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STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Imaging changes in the vertebral body after posterior lumbar interbody fusion (PLIF) are determined to be trabecular bone remodeling (TBR). This study aimed to investigate the influence of cage materials on TBR and segment stabilization in PLIF by studying image changes. METHODS: This was a retrospective study reviewing 101 cases who underwent one-level PLIF with three-dimensional porous titanium (3DTi) cages (53 patients) or polyether-ether-ketone (PEEK) cages (48 patients). Computed tomography images obtained 3 months, 1 year, and 2 years postoperatively were examined for TBR, vertebral endplate cyst formation as an instability sign, cage subsidence, and clear zone around pedicle screw (CZPS). RESULTS: No significant differences in the TBR-positivity rates were observed between the two cages at 3 months, 1 year, and 2 years postoperatively. However, all 3DTi cage segments that were TBR-positive at 3 months postoperatively showed no CZPS and fewer final instability segments than the TBR-negative segments (0% vs 9%). In contrast, although the PEEK cage segments that were TBR-positive at 3 months postoperatively were not associated with future segmental stabilization, those that were TBR-positive at 1 year postoperatively had fewer final instability segments than the TBR-negative segments (0% vs 33%). CONCLUSIONS: The 3DTi cage segments with TBR 3 months postoperatively showed significant final segmental stabilization, whereas TBR at 1 year rather than 3 months postoperatively was useful in determining final segmental stabilization for the PEEK cage segments. The timing of TBR, a new osseointegration assessment, were associated with the cage material.
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Signal transduction at the neuromuscular junction (NMJ) is compromised in a diverse array of diseases including congenital myasthenic syndromes (CMS). Germline mutations in CHRNE encoding the acetylcholine receptor (AChR) ε subunit are the most common cause of CMS. An active form of vitamin D, calcitriol, binds to vitamin D receptor (VDR) and regulates gene expressions. We found that calcitriol enhanced MuSK phosphorylation, AChR clustering, and myotube twitching in co-cultured C2C12 myotubes and NSC34 motor neurons. RNA-seq analysis of co-cultured cells showed that calcitriol increased the expressions of Rspo2, Rapsn, and Dusp6. ChIP-seq of VDR revealed that VDR binds to a region approximately 15 âkbp upstream to Rspo2. Biallelic deletion of the VDR-binding site of Rspo2 by CRISPR/Cas9 in C2C12 myoblasts/myotubes nullified the calcitriol-mediated induction of Rspo2 expression and MuSK phosphorylation. We generated Chrne knockout (Chrne KO) mouse by CRISPR/Cas9. Intraperitoneal administration of calcitriol markedly increased the number of AChR clusters, as well as the area, the intensity, and the number of synaptophysin-positive synaptic vesicles, in Chrne KO mice. In addition, calcitriol ameliorated motor deficits and prolonged survival of Chrne KO mice. In the skeletal muscle, calcitriol increased the gene expressions of Rspo2, Rapsn, and Dusp6. We propose that calcitriol is a potential therapeutic agent for CMS and other diseases with defective neuromuscular signal transmission.
