Implantable Subdural Cortical Stimulation for Chronic Intractable Pain Treatment-The Mayo Experience and Review of Literature.

OBJECTIVES: Motor cortex stimulation (MCS) is an effective technique in treating chronic intractable pain for some patients. However, most studies are small case series (n < 20). Heterogeneity in technique and patient selection makes it difficult to draw consistent conclusions. In this study, we present one of the largest case series of subdural MCS. MATERIALS AND METHODS: Medical records of patients who underwent MCS at our institute between 2007 and 2020 were reviewed. Studies with at least 15 patients were summarized for comparison. RESULTS: The study included 46 patients. Mean age was 56.2 ± 12.5 years (SD). Mean follow-up was 57.2 ± 41.9 months. Male-to-female ratio was 13:33. Of the 46 patients, 29 had neuropathic pain in trigeminal nerve territory/anesthesia dolorosa; nine had postsurgical/posttraumatic pain; three had phantom limb pain; two had postherpetic pain, and the rest had pain secondary to stroke, chronic regional pain syndrome, and tumor. The baseline numeric rating pain scale (NRS) was 8.2 ± 1.8 of 10, and the latest follow-up score was 3.5 ± 2.9 (mean improvement of 57.3%). Responders comprised 67% (31/46)(NRS ≥ 40% improvement). Analysis showed no correlation between percentage of improvement and age (p = 0.352) but favored male patients (75.3% vs 48.7%, p = 0.006). Seizures occurred in 47.8% of patients (22/46) at some point but were all self-limiting, with no lasting sequelae. Other complications included subdural/epidural hematoma requiring evacuation (3/46), infection (5/46), and cerebrospinal fluid leak (1/46). These complications resolved with no long-term sequelae after further interventions. CONCLUSION: Our study further supports the use of MCS as an effective treatment modality for several chronic intractable pain conditions and provides a benchmark to the current literature.

Comparison of the impact of skull density ratio with alternative skull metrics on magnetic resonance-guided focused ultrasound thalamotomy for tremor.

OBJECTIVE: One of the key metrics that is used to predict the likelihood of success of MR-guided focused ultrasound (MRgFUS) thalamotomy is the overall calvarial skull density ratio (SDR). However, this measure does not fully predict the sonication parameters that would be required or the technical success rates. The authors aimed to assess other skull characteristics that may also contribute to technical success. METHODS: The authors retrospectively studied consecutive patients with essential tremor who were treated by MRgFUS at their center between 2017 and 2021. They evaluated the correlation between the different treatment parameters, particularly maximum power and energy delivered, with a range of patients' skull metrics and demographics. Machine learning algorithms were applied to investigate whether sonication parameters could be predicted from skull density metrics alone and whether including combined local transducer SDRs with overall calvarial SDR would increase model accuracy. RESULTS: A total of 62 patients were included in the study. The mean age was 77.1 (SD 9.2) years, and 78% of treatments (49/63) were performed in males. The mean SDR was 0.51 (SD 0.10). Among the evaluated metrics, SDR had the highest correlation with the maximum power used in treatment (ρ = -0.626, p < 0.001; proportion of local SDR values ≤ 0.8 group also had ρ = +0.626, p < 0.001) and maximum energy delivered (ρ = -0.680, p < 0.001). Machine learning algorithms achieved a moderate ability to predict maximum power and energy required from the local and overall SDRs (accuracy of approximately 80% for maximum power and approximately 55% for maximum energy), and high ability to predict average maximum temperature reached from the local and overall SDRs (approximately 95% accuracy). CONCLUSIONS: The authors compared a number of skull metrics against SDR and showed that SDR was one of the best indicators of treatment parameters when used alone. In addition, a number of other machine learning algorithms are proposed that may be explored to improve its accuracy when additional data are obtained. Additional metrics related to eventual sonication parameters should also be identified and explored.

Clinical Characteristics of Patients with Gait Instability after MR-Guided Focused Ultrasound Thalamotomy.

