Expanded Combined Loading Injury Criterion for the Human Lumbar Spine Under Dynamic Compression.

Contemporary injury tolerance of the lumbar spine for under-body blast references axial compression and bending moments in a limited range. Since injuries often occur in a wider range of flexion and extension with increased moment contribution, this study expands a previously proposed combined loading injury criterion for the lumbar spine. Fifteen cadaveric lumbar spine failure tests with greater magnitudes of eccentric loading were incorporated into an existing injury criterion to augment its applicability and a combined loading injury risk model was proposed by means of survival analysis. A loglogistic distribution was the most representative of injury risk, resulting in optimized critical values of Fr,crit = 6011 N, and My,crit = 904 Nm for the proposed combined loading metric. The 50% probability of injury resulted in a combined loading metric value of 1, with 0.59 and 1.7 corresponding to 5 and 95% injury risk, respectively. The inclusion of eccentric loaded specimens resulted in an increased contribution of the bending moment relative to the previously investigated flexion/extension range (previous My,crit = 1155 Nm), with the contribution of the resultant sagittal force reduced by nearly 200 N (previous Fr,crit = 5824 N). The new critical values reflect an expanded flexion/extension range of applicability of the previously proposed combined loading injury criterion for the human lumbar spine during dynamic compression.

Cyclic Mechanism Affects Lumbar Spine Creep Response.

PURPOSE: This study aims to explore how cyclic loading influences creep response in the lumbar spine under combined flexion-compression loading. METHODS: Ten porcine functional spinal units (FSUs) were mechanically tested in cyclic or static combined flexion-compression loading. Creep response between loading regimes was compared using strain-time histories and linear regression. High-resolution computed tomography (µCT) visualized damage to FSUs. Statistical methods, ANCOVA and ANOVA, assessed differences in behavior between loading regimes. RESULTS: Cyclic and static loading regimes exhibited distinct creep response patterns and biphasic response. ANCOVA and ANOVA analyses revealed significant differences in slopes of creep behavior in both linear phases. Cyclic tests consistently showed endplate fractures in µCT imaging. CONCLUSION: The study reveals statistically significant differences in creep response between cyclic and static loading regimes in porcine lumbar spinal units under combined flexion-compression loading. The observed biphasic behavior suggests distinct phases of tissue response, indicating potential shifts in load transfer mechanisms. Endplate fractures in cyclic tests suggest increased injury risk compared to static loading. These findings underscore the importance of considering loading conditions in computational models and designing preventive measures for occupations involving repetitive spinal loading.

Accuracy of Instrumented Mouthguards During Direct Jaw Impacts Seen in Boxing.

PURPOSE: Measuring head kinematics data is important to understand and develop methods and standards to mitigate head injuries in contact sports. Instrumented mouthguards (iMGs) have been developed to address coupling issues with previous sensors. Although validated with anthropomorphic test devices (ATDs), there is limited post-mortem human subjects (PMHS) data which provides more accurate soft tissue responses. This study evaluated two iMGs (Prevent Biometrics (PRE) and Diversified Technical Systems (DTS) in response to direct jaw impacts. METHODS: Three unembalmed male cadaver heads were properly fitted with two different boil-and-bite iMGs and impacted with hook (4 m/s) and uppercut (3 m/s) punches. A reference sensor (REF) was rigidly attached to the base of the skull, impact kinematics were transformed to the head center of gravity and linear and angular kinematic data were compared to the iMGs including Peak Linear Acceleration, Peak Angular Acceleration, Peak Angular Velocity, Head Injury Criterion (HIC), HIC duration, and Brain Injury Criterion. RESULTS: Compared to the REF sensor, the PRE iMG underpredicted most of the kinematic data with slopes of the validation regression line between 0.72 and 1.04 and the DTS overpredicted all the kinematic data with slopes of the regression line between 1.4 and 8.7. CONCLUSION: While the PRE iMG was closer to the REF sensor compared to the DTS iMG, the results did not support the previous findings reported with use of ATDs. Hence, our study highlights the benefits of using PMHS for validating the accuracy of iMGs since they closely mimic the human body compared to any ATD's mandible.

