The primary motor cortex (M1) controls voluntary movements through the coordinated interactions between excitatory pyramidal neurons (Pyr) and inhibitory parvalbumin-expressing interneurons (PV-INs). Although PV-INs are critical for regulating motor output and motor coordination, their role in age-related motor decline remains unclear. Here, we investigated how aging alters PV-INs modulation of corticospinal tract (CST) in mice. Aged mice (>14 Months) exhibited significant motor impairments, including deficits in balance and coordination in the balance beam and rope-pulling tasks, while general locomotor activity remained largely preserved. To determine whether these deficits were associated with altered motor cortical circuitry, we combined optogenetics, ex-vivo electrophysiology, and in-vivo electromyographic (eEMG) recordings. Optogenetic activation of PV-INs in aged M1 slices elicited glutamate receptor-dependent depolarizing postsynaptic potentials in layer V pyramidal neurons, indicating recruitment of a glutamate-dependent excitatory circuit. Notably, inhibitory transmission from PV-INs to pyramidal neurons remained intact, suggesting functional remodeling rather than loss of inhibitory connectivity. In vivo, optogenetic activation of PV-INs significantly enhanced CST-mediated hindlimb eEMG responses in aged mice but had little effect in young animals, demonstrating an age-dependent change in PV-IN regulation of motor output. Together, these findings reveal a previously unrecognized form of age-related circuit plasticity in the motor cortex. We propose that PV-INs undergo functional remodeling during aging, preserving inhibitory signaling while enhancing the recruitment of excitatory network mechanisms that facilitate CST output. This adaptive reorganization may represent a compensatory response to age-related motor circuit dysfunction and identifies inhibitory microcircuits as potential therapeutic targets for improving motor function in the aging brain.

BACKGROUND:Interbody cage failure is associated with loss of disc height, nerve compression, and pseudarthrosis, and often requires reoperation. Revision of failed interbody cages is challenging due to subsidence of the cage into the adjacent endplates, causing bony defects and granulation tissue, resulting in difficult exposure and a higher risk of complications. OBSERVATIONS:In this case series, the authors present 2 cases of symptomatic interbody cage failure successfully revised using a minimally invasive lateral approach. The first case utilized a transpsoas lateral approach to replace a failed L2-3 cage from prior transforaminal lumbar interbody fusion. The second case used an anterior-to-psoas oblique lateral approach to revise a subsided L3 corpectomy cage. Postoperatively, both patients had significant symptom improvement. LESSONS:A lateral lumbar interbody approach-with its direct access to disc space, possibility for a relatively large-footprint cage while avoiding scar tissue from a prior approach, and favorable safety profile-is a promising option for the revision of failed interbody cages. https://thejns.org/doi/10.3171/CASE25750.

Respiratory depression is the leading cause of death during opioid overdoses. Epidural electrical stimulation (EES) may facilitate rhythmic motor activities such as locomotion and respiration. We investigated whether tonic, submotor threshold, EES of the ventral cervical spinal cord would activate muscles innervated by motor neurons outside the ventral cervical spinal site of stimulation and increase tidal volume, respiratory frequency, and decreased end-tidal PCO2, or activate a more restricted set of muscles innervated by motor neurons near the stimulating electrodes. We studied 24 patients who were anesthetized with propofol and low-dose or high-dose remifentanil for treatment of anterior cervical spinal impingement. Cervical EES was delivered between cervical levels 3 to 7 (C3 to C7) for up to 90 seconds at an intensity ranging from 0.5 mA to 5 mA and a frequency of 5, 30, or 90 Hz at each dose of remifentanil. Ventral cervical EES did not reset the respiratory rhythm. There were no significant changes, on average, in tidal volume, respiratory frequency, or end-tidal PCO2 during or after ventral cervical EES. In contrast, dorsal cervical EES reset the respiratory rhythm, augmented respiratory activity beyond the period of stimulation, and increased both tidal volume and respiratory frequency and decreased end-tidal PCO2 in a similar, previous study in anesthetized humans. These observations suggest that the mild to moderate intensity, ventral cervical EES at frequencies < 100 Hz cannot access ventral motor neurons directly or activate interneuronal circuits that might increase motor neuron output indirectly during opioid-induced respiratory depression.

