Use of differential stimulation of the nucleus accumbens and anterior limb of the internal capsule to improve outcomes of obsessive-compulsive disorder

J Neurosurg 139:1376–1385, 2023

Personalized stimulation is key to optimizing the outcomes of deep brain stimulation (DBS) for refractory obsessive-compulsive disorder (OCD). However, the contacts in a single conventional electrode cannot be programmed independently, which may affect the therapeutic efficacy of DBS for OCD. Therefore, a novel designed electrode and implantable pulse generator (IPG) that could achieve differential stimulation parameters for different contacts was implanted into the nucleus accumbens (NAc) and anterior limb of the internal capsule (ALIC) of a cohort of patients with OCD.

METHODS Thirteen consecutive patients underwent bilateral DBS of the NAc-ALIC between January 2016 and May 2021. Differential stimulation of the NAc-ALIC was applied at initial activation. Primary effectiveness was assessed on the basis of change in scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) from baseline to 6-month follow-up. Full-response was defined as a 35% decrease in Y-BOCS score. Secondary effectiveness measures were the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD). The local field potential of bilateral NAcALIC was recorded in 4 patients who were reimplanted with a sensing IPG after battery depletion of the previous IPG.

RESULTS The Y-BOCS, HAMA, and HAMD scores decreased remarkably during the first 6 months of DBS. Ten of 13 patients were categorized as responders (76.9%). Differential stimulation of the NAc-ALIC was favorable to optimization of the stimulation parameters by increasing the parameter configurations. Power spectral density analysis revealed pronounced delta-alpha frequency activity in the NAc-ALIC. Phase-amplitude coupling of the NAc-ALIC showed that strong coupling is present between the phase of delta-theta and broadband gamma amplitude.

CONCLUSIONS These preliminary findings indicate that differential stimulation of the NAc-ALIC can improve the efficacy of DBS for OCD.

Effect of lesion temperature on the durability of percutaneous radiofrequency rhizotomies to treat trigeminal neuralgia

J Neurosurg 139:625–632, 2023

Percutaneous radiofrequency rhizotomy is a common procedure for trigeminal neuralgia (TN) that creates thermocoagulative lesions in the trigeminal ganglion. Lesioning parameters for the procedure are left to the individual surgeon’s discretion, and published guidance is primarily anecdotal. The purpose of this work was to assess the role of lesioning temperature on long-term surgical outcomes.

METHODS This was a retrospective analysis of patients who underwent percutaneous radiofrequency rhizotomy from 2009 to 2020. Patient data, including demographics, disease presentation, surgical treatment, and outcomes, were collected from medical records. The primary endpoint was the recurrence of TN pain. Univariate and multivariate Cox proportional hazards regressions were used to assess the impact of chosen covariates on pain-free survival.

RESULTS A total of 280 patients who had undergone 464 procedures were included in the analysis. Overall, roughly 80% of patients who underwent rhizotomy would have a recurrence within 10 years. Lower lesion temperature was predictive of longer periods without pain recurrence (HR 1.05, p < 0.001). The inclusion of lesion time, postoperative numbness, prior history of radiofrequency rhizotomy, surgeon, and multiple sclerosis as confounding variables did not affect the hazard ratio or the statistical significance of this finding. Postoperative numbness and the absence of multiple sclerosis were significant protective factors in the model.

CONCLUSIONS The study findings suggest that lower lesion temperatures and, separately, postoperative numbness result in improved long-term outcomes for patients with TN who undergo percutaneous radiofrequency rhizotomies. Given the limitations of retrospective analysis, the authors suggest that a prospective multisite clinical trial testing lesion temperatures would provide definitive guidance on this issue with specific recommendations about the number needed to treat and trial design.

Altered brain network centrality in Parkinson’s disease patients after deep brain stimulation: a functional MRI study using a voxel-wise degree centrality approach

J Neurosurg 138:1712–1719, 2023

After deep brain stimulation (DBS), patients with Parkinson’s disease (PD) show improved motor symptoms and decreased verbal fluency, an effect that occurs before the initiation of DBS in the subthalamic nucleus. However, the underlying mechanism remains unclear. This study aimed to evaluate the effects of DBS on whole-brain degree centrality (DC) and seed-based functional connectivity (FC) in PD patients.

METHODS The authors obtained resting-state functional MRI data of 28 PD patients before and after DBS surgery. All patients underwent MRI scans in the off-stimulation state. The DC method was used to evaluate the effects of DBS on whole-brain FC at the voxel level. Seed-based FC analysis was used to examine network function changes after DBS.