Hydration State Throughout Porcine Lumbar Intervertebral Discs: Comparing Fresh and Frozen-Thawed Specimens.

Water content in intervertebral discs (IVDs) is essential for physiological and mechanical function. Freezing post-mortem tissue prior to biomechanical testing is a common practice to prevent tissue degradation, but this process has been theorized to alter hydration within IVDs. The hydration state throughout porcine lumbar IVDs, a common lumbar surrogate, is unknown as are the effects of freezing on porcine IVD hydration. Nineteen porcine lumbar spines were stored in one of the three conditions: frozen (- 20 °C) wrapped in saline-soaked gauze, frozen (- 20 °C) without saline, or fresh. Water content was measured in four disc regions within each of 89 discs: nucleus pulposus (NP), inner (AF-A), intermediate (AF-B), and outer (AF-C) annulus fibrosus. A three-factor, repeated measure analysis of variance was conducted for storage condition, spinal level, and repeated measure disc region. No significant differences were observed in spinal level or storage condition as a main effect. Mean hydration was significantly different in each disc region with mass percentage of water found to be 88.8 ± 1.7% in NP, 79.6 ± 3.8% in AF-A, 71.9 ± 3.7% in AF-B, and 62.3 ± 3.3% in AF-C. No significant differences were shown in NP and AF-C regions between storage conditions. Two significant differences in storage condition were observed in AF-A and AF-B regions, but there is likely no biological difference in these populations. Water content throughout porcine lumbar IVD was determined and results suggest one freeze-thaw cycle at - 20 °C does not alter the overall hydration within the porcine lumbar IVD.

Biofidelity and Limitations of Instrumented Mouthguard Systems for Assessment of Rigid Body Head Kinematics.

Instrumented mouthguard systems (iMGs) are commonly used to study rigid body head kinematics across a variety of athletic environments. Previous work has found good fidelity for iMGs rigidly fixed to anthropomorphic test device (ATD) headforms when compared to reference systems, but few validation studies have focused on iMG performance in human cadaver heads. Here, we examine the performance of two boil-and-bite style iMGs in helmeted cadaver heads. Three unembalmed human cadaver heads were fitted with two instrumented boil-and-bite mouthguards [Prevent Biometrics and Diversified Technical Systems (DTS)] per manufacturer instructions. Reference sensors were rigidly fixed to each specimen. Specimens were fitted with a Riddell SpeedFlex American football helmet and impacted with a rigid impactor at three velocities and locations. All impact kinematics were compared at the head center of gravity. The Prevent iMG performed comparably to the reference system up to ~ 60 g in linear acceleration, but overall had poor correlation (CCC = 0.39). Prevent iMG angular velocity and BrIC generally well correlated with the reference, while underestimating HIC and overestimating HIC duration. The DTS iMG consistently overestimated the reference across all measures, with linear acceleration error ranging from 10 to 66%, and angular acceleration errors greater than 300%. Neither iMG demonstrated consistent agreement with the reference system. While iMG validation efforts have utilized ATD testing, this study highlights the need for cadaver testing and validation of devices intended for use in-vivo, particularly when considering realistic (non-idealized) sensor-skull coupling, when accounting for interactions with the mandible and when subject-specific anatomy may affect device performance.

Human and Porcine Lumbar Endplate Injury Risk in Repeated Flexion-Compression.