INTRODUCTION: Few interventions have been shown to substantially modify neurologic outcome following acute traumatic spinal cord injury (SCI). Hyperosmolar therapy is an important adjunct in the treatment of traumatic brain injury (TBI); despite presumed overlap in the pathophysiology of SCI and TBI, there is no literature supporting the use of hyperosmolar therapy for acute SCI patients. METHODS: We performed a retrospective cohort study of SCI patients presenting to our institution between 2005 and 2020. We identified all patients admitted to our neurologic ICU between 2005 and 2020 with a new diagnosis of isolated SCI. We identified 143 patients for analysis. All patients either did or did not receive 3% hypertonic saline (HTS, 3% NaCl) at the discretion of the treatment team during index hospitalization. Primary outcomes were change in ASIA motor score and ASIA Impairment Scale at discharge. Secondary outcomes included intensive care unit length of stay (LOS), and hospital LOS. RESULTS: Administration of HTS within 18 hours of admission was associated with increased strength below injury (+21.0%, p<0.0001) and AIS grade improvement (+0.97 grade, p=0.004) compared to late (≥18 hours after admission) or no HTS administration. These effects seem to be strongest in patients admitted ASIA A (p=.001). There were no significant differences in ICU or total hospital LOS between subgroups. CONCLUSIONS: Our data identify 3% hypertonic saline as a potentially useful adjunctive therapy in early management of acute traumatic spinal cord injury. We hypothesize that by limiting edema and augmenting intravascular volume, HTS could limit secondary injury cascades by improving perfusion in the injury penumbra. This adds to mounting evidence that cranial neurotrauma principles applied to management of cord injury could result in superior outcomes.

IntroductionSpinal cord injury (SCI) presents a significant burden to patients, families, and the healthcare system. The ability to accurately predict functional outcomes for SCI patients is essential for optimizing rehabilitation strategies, guiding patient and family decision making, and improving patient care.MethodsWe conducted a retrospective analysis of 589 SCI patients admitted to a single acute rehabilitation facility and used the dataset to train advanced machine learning algorithms to predict patients' rehabilitation outcomes. The primary outcome was the Functional Independence Measure (FIM) score at discharge, reflecting the level of independence achieved by patients after comprehensive inpatient rehabilitation.ResultsTree-based algorithms, particularly Random Forest (RF) and XGBoost, significantly outperformed traditional statistical models and Generalized Linear Models (GLMs) in predicting discharge FIM scores. The RF model exhibited the highest predictive accuracy, with an R-squared value of 0.90 and a Mean Squared Error (MSE) of 0.29 on the training dataset, while achieving 0.52 R-squared and 1.37 MSE on the test dataset. The XGBoost model also demonstrated strong performance, with an R-squared value of 0.74 and an MSE of 0.75 on the training dataset, and 0.51 R-squared with 1.39 MSE on the test dataset. Our analysis identified key predictors of rehabilitation outcomes, including the initial FIM scores and specific demographic factors such as level of injury and prehospital living settings. The study also highlighted the superior ability of tree-based models to capture the complex, non-linear relationships between variables that impact recovery in SCI patients.DiscussionThis research underscores the potential of machine learning models to enhance the accuracy of outcome predictions in SCI rehabilitation. The findings support the integration of these advanced predictive tools in clinical settings to better guide decision making for patients and families, tailor rehabilitation plans, allocate resources efficiently, and ultimately improve patient outcomes.

BACKGROUND:Spondyloptosis is defined as more than 100% subluxation of adjacent vertebral bodies. Timely reduction and stabilization are important to promote rehabilitation and improve quality of life. OBSERVATIONS:A 32-year-old male sustained a sagittal T9-10 spondyloptosis in a bicycle accident. To reduce the dislocation, the authors used a posterior three-rod construct: one continuous rod secured caudal to the injury site and two temporary short rods placed on the contralateral side flanking the fracture for sequential distraction. This approach involved minimal bony removal, and reduction was accomplished in less than 20 minutes after initial exposure. Postoperative imaging showed stable, near-complete reduction (from grade V to grade I). The patient was discharged on postoperative day 9. At the 4-month follow-up, he regained toe movement and sphincter reflex and had increased trunk control. A literature review of 25 case reports/series involving 42 patients with thoracic spondyloptosis showed that more than 50% of patients required substantial bony resection during reduction. LESSONS:This case highlights the advantages of a posterior three-rod construct in a trauma setting to achieve rapid and controlled spondyloptosis reduction with minimal osteotomy. The selection of reduction techniques should consider injury characteristics, the patient's preoperative neurological status, and the time from initial injury to surgery. https://thejns.org/doi/10.3171/CASE25531.

