Motor Recovery Research Articles (Page 1)

Nerve implantation to the muscle after neuroma formation enables pain relief and motor function recovery with reinnervation in rats.

Neuroplasticity is the ability of the central nervous system (CNS) to adapt structurally and functionally in response to motor and sensory dysfunction caused by injury and disease. Spinal interneurons (INs) are key components of neuroplastic changes that ameliorate impaired motor function after CNS injury. A lateral spinal cord hemisection model exhibited spontaneous motor recovery of the hind limb on the affected side. Hence, neuroplastic changes within the spinal cord on the affected and/or unaffected side may occur during motor recovery following unilateral spinal cord injury (SCI). However, it remains unclear how the spinal neurons on the affected and unaffected side contribute to motor recovery in the ipsilesional hind limb following unilateral SCI. In this study, we aimed to explore whether the thoracic spinal neurons above the lesion were involved in the motor recovery of the ipsilesional hind limb in a unilateral SCI model. Following unilateral SCI, hind limb motor function on the ipsilateral side was initially impaired but showed spontaneous recovery in the behavioral tests, which was subsequently lost after ablation of thoracic spinal neurons in the ipsilesional spinal cord above the lesion. In contrast, changes in the ipsilesional hind limb motor function were not observed after ablation of the contralesional thoracic spinal neurons. These results suggest that thoracic spinal neurons on the ipsilesional side above the lesion are key components for hind limb motor recovery in a model of unilateral SCI.

This study examines the effects of combining transcranial direct current stimulation (tDCS) with extended reality (XR) exercises on brain connectivity and motor recovery in chronic stroke. We evaluate changes in electroencephalography (EEG) based connectivity and symmetry parameters, their correlation with clinical improvements, and their prognostic potential. Participants underwent XR rehabilitation with either active anodal tDCS or sham stimulation. EEG connectivity metrics and symmetry indices were assessed before and after the intervention alongside upper and lower limb motor function assessments. Correlation analyses were conducted to examine associations between EEG variations and motor improvements. As results, significant reductions in the brain symmetry index and the directional brain symmetry index were observed in the active tDCS group in the alpha, beta, and gamma EEG frequency bands, indicating an increase in symmetry after rehabilitation. Comparing the evolution of EEG features with clinical variations, in the active tDCS group greater correlations of changes in high frequency connectivity with upper and lower limb improvements were found. In conclusion, the addition of anodal tDCS to XR therapy seems to enhance neuroplasticity by modulating high-frequency power and connectivity, possibly also promoting more effective motor recovery. This study provides a comprehensive analysis of tDCS-enhanced XR rehabilitation, offering novel insights into brain connectivity changes and potential biomarkers for stroke recovery.

To compare the effects of different rehabilitation therapies on the scores of Fugl-Meyer assessment of motor recovery (FMA), the action research arm test (ARAT), and modified Barthel index in hemiplegic patients with stroke by a network meta-analysis. We searched Embase, PubMed, Web of Science, and Cochrane Library from their inception until April 1, 2024 for randomized controlled trials (RCTs) on the effects of rehabilitation therapies on upper extremity motor function and activities of daily living in hemiplegic patients with stroke. Data analyses were conducted using R software. Seventeen RCTs were included, involving 901 patients and 10 rehabilitation therapies. The network meta-analysis revealed that mirror therapy (mean difference [MD] = 4.94, 95% confidence interval [CI]: 4.3-5.59, P < .05), neuromuscular electrical stimulation (NMES) + robotic therapy (RT) (MD = 7.1, 95% CI: 3.15-11.10, P < .05), RT (MD = 4.7, 95% CI: 0.98-8.41, P < .05), and transcranial direct current stimulation (MD = -4.92, 95% CI: -6.12 to -3.72, P < .05) outperformed conventional therapies in the improvement of FMA. NMES + RT (MD = 4.6, 95% CI: 0.42-8.76, P < .05) and repetitive facilitative exercise (RFE) + botulinum toxin type A (BoNT-A) (MD = 8, 95% CI: 4.43-11.52, P < .05) outperformed conventional therapies in the improvement of ARAT. Action observation (AO) (MD = 6, 95% CI: 0.11-11.85, P < .05) was superior to conventional therapies in the improvement of activities of daily living. RFE + BoNT-A had the highest surface under the cumulative ranking curve value for FMA improvement and ARAT improvement. The surface under the cumulative ranking curve value for modified Barthel index improvement was the highest for AO. RFE + BoNT-A and AO exhibit advantages in improving upper extremity motor function and AO, respectively. Due to some limitations in this study, more high-quality RCTs are still required to validate our findings.

