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Sameer Kitab, Bryan S. Lee and Edward C. Benzel

OBJECTIVE

Using an imaging-based prospective comparative study of 709 eligible patients that was designed to assess lumbar spinal stenosis (LSS) in the ages between 16 and 82 years, the authors aimed to determine whether they could formulate radiological structural differences between the developmental and degenerative types of LSS.

METHODS

MRI structural changes were prospectively reviewed from 2 age cohorts of patients: those who presented clinically before the age of 60 years and those who presented at 60 years or older. Categorical degeneration variables at L1–S1 segments were compared. A multivariate comparative analysis of global radiographic degenerative variables and spinal dimensions was conducted in both cohorts. The age at presentation was correlated as a covariable.

RESULTS

A multivariate analysis demonstrated no significant between-groups differences in spinal canal dimensions and stenosis grades in any segments after age was adjusted for. There were no significant variances between the 2 cohorts in global degenerative variables, except at the L4–5 and L5–S1 segments, but with only small effect sizes. Age-related degeneration was found in the upper lumbar segments (L1–4) more than the lower lumbar segments (L4–S1). These findings challenge the notion that stenosis at L4–5 and L5–S1 is mainly associated with degenerative LSS.

CONCLUSIONS

Integration of all the morphometric and qualitative characteristics of the 2 LSS cohorts provides evidence for a developmental background for LSS. Based on these findings the authors propose the concept of LSS as a developmental syndrome with superimposed degenerative changes. Further studies can be conducted to clarify the clinical definition of LSS and appropriate management approaches.

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Syed K. Mehdi, Vincent J. Alentado, Bryan S. Lee, Thomas E. Mroz, Edward C. Benzel and Michael P. Steinmetz

OBJECTIVE

Ossification of the posterior longitudinal ligament (OPLL) is a pathological calcification or ossification of the PLL, predominantly occurring in the cervical spine. Although surgery is often necessary for patients with symptomatic neurological deterioration, there remains controversy with regard to the optimal surgical treatment. In this systematic review and meta-analysis, the authors identified differences in complications and outcomes after anterior or posterior decompression and fusion versus after decompression alone for the treatment of cervical myelopathy due to OPLL.

METHODS

A MEDLINE, SCOPUS, and Web of Science search was performed for studies reporting complications and outcomes after decompression and fusion or after decompression alone for patients with OPLL. A meta-analysis was performed to calculate effect summary mean values, 95% CIs, Q statistics, and I2 values. Forest plots were constructed for each analysis group.

RESULTS

Of the 2630 retrieved articles, 32 met the inclusion criteria. There was no statistically significant difference in the incidence of excellent and good outcomes and of fair and poor outcomes between the decompression and fusion and the decompression-only cohorts. However, the decompression and fusion cohort had a statistically significantly higher recovery rate (63.2% vs 53.9%; p < 0.0001), a higher final Japanese Orthopaedic Association score (14.0 vs 13.5; p < 0.0001), and a lower incidence of OPLL progression (< 1% vs 6.3%; p < 0.0001) compared with the decompression-only cohort. There was no statistically significant difference in the incidence of complications between the 2 cohorts.

CONCLUSIONS

This study represents the only comprehensive review of outcomes and complications after decompression and fusion or after decompression alone for OPLL across a heterogeneous group of surgeons and patients. Based on these results, decompression and fusion is a superior surgical technique compared with posterior decompression alone in patients with OPLL. These results indicate that surgical decompression and fusion lead to a faster recovery, improved postoperative neurological functioning, and a lower incidence of OPLL progression compared with posterior decompression only. Furthermore, decompression and fusion did not lead to a greater incidence of complications compared with posterior decompression only.

