Jules M. Nazzaro

Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy.

Purpose:  We report a multicenter, double‐blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization‐related epilepsy.

Long-term benefits in quality of life after unilateral thalamic deep brain stimulation for essential tremor.

OBJECT The goal of this study was to evaluate short- and long-term benefits in quality of life (QOL) after unilateral deep brain stimulation (DBS) for essential tremor (ET). METHODS Patients who received unilateral DBS of the ventral intermediate nucleus of the thalamus between 1997 and 2010 and who had at least 1 follow-up evaluation at least 1 year after surgery were included. Their QOL was assessed with the Parkinson Disease Questionnaire-39 (PDQ-39), and ET was measured with the Fahn-Tolosa-Marin tremor rating scale (TRS) prior to surgery and then postoperatively with the stimulation in the on mode. RESULTS Ninety-one patients (78 at 1 year; 42 at 2-7 years [mean 4 years]; and 22 at >7-12 years [mean 9 years]) were included in the analysis. The TRS total, targeted tremor, and activities of daily living (ADL) scores were significantly improved compared with presurgical scores up to 12 years. The PDQ-39 ADL, emotional well-being, stigma, and total scores were significantly improved up to 7 years after surgery compared with presurgical scores. At the longest follow-up, only the PDQ-39 stigma score was significantly improved, and the PDQ-39 mobility score was significantly worsened. CONCLUSIONS Unilateral thalamic stimulation significantly reduces ET and improves ADL scores for up to 12 years after surgery, as measured by the TRS. The PDQ-39 total score and the domains of ADL, emotional well-being, and stigma were significantly improved up to 7 years. Although scores were improved compared with presurgery, other than stigma, these benefits did not remain significant at the longest (up to 12 years) follow-up, probably related in part to changes due to aging and comorbidities.

Effect of deep brain stimulation of the subthalamic nucleus upon the contralateral subthalamic nucleus in Parkinson disease

High frequency stimulation (HFS) of the subthalamic nucleus (STN) is an effective treatment of idiopathic Parkinson disease (PD). Exactly how HFS works remains unclear. Although HFS of the STN is most effective in improving contralateral motor functions, clinical studies have shown bilateral beneficial effects suggesting that unilateral STN HFS affects both ipsilateral and contralateral basal ganglia networks. In this study we evaluated the effect of STN HFS upon the contralateral STN in 14 PD subjects. The neural recordings were done during stereotaxic neurosurgery for implantation of deep brain stimulation electrodes in the second STN. Neuronal activity of the STN was analyzed before and during two minutes of HFS. There was a significant increase in the multiunit spiking activity of the STN during HFS in the contralateral STN. Our study provides direct electrophysiological evidence that the STN HFS is associated with increased activity of the contralateral STN. These findings suggest that increased STN output underlies therapeutic mechanisms of action of HFS.

Transient, symptomatic, post-operative, non-infectious hypodensity around the deep brain stimulation (DBS) electrode

Post-operative edema around a deep brain stimulation (DBS) lead is a rare presentation. Post-operative edema that is symptomatic, self-limiting and not due to infection, in particular, is rarely reported as a separate entity. We aim to discuss the morphological characteristics of post-operative edema around a DBS lead with an insight into possible etiologies and management. We present eight patients with symptomatic, self-limiting peri-electrode edema post-DBS electrode implantation who presented post-operatively with distinct clinical presentations with imaging that revealed a hypodense area in the white matter surrounding the DBS electrode. Local and systemic tests for infection were negative. The edema resolved over time without surgical intervention. The etiology of the edema remains obscure. The transient nature of the edema and benign course with rapid and full resolution in all our patients cautions against any hasty decision to explant the electrode, in the absence of any obvious signs of infection.