Parkinson's disease remains a progressive and debilitating neurodegenerative disorder with limited therapeutic options that can modify disease progression. While conventional treatments like levodopa alleviate motor symptoms, they often fall short in addressing long-term neurodegeneration and may lead to significant side effects. Recent advances in regenerative medicine have highlighted the potential of combining stem cell therapy with Brain-Derived Neurotrophic Factor (BDNF) enhancement as a synergistic approach to restore dopaminergic function and promote neuronal survival. Stem cells not only offer the capacity to replace lost neurons but can also serve as delivery vectors for sustained BDNF expression, amplifying neuroprotective effects through Tropomyosin receptor kinase B-mediated signaling pathways. Preclinical studies in animal models demonstrate that this combined strategy enhances motor recovery, reduces neuroinflammation, and promotes neural circuit integration. As the field progresses, this dual therapy holds great promise for transforming the future management of Parkinson's disease by offering both symptomatic relief and disease modification.

Sex differences in stroke outcomes are well documented, but it is unknown how males and females differ in their timing and duration of the critical window– a limited period of heightened plasticity when the brain is most responsive to rehabilitative interventions. While this window is typically defined by motor recovery, the timeline for tactile feedback remains poorly understood and may follow a distinct trajectory. To explore critical windows of tactile recovery, we developed an isolated tactile model of photothrombotic stroke in mice, which allowed us to investigate the effect of various rehabilitation timing on recovery. Mice were trained to perform a whisker-mediated tactile detection task to establish baseline levels of perception. Focal ischemia was induced using photothrombosis, and were given varying periods of rest (1, 7, or 14 days) before resuming training. While animals did not completely recover to pre-lesion levels, earlier retraining led to better recovery. Separating the groups by sex revealed significant differences in timing of the critical window post stroke. Male mice improved in tactile sensation with immediate (1d) training post-stroke, while female mice benefited more from delayed (7d) training. Minimal recovery was observed in the 14d rest group suggesting the tactile critical window occurs within the first week post-stroke for both sexes, but offset in timing. Our work reveals significant differences in the neuroplastic timeline between sexes. These results shed light on an understudied aspect of stroke rehabilitation and motivate future studies that incorporate sex-specific timing strategies for rehabilitation paradigms.

Introduction: Spinal cord ischemic injury (SCII) is a devastating complication of aortic surgery that often leads to irreversible motor dysfunction. Despite its clinical severity, no effective treatment has been established. Multilineage-differentiating stress-enduring (Muse) cells are a non-tumorigenic, endogenous pluripotent-like stem cell population marked by SSEA-3 expression, with emerging evidence supporting their regenerative potential. However, their long-term therapeutic efficacy in SCII remains largely unexplored. Hypothesis: We hypothesized that intravenous administration of Muse cells would promote sustained motor function recovery in a rat model of severe SCII. Methods: Severe SCII was induced in eight-week-old male Wistar rats by bilaterally injecting endothelin-1 into the anterior horns of the 13th thoracic spinal cord segment. Muse cells were isolated from human bone marrow-derived mesenchymal stem cells (MSCs). At 24 hours post-injury, rats with a BBB locomotor score of 0 were randomly assigned to receive Muse cells, MSCs, or PBS via penile vein injection. Motor function was evaluated for 8 weeks. No immunosuppressants were administered. IVIS imaging and immunofluorescence were performed to assess in vivo biodistribution and engraftment. Cell differentiation was evaluated by double immunostaining with human-specific and lineage-specific markers. Results: At 8 weeks post-treatment, the Muse group showed significantly improved motor recovery compared to MSC and PBS groups (BBB score: Muse 9.5±1.7; MSC 4.7±1.7; PBS 4.5±1.3; p&lt;0.01). IVIS imaging at 1 week revealed stronger luminescence signals in the spinal cords of Muse-treated rats (p&lt;0.05), suggesting selective migration to the injury site. Human mitochondria-positive cells were mainly located 6 mm rostral and caudal to the lesion center (T13), indicating peri-lesional accumulation (p&lt;0.05). Double immunostaining confirmed differentiation into neurons (NeuN: 70.6±5.4%), neuronal dendrites (MAP-2: 68.0±11.4%), oligodendrocytes (GST-pi: 10.6±0.3%), and vascular endothelial cells (CD31: 17.6±1.8%). Conclusions: Intravenous administration of human Muse cells significantly enhanced and maintained hindlimb motor recovery in a rat model of SCII without immunosuppression. Muse cells homed to the damaged spinal cord and differentiated into neural and vascular lineages, contributing to structural and functional repair. These findings highlight Muse cells as a promising therapeutic approach for acute SCII.

