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Comparison of Dentatorubrothalamic Tractography Methods Based on the Anatomy of the Rubral Wing

Berger, Assaf; Chung, Jongchul; Schnurman, Zane; Stepanov, Valentin; Pan, Ling; Shepherd, Timothy M; Mogilner, Alon
BACKGROUND AND OBJECTIVES/OBJECTIVE:Precise localization of the dentatorubrothalamic (DRT) tract can facilitate anatomic targeting in MRI-guided high-intensity focused ultrasound (HIFU) thalamotomy and thalamic deep brain stimulation for tremor. The anatomic segment of DRT fibers adjacent to the ventral intermediate nucleus of the thalamus (VIM), referred to as the rubral wing (RW), may be directly visualized on the fast gray matter acquisition T1 inversion recovery. We compared reproducibility, lesion overlap, and clinical outcomes when reconstructing the DRT tract using a novel anatomically defined RW region of interest, DRT-RW, to an existing tractography method based on the posterior subthalamic area region of interest (DRT-PSA). METHODS:We reviewed data of 23 patients with either essential tremor (n = 18) or tremor-predominant Parkinson's disease (n = 5) who underwent HIFU thalamotomy, targeting the VIM. DRT tractography, ipsilateral to the lesion, was created based on either DRT-PSA or DRT-RW. Volume sections of each tract were created and dice similarity coefficients were used to measure spatial overlap between the 2 tractographies. Post-HIFU lesion size and location (on postoperative T2 MRI) was correlated with tremor outcomes and side effects for both DRT tractography methods and the RW itself. RESULTS:DRT-PSA passed through the RW and DRT-RW intersected with the ROIs of the DRT-PSA in all 23 cases. A higher percentage of the RW was ablated in patients who achieved tremor control (18.9%, 95% CI 15.1, 22.7) vs those without tremor relief (6.7%, 95% CI% 0, 22.4, P = .017). In patients with tremor control 6 months postoperatively (n = 12), those with side effects (n = 6) had larger percentages of their tracts ablated in comparison with those without side effects in both DRT-PSA (44.8, 95% CI 31.8, 57.8 vs 24.2%, 95% CI 12.4, 36.1, P = .025) and DRT-RW (35.4%, 95% CI 21.5, 49.3 vs 21.7%, 95% CI 12.7, 30.8, P = .030). CONCLUSION/CONCLUSIONS:Tractography of the DRT could be reconstructed by direct anatomic visualization of the RW on fast gray matter acquisition T1 inversion recovery-MRI. Anatomic planning is expected to be quicker, more reproducible, and less operator-dependent.
PMID: 38289086
ISSN: 2332-4260
CID: 5627462

Dorsal Root Ganglion Stimulation as a Salvage Therapy Following Failed Spinal Cord Stimulation

Chapman, Kenneth B; Spiegel, Matthew A; van Helmond, Noud; Patel, Kiran V; Yang, Ajax; Yousef, Tariq A; Mandelberg, Nataniel; Deer, Timothy; Mogilner, Alon Y
INTRODUCTION/BACKGROUND:Spinal cord stimulation (SCS) can provide long-term pain relief for various chronic pain conditions, but some patients have no relief with trial stimulation or lose efficacy over time. To "salvage" relief in patients who do not respond or have lost efficacy, alternative stimulation paradigms or anatomical targets can be considered. Dorsal root ganglion stimulation (DRG-S) has a different mechanism of action and anatomical target than SCS. OBJECTIVES/OBJECTIVE:We assessed DRG-S salvage therapy outcomes in patients who did not respond to SCS or had lost SCS efficacy. MATERIALS AND METHODS/METHODS:We retrospectively included consecutive patients from 2016 to 2020 who were salvaged with DRG-S after failed SCS trials (<50% pain reduction) or who had lost efficacy after permanent SCS. We compared numerical rating scale (NRS) pain, Oswestry disability index (ODI), health-related quality of life (EuroQol five-dimensions five-level), and oral morphine equivalent (OME) opioid requirements before DRG-S salvage and at patients' last follow-up. RESULTS:A total of 60 patients who had failed SCS were salvaged with DRG-S. The mean age was 56 ± 12 years, and the most common diagnoses were complex regional pain syndrome (n = 24) and failed back surgery syndrome (n = 24). The most common failed modalities included tonic (n = 32), Burst (n = 18), and high-frequency (n = 10) SCS. The median follow-up duration of salvage DRG-S was 34 months. With DRG-S, NRS decreased (8.7 ± 1.2 to 3.8 ± 2.1), and OME declined (median 23 mg to median 15 mg), whereas EuroQol 5D scores increased (0.40 ± 0.15 to 0.71 ± 0.15), and ODI improved (64 ± 14% to 31 ± 18%) (all p < 0.05). CONCLUSIONS:DRG-S can be used in patients with chronic pain who have previously failed to receive persistent benefit from SCS.
PMID: 35760751
ISSN: 1525-1403
CID: 5281082