Background: MRgFUS thalamotomy is an incisionless procedure which effectively treats patients with tremor, although the procedure can result in adverse side effects including gait instability. By determining whether certain pre-existing conditions predispose patients to developing gait instability, we will be able to better counsel patients regarding risk of MRgFUS thalamotomy. Methods: All patients diagnosed with essential tremor, mixed tremor syndrome, or tremor predominant Parkinson disease who underwent MRgFUS thalamotomy at Mayo Clinic, Rochester between 2017 and 2020 were retrospectively reviewed. Baseline demographic and clinical data was extracted, and gait symptoms were compared pre- versus post-operatively. Results: Of 45 patients who underwent MRgFUS thalamotomy, 42 had at least one follow-up visit within twelve months and were included in the study. 39 patients had essential tremor, 1 had tremor predominant Parkinson disease, and 2 had mixed tremor syndrome. 19 out of 42 patients (45%) had gait decline. There were 10 (24%) females, and median age was 77.6 years (IQR 71.5-83.2). Older age was not correlated with gait decline (p = 0.82). Patients with a history of neuropathy and joint replacements were more likely to have gait decline after MRgFUS thalamotomy (p = 0.0099 and p = 0.0376). Patients with pre-existing gait aids were not more likely to have gait instability (p = 0.20). Conclusion: Patients who undergo MRgFUS thalamotomy for each of the tremor conditions, have an increased risk of experiencing gait decline, when there is a pre-procedure history of peripheral neuropathy, or joint replacement surgery. Older age or pre-existing gait aid use is not associated with worsened gait outcomes. Highlights: Patients who undergo MRgFUS thalamotomy for tremor syndromes have a significantly increased risk of experiencing gait decline when there is comorbid peripheral neuropathy or joint replacementOlder age or pre-existing gait aid use is not associated with worsened gait outcomes.

MRI and tractography techniques to localize the ventral intermediate nucleus and dentatorubrothalamic tract for deep brain stimulation and MR-guided focused ultrasound: a narrative review and update.

The thalamic ventral intermediate nucleus (VIM) can be targeted for treatment of tremor by several procedures, including deep brain stimulation (DBS) and, more recently, MR-guided focused ultrasound (MRgFUS). To date, such targeting has relied predominantly on coordinate-based or atlas-based techniques rather than directly targeting the VIM based on imaging features. While general regional differences of features within the thalamus and some related white matter tracts can be distinguished with conventional imaging techniques, internal nuclei such as the VIM are not discretely visualized. Advanced imaging methods such as quantitative susceptibility mapping (QSM) and fast gray matter acquisition T1 inversion recovery (FGATIR) MRI and high-field MRI pulse sequences that improve the ability to image the VIM region are emerging but have not yet been shown to have reliability and accuracy to serve as the primary method of VIM targeting. Currently, the most promising imaging approach to directly identify the VIM region for clinical purposes is MR diffusion tractography.In this review and update, the capabilities and limitations of conventional and emerging advanced methods for evaluation of internal thalamic anatomy are briefly reviewed. The basic principles of tractography most relevant to VIM targeting are provided for familiarization. Next, the key literature to date addressing applications of DTI and tractography for DBS and MRgFUS is summarized, emphasizing use of direct targeting. This literature includes 1-tract (dentatorubrothalamic tract [DRT]), 2-tract (pyramidal and somatosensory), and 3-tract (DRT, pyramidal, and somatosensory) approaches to VIM region localization through tractography.The authors introduce a 3-tract technique used at their institution, illustrating the oblique curved course of the DRT within the inferior thalamus as well as the orientation and relationship of the white matter tracts in the axial plane. The utility of this 3-tract tractography approach to facilitate VIM localization is illustrated with case examples of variable VIM location, targeting superior to the anterior commissure-posterior commissure plane, and treatment in the setting of pathologic derangement of thalamic anatomy. Finally, concepts demonstrated with these case examples and from the prior literature are synthesized to highlight several potential advantages of tractography for VIM region targeting.

Global network modulation during thalamic stimulation for Tourette syndrome.

Background and objectives: Deep brain stimulation (DBS) of the thalamus is a promising therapeutic alternative for treating medically refractory Tourette syndrome (TS). However, few human studies have examined its mechanism of action. Therefore, the networks that mediate the therapeutic effects of thalamic DBS remain poorly understood. Methods: Five participants diagnosed with severe medically refractory TS underwent bilateral thalamic DBS stereotactic surgery. Intraoperative fMRI characterized the blood oxygen level-dependent (BOLD) response evoked by thalamic DBS and determined whether the therapeutic effectiveness of thalamic DBS, as assessed using the Modified Rush Video Rating Scale test, would correlate with evoked BOLD responses in motor and limbic cortical and subcortical regions. Results: Our results reveal that thalamic stimulation in TS participants has wide-ranging effects that impact the frontostriatal, limbic, and motor networks. Thalamic stimulation induced suppression of motor and insula networks correlated with motor tic reduction, while suppression of frontal and parietal networks correlated with vocal tic reduction. These regions mapped closely to major regions of interest (ROI) identified in a nonhuman primate model of TS. Conclusions: Overall, these findings suggest that a critical factor in TS treatment should involve modulation of both frontostriatal and motor networks, rather than be treated as a focal disorder of the brain. Using the novel combination of DBS-evoked tic reduction and fMRI in human subjects, we provide new insights into the basal ganglia-cerebellar-thalamo-cortical network-level mechanisms that influence the effects of thalamic DBS. Future translational research should identify whether these network changes are cause or effect of TS symptoms.

