Haddad, Alexander F. (15)
Ames, Christopher P. (6)
Deviren, Vedat (5)
Lau, Darryl (5)
Aghi, Manish K. (3)
Joshi, Rushikesh S. (3)
Young, Jacob S. (3)
Beniwal, Angad (2)
Blevins, Lewis S. (2)
Donohue, Kevin C. (2)
El-Sayed, Ivan H. (2)
Gurrola, José (2)
Jain, Saket (2)
Kunwar, Sandeep (2)
Morshed, Ramin A. (2)
Oh, Taemin (2)
Osorio, Robert C. (2)
Peeran, Zain (2)
Pereira, Kaitlyn M. (2)
Pereira, Matheus P. (2)
Scheer, Justin K. (2)
Sudhir, Sweta (2)
Barthélemy, Ernest J. (1)
Berven, Sigurd (1)
Braunstein, Steve E. (1)
Burch, Shane (1)
Cha, Soonmee (1)
Chopra, Ashley S. (1)
Dhall, Sanjay S. (1)
DiGiorgio, Anthony M. (1)
Eastlack, Robert K. (1)
Eichler, Charles M. (1)
Fessler, Richard G. (1)
Fu, Kai-Ming G. (1)
Fury, Marissa (1)
Hervey-Jumper, Shawn L. (1)
Huang, Michael C. (1)
Jamieson, Alysha (1)
Limb, Charles J. (1)
Lockney, Dennis T. (1)
Lyu, Qiunan (1)
Mahmoudieh, Yasmine (1)
Maloney, Patrick R. (1)
Manley, Geoffrey T. (1)
https://thejns.org/search?f_0=author&q_0=Alexander+F.+Haddad
Author or Editor: Alexander F. Haddad x
Using viral vectors to deliver local immunotherapy to glioblastoma
Alexander F. Haddad, Jacob S. Young, and Manish K. Aghi
The treatment for glioblastoma (GBM) has not seen significant improvement in over a decade. Immunotherapies target the immune system against tumor cells and have seen success in various cancer types. However, the efficacy of immunotherapies in GBM thus far has been limited. Systemic immunotherapies also carry with them concerns surrounding systemic toxicities as well as penetration of the blood-brain barrier. These concerns may potentially limit their efficacy in GBM and preclude the use of combinatorial immunotherapy, which may be needed to overcome the severe multidimensional immune suppression seen in GBM patients. The use of viral vectors to deliver immunotherapies directly to tumor cells has the potential to improve immunotherapy delivery to the CNS, reduce systemic toxicities, and increase treatment efficacy. Indeed, preclinical studies investigating the delivery of immunomodulators to GBM using viral vectors have demonstrated significant promise. In this review, the authors discuss previous studies investigating the delivery of local immunotherapy using viral vectors. They also discuss the future of these treatments, including the reasoning behind immunomodulator and vector selection, patient safety, personalized therapies, and the need for combinatorial treatment.
In Neurosurgical Focus Volume 50 (2021): Issue 2 (Feb 2021): Gene and Viral Therapy for Glioblastoma Multiforme
Asymmetrical pedicle subtraction osteotomy for correction of concurrent sagittal-coronal imbalance in adult spinal deformity: a comparative analysis
Darryl Lau, Alexander F. Haddad, Vedat Deviren, and Christopher P. Ames
Rigid multiplanar thoracolumbar adult spinal deformity (ASD) cases are challenging and many require a 3-column osteotomy (3CO), specifically asymmetrical pedicle subtraction osteotomy (APSO). The outcomes and additional risks of performing APSO for the correction of concurrent sagittal-coronal deformity have yet to be adequately studied.
The authors performed a retrospective review of all ASD patients who underwent 3CO during the period from 2006 to 2019. All cases involved either isolated sagittal deformity (patients underwent standard PSO) or concurrent sagittal-coronal deformity (coronal vertical axis [CVA] ≥ 4.0 cm; patients underwent APSO). Perioperative and 2-year follow-up outcomes were compared between patients with isolated sagittal imbalance who underwent PSO and those with concurrent sagittal-coronal imbalance who underwent APSO.
