Complications of Implanted Vagus Nerve Stimulation: A Systematic Review and Meta-analysis.

INTRODUCTION: Vagus Nerve Stimulation (VNS) has emerged as a promising tool in ischemic stroke rehabilitation. However, there has been no systematic review summarizing its adverse effects, critical information for patients and providers when obtaining informed consent for this novel treatment. This systematic review and meta-analysis reports the adverse effects of VNS. METHODS: A systematic review was performed in accordance with PRISMA guidelines to identify common complications after VNS therapy. The search was executed in: Cochrane Central Register of Controlled Trials, Embase, and Ovid MEDLINE. All prospective, randomized controlled trials using implanted VNS therapy in adult patients were eligible for inclusion. Case studies and studies lacking complete complication reports were excluded. Extracted data included technology name, location of implantation, follow-up duration, purpose of VNS, and adverse event rates. RESULTS: After title-and-abstract screening of 4933 studies, 21 were selected for final inclusion. Across these studies, 1474 patients received VNS implantation. VNS was used as a potential therapy for epilepsy (9), depression (8), anxiety (1), ischemic stroke (1), chronic heart failure (1), and fibromyalgia (1). The 5 most common post-implant adverse events were voice alteration/hoarseness (n=671, 45.5%), paresthesia (n = 233, 15.8%), cough (n = 221, 15.0%), dyspnea (n = 211, 14.3%), and pain (n = 170, 11.5%). CONCLUSIONS: Complications from VNS are mild and transient, with reduction in severity and number of adverse events with increasing follow-up time. In prior studies, VNS has served as treatment option in several instances of treatment-resistant conditions, such as epilepsy and psychiatric conditions, and its use in stroke recovery and rehabilitation should continue to be explored.

Focused Ultrasound for Treatment of Movement Disorders: A Review of Non-Food and Drug Administration Approved Indications.

INTRODUCTION: MRI-guided focused ultrasound (FUS) is an incisionless thermo-ablative procedure that may be used to treat medication-refractory movement disorders, with a growing number of potential anatomic targets and clinical applications. As of this article's publication, the only US Food and Drug Administration (FDA)-approved uses of FUS for movement disorders are thalamotomy for essential tremor (ET) and tremor-dominant Parkinson's Disease (PD), and pallidotomy for other cardinal symptoms of PD. We present a state-of-the-art review on all non-FDA approved indications of FUS for movement disorders, beyond the most well-described indications of ET and PD. Our objective was to summarize the safety and efficacy of FUS in this setting and provide a roadmap for future directions of FUS for movement disorders. METHODS: A state-of-the-art review was conducted on use of FUS for non-FDA approved movement disorders. All movement disorders excluding FDA-approved uses for ET and PD were included. RESULTS: A total of 25 studies on 172 patients were included. In patients with tremor plus dystonia syndromes (n = 6), ventralis intermediate nucleus of the thalamus (VIM)-FUS gave >50% tremor reduction, with no improvement in dystonia and worsened dystonia in 2/6 patients. Ventral-oralis complex (VO)-FUS gave >50% improvement for focal hand dystonia (n = 6) and 100% return to musical performance in musician's dystonia (n = 6). In patients with multiple sclerosis (MS) and tremor (n = 3), improvement in tremor was seen in 2 patients with a favorable skull density ratio; no MS disease change was noted after VIM-FUS. In patients with tremor and comorbid ataxia syndromes (n = 3), none were found to have worsened ataxia after VIM-FUS; all had clinically significant tremor improvement. Subthalamic nucleus (STN)-FUS for PD (n = 49) gave approximately 50% improvement in PD motor symptoms, with dystonia and mild dyskinesias as possible adverse effects. Cerebellothalamic tract (CTT-FUS) for ET (n = 42) gave 55-90% tremor improvement, with gait dysfunction as a rare persistent adverse effect. Pallidothalamic tract (PTT-FUS) for PD (n = 50) gave approximately 50% improvement in motor symptoms, with mild speech dysfunction as a possible adverse effect. CONCLUSION: VIM-FUS appeared safe and effective for heterogenous tremor etiologies, and VO-FUS appeared most effective for isolated segmental dystonia. STN-FUS was effective for PD symptom reduction; postoperative dystonia and mild on-medication dyskinesias required medical management. Tractography-based targeting with CTT-FUS for ET and PTT-FUS for PD demonstrated promising early results. Larger prospective trials with long-term follow-up are needed to the evaluate the safety and efficacy non-FDA approved indications for FUS.