RESULTS After DBS surgery, PD patients showed significantly weaker DC values in the left middle temporal gyrus, left supramarginal gyrus, and left middle frontal gyrus, but significantly stronger DC values in the midbrain, left precuneus, and right precentral gyrus. FC analysis revealed decreased FC values within the default mode network (DMN).

CONCLUSIONS This study demonstrated that the DC of DMN-related brain regions decreased in PD patients after DBS surgery, whereas the DC of the motor cortex increased. These findings provide new evidence for the neural effects of DBS on voxel-based whole-brain networks in PD patients.

Nucleus accumbens: a systematic review of neural circuitry and clinical studies in healthy and pathological states

J Neurosurg 138:337–346, 2023

The nucleus accumbens (NAcc) of the ventral striatum is critically involved in goal- and reward-based behavior. Structural and functional abnormalities of the NAcc or its associated neural systems are involved in neurological and psychiatric disorders. Studies of neural circuitry have shed light on the subtleties of the structural and functional derangements of the NAcc across various diseases. In this systematic review, the authors sought to identify human studies involving the NAcc and provide a synthesis of the literature on the known circuity of the NAcc in healthy and diseased states, as well as the clinical outcomes following neuromodulation.

METHODS A systematic review was conducted using the PubMed, Embase, and Scopus databases. Neuroimaging studies that reported on neural circuitry related to the human NAcc with sample sizes greater than 5 patients were included. Demographic data, aim, design and duration, participants, and clinical and neurocircuitry details and outcomes of the studies were extracted.

RESULTS Of 3591 resultant articles, 123 were included. The NAcc and its corticolimbic connections to other brain regions, such as the prefrontal cortex, are largely involved in reward and pain processes, with distinct functional circuitry between the shell and core in healthy patients. There is heterogeneity between clinical studies with regard to the NAcc indirect targeting coordinates, methods for postoperative confirmation, and blinded trial design. Neuromodulation studies provided promising clinical results in the context of addiction and substance misuse, obsessive-compulsive disorder, and mood disorders. The most common complications were impaired memory or concentration, and a notable serious complication was hypomania.

CONCLUSIONS The functional diversity of the NAcc highlights the importance of studying the NAcc in healthy and pathological states. The results of this review suggest that NAcc neuromodulation has been attempted in the management of diverse psychiatric indications. There is promising, emerging evidence that the NAcc may be an effective target for specific reward- or pain-based pathologies with a reasonable risk profile.

Increase in Trigeminal Nerve Cross-Sectional Area on Immediate Postoperative MRI Predicts Favorable Outcome After Microvascular Decompression for Classical Trigeminal Neuralgia

Neurosurgery 92:283–292, 2023

Although distortion or indentation of a trigeminal nerve due to neurovascular compression (NVC) is associated with classical trigeminal neuralgia, whether morphological change in the trigeminal nerve is relieved by eliminating NVC has not been studied.

OBJECTIVE: To estimate morphological change in the trigeminal nerve after microvascular decompression (MVD).

METHODS: Fifty patients with classical trigeminal neuralgia who underwent MVD were included. Using coronal images in both preoperative and postoperative MRI, the trigeminal nerve cross-sectional area (CSA) was measured at 4 mm anterior to the nerve entry into the pons. Clinical outcomes were assessed using the Barrow Neurological Institute Pain Intensity Scale (BNI-PS) at the patient’s latest follow-up.

RESULTS: Forty-one patients achieved favorable outcomes without medication (BNI-PS I or II), and 9 patients had residual pain (BNI-PS ≥ 3A). The mean symptomatic trigeminal nerve CSA was increased by 51.47% after MVD in the favorable outcome group (pre-operative: 4.37 ± 1.64 mm 2 vs postoperative: 6.26 ± 1.76 mm2 , P < .01), whereas it was not significantly changed in the unfavorable outcome group (preoperative: 4.20 ± 1.19 mm2 vs postoperative: 4.43 ± 1.24 mm2 , P = .69). Kaplan–Meier survival analysis showed that the 3-year probability of maintaining a favorable outcome was 92.3 ± 7.4% and 56.1 ± 11.9%, for those whose symptomatic trigeminal nerve CSA was increased by over 20% and less than 20%, respectively (P < .01).

CONCLUSION: Morphological changes in the trigeminal nerve due to NVC could be recovered by MVD, and increases in the trigeminal nerve CSA predicted favorable outcomes.

A population-normalized tractographic fiber atlas of the anterior limb of the internal capsule: relevance to surgical neuromodulation

J Neurosurg 137:1278–1288, 2022

The anterior limb of the internal capsule (ALIC) is a white matter highway that connects several subcortical structures to the prefrontal cortex. Although surgical interventions in the ALIC have been used to treat a number of psychiatric illnesses, there is significant debate regarding what fibers are targeted for intervention. This debate is partially due to an incomplete understanding of connectivity in the region.

