. R., Wilson, T. J., Al-Holou, W. N., Chaudhary, N., Gemmete, J. J., Thompson, B. G., Pandey, A. S. 2015; 7 (4): 262-265


    Endovascular treatment of small intracranial aneurysms has historically been technically challenging and has been associated with high rates of complications and intraprocedural rupture. In this study, we compared complication and recurrence rates for treatment of small aneurysms (≤ 4 mm) versus large aneurysms in the context of the advent of improvements in endovascular techniques and technologies.A retrospective cohort study was performed to include all patients who underwent coiling of an intracranial aneurysm between 2005 and 2012. Small aneurysms were defined as any aneurysm 4.0 mm or smaller in all dimensions. The primary outcome was a composite outcome of the occurrence of an intraoperative rupture or a perioperative thromboembolic event. The secondary outcome of interest was aneurysm recurrence.During the study period, 483 patients were treated using endovascular techniques; 85 (17.6%) of these patients had small aneurysms. In the small aneurysm group, there was only one (1.2%) intraoperative rupture, three (3.5%) perioperative thromboembolic events, and 11 (12.9%) incidents of aneurysm recurrence. Both the primary and secondary outcomes of interest were similar in patients presenting with small or large aneurysms. Small aneurysm size was not a risk factor for either the composite primary outcome or aneurysm recurrence in multivariate analysis.Treatment of small intracranial aneurysms via conventional endovascular coiling techniques is not inferior to endovascular treatment of larger aneurysms based on our single institution experience. While technically challenging, such aneurysms may be treated safely and effectively with acceptable rates of complications and recurrence.

    View details for DOI 10.1136/neurintsurg-2014-011133

    View details for Web of Science ID 000351619400012

    View details for PubMedID 24623836

  • Intraventricular Hemorrhage Is Associated with Early Hydrocephalus, Symptomatic Vasospasm, and Poor Outcome in Aneurysmal Subarachnoid Hemorrhage JOURNAL OF NEUROLOGICAL SURGERY PART A-CENTRAL EUROPEAN NEUROSURGERY Wilson, T. J., Stetler, W. R., Davis, M. C., Giles, D. A., Khan, A., Chaudhary, N., Gemmete, J. J., Xi, G., Thompson, B. G., Pandey, A. S. 2015; 76 (2): 126-132


    We hypothesized that the subset of patients with early hydrocephalus following aneurysmal subarachnoid hemorrhage may represent a subset of patients with a more vehement inflammatory reaction to blood products in the subarachnoid space. We thus examined risk factors for early hydrocephalus and examined the relationship between early hydrocephalus and symptomatic vasospasm as well as clinical outcome.We retrospectively analyzed all patients presenting to our institution with subarachnoid hemorrhage over a 7-year period. We examined for risk factors, including early hydrocephalus, for poor clinical outcome and symptomatic vasospasm.We found intraventricular hemorrhage to be strongly associated with the development of early hydrocephalus. In univariate analysis, early hydrocephalus was strongly associated with both poor functional outcome and symptomatic vasospasm. In multivariate analysis, intraventricular hemorrhage and tobacco use were associated with symptomatic vasospasm; intraventricular hemorrhage, intraparenchymal hemorrhage, and symptomatic vasospasm were associated with poor functional outcome.We found that intraventricular hemorrhage was strongly associated with early hydrocephalus. Further exploration of the mechanistic explanation is needed, but we suggest this may be from a combination of obstruction of cerebrospinal fluid pathways by blood products and inflammation in the choroid plexus resulting in increased cerebrospinal fluid production. Further, we suggest that both early hydrocephalus and cerebral vasospasm may be parts of the overall inflammatory cascade that occurs with intraventricular hemorrhage and ultimately results in a poorer clinical outcome.

    View details for DOI 10.1055/s-0034-1394189

    View details for Web of Science ID 000350742400006

    View details for PubMedID 25545809

  • Transfer Time to a High-volume Center for Patients with Subarachnoid Hemorrhage Does Not Affect Outcomes JOURNAL OF STROKE & CEREBROVASCULAR DISEASES Wilson, T. J., Saadeh, Y., Stetler, W. R., Pandey, A. S., Gemmete, J. J., Chaudhary, N., Thompson, B. G., Fletcher, J. J. 2015; 24 (2): 416-423


    The objective of our study was to examine patients with aneurysmal subarachnoid hemorrhage transferred and directly admitted to our institution in order to determine how transfer time affects outcomes.A retrospective cohort study was performed of all patients undergoing treatment for aneurysmal subarachnoid hemorrhage between 2005 and 2012 at the University of Michigan. Variables, including transfer time, were tested for their independent association with the primary outcomes of symptomatic vasospasm and 12-month outcome as well as secondary outcomes of aneurysm rebleeding and 12-month mortality.During the study period, 263 (87.4%) patients were transferred to our institution and 38 (12.6%) were directly admitted for treatment of aneurysmal subarachnoid hemorrhage. Transfer time was not associated with the occurrence of symptomatic vasospasm, 12-month outcome, rebleeding, or 12-month mortality. Higher Hunt-Hess grade was associated with the occurrence of symptomatic vasospasm as well as with poorer 12-month outcome.Transfer time was not associated with the occurrence of symptomatic vasospasm, 12-month outcome, rebleeding, or 12-month mortality. We believe our data argue that protocols should emphasize early resuscitation and stabilization followed by safe transfer rather than a hyperacute transfer paradigm. However, transfer time should be minimized as much as possible so as not to delay time to definitive treatment.

    View details for DOI 10.1016/j.jstrokecerebrovasdis.2014.09.009

    View details for Web of Science ID 000349177300025

    View details for PubMedID 25497722

  • Reducing costs while maintaining quality in endovascular neurosurgical procedures JOURNAL OF NEUROSURGERY Kashlan, O. N., Wilson, T. J., Chaudhary, N., Gemmete, J. J., Stetler, W. R., Dunnick, N. R., Thompson, B. G., Pandey, A. S. 2014; 121 (5): 1071-1076


    As medical costs continue to rise during a time of increasing medical resource utilization, both hospitals and physicians must attempt to limit superfluous health care expenses. Neurointerventional treatment has been shown to be costly, but it is often the best treatment available for certain neuropathologies. The authors studied the effects of 3 policy changes designed to limit the costs of performing neurointerventional procedures at the University of Michigan.The authors retrospectively analyzed the costs of performing neurointerventional procedures during the 6-month periods before and after the implementation of 3 cost-saving policies: 1) the use of an alternative, more economical contrast agent, 2) standardization of coil prices through negotiation with industry representatives to receive economies of scale, and 3) institution of a feedback method to show practitioners the costs of unused products per patient procedure. The costs during the 6-month time intervals before and after implementation were also compared with costs during the most recent 6-month time period.The policy requiring use of a more economical contrast agent led to a decrease in the cost of contrast usage of $42.79 per procedure for the first 6 months after implementation, and $137.09 per procedure for the most current 6-month period, resulting in an estimated total savings of $62,924.31 for the most recent 6-month period. The standardized coil pricing system led to savings of $159.21 per coil after the policy change, and $188.07 per coil in the most recent 6-month period. This yielded total estimated savings of $76,732.56 during the most recent 6-month period. The feedback system for unused items decreased the cost of wasted products by approximately $44.36 per procedure in the 6 months directly after the policy change and by $48.20 per procedure in the most recent 6-month period, leading to total estimated savings of $22,123.80 during the most recent 6-month period. According to extrapolation over a 1-year period, the 3 policy changes decreased costs by an estimated $323,561.34.Simple cost-saving policies can lead to substantial reductions in costs of neurointerventional procedures while maintaining high levels of quality and growth of services.