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The efficacy of intraoperative multimodal monitoring in pedicle subtraction osteotomies of the lumbar spine

Presented at the 2019 AANS/CNS Joint Section on Disorders of the Spine and Peripheral Nerves

Jianning Shao, Maxwell Y. Lee, Shreya Louis, Konrad Knusel, Bryan S. Lee, Dominic W. Pelle, Jason Savage, Joseph E. Tanenbaum, Thomas E. Mroz and Michael P. Steinmetz

OBJECTIVE

Iatrogenic spine injury remains one of the most dreaded complications of pedicle subtraction osteotomies (PSOs) and spine deformity surgeries. Thus, intraoperative multimodal monitoring (IOM), which has the potential to provide real-time feedback on spinal cord signal transmission, has become the gold standard in such operations. However, while the benefits of IOM are well established in PSOs of the thoracic spine and scoliosis surgery, its utility in PSOs of the lumbar spine has not been robustly documented. The authors’ aim was to determine the impact of IOM on outcomes in patients undergoing PSO of the lumbar spine.

METHODS

All patients older than 18 years who underwent lumbar PSOs at the authors’ institution from 2007 to 2017 were analyzed via retrospective chart review and categorized into one of two groups: those who had IOM guidance and those who did not. Perioperative complications were designated as the primary outcome measure and postoperative quality of life (QOL) scores, specifically the Parkinson’s Disease Questionnaire–39 (PDQ-39) and Patient Health Questionnaire–9 (PHQ-9), were designated as secondary outcome measures. Data on patient demographics, surgical and monitoring parameters, and outcomes were gathered, and statistical analysis was performed to compare the development of perioperative complications and QOL scores between the two cohorts. In addition, the proportion of patients who reached minimal clinically important difference (MCID), defined as an increase of 4.72 points in the PDQ-39 score or a decrease of 5 points in the PHQ-9 score, in the two cohorts was also determined.

RESULTS

A total of 95 patients were included in the final analysis. IOM was not found to significantly impact the development of new postoperative deficits (p = 0.107). However, the presence of preoperative neurological comorbidities was found to significantly correlate with postoperative neurological complications (p = 0.009). Univariate analysis showed that age was positively correlated with MCID achievement 3 months after surgery (p = 0.018), but this significance disappeared at the 12-month postoperative time point (p = 0.858). IOM was not found to significantly impact MCID achievement at either the 3- or 12-month postoperative period as measured by PDQ-39 (p = 0.398 and p = 0.156, respectively). Similarly, IOM was not found to significantly impact MCID achievement at either the 3- or 12-month postoperative period, as measured by PHQ-9 (p = 0.230 and p = 0.542, respectively). Multivariate analysis showed that female sex was significantly correlated with MCID achievement (p = 0.024), but this significance disappeared at the 12-month postoperative time point (p = 0.064). IOM was not found to independently correlate with MCID achievement in PDQ-39 scores at either the 3- or 12-month postoperative time points (p = 0.220 and p = 0.097, respectively).

CONCLUSIONS

In this particular cohort, IOM did not lead to statistically significant improvement in outcomes in patients undergoing PSOs of the lumbar spine (p = 0.220). The existing clinical equipoise, however, indicates that future studies in this arena are necessary to achieve systematic guidelines on IOM usage in PSOs of the lumbar spine.

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Rebecca L. Achey, Erin Yamamoto, Daniel Sexton, Christine Hammer, Bryan S. Lee, Robert S. Butler, Nicolas R. Thompson, Sean J. Nagel, Andre G. Machado and Darlene A. Lobel

OBJECTIVE

Deep brain stimulation (DBS) is an effective therapy for movement disorders such as idiopathic Parkinson’s disease (PD) and essential tremor (ET). However, some patients who demonstrate benefit on objective motor function tests do not experience postoperative improvement in depression or anxiety, 2 important components of quality of life (QOL). Thus, to examine other possible explanations for the lack of a post-DBS correlation between improved objective motor function and decreased depression or anxiety, the authors investigated whether patient perceptions of motor symptom severity might contribute to disease-associated depression and anxiety.

