Comparing reactive versus empiric cerebrospinal fluid drainage strategies for spinal perfusion pressure optimization in patients with acute traumatic spinal cord injuries.

BACKGROUND: Spinal cord hypoperfusion undermines clinical recovery in acute traumatic spinal cord injuries. New guidelines suggest cerebrospinal fluid (CSF) drainage is an important strategy for preventing spinal cord hypoperfusion in the acute post-injury phase. METHODS: This study included participants presenting to a single level 1 trauma center between 2018 and 2022 with cervical or thoracic traumatic spinal cord injury severity grade A-C, as evaluated by the American spinal injury association impairment scale (AIS). The primary objective of this study was to compare the efficacy of two CSF drainage protocols in preventing spinal cord hypoperfusion; 1) draining CSF only when spinal cord perfusion pressure (SCPP) drops below 65 mmHg (i.e. reactive) versus 2) empiric CSF drainage of 5-10 mL every hour. Intrathecal pressure, spinal cord perfusion pressure (SCPP), mean arterial pressure (MAP), and vasopressor utilization were compared using univariate T-test statistical analysis. RESULTS: While there was no difference in the incidence of sub-optimal SCPP (<65 mmHg; p = 0.1658), reactively drained participants were more likely to exhibit critical hypoperfusion (<50 mmHg; p = 0.0030) despite also having lower average intrathecal pressures (p < 0.001). There were no differences in average SCPP, mean arterial pressure (MAP), or vasopressor utilization between the two groups (p > 0.05). CONCLUSIONS: Empiric (vs reactive) CSF drainage resulted in fewer incidences of critical spinal cord hypoperfusion for patients with acute traumatic spinal cord injuries.

Intradiscal Osteotomy and Bilateral Expandable Transforaminal Interbody Fusion Cages for Iatrogenic Kyphotic Deformity: A Technical Report.

Objectives Expandable transforaminal interbody fusion (TLIF) devices have been developed to introduce more segmental lordosis through a narrow operative corridor, but there are concerns about the degree of achievable correction with a small graft footprint. In this report, we describe the technical nuances associated with placing bilateral expandable cages for correction of iatrogenic deformity. Materials and Methods A 60-year-old female with symptomatic global sagittal malalignment and a severe lumbar kyphotic deformity after five prior lumbar surgeries presented to our institution. We performed multilevel posterior column osteotomies, a L3-4 intradiscal osteotomy, and placed bilateral lordotic expandable TLIF cages at the level of maximum segmental kyphosis. Results We achieve a 21-degree correction of the patient's focal kyphotic deformity and restoration of the patient global sagittal alignment. Conclusion This case demonstrates both the feasibility and utility of placing bilateral expandable TLIF cages at a single disc space in the setting of severe focal sagittal malalignment. This technique expands the implant footprint and, when coupled with an intradiscal osteotomy, allows for a significant restoration of segmental lordosis.

A roadmap for implanting microelectrode arrays to evoke tactile sensations through intracortical microstimulation.

Intracortical microstimulation (ICMS) is a method for restoring sensation to people with paralysis as part of a bidirectional brain-computer interface to restore upper limb function. Evoking tactile sensations of the hand through ICMS requires precise targeting of implanted electrodes. Here we describe the presurgical imaging procedures used to generate functional maps of the hand area of the somatosensory cortex and subsequent planning that guided the implantation of intracortical microelectrode arrays. In five participants with cervical spinal cord injury, across two study locations, this procedure successfully enabled ICMS-evoked sensations localized to at least the first four digits of the hand. The imaging and planning procedures developed through this clinical trial provide a roadmap for other brain-computer interface studies to ensure successful placement of stimulation electrodes.

Time of day does not impact spinal serotonin levels in humans.

