Wireless Optofluidic Systems for Programmable In Vivo Pharmacology and Optogenetics.

In vivo pharmacology and optogenetics hold tremendous promise for dissection of neural circuits, cellular signaling, and manipulating neurophysiological systems in awake, behaving animals. Existing neural interface technologies, such as metal cannulas connected to external drug supplies for pharmacological infusions and tethered fiber optics for optogenetics, are not ideal for minimally invasive, untethered studies on freely behaving animals. Here, we introduce wireless optofluidic neural probes that combine ultrathin, soft microfluidic drug delivery with cellular-scale inorganic light-emitting diode (µ-ILED) arrays. These probes are orders of magnitude smaller than cannulas and allow wireless, programmed spatiotemporal control of fluid delivery and photostimulation. We demonstrate these devices in freely moving animals to modify gene expression, deliver peptide ligands, and provide concurrent photostimulation with antagonist drug delivery to manipulate mesoaccumbens reward-related behavior. The minimally invasive operation of these probes forecasts utility in other organ systems and species, with potential for broad application in biomedical science, engineering, and medicine.

Multiple sessions of therapeutic electrical stimulation using implantable thin-film wireless nerve stimulators improve functional recovery after sciatic nerve isograft repair.

INTRODUCTION/AIMS: Although therapeutic electrical stimulation (TES) of injured peripheral nerve promotes axon regeneration and functional recovery, clinical applications of this therapy are limited to the intraoperative timeframe. Implantable, thin-film wireless nerve stimulators offer a potential solution to this problem by enabling delivery of electrical stimuli to an injured nerve over a period of several days post-surgery. The aim of this study was to determine the optimal time course of stimulation for maximizing functional recovery in a rat sciatic nerve isograft repair model. METHODS: Adult male Lewis rats underwent thin-film wireless nerve stimulator implantation following sciatic nerve transection and 40 mm nerve isograft repair. Immediately after surgery, animals began a daily regimen of TES for up to 12 consecutive days. Functional recovery was assessed by compound muscle action potential (CMAP), evoked muscle force, wet muscle mass, and axon counting. RESULTS: Serial CMAP measurements increased in amplitude over the course of the study, yet no significant difference between cohorts for serial or terminal CMAPs was observed. Axon counts and wet muscle mass measurements were greatest in the 6-day stimulation group, which correlated with a significant increase in evoked muscle force for the 6-day stimulation group at the terminal time point. DISCUSSION: Six daily sessions of TES were found to be most effective for augmenting functional recovery compared to other time courses of stimulation. Future studies should incorporate additional subjects and track axonal sprouting or measure neurotrophin levels during the therapeutic window to further elucidate the mechanisms behind, and ideal amount of, TES.

Feasibility of postoperative diffusion-weighted imaging to assess representations of spinal cord microstructure in cervical spondylotic myelopathy.

OBJECTIVE: Diffusion basis spectrum imaging (DBSI) has shown promise in evaluating cervical spinal cord structural changes in patients with cervical spondylotic myelopathy (CSM). DBSI may also be valuable in the postoperative setting by serially tracking spinal cord microstructural changes following decompressive cervical spine surgery. Currently, there is a paucity of studies investigating this topic, likely because of challenges in resolving signal distortions from spinal instrumentation. Therefore, the objective of this study was to assess the feasibility of DBSI metrics extracted from the C3 spinal level to evaluate CSM patients postoperatively. METHODS: Fifty CSM patients and 20 healthy controls were enrolled in a single-center prospective study between 2018 and 2020. All patients and healthy controls underwent preoperative and postoperative diffusion-weighted MRI (dMRI) at a 2-year follow-up. All CSM patients underwent decompressive cervical surgery. The modified Japanese Orthopaedic Association (mJOA) score was used to categorize CSM patients as having mild, moderate, or severe myelopathy. DBSI metrics were extracted from the C3 spinal cord level to minimize image artifact and reduce partial volume effects. DBSI anisotropic tensors evaluated white matter tracts through fractional anisotropy, axial diffusivity, radial diffusivity, and fiber fraction. DBSI isotropic tensors assessed extra-axonal pathology through restricted and nonrestricted fractions. RESULTS: Of the 50 CSM patients, both baseline and postoperative dMR images with sufficient quality for analysis were obtained in 27 patients. These included 15 patients with mild CSM (mJOA scores 15-17), 7 with moderate CSM (scores 12-14), and 5 with severe CSM (scores 0-11), who were followed up for a mean of 23.5 (SD 4.1, range 11-31) months. All preoperative C3-level DBSI measures were significantly different between CSM patients and healthy controls (p < 0.05), except DBSI fractional anisotropy (p = 0.31). At the 2-year follow-up, the same significance pattern was found between CSM patients and healthy controls, except DBSI radial diffusivity was no longer statistically significant (p = 0.75). When assessing change (i.e., postoperative - preoperative values) in C3-level DBSI measures, CSM patients exhibited significant decreases in DBSI radial diffusivity (p = 0.02), suggesting improvement in myelin integrity (i.e., remyelination) at the 2-year follow-up. Among healthy controls, there was no significant difference in DBSI metrics over time. CONCLUSIONS: DBSI metrics derived from dMRI at the C3 spinal level can be used to provide meaningful insights into representations of the spinal cord microstructure of CSM patients at baseline and 2-year follow-up. DBSI may have the potential to characterize white matter tract recovery and inform outcomes following decompressive cervical surgery for CSM.

