Early neurological changes in aging cervical spine: insights from PROMIS mobility assessment.

Many studies have shown that the prevalence of degenerative spinal cord compression increases with age. However, most cases at early stages are asymptomatic, and their diagnosis remains challenging. Asymptomatic cervical spinal cord compression (ASCC) patients are more likely to experience annular tears, herniated disks, and later develop symptomatic compression. Asymptomatic individuals do not typically undergo spinal cord imaging; therefore, an assessment test that is both sensitive and specific in diagnosing ASCC may be helpful. It has been demonstrated that the Patient Reported Outcome Measure Information System (PROMIS) mobility test is sensitive in detecting degenerative cervical myelopathy (DCM) symptoms. We investigated the use of the PROMIS mobility test in assessing clinical dysfunction in ASCC. In this study, 51 DCM patients and 42 age-matched healthy control (HC) were enrolled. The degree of cervical spinal cord compression was assessed using the high-resolution cervical spinal cord T2 Weighted (T2w) MRIs, which were available for 14 DCM patients. Measurements of the spinal cords anterior-posterior (AP) diameter at the region(s) that were visibly compressed as well as at different cervical spine levels were used to determine the degree of compression. The age-matched HC cohort had a similar MRI to establish the normal range for AP diameter. Twelve (12) participants in the HC cohort had MRI evidence of cervical spinal cord compression; these individuals were designated as the ASCC cohort. All participants completed the PROMIS mobility, PROMIS pain interference (PI), PROMIS upper extremity (UE), modified Japanese orthopedic association (mJOA), and neck disability index (NDI) scoring scales. We examined the correlation between the AP diameter measurements and the clinical assessment scores to determine their usefulness in the diagnosis of ASCC. Furthermore, we examine the sensitivity and specificity of PROMIS mobility test and mJOA. Compared to the HC group, the participants in the ASCC and DCM cohorts were significantly older (p = 0.006 and p < 0.0001, respectively). Age differences were not observed between ASCC and DCM (p > 0.999). Clinical scores between the ASCC and the HC group were not significantly different using the mJOA (p > 0.99), NDI (p > 0.99), PROMIS UE (p = 0.23), and PROMIS PI (p = 0.82). However, there were significant differences between the ASCC and HC in the PROMIS mobility score (p = 0.01). The spinal cord AP diameter and the PROMIS mobility score showed a significant correlation (r = 0.44, p = 0.002). Decreasing PROMIS mobility was significantly associated with a decrease in cervical spinal cord AP diameter independent of other assessment measures. PROMIS mobility score had a sensitivity of 77.3% and specificity of 79.4% compared to 59.1% and 88.2%, respectively, for mJOA in detecting cervical spinal cord compression. Certain elements of ASCC are not adequately captured with the traditional mJOA and NDI scales used in DCM evaluation. In contrast to other evaluation scales utilized in this investigation, PROMIS mobility score shows a significant association with the AP diameter of the cervical spinal cord, suggesting that it is a sensitive tool for identifying early disability associated with degenerative change in the aging spine. In a comparative analysis of PROMIS mobility test against the standard mJOA, the PROMIS mobility demonstrated higher sensitivity for detecting cervical spinal cord compression. These findings underscore the potential use of PROMIS mobility score in clinical evaluation of the aging spine.

Systematic review protocol for complications following surgical decompression of degenerative cervical myelopathy.

BACKGROUND: Degenerative Cervical Myelopathy (DCM) is one of the most common degenerative disorders of cervical spine and sources of cord dysfunction in adults. It usually manifests with neurologic presentations such as loss of dexterity and gait issues. Treatment for moderate and severe cases of DCM is surgical decompression of the region. There are many approaches available for surgical intervention which could be categorized into anterior and posterior based on the side of neck where operation takes place. Additionally, for certain cases the hybridized anterior-posterior combined surgery is indicated. While there are many technical differences between these approaches with each having its own advantages, the complications and safety profiles of them are not fully disclosed. This protocol aims to systematically search for current reports on complications of surgical decompression methods of DCM and pool them for robust evidence generation. METHOD: Search will be carried out in PubMed, Scopus, and Cochrane databases for retrospective and prospective surgical series, cohorts, or trials being performed for DCM with at least a sample size of 20 patients. Query strings will be designed to capture reports with details of complications with no year limit. Studies not being original (e.g., review articles, case reports, etc.), not in English, having patients younger than 18-years-old, and not reporting at least one complication will be excluded. Two independent reviewers will review the titles and abstracts for first round of screening. Full text of retrieved studies from previous round will be screened again by the same reviewers. In case of discrepancy, the third senior reviewer will be consulted. Eligible studies will then be examined for data extraction where data will be recorded into standardized form. Cumulative incidence and 95% confidence intervals of complication will be then pooled based on generalized linear mixed models with consideration of approach of surgery as subgroups. Heterogeneity tests will be performed for assessment of risk of bias. DISCUSSION: This systematic review is aimed at providing practical information for spine surgeons on the rates of complications of different surgical approaches of DCM decompression. Proper decision-making regarding the surgical approach in addition to informing patients could be facilitated through results of this investigation.