Spinal serotonin enables neuro-motor recovery (i.e., plasticity) in patients with debilitating paralysis. While there exists time of day fluctuations in serotonin-dependent spinal plasticity, it is unknown, in humans, whether this is due to dynamic changes in spinal serotonin levels or downstream signaling processes. The primary objective of this study was to determine if time of day variations in spinal serotonin levels exists in humans. To assess this, intrathecal drains were placed in seven adults with cerebrospinal fluid (CSF) collected at diurnal (05:00 to 07:00) and nocturnal (17:00 to 19:00) intervals. High performance liquid chromatography with mass spectrometry was used to quantify CSF serotonin levels with comparisons being made using univariate analysis. From the 7 adult patients, 21 distinct CSF samples were collected: 9 during the diurnal interval and 12 during nocturnal. Diurnal CSF samples demonstrated an average serotonin level of 216.6 ± $ \pm $ 67.7 nM. Nocturnal CSF samples demonstrated an average serotonin level of 206.7 ± $ \pm $ 75.8 nM. There was no significant difference between diurnal and nocturnal CSF serotonin levels (p = .762). Within this small cohort of spine healthy adults, there were no differences in diurnal versus nocturnal spinal serotonin levels. These observations exclude spinal serotonin levels as the etiology for time of day fluctuations in serotonin-dependent spinal plasticity expression.

Preinjury Frailty Predicts 1-Year Mortality in Older Adults With Traumatic Spine Fractures.

BACKGROUND AND OBJECTIVES: Nearly 30% of older adults presenting with isolated spine fractures will die within 1 year. Attempts to ameliorate this alarming statistic are hindered by our inability to identify relevant risk factors. The primary objective of this study was to develop a prediction model that identifies feasible targets to limit 1-year mortality. METHODS: This retrospective cohort study included 703 older adults (65 years or older) admitted to a level I trauma center with isolated spine fractures, without neural deficit, from January 2013 to January 2018. Multivariable analysis was used to select for independently significant patient demographics, frailty variables, injury metrics, and management decisions to incorporate into distinct logistic regression models predicting 1-year mortality. Variables were considered significant, if P < .05. RESULTS: Of the 703 older adults, 199 (28.3%) died after hospital discharge, but within 1 year of index trauma. Risk Analysis Index (RAI; odds ratio [OR]: 1.116; 95% CI: 1.087-1.149; P < .001) and ambulation requiring a cane (OR: 2.601; 95% CI: 1.151-5.799; P = .02) or walker (OR: 4.942; 95% CI: 2.698-9.196; P < .001), ie, frailty variables, were associated with increased odds of 1-year mortality. Spine trauma scales were not associated with 1-year mortality. Longer hospital stays (OR: 1.112; 95% CI: 1.034-1.196; P = .004) and nursing home discharge (OR: 3.881; 95% CI: 2.070-7.378; P < .001) were associated with increased odds, while discharge to rehab (OR: 0.361; 95% CI: 0.155-0.799; P = .014) decreased 1-year mortality odds. A "preinjury" regression model incorporating Risk Analysis Index and ambulation status resulted in an area under receiver operating characteristic curve (AUROCC) of 0.914 (95% CI: 0.863-0.965). A "postinjury" model incorporating Glasgow Coma Scale, hospital stay duration, and discharge disposition resulted in AUROCC of 0.746 (95% CI: 0.642-0.849). Combining elements of the preinjury and postinjury models into an "integrated model" produced an AUROCC of 0.908 (95% CI: 0.852-0.965). CONCLUSION: Preinjury frailty measures are most strongly associated with 1-year mortality outcomes in older adults with isolated spine fractures. Incorporating injury metrics or management decisions did not enhance predictive accuracy. Further work is needed to understand how targeting frailty may reduce mortality.

A guide to selecting upper thoracic versus lower thoracic uppermost instrumented vertebra in adult spinal deformity correction.

