Inter-software and inter-threshold reliability of quantitative paraspinal muscle segmentation.

PURPOSE: Changes in the cross-sectional area (CSA) and functional cross-sectional area (FCSA) of the lumbar multifidus (MF) and erector spinae muscles (ES) are factors that can contribute to low back pain. For the assessment of muscle CSA and composition there are various software and threshold methods used for tissue segmentation in quantitative analysis. However, there is currently no gold standard for software as well as muscle segmentation. This study aims to analyze the measurement error between different image processing software and different threshold methods for muscle segmentation. METHODS: Magnetic resonance images (MRI) of 60 patients were evaluated. Muscle CSA and FCSA measurements were acquired from axial T2-weighted MRI of the MF and ES at L4/L5 and L5/S1. CSA, FCSA, and FCSA/CSA ratio were measured independently by two observers. The MRI images were measured using two different software programs (ImageJ and Amira) and with two threshold methods (Circle/Overlap method) for each software to evaluate FCSA and FCSA/CSA ratio. RESULTS: Inter-software comparisons revealed high inter-rater reliability. However, poor inter-rater reliability were obtained with different threshold methods. CSA, FCSA, and FCSA/CSA showed excellent inter-software agreement of 0.75-0.99 regardless of the threshold segmentation method. The inter-rater reliability between the two observers ranged between 0.75 and 0.99. Comparison of the two segmentation methods revealed agreement between 0.19 and 0.84. FCSA and FCSA/CSA measured via the Overlap method were significantly higher than those measured via the Circle method (P < 0.01). CONCLUSION: The present study showed a high degree of reliability with very good agreement between the two software programs. However, study results based on different threshold methods should not be directly compared.

Characteristics of lumbar spondylolysis: L5 versus non-L5.

BACKGROUND: Fifth lumbar vertebra (L5) spondylolysis has a lower bone union rate than non-L5 spondylolysis, but the reason for this is unknown. This study aimed to evaluate the differences in patient and lesion characteristics between L5 and non-L5 spondylolysis. METHODS: A total of 410 patients with lumbar spondylolysis aged 18 years or younger who were treated conservatively were enrolled. Patients and lesions were divided into L5 and non-L5 (L2-L4) spondylolysis. Factors, including sex, age, presence of spina bifida occulta, stage of the main side lesion, whether the lesion was unilateral or bilateral, presence and stage of the contralateral side lesion and treatment duration, were evaluated at the first visit and compared between the two groups. RESULTS: A total of 250 patients with 349 lesions were included. The bone union rate of L5 lesions was lower than that of non-L5 lesions (75% vs. 86%, p = 0.015). Patients with L5 spondylolysis were more likely to be male (86% vs. 66%) and younger (14.0 vs. 14.6 years) than patients with non-L5 spondylolysis. Lesions of L5 spondylolysis were more likely to be in a progressive stage (28% vs. 15%), less likely to be in a pre-lysis stage (28% vs. 43%) and more likely to be in a contralateral terminal stage (14% vs. 5.3%, p = 0.013) compared with lesions of non-L5 spondylolysis. CONCLUSIONS: L5 spondylolysis was characterised by a lower bone union rate, more males, younger age, more progressive stage and more contralateral pseudarthrosis than non-L5 spondylolysis.

Complications and local recurrence of chondrosarcoma and chordoma treated by total tumor resection in thoracic and lumbar spine.

