JNSPG 75th Anniversary Invited Review Article
Yu-Chun Chen, Chao-Hung Kuo, Chieh-Ming Cheng and Jau-Ching Wu
Cervical spondylotic myelopathy (CSM) has become a prevalent cause of spinal cord dysfunction among the aging population worldwide. Although great strides have been made in spine surgery in past decades, the optimal timing and surgical strategy to treat CSM have remained controversial. In this article the authors aimed to analyze the current trends in studies of CSM and to summarize the recent advances of surgical techniques in its treatment.
The PubMed database was searched using the keywords pertaining to CSM in human studies that were published between 1975 and 2018. Analyses of both the bibliometrics and contents, including the types of papers, authors, affiliations and countries, number of patients, and the surgical approaches were conducted. A systematic review of the literature was also performed with emphasis on the diagnosis and treatment of mild CSM.
A total of 1008 papers published during the span of 44 years were analyzed. These CSM studies mainly focused on the natural history, diagnosis, and treatment, and only a few prospective randomized trials were reported. For the authors and affiliations, there was a shift of clustering of papers toward Asian countries in the past decades. Regarding the treatment for CSM, there was an exponential growth of surgical series published, and there was a trend toward slightly more anterior than posterior approaches through the past decade. Patients with CSM had increased risks of neurological deterioration or spinal cord injury with nonoperative management. Because surgery might reduce the risks, and early surgery was likely to be correlated with better outcomes, there was a trend toward attention to mildly symptomatic CSM.
There is emerging enthusiasm for research on CSM worldwide, with more publications originating in Asian countries over the past few decades. The surgical management of CSM is evolving continuously toward early and anterior approaches. More prospective investigations on the optimal timing and choices of surgery are therefore needed.
Chun-Wei Yu, Kuan-Ting Chen, Yu-Lan Liu, Yi-Chiao Hsieh, Dun-Wei Huang, Yi-Feng Lee, Tsui-Jung Chien and Dueng-Yuan Hueng
Syu-Jyun Peng, Chien-Chen Chou, Hsiang-Yu Yu, Chien Chen, Der-Jen Yen, Shang-Yeong Kwan, Sanford P. C. Hsu, Chun-Fu Lin, Hsin-Hung Chen and Cheng-Chia Lee
In this study, the authors investigated high-frequency oscillation (HFO) networks during seizures in order to determine how HFOs spread from the focal cerebral cortex and become synchronized across various areas of the brain.
All data were obtained from stereoelectroencephalography (SEEG) signals in patients with drug-resistant temporal lobe epilepsy (TLE). The authors calculated intercontact cross-coefficients between all pairs of contacts to construct HFO networks in 20 seizures that occurred in 5 patients. They then calculated HFO network topology metrics (i.e., network density and component size) after normalizing seizure duration data by dividing each seizure into 10 intervals of equal length (labeled I1–I10).
From the perspective of the dynamic topologies of cortical and subcortical HFO networks, the authors observed a significant increase in network density during intervals I5–I10. A significant increase was also observed in overall energy during intervals I3–I8. The results of subnetwork analysis revealed that the number of components continuously decreased following the onset of seizures, and those results were statistically significant during intervals I3–I10. Furthermore, the majority of nodes were connected to a single dominant component during the propagation of seizures, and the percentage of nodes within the largest component grew significantly until seizure termination.
The consistent topological changes that the authors observed suggest that TLE is affected by common epileptogenic patterns. Indeed, the findings help to elucidate the epileptogenic network that characterizes TLE, which may be of interest to researchers and physicians working to improve treatment modalities for epilepsy, including resection, cortical stimulation, and neuromodulation treatments that are responsive to network topologies.
Jau-Ching Wu, Chin-Chu Ko, Yu-Shu Yen, Wen-Cheng Huang, Yu-Chun Chen, Laura Liu, Tsung-Hsi Tu, Su-Shun Lo and Henrich Cheng
This study aimed to determine the age- and sex-specific incidence of cervical spondylotic myelopathy (CSM) and its associated risk of causing subsequent spinal cord injury (SCI).