PURPOSE: Operative treatment of adult spinal deformity (ASD) has been shown to improve patient health-related quality of life (HRQOL). Selection of the uppermost instrumented vertebra (UIV) in either the upper thoracic (UT) or lower thoracic (LT) spine is a pivotal decision with effects on operative and postoperative outcomes. This review overviews the multifaceted decision-making process for UIV selection in ASD correction. METHODS: PubMed was queried for articles using the keywords "uppermost instrumented vertebra", "upper thoracic", "lower thoracic", and "adult spinal deformity". RESULTS: Optimization of UIV selection may lead to superior deformity correction, better patient-reported outcomes, and lower risk of proximal junctional kyphosis (PJK) and failure (PJF). Patient alignment characteristics, including preoperative thoracic kyphosis, coronal deformity, and the magnitude of sagittal correction influence surgical decision-making when selecting a UIV, while comorbidities such as poor body mass index, osteoporosis, and neuromuscular pathology should also be taken in to account. Additionally, surgeon experience and resources available to the hospital may also play a role in this decision. Currently, it is incompletely understood whether postoperative HRQOLs, functional and radiographic outcomes, and complications after surgery differ between selection of the UIV in either the UT or LT spine. CONCLUSION: The correct selection of the UIV in surgical planning is a challenging task, which requires attention to preoperative alignment, patient comorbidities, clinical characteristics, available resources, and surgeon-specific factors such as experience.

Surgical intervention ≤ 24 hours versus > 24 hours after injury for the management of acute traumatic central cord syndrome: a systematic review and meta-analysis.

OBJECTIVE: The objective was to evaluate the efficacy, outcomes, and complications of surgical intervention performed within 24 hours (≤ 24 hours) versus after 24 hours (> 24 hours) in managing acute traumatic central cord syndrome (ATCCS). METHODS: Articles pertinent to the study were retrieved from PubMed, Scopus, Web of Science, and Cochrane. The authors performed a systematic review and meta-analysis of treatment procedures and outcomes according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRIMSA) guidelines. RESULTS: Seven articles comprising 488 patients were included, with 188 (38.5%) patients in the ≤ 24-hour group and 300 (61.5%) in the > 24-hour group. Significant differences were not found between groups in terms of demographic characteristics, injury mechanism, spinal cord compression level, neuroimaging features, and the American Spinal Injury Association (ASIA) motor score at admission. Both groups had a similar approach to surgery and steroid administration. The surgical complication rate was significantly higher in the > 24-hour group (4.5%) compared to the ≤ 24-hour group (1.2%) (p = 0.05). Clinical follow-up duration was similar at 12 months (interquartile range 3-36) for both groups (p > 0.99). The ≤ 24-hour group demonstrated a not statistically significant greater improvement in ASIA motor score, with a mean difference of 12 (95% CI -20.7 to 44.6) compared to the > 24-hour group. CONCLUSIONS: The present study indicates potential advantages of early (≤ 24 hours) surgery in ATCCS patients, specifically in terms of lower complication rates. However, further research is needed to confirm these findings and their clinical implications.

Associating T1-Weighted and T2-Weighted Magnetic Resonance Imaging Radiomic Signatures With Preoperative Symptom Severity in Patients With Cervical Spondylotic Myelopathy.

BACKGROUND: Preoperative symptom severity in cervical spondylotic myelopathy (CSM) can be variable. Radiomic signatures could provide an imaging biomarker for symptom severity in CSM. This study utilizes radiomic signatures of T1-weighted and T2-weighted magnetic resonance imaging images to correlate with preoperative symptom severity based on modified Japanese Orthopaedic Association (mJOA) scores for patients with CSM. METHODS: Sixty-two patients with CSM were identified. Preoperative T1-weighted and T2-weighted magnetic resonance imaging images for each patient were segmented from C2-C7. A total of 205 texture features were extracted from each volume of interest. After feature normalization, each second-order feature was further subdivided to yield a total of 400 features from each volume of interest for analysis. Supervised machine learning was used to build radiomic models. RESULTS: The patient cohort had a median mJOA preoperative score of 13; of which, 30 patients had a score of >13 (low severity) and 32 patients had a score of ≤13 (high severity). Radiomic analysis of T2-weighted imaging resulted in 4 radiomic signatures that correlated with preoperative mJOA with a sensitivity, specificity, and accuracy of 78%, 89%, and 83%, respectively (P < 0.004). The area under the curve value for the ROC curves were 0.69, 0.70, and 0.77 for models generated by independent T1 texture features, T1 and T2 texture features in combination, and independent T2 texture features, respectively. CONCLUSIONS: Radiomic models correlate with preoperative mJOA scores using T2 texture features in patients with CSM. This may serve as a surrogate, objective imaging biomarker to measure the preoperative functional status of patients.