Beyond the aging spine - a systematic review of functional changes in the human brain in cervical spondylotic myelopathy.

Cervical Spondylotic Myelopathy (CSM) is a degenerative condition that leads to loss of cervical spinal cord integrity, typically affecting the aged population. Emerging fMRI-based evidence suggests that the brain is also affected by CSM. This systematic review aimed to understand the usefulness of brain fMRI in CSM. A comprehensive literature search was conducted until March 2023 according to PRISMA guidelines. The inclusion criteria included original research articles in English, primarily studying the human brain's functional changes in CSM using fMRI with at least 5 participants. The extracted data from each study included demographics, disease severity, MRI machine characteristics, affected brain areas, functional changes, and clinical utilities. A total of 30 studies met the inclusion criteria. Among the fMRI methods, resting-state fMRI was the most widely used experimental paradigm, followed by motor tasks. The brain areas associated with motor control were most affected in CSM, followed by the superior frontal gyrus and occipital cortex. Functional changes in the brain were correlated to clinical metrics showing clinical utility. However, the evidence that a specific fMRI metric correlating with a clinical metric was "very low" to "insufficient" due to a low number of studies and negative results. In conclusion, fMRI can potentially facilitate the diagnosis of CSM by quantitatively interrogating the functional changes of the brain, particularly areas of the brain associated with motor control. However, this field is in its early stages, and more studies are needed to establish the usefulness of brain fMRI in CSM.

Evaluating tissue injury in cervical spondylotic myelopathy with spinal cord MRI: a systematic review.

PURPOSE: Cervical Spondylotic Myelopathy (CSM) is a degenerative condition that leads to loss of cervical spinal cord (CSC) integrity. Various spinal cord Magnetic Resonance Imaging (MRI) methods can identify and characterize the extent of this damage. This systematic review aimed to evaluate the diagnostic, biomarker, and predictive utilities of different spinal cord MRI methods in clinical research studies of CSM. The aim was to provide a comprehensive understanding of the progress in this direction for future studies and effective diagnosis and management of CSM. METHODS: A comprehensive literature search was conducted on PubMed and EMBASE from 2010 to 2022 according to PRISMA guidelines. Studies with non-human subjects, less than 3T magnetic field strength, non-clinical design, or not quantitatively focusing on the structural integrity of CSC were excluded. The extracted data from each study included demographics, disease severity, MRI machine characteristics, quantitative metrics, and key findings in terms of diagnostic, biomarker, and predictive utilities of each MRI method. The risk of bias was performed using the guide from AHRQ. The quality of evidence was assessed separately for each type of utility for different MRI methods using GRADE. RESULTS: Forty-seven studies met the inclusion criteria, utilizing diffusion-weighted imaging (DTI) (n = 39), magnetization transfer (MT) (n = 6), MR spectroscopy (n = 3), and myelin water imaging (n = 1), as well as a combination of MRI methods (n = 12). The metric fractional anisotropy (FA) showed the highest potential in all facets of utilities, followed by mean diffusivity. Other promising metrics included MT ratio and intracellular volume fraction, especially in multimodal studies. However, the level of evidence for these promising metrics was low due to a small number of studies. Some studies, mainly DTI, also reported the usefulness of spinal cord MRI in mild CSM. CONCLUSIONS: Spinal cord MRI methods can potentially facilitate the diagnosis and management of CSM by quantitatively interrogating the structural integrity of CSC. DTI is the most promising MRI method, and other techniques have also shown promise, especially in multimodal configurations. However, this field is in its early stages, and more studies are needed to establish the usefulness of spinal cord MRI in CSM.

Degenerative cervical myelopathy: establishing severity thresholds for neuromotor dysfunction in the aging spine using the NIH Toolbox Assessment Scale.