Low back pain (LBP) affects 50-80% of adults at some point in their lifetime, yet the etiology of injury is not well understood. Those exposed to repeated flexion-compression are at a higher risk for LBP, such as helicopter pilots and motor vehicle operators. Animal injury models offer insight into in vivo injury mechanisms, but interspecies scaling is needed to relate animal results to human. Human (n = 16) and porcine (n = 20) lumbar functional spinal units (FSUs) were loaded in repeated flexion-compression (1 Hz) to determine endplate fracture risk over long loading exposures. Flexion oscillated from 0 to 6° and peak applied compressive stress ranged from 0.65 to 2.38 MPa for human and 0.64 to 4.68 MPa for porcine specimens. Five human and twelve porcine injuries were observed. The confidence intervals for human and porcine 50% injury risk curves in terms of stress and cycles overlapped, indicating similar failure behavior for this loading configuration. However, porcine specimens were more tolerant to the applied loading compared to human, demonstrated by a longer time-to-failure for the same applied stress. Optimization revealed that time-to-failure in human specimens was approximately 25% that of porcine specimens at a given applied stress within 0.65-2.38 MPa. This study determined human and porcine lumbar endplate fracture risks in long-duration repeated flexion-compression that can be directly used for future equipment and vehicle design, injury prediction models, and safety standards. The interspecies scale factor produced in this study can be used for previous and future porcine lumbar injury studies to scale results to relevant human injury.

Shear shock wave injury in vivo: High frame-rate ultrasound observation and histological assessment.

Using high frame-rate ultrasound and ¡1µm sensitive motion tracking we previously showed that shear waves at the surface of ex vivo and in situ brains develop into shear shock waves deep inside the brain, with destructive local accelerations. However post-mortem tissue cannot develop injuries and has different viscoelastodynamic behavior from in vivo tissue. Here we present the ultrasonic measurement of the high-rate shear shock biomechanics in the in vivo porcine brain, and histological assessment of the resulting axonal pathology. A new biomechanical model of brain injury was developed consisting of a perforated mylar surface attached to the brain and vibrated using an electromechanical shaker. Using a custom sequence with 8 interleaved wide beam emissions, brain imaging and motion tracking were performed at 2900 images/s. Shear shock waves were observed for the first time in vivo wherein the shock acceleration was measured to be 2.6 times larger than the surface acceleration ( 95g vs. 36g). Histopathology showed axonal damage in the impacted side of the brain from the brain surface, accompanied by a local shock-front acceleration of >70g. This shows that axonal injury occurs deep in the brain even though the shear excitation was at the brain surface, and the acceleration measurements support the hypothesis that shear shock waves are responsible for deep traumatic brain injuries.

Female vs. male relative fatality risk in fatal motor vehicle crashes in the US, 1975-2020.

Motor vehicle accidents are the leading cause of death for young adults 18-29 years old worldwide, resulting in nearly 1 million years of life lost annually in the United States. Despite improvements in vehicle safety technologies, young women are at higher risk of dying in car crashes compared with men in matched scenarios. Vehicle crash testing primarily revolves around test dummies representative of the 50th percentile adult male, potentially resulting in these differences in fatality risk for female occupants compared to males. Vehicle occupants involved in fatal car crashes were matched using seating location, vehicle type, airbag deployment, seatbelt usage, and age. The relative risk for fatality (R) between males and females was calculated using a Double Pair Comparison. Young women (20s-40s) are at approximately 20% higher risk of dying in car crashes compared with men of the same age in matched scenarios. In passenger cars, 25-year-old female occupants in passenger car crashes from 1975-2020 exhibit R = 1.201 (95% CI 1.160-1.250) compared to 25-year-old males, and R-1.117 (95% CI 1.040-1.207) for passenger car crashes from 2010-2020. This trend persists across vehicle type, airbag deployment, seatbelt use, and number of vehicles involved in a crash. Known sex-based differences do not explain this large risk differential, suggesting a need for expanded test methodologies and research strategies to address as-yet unexplored sex differences in crash fatalities. These differences should be further investigated to ensure equitable crash protection.

Facial Fracture Injury Criteria from Night Vision Goggle Impact.