Supraspinal control of motoneurons after paralysis enabled by spinal cord stimulation.

Spinal cord stimulation (SCS) restores motor control after spinal cord injury (SCI) and stroke. This evidence led to the hypothesis that SCS facilitates residual supraspinal inputs to spinal motoneurons. Instead, here we show that SCS does not facilitate residual supraspinal inputs but directly triggers motoneurons action potentials. However, supraspinal inputs can shape SCS-mediated activity, mimicking volitional control of motoneuron firing. Specifically, by combining simulations, intraspinal electrophysiology in monkeys and single motor unit recordings in humans with motor paralysis, we found that residual supraspinal inputs transform subthreshold SCS-induced excitatory postsynaptic potentials into suprathreshold events. We then demonstrated that only a restricted set of stimulation parameters enables volitional control of motoneuron firing and that lesion severity further restricts the set of effective parameters. Our results explain the facilitation of voluntary motor control during SCS while predicting the limitations of this neurotechnology in cases of severe loss of supraspinal axons.

SUPRASPINAL CONTROL OF MOTONEURONS AFTER PARALYSIS ENABLED BY SPINAL CORD STIMULATION.

Spinal cord stimulation (SCS) restores motor control after spinal cord injury (SCI) and stroke. This evidence led to the hypothesis that SCS facilitates residual supraspinal inputs to spinal motoneurons. Instead, here we show that SCS does not facilitate residual supraspinal inputs but directly triggers motoneurons action potentials. However, supraspinal inputs can shape SCS-mediated activity, mimicking volitional control of motoneuron firing. Specifically, by combining simulations, intraspinal electrophysiology in monkeys and single motor unit recordings in humans with motor paralysis, we found that residual supraspinal inputs transform subthreshold SCS-induced excitatory postsynaptic potentials into suprathreshold events. We then demonstrated that only a restricted set of stimulation parameters enables volitional control of motoneuron firing and that lesion severity further restricts the set of effective parameters. Our results explain the facilitation of voluntary motor control during SCS while predicting the limitations of this neurotechnology in cases of severe loss of supraspinal axons.

Infant Rudimentary Meningocele with Tethering of the Cervical Cord: A Case Report.

Rudimentary meningoceles of the spine with dural extension are very rare and warrant surgical excision to prevent infection and long-term neurological deficits in pediatric patients. We present the case of a 5-month-old infant with a tethered spinal cord secondary to a rudimentary meningocele. The patient presented shortly after birth with a midline cervical dimple that was evaluated for a suspected dermal sinus tract. Magnetic resonance imaging scan of the spine showed a sinus tract with intradural extension to C2-3 and external opening at the level of spinous process C5. En bloc surgical excision and spinal cord release were successfully performed. Histological analysis of the specimen confirmed the presence of two blunt sinus tracts and staining was consistent with a rudimentary meningocele. Intradural rudimentary meningoceles in infants can successfully be managed with surgical intervention. Surgery is indicated to prevent future motor complications from spinal cord tethering and neoplastic growth from the rudimentary meningocele.

Patterns in Follow-Up Imaging Usage for Pediatric Patients with Whiplash-Associated Disorder.