Abstract Purpose of Review This review synthesizes recent developments in vagus nerve stimulation (VNS) for stroke rehabilitation from 2021–2025, emphasizing the transition from experimental approaches to clinical implementation following FDA approval of implantable VNS. Recent Findings The 2021 FDA approval of the Vivistim Paired VNS System marked a watershed moment in stroke neuromodulation, providing the first regulatory-approved VNS therapy for upper extremity motor recovery. Long-term follow-up studies demonstrate sustained benefits at one year, with 66% of patients achieving clinically meaningful improvements. Concurrently, investigational transcutaneous approaches continue to evolve, though they remain limited by protocol heterogeneity and anatomical specificity concerns. Summary Implantable VNS paired with rehabilitation represents a paradigm shift in stroke care, offering evidence-based neuromodulation therapy for patients with chronic upper limb impairment. While transcutaneous approaches show promise in research settings, their clinical translation requires standardization and larger controlled trials. Current evidence strongly supports implantable VNS as a viable therapeutic option for carefully selected patients, while highlighting the importance of distinguishing proven treatments from investigational approaches in clinical practice.

Aim. To evaluate the prognostic significance of plasma neuron-specific enolase levels as a predictor of functional outcomes and motor recovery in the acute phase of ischemic stroke after mechanical thrombectomy. Materials and Methods. In 2023, 70 patients with acute cerebral vessel occlusion undergoing mechanical thrombectomy were examined. The cohort included 44 (63%) men and 26 (37%) women, aged 38 to 80 years (65.3±9.4). Stroke severity was assessed using the NIHSS (8-23 points), and functional status at discharge was evaluated using the mRS (mRS 0-3: positive outcome, mRS 4-6: negative outcome). Plasma neuron-specific enolase concentrations were measured by enzyme-linked immunosorbent assay on days 1 and 7 of the disease. Results and Discussion. A statistically significant correlation was found between neuron-specific enolase levels and the severity of neurological deficits in patients with NIHSS £15 and &gt;15 points during the acute phase of ischemic stroke. neuron-specific enolase levels were 3.4±0.2 vs. 5.5±0.6 µg/L on day 1 and 3.4±0.3 vs. 6.6±0.6 µg/L on day 7 (p&lt;0.01). Patients with a negative functional outcome had higher neuron-specific enolase levels both at admission (3.4±0.2 vs. 6.0±0.7 µg/L) and over time (3.7±0.3 vs. 7.1±0.7 µg/L; p&lt;0.01). Additionally, higher neuron-specific enolase levels were observed in patients with hemorrhagic transformation after thrombectomy compared to those without transformation: 7.2±0.8 vs. 3.2±0.2 µg/L on day 1 and 7.8±0.8 vs. 4.0±0.3 µg/L on day 7 (p&lt;0.01). Conclusions. Plasma neuron-specific enolase levels correlate with the severity of neurological deficits, functional status, and the presence of hemorrhagic transformation, making it a potential prognostic biomarker for the course and surgical outcomes of mechanical thrombectomy in patients with acute ischemic stroke.

Abstract Transcranial alternating current stimulation (tACS) is a noninvasive neuromodulatory tool that is thought to entrain intrinsic neural oscillations by supplying low electric currents over the scalp. Recent work has demonstrated the efficacy of theta-gamma phase-amplitude coupled tACS over primary motor cortex to enhance motor skill acquisition and motor recovery after stroke. Here, we wished to assess the efficacy of tACS delivered with 75-Hz gamma coupled to the peak of a 6-Hz theta envelope (theta-gamma peak; TGP) at an intensity of 2 mA peak-to-peak to enhance sensorimotor learning during speech production. Sensorimotor learning was measured by shifting the formant frequency of vowels in real-time as speech is produced and measuring the adaptation to this altered feedback. The study was a between-subjects, single-blind, sham-controlled design. We hypothesised that participants who performed the speech task while receiving TGP tACS over the speech motor cortex (N = 30) would show greater adaptation to altered auditory feedback than those receiving sham stimulation (N = 31). Contrary to this hypothesis, there was no effect of TGP tACS on adaptation to the upwards F1 shift in auditory feedback in either the final 30 trials of the learning phase or in the first 15 trials of the after-effect phase. However, a trend emerged in the TGP tACS group for greater retention of the adapted state and slower return to baseline F1 values in the after-effect phase. This finding was not predicted, and highlights the need for further investigation to deepen our understanding of the effects of TGP tACS on speech motor learning.