METHODS

The authors performed a retrospective chart review of PD and ET patients who had undergone DBS at the Cleveland Clinic in the period from 2009 to 2013. Patient demographics, diagnosis (PD, ET), motor symptom severity, and QOL measures (Primary Care Evaluation of Mental Disorders 9-item Patient Health Questionnaire [PHQ-9] for depression, Generalized Anxiety Disorder 7-item Scale [GAD-7], and patient-assessed tremor scores) were collected at 4 time points: preoperatively, postoperatively, 1-year follow-up, and 2-year follow-up. Multivariable prediction models with solutions for fixed effects were constructed to assess the correlation of predictor variables with PHQ-9 and GAD-7 scores. Predictor variables included age, sex, visit time, diagnosis (PD vs ET), patient-assessed tremor, physician-reported tremor, Unified Parkinson’s Disease Rating Scale part III (UPDRS-III) score, and patient-assessed tremor over time.

RESULTS

Seventy PD patients and 17 ET patients were included in this analysis. Mean postoperative and 1-year follow-up UPDRS-III and physician-reported tremor scores were significantly decreased compared with preoperative scores (p < 0.0001). Two-year follow-up physician-reported tremor was also significantly decreased from preoperative scores (p < 0.0001). Only a diagnosis of PD (p = 0.0047) and the patient-assessed tremor rating (p < 0.0001) were significantly predictive of depression. A greater time since surgery, in general, significantly decreased anxiety scores (p < 0.0001) except when a worsening of patient-assessed tremor was reported over the same time period (p < 0.0013).

CONCLUSIONS

Patient-assessed tremor severity alone was predictive of depression in PD and ET following DBS. This finding suggests that a patient’s perception of illness plays a greater role in depression than objective physical disability regardless of the time since surgical intervention. In addition, while anxiety may be attenuated by DBS, patient-assessed return of tremor over time can increase anxiety, highlighting the importance of long-term follow-up for behavioral health features in chronic neurological disorders. Together, these data suggest that the patient experience of motor symptoms plays a role in depression and anxiety—a finding that warrants consideration when evaluating, treating, and following movement disorder patients who are candidates for DBS.

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Bryan D. Choi, Daniel K. Lee, Jimmy C. Yang, Caroline M. Ayinon, Christine K. Lee, Douglas Maus, Bob S. Carter, Fred G. Barker II, Pamela S. Jones, Brian V. Nahed, Daniel P. Cahill, Reiner B. See, Mirela V. Simon and William T. Curry

OBJECTIVE

Intraoperative seizures during craniotomy with functional mapping is a common complication that impedes optimal tumor resection and results in significant morbidity. The relationship between genetic mutations in gliomas and the incidence of intraoperative seizures has not been well characterized. Here, the authors performed a retrospective study of patients treated at their institution over the last 12 years to determine whether molecular data can be used to predict the incidence of this complication.

METHODS

The authors queried their institutional database for patients with brain tumors who underwent resection with intraoperative functional mapping between 2005 and 2017. Basic clinicopathological characteristics, including the status of the following genes, were recorded: IDH1/2, PIK3CA, BRAF, KRAS, AKT1, EGFR, PDGFRA, MET, MGMT, and 1p/19q. Relationships between gene alterations and intraoperative seizures were evaluated using chi-square and two-sample t-test univariate analysis. When considering multiple predictive factors, a logistic multivariate approach was taken.

RESULTS

Overall, 416 patients met criteria for inclusion; of these patients, 98 (24%) experienced an intraoperative seizure. Patients with a history of preoperative seizure and those treated with antiepileptic drugs prior to surgery were less likely to have intraoperative seizures (history: OR 0.61 [95% CI 0.38–0.96], chi-square = 4.65, p = 0.03; AED load: OR 0.46 [95% CI 0.26–0.80], chi-square = 7.64, p = 0.01). In a univariate analysis of genetic markers, amplification of genes encoding receptor tyrosine kinases (RTKs) was specifically identified as a positive predictor of seizures (OR 5.47 [95% CI 1.22–24.47], chi-square = 5.98, p = 0.01). In multivariate analyses considering RTK status, AED use, and either 2007 WHO tumor grade or modern 2016 WHO tumor groups, the authors found that amplification of the RTK proto-oncogene, MET, was most predictive of intraoperative seizure (p < 0.05).