BACKGROUND: A clinical concern exists that pediatric patients with whiplash-associated disorder (WAD) might have missed structural injuries or, alternatively, subsequently develop structural injuries over time, despite initially negative imaging findings. The primary objective of this study is to assess follow-up imaging usage for pediatric patients presenting with WAD. METHODS: A retrospective review of 444 pediatric patients presenting to a level 1 pediatric trauma hospital from January 1, 2010 to December 31, 2019 was performed. Imaging was reviewed at the initial encounter and the 3- and 6-month follow-up appointments. RESULTS: At the initial evaluation, children aged <6 years were more likely to receive radiographs (P = 0.007) and magnetic resonance imaging (P = 0.048) than were children aged 6-11 and 12-18 years. At the 3- and 6-month follow-up appointments, persistent neck pain was rare, representing <15% of patients at either time. Regardless of pain persistence, 80.2% of patients seen at the 3-month follow-up and 100% of patients at the 6-month follow-up underwent additional imaging studies. At the 3-month follow-up, children with persistent neck pain were more likely to undergo magnetic resonance imaging than were patients without persistent pain (P < 0.001). Also, patients with persistent neck pain were also more likely to not undergo any imaging evaluation (P = 0.002). Follow-up imaging studies did not reveal new structural injuries at either time point. CONCLUSIONS: Follow-up imaging for pediatric patients with low-grade WAD did not identify new structural pathology-in patients with or without persistent neck pain.

Relationship of cervical soft tissue injury and surgical predication following pediatric cervical spinal trauma and its sequelae on long-term neurologic outcome.

Within the sample of 181 patients with cervical CT, CT identified unstable injury with a sensitivity of 100% and specificity of 95%. CT identified operable injury at the CCJ with 86% sensitivity and 91% specificity. CT was considered the gold standard for identification of fractures. Together, the presence of CT imaging suggestive of unstable injury or persistent neurologic complaint had a 100% sensitivity and 81% specificity. Finally, across all patients MRI had 100% sensitivity and 89% specificity for detection of unstable injury requiring surgery.

Top-ten most-cited articles on anterior column release in the context of minimally invasive lumbar interbody fusion.

Introduction: Lateral anterior column release (ACR) is a minimally invasive option for the correction of sagittal plane deformity. To assemble a homogeneous picture of published research on ACR, an advanced bibliometric analysis was conducted to compile the top-ten most-cited articles on the topic of ACR. Methods: A keyword search using the Thomson Reuters Web of Knowledge was conducted to identify articles discussing the role of lateral ACR. The articles were then ranked based on the total number of citations to identify the ten most-cited articles published. A subjective appraisal of the findings of these articles was conducted to provide a ranked literature review and to examine trends in the study of ACR between 2012 and 2019. Results: The earliest published article on ACR was in 2012 by Deukmedjian et al. Three articles were in vitro biomechanical assessments of ACR, and seven articles were on outcome analyses, which were either case series or case controlled. The most-cited article was a biomechanical study authored by Uribe et al. The article with the highest rate of citations/year was authored by Manwaring et al. Uribe and the European Spine Journal were the most frequently cited author and journal, respectively. Conclusions: The lateral ACR approach has enjoyed significant scholarly attention since its advent. Higher-level analyses with robust control groups, larger sample sizes, and long-term follow-up are necessary to improve our understanding of this approach.

POTENTIATION OF CORTICO-SPINAL OUTPUT VIA TARGETED ELECTRICAL STIMULATION OF THE MOTOR THALAMUS.

Cerebral white matter lesions prevent cortico-spinal descending inputs from effectively activating spinal motoneurons, leading to loss of motor control. However, in most cases, the damage to cortico-spinal axons is incomplete offering a potential target for new therapies aimed at improving volitional muscle activation. Here we hypothesized that, by engaging direct excitatory connections to cortico-spinal motoneurons, stimulation of the motor thalamus could facilitate activation of surviving cortico-spinal fibers thereby potentiating motor output. To test this hypothesis, we identified optimal thalamic targets and stimulation parameters that enhanced upper-limb motor evoked potentials and grip forces in anesthetized monkeys. This potentiation persisted after white matter lesions. We replicated these results in humans during intra-operative testing. We then designed a stimulation protocol that immediately improved voluntary grip force control in a patient with a chronic white matter lesion. Our results show that electrical stimulation targeting surviving neural pathways can improve motor control after white matter lesions.