Stroke-related long-term disability is primarily due to impaired motor function. Rehabilitation efforts have traditionally focused on central strategies while ignoring the affected muscles. Regenerative medicine approaches have emerged as a promising option for treating various conditions, including muscular disorders. The present study aims to compare the effects of intramuscular injections of mesenchymal stromal cells (MSCs) and Platelet-rich plasma (PRP) on motor recovery in poststroke survivors. A single-blind, randomized, controlled trial will be followed. Fifteen stroke patients who meet the eligibility criteria will be randomly assigned to the cell therapy, PRP, or waiting-list control groups. Patients in each group will receive a single injection of MSCs or PRP into their affected biceps brachii muscle. Patients in the waiting list control group will receive no intervention. The outcome measures include the Modified Modified Ashworth Scale (MMAS), Brunnstrom recovery stages for the upper limb, elbow range of motion, and sonographic evaluations. All outcome measures will be assessed at baseline, 1, 2, and 3 months after injection. The findings of this study will provide initial supportive evidence regarding the efficacy of MSCs and PRP therapy in improving biceps brachii muscle spasticity and function in patients with chronic stroke. IRCT20230208057351N1.

Propriospinal interneurons in the spinal cord integrate multiple modalities of supraspinal and sensory inputs to modulate motor activity and facilitate complex motor behaviors, such as locomotion, skilled reaching, or grasping. The important ability of modulating motor activity in response to changes in the environment is partly mediated by a population of spinal interneurons marked by the expression Isl1, called dI3 neurons. These dI3 neurons are located throughout the cervical and lumbar spinal cord, receive cutaneous and proprioceptive feedback, and project to motoneurons. Previous work has demonstrated that dI3s are implicated in cutaneous-evoked reflexes and play a role in behaviors such as locomotion and grip strength, as well as motor recovery after spinal cord injury; however, it is unclear how different dI3 populations are connected to motor networks across the spinal cord to facilitate these diverse and complex functions. Through optogenetic activation of individual dI3 subpopulations located in different segments of the spinal cord, we mapped the functional connectivity of dI3 premotor circuits across the lumbar and cervical enlargements. We demonstrate that individual dI3 subpopulations have unique connectivity patterns and together form short and long propriospinal circuits that are either ipsilateral or commissural. Our findings suggest that dI3 subpopulations modulate the activity of distinct motor pools to differentially modulate complex motor functions such as grasping or locomotion.NEW & NOTEWORTHY We used an isolated mouse spinal cord preparation to optogenetically stimulate individual subpopulations of dI3 neurons. We investigated for the first time the specific connectivity patterns of dI3 neurons and demonstrated that they activate premotor circuits beyond their local segment, including short propriospinal, long propriospinal, and commissural circuits.

