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Witham, Timothy F.

https://orcid.org/0000-0002-9397-8344

Mayo Clinic

Johns Hopkins University

Citations 12

Utility of direct wave intraoperative neuromonitoring for intramedullary spinal cord tumor resection
Jiang, Kelly , Zaitoun, Khaled J. , Xia, Yuanxuan , Ksabi, Noa , Papali, Pritika, Neerumalla, Sushanth , Davidar, A Daniel, Pennington, Zach, Gokaslan, Ziya L, Lim, Michael, Lin, Shih-Chun, Lo, Sheng-Fu Larry, Witham, Timothy, Sciubba, Daniel M, Jallo, George, Wolinsky, Jean-Paul, Weingart, Jon , Theodore, Nicholas, Lubelski, Daniel, Lim, Michael , Pennington, Zach , Pennington, Zach , Al‐Mistarehi, Abdel‐Hameed , Weber-Levine, Carly , Mendelson, Benjamin Z. , Papali, Pritika , Antar, Albert , Hersh, Andrew M. , Davidar, A. Daniel , Gokaslan, Ziya L., Lim, Michael, Lo, Sheng-Fu Larry , Witham, Timothy F. , Sciubba, Daniel M. , Jallo, George I. , Wolinsky, Jean‐Paul , Theodore, Nicholas , Lubelski, Daniel

Journal of Neurosurgery: Spine | May 21, 2026 | Volume: No volume available | Issue: No issue available | Pages: 1-10

10.3171/2025.11.spine25124 Get It

OBJECTIVE Intramedullary spinal cord tumors (IMSCTs) are typically treated with maximal safe resection, during which neurosurgeons often monitor for neurological injury using muscle motor evoked potential (mMEP) and direct wave (D-wave) neuromonitoring. The predictive value of changes in D-waves for identifying motor outcomes is underexplored. This study evaluated the utility of D-waves for predicting postoperative motor deficits. METHODS Patients who underwent resection of a primary IMSCT with mMEP neuromonitoring from 2003 to 2023 at a tertiary care hospital were identified. Patients who underwent D-wave monitoring in addition to mMEP monitoring were compared to those who underwent mMEP monitoring alone using the Mann-Whitney U-test, chi-square test, and Fisher’s exact test. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of D-wave and mMEP monitoring for identifying new neurological deficits immediately postoperatively and at 1 month, 6 months, and last follow-up were calculated. RESULTS After matching, 125 patients were included (median age 42.0 years; 57.6% male; median follow-up 34.0 months), of whom 88 had both mMEP and D-wave data. The most common pathologies were ependymoma (64.0%) and astrocytoma (17.6%). Patients who did and did not undergo D-wave neuromonitoring had similar preoperative neurological function, primary pathology, tumor grade, and tumor location. D-wave use was associated with increased gross-total resection (88.6% vs 64.9%, p = 0.002) and reduced mortality (5.7% vs 24.3%, p = 0.007), length of stay (5.0 vs 6.0 days, p = 0.033), and 30-day readmission (2.3% vs 13.5%, p = 0.013) and reoperation (1.1% vs 10.8%, p = 0.012). At the 6-month follow-up, D-wave monitoring alone was superior to mMEP and combination monitoring for detecting new motor deficits. D-wave monitoring had peak sensitivity (77.8%) and NPV (96.5%) at 6 months and peak specificity (95.8%) and PPV (76.9%) in the immediate postoperative period. CONCLUSIONS D-wave monitoring was associated with reduced mortality and was more accurate than mMEP monitoring alone or combination monitoring for detecting new postoperative neurological deficits. Further prospective studies are needed to validate these results.
Creation and preclinical evaluation of a novel mussel-inspired, biomimetic, bioactive bone graft scaffold: direct comparison with Infuse bone graft using a rat model of spinal fusion
Cottrill, Ethan , Pennington, Zach , Perdomo‐Pantoja, Alexander , Rajkovic, Christian , Lin, Jessica, Mageau, Ashlie, Stewart, Veronica , Sciubba, Daniel M. , Elisseeff, Jennifer H. , Pennington, Zach , Wolf, Matthew T. , Dirckx, Naomi , Ehresman, Jeff , Lin, Jessica, Maestas, David R. , Lambrechts, Dennis , Theodore, Nicholas , Witham, Timothy F.