CONCLUSIONS

This study describes a previously unreported association between genetic alterations in RTKs and the occurrence of intraoperative seizures during glioma resection with functional mapping. Future models estimating intraoperative seizure risk may be enhanced by inclusion of genetic criteria.

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The effect of C2–3 disc angle on postoperative adverse events in cervical spondylotic myelopathy

Presented at the 2018 AANS/CNS Joint Section on Disorders of the Spine and Peripheral Nerves

Bryan S. Lee, Kevin M. Walsh, Daniel Lubelski, Konrad D. Knusel, Michael P. Steinmetz, Thomas E. Mroz, Richard P. Schlenk, Iain H. Kalfas and Edward C. Benzel

OBJECTIVE

Complete radiographic and clinical evaluations are essential in the surgical treatment of cervical spondylotic myelopathy (CSM). Prior studies have correlated cervical sagittal imbalance and kyphosis with disability and worse health-related quality of life. However, little is known about C2–3 disc angle and its correlation with postoperative outcomes. The present study is the first to consider C2–3 disc angle as an additional radiographic predictor of postoperative adverse events.

METHODS

A retrospective chart review was performed to identify patients with CSM who underwent surgeries from 2010 to 2014. Data collected included demographics, baseline presenting factors, and postoperative outcomes. Cervical sagittal alignment variables were measured using the preoperative and postoperative radiographs. Univariable logistic regression analyses were used to explore the association between dependent and independent variables, and a multivariable logistic regression model was created using stepwise variable selection.

RESULTS

The authors identified 171 patients who had complete preoperative and postoperative radiographic and outcomes data. The overall rate of postoperative adverse events was 33% (57/171), and postoperative C2–3 disc angle, C2–7 sagittal vertical axis, and C2–7 Cobb angle were found to be significantly associated with adverse events. Inclusion of postoperative C2–3 disc angle in the analysis led to the best prediction of adverse events. The mean postoperative C2–3 disc angle for patients with any postoperative adverse event was 32.3° ± 17.2°, and the mean for those without any adverse event was 22.4° ± 11.1° (p < 0.0001).

CONCLUSIONS

In the present retrospective analysis of postoperative adverse events in patients with CSM, the authors found a significant association between C2–3 disc angle and postoperative adverse events. They propose that C2–3 disc angle be used as an additional parameter of cervical spinal sagittal alignment and predictor for operative outcomes.

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Bryan S. Lee, Jaes Jones, Min Lang, Rebecca Achey, Lu Dai, Darlene A. Lobel, Sean J. Nagel, Andre G. Machado and Francois Bethoux

OBJECTIVE

Multiple sclerosis (MS) is a chronic autoimmune disease that causes demyelination and axonal loss. Walking difficulties are a common and debilitating symptom of MS; they are usually caused by spastic paresis of the lower extremities. Although intrathecal baclofen (ITB) therapy has been reported to be an effective treatment for spasticity in MS, there is limited published evidence regarding its effects on ambulation. The goal of this study was to characterize ITB therapy outcomes in ambulatory patients with MS.

METHODS

Data from 47 ambulatory patients with MS who received ITB therapy were analyzed retrospectively. Outcome measures included Modified Ashworth Scale, Spasm Frequency Scale, Numeric Pain Rating Scale, and the Timed 25-Foot Walk. Repeated-measures ANOVA was used to test for changes in outcome measures between baseline and posttreatment (6 months and 1 year). Significance was set at p < 0.05. Descriptive data are expressed as the mean ± SD, and results of the repeated-measures ANOVA tests and the Wilcoxon rank-sum test are expressed as the mean ± SEM.