BACKGROUND: En bloc resection of spinal tumors is challenging and associated with a high incidence of complications; however, it offers the potential to reduce the risk of recurrence when a wide margin is achieved. This research aims to investigate the safety and efficacy of en bloc resection in treating thoracic and lumbar chondrosarcoma/chordoma. METHODS: Data from patients diagnosed with chondrosarcoma and chordoma in the thoracic or lumbar region, who underwent total en bloc or piecemeal resection at our institution over a 7-year period, were collected and regularly followed up. The study analyzed overall perioperative complications and compared differences in complications and local tumor recurrence between the two surgical methods. RESULTS: Seventeen patients were included, comprising 12 with chondrosarcoma and 5 with chordoma. Among them, 5 cases underwent intralesional piecemeal resection, while the remaining 12 underwent planned en bloc resection. The average surgical time was 684 min (sd = 287), and the mean estimated blood loss was 2300 ml (sd = 1599). Thirty-five complications were recorded, with an average of 2.06 perioperative complications per patient. 82% of patients (14/17) experienced at least one perioperative complication, and major complications occurred in 64.7% (11/17). Five patients had local recurrence during the follow-up, with a mean recurrence time of 16.2 months (sd = 7.2) and a median recurrence time of 20 months (IQR = 12.5). Hospital stays, operation time, blood loss, and complication rates did not significantly differ between the two surgical methods. The local recurrence rate after en bloc resection was lower than piecemeal resection, although not statistically significant (P = 0.067). CONCLUSIONS: The complication rates between the two surgical procedures were similar. Considering safety and local tumor control, en bloc resection is recommended as the primary choice for patients with chondrosarcoma/chordoma in the thoracic and lumbar regions who are eligible for this treatment.

Loss of lumbar disc height with age and its impact on pain and sensitivity associated behaviors in mice.

PURPOSE: Aging is a risk factor for several debilitating conditions including those related to chronic back pain and intervertebral disc degeneration, both of which have no cure. Mouse models are useful tools for studying disc degeneration and chronic back pain in a tightly controlled and clinically relevant aging environment. Moreover, mice offer the advantage of carrying out longitudinal studies to understand the etiology and progression of disc pathology induced by genetic or surgical strategies. Previously, age-related behavioral trends of discomfort and enhanced nociception in mice were reported; however, whether these measures are mediated by structural and pathological changes in the disc is unknown. METHODS: The goal of the present observational study was to identify behavioral correlates of age-related degenerative changes in the disc. Towards this, we collected radiographs from 150 mice (77 females) between three and 23 months of age and measured the disc height index for each level of lumbar disc. Behavioral measures were collected on several of these mice which included rearing and distance travelled in an open field test; time spent in rearing, reaching, immobile, and self-suspended in the tail suspension test; bilateral hind paw licking in response to cold allodynia using acetone; and unilateral hind paw licking in response to heat hyperalgesia using capsaicin. RESULTS: Results show that the lower lumbar discs lose height with age and these changes are independent of body composition measures including body weight, bone mineral density, fat mass, lean weight mass, percent fat mass, and percent lean mass. Disc height positively correlates with rearing and mobility in the open field test, immobility in the tail suspension test, and thermal hyperalgesia. Disc height negatively correlates with cold allodynia and rearing in the tail suspension test. Furthermore, mediation analysis shows that the lumbosacral disc significantly mediates the effect of age on rearing in the open field test, but not cold allodynia, suggesting this behavior is a useful measure of age-related axial discomfort due to disc degeneration. CONCLUSION: In summary, the findings from the current study show that disc height are associated with measures of axial discomfort and nociception in mice.

Do MRI-derived muscle moment-arms in patients with chronic low back pain differ from healthy individuals? A comparative study.