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Síndromes Miastênicas Congênitas , Animais , Camundongos , Síndromes Miastênicas Congênitas/tratamento farmacológico , Síndromes Miastênicas Congênitas/genética , Síndromes Miastênicas Congênitas/metabolismo , Calcitriol/metabolismo , Junção Neuromuscular/metabolismo , Receptores Colinérgicos/genética , Receptores Colinérgicos/metabolismo , Neurônios Motores/metabolismoRESUMO
BACKGROUND: Cervicobrachial pain frequently affects the quality of life (QOL) of the general public and has a significant economic impact on the health care systems of various countries. There are a number of treatment options for this disease, including widely-used drug therapy, but the effectiveness of each option is indeterminate, and there have been no published cost-effectiveness analysis studies so far. This prospective observational study aimed to examine the cost-effectiveness of drug treatment for cervicobrachial symptoms. METHODS: A 6-month medication regimen for each of five frequently-prescribed drugs for cervicobrachial symptoms was administered to 322 patients at 24 centers in Japan. Outcome measures, including of the EuroQol Group 5D, Short Form-8, and Visual Analog Scale (VAS), were investigated at baseline and every month thereafter. Incremental cost-effectiveness ratios (ICERs) of the drug cost to quality-adjusted life years (QALYs) were calculated. A stratified analysis of patient characteristics was also performed to identify baseline factors potentially affecting cost-effectiveness. RESULTS: The ICER of entire drug treatment for cervicobrachial symptoms was 7,491,640 yen. Compared with the reference willingness-to-pay, the ICER was assumed to not be cost-effective. A certain number of QALYs were gained during the first 3 months after the treatment intervention, but almost no QALYs were gained during the following 3 months. Stratified analysis showed that cost-effectiveness was extremely low for patients with high baseline VAS and high QOL. CONCLUSIONS: The available medications for cervicobrachial symptoms did not have excellent cost-effectiveness. Although a certain number of QALYs were gained during the first 3 months after medication, no QALYs were gained in the latter half of the study period, suggesting that it is not advisable to continue the medication needlessly. LEVEL OF EVIDENCE: II, prospective cohort study.
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BACKGROUND: Excess visceral fat can accumulate owing to lack of exercise. The relationship between metabolic syndrome (MetS) and spinal range of motion (ROM) is not clear. The purpose of this study was to investigate the relationship between MetS and spinal alignment and ROM. METHODS: Orthopedic evaluation was prospectively performed in 544 participants. The participants were classified into two groups on the basis of the Japanese-specific MetS criteria proposed by the Japanese Committee of the Criteria for MetS (JCCMS). Lower back pain (LBP), knee joint pain with the visual analog scale (VAS), Kellgren-Lawrence (K-L) grade for knee osteoarthritis, body mass index (BMI), and spinal alignment and ROM were evaluated. RESULTS: Forty-four (8.1%) were diagnosed as having MetS. The prevalence rate of K-L grade 4 in the MetS group was significantly higher than that in the non-MetS group (p < 0.05). When sex, age, and BMI were evaluated as covariates, there were significant differences in the VAS score for knee pain (non-MetS group vs MetS group: 13.7 vs 23.3, p < 0.05), L1-S1 flexion spinal ROM (44.1° vs 38.1°, p < 0.001), flexion spinal inclination angle (SIA) ROM (107.6° vs 99.3°, p < 0.01), and SIA ROM (135.4° vs 124.0°, p < 0.05). CONCLUSIONS: Knee pain increased and flexion spinal ROM decreased significantly in the MetS group as compared with non-MetS group. Systemic factors associated with MetS may have a specific impact on spinal ROM while promoting knee osteoarthrosis and increased knee pain.
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Dor Lombar , Síndrome Metabólica , Osteoartrite do Joelho , Humanos , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Coluna Vertebral , Articulação do Joelho , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Joelho/complicações , Dor Lombar/diagnóstico , Dor Lombar/epidemiologia , Dor Lombar/complicações , Amplitude de Movimento ArticularRESUMO
The diagnosis of pediatric spinal cord tumor is frequently delayed due to the presence of non-specific symptoms. We investigated the factors influencing the delay between the first symptom presentation and the diagnosis for pediatric spinal cord tumor. We retrospectively analyzed 31 patients of age <20 years (18 men, 13 women) who underwent surgery for spinal cord tumor at a single center during 1998-2018. We extracted the relevant data on patients' symptoms, affected spinal location (cervical: C1-7, thoracic: T1-T12, and lumbosacral: L1-S), and tumor anatomical location (extradural, intradural extramedullary, and intramedullary tumor) that could potentially affect the duration of symptom presentation prior to the diagnosis. The most common symptom presented in the patients was pain (n = 22, 71.0 %). Motor symptoms such as paralysis was associated with early diagnosis (P = 0.039). The duration of symptoms prior to diagnosis was found to be significantly longer in patients with spinal tumor in the lumbar-sacral region than in those with the involvement of the cervical and thoracic regions (2.1 ± 1.7 months vs 13.6 ± 12.1 months; P = 0.006 and 2.9 ± 2.2 months vs 13.6 ± 12.1 months; P = 0.012, respectively). Our study results demonstrated that pain was the most common symptom in the examined patients, although it did not affect the delay in diagnosis, whereas the presentation of motor symptoms was helpful in the diagnosis of pediatric spinal cord tumor and the diagnosis could be delayed in lumbar-sacral spinal tumors.