Neurosurgical treatment of spasticity: a potential return to the cerebellum.

OBJECTIVE: Neurosurgical targeting of the cerebellar dentate nucleus via ablative dentatotomy and stimulation of the dentate nucleus was historically used for effective treatment of spasticity. Yet for decades, neurosurgical treatment of spasticity targeting the cerebellum was bypassed in favor of alternative treatments such as intrathecal baclofen pumps and selective dorsal rhizotomies. Cerebellar neuromodulation has recently reemerged as a promising and effective therapy for spasticity and related movement disorders. METHODS: In this narrative review, the authors contextualize the historical literature of cerebellar neuromodulation, comparing it with modern approaches and exploring future directions with regard to cerebellar neuromodulation for spasticity. RESULTS: Neurosurgical intervention on the cerebellum dates to the use of dentatotomy in the 1960s, which had progressed to electrical stimulation of the cerebellar cortex and dentate nucleus by the 1980s. By 2024, modern neurosurgical approaches such as tractography-based targeting of the dentate nucleus and transcranial magnetic stimulation of cerebellar cortex have demonstrated promise for treating spasticity. CONCLUSIONS: Cerebellar neuromodulation of the dentate nucleus and cerebellar cortex are promising therapies for severe cases of spasticity. Open areas for exploration in the field include the following: tractography-based targeting, adaptive cerebellar stimulation, and investigations into the network dynamics between the cerebellar cortex, deep cerebellar nuclei, and the subcortical and cortical structures of the cerebrum.

A rare case of herpes simplex virus encephalitis from viral reactivation following surgically treated traumatic brain injury.

OBJECTIVE: Herpes simplex virus encephalitis (HSVE) is associated with significant morbidity and mortality. Here, we present the occurrence of HSVE in a 36-year-old immunocompetent patient following craniotomy for a traumatic acute subdural hematoma (ASDH). METHODS: Imaging after four days of progressive headache following a fall with head-strike demonstrated a 1 cm thick left holohemispheric ASDH with significant cerebral compression, edema, and 8 mm of left-to-right midline shift, and an emergent craniotomy and ASDH evacuation were performed, with additional treatment needed for reaccumulation. Postoperatively, the patient developed a worsening leukocytosis, became febrile, and was hypotensive requiring vasopressor support. RESULTS: Despite empiric antibiotics, the patient remained persistently febrile with significant leukocytosis. Repeat head CT showed a new left insular hypodensity and a subsequent viral encephalitis panel was positive for HSV-1. The patient was then started on intravenous acyclovir, with progressive neurological exam improvement. Of note, the patient was noted to have a positive serum HSV-1 IgG antibody titer, indicative of prior infection. CONCLUSIONS: Given the known systemic immunosuppression in brain injury and the high prevalence of HSV seropositivity, clinicians should consider the possibility of HSVE from HSV reactivation in TBI patients with persistent fever, leukocytosis, and/or neurological deficits without an obvious etiology.

Association of CDKN2A alterations with increased postoperative seizure risk after resection of brain metastases.

OBJECTIVE: Seizures are common and significantly disabling for patients with brain metastases (BMs). Although resection can provide seizure control, a subset of patients with BMs may continue to suffer seizures postoperatively. Genomic BM characteristics may influence which patients are at risk for postoperative seizures. This work explores correlations between genomic alterations and risk of postoperative seizures following BM resection. METHODS: All patients underwent BM resection at a single institution, with available clinical and sequencing data on more than 500 oncogenes. Clinical seizures were documented pre- and postoperatively. A random forest machine learning classification was used to determine candidate genomic alterations associated with postoperative seizures, and clinical and top genomic variables were correlated with postoperative seizures by using Cox proportional hazards models. RESULTS: There were 112 patients with BMs who underwent 114 surgeries and had at least 1 month of postoperative follow-up. Seizures occurred preoperatively in 26 (22.8%) patients and postoperatively in 25 (21.9%). The Engel classification achieved at 6 months for those with preoperative seizures was class I in 13 (50%); class II in 6 (23.1%); class III in 5 (19.2%), and class IV in 2 (7.7%). In those with postoperative seizures, only 8 (32.0%) had seizures preoperatively, and preoperative seizures were not a significant predictor of postoperative seizures (HR 1.84; 95% CI 0.79-4.37; p = 0.156). On random forest classification and multivariate Cox analysis controlling for factors including recurrence, extent of resection, and number of BMs, CDKN2A alterations were associated with postoperative seizures (HR 3.22; 95% CI 1.27-8.16; p = 0.014). Melanoma BMs were associated with higher risk of postoperative seizures compared with all other primary malignancies (HR 5.23; 95% CI 1.37-19.98; p = 0.016). Of 39 BMs with CDKN2A alteration, 35.9% (14/39) had postoperative seizures, compared to 14.7% (11/75) without CDKN2A alteration. The overall rate of postoperative seizures in melanoma BMs was 42.9% (15/35), compared with 12.7% (10/79) for all other primary malignancies. CONCLUSIONS: CDKN2A alterations and melanoma primary malignancy are associated with increased postoperative seizure risk following resection of BMs. These results may help guide postoperative seizure prophylaxis in patients undergoing resection of BMs.