    View details for DOI 10.3171/2014.7.JNS14236

    View details for Web of Science ID 000343530400011

    View details for PubMedID 25170667

  • Adenoviral vector-mediated gene therapy for gliomas: coming of age EXPERT OPINION ON BIOLOGICAL THERAPY Castro, M. G., Candolfi, M., Wilson, T. J., Calinescu, A., Paran, C., Kamran, N., Koschmann, C., Moreno-Ayala, M. A., Assi, H., Lowenstein, P. R. 2014; 14 (9): 1241-1257


    Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults and it carries a dismal prognosis. Adenoviral vector (Ad)-mediated gene transfer is being developed as a promising therapeutic strategy for GBM. Preclinical studies have demonstrated safety and efficacy of adenovirus administration into the brain and tumor mass in rodents and into the non-human primates' brain. Importantly, Ads have been safely administered within the tumor resection cavity in humans.This review gives background on GBM and Ads; we describe gene therapy strategies for GBM and discuss the value of combination approaches. Finally, we discuss the results of the human clinical trials for GBM that have used Ads.The transduction characteristics of Ads, and their safety profile, added to their capacity to achieve high levels of transgene expression have made them powerful vectors for the treatment of GBM. Recent gene therapy successes in the treatment of retinal diseases and systemic brain metabolic diseases encourage the development of gene therapy for malignant glioma. Exciting clinical trials are currently recruiting patients; although, it is the large randomized Phase III controlled clinical trials that will provide the final decision on the success of gene therapy for the treatment of GBM.

    View details for DOI 10.1517/14712598.2014.915307

    View details for Web of Science ID 000340460000004

    View details for PubMedID 24773178

    View details for PubMedCentralID PMC4127140

  • Large-Volume Blood Patch to Multiple Sites in the Epidural Space through a Single-Catheter Access Site for Treatment of Spontaneous Intracranial Hypotension AMERICAN JOURNAL OF NEURORADIOLOGY Griauzde, J., Gemmete, J. J., Chaudhary, N., Wilson, T. J., Pandey, A. S. 2014; 35 (9): 1841-1846


    Spontaneous intracranial hypotension can be a therapeutic challenge to the treating physician. In this study, we present our experience with the administration of a large-volume blood patch to multiple sites in the epidural space through a single-catheter access site.A retrospective review was conducted of patients with spontaneous intracranial hypotension who underwent a large-volume blood patch to multiple sites in the epidural space through a single-catheter access site from 2010 to 2012. Patient demographic data, clinical charts, indications for treatment, radiographic images, procedure notes, and postprocedure hospital course were reviewed.Overall, 9 patients were identified who underwent 20 blood patch procedures. Patients were selected to undergo the large-volume procedure either because they had a failed site-directed epidural blood patch or if imaging demonstrated multiple possible leak sites. There were 6 women and 3 men, with an average age of 33.5 years. The mean volume of blood injected per procedure was 54.1 mL (median=55 mL; range=38-70 mL). All patients had an orthostatic headache as one of their presenting symptoms; 22% also presented with neurocognitive decline and behavioral changes; 89% of patients had improvement or resolution of their symptoms; and 80% of patients who had a previously failed site-directed epidural blood or fibrin glue patch improved with a large volume catheter-directed blood patch.Our experience supports the use of a large-volume blood patch to multiple sites in the epidural space through a single-catheter access site for the treatment of spontaneous intracranial hypotension. Additionally, our results indicate a role for this procedure in refractory cases of spontaneous intracranial hypotension.

    View details for DOI 10.3174/ajnr.A3945

    View details for Web of Science ID 000341639900032

    View details for PubMedID 24788127

  • A case-cohort study with propensity score matching to evaluate the effects of mannitol on venous thromboembolism JOURNAL OF CLINICAL NEUROSCIENCE Fletcher, J. J., Kade, A. M., Sheehan, K. M., Wilson, T. J. 2014; 21 (8): 1323-1328


    Mannitol has been shown to damage endothelial cells and activate coagulation pathways leading to intravascular thrombosis. Dehydration and hemagglutination have also been associated with mannitol use, although the risk of clinically evident venous thromboembolism (VTE) disease is not well-defined. The aim of this study was to compare the risk of VTE in critically ill neurological patients who received mannitol compared to only hypertonic saline. A case-cohort study design with propensity score matching was used to evaluate the risk of VTE among patients who received mannitol compared to those who received hypertonic saline alone. The odds of thrombosis were evaluated by the Cochran-Mantel-Haenszel method and conditional logistic regression was used to adjust for year of treatment. Ninety-one of 330 patients (27.6%; 95% confidence interval [CI] 23-33%) developed a VTE; however, the yearly proportion remained unchanged over the 8 year study period. Cumulative use of mannitol declined and use of hypertonic saline increased significantly. The odds of thrombosis for those exposed to mannitol compared to hypertonic saline alone was 1.11 (95% CI 0.65-1.73; p=0.75). This remained insignificant after adjusting for year of injury. In conclusion, despite a significant change in the pattern of osmotic therapy used at our institution, the proportion of patients with VTE remained unchanged. We found no evidence that mannitol use was associated with VTE compared to hypertonic saline alone.

    View details for DOI 10.1016/j.jocn.2013.12.013

    View details for Web of Science ID 000339601400010

    View details for PubMedID 24685012

  • Filum terminale lipomas: imaging prevalence, natural history, and conus position JOURNAL OF NEUROSURGERY-PEDIATRICS Cools, M. J., Al-Holou, W. N., Stetler, W. R., Wilson, T. J., Muraszko, K. M., Ibrahim, M., La Marca, F., Garton, H. J., Maher, C. O. 2014; 13 (5): 559-567


    Filum terminale lipomas (FTLs) are being identified with increasing frequency due to the increasing utilization of MRI. Although an FTL may be associated with tethered cord syndrome (TCS), in many cases FTLs are diagnosed incidentally in patients without any symptoms of TCS. The natural history of FTLs is not well defined.The authors searched the clinical and imaging records at a single institution over a 14-year interval to identify patients with FTLs. For patients with an FTL, the clinical records were reviewed for indication for imaging, presenting symptoms, perceived need for surgery, and clinical outcome. A natural history analysis was performed using all patients with more than 6 months of clinical follow-up.A total of 436 patients with FTL were identified. There were 217 males and 219 females. Of these patients, 282 (65%) were adults and 154 (35%) were children. Symptoms of TCS were present in 22 patients (5%). Fifty-two patients underwent surgery for FTL (12%). Sixty-four patients (15%) had a low-lying conus and 21 (5%) had a syrinx. The natural history analysis included 249 patients with a mean follow-up time of 3.5 years. In the follow-up period, only 1 patient developed new symptoms.Filum terminale lipomas are a common incidental finding on spinal MRI, and most patients present without associated symptoms. The untreated natural history is generally benign for asymptomatic patients.