A total of 390 patients were included: 338 who underwent PSO and 52 who underwent APSO. The mean patient age was 64.6 years, and 65.1% of patients were female. APSO patients required significantly more fusions with upper instrumented vertebrae (UIV) in the upper thoracic spine (63.5% vs 43.3%, p = 0.007). Radiographically, APSO patients had greater deformity with more severe preoperative sagittal and coronal imbalance: sagittal vertical axis (SVA) 13.0 versus 10.7 cm (p = 0.042) and CVA 6.1 versus 1.2 cm (p < 0.001). In APSO cases, significant correction and normalization were achieved (SVA 13.0–3.1 cm, CVA 6.1–2.0 cm, lumbar lordosis [LL] 26.3°–49.4°, pelvic tilt [PT] 38.0°–20.4°, and scoliosis 25.0°–10.4°, p < 0.001). The overall perioperative complication rate was 34.9%. There were no significant differences between PSO and APSO patients in rates of complications (overall 33.7% vs 42.3%, p = 0.227; neurological 5.9% vs 3.9%, p = 0.547; medical 20.7% vs 25.0%, p = 0.482; and surgical 6.5% vs 11.5%, p = 0.191, respectively). However, the APSO group required significantly longer stays in the ICU (3.1 vs 2.3 days, p = 0.047) and hospital (10.8 vs 8.3 days, p = 0.002). At the 2-year follow-up, there were no significant differences in mechanical complications, including proximal junctional kyphosis (p = 0.352), pseudarthrosis (p = 0.980), rod fracture (p = 0.852), and reoperation (p = 0.600).
ASD patients with significant coronal imbalance often have severe concurrent sagittal deformity. APSO is a powerful and effective technique to achieve multiplanar correction without higher risk of morbidity and complications compared with PSO for sagittal imbalance. However, APSO is associated with slightly longer ICU and hospital stays.
In Journal of Neurosurgery: Spine Volume 33: Issue null (Dec 2020)
Complication profile associated with S1 pedicle subtraction osteotomy compared with 3-column osteotomies at other thoracolumbar levels for adult spinal deformity: series of 405 patients with 9 S1 osteotomies
There is an increased recognition of disproportional lumbar lordosis (LL) and artificially high pelvic incidence (PI) as a cause for positive sagittal imbalance and spinal pelvic mismatch. For such cases, a sacral pedicle subtraction osteotomy (PSO) may be indicated, although its morbidity is not well described. In this study, the authors evaluate the specific complication risks associated with S1 PSO.
A retrospective review of all adult spinal deformity patients who underwent a 3-column osteotomy (3CO) for thoracolumbar deformity from 2006 to 2019 was performed. Demographic, clinical baseline, and radiographic parameters were recorded. The primary outcome of interest was perioperative complications (surgical, neurological, and medical). Secondary outcomes of interest included case length, blood loss, and length of stay. Multivariate analysis was used to assess the risk of S1 PSO compared with 3CO at other levels.
A total of 405 patients underwent 3CO in the following locations: thoracic (n = 55), L1 (n = 25), L2 (n = 29), L3 (n = 141), L4 (n = 129), L5 (n = 17), and S1 (n = 9). After S1 PSO, there were significant improvements in the sagittal vertical axis (14.8 cm vs 6.7 cm, p = 0.004) and PI-LL mismatch (31.7° vs 9.6°, p = 0.025) due to decreased PI (80.3° vs 65.9°, p = 0.006). LL remained unchanged (48.7° vs 57.8°, p = 0.360). The overall complication rate was 27.4%; the surgical, neurological, and medical complication rates were 7.7%, 6.2%, and 20.0%, respectively. S1 PSO was associated with significantly higher rates of overall complications: thoracic (29.1%), L1 (32.0%), L2 (31.0%), L3 (19.9%), L4 (32.6%), L5 (11.8%), and S1 (66.7%) (p = 0.018). Similarly, an S1 PSO was associated with significantly higher rates of surgical (thoracic [9.1%], L1 [4.0%], L2 [6.9%], L3 [5.7%], L4 [10.9%], L5 [5.9%], and S1 [44.4%], p = 0.006) and neurological (thoracic [9.1%], L1 [0.0%], L2 [6.9%], L3 [2.8%], L4 [7.0%], L5 [5.9%], and S1 [44.4%], p < 0.001) complications. On multivariate analysis, S1 PSO was independently associated with higher odds of overall (OR 7.93, p = 0.013), surgical (OR 20.66, p = 0.010), and neurological (OR 14.75, p = 0.007) complications.