Epidural stimulation of the cervical spinal cord for post-stroke upper-limb paresis.

Cerebral strokes can disrupt descending commands from motor cortical areas to the spinal cord, which can result in permanent motor deficits of the arm and hand. However, below the lesion, the spinal circuits that control movement remain intact and could be targeted by neurotechnologies to restore movement. Here we report results from two participants in a first-in-human study using electrical stimulation of cervical spinal circuits to facilitate arm and hand motor control in chronic post-stroke hemiparesis ( NCT04512690 ). Participants were implanted for 29 d with two linear leads in the dorsolateral epidural space targeting spinal roots C3 to T1 to increase excitation of arm and hand motoneurons. We found that continuous stimulation through selected contacts improved strength (for example, grip force +40% SCS01; +108% SCS02), kinematics (for example, +30% to +40% speed) and functional movements, thereby enabling participants to perform movements that they could not perform without spinal cord stimulation. Both participants retained some of these improvements even without stimulation and no serious adverse events were reported. While we cannot conclusively evaluate safety and efficacy from two participants, our data provide promising, albeit preliminary, evidence that spinal cord stimulation could be an assistive as well as a restorative approach for upper-limb recovery after stroke.

GABA Increases Sensory Transmission In Monkeys.

Sensory input flow is central to voluntary movements. For almost a century, GABA was believed to modulate this flow by inhibiting sensory axons in the spinal cord to sculpt neural inputs into skilled motor output. Instead, here we show that GABA can also facilitate sensory transmission in monkeys and consequently increase spinal and cortical neural responses to sensory inputs challenging our understanding of generation and perception of movement.

Low Preoperative Prealbumin Levels Are a Strong Independent Predictor of Postoperative Cerebrospinal Fluid Leak Following Endoscopic Endonasal Skull Base Surgery.

OBJECTIVE: Prealbumin levels correlate with overall nutritional status, and low values are associated with poor wound healing. We investigated whether low preoperative prealbumin levels predict risk of endoscopic endonasal skull base surgery (EESBS) reconstruction failure, as demonstrated by postoperative cerebrospinal fluid (CSF) leak and/or infection. METHODS: Between October 2018 and February 2020, 98 patients with documented preoperative prealbumin levels were prospectively followed. The incidence of CSF leak and infection in patients with low prealbumin levels (≤20 mg/dL) was compared with those with normal prealbumin levels (>20 mg/dL). Numerous factors previously shown to influence CSF leak rates were assessed. Both univariate and multivariable analyses were performed to identify independent predictive factors. RESULTS: Within this prospectively gathered patient cohort composed of >95% "high-risk" expanded EESBS, 14 of 98 patients (14.3%) experienced a postoperative CSF leak. Factors univariately associated with postoperative complications at the 0.2 level of significance were used in a multivariable model. Low prealbumin levels (≤20 mg/dL) proved to be a strong independent predictive factor associated with a 5-fold increased risk of postoperative CSF leak (odds ratio 5.01, P = 0.01), and postoperative surgical-site infection (P = 0.0009). These associations remained after controlling for multiple other factors, including body mass index, surgical pathology, previous EESBS, risk assessment index, and high- versus low-flow intraoperative CSF leaks. CONCLUSIONS: Preoperative prealbumin levels are an independent predictor of EESBS associated CSF leak and infection. Future studies are needed to investigate the utility of screening and correcting prealbumin levels to limit postoperative complications.

Patient perception of scoliosis correction surgery on Instagram.