    View details for DOI 10.3171/2014.2.PEDS13528

    View details for Web of Science ID 000334903700013

    View details for PubMedID 24628511

  • Dual antiplatelet therapy plus postoperative heparin and dextran is safe and effective for reducing risk of embolic stroke during aneurysm coiling ACTA NEUROCHIRURGICA Wilson, T. J., Pandey, A. S., Stetler, W. R., Davis, M. C., Giles, D. A., Chaudhary, N., Gemmete, J. J., Thompson, B. G. 2014; 156 (5): 855-859


    Thromboembolic events represent a clinically significant cause of neurological morbidity during the endovascular management of cerebral aneurysms. We have implemented an anti-thromboembolic regimen consisting of pre- and postoperative dual antiplatelet therapy, as well as postoperative anticoagulation using heparin and dextran. The aims of our study were to examine the effect of this regimen on thromboembolic rates during elective aneurysm coiling, and to elucidate risk factors associated with the development of thromboembolic events in this setting.We conducted a retrospective review of patients who underwent elective intracranial aneurysm coiling between January 2005 and February 2012. The primary outcome of interest was the occurrence of a clinically significant peri-procedural thromboembolic event. Secondary outcomes included the occurrence of a central nervous system (CNS) or systemic hemorrhage.During the study period, 312 patients underwent elective aneurysm coiling and six (2 %) thromboembolic events occurred; three (1 %) occurred in the group that received the anti-thromboembolic regimen (261 patients) and three (6 %) occurred in the group that did not receive the regimen (51 patients), resulting in a statistically significant difference (P = 0.024). Both the presence of a hypercoagulable state (P = 0.014) and the lack of the anti-thromboembolic regimen (P = 0.043) were significantly associated with the occurrence of a thromboembolic event.This study provides evidence that the regimen described here is safe and reduces thromboembolic complications during elective aneurysm coiling. Ours is likely the most aggressive regimen in the published literature and significantly reduced the rate of thromboembolism without any significant increase hemorrhagic complications.

    View details for DOI 10.1007/s00701-014-2031-y

    View details for Web of Science ID 000334426000004

    View details for PubMedID 24595538

  • Efficacy of antibiotic-impregnated external ventricular drains in reducing ventriculostomy-associated infections JOURNAL OF CLINICAL NEUROSCIENCE Mikhaylov, Y., Wilson, T. J., Rajajee, V., Thompson, B. G., Maher, C. O., Sullivan, S. E., Jacobs, T. L., Kocan, M. J., Pandey, A. S. 2014; 21 (5): 765-768


    Use of an external ventricular drain (EVD) is essential for managing patients with hydrocephalus or intracranial hypertension. While this procedure is safe and efficacious, ventriculostomy-associated infections (VAI) continue to cause significant morbidity. In this study, we evaluated the efficacy of antibiotic-coated EVD (AC-EVD) in reducing the occurrence of VAI. Between July 2007 and July 2009, 203 patients underwent placement of an EVD. A total of 145 of these patients met the inclusion criteria, with 76 patients (52.4%) receiving AC-EVD and 69 patients (47.6%) receiving uncoated EVD. Ten patients (6.9%) developed VAI, of whom three were in the AC-EVD group and seven were in the uncoated EVD group (p=0.19). The mean duration between catheter insertion and positive cerebrospinal fluid culture was significantly greater in the AC-EVD group versus the uncoated EVD group (15±4days versus 4±2days, respectively; p=0.001). In the uncoated EVD group, 17 of 69 patients (24.6%) were dead at 3years versus 12 of 76 (15.8%) patients in the AC-EVD group (p=0.21). The overall VAI rate was 6.9% with a trend toward lower infection rates in the AC-EVD group compared to the uncoated EVD group (3.9% versus 10.1%, respectively; p>0.05).

    View details for DOI 10.1016/j.jocn.2013.09.002

    View details for Web of Science ID 000335805500011

    View details for PubMedID 24411330

  • Is Early Clinical Evidence of Autonomic Shift Predictive of Infection after Aneurysmal Subarachnoid Hemorrhage JOURNAL OF STROKE & CEREBROVASCULAR DISEASES Fletcher, J. J., Rajajee, V., Wilson, T. J., Zahuranec, D. B. 2014; 23 (5): 1062-1068


    Autonomic shift (AS), characterized by increased sympathetic nervous system activation, has been implicated in neurologically mediated cardiopulmonary dysfunction and immunodepression after stroke. We investigated the prevalence of AS defined by readily available clinical parameters and determined the association of AS with subsequent infection in a cohort of patients with aneurysmal subarachnoid hemorrhage (aSAH).Data were obtained from a single-center cohort study of aSAH patients admitted from January 1, 2007, through April 1, 2012. AS was defined as at least 1 early (<72 hours) routine clinical marker of neurologically mediated cardiopulmonary dysfunction based on electrocardiogram, echocardiogram, cardiac enzymes, or neurogenic pulmonary edema. Multivariable logistic regression models were developed to evaluate the association between AS and subsequent infection after adjusting for other covariates.A total of 167 patients were included in the analysis (mean age 56, 27% men). AS was seen in 66 of 167 patients (40%; 95% confidence interval [CI], 32%-47%), and infection was seen in 80 of 167 patients (48%; 95% CI, 40%-55%). AS was associated with subsequent infection on unadjusted analysis (odds ratio [OR] 2.11; 95% CI, 1.12-3.97); however, this association was no longer significant when adjusting for other predictors of infection (OR 1.36; 95% CI, .67-2.76). Age, clinical grade, and aneurysm location were all independent predictors of infection after aSAH.We identified AS based on readily available clinical markers in 40% of patients with aSAH, though AS defined by these clinical criteria was not an independent predictor of infection. Additional studies may be warranted to determine the optimal definition of AS and the clinical significance of this finding.

    View details for DOI 10.1016/j.jstrokecerebrovasdis.2013.09.007

    View details for Web of Science ID 000336482000053

    View details for PubMedID 24189451

    View details for PubMedCentralID PMC4007375

  • Endovascular treatment for aneurysmal subarachnoid hemorrhage in the ninth decade of life and beyond JOURNAL OF NEUROINTERVENTIONAL SURGERY Wilson, T. J., Davis, M. C., Stetler, W. R., Giles, D. A., Chaudhary, N., Gemmete, J. J., Thompson, B. G., Pandey, A. S. 2014; 6 (3): 175-177


    As the population ages, clinicians will be faced with difficult decisions regarding treatment of elderly patients presenting with aneurysmal subarachnoid hemorrhage (aSAH). Previous data have led to continued pessimism by some clinicians treating elderly and very elderly patients presenting with aSAH. The aim of this study was to present our experience in the very elderly treated with endovascular coiling after presentation with aSAH.Retrospective review of all patients 80 years of age or older presenting with aSAH who underwent coil embolization. Primary outcomes of interest were functional outcome, as assessed by the Glasgow Outcome Scale score, and inhospital mortality.During the study period, 16 patients aged 80 years or older presenting with aSAH underwent coil embolization; nine (56%) had a poor outcome at the 6 month follow-up while seven (44%) had a good outcome. The inhospital mortality rate was 50%. Of those patients alive at discharge, seven out of eight (88%) patients had a good outcome. Variables associated with poor outcome included higher Hunt and Hess score (p=0.010), use of balloon assistance/remodeling (p=0.025), and presence of coronary artery disease (p=0.006).Not surprisingly, we found that very elderly patients presenting with aSAH have a high inhospital mortality rate. However, those patients who survive to discharge have a surprisingly robust chance at good functional recovery when treated with coil embolization. We believe these results support offering endovascular coil embolization, when feasible, to very elderly patients presenting with aSAH.