S1 PSO is a powerful technique for correction of rigid sagittal imbalance due to an artificially elevated PI in patients with rigid high-grade spondylolisthesis and chronic sacral fractures. However, the technique and intraoperative corrective maneuvers are challenging and associated with high surgical and neurological complications. Additional investigations into the learning curve associated with S1 PSO and complication prevention are needed.
In Journal of Neurosurgery: Spine Volume 33: Issue 5 (Nov 2020)
Risk factors for determining length of intensive care unit and hospital stays following correction of cervical deformity: evaluation of early severe adverse events
Rushikesh S. Joshi, Darryl Lau, Alexander F. Haddad, Vedat Deviren, and Christopher P. Ames
Correction of rigid cervical deformities can be associated with high complication rates and result in prolonged intensive care unit (ICU) and hospital stays. In this study, the authors aimed to examine the risk factors contributing to length of stay (LOS) in both the hospital and ICU following adult cervical deformity (ACD) surgery and to identify severe adverse events that occurred in this setting.
A retrospective review of ACD patients who underwent posterior-based osteotomies for deformity correction from 2010 to 2019 was performed. Inclusion criteria were cervical kyphosis > 20° and/or cervical sagittal vertical axis (cSVA) > 4 cm. Multivariate analysis was used to identify risk factors independently associated with ICU and hospital LOS.
A total of 107 patients were included. The mean age was 63.5 years, and 61.7% were female. Over half (52.3%) underwent 3-column osteotomies, while 47.7% underwent posterior column osteotomies. There was significant correction of all cervical parameters: cSVA (6.0 vs 3.6 cm, p < 0.001), cervical lordosis (8.2° vs −5.3°, p < 0.001), cervical scoliosis (6.5° vs 2.2°, p < 0.001), and T1-slope (40.2° vs 34.5°, p < 0.001). There were also reciprocal changes to the distal spine: thoracic kyphosis (54.4° vs 46.4°, p < 0.001), lumbar lordosis (49.9° vs 45.8°, p = 0.003), and thoracolumbar scoliosis (13.9° vs 11.1°, p = 0.009). Overall, 4 patients (3.7%) suffered aspiration-related complications, 3 patients (2.8%) experienced dysphagia requiring a feeding tube, and 4 patients (3.7%) had compromised airways, with 1 resulting in death. The mean ICU and hospital LOS were 2.8 days and 7.9 days, respectively. Multivariate analysis identified three factors independently associated with longer ICU LOS: female sex (3.0 vs 2.4 days, p = 0.004), ≥ 12 segments fused (3.5 vs 1.9 days, p = 0.002), and postoperative complication (4.0 vs 1.9 days, p = 0.017). These same factors were independently associated with longer hospital LOS as well: female sex (8.3 vs 7.3 days, p = 0.013), ≥ 12 segments fused (9.4 vs 6.2 days, p = 0.001), and complication (9.7 vs 6.7 days, p = 0.026).
Posterior-based osteotomies are very effective for the correction of ACD, but postoperative hospital stays are relatively longer than those following surgery for degenerative disease. Risk factors for prolonged ICU and hospital LOS consist of both nonmodifiable (female sex) and modifiable (≥ 12 segments fused and presence of complication) risk factors. Additional multicenter prospective studies will be needed to validate these findings.
In Journal of Neurosurgery: Spine Volume 34: Issue null (Feb 2021)
Multiple-rod constructs and use of bone morphogenetic protein–2 in relation to lower rod fracture rates in 141 patients with adult spinal deformity who underwent lumbar pedicle subtraction osteotomy
Qiunan Lyu, Darryl Lau, Alexander F. Haddad, Vedat Deviren, and Christopher P. Ames
The purpose of this study was to compare rod fracture (RF) rates among three types of rod constructs (RCs) following lumbar pedicle subtraction osteotomy (PSO) for adult spinal deformity (ASD).
A retrospective review of consecutive patients with adult spinal deformity who were treated with lumbar PSO between 2007 and 2017 was performed. The minimum follow-up was 2 years. Three RCs were compared: standard (2 main rods), satellite (2 main rods with satellite rod), and nested (2 main rods and 2 short rods spanning osteotomy). Outcomes examined included RF rate, time to RF, pseudarthrosis, and reoperation. Multivariate analysis was used.