Journal of Neurosurgery: Spine | March 31, 2023 | Volume: 39 | Issue: 1 | Pages: 113-121

10.3171/2023.2.spine22936 Get It

OBJECTIVE Infuse bone graft is a widely used osteoinductive adjuvant; however, the simple collagen sponge scaffold used in the implant has minimal inherent osteoinductive properties and poorly controls the delivery of the adsorbed recombinant human bone morphogenetic protein–2 (rhBMP-2). In this study, the authors sought to create a novel bone graft substitute material that overcomes the limitations of Infuse and compare the ability of this material with that of Infuse to facilitate union following spine surgery in a clinically translatable rat model of spinal fusion. METHODS The authors created a polydopamine (PDA)–infused, porous, homogeneously dispersed solid mixture of extracellular matrix and calcium phosphates (BioMim-PDA) and then compared the efficacy of this material directly with Infuse in the setting of different concentrations of rhBMP-2 using a rat model of spinal fusion. Sixty male Sprague Dawley rats were randomly assigned to each of six equal groups: 1) collagen + 0.2 µg rhBMP-2/side, 2) BioMim-PDA + 0.2 µg rhBMP-2/side, 3) collagen + 2.0 µg rhBMP-2/side, 4) BioMim-PDA + 2.0 μg rhBMP-2/side, 5) collagen + 20 µg rhBMP-2/side, and 6) BioMim-PDA + 20 µg rhBMP-2/side. All animals underwent posterolateral intertransverse process fusion at L4–5 using the assigned bone graft. Animals were euthanized 8 weeks postoperatively, and their lumbar spines were analyzed via microcomputed tomography (µCT) and histology. Spinal fusion was defined as continuous bridging bone bilaterally across the fusion site evaluated via µCT. RESULTS The fusion rate was 100% in all groups except group 1 (70%) and group 4 (90%). Use of BioMim-PDA with 0.2 µg rhBMP-2 led to significantly greater results for bone volume (BV), percentage BV, and trabecular number, as well as significantly smaller trabecular separation, compared with the use of the collagen sponge with 2.0 µg rhBMP-2. The same results were observed when the use of BioMim-PDA with 2.0 µg rhBMP-2 was compared with the use of the collagen sponge with 20 µg rhBMP-2. CONCLUSIONS Implantation of rhBMP-2–adsorbed BioMim-PDA scaffolds resulted in BV and bone quality superior to that afforded by treatment with rhBMP-2 concentrations 10-fold higher implanted on a conventional collagen sponge. Using BioMim-PDA (vs a collagen sponge) for rhBMP-2 delivery could significantly lower the amount of rhBMP-2 required for successful bone grafting clinically, improving device safety and decreasing costs.
Comparing the efficacy of adipose‐derived and bone marrow‐derived cells in a rat model of posterolateral lumbar fusion
Perdomo‐Pantoja, Alexander , Elder, Benjamin D. , Cottrill, Ethan , Locke, John , Perdomo-Pantoja, Alexander , Holmes, Christina , Ishida, Wataru , Witham, Timothy F.

Journal of Orthopaedic Research | June 3, 2021 | Volume: 40 | Issue: 4 | Pages: 909-916

10.1002/jor.25111 Get It

AbstractAlthough bone marrow‐derived mesenchymal stem cells (BMCs) have been widely used in spinal fusion procedures, adipose‐derived stem cells (ASCs) offer a number of advantages as an alternative clinical cell source. This study directly compares the efficacy of ASCs and BMCs from the same donor animals to achieve successful fusion when combined with a clinical‐grade bone graft substitute in a rat lumbar fusion model. ASCs and BMCs were isolated from the same Lewis donor rats and grown to passage 2 (P2). Single‐level bilateral posterolateral intertransverse process lumbar fusion surgery was performed on syngeneic rats divided into three experimental groups: clinical‐grade bone graft substitute alone (CBGS); CBGS+ rat ASCs (rASC); and, CBGS+ rat BMCs (rBMC). Eight weeks postoperatively, fusion was evaluated via micro‐CT, manual palpation and histology. In vitro analysis of the osteogenic capacity of rBMCs and rASCs was also performed. Results indicated that the average fusion volume in the rASC group was the largest and was significantly larger than the CBGS group. Although the rASC group displayed the highest fusion rates via micro‐CT and manual palpation, this difference was not statistically significant. Cell‐seeded grafts showed more histological bone formation than cell‐free grafts. P2 rASCs and rBMCs displayed similar in vitro osteogenic differentiation capacities. Overall, this study showed that, when combined with a clinical‐grade bone graft substitute in a rat model, rASCs cells yielded the largest fusion masses and comparable fusion results to rBMCs. These results add to growing evidence that ASCs provide an attractive alternative to BMCs for spinal fusion procedures.
Comparing the Efficacy of Syngeneic Iliac and Femoral Allografts with Iliac Crest Autograft in a Rat Model of Lumbar Spinal Fusion
Elder, Benjamin D. , Perdomo‐Pantoja, Alexander , Locke, John , Cottrill, Ethan , Lo, Sheng-Fu Larry , Holmes, Christina , Ishida, Wataru , Witham, Timothy F.