Genomic alterations associated with rapid progression of brain metastases.

OBJECTIVE: The aim of this study was to investigate associations between genomic alterations in resected brain metastases and rapid local and distant CNS recurrence identified at the time of postoperative adjuvant radiosurgery. METHODS: This was a retrospective study on patients who underwent resection of intracranial brain metastases. Next-generation sequencing of more than 500 coding genes was performed on brain metastasis specimens. Postoperative and preradiosurgery MR images were compared to identify rapid recurrence. Genomic data were associated with rapid local and distant CNS recurrence of brain metastases using nominal regression analyses. RESULTS: The cohort contained 92 patients with 92 brain metastases. Thirteen (14.1%) patients had a rapid local recurrence, and 64 (69.6%) patients had rapid distant CNS progression by the time of postoperative adjuvant radiosurgery, which occurred in a median time of 25 days (range 3-85 days) from surgery. RB1 and CTNNB1 mutations were seen in 8.7% and 9.8% of the cohort, respectively, and were associated with a significantly higher risk of rapid local recurrence (RB1: OR 13.6, 95% CI 2.0-92.39, p = 0.008; and CTNNB1: OR 11.97, 95% CI 2.25-63.78, p = 0.004) on multivariate analysis. No genes were found to be associated with rapid distant CNS progression. However, the presence of extracranial disease was significantly associated with a higher risk of rapid distant recurrence on multivariate analysis (OR 4.06, 95% CI 1.08-15.34, p = 0.039). CONCLUSIONS: Genomic alterations in RB1 or CTNNB1 were associated with a significantly higher risk of rapid recurrence at the resection site. Although no genomic alterations were associated with rapid distant recurrence, having active extracranial disease was a risk factor for new lesions by the time of adjuvant radiotherapy after resection.

Hydroxyl Transfer to Carbon Radicals by Mn(OH) vs Fe(OH) Corrole Complexes.

The transfer of •OH from metal-hydroxo species to carbon radicals (R•) to give hydroxylated products (ROH) is a fundamental process in metal-mediated heme and nonheme C-H bond oxidations. This step, often referred to as the hydroxyl "rebound" step, is typically very fast, making direct study of this process challenging if not impossible. In this report, we describe the reactions of the synthetic models M(OH)(ttppc) (M = Fe (1), Mn (3); ttppc = 5,10,15-tris(2,4,6-triphenyl)phenyl corrolato3-) with a series of triphenylmethyl carbon radical (R•) derivatives ((4-X-C6H4)3C•; X = OMe, tBu, Ph, Cl, CN) to give the one-electron reduced MIII(ttppc) complexes and ROH products. Rate constants for 3 for the different radicals ranged from 11.4(1) to 58.4(2) M-1 s-1, as compared to those for 1, which fall between 0.74(2) and 357(4) M-1 s-1. Linear correlations for Hammett and Marcus plots for both Mn and Fe were observed, and the small magnitudes of the slopes for both correlations imply a concerted •OH transfer reaction for both metals. Eyring analyses of reactions for 1 and 3 with (4-X-C6H4)3C• (X = tBu, CN) also give good linear correlations, and a comparison of the resulting activation parameters highlight the importance of entropy in these •OH transfer reactions. Density functional theory calculations of the reaction profiles show a concerted process with one transition state for all radicals investigated and help to explain the electronic features of the OH rebound process.

Modeling Pyran Formation in the Molybdenum Cofactor: Protonation of Quinoxalyl-Dithiolene Promoting Pyran Cyclization.