Bioresorbable silicon electronic sensors for the brain.

Many procedures in modern clinical medicine rely on the use of electronic implants in treating conditions that range from acute coronary events to traumatic injury. However, standard permanent electronic hardware acts as a nidus for infection: bacteria form biofilms along percutaneous wires, or seed haematogenously, with the potential to migrate within the body and to provoke immune-mediated pathological tissue reactions. The associated surgical retrieval procedures, meanwhile, subject patients to the distress associated with re-operation and expose them to additional complications. Here, we report materials, device architectures, integration strategies, and in vivo demonstrations in rats of implantable, multifunctional silicon sensors for the brain, for which all of the constituent materials naturally resorb via hydrolysis and/or metabolic action, eliminating the need for extraction. Continuous monitoring of intracranial pressure and temperature illustrates functionality essential to the treatment of traumatic brain injury; the measurement performance of our resorbable devices compares favourably with that of non-resorbable clinical standards. In our experiments, insulated percutaneous wires connect to an externally mounted, miniaturized wireless potentiostat for data transmission. In a separate set-up, we connect a sensor to an implanted (but only partially resorbable) data-communication system, proving the principle that there is no need for any percutaneous wiring. The devices can be adapted to sense fluid flow, motion, pH or thermal characteristics, in formats that are compatible with the body's abdomen and extremities, as well as the deep brain, suggesting that the sensors might meet many needs in clinical medicine.

First in-human report of the clinical accuracy of thoracolumbar percutaneous pedicle screw placement using augmented reality guidance.

OBJECTIVE: Augmented reality (AR) is an emerging technology that has great potential for guiding the safe and accurate placement of spinal hardware, including percutaneous pedicle screws. The goal of this study was to assess the accuracy of 63 percutaneous pedicle screws placed at a single institution using an AR head-mounted display (ARHMD) system. METHODS: Retrospective analyses were performed for 9 patients who underwent thoracic and/or lumbar percutaneous pedicle screw placement guided by ARHMD technology. Clinical accuracy was assessed via the Gertzbein-Robbins scale by the authors and by an independent musculoskeletal radiologist. Thoracic pedicle subanalysis was also performed to assess screw accuracy based on pedicle morphology. RESULTS: Nine patients received thoracic or lumbar AR-guided percutaneous pedicle screws. The mean age at the time of surgery was 71.9 ± 11.5 years and the mean number of screws per patient was 7. Indications for surgery were spinal tumors (n = 4, 44.4%), degenerative disease (n = 3, 33.3%), spinal deformity (n = 1, 11.1%), and a combination of deformity and infection (n = 1, 11.1%). Presenting symptoms were most commonly low-back pain (n = 7, 77.8%) and lower-extremity weakness (n = 5, 55.6%), followed by radicular lower-extremity pain, loss of lower-extremity sensation, or incontinence/urinary retention (n = 3 each, 33.3%). In all, 63 screws were placed (32 thoracic, 31 lumbar). The accuracy for these screws was 100% overall; all screws were Gertzbein-Robbins grade A or B (96.8% grade A, 3.2% grade B). This accuracy was achieved in the thoracic spine regardless of pedicle cancellous bone morphology. CONCLUSIONS: AR-guided surgery demonstrated a 100% accuracy rate for the insertion of 63 percutaneous pedicle screws in 9 patients (100% rate of Gertzbein-Robbins grade A or B screw placement). Using an ARHMS system for the placement of percutaneous pedicle screws showed promise, but further validation using a larger cohort of patients across multiple surgeons and institutions will help to determine the true accuracy enabled by this technology.