No container title available | August 10, 2020 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.21203/rs.3.rs-27369/v2 Get It

Abstract Background: Despite widespread use of femoral-sourced allografts in clinical spinal fusion procedures and the increasing interest in using femoral reamer–irrigator–aspirator (RIA) autograft in clinical bone grafting, few studies have examined the efficacy of femoral grafts compared to iliac crest grafts in spinal fusion. The objective of this study was to directly compare the use of autologous iliac crest with syngeneic femoral and iliac allograft bone in the rat model of lumbar spinal fusion.Methods: Single-level bilateral posterolateral intertransverse process lumbar spinal fusion surgery was performed on Lewis rats divided into three experimental groups: iliac crest autograft; syngeneic iliac crest allograft; and syngeneic femoral allograft bone. Eight weeks postoperatively, fusion was evaluated via microCT analysis, manual palpation and histology. In vitro analysis of the colony-forming and osteogenic capacity of bone marrow cells derived from rat femurs and hips was also performed to determine whether there was a correlation with the fusion efficacy of these graft sources.Results: Although no differences were observed between groups in CT fusion mass volumes, iliac allografts displayed an increased number of radiographically fused fusion masses and a higher rate of bilateral fusion via manual palpation. Histologically, hip-derived grafts showed better integration with host bone than femur derived ones, likely associated with the higher concentration of osteogenic progenitor cells observed in hip-derived bone marrow. Conclusions: This study demonstrates the feasibility of using syngeneic allograft bone in place of autograft bone within inbred rat fusion models and highlights the need for further study of femoral-derived grafts in fusion.
Introduction. Lumbar spinal osteoporosis
Anderson, Paul A. , Freedman, Brett A. , Chou, Dean , Witham, Timothy F.

Neurosurgical Focus | August 1, 2020 | Volume: 49 | Issue: 2 | Pages: E1

10.3171/2020.5.focus20412 Get It

Comparing the Efficacy of Syngeneic Iliac and Femoral Allografts with Iliac Crest Autograft in a Rat Model of Lumbar Spinal Fusion
Elder, Benjamin D. , Pantoja, Alexander Perdomo, Locke, John , Cottrill, Ethan , Lo, Sheng-Fu Larry , Holmes, Christina , Ishida, Wataru , Witham, Timothy F.

No container title available | May 12, 2020 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.21203/rs.3.rs-27369/v1 Get It

Abstract Background: Despite widespread use of femoral-sourced allografts in clinical spinal fusion procedures and the increasing interest in using femoral reamer–irrigator–aspirator (RIA) autograft in clinical bone grafting, few studies have examined the efficacy of femoral grafts compared to iliac crest grafts in spinal fusion. The objective of this study was to directly compare the use of autologous iliac crest with syngeneic femoral and iliac allograft bone in the rat model of lumbar spinal fusion.Methods: Single-level bilateral posterolateral intertransverse process lumbar spinal fusion surgery was performed on Lewis rats divided into three experimental groups: iliac crest autograft; syngeneic iliac crest allograft; and syngeneic femoral allograft bone. Eight weeks postoperatively, fusion was evaluated via microCT analysis, manual palpation and histology. In vitro analysis of the colony-forming and osteogenic capacity of bone marrow cells derived from rat femurs and hips was also performed to determine whether there was a correlation with the fusion efficacy of these graft sources.Results: Although no differences were observed between groups in CT fusion rates or fusion mass volumes, iliac allografts displayed a higher rate of bilateral fusion via manual palpation. Histologically, hip-derived grafts showed better integration with host bone than femur derived ones, likely associated with the higher concentration of osteogenic progenitor cells observed in hip-derived bone marrow.Conclusions: This study demonstrates the feasibility of using syngeneic allograft bone in place of autograft bone within inbred rat fusion models and highlights the need for further study of femoral-derived grafts in fusion.
Effects of Intraoperative Intrawound Antibiotic Administration on Spinal Fusion
Ishida, Wataru , Perdomo‐Pantoja, Alexander , Elder, Benjamin D. , Locke, John , Holmes, Christina , Witham, Timothy F. , Lo, Sheng-Fu Larry , Lo, Sheng-Fu L

Journal of Bone and Joint Surgery | October 11, 2019 | Volume: 101 | Issue: 19 | Pages: 1741-1749