Hebbian stimulation, based on principles of spike timing-dependent plasticity (STDP), has been successfully used to enhance functional recovery in individuals with spinal cord injury (SCI). To advance therapies using Hebbian stimulation, this study aimed to establish STDP-based protocols targeting spinal motoneuron synapses in awake rats. Adult male and female Sprague-Dawley rats were implanted with stainless steel screws through the skull over the hindlimb area of the left motor cortex to enable epidural cortical stimulation. A custom-made cuff with embedded fine-wire electrodes was placed around the right posterior tibial nerve for peripheral stimulation. Fine-wire electrodes were inserted in the soleus muscle to record motor-evoked potentials (MEPs), H-reflexes, and the maximal motor response. During Hebbian stimulation, descending volleys evoked by cortical stimulation were timed to reach spinal motoneurons either 2.5 ms before (Hebbian+) or 15 ms after (Hebbian-) the arrival of antidromic potentials evoked by tibial nerve stimulation on different days. Rats received 180 paired pulses over 30 min, with measurements taken at baseline and every 10 min up to 40-min poststimulation. We found that MEP size increased by an average of 30% over baseline during the 40-min poststimulation period with Hebbian+ stimulation and decreased by an average of 27% with Hebbian- stimulation. These findings provide the first evidence that paired stimulation based on Hebbian STDP principles can bidirectionally modulate MEPs in awake rats. Our rat model of Hebbian stimulation paves the way for exploring experimental combination therapies to enhance motor recovery following SCI and other neurological disorders.NEW & NOTEWORTHY Hebbian stimulation, based on spike timing-dependent plasticity (STDP), has been used to enhance functional recovery in spinal cord injury (SCI). Here, we show that paired stimulation following STDP principles can bidirectionally modulate motor-evoked potential size in the soleus muscle of awake rats. This rat model provides a valuable platform for exploring combination therapies to improve motor recovery in SCI and other neurological disorders.

ABSTRACTBackgroundMicroglial overactivation‐driven neuroinflammation exacerbates secondary damage after spinal cord injury (SCI), but the role of mitochondrial iron metabolism in this process is not well understood. This study investigates the function of the mitochondrial iron transporter solute carrier family 25 member 28 (SLC25A28) in post‐SCI neuroinflammation.MethodsMicroglia‐specific SLC25A28 knockout (A28‐MGKO) mice were generated by crossing SLC25A28flox/flox mice with Cx3cr1‐CreERT2 mice and subjected to clip‐compression spinal cord injury (SCI) at the T9 level. Motor recovery was evaluated using the Basso Mouse Scale (BMS), while histological and biochemical assessments including hematoxylin–eosin and Nissl staining, Iba1 immunohistochemistry, Evans blue permeability, and tissue water content were performed to evaluate lesion severity, neuronal survival, microglial activation, and blood–spinal cord barrier integrity. In vitro, primary microglia isolated from A28‐MGKO mice and BV2 cells with SLC25A28 overexpression were used to investigate mitochondrial iron homeostasis, heme biosynthesis, and NOX2‐mediated oxidative stress. Mitochondrial iron content was quantified using a ferrozine‐based assay and Mito‐FerroGreen staining, while ROS production, cytokine release, and inflammatory signaling were analyzed by fluorescence imaging, ELISA, and Western blotting under pharmacological modulation of heme synthesis and NOX2 activity.ResultsWe found that SLC25A28 deficiency reduced spinal cord edema, blood‐spinal cord barrier disruption, and motor deficits. Mechanistically, SLC25A28 knockout suppressed mitochondrial iron accumulation, inhibited heme synthesis, and reduced NOX2‐mediated oxidative stress. However, SLC25A28 overexpression enhanced mitochondrial iron overload and NOX2‐driven inflammation, which could be reversed by pharmacological blockade of NOX2 or heme synthesis. Restoration of heme synthesis in A28‐MGKO microglia attenuated the anti‐inflammatory effects of SLC25A28 knockout.ConclusionThese findings demonstrate that microglial SLC25A28 regulates neuroinflammation and functional recovery after SCI by promoting mitochondrial iron‐dependent heme synthesis and NOX2 activation. Targeting the SLC25A28–heme–NOX2 axis may provide a novel therapeutic approach for SCI.

Evaluating generalization of arm movement identification using machine learning: From structured to semi-structured environments.