    View details for DOI 10.1136/neurintsurg-2013-010714

    View details for Web of Science ID 000332609900012

    View details for PubMedID 23535264

  • Repeat endoscopic transsphenoidal surgery for acromegaly: remission and complications PITUITARY Wilson, T. J., McKean, E. L., Barkan, A. L., Chandler, W. F., Sullivan, S. E. 2013; 16 (4): 459-464


    Reported biochemical remission rates following surgical intervention for acromegaly range from 38 to 83%. In patients not achieving surgical remission, few options remain, mostly limited to medical management and radiation therapy. There is debate over whether or not to offer reoperation to patients in whom surgical remission is not achieved with initial resection. Retrospective chart review was undertaken to determine all patients having acromegaly with persistently elevated GH and/or IGF-1 levels after initial pituitary adenoma resection, and who underwent reoperation using endoscopic endonasal approach at a single institution. Biochemical remission was defined as a postoperative GH level <1 ng/mL and a normal postoperative IGF-1 level in the absence of any medical therapy. In total, 14 patients underwent repeat surgical intervention for acromegaly via endoscopic transsphenoidal approach. Of the 14 patients, 8 (57%) achieved biochemical remission following repeat surgical intervention. Lower preoperative GH levels were associated with greater chance of biochemical remission (P = 0.048). New endocrinopathies were seen in 2 patients (14%), and both were transient diabetes insipidus. Meningitis occurred in 2 patients (14%); both were aseptic meningitis with no sequelae. No mortality was encountered. Repeat surgical intervention for acromegaly via endoscopic transsphenoidal approach appears safe and effective. With no mortality and minimal morbidity, repeat surgical intervention via endoscopic transsphenoidal approach appears a reasonable option for these hard-to-treat patients and should be considered for patients in whom surgical remission is not achieved with initial surgery.

    View details for DOI 10.1007/s11102-012-0457-x

    View details for Web of Science ID 000326891400005

    View details for PubMedID 23307479

  • Comparison of the accuracy of ventricular catheter placement using freehand placement, ultrasonic guidance, and stereotactic neuronavigation. Journal of neurosurgery Wilson, T. J., Stetler, W. R., Al-Holou, W. N., Sullivan, S. E. 2013; 119 (1): 66-70


    The objective of this study was to compare the accuracy of 3 methods of ventricular catheter placement during CSF shunt operations: the freehand technique using surface anatomy, ultrasonic guidance, and stereotactic neuronavigation.This retrospective cohort study included all patients from a single institution who underwent a ventricular CSF shunting procedure in which a new ventricular catheter was placed between January 2005 and March 2010. Data abstracted for each patient included age, sex, diagnosis, method of ventricular catheter placement, site and side of ventricular catheter placement, Evans ratio, and bifrontal ventricular span. Postoperative radiographic studies were reviewed for accuracy of ventricular catheter placement. Medical records were also reviewed for evidence of shunt failure requiring revision through December 2011. Statistical analysis was then performed comparing the 3 methods of ventricular catheter placement and to determine risk factors for inaccurate placement.There were 249 patients included in the study; 170 ventricular catheters were freehand passed, 51 were placed using stereotactic neuronavigation, and 28 were placed under intraoperative ultrasonic guidance. There was a statistically significant difference between freehand catheters and stereotactic-guided catheters (p<0.001), as well as between freehand catheters and ultrasound-guided catheters (p<0.001). The only risk factor for inaccurate placement identified in this study was use of the freehand technique. The use of stereotactic neuronavigation and ultrasonic guidance reduced proximal shunt failure rates (p<0.05) in comparison with a freehand technique.Stereotactic- and ultrasound-guided ventricular catheter placements are significantly more accurate than freehand placement, and the use of these intraoperative guidance techniques reduced proximal shunt failure in this study.

    View details for DOI 10.3171/2012.11.JNS111384

    View details for PubMedID 23330995

  • Comparison of catheter-related large vein thrombosis in centrally inserted versus peripherally inserted central venous lines in the neurological intensive care unit CLINICAL NEUROLOGY AND NEUROSURGERY Wilson, T. J., Stetler, W. R., Fletcher, J. J. 2013; 115 (7): 879-882


    To compare cumulative complication rates of peripherally (PICC) and centrally (CICVC) inserted central venous catheters, including catheter-related large vein thrombosis (CRLVT), central line-associated bloodstream infection (CLABSI), and line insertion-related complications in neurological intensive care patients.Retrospective cohort study and detailed chart review for 431 consecutive PICCs and 141 CICVCs placed in patients under neurological intensive care from March 2008 through February 2010. Cumulative incidence of CRLVT, CLABSI, and line insertion-related complications were compared between PICC and CICVC groups. Risk factors for CRLVT including mannitol therapy during dwell time, previous history of venous thromboembolism, surgery longer than 1h during dwell time, and line placement in a paretic arm were also compared between groups.During the study period, 431 unique PICCs were placed with cumulative incidence of symptomatic thrombosis of 8.4%, CLABSI 2.8%, and line insertion-related complications 0.0%. During the same period, 141 unique CICVCs were placed with cumulative incidence of symptomatic thrombosis of 1.4%, CLABSI 1.4%, and line insertion-related complications 0.7%. There was a statistically significant difference in CRLVT with no difference in CLABSI or line insertion-related complications.In neurological critical care patients, CICVCs appear to have a better risk profile compared to PICCs, with a decreased risk of CRLVT. As use of PICCs in critical care patients increases, a prospective randomized trial comparing PICCs and CICVCs in neurological critical care patients is necessary to assist in choosing the appropriate catheter and to minimize risks of morbidity and mortality associated with central venous access.

    View details for DOI 10.1016/j.clineuro.2012.08.025

    View details for Web of Science ID 000321403000006

    View details for PubMedID 22948189

  • Progress in gene therapy for neurological disorders NATURE REVIEWS NEUROLOGY Simonato, M., Bennett, J., Boulis, N. M., Castro, M. G., Fink, D. J., Goins, W. F., Gray, S. J., Lowenstein, P. R., Vandenberghe, L. H., Wilson, T. J., Wolfe, J. H., Glorioso, J. C. 2013; 9 (5): 277-291


    Diseases of the nervous system have devastating effects and are widely distributed among the population, being especially prevalent in the elderly. These diseases are often caused by inherited genetic mutations that result in abnormal nervous system development, neurodegeneration, or impaired neuronal function. Other causes of neurological diseases include genetic and epigenetic changes induced by environmental insults, injury, disease-related events or inflammatory processes. Standard medical and surgical practice has not proved effective in curing or treating these diseases, and appropriate pharmaceuticals do not exist or are insufficient to slow disease progression. Gene therapy is emerging as a powerful approach with potential to treat and even cure some of the most common diseases of the nervous system. Gene therapy for neurological diseases has been made possible through progress in understanding the underlying disease mechanisms, particularly those involving sensory neurons, and also by improvement of gene vector design, therapeutic gene selection, and methods of delivery. Progress in the field has renewed our optimism for gene therapy as a treatment modality that can be used by neurologists, ophthalmologists and neurosurgeons. In this Review, we describe the promising gene therapy strategies that have the potential to treat patients with neurological diseases and discuss prospects for future development of gene therapy.

