Direct Optic Tract Stimulation in Deep Brain Stimulation for Dystonia: A Case Report

Movement disorder surgery Part I: historical background and principle of surgery

Cortical visual evoked potentials recorded after optic tract near field stimulation during GPi-DBS in non-cooperative patients

Introduction: Precise electrode placement is critical for successful Globus Pallidus Internus (GPi) Deep Brain Stimulation (DBS). However, accurately identifying the ventral GPi border near the optic tract (OT) is challenging. Microelectrode recording (MER) signals can be ambiguous in dystonia,1 and the common use of general anesthesia precludes patient feedback for OT localization.2 We investigated direct OT stimulation with cortical visual evoked potential (CVEP) recording as an objective method to delineate the ventral GPi boundary and optimize electrode placement.Method: Nine patients undergoing bilateral GPi-DBS, some under general anesthesia, were prospectively studied with ethics approval. After initial MER-guided targeting, direct monopolar stimulation (3 Hz, 50μs, 1-3mA) was delivered near the OT to elicit CVEPs, recorded from occipital scalp electrodes. The N40-P70 wave amplitude was correlated with electrode position. The final DBS lead was placed immediately dorsal to the site of maximal CVEP amplitude. Post-operative MRI verified placement, and clinical outcomes were assessed at follow-up.Results: Direct OT stimulation consistently elicited N40-P70 CVEPs in all 18 hemispheres. Amplitudes increased significantly with proximity to the OT while latencies remained stable, providing a reliable localization signal. CVEP-guided placement resulted in optimal ventral GPi electrode locations confirmed on post-operative imaging. All patients had significant clinical improvement without visual side effects.Discussion: Our results show CVEP monitoring is a reliable method to define the ventral GPi limit, overcoming the limitations of subjective visual phosphenes, especially under general anesthesia where patient feedback is absent.1,3 This is particularly useful in dystonia surgery where MER signals can be ambiguous.2 Using an objective landmark for the OT enhances safety by preventing unwanted stimulation and avoiding deep exploratory penetrations, confirming its utility as a practical intraoperative tool.3 Conclusions: Direct OT stimulation with CVEP monitoring is a safe and effective adjunct to MER for GPi-DBS. It refines targeting by providing a clear physiological landmark for the ventral GPi border, improving accuracy and safety, especially for patients under general anesthesia.

The aim was to investigate the temporal response properties of magnocellular, parvocellular, and koniocellular visual pathways using increment/decrement changes in contrast to elicit visual evoked potentials (VEPs). Static achromatic and isoluminant chromatic gratings were generated on a monitor. Chromatic gratings were modulated along red/green (R/G) or subject-specific tritanopic confusion axes, established using a minimum distinct border criterion. Isoluminance was determined using minimum flicker photometry. Achromatic and chromatic VEPs were recorded to contrast increments and decrements of 0.1 or 0.2 superimposed on the static gratings (masking contrast 0-0.6). Achromatic increment/decrement changes in contrast evoked a percept of apparent motion when the spatial frequency was low; VEPs to such stimuli were positive in polarity and largely unaffected by high levels of static contrast, consistent with transient response mechanisms. VEPs to finer achromatic gratings showed marked attenuation as static contrast was increased. Chromatic VEPs to R/G or tritan chromatic contrast increments were of negative polarity and showed progressive attenuation as static contrast was increased, in keeping with increasing desensitization of the sustained responses of the color-opponent visual pathways. Chromatic contrast decrement VEPs were of positive polarity and less sensitive to pattern adaptation. The relative contribution of sustained/transient mechanisms to achromatic processing is spatial frequency dependent. Chromatic contrast increment VEPs reflect the sustained temporal response properties of parvocellular and koniocellular pathways. Cortical VEPs can provide an objective measure of pattern adaptation and can be used to probe the temporal response characteristics of different visual pathways.