Spinal Cord Stimulation: New Waveforms and Technology

London, Dennis; Mogilner, Alon
The efficacy of spinal cord stimulation for treating chronic pain has encouraged the development of a wide variety of different technologies for stimulation. In this review, the authors first discuss how parameters of stimulation determine the stimulation waveform. They then discuss new stimulation waveforms, including high frequency and burst stimulation, and the evidence supporting their use. Finally, the authors turn to emerging technologies and techniques including dorsal root ganglion stimulation, wireless stimulation, and closed-loop stimulation.
PMID: 35718398
ISSN: 1558-1349
CID: 5281732

Dorsal root ganglion stimulation device explantation: A multicenter pooled data analysis

Chapman, Kenneth B; Yang, Ajax; Mogilner, Alon Y; Mandelberg, Nataniel; Patel, Kiran V; Lubenow, Timothy; Deer, Timothy; Kallewaard, Jan Willem; van Helmond, Noud
INTRODUCTION/BACKGROUND:Dorsal root ganglion stimulation (DRG-S) is a relatively new neuromodulation modality. Therefore, data on long-term device explantation rates is limited. This investigation aimed to assess DRG-S device explantation rates at long-term follow-up. METHODS:We retrospectively reviewed individuals implanted with DRG-S in four pain centers from different continuous periods between April 2016 to September 2020. We recorded patient demographics, diagnoses, duration to explantation or last follow-up, treatment complications, and failure etiologies. RESULTS:A total of 249 patients with 756 leads and a mean 27-month follow-up were included. The mean age was 55 ± 15 years; 148 (63%) were female. Leading diagnoses were CRPS (n = 106, 43%), followed by FBSS (n = 64, 26%), and non-surgical low back pain (n = 23, 9%). The explantation rate was ~2% per year (n = 10 total). At explantation, the average time from implantation was 13 ± 10 months. Six patients were explanted for inadequate pain relief. Two patients were explanted due to device-related complications. One patient was explanted secondary to infection and subsequently reimplanted. Five explanted patients experienced a therapy-related complication before eventual explantation: one transient post-procedural neuritis and pocket site pain, one lead fracture, two lead migrations, and one experienced a fracture, a migration, and pocket site pain. DISCUSSION/CONCLUSIONS:This large retrospective study of DRG-S revealed a low therapy-termination rate. The rate of infection leading to explantation was objectively very low at 0.4%. The leading cause of explantation was inadequate pain relief. Explanted patients often had a therapy-related complication. Therefore, minimizing adverse treatment events may reduce ultimate explantation rates.
PMID: 35429364
ISSN: 1533-2500
CID: 5204562

A broad and variable lumbosacral myotome map uncovered by foraminal nerve root stimulation

London, Dennis; Birkenfeld, Ben; Thomas, Joel; Avshalumov, Marat; Mogilner, Alon Y; Falowski, Steven; Mammis, Antonios
OBJECTIVE:The human myotome is fundamental to the diagnosis and treatment of neurological disorders. However, this map was largely constructed decades ago, and its breadth, variability, and reliability remain poorly described, limiting its practical use. METHODS:The authors used a novel method to reconstruct the myotome map in patients (n = 42) undergoing placement of dorsal root ganglion electrodes for the treatment of chronic pain. They electrically stimulated nerve roots (n = 79) in the intervertebral foramina at T12-S1 and measured triggered electromyography responses. RESULTS:L4 and L5 stimulation resulted in quadriceps muscle (62% and 33% of stimulations, respectively) and tibialis anterior (TA) muscle (25% and 67%, respectively) activation, while S1 stimulation resulted in gastrocnemius muscle activation (46%). However, L5 and S1 both resulted in abductor hallucis (AH) muscle activation (17% and 31%), L5 stimulation resulted in gastrocnemius muscle stimulation (42%), and S1 stimulation in TA muscle activation (38%). The authors also mapped the breadth of the myotome in individual patients, finding coactivation of adductor and quadriceps, quadriceps and TA, and TA and gastrocnemius muscles under L3, L4, and both L5 and S1 stimulation, respectively. While the AH muscle was commonly activated by S1 stimulation, this rarely occurred together with TA or gastrocnemius muscle activation. Other less common coactivations were also observed throughout T12-S1 stimulation. CONCLUSIONS:The muscular innervation of the lumbosacral nerve roots varies significantly from the classic myotome map and between patients. Furthermore, in individual patients, each nerve root may innervate a broader range of muscles than is commonly assumed. This finding is important to prevent misdiagnosis of radicular pathologies.
PMID: 35561698
ISSN: 1547-5646
CID: 5215012