Patients with Alzheimer’s disease (AD) and mild dementia often present with motor deficits prior to observable cognitive decline. These deficits include slowed stepping and imbalanced gait. Our previous studies proposed amyloid-β and its precursor, amyloid precursor protein (APP), as having a role in AD-related gait disturbances by studying quadrupedal locomotion in APP-overexpressing transgenic J20 mice. However, the effect of Aβ/APP on spinal cord plasticity and recovery from injury has yet to be studied. We hypothesized that the presence of Aβ/APP in J20 mice will significantly impair recovery of locomotor function following spinal cord injury. Spinal cord injury was induced in wild type (WT) and J20 AD mice via complete transection of the spinal cord at the T10 level. To further evaluate whether the effect of Aβ/APP on plasticity was causative, we gave a gamma secretase-inhibitor (GSI) treatment, an Aβ inhibitor, to half of the mice at random. Mice were grouped by age, into 3-4 month and 10-13 month groups. Mice were fixed to a treadmill to assess their ability to produce hindlimb locomotion in congruence with the treadmill in a bipedal stepping task. To monitor long-term plasticity, hindlimb motor output data for both groups was collected at baseline and every week for 8 weeks post injury. Motion capture data was processed via SIMI, allowing for semi-automatic motion tracking and quantification of motion features. Extracted features included step length and height, average velocity, angle of movement, and angular velocity. Following the 8-week recovery period, both groups of mice showed improved motor control, which was signified by alternating step count during the recording period. There was a significant decrease of the alternating step count in 10-13mon J20 mice compared to their WT littermates (p=0.0259), but there was no significant difference in 3-4mon mice (p=0.4223). The J20 AD mice showed significantly less recovery at all time points throughout the recovery period. In the mice that received the GSI treatment, there was no significant difference between 10mon J20 and their WT littermates (p= 0.9804) or 3-4mon J20 mice and their WT littermates (p> 0.9999). We concluded that the spontaneous recovery of locomotion following complete thoracic transection was blocked in J20 AD mice as compared to WT, while introducing GSI to inhibit Aβ recovered locomotion in the affected mice. Our conclusions suggest that the presence of Aβ and APP can drastically effect plasticity even in the spinal cord, further exemplifying the role of these proteins in contributing to AD-related motor deficits. NIH National Institute of Biomedical Imaging and Bioengineering (NIBIB), U01EB015521-05; NIH, National Institute on Drug Abuse (NIDA), R01DA047637-01A1 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

OBJECTIVE Diabetes mellitus (DM) is a known risk factor for postsurgical and systemic complications after lumbar spinal surgery. Smaller studies have also demonstrated diminished improvements in patient -reported outcomes (PROs), with increased reoperation and readmission rates after lumbar surgery in patients with DM. The authors aimed to examine longer -term PROs in patients with DM undergoing lumbar decompression and/or arthrodesis for degenerative pathology. METHODS The Quality Outcomes Database was queried for patients undergoing elective lumbar decompression and/ or arthrodesis for degenerative pathology. Patients were grouped into DM and non -DM groups and optimally matched in a 1:1 ratio on 31 baseline variables, including the number of operated levels. Outcomes of interest were readmissions and reoperations at 30 and 90 days after surgery in addition to improvements in Oswestry Disability Index, back pain, and leg pain scores and quality -adjusted life -years at 90 days after surgery. RESULTS The matched decompression cohort comprised 7836 patients (3236 [41.3] females) with a mean age of 63.5 +/- 12.6 years, and the matched arthrodesis cohort comprised 7336 patients (3907 [53.3%] females) with a mean age of 64.8 +/- 10.3 years. In patients undergoing lumbar decompression, no significant differences in nonroutine discharge, length of stay (LOS), readmissions, reoperations, and PROs were observed. In patients undergoing lumbar arthrodesis, nonroutine discharge (15.7% vs 13.4%, p < 0.01), LOS (3.2 +/- 2.0 vs 3.0 +/- 3.5 days, p < 0.01), 30 -day (6.5% vs 4.4%, p < 0.01) and 90 -day (9.1% vs 7.0%, p < 0.01) readmission rates, and the 90 -day reoperation rate (4.3% vs 3.2%, p = 0.01) were all significantly higher in the DM group. For DM patients undergoing lumbar arthrodesis, subgroup analyses demonstrated a significantly higher risk of poor surgical outcomes with the open approach. CONCLUSIONS Patients with and without DM undergoing lumbar spinal decompression alone have comparable readmission and reoperation rates, while those undergoing arthrodesis procedures have a higher risk of poor surgical outcomes up to 90 days after surgery. Surgeons should target optimal DM control preoperatively, particularly for patients undergoing elective lumbar arthrodesis.