Mononuclear Mo and W enzymes require a unique ligand known as molybdopterin (MPT). This ligand binds the metal through a dithiolene chelate, and the dithiolene bridges a reduced pyranopterin group. Pyran scission and formation have been proposed as a reaction of the MPT ligand that may occur within the enzymes to adjust reactivity at the Mo atom. We address this issue by investigating oxo-Mo(IV) model complexes containing dithiolenes substituted by pterin or quinoxaline and a hydroxyalkyl poised to form a pyran ring. While the pterin-dithiolene model complex exhibits a low energy, reversible pyran cyclization, here we report that pyran cyclization does not spontaneously occur in the quinoxalyl-dithiolene model. However, protonating the quinoxalyl-dithiolene model induces pyran cyclization forming an unstable, pyrano-quinoxalyl-dithiolene complex which subsequently dehydrates and rearranges to a pyrrolo-quinoxlyl-dithiolene complex that was previously characterized. The protonated pyrano-quinoxalyl-dithiolene complex was characterized by absorption spectroscopy and cyclic voltammetry, and these results suggest pyran cyclization leads to a significant change in the Mo electronic structure exhibited as a strong intraligand charge transfer (ILCT) transition and 370 mV positive shift of the Mo(V/IV) reduction potential. The influence of protonation on quinoxaline reactivity supports the hypothesis that the local protein environment in the second coordination sphere of molybdenum cofactor (Moco) could control pyran cyclization. The results also demonstrate that the remarkable chemical reactivity of the pterin-dithiolene ligand is subtly distinct and not reproduced by the simpler quinoxaline analog that is often used to replace pterin in synthetic Moco models.

Hydrogen Atom Abstraction by High-Valent Fe(OH) versus Mn(OH) Porphyrinoid Complexes: Mechanistic Insights from Experimental and Computational Studies.

High-valent metal-hydroxide species have been implicated as key intermediates in hydroxylation chemistry catalyzed by heme monooxygenases such as the cytochrome P450s. However, in some classes of P450s, a bifurcation from the typical oxygen rebound pathway is observed, wherein the FeIV(OH)(porphyrin) species carries out a net hydrogen atom transfer reaction to form alkene metabolites. In this work, we examine the hydrogen atom transfer (HAT) reactivity of FeIV(OH)(ttppc) (1), ttppc = 5,10,15-tris(2,4,6-triphenyl)-phenyl corrole, toward substituted phenol derivatives. The iron hydroxide complex 1 reacts with a series of para-substituted 2,6-di-tert-butylphenol derivatives (4-X-2,6-DTBP; X = OMe, Me, Et, H, Ac), with second-order rate constants k2 = 3.6(1)-1.21(3) × 104 M-1 s-1 and yielding linear Hammett and Marcus plot correlations. It is concluded that the rate-determining step for O-H cleavage occurs through a concerted HAT mechanism, based on mechanistic analyses that include a KIE = 2.9(1) and DFT calculations. Comparison of the HAT reactivity of 1 to the analogous Mn complex, MnIV(OH)(ttppc), where only the central metal ion is different, indicates a faster HAT reaction and a steeper Hammett slope for 1. The O-H bond dissociation energy (BDE) of the MIII(HO-H) complexes were estimated from a kinetic analysis to be 85 and 89 kcal mol-1 for Mn and Fe, respectively. These estimated BDEs are closely reproduced by DFT calculations and are discussed in the context of how they influence the overall H atom transfer reactivity.

Pedicle Orientation in Free-Flap Microvascular Maxillofacial Reconstruction.

Oncologic and traumatic defects of the maxilla can pose a challenge to patients, reconstructive surgeons, and maxillofacial prosthodontists in an attempt to provide satisfactory treatment. Oral-nasal and oral-antral fistulas are frequently treated with soft tissue flaps, osteocutaneous flaps, or a maxillofacial obturator. The free fibula microvascular osteocutaneous flap has proved the workhorse of these maxillary and mandibular reconstructions. The success of microvascular reconstruction often hinges on flap viability in the immediate postoperative period. With most flap failures attributed to vascular compromise resulting from clot formation and venous congestion, uncompressed, and nontortuous pedicle positioning demands surgical attention. Although the use of the free fibula flap in maxillary reconstruction is a well-described and predictable procedure, the specifics of the flap inset with respect to pedicle positioning and technique within the maxilla and neck have not been clearly detailed in the available studies. In the present technique note, we have provided our surgical description for pedicle positioning and anatomic alterations in an attempt to improve microvascular anastomosis flap success.

Anterior lumbar interbody fusion versus transforaminal lumbar interbody fusion for correction of lumbosacral fractional curves in adult (thoraco)lumbar scoliosis: A systematic review.