Allergy Considerations in Implanted Neuromodulation Devices

Brown, Austin; Mandelberg, Nataniel J; Munoz-Mendoza, Diana; Palys, Viktoras; Schalock, Peter C; Mogilner, Alon; North, Richard; A Petersen, Erika
OBJECTIVES/OBJECTIVE:Allergic reactions are rare and poorly understood complications of neuromodulation device implantation. There are currently no guidelines for management of allergic reactions to these devices and their components. Here we review the published cases of allergic reactions to implanted neuromodulatory devices and leverage the experiences of other specialties that deal with similar complications to formulate recommendations for prevention and management. MATERIALS AND METHODS/METHODS:A review and assessment of the literature. RESULTS:Allergic reactions to a number of implantable devices have been observed and published. In dentistry and orthopedics, metals such as nickel are the most frequent cause of allergic reactions. In interventional cardiology, where devices closely resemble neuromodulatory devices, titanium, silicone, and polyurethanes are the most common causes of allergic reactions. In neurosurgery, allergic reactions to implantable neuromodulatory devices are rare, and we summarize 13 cases published to date. Such allergic reactions generally present as local dermatitis, erythema, and pruritus, which can be difficult to distinguish from surgical site infection. In one published case, symptoms resolved with corticosteroid treatment, but all other cases required explantation. The successful reimplantation with a modified device was reported in some cases. CONCLUSIONS:Patients should be screened for a personal history of contact allergy before implantation procedures. A multidisciplinary approach to suspected cases of postoperative allergic reactions involving collaboration between neurosurgeons and other implanting physicians, dermatologists or allergists, and device manufacturers is recommended. In cases where an allergic reaction is suspected, an infectious etiology should be ruled out first. Clinical suspicion can then be supported with the use of patch testing, interpreted by an experienced dermatologist or allergist. If patch testing supports an allergic etiology, the implanting physician and the device manufacturer can work together to modify the device for safe reimplantation.
PMID: 33428821
ISSN: 1525-1403
CID: 4767812

Lead migration and fracture rate in dorsal root ganglion stimulation using anchoring and non-anchoring techniques: A multicenter pooled data analysis

Chapman, Kenneth B; Mogilner, Alon Y; Yang, Ajax H; Yadav, Abhishek; Patel, Kiran V; Lubenow, Timothy; van Helmond, Noud; Deer, Timothy; Kallewaard, Jan Willem
INTRODUCTION/BACKGROUND:Dorsal root ganglion stimulation (DRG-S) is a neuromodulation technique introduced in the last decade with evolving implant methods. Initial prospective research found low incidences of lead migration and lead fracture with DRG-S. However, several recent studies have highlighted high lead migration and lead fracture rates with DRG-S. We investigated the influence of lead anchoring on migrations and fractures. METHODS:We performed a retrospective review between 2016 and 2020 of individuals implanted with DRG-S leads by 4 experienced implanters. The implanters independently changed their standard practice regarding lead anchoring over time, with opposing trends (no anchoring > anchoring, anchoring > no anchoring). We compared lead migration and lead fracture rates between anchored and unanchored DRG-S leads in the entire study cohort. Cox regression was performed on lead migration and fracture distributions. RESULTS:We included 756 leads (n = 565 anchored and n = 191 unanchored) from 249 patients. In unanchored leads, migration occurred in 16 leads (8.4%) from 13 patients (21.0%). In anchored leads, migration occurred in 8 leads (1.4%) from 5 patients (2.7%). Fracture in unanchored leads occurred in 6 leads (3.1%) from 6 patients (9.7%). Fractures in anchored leads occurred in 11 leads (1.9%) from 9 patients (4.8%). The migration survival distributions for the anchored and unanchored leads were statistically significantly different (p < 0.01) with decreased survival for unanchored leads (hazard ratio = 5.8, 95% confidence interval [CI] = 2.2-15.5). DISCUSSION/CONCLUSIONS:We found that anchoring DRG-S leads significantly reduces lead migration when compared to leads placed without an anchor. There was no significant difference in fracture rate between anchored and unanchored leads.
PMID: 34145740
ISSN: 1533-2500
CID: 4954652