OBJECTIVE Cervical spondylotic myelopathy (CSM) can cause significant difficulty with driving and a subsequent reduction in an individual’s quality of life due to neurological deterioration. The positive impact of surgery on postoperative patient-reported driving capabilities has been seldom explored. METHODS The CSM module of the Quality Outcomes Database was utilized. Patient-reported driving ability was assessed via the driving section of the Neck Disability Index (NDI) questionnaire. This is an ordinal scale in which 0 represents the absence of symptoms while driving and 5 represents a complete inability to drive due to symptoms. Patients were considered to have an impairment in their driving ability if they reported an NDI driving score of 3 or higher (signifying impairment in driving duration due to symptoms). Multivariable logistic regression models were fitted to evaluate mediators of baseline impairment and improvement at 24 months after surgery, which was defined as an NDI driving score < 3. RESULTS A total of 1128 patients who underwent surgical intervention for CSM were included, of whom 354 (31.4%) had baseline driving impairment due to CSM. Moderate (OR 2.3) and severe (OR 6.3) neck pain, severe arm pain (OR 1.6), mild-moderate (OR 2.1) and severe (OR 2.5) impairment in hand/arm dexterity, severe impairment in leg use/walking (OR 1.9), and severe impairment of urinary function (OR 1.8) were associated with impaired driving ability at baseline. Of the 291 patients with baseline impairment and available 24-month follow-up data, 209 (71.8%) reported postoperative improvement in their driving ability. This improvement seemed to be mediated particularly through the achievement of the minimal clinically important difference (MCID) in neck pain and improvement in leg function/walking. Patients with improved driving at 24 months noted higher postoperative satisfaction (88.5% vs 62.2%, p < 0.01) and were more likely to achieve a clinically significant improvement in their quality of life (50.7% vs 37.8%, p < 0.01). CONCLUSIONS Nearly one-third of patients with CSM report impaired driving ability at presentation. Seventy-two percent of these patients reported improvements in their driving ability within 24 months of surgery. Surgical management of CSM can significantly improve patients’ driving abilities at 24 months and hence patients’ quality of life.

Study Design: Retrospective review of a prospectively maintained database. Objective: Assess differences in preoperative status and postoperative outcomes among patients of different educational backgrounds undergoing surgical management of cervical spondylotic myelopathy (CSM). Summary of Background Data: Patient education level (EL) has been suggested to correlate with health literacy, disease perception, socioeconomic status (SES), and access to health care. Methods: The CSM data set of the Quality Outcomes Database (QOD) was queried for patients undergoing surgical management of CSM. EL was grouped as high school or below, graduate-level, and postgraduate level. The association of EL with baseline disease severity (per patient-reported outcome measures), symptoms >3 or <= 3 months, and 24-month patient-reported outcome measures were evaluated. Results: Among 1141 patients with CSM, 509 (44.6%) had an EL of high school or below, 471 (41.3%) had a graduate degree, and 161 (14.1%) had obtained postgraduate education. Lower EL was statistically significantly associated with symptom duration of >3 months (odds ratio=1.68), higher arm pain numeric rating scale (NRS) (coefficient=0.5), and higher neck pain NRS (coefficient=0.79). Patients with postgraduate education had statistically significantly lower Neck Disability Index (NDI) scores (coefficient=-7.17), lower arm pain scores (coefficient=-1), and higher quality-adjusted life-years (QALY) scores (coefficient=0.06). Twenty-four months after surgery, patients of lower EL had higher NDI scores, higher pain NRS scores, and lower QALY scores (P<0.05 in all analyses). Conclusions: Among patients undergoing surgical management for CSM, those reporting a lower educational level tended to present with longer symptom duration, more disease-inflicted disability and pain, and lower QALY scores. As such, patients of a lower EL are a potentially vulnerable subpopulation, and their health literacy and access to care should be prioritized.