Using the National Health Insurance Research Database (NHIRD), a 12-year nationwide database in Taiwan, this retrospective cohort study analyzed the incidence of hospitalization caused by CSM. All patients diagnosed with and admitted for CSM were identified during the study period. The CSM patients were divided into 2 groups, a control group and an operated group. An incidence density method was used to estimate age- and sex-specific incidence rates of CSM. The Kaplan-Meier method and Cox regression analyses were performed to compare the risk of SCI between the 2 groups.
From 1998 to 2009, covering 349.5 million person-years, 14,140 patients were hospitalized for CSM. The overall incidence of CSM-related hospitalization was 4.04 per 100,000 person-years. Specifically, males and older persons had a higher incidence rate of CSM. During the follow-up of these patients for 13,461 person-years, a total of 166 patients were diagnosed with SCI. The incidence of SCI was higher in the control group than the operated group (13.9 vs 9.4 per 1000 person-years, respectively). During the follow-up, SCI was more likely to occur in CSM patients who were treated conservatively (crude HR 1.48, p = 0.023; adjusted HR 1.57, p = 0.011) than in those who underwent surgery for CSM.
In a national cohort of eastern Asia, the incidence of CSM-caused hospitalization was 4.04 per 100,000 person-years, with higher incidences observed in older and male patients. Subsequent SCI was more likely to develop in patients who received nonoperative management than in those who underwent surgery. Therefore, patients with CSM managed without surgery should be cautioned about SCI. However, further investigations are still required to clarify the risks and complications associated with surgery for CSM.
Michael G. Fehlings and Jefferson R. Wilson
Jau-Ching Wu, Wen-Cheng Huang, Yu-Chun Chen, Tsung-Hsi Tu, Yun-An Tsai, Shih-Fong Huang, Hsueh-Chen Huang and Henrich Cheng
The study aimed to verify the safety and feasibility of applying acidic fibroblast growth factor (aFGF) with fibrin glue in combination with surgical neurolysis for nonacute spinal cord injury.
This open-label, prospective, uncontrolled human clinical trial recruited 60 patients with spinal cord injuries (30 cervical and 30 thoracolumbar). The mean patient age was 36.5 ± 15.33 (mean ± SD) years, and the male/female ratio was 3:1. The mean time from injury to treatment was 25.7 ± 26.58 months, and the cause of injury included motor vehicle accident (26 patients [43.3%]), fall from a height (17 patients [28.3%]), sports (4 patients [6.7%]), and other (13 patients [21.7%]). Application of aFGF with fibrin glue and duraplasty was performed via laminectomy, and an adjuvant booster of combined aFGF and fibrin glue (2 ml) was given at 3 and 6 months postsurgery via lumbar puncture. Outcome measurements included the American Spinal Injury Association (ASIA) motor scores, sensory scores, impairment scales, and neurological levels. Examination of functional independence measures, visual analog scale, MR imaging, electrophysiological and urodynamic studies, hematology and biochemistry tests, tumor markers, and serum inflammatory cytokines were all conducted. All adverse events were monitored and reported. Exclusions were based on refusal, unrelated adverse events, or failure to participate in the planned rehabilitation.
