Joshua L. Golubovsky, Arbaz Momin, Nicolas R. Thompson and Michael P. Steinmetz
Bertolotti syndrome is a rare spinal condition that causes low-back pain due to a lumbosacral transitional vertebra (LSTV), which is a pseudoarticulation between the fifth lumbar transverse process and the sacral ala. Bertolotti syndrome patients are rarely studied, particularly with regard to their quality of life. This study aimed to examine the quality of life and prior treatments in patients with Bertolotti syndrome at first presentation to the authors’ center in comparison with those with lumbosacral radiculopathy.
This study was a retrospective cohort analysis of patients with Bertolotti syndrome and lumbosacral radiculopathy due to disc herniation seen at the authors’ institution’s spine center from 2005 through 2018. Diagnoses were confirmed with provider notes and imaging. Variables collected included demographics, diagnostic history, prior treatment, patient-reported quality of life metrics, and whether or not they underwent surgery at the authors’ institution. Propensity score matching by age and sex was used to match lumbosacral radiculopathy patients to Bertolotti syndrome patients. Group comparisons were made using t-tests, Fisher’s exact test, Mann-Whitney U-tests, Cox proportional hazards models, and linear regression models where variables found to be different at the univariate level were included as covariates.
The final cohort included 22 patients with Bertolotti syndrome who had patient-reported outcomes data available and 46 propensity score–matched patients who had confirmed radiculopathy due to disc herniation. The authors found that Bertolotti syndrome patients had significantly more prior epidural steroid injections (ESIs) and a longer time from symptom onset to their first visit. Univariate analysis showed that Bertolotti syndrome patients had significantly worse Patient-Reported Outcomes Measurement Information System (PROMIS) mental health T-scores. Adjustment for prior ESIs and time from symptom onset revealed that Bertolotti syndrome patients also had significantly worse PROMIS physical health T-scores. Time to surgery and other quality of life metrics did not differ between groups.
Patients with Bertolotti syndrome undergo significantly longer workup and more ESIs and have worse physical and mental health scores than age- and sex-matched patients with lumbosacral radiculopathy. However, both groups of patients had mild depression and clinically meaningful reduction in their quality of life according to all instruments. This study shows that Bertolotti syndrome patients have a condition that affects them potentially more significantly than those with lumbosacral radiculopathy, and increased attention should be paid to these patients to improve their workup, diagnosis, and treatment.
Daniel Lubelski, Nicolas R. Thompson, Sachin Bansal, Thomas E. Mroz, Daniel J. Mazanec, Edward C. Benzel and Tagreed Khalaf
The goal of this study was to determine whether pretreatment depression is predictive of quality of life (QOL) improvement for patients with lumbar spinal stenosis (LSS) who are treated conservatively.
This retrospective cohort study included patients with LSS and concordant neurogenic claudication who were treated nonoperatively at a single institution between September 2010 and March 2013. Patient QOL measures were recorded pretreatment and then 4 months after treatment. Pretreatment depression was assessed using the Patient Health Questionnaire–9 (PHQ-9). Successful outcome was defined as posttreatment improvement in EuroQol-5D (EQ-5D) index or in Pain and Disability Questionnaire (PDQ) scores. Regression analysis was performed to identify independent predictors of outcome while controlling for confounding variables.
A total of 502 patients were included in the study. The average age for these patients was 66.1 years, with 51% female and 90.6% white. After adjusting for baseline demographic and clinical variables, there was a statistically significant association between baseline PHQ-9 score and posttreatment change in EQ-5D index (β = −0.007, p = 0.0002). All other things being equal, a patient with a baseline PHQ-9 score of 0 (no depression) would be expected to improve in the EQ-5D index by 0.14 points (greater than the minimum clinically important difference) more than would a patient with a baseline PHQ-9 score of 20 (major depression). There was no significant association between baseline PHQ-9 score and change in Pain and Disability Questionnaire scores.
When controlling for other baseline characteristics, severely depressed patients with LSS who are treated nonoperatively have significantly less improvement in their QOL compared with those with little or no depression. These data are similar to the negative predictive effects of depression on posttreatment QOL following lumbar fusion surgery.
Jaes C. Jones, Jacob A. Miller, Dattanand M. Sudarshana, Nicolas R. Thompson, Edward C. Benzel and Thomas E. Mroz
In 2009, 2 randomized controlled trials demonstrated no improvement in pain following vertebral augmentation compared with sham surgery. However, a recent randomized trial demonstrated significant pain relief in patients following vertebroplasty compared to controls treated with conservative medical management. This study is a retrospective review of prospectively collected patient-reported quality of life (QOL) outcomes. The authors hypothesized that vertebral augmentation procedures offer a QOL benefit, but that this benefit would be diminished in patients with a history of depression and/or in patients undergoing vertebral augmentation at more than 1 level.
Multivariable linear regression was used to identify predictors of postoperative pain assessed using the Pain Disability Questionnaire (PDQ), Patient Health Questionnaire 9 (PHQ-9), and EQ-5D scores. Eleven candidate predictors were selected a priori: age, sex, smoking history, coronary artery disease, depression, diabetes, procedure location (thoracic, lumbar), BMI, prior spine surgery, procedure indication (metastases, osteoporosis/osteopenia, other), and number of levels (1, 2, 3, or more).