METHODS To better understand this complex structure, the authors employed a novel tractography-based approach to examine how fibers from the thalamus and subthalamic nucleus (STN) traverse the ALIC. Furthermore, the authors analyzed connections from the medial dorsal nucleus, anterior nucleus, and ventral anterior nucleus of the thalamus.

RESULTS The results showed that there is an organizational gradient of thalamic fibers medially and STN fibers laterally in the ALIC that fades more anteriorly. These findings, in combination with the known corticotopic organization described by previous studies, allow for a more thorough understanding of the organization of the white matter fibers in the ALIC.

CONCLUSIONS These results are important for understanding and targeting of neuromodulatory therapies in the ALIC and may help explain why differences in therapeutic effect are observed for different areas of the ALIC.

Initial experience with magnetic resonance–guided focused ultrasound stereotactic surgery for central brain lesions in young adults

J Neurosurg 137:760–767, 2022

Magnetic resonance–guided focused ultrasound (MRgFUS) is an incisionless procedure capable of thermoablation through the focus of multiple acoustic beams. Although MRgFUS is currently approved for the treatment of tremor in adults, its safety and feasibility profile for intracranial lesions in the pediatric and young adult population remains unknown.

METHODS The long-term outcomes of a prospective single-center, single-arm trial of MRgFUS at Nicklaus Children’s Hospital in Miami, Florida, are presented. Patients 15–22 years of age with centrally located lesions were recruited, clinically consistent with WHO grade I tumors that require surgical intervention. This cohort consisted of 4 patients with hypothalamic hamartoma (HH), and 1 patient with tuberous sclerosis complex harboring a subependymal giant cell astrocytoma (SEGA).

RESULTS In each case, high-intensity FUS was used to target the intracranial lesion. Real-time MRI was used to monitor the thermoablations. Primary outcomes of interest were tolerability, feasibility, and safety of FUS. The radiographic ablation volume on intra- and postoperative MRI was also assessed. All 5 patients tolerated the procedure without any complications. Successful thermoablation was achieved in 4 of the 5 cases; the calcified SEGA was undertreated due to intratumor calcification, which prevented attainment of the target ablation temperature. The HHs underwent target tissue thermoablations that led to MR signal changes at the treatment site. For the patients harboring HHs, FUS thermoablations occurred without procedure-related complications and led to improvement in seizure control or hypothalamic hyperphagia. All 5 patients were discharged home on postoperative day 1 or 2, without any readmissions. There were no cases of hemorrhage, electrolyte derangement, endocrinopathy, or new neurological deficit in this cohort.

CONCLUSIONS This experience demonstrates that FUS thermoablation of centrally located brain lesions in adolescents and young adults can be performed safely and that it provides therapeutic benefit for associated symptoms. Clinical trial registration no.: NCT03028246


Direct targeting of the ventral intermediate nucleus of the thalamus in deep brain stimulation for essential tremor

J Neurosurg 136:662–671, 2022

The ventral intermediate nucleus of the thalamus (VIM) is an effective target for deep brain stimulation (DBS) to control symptoms related to essential tremor. The VIM is typically targeted using indirect methods, although studies have reported visualization of the VIM on proton density–weighted MRI. This study compares the outcomes between patients who underwent VIM DBS with direct and indirect targeting.

METHODS Between August 2013 and December 2019, 230 patients underwent VIM DBS at the senior author’s institution. Of these patients, 92 had direct targeting (direct visualization on proton density 3-T MRI). The remaining 138 patients had indirect targeting (relative to the third ventricle and anterior commissure–posterior commissure line).

RESULTS Coordinates of electrodes placed with direct targeting were significantly more lateral (p < 0.001) and anterior (p < 0.001) than those placed with indirect targeting. The optimal stimulation amplitude for devices measured in voltage was lower for those who underwent direct targeting than for those who underwent indirect targeting (p < 0.001). Patients undergoing direct targeting had a greater improvement only in their Quality of Life in Essential Tremor Questionnaire hobby score versus those undergoing indirect targeting (p = 0.04). The direct targeting group had substantially more symptomatic hemorrhages than the indirect targeting group (p = 0.04). All patients who experienced a postoperative hemorrhage after DBS recovered without intervention.

CONCLUSIONS Patients who underwent direct VIM targeting for DBS treatment of essential tremor had similar clinical outcomes to those who underwent indirect targeting. Direct VIM targeting is safe and effective.