Degenerative cervical myelopathy (DCM) is a leading cause of age-related non-traumatic spinal cord disorders resulting from chronic degeneration of the cervical spine. While traditional clinical assessments rely on patient-reported measures, this study used the NIH Toolbox Motor Battery (NIHTBm) as an objective, quantitative measure to determine DCM severity. The objective is to define NIHTBm cutoff values that can accurately classify the severity of DCM neuromotor dysfunction. A case-controlled pilot study of patients with DCM and age-matched controls. The focus was an in-depth quantitative motor assessment using the NIHTBm to understand the severity of neuromotor deficits due to degenerative spine disease. Motor assessments, dexterity, grip strength, balance, and gait speed were measured in 45 DCM patients and 37 age-matched healthy subjects (HC). Receiver operating curve (ROC) analysis determined cutoff values for mild and moderate-to-severe myelopathy which were validated by comparing motor assessment scores with disability scores. The ROC curves identified thresholds for mild dexterity impairment (T-score range 38.4 - 33.5, AUC 0.77), moderate-to-severe dexterity impairment (< 33.5, AUC 0.70), mild grip strength impairment (47.4 - 32.0, AUC 0.80), moderate-to-severe grip strength impairment (< 32.0, AUC 0.75), mild balance impairment (36.4 - 33.0, AUC 0.61), and moderate-to-severe balance impairment (< 33.0, AUC 0.78). Mild gait speed impairment was defined as 0.78-0.6 m/sec (AUC 0.65), while moderate-to-severe gait speed impairment was < 0.6 m/sec (AUC 0.65). The NIHTB motor score cutoff points correlated negatively with the DCM neck disability index (NDI) and showed balance and dexterity measures as independent indicators of DCM dysfunction. The use of NIHTB allows for precise delineation of DCM severity by establishing cutoff values corresponding to mild and moderate-to-severe myelopathy. The use of NIHTB in DCM allows enhanced clinical precision, enabling clinicians to better pinpoint specific motor deficits in DCM and other neurological disorders with motor deficits, including stroke and traumatic brain injury (TBI). Furthermore, the utility of objective assessment, NIHTB, allows us to gain a better understanding of the heterogeneity of DCM, which will enhance treatment strategies. This study serves as a foundation for future research to facilitate the discovery of innovative treatment strategies for DCM and other neurological conditions.

Cakes fortified with papaya seeds effectively protects against CCl4-induced immunotoxicity.

Maintaining a robust immune system and safeguarding the liver from toxins are crucial for overall health. The study aimed to investigate the immunostimulant effects of papaya seed-enriched cakes (CPS) in countering carbon tetrachloride (CCl4)-induced immunocytotoxicity in rats (n = 48). The rats were divided into six groups (8 each): a control group (Group 1), rats fed cakes containing 15% papaya seeds (Group 2 - CPS), rats exposed only to CCl4 (Group 3 - CCl4), rats injected with CCl4 and administered silymarin (Group 4 - CCl4 + S), rats receiving both CCl4 and cakes with papaya seeds (Group 5 - CCl4 + CPS), and rats receiving both CCl4 and silymarin with papaya seed-enriched cakes (Group 6 - CCl4 + CPS + S). HPLC analysis of papaya seeds revealed the presence of ten polyphenol compounds, with quercetin, apigenin, and catechin identified as major flavonoids, along with pyrogallol, ellagic, and gallic acid as predominant phenolic acids. These compounds displayed potent antioxidant activity, attributed to the seeds' high total phenolic and flavonoid content. The administration of CCl4 significantly affected hematological parameters, liver enzymes, hepatic oxidative stress, levels of TNF-α, IL-6, IgG, as well as IgM. However, rats fed with CPS exhibited mitigation of CCl4-induced toxic effects on hematological parameters and hepatotoxicity. CPS consumption enhanced the antioxidant system, improved inflammatory markers, and immune parameters, restoring them to normal levels. Histopathological analysis confirmed CPS's ability to reduce CCl4-induced hepatocellular necrosis. Immunohistochemical assessment further revealed reduced immunoreactivity against cleaved caspase-3 expression and increased COX2 immunoreactivity, indicating hepatocellular regeneration in CPS. The combination of CPS and silymarin demonstrated even more notable improvements, suggesting augmented protective impacts against CCl4-induced immunosuppression and hepatotoxicity. In conclusion, CPS exhibited antioxidant properties and effectively protected against CCl4-induced immunotoxicity and hepatotoxicity, with additional benefits observed when combined with silymarin. These findings emphasize the potential health advantages of incorporating papaya seeds into food products, promoting immune system health, and safeguarding against liver damage induced by hazardous agents like CCl4.

Utility of MRI in Quantifying Tissue Injury in Cervical Spondylotic Myelopathy.