    View details for DOI 10.1038/nrneurol.2013.56

    View details for Web of Science ID 000318851000008

    View details for PubMedID 23609618

    View details for PubMedCentralID PMC3908892

  • Management of intracranial hemorrhage in patients with left ventricular assist devices. Journal of neurosurgery Wilson, T. J., Stetler, W. R., Al-Holou, W. N., Sullivan, S. E., Fletcher, J. J. 2013; 118 (5): 1063-1068


    The authors conducted a study to review outcomes and management in patients in whom intracranial hemorrhage (ICH) develops during left ventricular assist device (LVAD) therapy.This retrospective cohort study included all adult patients (18 years of age or older) at a single institution who underwent placement of an LVAD between January 1, 2003, and March 1, 2012. The authors conducted a detailed medical chart review, and data were abstracted to assess outcomes in patients in whom ICH developed compared to those in patients in whom ICH did not develop; to compare management of antiplatelet agents and anticoagulation with outcomes; to describe surgical management employed and outcomes achieved; to compare subtypes of ICH (intraparenchymal, subdural, and subarachnoid hemorrhage) and their outcomes; and to determine any predictors of outcome.During the study period, 330 LVADs were placed and 36 patients developed an ICH (traumatic subarachnoid hemorrhage in 10, traumatic subdural hematoma in 8, spontaneous intraventricular hemorrhage in 1, and spontaneous intraparenchymal hemorrhage in 17). All patients were treated with aspirin and warfarin at the time of presentation. With suspension of these agents, no thromboembolic events or pump failures were seen and no delayed rehemorrhages occurred after resuming these medications. Intraparenchymal hemorrhages had the worst outcomes, with a 30-day mortality rate in 59% compared with a 30-day mortality rate of 0% in patients with traumatic subarachnoid hemorrhages and 13% in those with traumatic subdural hematomas. Five patients with intraparenchymal hemorrhages were managed with surgical intervention, 4 of whom died within 60 days. The only factor found to be predictive of outcome was initial Glasgow Coma Scale score. No patients with a Glasgow Coma Scale score less than 11 survived beyond 30 days. Overall, the development of an ICH significantly reduced survival compared with the natural history of patients on LVAD therapy.The authors' data suggest that withholding aspirin for 1 week and warfarin for 10 days is sufficient to reduce the risk of hemorrhage expansion or rehemorrhage while minimizing the risk of thromboembolic events and pump failure. Patients with intraparenchymal hemorrhage have poor outcomes, whereas patients with traumatic subarachnoid hemorrhage or subdural hematoma have better outcomes.

    View details for DOI 10.3171/2013.1.JNS121849

    View details for PubMedID 23451903

  • Subarachnoid haemorrhage with bilateral intracranial vertebral artery dissecting aneurysms treated by staged endovascular stenting. BMJ case reports Wilkinson, D. A., Wilson, T. J., Stetler, W. R., Pandey, A. S. 2013; 2013


    Bilateral vertebral artery dissecting aneurysms (VADAs) presenting with subarachnoid haemorrhage (SAH) are an exceedingly rare and deadly clinical dilemma. Prompt intervention in the case of unilateral VADAs is advocated to prevent rebleed; however, in the case of bilateral VADAs, the optimal therapeutic intervention is unclear. We describe the case of a patient presenting with SAH with bilateral VADAs treated by staged endovascular stenting. This led to resolution of the aneurysms with patency of both vertebral arteries. Stent-based therapy of the symptomatic aneurysm followed by staged stenting of the asymptomatic, contralateral aneurysm appears to be a viable treatment option. This method allows the ability to preserve flow in both vertebral arteries with minimal changes in flow characteristics that may threaten the contralateral, asymptomatic VADA, and appears to be the ideal treatment in these rare cases.

    View details for DOI 10.1136/bcr-03-2012-6002

    View details for PubMedID 23417929

    View details for PubMedCentralID PMC3603424

  • Indirect carotid-cavernous fistula following minor head trauma treated with incomplete radiographic endovascular occlusion. BMJ case reports Stetler, W. R., Chaudhary, N., Wilson, T. J., Pandey, A. S. 2012; 2012


    We report the unusual case of a patient with an indirect carotid-cavernous fistula treated with only partial angiographic embolisation of the fistula; however, by 8 weeks postembolisation, she was found to have both symptomatic and angiographic cure. This case highlights the potential for treating indirect carotid-cavernous fistulas with partial embolisation as a means of achieving angiographic and symptomatic cure by altering flow dynamics to attain spontaneous thrombosis.

    View details for DOI 10.1136/bcr-03-2012-6004

    View details for PubMedID 23008364

    View details for PubMedCentralID PMC4543146

  • Perioperative management of a neurosurgical patient requiring antiplatelet therapy. Journal of clinical neuroscience Than, K. D., Rohatgi, P., Wilson, T. J., Gregory Thompson, B. 2012; 19 (9): 1316-1320


    In patients who undergo neurovascular stent placement with postoperative dual antiplatelet therapy to prevent in-stent thrombosis, there is no protocol for balancing the risk of acute stent thrombosis and bleeding if urgent neurosurgical procedures are required. We detail perioperative management of dual antiplatelet therapy in a 66-year-old man with a dolichoectatic aneurysm of the basilar artery treated with a Pipeline stent. Postoperatively, the patient was placed on aspirin and clopidogrel to prevent in-stent thrombosis. One month after the procedure, his neurological status declined secondary to obstructive hydrocephalus. His condition necessitated urgent placement of a ventriculoperitoneal shunt, despite the dual antiplatelet therapy for the flow-diverting Pipeline stent. Aspirin and clopidogrel were discontinued seven days prior to the planned shunt placement. To minimize time off antiplatelet therapy, aspirin was immediately replaced with ibuprofen. Eptifibatide was then started three days prior to surgery. The ibuprofen/eptifibatide bridge was discontinued at midnight prior to surgery. Aspirin was restarted on the first postoperative day and clopidogrel was restarted on the second postoperative day. The patient tolerated shunt placement without excessive bleeding or hemorrhagic complications. During the remainder of his hospital course, no evidence of stent thrombosis or intracranial hemorrhage was noted. We conclude that management of antiplatelet prophylaxis for neurovascular stent thrombosis in patients requiring urgent neurosurgical procedures may be successfully achieved by bridging aspirin and clopidogrel with ibuprofen and eptifibatide in the preoperative period.

    View details for DOI 10.1016/j.jocn.2011.12.018

    View details for PubMedID 22784876

  • Pineal region myeloid sarcoma JOURNAL OF CLINICAL NEUROSCIENCE Wilson, T. J., Than, K. D., Parmar, H. A., Lieberman, A. P., Valdivia, J. M., Sullivan, S. E. 2012; 19 (7): 1037-1039


    The overwhelming majority of pineal region tumors are malignant germ cell tumors, pineal cell tumors, or glial tumors. To our knowledge we report the first patient with myeloid sarcoma in the pineal region. Myeloid sarcomas are composed of immature granulocytic precursor cells and are associated with acute myelogenous leukemia. Thus, myeloid sarcoma should be considered in the differential diagnosis of pineal region masses in patients with a known history of acute myelogenous leukemia.

    View details for DOI 10.1016/j.jocn.2011.11.014

    View details for Web of Science ID 000311323800025

    View details for PubMedID 22560847

  • Regression of a meningioma during paclitaxel and bevacizumab therapy for breast cancer JOURNAL OF CLINICAL NEUROSCIENCE Wilson, T. J., Heth, J. A. 2012; 19 (3): 468-469


    Meningiomas often are not amenable to total resection, and subtotally resected meningiomas often recur. Recurrent meningiomas present a clinical dilemma, particularly when surgical and radiotherapy options are exhausted, as there are no chemotherapeutic options that demonstrate consistent, significant efficacy. We report a patient with the regression of a recurrent World Health Organization grade I meningioma during combination chemotherapy with bevacizumab and paclitaxel for breast cancer. This chemotherapy regimen has never been explored for recurrent meningiomas. While further data are necessary, we suggest that combination chemotherapy with bevacizumab and paclitaxel may be an option for treatment of recurrent meningiomas when no further surgical or radiotherapy options exist.