Results of three or more Gamma Knife radiosurgery procedures for recurrent trigeminal neuralgia

J Neurosurg 135:1789–1798, 2021

Gamma Knife radiosurgery (GKRS) is an established surgical option for the treatment of trigeminal neuralgia (TN), particularly for high-risk surgical candidates and those with recurrent pain. However, outcomes after three or more GKRS treatments have rarely been reported. Herein, the authors reviewed outcomes among patients who had undergone three or more GKRS procedures for recurrent TN.

METHODS The authors conducted a multicenter retrospective analysis of patients who had undergone at least three GKRS treatments for TN between July 1997 and April 2019 at two different institutions. Clinical characteristics, radiosurgical dosimetry and technique, pain outcomes, and complications were reviewed. Pain outcomes were scored on the Barrow Neurological Institute (BNI) scale, including time to pain relief (BNI score ≤ III) and recurrence (BNI score > III).

RESULTS A total of 30 patients were identified, including 16 women and 14 men. Median pain duration prior to the first GKRS treatment was 10 years. Three patients (10%) had multiple sclerosis. Time to pain relief was longer after the third treatment (p = 0.0003), whereas time to pain recurrence was similar across each of the successive treatments (p = 0.842). Complete or partial pain relief was achieved in 93.1% of patients after the third treatment. The maximum pain relief achieved after the third treatment was significantly better among patients with no prior percutaneous procedures (p = 0.0111) and patients with shorter durations of pain before initiation of GKRS therapy (p = 0.0449). New or progressive facial sensory dysfunction occurred in 29% of patients after the third GKRS treatment and was reported as bothersome in 14%. One patient developed facial twitching, while another experienced persistent lacrimation. No statistically significant predictors of adverse effects following the third treatment were found. Over a median of 39 months of follow-up, 77% of patients maintained complete or partial pain relief. Three patients underwent a fourth GKRS treatment, including one who ultimately received five treatments; all of them reported sustained pain relief at the extended follow-up.

CONCLUSIONS The authors describe the largest series to date of patients undergoing three or more GKRS treatments for refractory TN. A third treatment may produce outcomes similar to those of the first two treatments in terms of longterm pain relief, recurrence, and adverse effects.


Awake CT-guided percutaneous stylomastoid foramen puncture and radiofrequency ablation of facial nerve for treatment of hemifacial spasm

J Neurosurg 135:1459–1465, 2021

Hemifacial spasm (HFS) is a debilitating neuromuscular disorder with limited treatment options. The current study describes a novel minimally invasive procedure that provided effective and sustained relief for patients with HFS. The authors provide a detailed description of the awake CT-guided percutaneous radiofrequency ablation (RFA) of the facial nerve for treatment of HFS, and they examine its clinical efficacy. This is the first time in the literature that this procedure has been applied and systematically analyzed for HFS.

METHODS Patients with a history of HFS were recruited between August 2018 and April 2020. Those with a history of cerebellopontine lesions, coagulopathy, ongoing pregnancy, cardiac pacemaker or defibrillator implants, or who declined the procedure were excluded from the study. Fifty-three patients who met the study criteria were included and underwent awake CT-guided RFA. Under minimal sedation, a radiofrequency (RF) needle was used to reach the stylomastoid foramen on the affected side under CT guidance, and the facial nerve was localized using a low-frequency stimulation current. Patients were instructed to engage facial muscles as a proxy for motor monitoring during RFA. Ablation stopped when the patients’ hemifacial contracture resolved. Patients were kept for inpatient monitoring for 24 hours postoperatively and were followed up monthly to monitor resolution of HFS and complications for up to 19 months.

RESULTS The average duration of the procedure was 32–34 minutes. Postoperatively, 91% of the patients (48/53) had complete resolution of HFS, whereas the remaining individuals had partial resolution. A total of 48 patients reported mild to moderate facial paralysis immediately post-RFA, but most resolved within 1 month. No other significant complication was observed during the study period. By the end of the study period, 5 patients had recurrence of mild HFS symptoms, whereas only 2 patients reported dissatisfaction with the treatment results.

CONCLUSIONS The authors report for the first time that awake CT-guided RFA of the facial nerve at the stylomastoid foramen is a minimally invasive procedure and can be an effective treatment option for HFS.

Perioperative complications of deep brain stimulation among patients with advanced age

J Neurosurg 135:1421–1428, 2021

Deep brain stimulation (DBS) is an elective procedure that can dramatically enhance quality of life. Because DBS is not considered lifesaving, it is important that providers produce consistently good outcomes, and one factor they usually consider is patient age. While older age may be a relative contraindication for some elective surgeries, the progressive nature of movement disorders treated with DBS may suggest that older patients stand to benefit substantially from surgery. To better understand the risks of treating patients of advanced age with DBS, this study compares perioperative complication rates in patients ≥ 75 to those < 75 years old.