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Neoplasias da Medula Espinal , Neoplasias da Coluna Vertebral , Adulto , Criança , Feminino , Humanos , Masculino , Dor , Estudos Retrospectivos , Neoplasias da Medula Espinal/diagnóstico , Neoplasias da Medula Espinal/cirurgia , Adulto JovemRESUMO
PURPOSE: Although the understanding of the mechanisms of low back pain due to spinopelvic sagittal imbalance has strengthened, the understanding of the mechanisms of neck pain remains insufficient. Thus, this study aimed to identify the factors associated with preoperative and postoperative neck pain in patients with degenerative cervical myelopathy who underwent laminoplasty. METHODS: In this prospective multicenter study, we prospectively enrolled patients who were scheduled for laminoplasty for degenerative cervical myelopathy. The associations between different variables and the Numerical Pain Rating Scale (NRS) scores for neck pain were investigated using univariate and multiple linear regression models. RESULTS: In total, 92 patients were included in the current study. The univariate analysis showed that age, sex, cervical lordosis in neutral and extension, and thoracic kyphosis were significantly associated with the preoperative NRS score for neck pain; moreover, preoperative cervical lordosis in extension and range of motion and postoperative cervical lordosis in neutral, flexion, and extension were significantly associated with the postoperative NRS Scale score for neck pain. Stepwise multiple regression analysis showed that the independent factors contributing to preoperative neck pain were preoperative cervical lordosis in extension, sex, and age. The independent preoperative predictor and contributor to postoperative neck pain were preoperative cervical lordosis in extension and postoperative cervical lordosis in extension, respectively. CONCLUSIONS: Cervical lordosis in extension showed significant association with neck pain in patients with degenerative cervical myelopathy. Therefore, when performing laminoplasty for patients with a low cervical lordosis in extension, attention should be paid to residual postoperative neck pain.
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Laminoplastia , Lordose , Doenças da Medula Espinal , Vértebras Cervicais/cirurgia , Humanos , Lordose/cirurgia , Cervicalgia/etiologia , Cervicalgia/cirurgia , Estudos Prospectivos , Doenças da Medula Espinal/complicações , Doenças da Medula Espinal/cirurgia , Resultado do TratamentoRESUMO
OBJECTIVES: To clarify whether the prevalence of locomotive syndrome (LS) and osteoporosis differed according to region, gender, and physical functions in Japan. METHODS: Data were collected in Kashiwara City (urban region) and Yakumo Town (rural region). Totally, 208 participants from the urban region and 782 participants from the rural region were included in this study. LS was assessed using the 25-item Geriatric Locomotive Function Scale and osteoporosis was assessed using a quantitative ultrasound. Physical functions were measured using grip strength and the 3-m timed up-and-go test. Differences between urban and rural regions were investigated using standardized incidence ratio and multivariate analysis. RESULTS: The prevalence of LS and osteoporosis was 24.5% and 42.8% in the urban region and 10.9% and 28.8% in the rural region, respectively. The standardized incidence ratio of the urban region versus the rural region was 1.80 (95% confidence intervals [CI] = 1.35-2.39) for LS and 1.21 (95% CI = 1.32-2.43) for osteoporosis, showing that the prevalence of LS was significantly higher in the urban region. Multivariate analysis indicated that LS was significantly associated with the urban sample and timed up-and-go was significantly longer in the urban sample. CONCLUSION: Regional differences may be considered when evaluating LS in health checkups. Understanding the results of this study may help reduce LS prevalence.