    View details for DOI 10.1016/j.jocn.2011.07.024

    View details for Web of Science ID 000301165100029

    View details for PubMedID 22245272

  • Risk factors associated with peripherally inserted central venous catheter-related large vein thrombosis in neurological intensive care patients INTENSIVE CARE MEDICINE Wilson, T. J., Brown, D. L., Meurer, W. J., Stetler, W. R., Wilkinson, D. A., Fletcher, J. J. 2012; 38 (2): 272-278


    Using Virchow's triad as a framework, we sought to identify risk factors independently associated with symptomatic peripherally inserted central venous catheter (PICC)-related large vein thrombosis (PRLVT) in neurological intensive care patients.A retrospective cohort study and detailed chart review were performed for 431 consecutive PICCs placed in patients admitted to our neurological intensive care unit between March 2008 and February 2010. Variables theorized to potentially increase the risk of PRLVT were abstracted from the medical record. Each variable was then tested for its independent association with PRLVT.During the study period, 431 PICCs were placed with an incidence rate for symptomatic thrombosis of 8.4%. In adjusted analysis, catheter placement in a paretic arm (OR, 9.85; 95% CI, 4.42-21.95), surgery longer than 1 h during dwell time of the catheter (OR, 3.26; 95% CI, 1.48-7.17), a history of venous thromboembolism (OR, 6.66; 95% CI, 2.38-18.62), and mannitol use (OR, 3.27; 95% CI 1.27-8.43) were independently associated with the development of thrombosis.Alterations in blood flow and consistency, but not vessel injury, appear associated with symptomatic thrombosis following placement of PICCs in neurological intensive care patients. Mannitol use and placement in a paretic arm are potentially modifiable risk factors. Given the high incidence rate of symptomatic thrombosis, future studies should focus on comparing cumulative complications of centrally inserted venous catheters and PICCs in intensive care patients.

    View details for DOI 10.1007/s00134-011-2418-7

    View details for Web of Science ID 000299501700012

    View details for PubMedID 22113818

  • An L-2 burst fracture and cauda equina syndrome due to tetanus Case report JOURNAL OF NEUROSURGERY-SPINE Wilson, T. J., Orringer, D. A., Sullivan, S. E., Patil, P. G. 2012; 16 (1): 82-85


    Thoracic vertebral compression fractures are a known complication of generalized tetanus. The authors report the first known case of an L-2 burst fracture leading to cauda equina syndrome, as a result of generalized tetanus. This 51-year-old man had generalized tetanus with a constellation of symptoms including compartment syndrome requiring fasciotomies, severe axial spasms and spasms of the extremities, autonomic dysreflexia, hypercarbic respiratory failure, and rhabdomyolysis. During the course of his illness, areflexic paraparesis developed in his lower extremities. He was found to have an L-2 burst fracture with retropulsion of a bone fragment resulting in cauda equina syndrome. Operative intervention was undertaken to decompress the cauda equina and stabilize the spine. The natural progression of tetanus can be complex, with a mixed picture ranging from spasms plus increased tone and reflexes to reduced tone and reflexes as presynaptic nerve terminals become damaged. The authors suggest that all sudden changes in the neurological examination should prompt consideration of diagnostic imaging before attributing such changes to natural progression of the disease.

    View details for DOI 10.3171/2011.7.SPINE11335

    View details for Web of Science ID 000298631100018

    View details for PubMedID 21854128

  • The Clinical Significance of Peripherally Inserted Central Venous Catheter-Related Deep Vein Thrombosis NEUROCRITICAL CARE Fletcher, J. J., Stetler, W., Wilson, T. J. 2011; 15 (3): 454-460


    Peripherally inserted central venous catheters (PICCs) are being increasingly utilized in hospitalized patients as alternatives to centrally inserted central venous catheters (CICVCs). However, concern exists over the risk of PICC-related large vein thrombosis (PRLVT). The incidence rate and significance of symptomatic PRLVT in critically ill patients admitted to the neurological intensive care unit (ICU) is not known.Retrospective descriptive study of consecutive PICCs placed in critically ill patients admitted to a tertiary care neurological ICU between March 2008 and February 2010. Symptomatic PRVLT was defined as an event that prompted Duplex ultrasound of the ipsilateral extremity in which an acute, proximal large vein thrombosis was confirmed in association with the PICC or confirmed within 5 days of PICC removal. Incidence rate of PRLVT and catheter-related complications were calculated per "line" (catheter). Descriptive statistics were performed with two-sample, and t-tests for age and categorical variables were assessed by Chi-square test or Fishers exact test as appropriateFour hundred and seventy-nine lines were placed during the study period with 39 developing a symptomatic PRLVT (incidence rate = 8.1%). Male gender was associated with development of a thrombosis (P = 0.02), but size (P = 0.21) and location of catheter were not (P = 0.30). Median line dwell time was 12 days (IQR 16) with a dwell time of 8 days (IQR 9) until thrombosis diagnosis. Pulmonary embolus attributed to PRLVT occurred in 1.3% of line placements and 15% of symptomatic PRLVT. The majority of patients had their line removed. In addition, some patients also had anticoagulation initiated or a superior vena cava filter placed.Symptomatic PRLVT is not uncommon in critically ill patients admitted to the neurological ICU. Future research should focus on indentifying modifiable risk factors for PRLVT and on comparing major cumulative complication rates between PICCs and CICVCs.

    View details for DOI 10.1007/s12028-011-9554-3

    View details for Web of Science ID 000297365400015

    View details for PubMedID 21541826

  • Incidental findings on cranial imaging in nonagenarians NEUROSURGICAL FOCUS Al-Holou, W. N., Khan, A., Wilson, T. J., Stetler, W. R., Shah, G. V., Maher, C. O. 2011; 31 (6)


    The aim of this article was to report on the nature and prevalence of incidental imaging findings in a consecutive series of patients older than 90 years of age who underwent intracranial imaging for any reason.The authors retrospectively reviewed the electronic medical and imaging records of consecutive patients who underwent brain MR imaging at a single institution over a 153-month interval and were at least 90 but less than 100 years of age at the time of the imaging study. The prevalence of lesions by type in this consecutive series of MR imaging evaluations was calculated for all patients. The authors reviewed the medical record to evaluate whether a change in management was recommended based on MR imaging findings. They evaluated patient age at the time of death and the time interval between MR imaging and death.The authors identified 177 patients who met the study criteria. The group included 119 women (67%) and 58 (33%) men. Their mean age was 92.3 ± 1.8 years. Evidence of acute ischemic changes or cerebrovascular accident (CVA) was found in 36 patients (20%). Fifteen patients (8%) had an intracranial tumor. Intracranial aneurysms were incidentally identified in 6 patients (3%). Chronic subdural hematomas were found in 3 patients (2%). Overall, 25 patients (14%) had some change in medical management as a result of the MR imaging findings. The most common MR imaging finding that resulted in a change in medical management was an acute CVA (p < 0.0001). The mean time to death from date of MR imaging was 2.5 ± 2.3 years.Intracranial imaging is rarely performed in patients older than 90 years. In cases of suspected stroke, MR imaging findings may influence treatment decisions. Brain MR imaging studies ordered for other indications in this age group rarely influence treatment decisions. Incidentally discovered lesions in this age group are generally not treated.