Frequency and Risk Factors for Prolonged Opioid Prescriptions After Surgery for Brachial Plexus Injury.

PURPOSE: We hypothesized that patients with preoperative opioid prescriptions and diagnoses of depression and anxiety would be at increased risk for prolonged opioid prescriptions after surgery for brachial plexus injury (BPI). METHODS: Using an administrative database of privately insured patients, we assembled a cohort of BPI surgery patients and a control group of non-BPI patients, matching for age, sex, and year. Pharmacy claims for prescriptions filled for opioids and neuropathic pain medications were examined 12 months before surgery to 180 days after surgery. The primary outcome was prolonged opioid prescription, defined as receiving a prescription 90 to 180 days after the index (BPI surgery or randomly selected date of service for controls). Multivariable regression was used to examine risk factors for postoperative opioid use, including diagnoses of depression, anxiety, drug abuse, tobacco use, and preoperative use of opioids and neuropathic pain medications. A subgroup analysis was performed for opioid-naive BPI patients between 30 days to 1 year before surgery. RESULTS: Among BPI surgery patients (n = 1,936), 27.7% had prolonged opioid prescriptions. Among opioid-naive BPI patients (n = 911), 10.8% had prolonged opioid prescriptions. In controls (n = 19,360), frequency of prolonged opioid prescriptions was 0.11%. Among all BPI patients, after adjustment for age and sex, predictors of prolonged postoperative opioid prescriptions in BPI patients were preoperative opioids, preoperative neuropathic pain medication use, histories of drug abuse, tobacco use, and anxiety. CONCLUSIONS: Prolonged postoperative opioids prescriptions after BPI reconstruction are higher than previous estimates among other surgical patients. In addition to establishing normative data among this population, our findings serve to increase awareness of risk factors for prolonged opioids after BPI reconstruction and encourage coordinated multidisciplinary care. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Minimally invasive transforaminal lumbar interbody fusion with expandable versus static interbody devices: radiographic assessment of sagittal segmental and pelvic parameters.

OBJECTIVE Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) has been adopted as an alternative technique to hasten recovery and minimize postoperative morbidity. Advances in instrumentation technologies and operative techniques have evolved to maximize patient outcomes as well as radiographic results. The development of expandable interbody devices allows a surgeon to perform MIS-TLIF with minimal tissue disruption. However, sagittal segmental and pelvic radiographic outcomes after MIS-TLIF with expandable interbody devices are not well characterized. The object of this study is to evaluate the radiographic sagittal lumbar segmental and pelvic parameter outcomes of MIS-TLIF performed using an expandable interbody device. METHODS A retrospective review of MIS-TLIFs performed between 2014 and 2016 at a high-volume center was performed. Radiographic measurements were performed on lateral radiographs before and after MIS-TLIF with static or expandable interbody devices. Radiographic measurements included disc height, foraminal height, fused disc angle, lumbar lordosis, pelvic incidence, sacral slope, and pelvic tilt. Mismatch between pelvic incidence and lumbar lordosis were calculated for each radiograph. RESULTS A total of 48 MIS-TLIFs were performed, predominantly at the L4-5 level, in 44 patients. MIS-TLIF with an expandable interbody device led to a greater and more sustained increase in disc height when compared with static interbody devices. Foraminal height increased after MIS-TLIF with expandable but not with static interbody devices. MIS-TLIF with expandable interbody devices increased index-level segmental lordosis more than with static interbody devices. The increase in segmental lordosis was sustained in the patients with expandable interbody devices but not in patients with static interbody devices. For patients with a collapsed disc space, MIS-TLIF with an expandable interbody device provided superior and longer-lasting increases in disc height, foraminal height, and index-level segmental lordosis than in comparison with patients with static interbody devices. Using an expandable interbody device improved the Oswestry Disability Index scores more than using a static interbody device, and both disc height and segmental lordosis were correlated with improved clinical outcome. Lumbar MIS-TLIF with expandable or static interbody devices had no effect on overall lumbar lordosis, pelvic parameters, or pelvic incidence-lumbar lordosis mismatch. CONCLUSIONS Performing MIS-TLIF with an expandable interbody device led to a greater and longer-lasting restoration of disc height, foraminal height, and index-level segmental lordosis than MIS-TLIF with a static interbody device, especially for patients with a collapsed disc space. However, neither technique had any effect on radiographic pelvic parameters.