OBJECTIVES: The present study aimed to estimate the trunk muscles moment-arms in low back pain (LBP) patients and compare this data to those of healthy individuals. This research further explored whether the difference of the moment-arms between these two is a contributing factor to LBP. METHODOLOGY: Fifty patients with CLBP (group A) and 25 healthy controls (group B) were enrolled. All participants were subjected to magnetic resonance imaging of lumbar spine. Muscle moment-arms were estimated on a T2W axial section parallel to the disc. RESULTS: There was statistically significant differences (p < 0.05) in the sagittal plane moment-arms at L1-L2 for right erector spinae (ES), bilateral psoas and rectus abdominis (RA), right quadratus lumborum (QL), and left obliques; bilateral ES, QL, RA, and right psoas at L2-L3; bilateral QL, RA, and obliques at L3-L4; bilateral RA and obliques at L4-L5; and bilateral psoas, RA, and obliques at L5-S1. There was no statistically significant difference (p < 0.05) in the coronal plane moment-arms except for left ES and QL at L1-L2; left QL and right RA at L3-L4; right RA and obliques at L4-L5; and bilateral ES and right RA at L5-S1. CONCLUSIONS: There was a significant difference in muscle moment-arms of the lumbar spine's prime stabilizer (psoas) and primary locomotors (rectus abdominis and obliques) between LBP patients and healthy individuals. This difference in the moment-arms leads to altered compressive forces at intervertebral discs and may be one of the risk factors for LBP.

Do Modic changes contribute to lumbar instability or other way around? A retrospective study based on their types, extents, and affected lumbar segments.

BACKGROUND: Which types of Modic changes (MCs) and whether or how specific factors associated to MCs work on lumbar instability have yet to be well understood. The purpose of this study was to investigate the influences of the types of MCs, the extent of MCs lesion involvement, and different lumbar levels involved by MCs on lumbar instability. METHODS: This retrospective study included 263 adult subjects with MCs who underwent lumbar X-ray examinations in the neutral, flexion, and extension positions. All patients who met our inclusion criteria were examined with 1.5 Tesla magnetic resonance units. Two experienced authors with more than three-year clinical experience independently evaluated and measured the subjects' radiographic images. The subgroup analysis was performed to detect the differences in subjects' baseline characteristics and lumbar segmental motions among three types of MCs, the extent of MCs lesion involvement and different lumbar levels involved by MCs. RESULTS: There was a statistical difference in body mass index (BMI) between different involvement extent of MCs (p < 0.01), indicating that the subjects with high BMI are more likely to develop severe MCs. The subjects with Modic type 1 change (MC1) had a significant increase in lumbar angular motion than those with Modic type 2 change (MC2) and Modic type 3 change (MC3) (p < 0.01) and compared with MC3, a significant increase in lumbar translation motion was detected in subjects with MC1 and MC2 (p < 0.01). While, angular motion decreased, translation motion increased significantly as the extent of MCs lesion involvement aggravated (p < 0.01). However, there were no statistical differences in lumbar angular and translation motions between different lumbar levels involved by MCs (p > 0.05). CONCLUSIONS: Higher BMI might be a risk factor for the development of severe MCs. MC1 and MC2 significantly contribute to lumbar instability. The extents of MCs lesion involvement are strongly associated with lumbar instability. However, different lumbar levels involved by MCs have little effect on lumbar stability.

PILLAR: ParaspInaL muscLe segmentAtion pRoject - a comprehensive online resource to guide manual segmentation of paraspinal muscles from magnetic resonance imaging.

BACKGROUND: There is an increasing interest in assessing paraspinal morphology and composition in relation to low back pain (LBP). However, variations in methods and segmentation protocols contribute to the inconsistent findings in the literature. We present an on-line resource, the ParaspInaL muscLe segmentAtion pRoject (PILLAR, https://projectpillar.github.io/ ), to provide a detailed description and visual guide of a segmentation protocol by using the publicly available ITK-SNAP software and discuss related challenges when performing paraspinal lumbar muscles segmentations from magnetic resonance imaging (MRI). METHODS: T2-weighted and corresponding fat-water IDEAL axial MRI from 3 males and 3 females (2 chronic LBP and 1 control for each sex) were used to demonstrate our segmentation protocol for each lumbar paraspinal muscle (erector spinae, lumbar multifidus, quadratus lumborum and psoas) and lumbar spinal level (L1-L5). RESULTS: Proper segmentation requires an understanding of the anatomy of paraspinal lumbar muscles and the variations in paraspinal muscle morphology and composition due to age, sex, and the presence of LBP or related spinal pathologies. Other challenges in segmentation includes the presence and variations of intramuscular and epimuscular fat, and side-to-side asymmetry. CONCLUSION: The growing interest to assess the lumbar musculature and its role in the development and recurrence of LBP prompted the need for comprehensive and easy-to-follow resources, such as the PILLAR project to reduce inconsistencies in segmentation protocols. Standardizing manual muscle measurements from MRI will facilitate comparisons between studies while the field is progressively moving towards the automatization of paraspinal muscle measurements for large cohort studies.