Background: Anterior lumbar interbody fusion (ALIF) or transforaminal lumbar interbody fusion (TLIF) may be used to correct the lumbosacral fractional curve (LsFC) in de novo adult (thoraco) lumbar scoliosis. Yet, the relative benefits of ALIF and TLIF for LsFC correction remain largely undetermined. Purpose: To compare the currently available data comparing radiographic correction of the LsFC provided by ALIF and TLIF of LsFC in adult (thoraco)lumbar scoliosis. Methods: A systematic review was performed on original articles discussing fractional curve correction of lumbosacral spinal deformity (using search criteria: "lumbar" and "fractional curve"). Articles which discussed TLIF or ALIF for LsFC correction were presented and radiographic results for TLIF and ALIF were compared. Results: Thirty-one articles were returned in the original search criteria, with 7 articles included in the systematic review criteria. All 7 articles presented radiographic results using TLIF for LsFC correction. Three of these articles also discussed results for patients whose LsFC were treated with ALIFs; 2 articles directly compared TLIF and ALIF for LsFC correction. Level III and level IV evidence indicated ALIF as advantageous for reducing the coronal Cobb angle of the LsFC. There were mixed results on relative efficacy of ALIF and TLIF in the LsFC for restoration of adequate global coronal alignment. Conclusions: Limited level III and IV evidence suggests ALIF as advantageous for reducing the coronal Cobb angle of the LsFC in de novo adult (thoraco) lumbar scoliosis. Relative efficacy of ALIF and TLIF in the LsFC for restoration of global coronal alignment may be dictated by several factors, including directionality and magnitude of preoperative coronal deformity. Given the limited and low-quality evidence, additional research is warranted to determine the ideal interbody support strategies to address the LsFC in adult (thoraco) lumbar scoliosis.

Asleep triple-modality motor mapping for perirolandic gliomas: an update on outcomes.

OBJECTIVE: Maximal safe resection of gliomas near motor pathways is facilitated by intraoperative mapping. Here, the authors review their results with triple-modality asleep motor mapping with motor evoked potentials and bipolar and monopolar stimulation for cortical and subcortical mapping during glioma surgery in an expanded cohort. METHODS: This was a retrospective analysis of patients who underwent resection of a perirolandic glioma near motor pathways. Clinical and neuromonitoring data were extracted from the electronic medical records for review. All patients with new or worsened postoperative motor deficits were followed for at least 6 months. Regression analyses were performed to assess factors associated with a persistent motor deficit. RESULTS: Between January 2018 and December 2021, 160 operations were performed in 151 patients with perirolandic glioma. Sixty-four patients (40%) had preoperative motor deficits, and the median extent of resection was 98%. Overall, patients in 38 cases (23.8%) had new or worse immediate postoperative deficits by discharge, and persistent deficits by 6 months were seen in 6 cases (3.8%), all in patients with high-grade gliomas. There were no new persistent deficits in low-grade glioma patients (0%). The risk factors for a persistent deficit included an insular tumor component (OR 8.6, p = 0.01), preoperative motor weakness (OR 8.1, p = 0.03), intraoperative motor evoked potential (MEP) changes (OR 36.5, p < 0.0001), and peri-resection cavity ischemia (OR 7.5, p = 0.04). Most persistent deficits were attributable to ischemic injury despite structural preservation of the descending motor tracts. For patients with persistent motor deficits, there were 3 cases (50%) in which a change in MEP was noted but subsequent subcortical monopolar stimulation still elicited a response in the corresponding muscle groups, suggesting axonal activation distal to a point of injury. CONCLUSIONS: Asleep triple motor mapping results in a low rate of permanent deficits, especially for low-grade gliomas. Peri-resection cavity ischemia continues to be a significant risk factor for permanent deficit despite maintaining appropriate distance for subcortical tracts based on monopolar feedback.

Correlation of Brain Metastasis Genomic Alterations with Preoperative Imaging Features.