An update on addressing important peripheral nerve problems: challenges and potential solutions.

From time to time it is thoughtful and productive to review a medical field and reflect upon what are the major issues that need to be addressed and what is being done to do so. This review article is not meant to be all-inclusive but rather focuses on four evolving areas in the field of peripheral nerve disorders and treatments: (1) nerve surgery under ultrasound guidance using a new ultra-minimally invasive thread technique; (2) evolving magnetic resonance imaging (MRI) and ultrasound imaging techniques that are helping to both diagnose and treat a variety of peripheral nerve problems including entrapment neuropathies, traumatic nerve injuries, and masses arising from nerves; (3) promoting recovery after nerve injury using electrical stimulation; and (4) developing animal models to reproduce a severe nerve injury (neurotmetic grade in continuity) that requires a surgical intervention and repair. In each area we first describe the current challenges and then discuss new and emerging techniques and approaches. It is our hope that this article will bring added attention and resources to help better address peripheral nerve problems that remain a challenge for both patients and physicians.

Serial assessment of functional recovery following nerve injury using implantable thin-film wireless nerve stimulators.

INTRODUCTION: Comprehensive assessment of the time course of functional recovery following peripheral nerve repair is critical for surgical management of peripheral nerve injuries. This study describes the design and implementation of a novel implantable wireless nerve stimulator capable of repeatedly interfacing peripheral nerve tissue and providing serial evaluation of functional recovery postoperatively. METHODS: Thin-film wireless implants were fabricated and subcutaneously implanted into Lewis rats. Wireless implants were used to serially stimulate rat sciatic nerve and assess functional recovery over 3 months following various nerve injuries. RESULTS: Wireless stimulators demonstrated consistent performances over 3 months in vivo and successfully facilitated serial assessment of nerve and muscle function following nerve crush and nerve transection injuries. CONCLUSIONS: This study highlights the ability of implantable wireless nerve stimulators to provide a unique view into the time course of functional recovery in multiple motor targets. Muscle Nerve 54: 1114-1119, 2016.

Increased spasticity from a fracture in the baclofen catheter caused by Charcot spine: case report.

In patients with Charcot spine, a loss of normal feedback response from the insensate spine results in spinal neuropathy. Increasing deformity, which can manifest as sitting imbalance, crepitus, or increased back pain, can result. We present the case of a patient with a high-thoracic spinal cord injury (SCI) who subsequently developed a Charcot joint at the T10-11 level that resulted in a dramatic increase in previously controlled spasticity after fracture of an existing baclofen catheter. The 68-year-old man with T4 paraplegia presented with increasing baclofen requirements and radiographic evidence of fracture of the intrathecal baclofen catheter with an associated Charcot joint with extensive bony destruction. The neuropathic spinal arthropathy caused mechanical baclofen catheter malfunction and resulting increased spasticity. The patient was found to have transected both his spinal cord and the baclofen catheter. Treatment consisted of removal of the catheter and stabilization with long-segment instrumentation and fusion from T6 to L2. Follow-up radiographs obtained a year and a half after surgery showed no evidence of hardware failure or significant malalignment. The patient has experienced resolution of symptoms and does not require oral or intrathecal baclofen. This is the only reported case of a Charcot spine causing intrathecal catheter fracture, leading to increased spasticity. This noteworthy case suggests that late spinal instability should be considered in the setting of SCI and increased spasticity.

Schwann cells seeded in acellular nerve grafts improve functional recovery.