INTRODUCTION: Military personnel extensively use night vision goggles (NVGs) in contemporary scenarios. Since NVGs may induce or increase injuries from falls or vehicular accidents, biomechanical risk assessments would aid design goal or mitigation strategy development.METHODS: This study assesses injury risks from NVG impact on cadaver heads using impactors modeled on the PVS-14 NVG. Impacts to the zygoma and maxilla were performed at 20° or 40° angles. Risks of facial fracture, neurotrauma, and neck injury were assessed. Acoustic sensors and accelerometers assessed time of fracture and provided input variables for injury risk functions. Injuries were assessed using the Abbreviated Injury Scale (AIS); injury severity was assessed using the Rhee and Donat scales. Risk functions were developed for the input variables using censored survival analyses.RESULTS: The effects of impact angle and bone geometry on injury characteristics were determined with loading area, axial force, energy attenuation, and stress at fracture. Probabilities of facial fracture were quantified through survival analysis and injury risk functions. These risk functions determined a 50% risk of facial bone fracture at 1148 N (axial force) at a 20° maxillary impact, 588 N at a 40° maxillary impact, and 677 N at a 20° zygomatic impact. A cumulative distribution function indicates 769 N corresponds to 50% risk of fracture overall.DISCUSSION: Results found smaller impact areas on the maxilla are correlated with higher angles of impact increasing risk of facial fracture, neck injuries are unlikely to occur before fracture or neurotrauma, and a potential trade-off mechanism between fracture and brain injury.Davis MB, Pang DY, Herring IP, Bass CR. Facial fracture injury criteria from night vision goggle impact. Aerosp Med Hum Perform. 2023; 94(11):827-834.

Using Wavelet Analysis to Distinguish Cavitation Acoustic Emissions From Blunt Impact Noise.

Cavitation has been shown to have implications for head injury, but currently there is no solution for detecting the formation of cavitation through the skull during blunt impact. The goal of this communication is to confirm the wideband acoustic wavelet signature of cavitation collapse, and determine that this signature can be differentiated from the noise of a blunt impact. A controlled, laser induced cavitation study was conducted in an isolated water tank to confirm the wide band acoustic signature of cavitation collapse in the absence of a blunt impact. A clear acrylic surrogate head was impacted to induce blunt impact cavitation. The bubble formation was imaged using a high speed camera, and the collapse was synched up with the wavelet transform of the acoustic emission. Wideband acoustic response is seen in wavelet transform of positive laser induced cavitation tests, but absent in laser induced negative controls. Clear acrylic surrogate tests showed the wideband acoustic wavelet signature of collapse can be differentiated from acoustic noise generated by a blunt impact. Broadband acoustic signal can be used as a biomarker to detect the incidence of cavitation through the skull as it consists of frequencies that are low enough to potentially pass through the skull but high enough to differentiate from blunt impact noise. This lays the foundation for a vital tool to conduct CSF cavitation research in-vivo.

The Human Lumbar Spine During High-Rate Under Seat Loading: A Combined Metric Injury Criteria.

Modern changes in warfare have shown an increased incidence of lumbar spine injuries caused by underbody blast events. The susceptibility of the lumbar spine during these scenarios could be exacerbated by coupled moments that act with the rapid compressive force depending on the occupant's seated posture. In this study, a combined loading lumbar spine vertebral body fracture injury criteria (Lic) across a range of postures was established from 75 tests performed on instrumented cadaveric lumbar spine specimens. The spines were predominantly exposed to axial compressive forces from an upward vertical thrust with 64 of the tests resulting in at least one vertebral body fracture and 11 in no vertebral body injury. The proposed Lic utilizes a recommended metric (κ), based on prismatic beam failure theory, resulting from the combination of the T12-L1 resultant sagittal force and the decorrelated bending moment with optimized critical values of Fr,crit = 5824 N and My,crit = 1155 Nm. The 50% risk of lumbar spine injury corresponded to a combined metric of 1, with the risk decreasing with the combined metric value. At 50% injury risk the Normalized Confidence Interval Size improved from 0.24 of a force-based injury reference curve to 0.17 for the combined loading metric.