Use of Brain MRI after Deep Brain Stimulation Hardware Implantation

ABSTRACT The objective of this study was to examine the experience with and safety of brain 1.5 Tesla (T) magnetic resonance imaging (MRI) in deep brain stimulation (DBS) patients. This was a retrospective review of brain MRI scanning performed on DBS patients at the University of Kansas Medical Center between January 1995 and December 2007. A total of 249 DBS patients underwent 445 brain 1.5 T MRI scan sessions encompassing 1,092 individual scans using a transmit-receive head coil, representing the cumulative scanning of 1,649 DBS leads. Patients with complete implanted DBS systems as well as those with externalized leads underwent brain imaging. For the majority of scans, specific absorption rates localized to the head (SARH) were estimated and in all cases SARH were higher than that specified in the present product labeling. There were no clinical or hardware related adverse events secondary to brain MRI scanning. Our data should not be extrapolated to encourage MRI scanning beyond the present labeling. Rather, our data may contribute to further defining safe MRI scanning parameters that might ultimately be adopted in future product labeling as more centers report in detail their experiences.

Chapter 13 - Deep brain stimulation for essential tremor

Essential tremor is the most common tremor disorder and is characterized by a postural and kinetic tremor. Most commonly, the disease involves the upper extremities, although other body parts may be affected. Essential tremor is seen most often in adults and may markedly limit abilities to perform daily activities. Medications often fail to control the tremor adequately. In the past, ventral intermediate nucleus of the thalamus (VIM) thalamotomy was the surgery of choice for medication-resistant patients with disabling tremor. With technological advances, deep brain stimulation (DBS) to the VIM has replaced thalamotomy as the operation of choice for patients with essential tremor, given the heightened risk of permanent neurological deficits associated with ablative surgery. Multiple studies have demonstrated that unilateral VIM DBS has significant short- and long-term benefits for targeted tremor. Unilateral VIM DBS may also improve head and voice tremor, although most commonly bilateral stimulation is required for adequate control. However, bilateral thalamic stimulation is associated with a higher incidence of neurological deficits, particularly speech and gait problems. Investigations of DBS of other brain target areas for essential tremor, such as the posterior subthalamic area and the subthalamic nucleus, are ongoing.

Isolation of the brain-related factor of the error between intended and achieved position of deep brain stimulation electrodes implanted into the subthalamic nucleus for the treatment of Parkinson's disease.

OBJECTIVE Although a few studies have quantified errors in the implantation of deep brain stimulation electrodes into the subthalamic nucleus (STN), a significant trend in error direction has not been reported. We have previously found that an error in axial plane, which is of most concern because it cannot be compensated for during deep brain stimulation programming, had a posteromedial trend. We hypothesized that this trend results from a predominance of a directionally oriented error factor of brain origin. Accordingly, elimination of nonbrain (technical) error factors could augment this trend. Thus, implantation accuracy could be improved by anterolateral compensation during target planning. METHODS Surgical technique was revised to minimize technical error factors. During 22 implantations, targets were selected on axial magnetic resonance imaging scans up to 1.5 mm anterolateral from the STN center. Using fusion of postoperative computed tomographic and preoperative magnetic resonance imaging scans, implantation errors in the axial plane were obtained and compared with distances from the lead to the STN to evaluate the benefit of anterolateral compensation. RESULTS Twenty errors and the mean error had a posteromedial direction. The average distances from the lead to the target and to the STN were 1.7 mm (range, 0.8–3.1 mm) and 1.1 mm (range, 0.1–1.9 mm), respectively. The difference between the 2 distances was significant (paired t test, P < 0.0001). The lower parts of the lead were consistently bent in the posteromedial direction on postoperative scout computed tomographic scans, suggesting that a brain-related factor is responsible for the reported error. CONCLUSION Elimination of the technical factors of error during STN deep brain stimulation implantation can result in a consistent posteromedial error. Implantation accuracy may be improved by compensation for this error in advance.