INTRODUCTION: This study evaluated whether Schwann cells (SCs) from different nerve sources transplanted into cold-preserved acellular nerve grafts (CP-ANGs) would improve functional regeneration compared with nerve isografts. METHODS: SCs isolated and expanded from motor and sensory branches of rat femoral and sciatic nerves were seeded into 14mm CP-ANGs. Growth factor expression, axonal regeneration, and functional recovery were evaluated in a 14-mm rat sciatic injury model and compared with isografts. RESULTS: At 14 days, motor or sensory-derived SCs increased expression of growth factors in CP-ANGs versus isografts. After 42 days, histomorphometric analysis found CP-ANGs with SCs and isografts had similar numbers of regenerating nerve fibers. At 84 days, muscle force generation was similar for CP-ANGs with SCs and isografts. SC source did not affect nerve fiber counts or muscle force generation. CONCLUSIONS: SCs transplanted into CP-ANGs increase functional regeneration to isograft levels; however SC nerve source did not have an effect.

Academic career progression in AANS/CNS Spine Section award recipients.

OBJECTIVE: The American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) Joint Spine Section awards highlight outstanding abstracts submitted to the AANS/CNS Section on Disorders of the Spine and Peripheral Nerves by trainees interested in spine surgery, although the academic trajectory of awardees has not been studied. The aim of this study was to assess the academic career progression of prior recipients of the Journalistic and Academic Neurosurgical Excellence (JANE), Mayfield, and Kuntz research awards. METHODS: Prior JANE, Mayfield, and Kuntz award recipients were identified using awardee records accrued between 1984 and February 2022. Awardee sex, country of residence, specialty, subspecialty focus, and current academic appointment status (if applicable) were searched online. Awardee h-indices and number of peer-reviewed publications were assessed via Google Scholar profiles (or Scopus if unavailable) and PubMed, respectively. Receipt of federal research funding as principal investigator (PI) was determined using the websites of the National Institutes of Health, the National Science Foundation, and the Department of Defense Congressionally Directed Medical Research Programs. The abstract-to-publication rate was assessed. RESULTS: A total of 7 JANE awards, 57 Mayfield awards, and 149 Kuntz awards were identified. Of the JANE awardees, all recipients were male. Of the 4 unique JANE awardees who completed training, 2 (50.0%) held academic appointments at the time of the study. All of the JANE abstracts were published in peer-reviewed journals. The mean h-index of all JANE awardees was 28 and the mean number of publications was 126. None of the awardees have received federal research funding. Of the Mayfield awards, 98.2% were awarded to males. Of the 43 unique Mayfield awardees who completed training, 20 (46.5%) held faculty appointments at academic medical centers. All of the Mayfield abstracts since 2011 were published in peer-reviewed journals. The mean h-index of all Mayfield awardees was 26 and the mean number of publications was 82. Five Mayfield awardees received National Institutes of Health funding as PI, and 7 awardees received Department of Defense funding as PI. Of the Kuntz awards, 95.3% were awarded to males. Most awards were given to current residents and fellows (46.3%). Of the 55 unique Kuntz awardees who completed training, 31 (56.4%) held faculty appointments at academic medical centers. The abstract-to-publication rate of the total Kuntz abstracts was 70.5%. The mean h-index of all Kuntz awardees was 15 and the mean number of publications was 58. Five Kuntz awardees (3.4%) received federal research funding as PI. CONCLUSIONS: Many recipients of the JANE, Mayfield, and Kuntz Joint Spine Section awards have successfully translated award abstracts into peer-reviewed publications. Furthermore, approximately one-third of the awardees are active in academic neurosurgery, with some having secured federal research funding.

The Importance of Planning Ahead: A Three-Dimensional Analysis of the Novel Trans-Facet Corridor for Posterior Lumbar Interbody Fusion Using Segmentation Technology.