Forty-nine patients (26 with cervical and 23 with thoracolumbar injuries) completed the 24-month trial. Compared with preoperative conditions, the 24-month postoperative ASIA motor scores improved significantly in the cervical group (from 27.6 ± 15.55 to 37.0 ± 19.93, p < 0.001) and thoracolumbar group (from 56.8 ± 9.21 to 60.7 ± 10.10, p < 0.001). The ASIA sensory scores also demonstrated significant improvement in light touch and pinprick in both groups: from 55.8 ± 24.89 to 59.8 ± 26.47 (p = 0.049) and 56.3 ± 23.36 to 62.3 ± 24.87 (p = 0.003), respectively, in the cervical group and from 75.7 ± 15.65 to 79.2 ± 15.81 (p < 0.001) and 78.2 ± 14.72 to 82.7 ± 16.60 (p < 0.001), respectively, in the thoracolumbar group. At 24-month follow-up, the ASIA impairment scale improved significantly in both groups (30% cervical [p = 0.011] and 30% thoracolumbar [p = 0.003]). There was also significant improvement in neurological level in the cervical (from 5.17 ± 1.60 to 6.27 ± 3.27, p = 0.022) and thoracolumbar (from 18.03 ± 4.19 to 18.67 ± 3.96, p = 0.001) groups. The average sum of motor items in functional independence measure also had significant improvement in both groups (p < 0.05). The walking/wheelchair locomotion subscale showed increased percentages of patients who were ambulatory (from 3.4% to 13.8% and from 17.9% to 35.7% in the cervical and thoracolumbar groups, respectively). There were no related adverse events.
The use of aFGF for spinal cord injury was safe and feasible in the present trial. There were significant improvements in ASIA motor and sensory scale scores, ASIA impairment scales, neurological levels, and functional independence measure at 24 months after treatment. Further large-scale, randomized, and controlled investigations are warranted to evaluate the efficacy and long-term results.
Li-Fu Chen, Tsung-Hsi Tu, Yu-Chun Chen, Jau-Ching Wu, Peng-Yuan Chang, Laura Liu, Wen-Cheng Huang, Su-Shun Lo and Henrich Cheng
This study aimed to estimate the risk of spinal cord injury (SCI) in patients with cervical spondylotic myelopathy (CSM) with and without ossification of posterior longitudinal ligament (OPLL). Also, the study compared the incidence rates of SCI in patients who were managed surgically and conservatively.
This retrospective cohort study covering 15 years analyzed the incidence of SCI in patients with CSM. All patients, identified from the National Health Insurance Research Database, were hospitalized with the diagnosis of CSM and followed up during the study period. These patients with CSM were categorized into 4 groups according to whether they had OPLL or not and whether they received surgery or not: 1) surgically managed CSM without OPLL; 2) conservatively managed CSM without OPLL; 3) surgically managed CSM with OPLL; and 4) conservatively managed CSM with OPLL. The incidence rates of subsequent SCI in each group during follow-up were then compared. Kaplan-Meier and Cox regression analyses were performed to compare the risk of SCI between the groups.
Between January 1, 1999, and December 31, 2013, there were 17,258 patients with CSM who were followed up for 89,003.78 person-years. The overall incidence of SCI in these patients with CSM was 2.022 per 1000 person-years. Patients who had CSM with OPLL and were conservatively managed had the highest incidence of SCI, at 4.11 per 1000 person-years. Patients who had CSM with OPLL and were surgically managed had a lower incidence of SCI, at 3.69 per 1000 person-years. Patients who had CSM without OPLL and were conservatively managed had an even lower incidence of SCI, at 2.41 per 1000 person-years. Patients who had CSM without OPLL and were surgically managed had the lowest incidence of SCI, at 1.31 per 1000 person-years. The Cox regression model demonstrated that SCIs are significantly more likely to happen in male patients and in those with OPLL (HR 2.00 and 2.24, p < 0.001 and p = 0.007, respectively). Surgery could significantly lower the risk for approximately 50% of patients (HR 0.52, p < 0.001).
Patients with CSM had an overall incidence rate of SCI at approximately 0.2% per year. Male sex, the coexistence of OPLL, and conservative management are twice as likely to be associated with subsequent SCI. Surgery is therefore suggested for male patients with CSM who also have OPLL.
Jau-Ching Wu, Laura Liu, Yu-Chun Chen, Wen-Cheng Huang, Tzeng-Ji Chen and Henrich Cheng
This study aimed to calculate the incidence and prevalence of ossification of the posterior longitudinal ligament (OPLL) in the cervical spine with its comorbid disability.