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Locomoção , Osteoporose , Idoso , Humanos , Japão/epidemiologia , Osteoporose/diagnóstico por imagem , Osteoporose/epidemiologia , Prevalência , SíndromeRESUMO
STUDY DESIGN: This was a retrospective study of prospectively collected data. OBJECTIVE: In this study, we aimed to characterize a population of patients with degenerative cervical myelopathy (DCM) and a history of poor postoperative neurological recovery and to identify risk factors associated with poor neurological recovery after laminoplasty. SUMMARY OF BACKGROUND DATA: Kyphotic cervical alignment has been considered a relative contraindication to laminoplasty in recent years; hence, laminoplasty has been decreasingly performed for the treatment of DCM in patients with cervical kyphosis. However, the effect of global spinal alignment on postoperative outcomes has not been extensively investigated. MATERIALS AND METHODS: We prospectively enrolled patients who were scheduled for laminoplasty for DCM. Outcome (at enrollment and 1 y after surgery) and risk factor analyses were performed by comparing the good recovery and poor recovery groups. The Spearman correlation coefficient was used to evaluate the relationships between the recovery rate and the preoperative radiographic factors. RESULTS: In total, 101 patients completed the 1-year follow-up. Regarding clinical outcomes, the Japanese Orthopedic Association score for the assessment of cervical myelopathy, European Quality of Life-5 Dimensions, and Neck Disability Index scores improved postoperatively. The recovery rate was significantly correlated with the preoperative sagittal vertical axis (SVA). The patients in the poor recovery group were older than those in the good recovery group. Univariate analyses showed that the SVA and T1 pelvic angle were significantly higher in the poor recovery group. Lastly, stepwise logistic regression analysis showed that a higher SVA was an independent predictor of poor recovery after laminoplasty. CONCLUSIONS: The SVA and T1 pelvic angle were significantly higher in the poor recovery group. A high preoperative SVA is an independent predictor for poor recovery after laminoplasty. Therefore, indications for laminoplasty in elderly DCM patients with a high preoperative SVA should be carefully considered. LEVEL OF EVIDENCE: Level III.
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Laminoplastia , Doenças da Medula Espinal , Idoso , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Humanos , Laminoplastia/métodos , Qualidade de Vida , Estudos Retrospectivos , Doenças da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/etiologia , Doenças da Medula Espinal/cirurgia , Resultado do TratamentoRESUMO
STUDY DESIGN: A cross-sectional study. OBJECTIVE: The present study aimed to investigate the prevalence of NeP in subjects suffering from NSP to reveal the impact of NeP on the health-related QOL (HRQOL) in middle-aged and elderly people with NSP in a health checkup. SUMMARY OF BACKGROUND DATA: No previous studies have established the relationship between NSP and NeP as potential risk factors contributing to a decreased QOL in the general population. METHODS: The present study involved 203 participants (men: 84, women: 119; mean age: 63.3 yr). For each subject, anthro-pometric measurements, physical function examinations, and blood testing were performed. A cut-off score of >0 on the short-form spine painDETECT questionnaire defined the presence of NeP. Subsequently, the NSP (+) subjects were divided into 2 sub-groups: the NeP (+) and NeP (-) groups. For the assessment of QOL, the short form 36 health survey and the EuroQol 5 dimension 5 level version (EQ-5D-5L) tool were used. RESULTS: The study included 100 NSP (+) and 103 NSP (-) subjects. Among the NSP (+) subjects, 46 and 54 subjects were found to be NeP (+) and NeP (-), respectively. For the short form 36 health survey, the multivariate regression analysis revealed that the prevalence of NeP was associated with a lower physical QOL (OR 3.56) and lower mental QOL (OR 4.04). Similarly, the NeP prevalence was found to be the predictor for low QOL scores in EQ-5D-5L (EQ-5D-5L index value <0.875; OR 3.61). CONCLUSION: The prevalence of NeP was reported to be 46.0% in healthy middle-aged and elderly population suffering from NSP, where it was associated with poor HRQOL. Therefore, strategies aimed at alleviating NeP may contribute significantly to the improvement of QOL in middle-aged and elderly people with NSP.Level of Evidence: 2.