BACKGROUND: The aim of this study was to examine associations between genomic alterations in brain metastases and common preoperative imaging findings including overt intratumoral hemorrhage, cystic features, and edema. METHODS: A single-center, retrospective study was performed including patients who underwent surgical resection of brain metastasis with available preoperative magnetic resonance imaging (MRI). Next-generation sequencing of more than 500 coding genes was performed on the resected brain metastases. Preoperative MRI was reviewed to identify the presence of intratumoral hemorrhage, cystic features, and edema in the resected brain metastasis. Genomic data were then correlated with the imaging features using univariate and multivariate nominal logistic regression analyses. RESULTS: We included 144 brain metastases from 141 patients in the study cohort. Half (72) of the metastases had an intratumoral hemorrhage, 26 (18%) had cystic features, and 130 (90%) had edema. Mutations in TP53 were associated with a reduced risk of intratumoral hemorrhage (odds ratio [OR] 0.2, 95% confidence interval [CI] 0.07-0.5, P < 0.001). Mutations in RB1 and CCND1 were associated with elevated risk of the metastasis having cystic features (OR 10.3, 95% CI 2.0-52.6, P = 0.005, OR 18.4, 95% CI 2.2-155.3, P = 0.008, respectively). PIK3CA mutations were associated with a reduced risk of peritumoral edema (OR 0.2, 95% CI 0.04-0.8, P = 0.03). CONCLUSIONS: Several genomic alterations in brain metastases are associated with MRI features including hemorrhage, cystic features, and edema. These results provide insight into tumor biology and patients at risk of developing these imaging features.

Intraventricular meningioma resection and visual outcomes.

OBJECTIVE: Intraventricular meningiomas (IVMs) of the lateral ventricle are rare tumors that present surgical challenges because of their deep location. Visual field deficits (VFDs) are one risk associated with these tumors and their treatment. VFDs may be present preoperatively due to the tumor and mass effect (tumor VFDs) or may develop postoperatively due to the surgical approach (surgical VFDs). This institutional series aimed to review surgical outcomes following resection of IVMs, with a focus on VFDs. METHODS: Patients who received IVM resection at one academic institution between the years 1996 and 2021 were retrospectively reviewed. Diffusion tensor imaging (DTI) reconstructions of the optic radiations around the tumor were performed from preoperative IVM imaging. The VFD course and resolution were documented. RESULTS: Thirty-two adult patients underwent IVM resection, with gross-total resection in 30 patients (93.8%). Preoperatively, tumor VFDs were present in 6 patients, resolving after surgery in 5 patients. Five other patients (without preoperative VFD) had new persistent surgical VFDs postoperatively (5/32, 15.6%) that persisted to the most recent follow-up. Of the 5 patients with persistent surgical VFDs, 4 received a transtemporal approach and 1 received a transparietal approach, and all these deficits occurred prior to regular use of DTI in preoperative imaging. CONCLUSIONS: New surgical VFDs are a common neurological deficit after IVM resection. Preoperative DTI may demonstrate distortion of the optic radiations around the tumor, thus revealing safe operative corridors to prevent surgical VFDs.

Physiological effects of dual target DBS in an individual with Parkinson's disease and a sensing-enabled pulse generator.

INTRODUCTION: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus (GP) is an established therapy for Parkinson's disease (PD). Novel DBS devices can record local field potential (LFP) physiomarkers from the STN or GP. While beta (13-30 Hz) and gamma (40-90 Hz) STN and GP LFP oscillations correlate with PD motor severity and with therapeutic effects of treatments, STN-GP interactions in electrophysiology in patients with PD are not well characterized. METHODS: Simultaneous bilateral STN and GP LFPs were recorded in a patient with PD who received bilateral STN-DBS and GP-DBS. Power spectra in each target and STN-GP coherence were assessed in various ON- and OFF-levodopa and DBS states, both at rest and with voluntary movement. RESULTS: OFF-levodopa and OFF-DBS, beta peaks were present at bilateral STN and GP, coincident with prominent STN-GP beta coherence. Levodopa and dual-target-DBS (simultaneous STN-DBS and GP-DBS) completely suppressed STN-GP coherence. Finely-tuned gamma (FTG) activity at half the stimulation frequency (62.5 Hz) was seen in the STN during GP-DBS at rest. To assess the effects of movement on FTG activity, we recorded LFPs during instructed movement. We observed FTG activity in bilateral GP and bilateral STN during contralateral body movements while on GP-DBS and ON-levodopa. No FTG was seen with STN-DBS or dual-target-DBS. CONCLUSION: Dual-target-DBS and levodopa suppressed STN-GP coherence. FTG throughout the basal ganglia was induced by GP-DBS in the presence of levodopa and movement. This bilateral STN-FTG and GP-FTG corresponded with the least severe bradykinesia state, suggesting a pro-kinetic role for FTG.

Vagus nerve stimulation for enhanced stroke recovery after intracerebral hemorrhage: illustrative case.