The Impact of Mirth-Inducing Ventral Striatal Deep Brain Stimulation on Functional and Effective Connectivity.

Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is an investigational therapy for treatment-resistant obsessive-compulsive disorder. The ability of VC/VS DBS to evoke spontaneous mirth in patients, often accompanied by smiling and laughter, is clinically well documented. However, the neural correlates of DBS-evoked mirth remain poorly characterized. Patients undergoing VC/VS DBS surgery underwent intraoperative evaluation in which mirth-inducing and non-mirth-inducing stimulation localizations were identified. Using dynamic causal modeling (DCM) for fMRI, the effect of mirth-inducing DBS on functional and effective connectivity among established nodes in limbic cortico-striato-thalamo-cortical (CSTC) circuitry was investigated. Both mirth-inducing and non-mirth-inducing VC/VS DBS consistently resulted (conjunction, global null, family-wise error-corrected P < 0.05) in activation of amygdala, ventral striatum, and mediodorsal thalamus. However, only mirth-inducing DBS resulted in functional inhibition of anterior cingulate cortex. Dynamic causal modeling revealed that mirth-inducing DBS enhanced effective connectivity from anterior cingulate to ventral striatum, while attenuating connectivity from thalamus to ventral striatum relative to non-mirth-inducing stimulation. These results suggest that DBS-evoked mood elevation is accompanied by distinct patterns of limbic thalamocortical connectivity. Using the novel combination of DBS-evoked mood alteration and functional MRI in human subjects, we provide new insights into the network-level mechanisms that influence affect.

Centromedian-Parafascicular Complex Deep Brain Stimulation for Tourette Syndrome: A Retrospective Study.

Deep brain stimulation (DBS) of the thalamic centromedian/parafascicular (CM-Pf) complex has been reported as a promising treatment for patients with severe, treatment-resistant Tourette syndrome (TS). In this study, safety and clinical outcomes of bilateral thalamic CM-Pf DBS were reviewed in a series of 12 consecutive patients with medically refractory TS, 11 of whom met the criteria of postsurgical follow-up at our institution for at least 2 months. Five patients were followed for a year or longer. Consistent with many patients with TS, all patients had psychiatric comorbidities. Tic severity and frequency were measured by using the Yale Global Tic Severity Scale (YGTSS) over time (average, 26 months) in 10 subjects. One patient was tested at 2-week follow-up only and thus was excluded from group YGTSS analysis. Final YGTSS scores differed significantly from the preoperative baseline score. The average (n=10) improvement relative to baseline in the total score was 54% (95% CI, 37-70); average improvement relative to baseline in the YGTSS Motor tic, Phonic tic, and Impairment subtests was 46% (95% CI, 34-64), 52% (95% CI, 34-72), and 59% (95% CI, 39-78), respectively. There were no intraoperative complications. After surgery, 1 subject underwent wound revision because of a scalp erosion and wound infection; the implanted DBS system was successfully salvaged with surgical revision and combined antibiotic therapy. Stimulation-induced adverse effects did not prevent the use of the DBS system, although 1 subject is undergoing a trial period with the stimulator off. This surgical series adds to the literature on CM-Pf DBS and supports its use as an effective and safe therapeutic option for severe refractory TS.

Chronic subthreshold subdural cortical stimulation for the treatment of focal epilepsy originating from eloquent cortex.

Medically refractory epilepsy remains a major medical problem worldwide. Although some patients are eligible for surgical resection of seizure foci, a proportion of patients are ineligible for a variety of reasons. One such reason is that the foci reside in eloquent cortex of the brain and therefore resection would result in significant morbidity. This retrospective study reports our experience with a novel neurostimulation technique for the treatment of these patients. We identified three patients who were ineligible for surgical resection of the intracranially identified seizure focus because it resided in eloquent cortex, who underwent therapeutic trial of focal cortical stimulation delivered through the subdural monitoring grid. All three patients had a significant reduction in seizures, and two went on to permanent implantation, which resulted in long-term reduction in seizure frequency. In conclusion, this small case report provides some evidence of proof of concept of the role of targeted continuous neocortical neurostimulation in the treatment of medically refractory focal epilepsy, and provides support for ongoing investigations into this treatment modality.