OBJECTIVE: Patient feedback surveys provide important insight into patient outcomes, satisfaction, and perioperative needs. Recent critiques have questioned provider-initiated surveys and their capacity to accurately gauge patient perspectives due to intrinsic biases created by question framing. In this study, the authors sought to evaluate provider-independent, patient-controlled social media Instagram posts in order to better understand the patient experience following scoliosis correction surgery. METHODS: Twitter and Instagram were queried for posts with two tagged indicators, #scoliosissurgery or @scoliosissurgery, resulting in no relevant Twitter posts and 25,000 Instagram posts. Of the initial search, 24,500 Instagram posts that did not directly involve the patient's own experience were eliminated. Posts were analyzed and coded for the following criteria: the gender of the patient, preoperative or postoperative timing discussed in the post, and classified themes related to the patient's experiences with scoliosis correction surgery. RESULTS: Females made 87.6% of the Instagram posts about their experience following scoliosis correction surgery. The initial postoperative stage of surgery was mentioned in 7.6% of Instagram posts. The most common theme on Instagram involved offering or seeking online support from other patients, which constituted 85.2% of all posts. Other common themes included concern about the surgical scar (31.8%), discussing the results of treatment (28.8%), and relief regarding results (21.2%). CONCLUSIONS: Social media provided a platform to analyze unprompted feedback from patients. Patients were most concerned with their scoliosis correction surgery in the period of time 2 weeks or more after surgery. Themes that were most commonly found on Instagram posts were offering or seeking online support from other patients and concern about the surgical scar. Patient-controlled social media platforms, like Instagram, may provide a useful mechanism for healthcare providers to understand the patient experience following scoliosis correction surgery. Such platforms may help in evaluating postoperative satisfaction and improving postoperative quality of care.

Retinoic acid receptor alpha activation is necessary and sufficient for plasticity induced by recurrent central apnea.

Reductions in respiratory-related synaptic inputs to inspiratory motor neurons initiate a form of plasticity that proportionally enhances inspiratory motor output, even in the absence of changing blood gases. This form of plasticity is known as inactivity-induced inspiratory motor facilitation (iMF). iMF triggered by brief, recurrent reductions in respiratory neural activity requires local retinoic acid (RA) synthesis, but receptor subtypes activated by RA are unknown. To test the hypothesis that retinoic acid receptor alpha (RARα) is necessary for iMF, RAR subtype-specific inhibitors were delivered intrathecally above the phrenic motor pool in urethane-anesthetized, ventilated rats before 5, ∼1 min central apneas (without hypoxia; separated by 5 min) while monitoring phrenic inspiratory output. Pretreatment with a spinal RARα inhibitor impaired the capacity for recurrent central apnea to trigger long-lasting increases in phrenic inspiratory output, but plasticity was expressed in rats pretreated with an RARß/γ inhibitor. Intrathecal RA application in the absence of reduced respiratory neural activity elicited an increase in phrenic inspiratory output, which was prevented by pretreatment with an RARα inhibitor. These data indicate that spinal RARα activation is necessary for iMF triggered by recurrent reductions in respiratory neural activity, and that RARα activation in/near the phrenic motor pool in the absence of respiratory neural activity deprivation is sufficient to elicit phrenic inspiratory motor facilitation. Understanding cellular cascades underlying plasticity induced by reductions in respiratory neural activity may define avenues for pharmacological intervention in disorders in which endogenous compensatory mechanisms that defend ongoing inspiratory motor output are impaired.NEW & NOTEWORTHY Local mechanisms near phrenic motor neurons respond to reductions in respiratory-related synaptic inputs by triggering a chemoreflex-independent, proportional enhancement in inspiratory output, a form of plasticity called inactivity-induced inspiratory motor facilitation (iMF). Here, we show that activation of spinal retinoic acid receptor alpha (RARα) is necessary to trigger phrenic iMF, and that spinal RARα activation in the absence of respiratory neural activity deprivation is sufficient to elicit phrenic inspiratory facilitation.