Using an 11-year nationwide database in Taiwan (National Health Insurance Research Database), this retrospective study cohort analyzed the incidences of cervical OPLL causing hospitalization. All patients admitted for the diagnosis of OPLL, regardless of surgery, were identified. Age- and sex-specific incidences, Poisson regression, and multivariate logistic regression analysis were conducted.
Between 1997 and 2007 covering 241,800,725.8 person-years, 1651 patients were admitted for OPLL. The overall incidence of OPLL-related admission was 6.1 per 1 million person-years. Specifically, male sex and older age were associated with higher OPLL incidences (both p < 0.001). Among the 1651 OPLL patients, 542 (32.8%) received conservative management, 612 (37.1%) had anterior only surgery, 353 (21.4%) had posterior only surgery, and 144 (8.7%) had anterior and posterior surgery. Eighty-five patients were moderately to severely disabled (5.2% cumulative incidence rate). The incidences of disability varied by age, in a decreasing trend, except for the 60- to 69-year-old age group (p = 0.05). Patients who received posterior-only surgery were more likely to have disability.
In a large cohort of the Chinese population, the incidence of cervical OPLL-related admission is 6.1 per 1 million person-years, and the prevalence rate is 7.7 per 100,000 person-years. Higher incidences are observed in elderly and male patients, which implies the disease's degenerative nature. After adjustments for demographics, the incidences and trends of OPLL-related comorbid disability are associated with age and surgical approaches.
Dar-Yu Yang, Meei-Ling Sheu, Hong-Lin Su, Fu-Chou Cheng, Ying-Ju Chen, Chun-Jung Chen, Wen-Ta Chiu, Jia-Jean Yiin, Jason Sheehan and Hung-Chuan Pan
Human amniotic fluid–derived mesenchymal stem cells (AFMSCs) have been shown to promote peripheral nerve regeneration. The expression of stromal cell–derived factor-1α (SDF-1α) in the injured nerve exerts a trophic effect by recruiting progenitor cells that promote nerve regeneration. In this study, the authors investigated the feasibility of intravenous administration of AFMSCs according to SDF-1α expression time profiles to facilitate neural regeneration in a sciatic nerve crush injury model.
Peripheral nerve injury was induced in 63 Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The animals were randomized into 1 of 3 groups: Group I, crush injury as the control; Group II, crush injury and intravenous administration of AFMSCs (5 × 106 cells for 3 days) immediately after injury (early administration); and Group III, crush injury and intravenous administration of AFMSCs (5 × 106 cells for 3 days) 7 days after injury (late administration). Evaluation of neurobehavior, electrophysiological study, and assessment of regeneration markers were conducted every week after injury. The expression of SDF-1α and neurotrophic factors and the distribution of AFMSCs in various time profiles were also assessed.
Stromal cell–derived factor-1α increased the migration and wound healing of AFMSCs in vitro, and the migration ability was dose dependent. Crush injury induced the expression of SDF-1α at a peak of 10–14 days either in nerve or muscle, and this increased expression paralleled the expression of its receptor, chemokine receptor type-4 (CXCR-4). Most AFMSCs were distributed to the lung during early or late administration. Significant deposition of AFMSCs in nerve and muscle only occurred in the late administration group. Significantly enhanced neurobehavior, electrophysiological function, nerve myelination, and expression of neurotrophic factors and acetylcholine receptor were demonstrated in the late administration group.
Amniotic fluid–derived mesenchymal stem cells can be recruited by expression of SDF-1α in muscle and nerve after nerve crush injury. The increased deposition of AFMSCs paralleled the expression profiles of SDF-1α and its receptor CXCR-4 in either muscle or nerve. Administration of AFMSCs led to improvements in neurobehavior and expression of regeneration markers. Intravenous administration of AFMSCs may be a promising alternative treatment strategy in peripheral nerve disorder.