METHODS Patients undergoing DBS surgery for various indications by a single surgeon (May 2013–July 2019) were stratified into elderly (age ≥ 75 years) and younger (age < 75 years) cohorts. The risks of common perioperative complications and various outcome measures were compared between the two age groups using risk ratios (RRs) and 95% confidence intervals (CIs).

RESULTS A total of 861 patients were available for analysis: 179 (21%) were ≥ 75 years old and 682 (79%) were < 75 years old (p < 0.001). Patients ≥ 75 years old, compared with those < 75 years old, did not have significantly different RRs (95% CIs) of seizure (RR 0.4, 95% CI 0.1–3.3), cerebrovascular accident (RR 1.9, 95% CI 0.4–10.3), readmission within 90 days of discharge (RR 1.22, 95% CI 0.8–1.8), explantation due to infection (RR 2.5, 95% CI 0.4–15.1), or surgical revision (for lead, RR 2.5, 95% CI 0.4–15.1; for internal pulse generator, RR 3.8, 95% CI 0.2–61.7). Although the risk of postoperative intracranial bleeding was higher in the elderly group (6.1%) than in the younger group (3.1%), this difference was not statistically significant (p = 0.06). However, patients ≥ 75 years old did have significantly increased risk of altered mental status (RR 2.5, 95% CI 1.6–4.0), experiencing more than a 1-night stay (RR 1.7, 95% CI 1.4–2.0), and urinary retention (RR 2.3, 95% CI 1.2–4.2; p = 0.009).

CONCLUSIONS Although elderly patients had higher risks of certain outcome measures than younger patients, this study showed that elderly patients undergoing DBS for movement disorders did not have an increased risk of more serious complications, such as intracranial hemorrhage, infection, or readmission. Advanced age alone should not be considered a contraindication for DBS.

What have we learned from 8 years of deep brain stimulation of the anterior thalamic nucleus? Experiences and insights of a single center

J Neurosurg 135:619–628, 2021

In the absence of a standard or guideline for the treatment of epilepsy patients with deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT), systematic single-center investigations are essential to establish effective approaches. Here, the authors report on the long-term results of one of the largest single-center ANT DBS cohorts.

METHODS The outcome data of 23 consecutive patients with transventricularly implanted electrodes were retrospectively analyzed with regard to adverse events, lead placement, stimulation-related side effects, and changes in seizure frequency. Depression and quality-of-life scores were collected in a subgroup of 9 patients.

RESULTS All but 2 patients initially underwent bilateral implantation, and 84.4% of all DBS leads were successfully located within the ANT. The mean follow-up time was 46.57 ± 23.20 months. A seizure reduction > 50% was documented in 73.9% of patients, and 34.6% achieved an Engel class I outcome. In 3 patients, clinical response was achieved by switching the electrode contact or changing from the monopolar to bipolar stimulation mode. Unilateral implantation seemed ineffective, whereas bilateral stimulation with successful ANT implantation only on one side led to a clinical response. Double stimulation with additional vagus nerve stimulation was safe. Changes in cycling mode or stimulation amplitude influenced therapy tolerability and, only to a lesser extent, seizure frequency. Side effects were rare and typically vanished by lowering the stimulation amplitude or changing the active electrode contact. Furthermore, depression and aspects of quality of life significantly improved with ANT DBS treatment.

CONCLUSIONS The transventricular approach as well as double stimulation proved safe. The anteroventral ANT appeared to be the most efficacious stimulation site. This systematic investigation with reluctant medication changes allowed for the development of a better idea of the association between parameter changes and outcome in ANT DBS patients, but larger samples are still needed to assess the potential of bipolar stimulation and distinct cycling frequencies. Furthermore, more multifaceted and objective assessments of treatment outcome are needed to fully assess the effects of ANT DBS treatment.

Seizure and neuropsychological outcomes in a large series of selective amygdalohippocampectomies with a minimally invasive subtemporal approach

J Neurosurg 134:1685–1693, 2021

Debate continues over proper surgical treatment for mesial temporal lobe epilepsy (MTLE). Few large comprehensive studies exist that have examined outcomes for the subtemporal selective amygdalohippocampectomy (sSAH) approach. This study describes a minimally invasive technique for sSAH and examines seizure and neuropsychological outcomes in a large series of patients who underwent sSAH for MTLE.