BACKGROUND: The rise of minimally invasive lumbar fusions and advanced imaging technologies has facilitated the introduction of novel surgical techniques with the trans-facet approach being one of the newest additions. We aimed to quantify any pathology-driven anatomic changes to the trans-facet corridor, which could thereby alter the ideal laterality of approach to the disc space. METHODS: In this retrospective cohort study, we measured the areas and maximum permissible cannula diameters of the trans-facet corridor using commercially available software (BrainLab, Munich, Germany). Exiting and traversing nerve roots, thecal sacs, and lumbar vertebrae were manually segmented on T2-SPACE magnetic resonance imaging. Spondylolisthesis, disc protrusions, and disc space heights were recorded. RESULTS: A total of 118 trans-facet corridors were segmented bilaterally in 16 patients (65.6 ± 12.1 years, 43.8% female, body mass index 29.2 ± 5.1 kg/m2). The mean areas at L1-L2, L2-L3, L3-L4, and L4-L5 were 89.4 ± 24.9 mm2, 124 ± 39.4 mm2, 123 ± 26.6 mm2, and 159 ± 42.7 mm2, respectively. The mean permissible cannula diameter at the same levels were 7.85 ± 1.43 mm, 8.98 ± 1.72 mm, 8.93 ± 1.26 mm, and 10.2 ± 1.94 mm, respectively. Both parameters increased caudally. Higher degrees for spondylolisthesis were associated with larger areas and maximum cannula diameters on regression analysis (P < 0.001). CONCLUSIONS: Our results illustrate that pathology, like spondylolisthesis, can increase the area of the trans-facet corridor. By understanding this effect, surgeons can better decide on the optimal approach to the disc while taking into consideration a patient's unique anatomy.

Evolution of the Transforaminal Lumbar Interbody Fusion (TLIF): From Open to Percutaneous to Patient-Specific.

The transforaminal lumbar interbody fusion (TLIF) has seen significant evolution since its early inception, reflecting advancements in surgical techniques, patient safety, and outcomes. Originally described as an improvement over the posterior lumbar interbody fusion (PLIF), the TLIF began as an open surgical procedure, that notably reduced the need for the extensive neural retractation that hindered the PLIF. In line with the broader practice of surgery, trending toward minimally invasive access, the TLIF was followed by the development of the minimally invasive TLIF (MIS-TLIF), a technique that further decreased tissue trauma and postoperative complications. Subsequent advancements, including Trans-Kambin's Triangle TLIF (percLIF) and transfacet LIF, have continued to refine surgical access, minimize surgical footprint, and reduce the risk of injury to the patient. The latest evolution, as we will describe it, the patient-specific TLIF, is a culmination of the aforementioned adaptations and incorporates advanced imaging and segmentation technologies into perioperative planning, allowing surgeons to tailor approaches based on individual patient anatomy and pathology. These developments signify a shift towards more precise methods in spine surgery. The ongoing evolution of the TLIF technique illustrates the dynamic nature of surgery and emphasizes the need for continued adaptation and refinement.

Implications of Preoperative Depression for Lumbar Spine Surgery Outcomes: A Systematic Review and Meta-Analysis.

Importance: Comorbid depression is common among patients with degenerative lumbar spine disease. Although a well-researched topic, the evidence of the role of depression in spine surgery outcomes remains inconclusive. Objective: To investigate the association between preoperative depression and patient-reported outcome measures (PROMs) after lumbar spine surgery. Data Sources: A systematic search of PubMed, Cochrane Database of Systematic Reviews, Embase, Scopus, PsychInfo, Web of Science, and ClinicalTrials.gov was performed from database inception to September 14, 2023. Study Selection: Included studies involved adults undergoing lumbar spine surgery and compared PROMs in patients with vs those without depression. Studies evaluating the correlation between preoperative depression and disease severity were also included. Data Extraction and Synthesis: All data were independently extracted by 2 authors and independently verified by a third author. Study quality was assessed using Newcastle-Ottawa Scale. Random-effects meta-analysis was used to synthesize data, and I2 was used to assess heterogeneity. Metaregression was performed to identify factors explaining the heterogeneity. Main Outcomes and Measures: The primary outcome was the standardized mean difference (SMD) of change from preoperative baseline to postoperative follow-up in PROMs of disability, pain, and physical function for patients with vs without depression. Secondary outcomes were preoperative and postoperative differences in absolute disease severity for these 2 patient populations. Results: Of the 8459 articles identified, 44 were included in the analysis. These studies involved 21 452 patients with a mean (SD) age of 57 (8) years and included 11 747 females (55%). Among these studies, the median (range) follow-up duration was 12 (6-120) months. The pooled estimates of disability, pain, and physical function showed that patients with depression experienced a greater magnitude of improvement compared with patients without depression, but this difference was not significant (SMD, 0.04 [95% CI, -0.02 to 0.10]; I2 = 75%; P = .21). Nonetheless, patients with depression presented with worse preoperative disease severity in disability, pain, and physical function (SMD, -0.52 [95% CI, -0.62 to -0.41]; I2 = 89%; P < .001), which remained worse postoperatively (SMD, -0.52 [95% CI, -0.75 to -0.28]; I2 = 98%; P < .001). There was no significant correlation between depression severity and the primary outcome. A multivariable metaregression analysis suggested that age, sex (male to female ratio), percentage of comorbidities, and follow-up attrition were significant sources of variance. Conclusions and Relevance: Results of this systematic review and meta-analysis suggested that, although patients with depression had worse disease severity both before and after surgery compared with patients without depression, they had significant potential for recovery in disability, pain, and physical function. Further investigations are needed to examine the association between spine-related disability and depression as well as the role of perioperative mental health treatments.

