Caio M. Matias, Leonardo A. Frizon, Sean J. Nagel, Darlene A. Lobel and André G. Machado
The authors’ aim in this study was to evaluate placement accuracy and clinical outcomes in patients who underwent implantation of deep brain stimulation devices with the aid of frame-based stereotaxy and intraoperative MRI after induction of general anesthesia.
Thirty-three patients with movement disorders (27 with Parkinson’s disease) underwent implantation of unilateral or bilateral deep brain stimulation systems (64 leads total). All patients underwent the implantation procedure with standard frame-based techniques under general anesthesia and without microelectrode recording. MR images were acquired immediately after the procedure and fused to the preoperative plan to verify accuracy. To evaluate clinical outcome, different scales were used to assess quality of life (EQ-5D), activities of daily living (Unified Parkinson’s Disease Rating Scale [UPDRS] part II), and motor function (UPDRS part III during off- and on-medication and off- and on-stimulation states). Accuracy was assessed by comparing the coordinates (x, y, and z) from the preoperative plan and coordinates from the tip of the lead on intraoperative MRI and postoperative CT scans.
The EQ-5D score improved or remained stable in 71% of the patients. When in the off-medication/on-stimulation state, all patients reported significant improvement in UPDRS III score at the last follow-up (p < 0.001), with a reduction of 25.2 points (46.3%) (SD 14.7 points and 23.5%, respectively). There was improvement or stability in the UPDRS II scores for 68% of the Parkinson’s patients. For 2 patients, the stereotactic error was deemed significant based on intraoperative MRI findings. In these patients, the lead was removed and replaced after correcting for the error during the same procedure. Postoperative lead revision was not necessary in any of the patients. Based on findings from the last intraoperative MRI study, the mean difference between the tip of the electrode and the planned target was 0.82 mm (SD 0.5 mm, p = 0.006) for the x-axis, 0.67 mm (SD 0.5 mm, p < 0.001) for the y-axis, and 0.78 mm (SD 0.7 mm, p = 0.008) for the z-axis. On average, the euclidian distance was 1.52 mm (SD 0.6 mm). In patients who underwent bilateral implantation, accuracy was further evaluated comparing the first implanted side and the second implanted side. There was a significant mediolateral (x-axis) difference (p = 0.02) in lead accuracy between the first (mean 1.02 mm, SD 0.57 mm) and the second (mean 0.66 mm, SD 0.50 mm) sides. However, no significant difference was found for the y- and z-axes (p = 0.10 and p = 0.89, respectively).
Frame-based DBS implantation under general anesthesia with intraoperative MRI verification of lead location is safe, accurate, precise, and effective compared with standard implantation performed using awake intraoperative physiology. More clinical trials are necessary to directly compare outcomes of each technique.
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.
Bryan S. Lee, Jaes Jones, Min Lang, Rebecca Achey, Lu Dai, Darlene A. Lobel, Sean J. Nagel, Andre G. Machado and Francois Bethoux
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.
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.
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.
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.
Peter J. Grahn, Kendall H. Lee, Aimen Kasasbeh, Grant W. Mallory, Jan T. Hachmann, John R. Dube, Christopher J. Kimble, Darlene A. Lobel, Allan Bieber, Ju Ho Jeong, Kevin E. Bennet and J. Luis Lujan
Despite a promising outlook, existing intraspinal microstimulation (ISMS) techniques for restoring functional motor control after spinal cord injury are not yet suitable for use outside a controlled laboratory environment. Thus, successful application of ISMS therapy in humans will require the use of versatile chronic neurostimulation systems. The objective of this study was to establish proof of principle for wireless control of ISMS to evoke controlled motor function in a rodent model of complete spinal cord injury.
The lumbar spinal cord in each of 17 fully anesthetized Sprague-Dawley rats was stimulated via ISMS electrodes to evoke hindlimb function. Nine subjects underwent complete surgical transection of the spinal cord at the T-4 level 7 days before stimulation. Targeting for both groups (spinalized and control) was performed under visual inspection via dorsal spinal cord landmarks such as the dorsal root entry zone and the dorsal median fissure. Teflon-insulated stimulating platinum-iridium microwire electrodes (50 μm in diameter, with a 30- to 60-μm exposed tip) were implanted within the ventral gray matter to an approximate depth of 1.8 mm. Electrode implantation was performed using a free-hand delivery technique (n = 12) or a Kopf spinal frame system (n = 5) to compare the efficacy of these 2 commonly used targeting techniques. Stimulation was controlled remotely using a wireless neurostimulation control system. Hindlimb movements evoked by stimulation were tracked via kinematic markers placed on the hips, knees, ankles, and paws. Postmortem fixation and staining of the spinal cord tissue were conducted to determine the final positions of the stimulating electrodes within the spinal cord tissue.
The results show that wireless ISMS was capable of evoking controlled and sustained activation of ankle, knee, and hip muscles in 90% of the spinalized rats (n = 9) and 100% of the healthy control rats (n = 8). No functional differences between movements evoked by either of the 2 targeting techniques were revealed. However, frame-based targeting required fewer electrode penetrations to evoke target movements.
Clinical restoration of functional movement via ISMS remains a distant goal. However, the technology presented herein represents the first step toward restoring functional independence for individuals with chronic spinal cord injury.