Time and temperature sensitivity of the hybrid III lumbar spine.

OBJECTIVE: Researchers have found a variety of uses for the Hybrid III (HIII) dummy that fall beyond the scope of its original purpose as an automotive crash test dummy. Some of these expanded roles for the HIII introduce situations that were not envisioned in the dummy's original design parameters, such as a relatively rapid succession of tests or outdoor testing scenarios where temperature is not easily controlled. This study investigates how the axial compressive stiffness of the HIII lumbar spine component is affected by the duration of the time interval between tests. Further, it measures the effect of temperature on the compressive stiffness of the lumbar spine through a range of temperatures relevant to indoor and outdoor testing. METHODS: High-rate axial compression tests were run on a 50th percentile male HIII lumbar component in a materials testing machine. To characterize the effects of tests recovery intervals, between-test recovery was varied from 2 hours to 1 minute. To quantify temperature effects, environmental temperature conditions of 12.5°, 25°, and 37.5 °C were tested. RESULTS: During repeated compressive loading, the force levels decreased consistently across long and short rest intervals. Even after 2 hours of rest between tests, full viscoelastic recovery was not observed. Temperature effects were pronounced, resulting in compressive force differences of 261% over the range of 12.5° to 37.5 °C. Compared to the stiffness of the lumbar at 25 °C, the stiffness at 37.5 °C fell by 40%; at 12.5 °C, the stiffness more than doubled, increasing by 115%. CONCLUSIONS: A modest decrease in temperature can be sufficient to dramatically change the response and repeatability of the lumbar HIII component in compressive loading. The large magnitude of the temperature effect has severe implications in its ability to overwhelm the contributions of targeted test variables. These findings highlight the importance of controlling, monitoring and reporting temperature conditions during HIII testing, even in indoor laboratory environments.

Acoustic emissions in vertebral cortical shell failure.

Understanding the initiation of bony failure is critical in assessing the progression of bone fracture and in developing injury criteria. Detection of acoustic emissions in bone can be used to identify fractures more sensitively and at an earlier inception time compared to traditional methods. However, high rate loading conditions, complex specimen-device interaction or geometry may cause other acoustic signals. Therefore, characterization of the isolated local acoustic emission response from cortical bone fracture is essential to distinguish its characteristics from other potential acoustic sources. This work develops a technique to use acoustic emission signals to determine when cortical bone failure occurs by characterization using both a Welch power spectral density estimate and a continuous wavelet transform. Isolated cortical shell specimens from thoracic vertebral bodies with attached acoustic sensors were subjected to quasistatic loading until failure. The resulting acoustic emissions had a wideband frequency response with peaks from 20 to 900 kHz, with the spectral peaks clustered in three bands of frequencies (166 ± 52.6 kHz, 379 ± 37.2 kHz, and 668 ± 63.4 kHz). Using these frequency bands, acoustic emissions can be used as a monitoring tool in biomechanical spine testing, distinguishing bone failure from structural response. This work presents a necessary set of techniques for effectively utilizing acoustic emissions to determine the onset of cortical bone fracture in biological material testing. Acoustic signatures can be developed for other cortical bone regions of interest using the presented methods.

Assessing Surgical Task Load and Performance: A Comparison of Simulation and Maritime Operation.

INTRODUCTION: This study examined the effects of simulated and actual vessel motion at high seas on task load and surgical performance. METHODS: This project was performed in phases. Phase I was a feasibility study. Phase II utilized a motion base simulator to replicate vessel motion. Phase III was conducted aboard the U.S. Naval Ship Brunswick. After performing surgical tasks on a surgical simulation mannequin, participants completed the Surgical Task Load Index (TLX) designed to collect workload data. Simulated surgeries were evaluated by subject matter experts. RESULTS: TLX scores were higher in Phase III than Phase II, particularly at higher sea states. Surgical performance was not significantly different between Phase II (84%) and Phase III (89%). Simulated motions were comparable in both phases. CONCLUSIONS: Simulated motion was not associated with a significant difference in surgical performance or deck motion, suggesting that this simulator replicates the conditions experienced during surgery at sea on the U.S. Naval Ship Brunswick. However, Surgical TLX scores were dramatically different between the two phases, suggesting increased workload at sea, which may be the result of time at sea, the stress of travel, or other factors. Surgical performance was not affected by sea state in either phase.