A total of 141 patients were included 55 with standard, 23 with satellite, and 63 with nested RCs. The mean age was 65.2 years and 34.8% of patients were male. Radiographic preoperative and postoperative results were as follows: sagittal vertical axis (11.0 vs 3.9 cm), lumbar lordosis (28.5° vs 57.1°), pelvic tilt (30.6° vs 21.0°), pelvic incidence (61.5° vs 60.0°), distance between central sacral vertical line and C7 plumb line (2.2 vs 1.5 cm), and scoliosis (18.9° vs 11.3°). The average time to RF was 12.4 months. Overall RF, bilateral RF, pseudarthrosis, and reoperation rates were 22.7%, 5.0%, 20.6%, and 17.7%, respectively. Standard RCs had a significantly higher RF (36.4% vs 13.0% vs 14.3%, p = 0.008), bilateral RF (35.0% vs 0.0% vs 0.0%, p = 0.021), pseudarthrosis (34.5% vs 8.7% vs 12.7%, p = 0.004), and reoperation (30.9% vs 4.3% vs 11.1%, p = 0.004) rates. Satellite RCs (OR 0.21, p = 0.015), nested RCs (OR 0.24, p = 0.003), and bone morphogenetic protein–2 (OR 0.28, p = 0.005) were independently associated with lower odds of RF.
Use of multiple rods in the satellite RC and nested RC groups was associated with lower rates of RF, pseudarthrosis, and reoperations following lumbar PSO. Bone morphogenetic protein–2 was associated with a reduction in RF rate as well.
Reduced proximal junctional failure with ligament augmentation in adult spinal deformity: a series of 242 cases with a minimum 1-year follow-up
Michael M. Safaee, Alexander F. Haddad, Marissa Fury, Patrick R. Maloney, Justin K. Scheer, Darryl Lau, Vedat Deviren, and Christopher P. Ames
Proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) are well-recognized complications of long-segment spinal fusion. Previous studies have suggested that ligament augmentation can decrease rates of PJF by reducing junctional stress and strengthening upper instrumented vertebrae (UIVs) and adjacent segments. However, there is a paucity of long-term data on the efficacy of ligament augmentation in preventing PJF. In this study, the authors sought to determine the effect of ligament augmentation on rates of PJF in a cohort of adult spinal deformity patients with at least 1 year of follow-up.
They conducted a retrospective analysis of ligament augmentation in a consecutive series of surgical patients with adult spinal deformity. Data on patient demographics, surgical characteristics, and surgery for PJF were collected. The minimum follow-up was 12 months. Univariate and multivariate analyses were performed to identify factors associated with reoperation for PJF.
The authors identified a total of 242 patients (166 women [68.6%]) with ligament augmentation whose mean age was 66 years. The mean number of fused levels was 10, with a UIV distribution as follows: 90 upper thoracic UIVs (37.2%) and 152 lower thoracic UIVs (62.8%). Compared to a historical cohort of 77 patients treated before implementation of ligament augmentation, reoperation for PJF was significantly lower with ligament augmentation (15.6% vs 3.3%, p < 0.001). In a multivariate model, only ligament augmentation (OR 0.184, 95% CI 0.071–0.478, p = 0.001) and number of fused levels (OR 0.762, 95% CI 0.620–0.937, p = 0.010) were associated with reductions in reoperation for PJF.
Ligament augmentation was associated with significant reductions in the rate of reoperation for PJF at 12 months in a cohort of adult spinal deformity patients. The most dramatic reduction was seen among patients with lower thoracic UIV. These data suggest that in appropriately selected patients, ligament augmentation may be a valuable adjunct for PJF reduction; however, long-term follow-up is needed.
Microsurgical resection of an intravestibular schwannoma: a review of surgical technique and management considerations
Ramin A. Morshed, Alexander F. Haddad, Kunal P. Raygor, Mary Jue Xu, Charles J. Limb, and Philip V. Theodosopoulos
Intravestibular schwannomas are rare tumors within the intralabyrinthine region and involve different management considerations compared to more common vestibular schwannomas. In this report, the authors review a case of a 52-year-old woman who presented with hearing loss and vestibular symptoms and was found to have a left intravestibular schwannoma. Given her debilitating vestibular symptoms, she underwent microsurgical resection. In this video, the authors review the relevant anatomy, surgical technique, and management considerations in these patients.