Purpose To investigate the temporal response properties of magnocellular, parvocellular and koniocellular pathways using contrast increment/decrement visual evoked potentials (VEPs). Methods Static achromatic and isoluminant chromatic gratings were generated on a monitor (Michelson contrast 0.05 to 0.6). Chromatic gratings were modulated along R/G or subject‐specific tritanopic confusion axes, established using a minimum distinct border criterion. Isoluminance was determined using minimum flicker photometry for a 1‐degree field. Achromatic and chromatic VEPs were recorded to contrast increments and decrements of 0.1 superimposed on the static gratings. Field size for Tritan gratings was restricted to 3‐degrees to minimize the effects of luteal pigment. Results Achromatic increment/decrement VEPs were positive in polarity and largely unaffected by high levels of static contrast at low spatial frequencies. Responses to finer achromatic gratings showed marked attenuation as static contrast was increased. Chromatic VEPs to R/G or Tritan chromatic contrast increments were of negative polarity and showed progressive attenuation as static contrast was increased. Chromatic contrast decrement VEPs were of positive polarity and less sensitive to pattern adaptation. Conclusion The relative contribution of sustained and transient response mechanisms to achromatic processing is spatial‐frequency dependent. Chromatic contrast increment VEPs are highly sensitive to pattern adaptation consistent with high stimulus selectivity and the sustained temporal response properties of the parvocellular and koniocellular pathways.

Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) has been demonstrated to be an effective therapy for the treatment of primary dystonia as well as tardive dystonia. Results for other forms of secondary dystonia have been less consistent. Although a number of target sites have been explored for the treatment of dystonia, most notably the motor thalamus, the target of choice remains the sensorimotor portion of the GPi. Although the optimal site within the GPi has not been determined, most centers agree that the optimal site involves the posteroventral lateral "sensorimotor" portion of the GPi. Microelectrode recording (MER) can be used to identify boundaries of the GPi and nearby white matter tracts, including the corticospinal tract and optic tract, and the sensorimotor GPi. However, whether or not the use of MER leads to improved outcomes compared with procedures performed without MER has not been determined. Currently, there is no evidence to support or refute the hypothesis that mapping structures with MER provides better short- or long-term outcomes. Centers using MER do not report a preference of one system over another, but there have not been any studies to compare the relative benefits or risks of using more than 1 electrode simultaneously. Comparison studies of different target structures and targeting techniques in dystonia have not been performed. Additional research, which includes comparative studies, is needed to advance our understanding and optimization of DBS targets, techniques, and approaches along with their relative benefits and risks in dystonia.

Introduction: Deep brain stimulation (DBS) is an established treatment for Parkinson’s disease (PD). The traditional method for accurate implantation is awake microelectrode recordings (MERs) to map out the borders of the target nucleus. However, a significant portion of patients are unable to tolerate awake surgical procedures. Asleep MER techniques under different general anesthesia regimens have been described with variable effects on recording quality and required a lower inhaled sevoflurane level to obtain single unit recordings. Hence, a reliable method for asleep MER mapping is needed without compromising patient safety and comfort. We aimed to assess the feasibility and quality of basal ganglia MER under general anesthesia using inhalational agents including adding nitrous oxide as an adjunct to sevoflurane (N2O-GA). Methods: This study retrospectively examined PD patients undergoing DBS implantation targeting either the subthalamic nucleus (STN) or the globus pallidus internus (GPi) at a single center. Anesthetic data on end-tidal (ET) sevoflurane and nitrous oxide, with the derived minimum alveolar concentration (MAC) were captured during the time of MER mapping. We evaluated the feasibility of identifying target nuclei borders, the quality of neuronal unit isolation, and the physiological dimensions of the targeted nuclei. We calculated the concordance between the nuclei sizes based on MER mapping and imaging. We also reported the firing characteristics of isolated units. Results: We identified 18 patients (34 nuclei) who underwent STN (n = 11) and GPi (n = 7) DBS implantation. Background activity changes were reliable in all patients for border identification. The length of the tract identified by MER was highly concordant with the anatomical tract length identified by postoperative imaging (concordance correlation coefficient: 0.84, p < 0.001). Firing in both nuclei showed higher bursting rates. Pallidal cells showed typical firing patterns with “pauser” cells in the GPe and continuous firing in the GPi. No complications were observed during follow-up. A total of 16 patients had MER data available for offline analysis. We identified 516 units (single/multi) across MER 28 tracts (STN = 284, GP = 232). In the 14 patients received the N2O-GA, anesthetic depth was maintained at 0.97 ± 0.06 MAC, compared to 0.525 ± 0.04 MAC in the sevoflurane-only cases. Conclusion: MER under N2O-GA is feasible for DBS target nuclei identification for both STN and GPi and offers a safe and accurate surgical approach for PD patients unable to tolerate awake mapping.