METHODS Data for 152 patients (94 women, 61.8%; 58 men, 38.2%) who underwent sSAH performed by a single surgeon were retrospectively reviewed. The sSAH technique involves a small, minimally invasive opening and preserves the anterolateral temporal lobe and the temporal stem. RESULTS All patients in the study had at least 1 year of follow-up (mean [SD] 4.52 [2.57] years), of whom 57.9% (88/152) had Engel class I seizure outcomes. Of the patients with at least 2 years of follow-up (mean [SD] 5.2 [2.36] years), 56.5% (70/124) had Engel class I seizure outcomes. Preoperative and postoperative neuropsychological test results indicated no significant change in intelligence, verbal comprehension, perceptual reasoning, attention and processing, cognitive flexibility, visuospatial memory, or mood. There was a significant change in word retrieval regardless of the side of surgery and a significant change in verbal memory in patients who underwent dominant-side resection (p < 0.05). Complication rates were low, with a 1.3% (2/152) permanent morbidity rate and 0.0% mortality rate.

CONCLUSIONS This study reports a large series of patients who have undergone sSAH, with a comprehensive presentation of a minimally invasive technique. The sSAH approach described in this study appears to be a safe, effective, minimally invasive technique for the treatment of MTLE.

Neurostimulation for treatment-resistant posttraumatic stress disorder

J Neurosurg 134:1715–1723, 2021

Posttraumatic stress disorder (PTSD) is a widespread and often devastating psychiatric condition. Core symptoms include intrusive and distressing thoughts, heightened reactivity, mood changes, cognitive impairments, and consequent avoidance of trauma-related stimuli. Symptoms of PTSD are often refractory to standard treatments, and neuromodulatory techniques have therefore drawn significant interest among the most treatment-resistant patients.

Transcranial magnetic stimulation has demonstrated minimal efficacy, and deep brain stimulation trials are currently ongoing.

PTSD is a disorder of neural circuitry; the current understanding includes involvement of the amygdala (basolateral and central nuclei), the prefrontal cortex (ventral medial and dorsolateral regions), and the hippocampus. Neuroimaging and optogenetic studies have improved the understanding of large-scale neural networks and the effects of microcircuitry manipulation, respectively.

This review discusses the current PTSD literature and ongoing neurostimulation trials, and it highlights the current understanding of neuronal circuit dysfunction in PTSD. The authors emphasize the anatomical correlations of PTSD’s hallmark symptoms, offer another potential deep brain stimulation target for PTSD, and note the need for continued research to identify useful biomarkers for the development of closed-loop therapies. Although there is hope that neuromodulation will become a viable treatment modality for PTSD, this concept remains theoretical, and further research should involve institutional review board–approved controlled prospective clinical studies.


Electrocorticography During Deep Brain Stimulation Surgery

Neurosurgery 88:E420–E426, 2021

Intraoperative research during deep brain stimulation (DBS) surgery has enabled major advances in understanding movement disorders pathophysiology and potential mechanisms for therapeutic benefit. In particular, over the last decade, recording electrocorticography (ECoG) from the cortical surface, simultaneously with subcortical recordings, has become an important research tool for assessing basal gangliathalamocortical circuit physiology.

OBJECTIVE: To provide confirmation of the safety of performing ECoG duringDBS surgery, using data fromcenters involved in 2 BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative-funded basic human neuroscience projects. METHODS: Datawere collected separately at 4 centers. The primary endpoint was complication rate, defined as any intraoperative event, infection, or postoperative magnetic resonance imaging abnormality requiring clinical follow-up. Complication rates for explanatory variables were compared using point biserial correlations and Fisher exact tests.

RESULTS: A total of 367 DBS surgeries involving ECoG were reviewed. No cortical hemorrhages were observed. Seven complications occurred: 4 intraparenchymal hemorrhages and 3 infections (complication rate of 1.91%; CI=0.77%-3.89%). The placement of 2 separate ECoG research electrodes through a single burr hole (84 cases) did not result in a significantly different rate of complications, compared to placement of a single electrode (3.6% vs 1.5%; P = .4). Research data were obtained successfully in 350 surgeries (95.4%).

CONCLUSION: Combined with the single report previously available, which described no ECoG-related complications in a single-center cohort of 200 cases, these findings suggest that research ECOG during DBS surgery did not significantly alter complication rates.

Deep brain stimulation for aggressiveness: long-term follow-up and tractography study of the stimulated brain areas

J Neurosurg 134:366–375, 2021

Initial studies applying deep brain stimulation (DBS) of the posteromedial hypothalamus (PMH) to patients with pathological aggressiveness have yielded encouraging results. However, the anatomical structures involved in its therapeutic effect have not been precisely identified. The authors’ objective was to describe the long-term outcome in their 7-patient series, and the tractography analysis of the volumes of tissue activated in 2 of the responders.

METHODS This was a retrospective study of 7 subjects with pathological aggressiveness. The findings on MRI with diffusion tensor imaging (DTI) in 2 of the responders were analyzed. The authors generated volumes of tissue activated according to the parameters used, and selected those volumes as regions of interest to delineate the tracts affected by stimulation.