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Neuralgia , Dor de Ombro , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia/diagnóstico , Neuralgia/epidemiologia , Qualidade de Vida , Dor de Ombro/diagnóstico , Dor de Ombro/epidemiologia , Inquéritos e QuestionáriosRESUMO
An annual physical checkup is provided as part of the long-term Yakumo study. The checkup is voluntary and there is variation in the frequency of participation. The aim of this study was to examine relationship of physical fitness with frequency of participation in this checkup. The subjects had all attended at least one annual physical checkup from 2006 to 2018. Data from 1,804 initial checkups were used for analysis. At the checkups, age, gender, height, weight, body mass index (BMI), and bone mineral density (BMD) were recorded, and physical activity was measured. The average number of physical checkups per participant for 13 years was 2.4 (1-13). Daily exercise habits were found to be significantly associated with higher participation in physical checkups. Furthermore, between groups with low (1-5 times; <90th percentile of participants) and high (≥6 times) participation, weight and BMI were significantly higher, and BMD, grip strength, 10-m gait time, back muscle strength, and two-step test were all significantly lower in the group with lower frequency of participation in the checkup. In conclusions, our results show that frequency of participation in a voluntary annual physical checkup is significantly associated with physical fitness in middle-aged and elderly people.
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Nível de Saúde , Exame Físico/estatística & dados numéricos , Aptidão Física , Atenção Primária à Saúde/estatística & dados numéricos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A 48-year-old female patient presented with discomfort in the front of the chest. Whole spinal X-ray revealed a thoracic curve of 52°, and thoracic computed tomography (CT) myelography and magnetic resonance imaging (MRI) showed that ossification of the posterior longitudinal ligament (OPLL) on the concave side of the apex vertebra (T9) had highly compressed the spinal cord. Cervical MRI also showed that the C4-C5 intervertebral disc herniation mildly compressed the spinal nerve. In concomitant surgery, the patient underwent cervical laminoplasty, in which OPLL was removed by decompressive laminectomy and posterior correction surgery.In patients with adult spinal deformity (ASD), asymmetric mechanical stress at the apex vertebra can cause various abnormal conditions. Long-term local mechanical stress on the concave side of the apex vertebra might have affected OPLL formation in the present case. This is the first report of a surgical case for an ossification located on the concave side of the apex vertebra in a patient with ASD. Mechanical stress at the concave side of the apex vertebra was suspected to be a cause of formation of OPLL.
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Laminoplastia , Ossificação do Ligamento Longitudinal Posterior , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Feminino , Humanos , Ligamentos Longitudinais , Pessoa de Meia-Idade , Ossificação do Ligamento Longitudinal Posterior/diagnóstico por imagem , Ossificação do Ligamento Longitudinal Posterior/cirurgia , Osteogênese , Coluna VertebralRESUMO
The ratio of human nonmercaptalbumin (HNA) and reduced albumin (HMA) may be a new marker for oxidative stress. Locomotive syndrome (LS) is reduced mobility due to impairment of locomotive organs. We investigated whether the HNA/HMA ratio could be a new biomarker of LS. This study included 306 subjects (mean age 64.24 ± 10.4 years) who underwent LS tests, grip strength, walking speed, and tests for HNA and HMA. Oxidative stress was measured by the ratio of HMA (f(HMA) = (HMA/(HMA + HNA) × 100)), and the subjects were divided into normal (N group; f[HMA] ≥ 70%) and low (L group; f[HMA] < 70%) groups. There were 124 non-elderly (<65 years) and 182 elderly subjects (≥65 years). There were no significant differences in LS, grip strength, and walking speed between the L and N groups in the non-elderly subjects. However, significant differences were found in the elderly subjects. In logistic regression analysis, there was an association between f(HMA) and the LS severity at older ages. LS in the elderly is associated with a decline in HMA and, thus, an increase in oxidative stress. Thus, f(HMA) is a new biomarker of LS.