RESULTS

There was a statistically significant reduction in the following variables: 1) aggregate lower-extremity Modified Ashworth Scale scores (from 14.8 ± 1.0 before ITB therapy to 5.8 ± 0.8 at 6 months posttreatment and 6.4 ± 0.9 at 1 year [p < 0.05]); 2) Numeric Pain Rating Scale scores (4.4 ± 0.5 before ITB, 2.8 ± 0.5 at 6 months, and 2.4 ± 0.4 at 1 year [p < 0.05]); 3) spasm frequency (45.7% of the patients reported a spasm frequency of ≥ 1 event per hour before ITB therapy, whereas 15.6% and 4.3% of the patients reported the same at 6 months and 1 year posttreatment, respectively [p < 0.05]); and 4) the number of oral medications taken for spasticity (p < 0.05). Of the 47 patients, 34 remained ambulatory at 6 months, and 32 at 1 year posttreatment. There was no statistically significant change in performance on the Timed 25-Foot Walk test over time for those patients who remained ambulatory.

CONCLUSIONS

In this retrospective study, the authors found that ITB therapy is effective in reducing spasticity and related symptoms in ambulatory patients with MS. Because the use of ITB therapy is increasing in ambulatory patients with MS, randomized, prospective studies are important to help provide a more useful characterization of the effects of ITB therapy on ambulation.

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Benjamin B. Whiting, Bryan S. Lee, Vaidehi Mahadev, Hamid Borghei-Razavi, Sanchit Ahuja, Xuefei Jia, Alireza M. Mohammadi, Gene H. Barnett, Lilyana Angelov, Shobana Rajan, Rafi Avitsian and Michael A. Vogelbaum

OBJECTIVE

Current management of gliomas involves a multidisciplinary approach, including a combination of maximal safe resection, radiotherapy, and chemotherapy. The use of intraoperative MRI (iMRI) helps to maximize extent of resection (EOR), and use of awake functional mapping supports preservation of eloquent areas of the brain. This study reports on the combined use of these surgical adjuncts.

METHODS

The authors performed a retrospective review of patients with gliomas who underwent minimal access craniotomy in their iMRI suite (IMRIS) with awake functional mapping between 2010 and 2017. Patient demographics, tumor characteristics, intraoperative and postoperative adverse events, and treatment details were obtained. Volumetric analysis of preoperative tumor volume as well as intraoperative and postoperative residual volumes was performed.

RESULTS

A total of 61 patients requiring 62 tumor resections met the inclusion criteria. Of the tumors resected, 45.9% were WHO grade I or II and 54.1% were WHO grade III or IV. Intraoperative neurophysiological monitoring modalities included speech alone in 23 cases (37.1%), motor alone in 24 (38.7%), and both speech and motor in 15 (24.2%). Intraoperative MRI demonstrated residual tumor in 48 cases (77.4%), 41 (85.4%) of whom underwent further resection. Median EOR on iMRI and postoperative MRI was 86.0% and 98.5%, respectively, with a mean difference of 10% and a median difference of 10.5% (p < 0.001). Seventeen of 62 cases achieved an increased EOR > 15% related to use of iMRI. Seventeen (60.7%) of 28 low-grade gliomas and 10 (30.3%) of 33 high-grade gliomas achieved complete resection. Significant intraoperative events included at least temporary new or worsened speech alteration in 7 of 38 cases who underwent speech mapping (18.4%), new or worsened weakness in 7 of 39 cases who underwent motor mapping (18.0%), numbness in 2 cases (3.2%), agitation in 2 (3.2%), and seizures in 2 (3.2%). Among the patients with new intraoperative deficits, 2 had residual speech difficulty, and 2 had weakness postoperatively, which improved to baseline strength by 6 months.

CONCLUSIONS

In this retrospective case series, the combined use of iMRI and awake functional mapping was demonstrated to be safe and feasible. This combined approach allows one to achieve the dual goals of maximal tumor removal and minimal functional consequences in patients undergoing glioma resection.