Study Design. Prospective randomized. Objective. Intraoperative methylprednisolone is a common adjunct following microscopic laminectomy/microdiscectomy. The goal of epidural instillation is a rapid symptomatic reduction in irritation of neural elements. There is inconsistent data supporting its use intraoperatively. To understand whether this maneuver results in any clinical effect, we performed a multiyear prospective study. Summary of Background Data. Previous work has demonstrated equivocal effects on pain with a suggestion of an increased risk of complication. These studies tend to suffer from small sample sizes and short follow-ups. Materials and Methods. Study obtained IRB approval. During the study period from 2013 to 2019, nearly equivalent numbers of patients who had received steroids during MIS decompressions were followed. Primary outcomes included pain (visual analog scale) and disability [Oswestry Disability Index (ODI)] at 2 weeks and 4 months. Secondary outcomes included complications, readmissions, and reoperation rates during the study period. Results. Four hundred eighty-six patients were followed for a mean follow-up of 5.17 years. The index case was more likely to be a revision surgery in the steroid group. Across all patients, there was no difference in pain at 2 weeks or 4 months. Disability was reduced at 2 weeks in the steroid group (ODI: 16.71 vs. 21.02, P = 0.04) but not at 4 months. By subgroup analysis, this is largely explained by ODI reduction in patients with high preoperative ODI (13.00 vs. 43.43, P = 0.03). Patients in the steroid cohort were more likely to undergo subsequent spinal surgery during the study period. Conclusion. Methylprednisolone instillation is associated with a large, transient reduction in ODI for patients with high preoperative ODI; there is no measurable effect on pain. There is equivocal effect on risk of subsequent reoperation. This issue was clarified in peer review but changes did not make it to the abstract. Therefore, the technique is likely best reserved for patients with significant preoperative disability.

Aim After spinal cord injuries (SCIs), patients may develop either detrusor-sphincter dyssynergia (DSD) or urinary incontinence, depending on the level of the spinal injury. DSD and incontinence reflect the loss of coordinated neural control among the detrusor muscle, which increases bladder pressure to facilitate urination, and urethral sphincters and pelvic floor muscles, which control the bladder outlet to restrict or permit bladder emptying. Transcutaneous magnetic stimulation (TMS) applied to the spinal cord after SCI reduced DSD and incontinence. We defined, within a mathematical model, the minimum neuronal elements necessary to replicate neurogenic dysfunction of the bladder after a SCI and incorporated into this model the minimum additional neurophysiological features sufficient to replicate the improvements in bladder function associated with lumbar TMS of the spine in patients with SCI. Methods We created a computational model of the neural circuit of micturition based on Hodgkin-Huxley equations that replicated normal bladder function. We added interneurons and increased network complexity to reproduce dysfunctional micturition after SCI, and we increased the density and complexity of interactions of both inhibitory and excitatory lumbar spinal interneurons responsive to TMS to provide a more diverse set of spinal responses to intrinsic and extrinsic activation of spinal interneurons that remains after SCI. Results The model reproduced the re-emergence of a spinal voiding reflex after SCI. When we investigated the effect of monophasic and biphasic TMS at two frequencies applied at or below T10, the model replicated the improved coordination between detrusor and external urethral sphincter activity that has been observed clinically: low-frequency TMS (1 Hz) within the model normalized control of voiding after SCI, whereas high-frequency TMS (30 Hz) enhanced urine storage. Conclusion Neuroplasticity and increased complexity of interactions among lumbar interneurons, beyond what is necessary to simulate normal bladder function, must be present in order to replicate the effects of SCI on control of micturition, and both neuronal and network modifications of lumbar interneurons are essential to understand the mechanisms whereby TMS reduced bladder dysfunction after SCI.