    View details for DOI 10.3171/2011.9.FOCUS11205

    View details for Web of Science ID 000297743200013

    View details for PubMedID 22133167

  • Non-ketotic hyperglycemic chorea-hemiballismus mimicking basal ganglia hemorrhage JOURNAL OF CLINICAL NEUROSCIENCE Wilson, T. J., Than, K. D., Stetler, W. R., Heth, J. A. 2011; 18 (11): 1560-1561


    Radiographic findings of hyperglycemic non-ketotic chorea-hemiballismus and basal ganglia hemorrhage can be highly similar. A 58-year-old female presented with a 1-week history of choreiform and ballistic movements of the left arm. Based on CT imaging, the patient was diagnosed with a basal ganglia hemorrhage. After transfer to our institution, further imaging and work-up led to a diagnosis of non-ketotic hyperglycemic chorea-hemiballismus. Aggressive glycemic control was started and the patient's symptoms resolved. Despite its rarity, non-ketotic hyperglycemic chorea-hemiballismus should be included in the differential diagnosis of basal ganglia hyperdensity on CT scan, as it can mimic basal ganglia hemorrhage. Resolution of this clinical entity and implementation of aggressive glycemic control can lead to complete resolution of symptoms. It is important for neurosurgeons to be aware of this clinical entity as prompt treatment often yields good outcomes.

    View details for DOI 10.1016/j.jocn.2011.03.010

    View details for Web of Science ID 000296402800035

    View details for PubMedID 21871808

  • Complication avoidance and management in anterior lumbar interbody fusion NEUROSURGICAL FOCUS Than, K. D., Wang, A. C., Rahman, S. U., Wilson, T. J., Valdivia, J. M., Park, P., La Marca, F. 2011; 31 (4)


    The goal of this study was to review the literature to compare strategies for avoiding and treating complications from anterior lumbar interbody fusion (ALIF), and thus provide a comprehensive aid for spine surgeons. A thorough review of databases from the US National Library of Medicine and the National Institutes of Health was conducted. The complications of ALIF addressed in this paper include pseudarthrosis and subsidence, vascular injury, retrograde ejaculation, ileus, and lymphocele (chyloretroperitoneum). Strategies identified for improving fusion rates included the use of frozen rather than freeze-dried allograft, cage instrumentation, and bone morphogenetic protein. Lower cage heights appear to reduce the risk of subsidence. The most common vascular injury is venous laceration, which occurs less frequently when using nonthreaded interbody grafts such as iliac crest autograft or femoral ring allograft. Left iliac artery thrombosis is the most common arterial injury, and its occurrence can be minimized by intermittent release of retraction intraoperatively. The risk of retrograde ejaculation is significantly higher with laparoscopic approaches, and thus should be avoided in male patients. Despite precautionary measures, complications from ALIF may occur, but treatment options do exist. Bowel obstruction can be treated conservatively with neostigmine or with decompression. In cases of postoperative lymphocele, resolution can be attained by creating a peritoneal window. By recognizing ways to minimize complications, the spine surgeon can safely use ALIF procedures.

    View details for DOI 10.3171/2011.7.FOCUS11141

    View details for Web of Science ID 000295406500007

    View details for PubMedID 21961869

  • Dural arteriovenous fistula associated with superior sagittal sinus occlusion secondary to invasion by a parafalcine meningioma: case report. Neurosurgery Toledo, M. M., Wilson, T. J., Dashti, S., McDougall, C. G., Spetzler, R. F. 2010; 67 (1): 205-207


    We report a rare case of thrombosis of the superior sagittal sinus associated with a parafalcine meningioma resulting in a superior sagittal sinus dural arteriovenous fistula (dAVF). We conclude that dural sinus thrombosis is a significant predisposing factor for development of a dAVF.A 60-year-old man had a left parietal parafalcine meningioma that invaded the posterior third of his superior sagittal sinus, leading to its occlusion and presumably resulting in an associated dAVF. The fistula was fed by the middle meningeal and superficial temporal arteries on both sides and drained through a superior interhemispheric cortical vein into the vein of Galen and straight sinus.The parafalcine mass, which involved the sagittal sinus, was excised via a left parieto-occipital craniotomy. It was decided to resect the dAVF at a later date. Seven days after the original operation, the patient underwent a parietal interhemispheric approach for occlusion of the dAVF. Dissection proceeded until a large arterialized vein and venous pouch with multiple feeders from both external carotid arteries were observed. The vein, which was partially embedded within the falx cerebri, was collapsed, and a second indocyanine green injection confirmed cessation of blood flow.This report supports that dAVFs are acquired lesions and that venousoutflow obstruction is a significant contributing factor to their development. In meningiomas associated with the dural sinuses, diagnostic evaluation for possible dAVFs should be considered. Treatment of these lesions should be based on risk factors because spontaneous resolution after tumor excision has been reported.

    View details for DOI 10.1227/01.NEU.0000370089.94032.4F

    View details for PubMedID 20559067

  • Cathepsin G-mediated enhanced TGF-beta signaling promotes angiogenesis via upregulation of VEGF and MCP-1 CANCER LETTERS Wilson, T. J., Nannuru, K. C., Futakuchi, M., Singh, R. K. 2010; 288 (2): 162-169


    Transforming growth factor (TGF)-beta signaling makes a significant contribution to the pathogenesis of breast cancer bone metastasis. In other tumor types, TGF-beta has been shown to promote tumor vascularity. Here, we report that inhibition of TGF-beta significantly reduces microvessel density in mammary tumor-induced bone lesions, mediated by decreased expression of both vascular endothelial growth factor (VEGF) and monocyte chemotactic protein (MCP)-1, both known angiogenic factors. Cathepsin G upregulation at the tumor-bone interface has been linked to increased TGF-beta signaling, and we also report that inhibition of Cathepsin G reduced tumor vascularity, as well as VEGF and MCP-1 expression.

    View details for DOI 10.1016/j.canlet.2009.06.035

    View details for Web of Science ID 000275150800004

    View details for PubMedID 19646811

    View details for PubMedCentralID PMC2815079

  • Enhanced expression and shedding of receptor activator of NF-kappa B ligand during tumor-bone interaction potentiates mammary tumor-induced osteolysis CLINICAL & EXPERIMENTAL METASTASIS Nannuru, K. C., Futakuchi, M., Sadanandam, A., Wilson, T. J., Varney, M. L., Myers, K. J., Li, X., Marcusson, E. G., Singh, R. K. 2009; 26 (7): 797-808


    The bone microenvironment plays a critical role in tumor-induced osteolysis and osteolytic metastasis through tumor-bone (TB)-interaction. Receptor activator of nuclear factor-kappaB (RANK) ligand (RANKL) is one of the critical signaling molecules involved in osteolysis and bone metastasis. However, the regulation and functional significance of RANKL at the TB-interface in tumor-induced osteolysis remains unclear. In this report, we examined the role of tumor-stromal interaction in the regulation of RANKL expression and its functional significance in tumor-induced osteolysis. Using a novel mammary tumor model, we identified that RANKL expression was upregulated at the TB-interface as compared to the tumor alone area. We demonstrate increased generation of sRANKL at the TB-interface, which is associated with tumor-induced osteolysis. The ratio of RANKL to osteoprotegrin (OPG), a decoy receptor for RANKL, at the TB-interface was also increased. Targeting RANKL expression with antisense oligonucleotides (RANKL-ASO), significantly abrogated tumor-induced osteolysis, decreased RANKL expression and the RANKL:OPG ratio at the TB-interface. Together, these results demonstrate that upregulation of RANKL expression and sRANKL generation at the TB-interface potentiates tumor-induced osteolysis.