Distinct population code for movement kinematics and changes of ongoing movements in human subthalamic nucleus

London, Dennis; Fazl, Arash; Katlowitz, Kalman; Soula, Marisol; Pourfar, Michael H; Mogilner, Alon Y; Kiani, Roozbeh
The subthalamic nucleus (STN) is theorized to globally suppress movement through connections with downstream basal ganglia structures. Current theories are supported by increased STN activity when subjects withhold an uninitiated action plan, but a critical test of these theories requires studying STN responses when an ongoing action is replaced with an alternative. We perform this test in subjects with Parkinson's disease using an extended reaching task where the movement trajectory changes mid-action. We show that STN activity decreases during action switches, contrary to prevalent theories. Furthermore, beta oscillations in the STN local field potential, which are associated with movement inhibition, do not show increased power or spiking entrainment during switches. We report an inhomogeneous population neural code in STN, with one sub-population encoding movement kinematics and direction and another encoding unexpected action switches. We suggest an elaborate neural code in STN that contributes to planning actions and changing the plans.
PMCID:8500714
PMID: 34519273
ISSN: 2050-084x
CID: 5061332

Awake Laser Ablation for Patients With Tumors in Eloquent Brain Areas: Operative Technique and Case Series

Hajtovic, Sabastian; Mogilner, Alon; Ard, John; Gautreaux, Jose E; Britton, Hannah; Fatterpekar, Girish; Young, Matthew G; Placantonakis, Dimitris G
Background Magnetic resonance imaging (MRI)-guided laser interstitial thermal therapy (LITT) is a minimally invasive treatment modality that has been gaining traction in neuro-oncology. Laser ablation is a particularly appealing treatment option when eloquent neurologic function at the tumor location precludes conventional surgical excision. Although typically performed under general anesthesia, LITT in awake patients may help monitor and preserve critical neurologic functions. Objective To describe intraoperative workflow and clinical outcomes in patients undergoing awake laser ablation of brain tumors. Methods We present a cohort of six patients with tumors located in eloquent brain areas that were treated with awake LITT and report three different workflow paradigms involving diagnostic or intraoperative MRI. In all cases, we used NeuroBlate® (Monteris Medical, Plymouth, MN) fiberoptic laser probes for stereotactic laser ablation of tumors. The neurologic status of patients was intermittently assessed every few minutes during the ablation. Results The mean preoperative tumor volume that was targeted was 12.09 ± 3.20 cm3, and the estimated ablation volume was 12.06 ± 2.75 cm3. Performing the procedure in awake patients allowed us close monitoring of neurologic function intraoperatively. There were no surgical complications. The length of stay was one day for all patients except one. Three patients experienced acute or delayed worsening of pre-existing neurologic deficits that responded to corticosteroids. Conclusion We propose that awake LITT is a safe approach when tumors in eloquent brain areas are considered for laser ablation.
PMCID:7815262
PMID: 33489596
ISSN: 2168-8184
CID: 5018232

A Systematic Literature Review of Brain Neurostimulation Therapies for the Treatment of Pain

Deer, Timothy R; Falowski, Steven; Arle, Jeff E; Vesper, Jan; Pilitsis, Julie; Slavin, Konstantin V; Hancu, Maria; Grider, Jay S; Mogilner, Alon Y
OBJECTIVE:To conduct a systematic literature review of brain neurostimulation for pain. DESIGN/METHODS:Grade the evidence for deep brain neurostimulation (DBS). METHODS:An international, interdisciplinary work group conducted a literature search for brain stimulation. Abstracts were reviewed to select studies for grading. Randomized controlled trials (RCTs) meeting inclusion/exclusion criteria were graded by two independent reviewers. General inclusion criteria were prospective trials (RCTs and observational) that were not part of a larger or previously reported group. Excluded studies were retrospective or existed only as abstracts. Studies were graded using the modified Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment, the Cochrane Collaborations Risk of Bias assessment, and the United States Preventative Services Task Force level-of-evidence criteria. RESULTS:Two high-quality RCTs and three observational trials supported DBS, resulting in Level II (moderate) evidence. CONCLUSION/CONCLUSIONS:Moderate evidence supports DBS to treat chronic pain. Additional Level I RCTs are needed to further the strength of the evidence in this important area of medicine, but the current evidence suggests that DBS should be considered as an option in treating complex pain cases.
PMID: 32034418
ISSN: 1526-4637
CID: 4301642