Spinal myelolipoma - an extremely rare pathology within the lumbar spine: a case report and literature review.

Myelolipoma is a benign tumor containing mature adipose cells and a combination of myeloid and erythroid elements. This tumor is typically found in the adrenal glands; however, it has been detected outside the adrenal glands in rare cases. We report an extremely rare case of myelolipoma in the lumbar spine causing significant neural compression due to the involvement of the posterior spinal elements. Given the significant neurological deficit, the patient was surgically managed as soon as possible. Extra-adrenal myelolipomas are rare lesions, and only one case has been reported in the spine so far. However, this diagnosis should be considered in cases with its characteristic imaging features.

Treatment of L5-S1 spondyloptosis with stand-alone anterior lumbar interbody fusion in a patient with neurofibromatosis.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a multisystem disorder that causes multiple tumor formations throughout the nervous system. Common spinal dysplasias seen with NF1, such as dural ectasia (DE), often undergo modulation and predispose these patients to spondylolisthesis, making surgical treatment challenging. CASE DESCRIPTION: A patient with NF1 presented with a 12-year-history of back and left lower extremity radicular pain. Lumbar spine magnetic resonance imaging revealed developmental anomalies with severe DE and associated scalloping of the L4-S1 vertebral bodies and severe L5-S1 Meyerding grade 4 spondylolisthesis. During surgery, post-positioning x-rays demonstrated a grade 5 spondyloptosis. The patient underwent an L5-S1 stand-alone anterior lumbar interbody fusion (ALIF). The final construct was an ALIF cage with one screw into S1, without an anterior plate. By 3-months post-operative, there was complete resolution of preoperative symptoms and at 2 year follow-up the patient was asymptomatic with stable hardware and solid bony fusion. To the authors' knowledge, this is the first report of spondyloptosis treated with a stand-alone ALIF in a patient with NF1 and severe DE.

A rare discal cyst with concurrent double-level isthmic lumbar spondylolisthesis: a case report and literature review.

We presented a 47-year old male diagnosed as a discal cyst with concurrent isthmic lumbar spondylolisthesis, which was not reported in the literature previously. A cystectomy with two-segmental transforaminal lumbar interbody fusion and instruments was performed. The association between concurrent discal cyst and isthmic spondylolisthesis may be illuminated by excessive strain and focal degeneration of the disc. Preoperative discography is probably unnecessary when surgical resection and histopathology are indicated for the patient.

Recurrent spinal meningeal melanocytoma at lumbar spine level: a case report.

INTRODUCTION: Spinal meningeal melanocytoma is an extremely rare tumour with an estimated annual incidence of 1 per 10 million people. It usually arises from the intradural extramedullary compartment at the cervical levels. Although these tumours are histologically benign, they may behave aggressively. Local recurrence could occur even after total tumour excision. CASE REPORT: We report a case of a 33-year-old Asian male who developed progressive weakness and numbness of the bilateral lower extremities as well as urinary retention five years after complete tumour resection of lumbar spinal meningeal melanocytoma. Magnetic resonance imaging of the lumbar spine revealed a mass with thecal sac compression which was hypointense on T2-weighted images and hyperintense on T1-weighted images. The patient underwent total tumour removal. Histologic examination was compatible with recurrent meningeal melanocytoma. After a 4-week inpatient rehabilitation programme, he was able to ambulate without assistance and to do clean intermittent catheterisation for micturition on a regular basis. DISCUSSION: This is the first reported case of intradural extramedullary meningeal melanocytoma located at the lumbar region. Clinicians should consider the possibility of these rare tumours at any level of the spine, and be aware of sphincter dysfunction in addition to motor and sensory deficits of extremities.