Primary blast wave protection in combat helmet design: A historical comparison between present day and World War I.

Since World War I, helmets have been used to protect the head in warfare, designed primarily for protection against artillery shrapnel. More recently, helmet requirements have included ballistic and blunt trauma protection, but neurotrauma from primary blast has never been a key concern in helmet design. Only in recent years has the threat of direct blast wave impingement on the head-separate from penetrating trauma-been appreciated. This study compares the blast protective effect of historical (World War I) and current combat helmets, against each other and 'no helmet' or bare head, for realistic shock wave impingement on the helmet crown. Helmets included World War I variants from the United Kingdom/United States (Brodie), France (Adrian), Germany (Stahlhelm), and a current United States combat variant (Advanced Combat Helmet). Helmets were mounted on a dummy head and neck and aligned along the crown of the head with a cylindrical shock tube to simulate an overhead blast. Primary blast waves of different magnitudes were generated based on estimated blast conditions from historical shells. Peak reflected overpressure at the open end of the blast tube was compared to peak overpressure measured at several head locations. All helmets provided significant pressure attenuation compared to the no helmet case. The modern variant did not provide more pressure attenuation than the historical helmets, and some historical helmets performed better at certain measurement locations. The study demonstrates that both historical and current helmets have some primary blast protective capabilities, and that simple design features may improve these capabilities for future helmet systems.

Direct Observation of Low Strain, High Rate Deformation of Cultured Brain Tissue During Primary Blast.

The Veterans Health Administration determined that over 250,000 U.S. service members were diagnosed with a traumatic brain injury (TBI) between 2008 and 2018, of which a great proportion were due to blast exposure. Although the penetrating (secondary) and inertia-driven (tertiary) phases of blast-induced TBI (bTBI) have been studied thoroughly and are known to be injurious, primary blast brain injury has been less studied. We investigated the biomechanics of primary bTBI in our previously developed in vitro shock tube model with a fluid-filled sample receiver. Using stereoscopic, high-speed cameras and digital image correlation (DIC), we mapped the deformation of organotypic hippocampal slice cultures (OHSCs) following a range of blast exposures to characterize the induced strains. As blast exposure increased, tissue strain increased, although the levels remained relatively low (maximum < 9%), with strains rates between 25 and 85 s-1. Both strain magnitude and rate were highly correlated with the in-air blast impulse and in-fluid peak pressure parameters. Comparing biomechanical parameters to previously reported blast-induced electrophysiological dysfunction, a threshold for deficits in long-term potentiation (LTP) was observed for strains between 3.7 and 6.7% and strain rates between 25 and 33 s-1. This is the first study to experimentally determine primary blast-induced strain and strain rates in hippocampal tissue.

The role of cervical muscles in mitigating concussion.