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PURPOSE: Neck and shoulder pain (NSP) is very common in the general population. However, scarce information exists on the relationship between NSP and health-related quality of life (HRQOL) outcomes in this population. The present study described NSP prevalence and its impact on the HRQOL of middle-aged and older persons undergoing a routine medical checkup. METHODS: This study recruited 318 subjects (125 males and 193 females; average age, 63.4 years) in good health, collected underwent anthropometric measurements, physical function examinations, and blood testing. This study defined NSP as the presence of muscle tension, stiffness, pressure, or dull pain in areas between the neck and the arch of the scapular. Study subjects were divided into two groups (NSP (+) and NSP (-) groups). The subjects completed questions on the Medical Outcomes Study 36-item short-form health survey (SF-36) and the EuroQol 5-dimension, 5-level version (EQ-5D-5L) tool. RESULTS: Of the patients, 150 and 168 were NSP (+) and NSP (-), respectively. The NSP complaint rate was 47.2%. The NSP (+) group had younger and more female participants than the NSP (-) group. In the multivariate regression analysis, the NSP (+) group had lower physical QOL based on the SF-36 physical component summary (odds ratio (OR), 2.45) and lower mental QOL based on the SF-36 mental component summary (OR, 2.05). Overall, the NSP (+) group had a higher risk of having low QOL scores (EQ-5D-5L index; OR, 1.76). CONCLUSIONS: The NSP (+) rate in healthy middle-aged and older persons was 47.2%. Furthermore, NSP (+) status was directly related poor HRQOL. NSP is a predictor of suboptimal physical and mental QOL. Therefore, NSP prevention or intervention for NSP may improve middle-aged and older adults' QOL.
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Cervicalgia/fisiopatologia , Pescoço/fisiopatologia , Dor de Ombro/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Dor Musculoesquelética/fisiopatologia , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
PURPOSE: To quantify calcification in spinal meningiomas using Hounsfield unit (HU) values on CT, and to analyze the characteristics of cases with and without calcification and with different histologic subtypes. METHODS: The subjects were 53 patients who underwent surgical resection of spinal meningioma between January 1999 and December 2019. Clinical and surgical data were collected, and all patients were examined neurologically preoperatively and at final follow-up using the modified McCormick scale and the American Spinal Injury Association scale. Calcification was quantified on CT of the spine prior to surgery. A HU value >60 was considered to indicate calcification. RESULTS: The 53 patients (11 males, 42 females) were aged 62.4 ± 14.3 (range 19 to 91) years at surgery, and had a symptom duration of 10.8 ± 9.0 (1-36) months. The histological type was meningothelial in 35 cases, psammomatous in 13, and others in 5. The mean tumor volume was 1166 ± 350 (593-2176) mm3, and the mean HU value was 212.2 ± 192.8 (43-648). Forty cases (75%) had calcification (HU value > 60). HU values were significantly related to duration of symptoms (R = 0.590, p < 0.05) and significantly higher in psammomatous cases (p < 0.05). Cases with calcification had longer operative times and greater blood loss, and a significantly lower rate of neurological improvement. CONCLUSION: CT was effective for detecting calcification based on HU values. Detection of a HU value > 60 in spinal meningioma may be useful to narrow the differential diagnosis, evaluate the difficulty of resection, and improve intraoperative management, all of which may improve outcomes.