    View details for DOI 10.1007/s10585-009-9279-2

    View details for Web of Science ID 000271722300021

    View details for PubMedID 19590968

  • Cathepsin G-Mediated Activation of Pro-Matrix Metalloproteinase 9 at the Tumor-Bone Interface Promotes Transforming Growth Factor-beta Signaling and Bone Destruction MOLECULAR CANCER RESEARCH Wilson, T. J., Nannuru, K. C., Singh, R. K. 2009; 7 (8): 1224-1233


    Increased transforming growth factor-beta (TGF-beta) signaling has been observed at the tumor-bone interface of mammary tumor-induced osteolytic lesions despite no observed transcriptional up-regulation of TGF-beta. To this point, the mechanism for enhanced TGF-beta signaling remains unclear. The bulk of TGF-beta that is released at the tumor-bone interface is in an inactive form secondary to association with beta-latency-associated protein and latency TGF-beta binding protein. We hypothesized that the observed increase in TGF-beta signaling is due to increased cathepsin G-dependent, matrix metalloproteinase 9 (MMP9)-mediated activation of latent TGF-beta. MMP9 is capable of activating latent TGF-beta, and we observed that decreased production of MMP9 was associated with reduced TGF-beta signaling. Similar to TGF-beta, MMP9 is released in an inactive form and requires proteolytic activation. We showed that cathepsin G, which we have previously shown to be up-regulated at the tumor-bone interface, is capable of activating pro-MMP9. Inhibition of cathepsin G in vivo significantly reduced MMP9 activity, increased the ratio of latent TGF-beta to active TGF-beta, and reduced the level of TGF-beta signaling. Our proposed model based on these results is that cathepsin G is up-regulated through tumor-stromal interactions and activates pro-MMP9, active MMP9 cleaves and releases active TGF-beta, and active TGF-beta can then promote tumor growth and enhance osteoclast activation and subsequent bone resorption. Thus, for the first time, we have identified cathepsin G and MMP9 as proteases involved in enhanced TGF-beta signaling at the tumor-bone interface of mammary tumor-induced osteolytic lesions and have identified these proteases as potential therapeutic targets.

    View details for DOI 10.1158/1541-7786.MCR-09-0028

    View details for Web of Science ID 000269170200004

    View details for PubMedID 19671689

  • Cathepsin G Recruits Osteoclast Precursors via Proteolytic Activation of Protease-Activated Receptor-1 CANCER RESEARCH Wilson, T. J., Nannuru, K. C., Singh, R. K. 2009; 69 (7): 3188-3195


    Metastatic breast cancer shows extreme tropism for the bone microenvironment, leading to the establishment of osteolytic metastases. Perpetuation of tumor-induced osteolysis requires a continuous supply of osteoclast precursors migrating into the bone microenvironment that can subsequently differentiate into mature osteoclasts and resorb bone. Thus, identification and subsequent targeting of chemoattractants of osteoclast precursors that are up-regulated at the tumor-bone interface represents a potential avenue to interrupt osteolysis. We report that cathepsin G, a serine protease, plays a vital role in the bone microenvironment by modulating tumor-stromal interaction in a manner that favors tumor establishment and regulates chemotaxis of monocytes, a subset of which has the potential to differentiate into osteoclasts. Our data show that cathepsin G-induced chemotaxis of monocytes is mediated by proteolytic activation of protease-activated receptor-1 (PAR-1). Attenuation of PAR-1 activation abrogates cathepsin G-mediated induction of monocyte chemotaxis. We also show that in vivo inhibition of cathepsin G reduces the number of CD11b(+) osteoclast precursors and mature osteoclasts at the tumor-bone interface. Together, these data suggest that therapeutic targeting of both PAR-1 signaling in osteoclast precursors as well as cathepsin G at the tumor-bone interface has the potential to reduce osteolysis by inhibiting the recruitment, differentiation, and activation of osteoclast precursors.

    View details for DOI 10.1158/0008-5472.CAN-08-1956

    View details for Web of Science ID 000264908100064

    View details for PubMedID 19293192

  • Cathepsin g enhances mammary tumor-induced osteolysis by generating soluble receptor activator of nuclear factor-kappa B ligand CANCER RESEARCH Wilson, T. J., Nannuru, K. C., Futakuchi, M., Sadanandam, A., Singh, R. K. 2008; 68 (14): 5803-5811


    Breast cancer commonly causes osteolytic metastases in bone, a process that is dependent on tumor-stromal interaction. Proteases play an important role in modulating tumor-stromal interactions in a manner that favors tumor establishment and progression. Whereas several studies have examined the role of proteases in modulating the bone microenvironment, little is currently known about their role in tumor-bone interaction during osteolytic metastasis. In cancer-induced osteolytic lesions, cleavage of receptor activator of nuclear factor-kappaB ligand (RANKL) to a soluble version (sRANKL) is critical for widespread osteoclast activation. Using a mouse model that mimics osteolytic changes associated with breast cancer-induced bone metastases, we identified cathepsin G, cathepsin K, matrix metalloproteinase (MMP)-9, and MMP13 to be proteases that are up-regulated at the tumor-bone interface using comparative cDNA microarray analysis and quantitative reverse transcription-PCR. Moreover, we showed that cathepsin G is capable of shedding the extracellular domain of RANKL, generating active sRANKL that is capable of inducing differentiation and activation of osteoclast precursors. The major source of cathepsin G at the tumor-bone interface seems to be osteoclasts that up-regulate production of cathepsin G via interaction with tumor cells. Furthermore, we showed that in vitro osteoclastogenesis is reduced by inhibition of cathepsin G in a coculture model and that in vivo inhibition of cathepsin G reduces mammary tumor-induced osteolysis. Together, our data indicate that cathepsin G activity at the tumor-bone interface plays an important role in mammary tumor-induced osteolysis and suggest that cathepsin G is a potentially novel therapeutic target in the treatment of breast cancer bone metastasis.

    View details for DOI 10.1158/0008-5472.CAN-07-5889

    View details for Web of Science ID 000257768300038

    View details for PubMedID 18632634

  • Proteases as modulators of tumor-stromal interaction: Primary tumors to bone metastases BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER Wilson, T. J., Singh, R. K. 2008; 1785 (2): 85-95


    As cells undergo oncogenic transformation and as malignant cells arrive at metastatic sites, a complex interplay occurs with the surrounding stroma. This dialogue between the tumor and stroma ultimately dictates the success of the tumor cells in the given microenvironment. As a result, understanding the molecular mechanisms at work is important for developing new therapeutic modalities. Proteases are major players in the interaction between tumor and stroma. This review will focus on the role of proteases in modulating tumor-stromal interactions of both primary breast and prostate tumors as well as at bone metastatic sites in a way that favors tumor growth.

    View details for DOI 10.1016/j.bbcan.2007.11.001

    View details for Web of Science ID 000256211800001

    View details for PubMedID 18082147

    View details for PubMedCentralID PMC2418859