10.2106/jbjs.18.00988 Get It

Background: Local, intrawound use of antibiotic powder, such as vancomycin and tobramycin, in spinal fusion surgery has become an increasingly common prophylactic measure in an attempt to reduce rates of postsurgical infection. However, the effects of localized antibiotic delivery on fusion remain unclear. The objective of this study was to examine the in vivo effects of intraoperative local delivery of 2 antibiotics commonly used in bone-grafting surgery on spinal fusion outcomes in a rat model. Methods: Single-level (L4-L5), bilateral posterolateral intertransverse process lumbar fusion surgery was performed on 60 female Lewis rats (6 to 8 weeks of age) using syngeneic iliac crest allograft mixed with clinical bone-graft substitute and varying concentrations of antibiotics (n = 12 each): (1) control without any antibiotics, (2) low-dose vancomycin (14.3 mg/kg), (3) high-dose vancomycin (71.5 mg/kg), (4) low-dose tobramycin (28.6 mg/kg), and (5) high-dose tobramycin (143 mg/kg). Eight weeks postoperatively, fusion was evaluated via micro-computed tomography (µCT), manual palpation, and histological analysis, with blinding to treatment group. In the µCT analysis, fusion-mass volumes were measured for each rat. Each spine specimen (L4-L5) was rated (manual palpation score) on a scale of 2 to 0 (2 = fused, 1 = partially fused, and 0 = non-fused). Results: The mean fusion-mass volume on µCT (mm 3 ) was as follows: control, 29.3 ± 6.2; low-dose vancomycin, 26.3 ± 8.9; high-dose vancomycin, 18.8 ± 7.9; low-dose tobramycin, 32.7 ± 9.0; and high-dose tobramycin, 43.8 ± 11.9 (control versus high-dose vancomycin, p < 0.05; and control versus high-dose tobramycin, p < 0.05). The mean manual palpation score for each group was as follows: control, 1.46 ± 0.58; low-dose vancomycin, 0.86 ± 0.87; high-dose vancomycin, 0.68 ± 0.62; low-dose tobramycin, 1.25 ± 0.71; and high-dose tobramycin, 1.32 ± 0.72 (control versus high-dose vancomycin, p < 0.05). The histological analyses demonstrated a similar trend with regard to spinal fusion volume. Conclusions: Intraoperative local application of vancomycin, particularly at a supraphysiological dosage, may have detrimental effects on fusion-mass formation. No inhibitory effect of tobramycin on fusion-mass formation was observed. Clinical Relevance: When spine surgeons decide to use intraoperative intrawound antibiotics in spinal fusion surgery, they should weigh the reduction in surgical site infection against a possible inhibitory effect on fusion.
Safety Profile of Lumbosacropelvic Fixation in Patients Aged 60 Years or Older
Ishida, Wataru , Ramhmdani, Seba , Casaos, Joshua, Perdomo‐Pantoja, Alexander , Elder, Benjamin D. , Gokaslan, Ziya L. , Wolinsky, Jean‐Paul , Sciubba, Daniel M. , Bydon, Ali , Witham, Timothy F. , Lo, Sheng-Fu Larry , Theodore, Nicholas

Clinical Spine Surgery: A Spine Publication | February 21, 2019 | Volume: 32 | Issue: 4 | Pages: E200-E205

10.1097/bsd.0000000000000806 Get It

Study Design: This is a retrospective study. Objective: To report the safety profile of S2-alar-iliac (S2AI) in patients over 60, comparing S2AI screws with iliac screws (ISs). Summary of Background Data: The surgical management involving the lumbosacropelvic spine remains a challenge due to high mechanical demand and risk of pseudarthrosis. Previous articles showed lower rates of complications in patients receiving S2AI screws than ISs; however, none of them have focused on patients aged over 60 who may harbor significant comorbidities and thus require more meticulous perioperative management, given these invasive and lengthy procedures. Materials and Methods: Retrospective review of clinical records from 2010 to 2015 identified 60 patients undergoing lumbosacropelvic fixation (17 patients with ISs and 43 patients with S2AI screws) who satisfied the following criteria: (1) patients aged over 60 years old and (2) patients with >1-year follow-up periods. Rates of complications such as unplanned reoperation and cardiorespiratory complications were collected and statistically analyzed. Results: Baseline characteristics such as age, sex, and comorbidities were similar in both groups. The S2AI group had lower rates of reoperation (18.6% vs. 47.4%; P=0.02), surgical site infection (2.3% vs. 29.4%; P=0.006), wound dehiscence (2.3% vs. 29.4%; P=0.006), and postoperative anemia (7.0% vs. 29.4%; P=0.03) and had lower total volume of estimated blood loss (EBL) (mL) (1846.4 vs. 2721.2; P=0.02) and transfused red blood cell units (7.2 vs. 4.7; P=0.04) than the IS group, while rates of L5–S1 pseudarthrosis and other cardiorespiratory complications were similar in both groups. In multivariate analysis, operative time, body mass index, and use of S2AI screws over ISs were independent predictors of EBL. Conclusions: Use of S2AI screws over ISs in patients aged over 60 was associated with lower rates of reoperation, surgical site infection, wound dehiscence, and lower volume of EBL and red blood cell transfusion and is a viable surgical option.
Long-term clinical outcomes following 3- and 4-level anterior cervical discectomy and fusion
Ramos, Rafael De la Garza , Ramhmdani, Seba , Kosztowski, Thomas, Bydon, Mohamad , Sciubba, Daniel M. , Wolinsky, Jean‐Paul , Witham, Timothy F. , Gokaslan, Ziya L. , Bydon, Ali , Xu, Risheng , De la Garza Ramos, Rafael