Diffusion MRI Metrics Characterize Postoperative Clinical Outcomes After Surgery for Cervical Spondylotic Myelopathy.

BACKGROUND AND OBJECTIVES: Advanced diffusion-weighted MRI (DWI) modeling, such as diffusion tensor imaging (DTI) and diffusion basis spectrum imaging (DBSI), may help guide rehabilitation strategies after surgical decompression for cervical spondylotic myelopathy (CSM). Currently, however, postoperative DWI is difficult to interpret, owing to signal distortions from spinal instrumentation. Therefore, we examined the relationship between postoperative DTI/DBSI-extracted from the rostral C3 spinal level-and clinical outcome measures at 2-year follow-up after decompressive surgery for CSM. METHODS: Fifty patients with CSM underwent complete clinical and DWI evaluation-followed by DTI/DBSI analysis-at baseline and 2-year follow-up. Clinical outcomes included the modified Japanese Orthopedic Association score and comprehensive patient-reported outcomes. DTI metrics included apparent diffusion coefficient, fractional anisotropy, axial diffusivity, and radial diffusivity. DBSI metrics evaluated white matter tracts through fractional anisotropy, fiber fraction, axial diffusivity, and radial diffusivity as well as extra-axonal pathology through restricted and nonrestricted fraction. Cross-sectional Spearman's correlations were used to compare postoperative DTI/DBSI metrics with clinical outcomes. RESULTS: Twenty-seven patients with CSM, including 15, 7, and 5 with mild, moderate, and severe disease, respectively, possessed complete baseline and postoperative DWI scans. At 2-year follow-up, there were 10 significant correlations among postoperative DBSI metrics and postoperative clinical outcomes compared with 3 among postoperative DTI metrics. Of the 13 significant correlations, 7 involved the neck disability index (NDI). The strongest relationships were between DBSI axial diffusivity and NDI (r = 0.60, P < .001), DBSI fiber fraction and NDI (rs = -0.58, P < .001), and DBSI restricted fraction and NDI (rs = 0.56, P < .001). The weakest correlation was between DTI apparent diffusion coefficient and NDI (r = 0.35, P = .02). CONCLUSION: Quantitative measures of spinal cord microstructure after surgery correlate with postoperative neurofunctional status, quality of life, and pain/disability at 2 years after decompressive surgery for CSM. In particular, DBSI metrics may serve as meaningful biomarkers for postoperative disease severity for patients with CSM.

Impact of Upper Limb Motor Recovery on Functional Independence After Traumatic Low Cervical Spinal Cord Injury.