Spinal changes after 5-day dry immersion as shown by magnetic resonance imaging (DI-5-CUFFS).

Astronauts frequently report microgravity-induced back pain, which is generally more pronounced in the beginning of a spaceflight. The dry immersion (DI) model reproduces the early effects of microgravity in terms of global support unloading and fluid shift, both of which are involved in back pain pathogenesis. Here, we assessed spinal changes induced by exposure to 5 days of strict DI in 18 healthy men (25-43-yr old) with (n = 9) or without (n = 9) thigh cuffs countermeasure. Intervertebral disk (IVD) height, spinal cord position, and apparent diffusion coefficient (ADC; reflecting global water motion) were measured using magnetic resonance imaging before and after DI. After DI, IVD height increased in thoracic (+3.3 ± 0.8 mm; C7-T12) and lumbar (+4.5 ± 0.4 mm; T12-L5) regions but not in the cervical region (C2-C7) of the spine. An increase in ADC after DI was observed at the L1 (∼6% increase, from 3.2 to 3.4 × 10-3 mm2/s; P < 0.001) and L2 (∼3% increase, from 3.4 to 3.5 × 10-3 mm2/s; P = 0.005) levels. There was no effect of thigh cuffs on spinal parameters. This change in IVD after DI follows the same "gradient" pattern of height increase from the cervical to the lumbar region as observed after bed rest and spaceflight. The increase in ADC at L1 level positively correlated with reported back pain. These findings emphasize the utility of the DI model for studying early spinal changes observed in microgravity.

Cartilage endplate stem cells inhibit intervertebral disc degeneration by releasing exosomes to nucleus pulposus cells to activate Akt/autophagy.

Degeneration of the cartilage endplate (CEP) induces intervertebral disc degeneration (IVDD). Nucleus pulposus cell (NPC) apoptosis is also an important exacerbating factor in IVDD, but the cascade mechanism in IVDD is not clear. We investigated the apoptosis of NPCs and IVDD when stimulated by normal cartilage endplate stem cell (CESC)-derived exosomes (N-Exos) and degenerated CESC-derived exosomes (D-Exos) in vitro and in vivo. Tert-butyl hydroperoxide (TBHP) was used to induce inflammation of CESCs. The bioinformatics differences between N-Exos and D-Exos were analyzed using mass spectrometry, heat map, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. NPC apoptosis was examined using TUNEL staining. The involvement of the AKT and autophagy signaling pathways was investigated using the signaling inhibitor LY294002. Magnetic resonance imaging, Western blotting, and immunofluorescence staining were used to evaluate the therapeutic effects of N-Exos in rats with IVDD. TBHP effectively induced inflammation and the degeneration of CEP in rat. N-Exos were more conducive to autophagy activation than D-Exos. The apoptotic rate of NPCs decreased obviously after treatment with N-Exos compared to D-Exos. N-Exos inhibited NPCs apoptosis and attenuated IVDD in rat via activation of the AKT and autophagy pathways. These results are the first findings to confirm that CEP delayed the progression of IVDD via exosomes. The therapeutic effects of N-Exos on NPC apoptosis inhibition and the slowing of IVDD progression were more effective than D-Exos due to activation of the PI3K/AKT/autophagy pathway, which explained the increase in the incidence of IVDD after inflammation of the CEP.

Diagnostic Role of Magnetic Resonance Imaging in Low Back Pain Caused by Vertebral Endplate Degeneration.