RESULTS The series consisted of 5 men and 2 women. Of the 7 patients, 5 significantly improved with stimulation. The PMH, ventral tegmental area, dorsal longitudinal fasciculus, and medial forebrain bundle seem to be involved in the stimulation field.

CONCLUSIONS In this series, 5 of 7 medication-resistant patients with severe aggressiveness who were treated with bilateral PMH DBS showed a significant long-lasting improvement. The PMH, ventral tegmental area, dorsal longitudinal fasciculus, and medial forebrain bundle seem to be in the stimulation field and might be responsible for the therapeutic effect of DBS.


Tractography-based targeting of the ventral intermediate nucleus

J Neurosurg 133:1002–1009, 2020

Tractography-based targeting of the thalamic ventral intermediate nucleus (T-VIM) is a novel method conferring patient-specific selection of VIM coordinates for tremor surgery; however, its accuracy and clinical utility in magnetic resonance imaging–guided focused ultrasound (MRgFUS) thalamotomy compared to conventional indirect targeting has not been specifically addressed. This retrospective study sought to compare the treatment locations and potential adverse effect profiles of T-VIM with indirect targeting in a large cohort of MRgFUS thalamotomy patients.

METHODS T-VIM was performed using diffusion tractography outlining the pyramidal and medial lemniscus tracts in 43 MRgFUS thalamotomy patients. T-VIM coordinates were compared with the indirect treatment coordinates used in the procedure. Thalamotomy lesions were delineated on postoperative T1-weighted images and displaced (“translated”) by the anteroposterior and mediolateral difference between T-VIM and treatment coordinates. Both translated and actual lesions were normalized to standard space and subsequently overlaid with areas previously reported to be associated with an increased risk of motor and sensory adverse effects when lesioned during MRgFUS thalamotomy.

RESULTS T-VIM coordinates were 2.18 mm anterior and 1.82 mm medial to the “final” indirect treatment coordinates. Translated lesions lay more squarely within the boundaries of the VIM compared to nontranslated lesions and showed significantly less overlap with areas associated with sensory adverse effects. Translated lesions overlapped less with areas associated with motor adverse effects; however, this difference was not significant.

CONCLUSIONS T-VIM leads to the selection of more anterior and medial coordinates than the conventional indirect methods. Lesions moved toward these anteromedial coordinates avoid areas associated with an increased risk of motor and sensory adverse effects, suggesting that T-VIM may improve clinical outcomes.

First application of 7-T ultra–high field diffusion tensor imaging to detect altered microstructure of thalamic-somatosensory anatomy in trigeminal neuralgia

J Neurosurg 133:839–847, 2020

Trigeminal neuralgia (TN) is a debilitating neurological disease that commonly results from neurovascular compression of the trigeminal nerve (CN V). Although the CN V has been extensively studied at the site of neurovascular compression, many pathophysiological factors remain obscure. For example, thalamic-somatosensory function is thought to be altered in TN, but the abnormalities are inadequately characterized. Furthermore, there are few studies using 7-T MRI to examine patients with TN. The purpose of the present study was to use 7-T MRI to assess microstructural alteration in the thalamic-somatosensory tracts of patients with TN by using ultra–high field MRI.

METHODS Ten patients with TN and 10 age- and sex-matched healthy controls underwent scanning using 7-T MRI with diffusion tensor imaging. Structural images were segmented with an automated algorithm to obtain thalamus and primary somatosensory cortex (S1). Probabilistic tractography was performed between the thalamus and S1, and the microstructure of the thalamic-somatosensory tracts was compared between patients with TN and controls.

RESULTS Fractional anisotropy of the thalamic-somatosensory tract ipsilateral to the site of neurovascular compression was reduced in patients (mean 0.43) compared with side-matched controls (mean 0.47, p = 0.01). The mean diffusivity was increased ipsilaterally in patients (mean 6.58 × 10 −4 mm 2 /second) compared with controls (mean 6.15 × 10 −4 mm 2 / second, p = 0.02). Radial diffusivity was increased ipsilaterally in patients (mean 4.91 × 10 −4 mm 2 /second) compared with controls (mean 4.44 × 10 −4 mm 2 /second, p = 0.01). Topographical analysis revealed fractional anisotropy reduction and diffusivity elevation along the entire anatomical S1 arc in patients with TN.

CONCLUSIONS The present study is the first to examine microstructural properties of the thalamic-somatosensory anatomy in patients with TN and to evaluate quantitative differences compared with healthy controls. The finding of reduced integrity of these white matter fibers provides evidence of microstructural alteration at the level of the thalamus and S1, and furthers the understanding of TN neurobiology.