EPV 7. PAS-induced plasticity relates to symptom severity and benefit from deep brain stimulation in cervical dystonia

Previous literature has consistently revealed attentional modulation of the Visual Evoked Potential (VEP) response to achromatic pattern reversal stimuli but little to no attentional modulation of the VEP response to chromatic pattern onsets. Magnetic Resonance Imaging (MRI) research, however, has reported modulation of the responses to both achromatic and chromatic pattern reversal stimuli. Numerous methodological differences including mode of presentation, stimulus contrast, and attentional demand, make comparison of these results difficult. In this study, we report the results of experiments using comparable perceptual contrasts, pattern reversals, and a coextensive and highly-demanding, multiple object tracking (MOT) task. Our findings support prior VEP results indicating that although achromatic VEPs are modulated by attention, chromatic VEPs are more robust to attentional modulation, even for highly demanding distractor tasks. We also found that when compared to a non-attentional condition, the attenuation of the VEP when attending to the MOT task was greater in magnitude than the enhancement of the VEP when attending to the VEP stimulus. This supports prior conclusions, that while avoiding active distraction is likely important, insuring an "attentive state" is not always necessary when recording VEPs. Further experiments are underway to investigate why attentional modulation of chromatic signals in early visual cortex are observed in MRI but not VEP recordings.

It has been difficult to obtain anatomic and functional information about the visual pathway during neurosurgical operations. The aim of this study was to combine the information of the visual evoked potentials (VEPs) and the anatomic navigation of the optic radiation by diffusion tensor imaging-based tractography for functional monitoring of the visual pathway. The subjects were two patients with brain lesions adjacent to the visual pathway. Diffusion tensor imaging-based tractography of the optic radiation was performed by selecting appropriate regions of interest and by fractional anisotropy. During surgery, cortical VEPs were recorded continuously under general anesthesia with sevoflurane. In Patient 2, the results of optic radiation tractography were imported to a neuronavigation system to better understand the spatial relationships between the lesions and the visual pathway (functional neuronavigation). In Patient 1, the lesion did not seem to be attached to the optic radiation, and VEP profiles remained stable during resection. In Patient 2, who had a lesion adjacent to the posterior horn of the lateral ventricle, VEPs suddenly diminished when resection reached the optic radiation as illustrated on the neuronavigation system. As a result, complete left hemianopia developed after surgery in Patient 2. We confirmed functional correlations of the results of diffusion tensor imaging-based tractography by monitoring intraoperative VEPs. The combination of continuous VEP and optic-radiation tractography is reliable to monitor the visual function and is helpful in performing neurosurgical planning near the visual pathway.

The most common anesthetic technique for patients undergoing insertion of deep brain stimulators (DBS) is local anesthesia with or without conscious sedation as this facilitates intraoperative microelectrode recordings (MERs) for target localization. However, general anesthesia (GA) may be needed in some of the patients especially those with dystonia. The purpose of our study was to determine the effects of GA on MERs from pallidal neurons in patients with dystonia undergoing DBS implantation surgery. After IRB approval, we retrospectively reviewed the medical records of all patients who had insertion of DBS from January 2009 to December 2013. Data collected and analyzed included demographics, indications for DBS, targets of insertion, MER, and anesthetic management. From the records we identified patients with dystonia who received GA for DBS insertion. We then compared the MER data under GA with the data from patients who had surgery under local anesthesia only during the same time period. Because of the small sample size, the effects of various anesthetic regiments on MER and localization of target nuclei were compared qualitatively. Of the 435 patients who underwent DBS insertion during the study period, 20 (4.3%) patients had GA for the procedure. Dystonia was the most common indication for GA (16/20 patients, 80%). Good-quality MER data obtained from 10 patients with dystonia under GA was compared with 8 patients who had no sedation for the procedure. Administration of GA made target localization difficult due to suppression of both spontaneous and evoked neuronal discharges from internal globus pallidus. Although not studied systematically, propofol (>100 mcg/kg/min) seemed to suppress pallidal discharges more than GA with a lower dose of propofol (<75 mcg/kg/min), remifentanil, and 0.2% to 0.4% end-tidal sevoflurane or desflurane. Our retrospective review suggests that there was a difference in spontaneous and evoked neuronal discharges with MER performed under GA compared with no sedation. MER recordings during GA appeared most robust during a combination of anesthetics including low-dose propofol infusion, remifentanil, and a low concentration of either sevoflurane or desflurane. Our findings can inform a power analysis to determine the sample size that would be required to prospectively test the hypothesis that there is a difference in spontaneous and evoked neuronal discharges with MER performed under GA compared with no sedation.