Low back pain (LBP) is a common health issue worldwide with a huge economic burden on healthcare systems. In the United States alone, the cost is estimated to be $100 billion each year. Intervertebral disc degeneration is considered one of the primary causes of LBP. Moreover, the critical role of the vertebral endplates in disc degeneration and LBP is becoming apparent. Endplate abnormalities are closely correlated with disc degeneration and pain in the lumbar spine. Imaging modalities such as plain film radiography, computed tomography, and fluoroscopy are helpful but not very effective in detecting the causes behind LBP. Magnetic resonance imaging (MRI) can be used to acquire high-quality three-dimensional images of the lumbar spine without using ionizing radiation. Therefore, it is increasingly being used to diagnose spinal disorders. However, according to the American College of Radiology, current referral and justification guidelines for MRI are not sufficiently clear to guide clinical practice. This review aimed to evaluate the role of MRI in diagnosing LBP by considering the correlative contributions of vertebral endplates. The findings of the review indicate that MRI allows for fine evaluations of endplate morphology, endplate defects, diffusion and perfusion properties of the endplate, and Modic changes. Changes in these characteristics of the endplate were found to be closely correlated with disc degeneration and LBP. The collective evidence from the literature suggests that MRI may be the imaging modality of choice for patients suffering from LBP. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 3.

An externally validated deep learning model for the accurate segmentation of the lumbar paravertebral muscles.

PURPOSE: Imaging studies about the relevance of muscles in spinal disorders, and sarcopenia in general, require the segmentation of the muscles in the images which is very labour-intensive if performed manually and poses a practical limit to the number of investigated subjects. This study aimed at developing a deep learning-based tool able to fully automatically perform an accurate segmentation of the lumbar muscles in axial MRI scans, and at validating the new tool on an external dataset. METHODS: A set of 60 axial MRI images of the lumbar spine was retrospectively collected from a clinical database. Psoas major, quadratus lumborum, erector spinae, and multifidus were manually segmented in all available slices. The dataset was used to train and validate a deep neural network able to segment muscles automatically. Subsequently, the network was externally validated on images purposely acquired from 22 healthy volunteers. RESULTS: The median Jaccard index for the individual muscles calculated for the 22 subjects of the external validation set ranged between 0.862 and 0.935, demonstrating a generally excellent performance of the network, although occasional failures were noted. Cross-sectional area and fat fraction of the muscles were in agreement with published data. CONCLUSIONS: The externally validated deep neural network was able to perform the segmentation of the paravertebral muscles in an accurate and fully automated manner, although it is not without limitations. The model is therefore a suitable research tool to perform large-scale studies in the field of spinal disorders and sarcopenia, overcoming the limitations of non-automated methods.

External validation of the deep learning system "SpineNet" for grading radiological features of degeneration on MRIs of the lumbar spine.

BACKGROUND: Magnetic resonance imaging (MRI) is used to detect degenerative changes of the lumbar spine. SpineNet (SN), a computer vision-based system, performs an automated analysis of degenerative features in MRI scans aiming to provide high accuracy, consistency and objectivity. This study evaluated SN's ratings compared with those of an expert radiologist. METHOD: MRIs of 882 patients (mean age, 72 ± 8.8 years) with degenerative spinal disorders from two previous trials carried out in our spine center between 2011 and 2019, were analyzed by an expert radiologist. Lumbar segments (L1/2-L5/S1) were graded for Pfirrmann Grades (PG), Spondylolisthesis (SL) and Central Canal Stenosis (CCS). SN's analysis for the equivalent parameters was generated. Agreement between methods was analyzed using kappa (κ), Spearman correlation (ρ) and Lin's concordance correlation (ρc) coefficients and class average accuracy (CAA). RESULTS: 4410 lumbar segments were analyzed. κ statistics showed moderate to substantial agreement in PG between the radiologist and SN depending on spinal level (range κ 0.63-0.77, all levels together 0.72; range CAA 45-68%, all levels 55%), slight to substantial agreement for SL (range κ 0.07-0.60, all levels 0.63; range CAA 47-57%, all levels 56%) and CCS (range κ 0.17-0.57, all levels 0.60; range CAA 35-41%, all levels 43%). SN tended to record more pathological features in PG than did the radiologist whereas the contrary was the case for CCS. SL showed an even distribution between methods. CONCLUSION: SN is a robust and reliable tool with the ability to grade degenerative features such as PG, SL or CCS in lumbar MRIs with moderate to substantial agreement compared to the current gold-standard, the radiologist. It is a valuable alternative for analyzing MRIs from large cohorts for diagnostic and research purposes.