Cervical spondylotic myelopathy (CSM) is a progressive disease that worsens over time if untreated. However, the rate of progression can vary among individuals and may be influenced by various factors, such as the age of the patients, underlying conditions, and the severity and location of the spinal cord compression. Early diagnosis and prompt treatment can help slow the progression of CSM and improve symptoms. There has been an increased use of magnetic resonance imaging (MRI) methods in diagnosing and managing CSM. MRI methods provide detailed images and quantitative structural and functional data of the cervical spinal cord and brain, allowing for an accurate evaluation of the extent and location of tissue injury. This review aims to provide an understanding of the use of MRI methods in interrogating functional and structural changes in the central nervous system in CSM. Further, we identified several challenges hindering the clinical utility of these neuroimaging methods.

Assessment of Bioactive Phytochemicals and Utilization of Rosa canina Fruit Extract as a Novel Natural Antioxidant for Mayonnaise.

The oxidation of food emulsions causes rancidity, which reduces their shelf life. To prevent rancidity, synthetic antioxidants are widely used in the food industry. However, due to their potential health risks, researchers are exploring natural alternatives. This study aimed to investigate whether Rosa canina fruit extract (RCFE) could be used as a natural antioxidant to extend the shelf life of mayonnaise. Mayonnaise containing varying concentrations of RCFE [0.125% (T1), 0.25% (T2), 0.50% (T3), 0.75% (T4)] was compared to a mayonnaise control sample (C1) and a mayonnaise sample containing 0.02% BHT (C2) for 60 days of storage at 4 °C. RCFE was found to have high levels of total phenols content (52.06 ± 1.14 mg GAE g-1), total flavonoids content (26.31 ± 1.03 mg QE g-1), and free radical scavenging activity. The GC-MS analysis of RCFE revealed 39 different peaks, whereas the HPLC analysis showed the presence of 13 polyphenolic compounds in RCFE. The pH values of T2, T3, and T4 mayonnaise samples substantially declined as storage progressed; however, the reduction was less than that of C1 and C2. After 60 days, mayonnaise samples T2, T3, and T4 had greatly reduced peroxide and free fatty acid levels compared to C1 and C2. The mayonnaise enriched with RCFE (T3 and T4) had the most potent antioxidative ability and the lowest value of lipid hydroperoxides (peroxide value, POV) and the lowest value of thiobarbituric-acid-reactive substances (TBARS). The sensory evaluation revealed that the T3 sample exhibited the highest overall acceptability. In conclusion, this study recommends that RCFE could be used as a natural preservative to enhance the shelf life of functional foods.

Specific gene expression signatures of low grade meningiomas.

Introduction: Meningiomas are the most common primary central nervous system (CNS) tumors in adults, representing approximately one-third of all primary adult CNS tumors. Although several recent publications have proposed alternative grading systems of meningiomas that incorporate genomic and/or epigenomic data to better predict meningioma recurrence and progression-free survival, our understanding of driving forces of meningioma development is still limited. Objective: To define gene expression signatures of the most common subtypes of meningiomas to better understand cellular processes and signaling pathways specific for each tumor genotype. Methods: We used RNA sequencing (RNA-seq) to determine whole transcriptome profiles of twenty meningiomas with genomic alterations including NF2 inactivation, loss of chr1p, and missense mutations in TRAF7, AKT1 and KLF4. Results: The analysis revealed that meningiomas with NF2 gene inactivation expressed higher levels of BCL2 and GLI1 compared with tumors harboring TRAF7 missense mutations. Moreover, NF2 meningiomas were subdivided into two distinct groups based on additional loss of chr1p. NF2 tumors with intact chr1p were characterized by the high expression of tumor suppressor PTCH2 compared to NF2 tumors with chr1p loss. Taken together with the high expression of BCL2 and GLI1, these results suggest that activation of Sonic Hedgehog pathway may contribute to NF2 meningioma development. In contrast, NF2 tumors with chr1p loss expressed high levels of transcription factor FOXD3 and its antisense RNA FOXD3-AS1. Examination of TRAF7 tumors demonstrated that TRAF7 regulates a number of biomechanically responsive genes (KRT6a, KRT16, IL1RL1, and AQP3 among others). Interestingly, AKT1 and KLF4 meningiomas expressed genes specific for PI3K/AKT signaling pathway, suggesting overlapping gene signatures between the two subtypes. In addition, KLF4 meningiomas had high expression of carcinoembryonic antigen family members CEACAM6 and CEACAM5. Conclusions: Each group of meningiomas displayed a unique gene expression signature suggesting signaling pathways potentially implicated in tumorigenesis. These findings will improve our understanding of meningioma tumorigenesis and prognosis.