A total of 143 patients were included in the study. For each 10-year increase in age, postoperative PDQ scores decreased (improved) by 9.7 points (p < 0.001). Patients with osteoporosis/osteopenia had significantly higher (worse) postoperative PDQ scores (+17.97, p = 0.028) than patients with metastatic lesions. Male sex was associated with higher (worse) postoperative PHQ-9 scores (+2.48, p = 0.010). Compared to single-level augmentation, operations at 2 levels were associated with significantly higher PHQ-9 scores (+2.58, p = 0.017). Current smokers had significantly lower PHQ-9 scores (−1.98, p = 0.023) than never smokers. No predictors were associated with significantly different EQ-5D score.
Variables associated with worse postoperative PDQ scores included younger age and osteoporosis/osteopenia. Variables associated with decreased (better) postoperative PHQ-9 scores included female sex, single operative vertebral level, and positive smoking status (i.e., current smoker). These clinically relevant predictors may permit identification of patients who may benefit from vertebral augmentation.
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
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.
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.
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).
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.
Daniel Lubelski, Matthew D. Alvin, Sergiy Nesterenko, Swetha J. Sundar, Nicolas R. Thompson, Edward C. Benzel and Thomas E. Mroz
Studies comparing surgical treatments for cervical spondylotic myelopathy (CSM) are heterogeneous, using a variety of different quality of life (QOL) outcomes and myelopathy-specific measures. This study sought to evaluate the relationship of these measures to each other, and to better understand their use in evaluating patients with CSM.
A retrospective study was performed in all patients with CSM who underwent either ventral or dorsal cervical spine surgery at a single tertiary-care institution between January 2008 and July 2013. Severity of myelopathy was assessed pre- and postoperatively using both the Nurick scale and the modified Japanese Orthopaedic Association (mJOA) classification of disability. Prospectively collected QOL outcomes data included Pain Disability Questionnaire (PDQ), Patient Health Questionnaire–9 (PHQ-9), and EQ-5D. Spearman rank correlations were calculated to assess the construct convergent validity for each pair of health status measures (HSMs). To assess each HSM’s ability to discriminate favorable EQ-5D index, we performed receiver operating characteristic (ROC) curve analysis and assessed the area under the curve (AUC).
A total of 119 patients were included. The PDQ total score had the highest correlation with EQ-5D index (Spearman’s rho = −0.82). Neither of the myelopathy scales (mJOA or Nurick) had strong correlations between themselves (0.41) or with the other QOL measures (absolute value range 0.13–0.49). In contrast, the QOL measures correlated relatively well with each other (absolute value range 0.68–0.97). For predicting favorable EQ-5D outcomes, PDQ total score had an AUC of 0.909. The AUCs were significantly greater for the QOL measures in comparison with the myelopathy measures (AUCs were 0.677 and 0.607 for mJOA and Nurick scale scores, respectively).
The authors found that all included measures of QOL and CSM-specific (mJOA or Nurick scale) measures were valid and responsive. The PDQ was the most predictive of positive QOL after surgery (as measured by the EQ-5D index) for patients with CSM. The substantially lower correlation between myelopathy and QOL outcomes, compared with the various QOL measures themselves, suggests that these questionnaires are measuring different aspects of the patient experience. Solely assessing the myelopathy or disease-specific signs and symptoms is likely insufficient to fully understand and appreciate clinical outcome in its totality. These questionnaire types should be used together to best evaluate patients pre- and postoperatively.
Niklas Marklund, Florence M. Bareyre, Nicolas C. Royo, Hilaire J. Thompson, Anis K. Mir, M. Sean Grady, Martin E. Schwab and Tracy K. McIntosh
Central nervous system axons regenerate poorly after traumatic brain injury (TBI), partly due to inhibitors such as the protein Nogo-A present in myelin. The authors evaluated the efficacy of anti–Nogo-A monoclonal antibody (mAb) 7B12 administration on the neurobehavioral and cognitive outcome of rats following lateral fluid-percussion brain injury, characterized the penetration of the 7B12 or control antibodies into target brain regions, and evaluated the effects of Nogo-A inhibition on hemispheric tissue loss and sprouting of uninjured motor tracts in the cervical cord. To elucidate a potential molecular response to Nogo-A inhibition, we evaluated the effects of 7B12 on hippocampal GAP-43 expression.
Beginning 24 hours after lateral fluid-percussion brain injury or sham injury in rats, the mAb 7B12 or control antibody was infused intracerebroventricularly over 14 days, and behavior was assessed over 4 weeks.
Immunoreactivity for 7B12 or immunoglobulin G was detected in widespread brain regions at 1 and 3 weeks postinjury. The brain-injured animals treated with 7B12 showed improvement in cognitive function (p < 0.05) at 4 weeks but no improvement in neurological motor function from 1 to 4 weeks postinjury compared with brain-injured, vehicle-treated controls. The enhanced cognitive function following inhibition of Nogo-A was correlated with an attenuated postinjury downregulation of hippocampal GAP-43 expression (p < 0.05).
Increased GAP-43 expression may be a novel molecular mechanism of the enhanced cognitive recovery mediated by Nogo-A inhibition after TBI in rats.
Phoenix, Arizona • March 6–9, 2013
2010 AANS Annual Meeting Philadelphia, Pennsylvania May 1–5, 2010