Paraspinal Muscle Health is Related to Fibrogenic, Adipogenic, and Myogenic Gene Expression in Patients with Lumbar Spine Pathology.

BACKGROUND: Lumbar spine pathology is a common feature of lower back and/or lower extremity pain and is associated with observable degenerative changes in the lumbar paraspinal muscles that are associated with poor clinical prognosis. Despite the commonly observed phenotype of muscle degeneration in this patient population, its underlying molecular mechanisms are not well understood. The aim of this study was to investigate the relationships between groups of genes within the atrophic, myogenic, fibrogenic, adipogenic, and inflammatory pathways and multifidus muscle health in individuals undergoing surgery for lumbar spine pathology. METHODS: Multifidus muscle biopsies were obtained from patients (n = 59) undergoing surgery for lumbar spine pathology to analyze 42 genes from relevant adipogenic/metabolic, atrophic, fibrogenic, inflammatory, and myogenic gene pathways using quantitative polymerase chain reaction. Multifidus muscle morphology was examined preoperatively in these patients at the level and side of biopsy using T2-weighted magnetic resonance imaging to determine whole muscle compartment area, lean muscle area, fat cross-sectional areas, and proportion of fat within the muscle compartment. These measures were used to investigate the relationships between gene expression patterns and muscle size and quality. RESULTS: Relationships between gene expression and imaging revealed significant associations between decreased expression of adipogenic/metabolic gene (PPARD), increased expression of fibrogenic gene (COL3A1), and lower fat fraction on MRI (r = -0.346, p = 0.018, and r = 0.386, p = 0.047 respectively). Decreased expression of myogenic gene (mTOR) was related to greater lean muscle cross-sectional area (r = 0.388, p = 0.045). CONCLUSION: Fibrogenic and adipogenic/metabolic genes were related to pre-operative muscle quality, and myogenic genes were related to pre-operative muscle size. These findings provide insight into molecular pathways associated with muscle health in the presence of lumbar spine pathology, establishing a foundation for future research that addresses how these changes impact outcomes in this patient population.

Age- and sex-dependent differences in the morphology and composition of paraspinal muscles between subjects with and without lumbar degenerative diseases.

BACKGROUND: The quality of the paraspinal muscles has been recommended as a surrogate marker for the evaluation of the severity of the lumbar degenerative diseases (LDD). The purpose of this study is to determine the age- and sex-dependent differences in the morphology and composition of the paraspinal muscles between LDD and asymptomatic subjects. METHODS: We analyzed data from 370 patients and 327 asymptomatic volunteers aged between 18-85 years. The measurement of the cross-sectional area (CSA) of the erector spinae, multifidus, and psoas at the L4/5-disc level was performed by the magnetic resonance imaging (MRI). The fatty infiltration ratio (FI %) of the multifidus and erector spinae was calculated. RESULTS: FI % of the lumbar paraspinal muscles were significantly and positively correlated with the severity of LDD instead of the CSA. Males had greater CSA than females, and females showed higher FI % than males in the paraspinal muscles. With the increase of age, the CSA of the lumbar paraspinal muscles gradually decreased, and the psoas showed the most significant decreasing trend. However, the FI % gradually increased in both LDD and asymptomatic groups with aging. CONCLUSION: Age- and sex-dependent differences were found in the morphology and composition of the paraspinal muscles between subjects with and without LDD. Further long-term follow up investigations and basic studies will continue to confirm the natural history of the paraspinal muscles with aging and their association with LDD.