Magnetic resonance–guided focused ultrasound thalamotomy for essential tremor

J Neurosurg 133:417–424, 2020

The authors report their experience in treating patients suffering from medication-resistant essential tremor (ET) with MR-guided focused ultrasound (MRgFUS) thalamotomy over a 5-year period.

METHODS Forty-four ET patients treated with unilateral MRgFUS ventral intermediate nucleus (VIM) thalamotomy were assessed using the Clinical Rating Scale for Tremor (CRST) score and the Quality of Life in Essential Tremor Questionnaire (QUEST) over a 5-year span.

RESULTS Tremor was significantly improved immediately following MRgFUS in all patients and ceased completely in 24 patients. CRST scores in the treated hand at baseline (median 19; range 7–32, 44 patients) improved by a median of 16 at 1 month (44 patients; p < 0.0001), 17 at 6 months (31 patients; p < 0.0001), 15 at 1 year (24 patients; p < 0.0001), 18 at 2 years (15 patients; p < 0.0001), 19 at 3 years, (10 patients; p < 0.0001), 21 at 4 years (6 patients; p < 0.01), and 23 at 5 years (2 patients, significance not tested). Return of tremor that impacted activities of daily living was reported in 5 patients (11%). QUEST scores showed significant improvement, with median change of 35 points (p < 0.0001; 44 patients) at 1 month, 33 (p < 0.0001; 31 patients) at 6 months, 27 (p < 0.0001; 24 patients) at 1 year, 26 (p < 0.001; 15 patients) at 2 years, 25 (p < 0.001; 10 patients) at 3 years, 33 (p < 0.001; 6 patients) at 4 years, and 28 (significance not tested, 2 patients) at 5 years. Adverse events after the procedure were reversible in all but 5 patients (11%).

CONCLUSIONS MRgFUS thalamotomy for ET is an effective and safe procedure that provides long-term tremor relief and improvement in quality of life even in patients with medication-resistant disabling tremor. Additional studies with a larger group of patients is needed to substantiate these favorable results.

Utilization of 3D imaging reconstructions and assessment of symptom-free survival after microvascular decompression of the facial nerve in hemifacial spasm

J Neurosurg 133:425–432, 2020

Hemifacial spasm (HFS), largely caused by neurovascular compression (NVC) of the facial nerve, is a rare condition characterized by paroxysmal, unilateral, involuntary contraction of facial muscles. It has long been suggested that these symptoms are due to compression at the transition zone of the facial nerve. The aim of this study was to examine symptom-free survival and long-term quality of life (QOL) in HFS patients who underwent microvascular decompression (MVD). A secondary aim was to examine the benefit of utilizing fused MRI and MRA post hoc 3D reconstructions to better characterize compression location at the facial nerve root exit zone (fREZ).

METHODS The authors retrospectively analyzed patients with HFS who underwent MVD at a single institution, combined with a modified HFS-7 telephone questionnaire. Kaplan-Meier analysis was used to determine event-free survival, and the Wilcoxon signed-rank test was used to compare pre- and postoperative HFS-7 scores.

RESULTS Thirty-five patients underwent MVD for HFS between 2002 and 2018 with subsequent 3D reconstructions of preoperative images. The telephone questionnaire response rate was 71% (25/35). If patients could not be reached by telephone, then the last clinic follow-up date was recorded and any recurrence noted. Twenty-four patients (69%) were symptom free at longest follow-up. The mean length of follow-up was 2.4 years (1 month to 8 years). The mean symptom- free survival time was 44.9 ± 5.8 months, and the average symptom-control survival was 69.1 ± 4.9 months. Four patients (11%) experienced full recurrence. Median HFS-7 scores were reduced by 18 points after surgery (Z = −4.013, p < 0.0001). Three-dimensional reconstructed images demonstrated that NVC most commonly occurred at the attached segment (74%, 26/35) of the facial nerve within the fREZ and least commonly occurred at the traditionally implicated transition zone (6%, 2/35).

CONCLUSIONS MVD is a safe and effective treatment that significantly improves QOL measures for patients with HFS. The vast majority of patients (31/35, 89%) were symptom free or reported only mild symptoms at longest follow-up. Symptom recurrence, if it occurred, was within the first 2 years of surgery, which has important implications for patient expectations and informed consent. Three-dimensional image reconstruction analysis determined that culprit compression most commonly occurs proximally along the brainstem at the attached segment. The success of this procedure is dependent on recognizing this pattern and decompressing appropriately. Three-dimensional reconstructions were found to provide much clearer characterization of this area than traditional preoperative imaging. Therefore, the authors suggest that use of these reconstructions in the preoperative setting has the potential to help identify appropriate surgical candidates, guide operative planning, and thus improve outcome in patients with HFS.