Journal of Neurosurgery: Spine | February 19, 2016 | Volume: 24 | Issue: 6 | Pages: 885-891

10.3171/2015.10.spine15795 Get It

OBJECTIVE The purpose of this study was to report the long-term clinical outcomes following 3- and 4-level anterior cervical discectomy and fusion (ACDF). METHODS A retrospective review of all adult neurosurgical patients undergoing elective ACDF for degenerative disease at a single institution between 1996 and 2013 was performed. Patients who underwent first-time 3- or 4-level ACDF were included; patients with previous cervical spine surgery, those undergoing anterior/posterior approaches, and those with corpectomy were excluded. Outcome measures included perioperative complication rates, fusion rates, need for revision surgery, Nurick Scores, Odom's criteria, symptom resolution, neck visual analog scale (VAS) pain score, and persistent narcotics usage. RESULTS Seventy-one patients who underwent 3-level ACDF and 26 patients who underwent 4-level ACDF were identified and followed for an average of 7.6 ± 4.2 years. There was 1 case (3.9%) of deep wound infection in the 4-level group and 1 case in the 3-level group (1.4%; p = 0.454). Postoperatively, 31% of patients in the 4-level group complained of dysphagia, compared with 12.7% in the 3-level group (p = 0.038). The fusion rate was 84.6% after 4-level ACDF and 94.4% after 3-level ACDF (p = 0.122). At last follow-up, a significantly higher proportion of patients in the 4-level group continued to have axial neck pain (53.8%) than in the 3-level group (31%; p = 0.039); the daily oral morphine equivalent dose was significantly higher in the 4-level group (143 ± 97 mg/day) than in the 3-level group (25 ± 10 mg/day; p = 0.030). Outcomes based on Odom's criteria were also different between cohorts (p = 0.044), with a significantly lower proportion of patients in the 4-level ACDF group experiencing an excellent/good outcome. CONCLUSIONS In this study, patients who underwent 4-level ACDF had significantly higher rates of dysphagia, postoperative neck pain, and postoperative narcotic usage when compared with patients who underwent 3-level ACDF. Pseudarthrosis and deep wound infection rates were also higher in the 4-level group, although this did not reach statistical significance. Additionally, a smaller proportion of patients achieved a good/excellent outcome in the 4-level group than in the 3-level group. These findings suggest a significant increase of perioperative morbidity and worsened outcomes for patients who undergo 4- versus 3-level ACDF.
Fusion following lateral mass reconstruction in the cervical spine
Zadnik, Patricia L., Groves, Mari L. , Sciubba, Daniel M. , Witham, Timothy F. , Bydon, Ali , Gokaslan, Ziya L. , Wolinsky, Jean‐Paul , Clarke, Michelle J.

Journal of Neurosurgery: Spine | November 28, 2014 | Volume: 22 | Issue: 2 | Pages: 139-150

10.3171/2014.10.spine13858 Get It

OBJECT Recently, aggressive surgical techniques and a push toward en bloc resections of certain tumors have resulted in a need for creative spinal column reconstruction. Iatrogenic instability following these resections requires a thoughtful approach to adequately transfer load-bearing forces from the skull and upper cervical spine to the subaxial spine. METHODS The authors present a series of 7 cases in which lateral mass reconstruction with a cage or fibular strut graft was used to provide load-bearing support, including 1 case of bilateral cage placement. RESULTS The authors discuss the surgical nuances of en bloc resection of high cervical tumors and explain their technique for lateral mass cage placement. Additionally, they provide their rationale for the use of these constructs throughout the craniocervical junction and subaxial spine. CONCLUSIONS Lateral mass reconstruction provides a potential alternative or adjuvant method of restoring the load-bearing capabilities of the cervical spine.