BACKGROUND: Randomized controlled trial (RCT) evidence has revealed the efficacy of vagus nerve stimulation (VNS) paired with rehabilitation therapy, over therapy alone, for upper-limb functional recovery after ischemic stroke. However, this technique has not yet been described for the recovery of chronic motor deficits after hemorrhagic stroke. OBSERVATIONS: Three years after left putaminal intracerebral hemorrhagic stroke with chronic upper-limb functional deficits, a patient was treated with VNS for enhanced stroke recovery. VNS was paired with 6 weeks of in-clinic physical therapy, resulting in upper-limb functional improvement of 14 points on the Fugl-Meyer Assessment Upper Extremity (FMA-UE) index for stroke recovery (maximum score of 66 equating to normal function). This improvement was more than 1 standard deviation above the improvement documented in the first successful RCT of VNS paired with therapy for ischemic stroke (5.0 ± 4.4 improvement on FMA-UE). LESSONS: VNS is a promising therapy for enhanced recovery after hemorrhagic stroke and may offer greater improvement in function compared to that after ischemic stroke. Improvement in function can occur years after the time of intracerebral hemorrhage.

Interpretable video-based tracking and quantification of parkinsonism clinical motor states.

Quantification of motor symptom progression in Parkinson's disease (PD) patients is crucial for assessing disease progression and for optimizing therapeutic interventions, such as dopaminergic medications and deep brain stimulation. Cumulative and heuristic clinical experience has identified various clinical signs associated with PD severity, but these are neither objectively quantifiable nor robustly validated. Video-based objective symptom quantification enabled by machine learning (ML) introduces a potential solution. However, video-based diagnostic tools often have implementation challenges due to expensive and inaccessible technology, and typical "black-box" ML implementations are not tailored to be clinically interpretable. Here, we address these needs by releasing a comprehensive kinematic dataset and developing an interpretable video-based framework that predicts high versus low PD motor symptom severity according to MDS-UPDRS Part III metrics. This data driven approach validated and robustly quantified canonical movement features and identified new clinical insights, not previously appreciated as related to clinical severity, including pinkie finger movements and lower limb and axial features of gait. Our framework is enabled by retrospective, single-view, seconds-long videos recorded on consumer-grade devices such as smartphones, tablets, and digital cameras, thereby eliminating the requirement for specialized equipment. Following interpretable ML principles, our framework enforces robustness and interpretability by integrating (1) automatic, data-driven kinematic metric evaluation guided by pre-defined digital features of movement, (2) combination of bi-domain (body and hand) kinematic features, and (3) sparsity-inducing and stability-driven ML analysis with simple-to-interpret models. These elements ensure that the proposed framework quantifies clinically meaningful motor features useful for both ML predictions and clinical analysis.

Genomic alterations associated with postoperative nodular leptomeningeal disease after resection of brain metastases.

OBJECTIVE: The relationship between brain metastasis resection and risk of nodular leptomeningeal disease (nLMD) is unclear. This study examined genomic alterations found in brain metastases with the aim of identifying alterations associated with postoperative nLMD in the context of clinical and treatment factors. METHODS: A retrospective, single-center study was conducted on patients who underwent resection of brain metastases between 2014 and 2022 and had clinical and genomic data available. Postoperative nLMD was the primary endpoint of interest. Targeted next-generation sequencing of > 500 oncogenes was performed in brain metastases. Cox proportional hazards analyses were performed to identify clinical features and genomic alterations associated with nLMD. RESULTS: The cohort comprised 101 patients with tumors originating from multiple cancer types. There were 15 patients with nLMD (14.9% of the cohort) with a median time from surgery to nLMD diagnosis of 8.2 months. Two supervised machine learning algorithms consistently identified CDKN2A/B codeletion and ERBB2 amplification as the top predictors associated with postoperative nLMD across all cancer types. In a multivariate Cox proportional hazards analysis including clinical factors and genomic alterations observed in the cohort, tumor volume (× 10 cm3; HR 1.2, 95% CI 1.01-1.5; p = 0.04), CDKN2A/B codeletion (HR 5.3, 95% CI 1.7-16.9; p = 0.004), and ERBB2 amplification (HR 3.9, 95% CI 1.1-14.4; p = 0.04) were associated with a decreased time to postoperative nLMD. CONCLUSIONS: In addition to increased resected tumor volume, ERBB2 amplification and CDKN2A/B deletion were independently associated with an increased risk of postoperative nLMD across multiple cancer types. Additional work is needed to determine if targeted therapy decreases this risk in the postoperative setting.