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Calcinose/diagnóstico por imagem , Calcinose/cirurgia , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/cirurgia , Carga Tumoral , Adulto JovemRESUMO
Decreased acetylcholine receptor (AChR) clustering compromises signal transmission at the neuromuscular junction (NMJ) in myasthenia gravis, congenital myasthenic syndromes, and motor neuron diseases. Although the enhancement of AChR clustering at the NMJ is a promising therapeutic strategy for these maladies, no drug is currently available for this enhancement. We previously reported that zonisamide (ZNS), an anti-epileptic and anti-Parkinson's disease drug, enhances neurite elongation of the primary spinal motor neurons (SMNs). As nerve sprouting occurs to compensate for the loss of AChR clusters in human diseases, we examined the effects of ZNS on AChR clustering at the NMJ. To this end, we established a simple and quick co-culture system to reproducibly make in vitro NMJs using C2C12 myotubes and NSC34 motor neurons. ZNS at 1-20 µM enhanced the formation of AChR clusters dose-dependently in co-cultured C2C12 myotubes but not in agrin-treated single cultured C2C12 myotubes. We observed that molecules that conferred responsiveness to ZNS were not secreted into the co-culture medium. We found that 10 µM ZNS upregulated the expression of neuregulin-1 (Nrg1) in co-cultured cells but not in single cultured C2C12 myotubes or single cultured NSC34 motor neurons. In accordance with this observation, inhibition of the Nrg1/ErbB signaling pathways nullified the effect of 10 µM ZNS on the enhancement of AChR clustering in in vitro NMJs. Although agrin was not induced by 10 µM ZNS in co-cultured cells, anti-agrin antibody attenuated ZNS-mediated enhancement of AChR clustering. We conclude that ZNS enhances agrin-dependent AChR-clustering by upregulating the Nrg1/ErbB signaling pathways in the presence of NMJs.
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Regulação da Expressão Gênica/efeitos dos fármacos , Neuregulina-1/genética , Junção Neuromuscular/efeitos dos fármacos , Receptores Colinérgicos/metabolismo , Zonisamida/farmacologia , Animais , Linhagem Celular , Técnicas de Cocultura , Camundongos , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/metabolismo , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Neuregulina-1/metabolismo , Junção Neuromuscular/genética , Junção Neuromuscular/metabolismoRESUMO
BACKGROUND: Degenerative cervical myelopathy (DCM) can significantly impair a patient's quality of life (QOL). In this study, we aimed to identify predictors associated with QOL improvement after surgery for DCM. METHODS: This study included 148 patients who underwent surgery for DCM. The European QOL-5 Dimension (EQ-5D) score, the Japanese Orthopedic Association for the assessment of cervical myelopathy (C-JOA) score, and the Nurick grade were used as outcome measures. Radiographic examinations were performed at enrollment. The associations of baseline variables with changes in EQ-5D scores from preoperative to 1-year postoperative assessment were investigated using a multivariable linear regression model. RESULTS: The EQ-5D and C-JOA scores and the Nurick grade improved after surgery (P < 0.001, P < 0.001, and P < 0.001, respectively). Univariable analysis revealed that preoperative EQ-5D and C-JOA scores were significantly associated with increased EQ-5D scores from preoperative assessment to 1 year after surgery (P < 0.0001 and P = 0.045). Multivariable regression analysis showed that the independent preoperative predictors of change in QOL were lumbar lordosis (LL), sacral slope (SS), and T1 pelvic angle (TPA). According to the prediction model, the increased EQ-5D score from preoperatively to 1 year after surgery = 0.308 - 0.493 × EQ-5D + 0.006 × LL - 0.008 × SS + 0.004 × TPA. CONCLUSIONS: Preoperative LL, SS, and TPA significantly impacted the QOL of patients who underwent surgery for DCM. Less improvement in QOL after surgery was achieved in patients with smaller LL and TPA and larger SS values. Patients with these risk factors may therefore require additional support to experience adequate improvement in QOL.