LIFU Alleviates Neuropathic Pain by Improving the KCC2 Expression and Inhibiting the CaMKIV-KCC2 Pathway in the L4-L5 Section of the Spinal Cord.

Effective treatment remains lacking for neuropathic pain (NP), a type of intractable pain. Low-intensity focused ultrasound (LIFU), a noninvasive, cutting-edge neuromodulation technique, can effectively enhance inhibition of the central nervous system (CNS) and reduce neuronal excitability. We investigated the effect of LIFU on NP and on the expression of potassium chloride cotransporter 2 (KCC2) in the spinal cords of rats with peripheral nerve injury (PNI) in the lumbar 4-lumbar 5 (L4-L5) section. In this study, rats received PNI surgery on their right lower legs followed by LIFU stimulation of the L4-L5 section of the spinal cord for 4 weeks, starting 3 days after surgery. We used the 50% paw withdraw threshold (PWT50) to evaluate mechanical allodynia. Western blotting (WB) and immunofluorescence (IF) were used to calculate the expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), calcium/calmodulin-dependent protein kinase type IV (CaMKIV), phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB), and KCC2 in the L4-L5 portion of the spinal cord after the last behavioral tests. We found that PWT50 decreased (P < 0.05) 3 days post-PNI surgery in the LIFU- and LIFU+ groups and increased (P < 0.05) after 4 weeks of LIFU stimulation. The expression of p-CREB and CaMKIV decreased (P < 0.05) and that of KCC2 increased (P < 0.05) after 4 weeks of LIFU stimulation, but that of p-ERK1/2 (P > 0.05) was unaffected. Our study showed that LIFU could effectively alleviate NP behavior in rats with PNI by increasing the expression of KCC2 on spinal dorsal corner neurons. A possible explanation is that LIFU could inhibit the activation of the CaMKIV-KCC2 pathway.

Differential proteomic analysis of fetal and geriatric lumbar nucleus pulposus: immunoinflammation and age-related intervertebral disc degeneration.

BACKGROUND: Intervertebral disc degeneration (IVDD) is a major cause of low back pain. Although the mechanism of degeneration remains unclear, aging has been recognized as a key risk factor for IVDD. Most studies seeking to identify IVDD-associated molecular alterations in the context of human age-related IVDD have focused only on a limited number of proteins. Differential proteomic analysis is an ideal method for comprehensively screening altered protein profiles and identifying the potential pathways related to pathological processes such as disc degeneration. METHODS: In this study, tandem mass tag (TMT) labeling was combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for differential proteomic analysis of human fetal and geriatric lumbar disc nucleus pulposus (NP) tissue. Parallel reaction monitoring (PRM) and Western blotting (WB) techniques were used to identify target proteins. Bioinformatic analyses, including Gene Ontology (GO) annotation, domain annotation, pathway annotation, subcellular localization and functional enrichment analyses, were used to interpret the potential significance of the protein alterations in the mechanism of IVDD. Student's t-tests and two-tailed Fisher's exact tests were used for statistical analysis. RESULTS: Six hundred forty five proteins were significantly upregulated and 748 proteins were downregulated in the geriatric group compared with the fetal group. Twelve proteins were verified to have significant differences in abundance between geriatric and fetal NP tissue; most of these have not been previously identified as being associated with human IVDD. The potential significance of the differentially expressed proteins in age-related IVDD was analyzed from multiple perspectives, especially with regard to the association of the immunoinflammatory response with IVDD. CONCLUSIONS: Differential proteomic analysis was used as a comprehensive strategy for elucidating the protein alterations associated with age-related IVDD. The findings of this study will aid in the screening of new biomarkers and molecular targets for the diagnosis and therapy of IVDD. The results may also significantly enhance our understanding of the pathophysiological process and mechanism of age-related IVDD.