INTRODUCTION: Minimum clinically important differences (MCID) for quality-adjusted life years (QALYs) and arm pain patient-reported outcome metrics (PROMs) in cervical spondylotic myelopathy (CSM) have yet to be determined, while data for myelopathy severity, impairment, and neck pain remain limited by small series and low rates of follow-up. METHODS: The CSM database of the QOD Study Group was utilized for this analysis. Patients were prospectively enrolled and followed for 24 months, with a follow-up rate of 85.2%. The MCIDs were computed for five standardized instruments: Neck Disability Index (NDI), five-dimension Euro-QoL (EQ-5D) in QALYs, neck and arm pain numeric rating scale (NRS), and modified Japanese Orthopedic Association score (mJOA) at both 3 and 24-month follow-up. Seven previously validated measures of MCID were compared using the area-under-the-curve (AUC). The North American Spine Society (NASS) satisfaction scale was the anchor, with scores of 1-2 meeting criteria for satisfaction. RESULTS: A total of 1,141 patients underwent surgery for CSM. Improvement of =30% from baseline was the optimal MCID across time points for NDI and neck/arm NRS. At 24 months, 30% improvement for these three instruments resulted in AUCs of 0.73, 0.71, and 0.67, respectively. Numeric cut-offs (0.065 at 3 months and 0.149 at 24 months) were the superior MCIDs for EQ-5D-derived QALYs. For mJOA, a severity-adjusted MCID outperformed the other methods, yielding an AUC of 0.67 at 24 months. CONCLUSIONS: We used the QOD dataset to define previously unknown MCIDs for several outcome measures. A =30% improvement from baseline was a consistent, high-performing MCID in NDI and arm/neck NRS. However, an absolute numeric cut-off (0.149) was the superior MCID for EQ-5D QALYs. mJOA exhibited the lowest predictive capacity for patient satisfaction.

We tested the hypothesis that dorsal cervical epidural electrical stimulation (CEES) increases respiratory activity in male and female anesthetized rats. Respiratory frequency and minute ventilation were significantly increased when CEES was applied dorsally to the C2–C6 region of the cervical spinal cord. By injecting pseudorabies virus into the diaphragm and using c-Fos activity to identify neurons activated during CEES, we found neurons in the dorsal horn of the cervical spinal cord in which c-Fos and pseudorabies were co-localized, and these neurons expressed somatostatin (SST). Using dual viral infection to express the inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADD), hM4D(Gi), selectively in SST-positive cells, we inhibited SST-expressing neurons by administering Clozapine N-oxide (CNO). During CNO-mediated inhibition of SST-expressing cervical spinal neurons, the respiratory excitation elicited by CEES was diminished. Thus, dorsal cervical epidural stimulation activated SST-expressing neurons in the cervical spinal cord, likely interneurons, that communicated with the respiratory pattern generating network to effect changes in ventilation.SIGNIFICANCE STATEMENTA network of pontomedullary neurons within the brainstem generates respiratory behaviors that are susceptible to modulation by a variety of inputs; spinal sensory and motor circuits modulate and adapt this output to meet the demands placed on the respiratory system. We explored dorsal cervical epidural electrical stimulation (CEES) excitation of spinal circuits to increase ventilation in rats. We identified dorsal somatostatin (SST)-expressing neurons in the cervical spinal cord that were activated (c-Fos-positive) by CEES. CEES no longer stimulated ventilation during inhibition of SST-expressing spinal neuronal activity, thereby demonstrating that spinal SST neurons participate in the activation of respiratory circuits affected by CEES. This work establishes a mechanistic foundation to repurpose a clinically accessible neuromodulatory therapy to activate respiratory circuits and stimulate ventilation.