IntroductionApproximately half of stroke survivors experience persistent upper limb dysfunction, which impairs self-care, reduces independence and lowers quality of life. Electroacupuncture is an established intervention with evidence supporting its role in improving upper limb motor function following ischaemic stroke. Motor imagery training (MIT), which activates the sensorimotor cortex through the mental rehearsal of movement, has shown promise as an adjunctive therapy in stroke rehabilitation. The concurrent application of electroacupuncture and MIT may enhance sensorimotor recovery by promoting the integration of central and peripheral neural pathways, potentially establishing a central–peripheral–central closed-loop circuit. However, empirical evidence supporting this integrative approach remains limited.This study aims to investigate the effects of electroacupuncture synchronised with MIT on upper limb function in patients with ischaemic stroke. In addition, longitudinal analysis of multimodal neuroimaging data will be used to explore the associated neural mechanisms.Methods and analysisA total of 72 patients with ischaemic stroke will be enrolled and randomly assigned (1:1) to receive either electroacupuncture synchronised with MIT or electroacupuncture. Each group will undergo 20 treatment sessions over 4 weeks (5 times per week). All participants will also receive standardised conventional rehabilitation training.The primary outcome is the Fugl-Meyer Assessment for the upper extremity. Secondary outcomes include the Modified Barthel Index for activities of daily living, the Modified Ashworth Scale (MAS) for spasticity, Brunnstrom stages, the 17-item Hamilton Depression Rating Scale, the Chinese version of the Massachusetts Acupuncture Sensation Scale and the Kinaesthetic and Visual Imagery Questionnaire. Assessments will be conducted at baseline, mid-treatment, post-treatment and at 8-week follow-up. In addition, functional connectivity of the cerebral cortex will be assessed using functional near-infrared spectroscopy and electroencephalography, which may serve as potential biomarkers of treatment response.Ethics and disseminationThis study has been approved by the Ethics Committee of Shanghai Second Rehabilitation Hospital (approval number: 2025-18-01) and has been registered with the International Traditional Medicine Clinical Trial Registry (ITMCTR; registration number: ITMCTR2025001311). The study will be conducted in accordance with the Declaration of Helsinki, relevant local regulations and applicable clinical guidelines. Informed consent will be obtained from all participants or their legal guardians, where applicable. The results will be disseminated through peer-reviewed publications and presentations at scientific conferences.Trial registration numberITMCTR2025001311.

Paired associative stimulation improves outcomes when applied at the subacute stage after incomplete cervical spinal cord injury.

Salvigenin mitigates neuronal ferroptosis by binding to PI3K and enhancing the interaction between VCP and PI3K in the repair of spinal cord injury.

Spinal cord injury (SCI) is a debilitating neurological condition with far-reaching consequences for patients, including loss of motor function and significant limitations to quality of life. Implantable biomaterials have emerged as a therapeutic strategy to modulate the SCI microenvironment and facilitate regeneration of axons. In this study, plant-derived lignocellulosic scaffolds coated with poly-L-ornithine (PLO) are shown to support locomotor recovery and neural tissue repair in a rat model of spinal cord injury. Upon complete transection of the spinal cord, animals were implanted with a plant-derived scaffold coated in PLO, a positively charged amino acid chain that is known to promote neural stem cell differentiation into neurons and enhance myelin regeneration. Recovery of motor function was evaluated by the Basso, Beattie and Bresnahan (BBB) locomotor scale as well as the Karolinska Institutet Swim Assessment Tool (KSAT). Retrograde tracing of ascending sensory tracts revealed enhanced regeneration in animals that received the PLO-coated scaffold. Numerous β-III tubulin and neurofilament 200 positive fibers may indicate axonal sprouting within the lignocellulosic scaffold and LFB staining highlights myelination around the PLO-coated scaffold. These results demonstrate the potential of plant-based biomaterials in a rat model of acute spinal cord injury and highlight their enhancement after PLO functionalization.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-21856-z.

The decision to cross the cervicothoracic junction (CTJ) during multilevel posterior cervical fusion remains controversial. While constructs extending into the thoracic spine may enhance stability, they may also increase surgical complexity. The clinical relevance of these differences, particularly regarding patient-reported outcomes (PROMs), is still unclear. We hence aimed to determine whether extending fusion across the CTJ impacts PROMs and perioperative complication rates in a nationwide cohort. This retrospective cohort study used prospectively collected data from the Swedish Spine Registry (Swespine). Adult patients who underwent multilevel posterior cervical fusion were divided into two groups: those ending at C7 and those extending beyond the CTJ. Baseline characteristics, surgical details, complication rates, and PROMs at 1- and 5-years were compared. Baseline characteristics were similar between groups (p ≥ 0.5). Perioperative complication and reoperation rates did not differ significantly between groups (p ≥ 0.5). Similarly, at both one- and five-years of follow-up, PROMs, including pain scores, disability indices, and satisfaction, were comparable (p ≥ 0.5). However, a significant difference was observed in terms of fine motor recovery, with patients whose constructs crossed the CTJ demonstrating a greater degree of improvement (p = 0.009). Crossing the CTJ in multilevel posterior cervical fusion does not significantly affect complication rates, reoperations, or most PROMs at one and five years. Surgical decisions should prioritize anatomical and clinical factors, rather than expected differences in PROMs.