OBJECTIVES: Increased neck strength has been hypothesized to lower sports related concussion risk, but lacks experimental evidence. The goal is to investigate the role cervical muscle strength plays in blunt impact head kinematics and the biofidelity of common experimental neck conditions. We hypothesize head kinematics do not vary with neck activation due to low short term human head-to-neck coupling; because of the lack of coupling, free-head experimental conditions have higher biofidelity than Hybrid III necks. METHODS: Impacts were modeled using the Duke University Head and Neck Model. Four impact types were simulated with six neck conditions at eight impact positions. Peak resultant linear acceleration, peak resultant angular acceleration, Head Injury Criterion, and Head Impact Power compared concussion risk. To determine significance, maximum metric difference between activation states were compared to critical effect sizes (literature derived differences between mild and severe impact metrics). RESULTS: Maximum differences between activation conditions did not exceed critical effect sizes. Kinematic differences from impact location and strength can be ten times cervical muscle activation differences. Hybrid III and free-head linear acceleration metrics were 6±1.0% lower and 12±1.5% higher than relaxed condition respectively. Hybrid III and free-head angular acceleration metrics were 12±4.0% higher and 2±2.7% lower than relaxed condition respectively. CONCLUSIONS: Results from a validated neck model suggest increased cervical muscle force does not influence short term (<50ms) head kinematics in four athletically relevant scenarios. Impact location and magnitude influence head kinematics more than cervical muscle state. Biofidelic limitations of both Hybrid III and free-head experimental conditions must be considered.

On the relative importance of bending and compression in cervical spine bilateral facet dislocation.

BACKGROUND: Cervical bilateral facet dislocations are among the most devastating spine injuries in terms of likelihood of severe neurological sequelae. More than half of patients with tetraparesis had sustained some form of bilateral facet fracture dislocation. They can occur at any level of the sub-axial cervical spine, but predominate between C5 and C7. The mechanism of these injuries has long been thought to be forceful flexion of the chin towards the chest. This "hyperflexion" hypothesis comports well with intuition and it has become dogma in the clinical literature. However, biomechanical studies of the human cervical spine have had little success in producing this clinically common and devastating injury in a flexion mode of loading. METHODS: The purpose of this manuscript is to review the clinical and engineering literature on the biomechanics of bilateral facet dislocations and to describe the mechanical reasons for the causal role of compression, and the limited role of head flexion, in producing bilateral facet dislocations. FINDINGS: Bilateral facet dislocations have only been produced in experiments where compression is the primary loading mode. To date, no biomechanical study has produced bilateral facet dislocations in a whole spine by bending. Yet the notion that it is primarily a hyper-flexion injury persists in the clinical literature. INTERPRETATION: Compression and compressive buckling are the primary causes of bilateral facet dislocations. It is important to stop using the hyper-flexion nomenclature to describe this class of cervical spines injuries because it may have a detrimental effect on designs for injury prevention.

Long-term complications of glycogen storage disease type Ia in the canine model treated with gene replacement therapy.

BACKGROUND: Glycogen storage disease type Ia (GSD Ia) in dogs closely resembles human GSD Ia. Untreated patients with GSD Ia develop complications associated with glucose-6-phosphatase (G6Pase) deficiency. Survival of human patients on intensive nutritional management has improved; however, long-term complications persist including renal failure, nephrolithiasis, hepatocellular adenomas (HCA), and a high risk for hepatocellular carcinoma (HCC). Affected dogs fail to thrive with dietary therapy alone. Treatment with gene replacement therapy using adeno-associated viral vectors (AAV) expressing G6Pase has greatly prolonged life and prevented hypoglycemia in affected dogs. However, long-term complications have not been described to date. METHODS: Five GSD Ia-affected dogs treated with AAV-G6Pase were evaluated. Dogs were euthanized due to reaching humane endpoints related to liver and/or kidney involvement, at 4 to 8 years of life. Necropsies were performed and tissues were analyzed. RESULTS: Four dogs had liver tumors consistent with HCA and HCC. Three dogs developed renal failure, but all dogs exhibited progressive kidney disease histologically. Urolithiasis was detected in two dogs; uroliths were composed of calcium oxalate and calcium phosphate. One affected and one carrier dog had polycystic ovarian disease. Bone mineral density was not significantly affected. CONCLUSIONS: Here, we show that the canine GSD Ia model demonstrates similar long-term complications as GSD Ia patients in spite of gene replacement therapy. Further development of gene therapy is needed to develop a more effective treatment to prevent long-term complications of GSD Ia.