MDS-UPDRS to assess non-motor symptoms after STN DBS for Parkinson's disease

Objective: To determine if the non-motor sections of the Movement Disorder Societys (MDS) version of the Unified Parkinsons Disease Rating Scale (UPDRS) could supplement the original UPDRS as a patient completed assessment of changes in non-motor symptoms in Parkinsons disease (PD) patients after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS). Methods: Thirty PD patients who underwent bilateral STN DBS were assessed using the total UPDRS and the non-motor sections of the MDS-UPDRS prior to surgery and one year following surgery. This study focuses on non-motor symptoms as assessed by Part I of the UPDRS and Part 1A and 1B of the MDS-UPDRS. Results: One year following surgery, no individual non-motor symptoms or the total mentation score of the UPDRS were significantly changed. In comparison, the MDS-UPDRS showed significant improvements in sleep and urinary problems and a trend towards improvement in anxiety, constipation, daytime sleepiness, fatigue and pain. Conclusions: This study provides evidence that the MDS-UPDRS non-motor sections, when completed by the patients, can supplement the original version of the UPDRS as an effective method of measuring changes in non-motor symptoms after DBS. It also reinforces the benefits of bilateral STN DBS on non-motor symptoms of PD.

Deep brain stimulation lead-contact heating during 3T MRI: single- versus dual-channel pulse generator configurations

Background: Magnetic resonance imaging (MRI) after deep brain stimulation (DBS) carries the risk of heating at the lead-contacts within the brain. Objective/Hypothesis: To compare the effect of single- and dual-channel DBS implantable pulse generator (IPG) configurations on brain lead-contact heating during 3T MRI. Methods: A phantom with bilateral brain leads and extensions connected to two single-channel IPGs or a dual-channel right or left IPG was utilized. Using a transmit/receive head coil, seven scan sequences were conducted yielding a range of head-specific absorption rates (SAR-H). Temperature changes (ΔT) at the bilateral 0 and 3 lead-contacts were recorded, and normalized temperatures (ΔT/SAR-H) and slopes defining the ΔT/SAR-H over the SAR-H range were compared. Results: Greater heating was strongly correlated with higher SAR-H in all configurations. For each scan sequence, the ΔT/SAR-H of single-channel left lead-contacts was significantly greater than the ΔT/SAR-H of either dual-channel configuration. The slope defining the relationship between ΔT and SAR-H for the single-channel left lead (1.68°C/SAR-H) was significantly greater (p < 0.0001) than the ΔT/SAR-H slope for the single-channel right lead (0.97°C/SAR-H), both of which were significantly greater (p < 0.0001) than the ΔT/SAR-H slopes of left or right leads (range 0.68 to 0.70°C/SAR-H) in the dual-channel configurations. There were no significant differences in ΔT/SAR-H slope values between the dual-channel configurations. Conclusion: DBS hardware configuration using bilateral single-channel versus unilateral dual-channel IPGs significantly affects DBS lead-contact heating during 3T MRI brain scanning.

The importance of testing deep brain stimulation lead impedances before final lead implantation.

Background: In the setting of a deep brain stimulation (DBS) lead with defective electrical circuitry, potential patient morbidity and additional surgery may be avoided if impedance testing of the brain lead is performed prior to final lead implantation. In the present report, detection of a short circuit upon lead placement and prior to lead anchoring was detected utilizing recently released DBS hardware and software (Medtronic, Minneapolis, MN). This report suggests that neurosurgeons need to be aware and consider the use of the newly available DBS testing equipment. Methods: During the first DBS lead placement in a 69-year-old man with advanced idiopathic Parkinsons disease undergoing bilateral subthalamic nucleus DBS over staged procedures, test stimulation and lead impedance testing were accomplished prior to lead anchoring. An external neurostimulator (ENS) was affixed to an updated clinician programmer and connected to the DBS lead with a screening cable specific for the ENS and DBS. Results: Impedance testing demonstrated a short circuit involving the 1 and 3 lead-electrode bipolar combination in a visually intact lead. The lead was replaced, repeat impedance testing and test stimulation were completed and the intact lead was secured. Subsequent DBS surgeries were completed uneventfully. The lead abnormality was verified by the manufacturer. Conclusions: This case highlights a new method to test DBS lead circuitry at the time of placement. The method may also be employed to directly test lead integrity when localizing a DBS system short or open circuit of unclear etiology. Our case suggests that the method is valuable and should be utilized.