EP 10. Pallidal stimulation affects speech fluency in dystonia

Optical tract stimulated visual evoked potential (VEP) is useful during deep brain stimulation (DBS) in the globus pallidus internum (Gpi) for the treatment of primary dystonia. Recordings of cortical VEPs obtained after stimulation of the optic tract may be a potential option to microelectrode recordings (MERs), since optic tract lies just beneath the best target for Gpi DBS.

Long-term results show that benefits from chronic deep brain stimulation in dystonia are maintained for many years. Despite this, the neurophysiological long-term consequences of treatment and their relationship to clinical effects are not well understood. Previous studies have shown that transcranial magnetic stimulation measures of abnormal long-term potentiation-like plasticity (paired associative stimulation) and GABAa-ergic inhibition (short-interval intracortical inhibition), which are seen in dystonia, normalize after several months of deep brain stimulation. In the present study, we examine the same measures in a homogenous group of 10 DYT1 gene-positive patients after long-term deep brain stimulation treatment for at least 4.5 years. Recordings were made 'on' deep brain stimulation and after stopping deep brain stimulation for 2 days. The results show that: (i) on average, prior to discontinuing deep brain stimulation, the paired associative stimulation response was almost absent and short-interval intracortical inhibition was reduced compared with normal. This pattern differs from that in both healthy volunteers and from the typical pattern of enhanced plasticity and reduced inhibition seen in deep brain stimulation-naïve dystonia. It is similar to that seen in untreated Parkinson's disease and may relate to thus far unexplained clinical phenomena like parkinsonian symptoms that have sometimes been observed in patients treated with deep brain stimulation. (ii) Overall, there was no change in average physiological or clinical status when deep brain stimulation was turned off for 2 days, suggesting that deep brain stimulation had produced long-term neural reorganization in the motor system. (iii) However, there was considerable variation between patients. Those who had higher levels of plasticity when deep brain stimulation was 'on', had the best retention of clinical benefit when deep brain stimulation was stopped and vice versa. This may indicate that better plasticity is required for longer term retention of normal movement when deep brain stimulation is off. (iv) Patients with the highest plasticity 'on' deep brain stimulation were those who had been receiving stimulation with the least current drain. This suggests that it might be possible to 'shape' deep brain stimulation of an individual patient to maximize beneficial neurophysiological patterns that have an impact on clinical status. The results are relevant for understanding long-term consequences and management of deep brain stimulation in dystonia.

INTRODUCTION Recent studies show similar clinical outcomes in Parkinson's disease (PD) patients treated by deep brain stimulation (DBS) under general anesthesia without microelectrode recording (MER), so-called “asleep” DBS, compared to historical cohorts undergoing “awake” DBS with MER guidance. Very few studies, however, include internal controls. This study compares clinical outcomes following globus pallidus interna (GPi) and subthalamic nucleus (STN) DBS using awake and asleep techniques at a single institution. METHODS PD patients undergoing awake or asleep bilateral GPi or STN DBS were prospectively followed. The primary outcome measure was stimulation-induced change in motor function 6 months postoperatively, measured by the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) with the patient off medication. Secondary outcomes included change in quality of life, measured by the 39-item Parkinson's Disease Questionnaire (PDQ-39), change in levodopa daily equivalent dose (LEDD), stereotactic accuracy, stimulation parameters, and adverse events. RESULTS &gt;Six-month outcome data were available for 133 patients treated over 45 months (78 GPi [16 awake, 62 asleep] and 55 STN [14 awake and 41 asleep]). UPDRS-III score improvement with stimulation did not differ between awake and asleep groups for GPi (awake = 20.8 points [38.5%], asleeP = 18.8 points [37.5%], P = 0.45) or STN (awake = 21.6 points [40.3%], asleeP = 26.1 points [48.8%], P = 0.20) targets. The percentage improvement in PDQ-39 and LEDD was similar for awake and asleep groups for both GPi (P = 0.80, P = 0.54, respectively) and STN cohorts (P = 0.85, P = 0.49, respectively). CONCLUSION In PD patients, bilateral GPi and STN DBS utilizing the asleep method resulted in motor, quality-of-life, and medication reduction outcomes comparable to the awake method.