Cervical spinal cord injury (SCI) causes devastating loss of upper limb function and independence. Restoration of upper limb function can have a profound impact on independence and quality of life. In low-cervical SCI (level C5-C8), upper limb function can be restored via reinnervation strategies such as nerve transfer surgery. The translation of recovered upper limb motor function into functional independence in activities of daily living (ADLs), however, remains unknown in low cervical SCI (i.e., tetraplegia). The objective of this study was to evaluate the association of patterns in upper limb motor recovery with functional independence in ADLs. This will then inform prioritization of reinnervation strategies focused to maximize function in patients with tetraplegia. This retrospective study performed a secondary analysis of patients with low cervical (C5-C8) enrolled in the SCI Model Systems (SCIMS) database. Baseline neurological examinations and their association with functional independence in major ADLs-i.e., eating, bladder management, and transfers (bed/wheelchair/chair)-were evaluated. Motor functional recovery was defined as achieving motor strength, in modified research council (MRC) grade, of ≥ 3 /5 at one year from ≤ 2/5 at baseline. The association of motor function recovery with functional independence at one-year follow-up was compared in patients with recovered elbow flexion (C5), wrist extension (C6), elbow extension (C7), and finger flexion (C8). A multi-variable logistic regression analysis, adjusting for known factors influencing recovery after SCI, was performed to evaluate the impact of motor function at one year on a composite outcome of functional independence in major ADLs. Composite outcome was defined as functional independence measure score of 6 or higher (complete independence) in at least two domains among eating, bladder management, and transfers. Between 1992 and 2016, 1090 patients with low cervical SCI and complete neurological/functional measures were included. At baseline, 67% of patients had complete SCI and 33% had incomplete SCI. The majority of patients were dependent in eating, bladder management, and transfers. At one-year follow-up, the largest proportion of patients who recovered motor function in finger flexion (C8) and elbow extension (C7) gained independence in eating, bladder management, and transfers. In multi-variable analysis, patients who had recovered finger flexion (C8) or elbow extension (C7) had higher odds of gaining independence in a composite of major ADLs (odds ratio [OR] = 3.13 and OR = 2.87, respectively, p < 0.001). Age 60 years (OR = 0.44, p = 0.01), and complete SCI (OR = 0.43, p = 0.002) were associated with reduced odds of gaining independence in ADLs. After cervical SCI, finger flexion (C8) and elbow extension (C7) recovery translate into greater independence in eating, bladder management, and transfers. These results can be used to design individualized reinnervation plans to reanimate upper limb function and maximize independence in patients with low cervical SCI.

Core outcomes in nerve surgery: development of a core outcome set for ulnar neuropathy at the elbow.

OBJECTIVE: Ulnar neuropathy at the elbow (UNE) is common, affecting 1%-6% of the population. Despite this, there remains a lack of consensus regarding optimal treatment. This is primarily due to the difficulty one encounters when trying to assess the literature. Outcomes are inconsistently reported, which makes comparing studies or developing meta-analyses difficult or even impossible. Thus, there is a need for a core outcome set (COS) for UNE (COS-UNE) to help address this problem. The objective of this study was to utilize a modified Delphi method to develop COS-UNE. METHODS: A 5-stage approach was utilized to develop COS-UNE: stage 1, consortium development; 2, literature review to identify potential outcome measures; 3, Delphi survey to develop consensus on outcomes for inclusion; 4, Delphi survey to develop definitions; and 5, consensus meeting to finalize the COS and definitions. The study followed the Core Outcome Set-STAndards for Development (COS-STAD) recommendations. RESULTS: The Core Outcomes in Nerve Surgery (COINS) Consortium comprised 21 participants, all neurological surgeons representing 11 countries. The final COS-UNE consisted of 22 data points/outcomes covering the domains of demographic characteristics, diagnostics, patient-reported outcomes, motor/sensory outcomes, and complications. Appropriate instruments, methods of testing, and definitions were set. The consensus minimum duration of follow-up was 6 months, with the consensus optimal timepoints for assessment identified as preoperatively and 3, 6, and 12 months postoperatively. CONCLUSIONS: The authors identified consensus data points/outcomes and also provided definitions and specific scales to be utilized to help ensure that clinicians are consistent in their reporting across studies on UNE. This COS should serve as a minimum set of data to be collected in all future neurosurgical studies on UNE. The authors hope that clinicians evaluating ulnar neuropathy will incorporate this COS into routine practice and that future studies will consider this COS in the design phase.

Bioresorbable shape-adaptive structures for ultrasonic monitoring of deep-tissue homeostasis.

Monitoring homeostasis is an essential aspect of obtaining pathophysiological insights for treating patients. Accurate, timely assessments of homeostatic dysregulation in deep tissues typically require expensive imaging techniques or invasive biopsies. We introduce a bioresorbable shape-adaptive materials structure that enables real-time monitoring of deep-tissue homeostasis using conventional ultrasound instruments. Collections of small bioresorbable metal disks distributed within thin, pH-responsive hydrogels, deployed by surgical implantation or syringe injection, allow ultrasound-based measurements of spatiotemporal changes in pH for early assessments of anastomotic leaks after gastrointestinal surgeries, and their bioresorption after a recovery period eliminates the need for surgical extraction. Demonstrations in small and large animal models illustrate capabilities in monitoring leakage from the small intestine, the stomach, and the pancreas.