Study Design: Prospective observational study, level of evidence 1 for prognostic investigations. Objectives: To evaluate the prevalence of sleep impairment and predictors of improved sleep quality 24 months postoperatively in cervical spondylotic myelopathy (CSM) using the quality outcomes database. Summary of Background Data: Sleep disturbances are a common yet understudied symptom in CSM. Materials and Methods: The quality outcomes database was queried for patients with CSM, and sleep quality was assessed through the neck disability index sleep component at baseline and 24 months postoperatively. Multivariable logistic regressions were performed to identify risk factors of failure to improve sleep impairment and symptoms causing lingering sleep dysfunction 24 months after surgery. Results: Among 1135 patients with CSM, 904 (79.5%) had some degree of sleep dysfunction at baseline. At 24 months postoperatively, 72.8% of the patients with baseline sleep symptoms experienced improvement, with 42.5% reporting complete resolution. Patients who did not improve were more like to be smokers [adjusted odds ratio (aOR): 1.85], have osteoarthritis (aOR: 1.72), report baseline radicular paresthesia (aOR: 1.51), and have neck pain of ≥4/10 on a numeric rating scale. Patients with improved sleep noted higher satisfaction with surgery (88.8% vs 72.9%, aOR: 1.66) independent of improvement in other functional areas. In a multivariable analysis including pain scores and several myelopathy-related symptoms, lingering sleep dysfunction at 24 months was associated with neck pain (aOR: 1.47) and upper (aOR: 1.45) and lower (aOR: 1.52) extremity paresthesias. Conclusion: The majority of patients presenting with CSM have associated sleep disturbances. Most patients experience sustained improvement after surgery, with almost half reporting complete resolution. Smoking, osteoarthritis, radicular paresthesia, and neck pain ≥4/10 numeric rating scale score are baseline risk factors of failure to improve sleep dysfunction. Improvement in sleep symptoms is a major driver of patient-reported satisfaction. Incomplete resolution of sleep impairment is likely due to neck pain and extremity paresthesia.

Opioid overdose is one of the leading causes of overdose related deaths in the United States of America, accounting for 70.6% of overdose fatalities in 2019 alone. A leading cause of death among opioid overdoses is respiratory depression. Epidural electrical stimulation (EES) emerges as a novel approach of facilitating rhythmic motor activities such as locomotion and respiration. Previous studies conducted in humans and rodent models demonstrated respiratory augmentations induced by EES delivered to the dorsal cervical spinal cord. Importantly, EES at the dorsal cervical spinal cord opposes opioid-induced respiratory depression in human. To reveal the mechanism underpins how cervical EES modulate the respiratory neural circuit, we conducted this comparative study between dorsal cervical EES to the ventral EES in patients with opioid-induced respiratory suppression or depression. We hypothesize that the ventral cervical EES activates the local motor neuronal pools while the dorsal EES recruits both sensory and motor cervical circuits as well as accesses supraspinal structures such as medulla. We recruited and consented 25 patients who underwent anterior (ventral) cervical spinal cord surgery and compared the effect of ventral cervical EES to to the effect of dorsal cervical ESS in a dataset that we collected from 18 patients undergoing cervical spinal surgery. In the 25 patients, the EES was deliver to the ventral surface of spinal cord ranging from cervical level 3 to 7 (C3 to C7) for no more than 90 seconds at the optimal intensity ranging from 0.5 mA to 5 mA with stimulation frequencies 5 Hz or 30 Hz. In both the dorsal and ventral EES groups, the subjects were anesthetized with low dose or high dose remifentanil that partially or completely depressed voluntary respiration. We observed three main differences between the dorsal and ventral cervical EEST in regulating respiration in the presence of remifentanil. First, dorsal cervical EES induced the resetting of inspiratory rhythm while ventral cervical EES did not. Second, dorsal but not ventral cervical EES induced longer lasting respiratory modulation after the stimulation stopped. Third, dorsal cervical EES induced both frequency and amplitude changes of respiration while ventral cervical EES modulated the amplitude of the respiration more significantly. These observations suggest that the dorsal and ventral cervical EES facilitate respiration via different neural circuits. This work was supported by the National Institute of Drug Abuse in the National Institutes of Health: R01 DA047637, Louis and Harold Price Foundation, H & H Evergreen Foundation, and J. Yang Family Foundation. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.