Computer-assisted Navigation in Lumbar Spine Instrumented Fusions: Comparison of In-hospital and 30-Day Postoperative Complications With Nonnavigated Fusions in a National Database.

OBJECTIVE: To compare in-hospital and 30-day postoperative complications for lumbar spine operations with and without use of computer-assisted navigation. METHODS: Patients who underwent 1-level to 3-level lumbar spinal instrumentation and fusions 2011 to 2014 were identified in the American College of Surgeons National Surgical Quality Improvement Program database. Emergent procedures and patients aged younger than 18 years were excluded. Patients whose surgery involved the use of computer-assisted navigation were propensity score matched 1:4 based on preoperative demographics and comorbidities to operations without the use of navigation. Multivariate analysis was done to compare postoperative complications. RESULTS: In total, 8,500 patients (average age: 60.7 ± 12.9, male 3,866, female 4,634) were analyzed (1,700 navigation, 6,800 Non-Navigated). Operations with navigation had significantly fewer overall complications (24% vs. 27%, P = 0.008; odds ratio [OR] = 0.83; CI = 0.73 to 0.95), fewer minor complications (20% vs. 24%, P = 0.002; OR = 0.80; CI = 0.70 to 0.91), fewer blood transfusions (17% v. 20%, P = 0.013; OR = 0.82; CI = 0.71 to 0.95), more wound dehiscences (0.4% vs. 0.8%, P = 0.022; OR = 2.16; CI = 1.12,4.19), and shorter average lengths of hospital stays (4.8 ± 4.8 vs. 5.1 ± 5.8 days, P = 0.01). Operations with computer navigation had significantly longer average surgical times (247 ± 129 vs 221 ± 115 minutes, P < 0.001). No significant differences were observed in 30-day revision rates, readmissions, and mortality. CONCLUSION: Although use of computer-assisted navigation in short-segment lumbar spine fusions (1 to 3 levels) did not decrease revision rates for screw misplacement within 30 days postoperatively, it independently reduced the frequency of blood transfusions and minor complications and decreased hospital lengths of stay compared with operations without navigation. These benefits came at the expense of increased surgical times and wound dehiscences within 30 days postoperatively. Given the inherent limitations of large national databases, these results warrant confirmation through prospective, multicenter investigations.

Predictive models to assess risk of extended length of stay in adults with spinal deformity and lumbar degenerative pathology: development and internal validation.

BACKGROUND CONTEXT: Postoperative recovery after adult spinal deformity (ASD) operations is arduous, fraught with complications, and often requires extended hospital stays. A need exists for a method to rapidly predict patients at risk for extended length of stay (eLOS) in the preoperative setting. PURPOSE: To develop a machine learning model to preoperatively estimate the likelihood of eLOS following elective multi-level lumbar/thoracolumbar spinal instrumented fusions (≥3 segments) for ASD. STUDY DESIGN/SETTING: Retrospectively from a state-level inpatient database hosted by the Health care cost and Utilization Project. PATIENT SAMPLE: Of 8,866 patients of age ≥50 with ASD undergoing elective lumbar or thoracolumbar multilevel instrumented fusions. OUTCOME MEASURES: The primary outcome was eLOS (>7 days). METHODS: Predictive variables consisted of demographics, comorbidities, and operative information. Significant variables from univariate and multivariate analyses were used to develop a logistic regression-based predictive model that use six predictors. Model accuracy was assessed through area under the curve (AUC), sensitivity, and specificity. RESULTS: Of 8,866 patients met inclusion criteria. A saturated logistic model with all significant variables from multivariate analysis was developed (AUC=0.77), followed by generation of a simplified logistic model through stepwise logistic regression (AUC=0.76). Peak AUC was reached with inclusion of six selected predictors (combined anterior and posterior approach, surgery to both lumbar and thoracic regions, ≥8 level fusion, malnutrition, congestive heart failure, and academic institution). A cutoff of 0.18 for eLOS yielded a sensitivity of 77% and specificity of 68%. CONCLUSIONS: This predictive model can facilitate identification of adults at risk for eLOS following elective multilevel lumbar/thoracolumbar spinal instrumented fusions for ASD. With a fair diagnostic accuracy, the predictive calculator will ideally enable clinicians to improve preoperative planning, guide patient expectations, enable optimization of modifiable risk factors, facilitate appropriate discharge planning, stratify financial risk, and accurately identify patients who may represent high-cost outliers. Future prospective studies that validate this risk assessment tool on external datasets would be valuable.