The video can be found here: https://stream.cadmore.media/r10.3171/2021.7.FOCVID2187
In Neurosurgical Focus: Video Volume 5: Issue 2 (Oct 2021): Vestibular Schwannoma Surgery
Pseudo-insular glioma syndrome: illustrative cases
Alexander F. Haddad, Jacob S. Young, Ramin A. Morshed, S. Andrew Josephson, Soonmee Cha, and Mitchel S. Berger
Lower-grade insular gliomas often appear as expansile and infiltrative masses on magnetic resonance imaging (MRI). However, there are nonneoplastic lesions of the insula, such as demyelinating disease and vasculopathies, that can mimic insular gliomas.
The authors report two patients who presented with headaches and were found to have mass lesions concerning for lower-grade insular glioma based on MRI obtained at initial presentation. However, on the immediate preoperative MRI obtained a few weeks later, both patients had spontaneous and complete resolution of the insular lesions.
Tumor mimics should always be in the differential diagnosis of brain masses, including those involving the insula. The immediate preoperative MRI (within 24–48 hours of surgery) must be compared carefully with the initial presentation MRI to assess interval change that suggests tumor mimics to avoid unnecessary surgical intervention.
In Journal of Neurosurgery: Case Lessons Volume 2 (2021): Issue 26 (Dec 2021)
Lymphocele after anterior lumbar interbody fusion: a review of 1322 patients
Justin K. Scheer, Alexander F. Haddad, Andrew K. Chan, Charles M. Eichler, Bobby Tay, Shane Burch, Dean Chou, Christopher P. Ames, and Praveen V. Mummaneni
Anterior lumbar interbody fusion (ALIF) is an effective surgical modality for many lumbar degenerative pathologies, but a rare and infrequently reported complication is postoperative lymphocele. The goals of the present study were to review a large consecutive series of patients who underwent ALIF at a high-volume institution, estimate the rate of lymphocele occurrence after ALIF, and investigate the outcomes of patients who developed lymphocele after ALIF.
A retrospective review of the electronic medical record was completed, identifying all patients (≥ 18 years old) who underwent at a minimum a single-level ALIF from 2012 through 2019. Postoperative spinal and abdominal images, as well as radiologist reports, were reviewed for mention of lymphocele. Clinical data were collected and reported.
A total of 1322 patients underwent a minimum 1-level ALIF. Of these patients, 937 (70.9%) had either postoperative abdominal or lumbar spine images, and the resulting lymphocele incidence was 2.1% (20/937 patients). The mean ± SD age was 67 ± 10.9 years, and the male/female ratio was 1:1. Patients with lymphocele were significantly older than those without lymphocele (66.9 vs 58.9 years, p = 0.006). In addition, patients with lymphocele had a greater number of mean levels fused (2.5 vs 1.8, p < 0.001) and were more likely to have undergone ALIF at L2–4 (95.0% vs 66.4%, p = 0.007) than patients without lymphocele. On subsequent multivariate analysis, age (OR 1.07, 95% CI 1.01–1.12, p = 0.013), BMI (OR 1.10, 95% CI 1.01–1.18, p = 0.021), and number of levels fused (OR 1.82, 95% CI 1.05–3.14, p = 0.032) were independent prognosticators of postoperative lymphocele development. Patients with symptomatic lymphocele were successfully treated with either interventional radiology (IR) drainage and/or sclerosis therapy and achieved radiographic resolution. The mean ± SD length of hospital stay was 9.1 ± 5.2 days. Ten patients (50%) were postoperatively discharged to a rehabilitation center: 8 patients (40%) were discharged to home, 1 (5%) to a skilled nursing facility, and 1 (5%) to a long-term acute care facility.
After ALIF, 2.1% of patients were diagnosed with radiographically identified postoperative lymphocele and had risk factors such as increased age, BMI, and number of levels fused. Most patients presented within 1 month postoperatively, and their clinical presentations included abdominal pain, abdominal distension, and/or wound complications. Of note, 25% of identified lymphoceles were discovered incidentally. Patients with symptomatic lymphocele were successfully treated with either IR drainage and/or sclerosis therapy and achieved radiographic resolution.