Wen-Cheng Huang

Endoscopic transnasal transclival odontoidectomy: a new approach to decompression: technical case report.

OBJECTIVE Endoscopic transnasal transclival resection of the odontoid process is less invasive than the standard transoral odontoidectomy. In this article, we describe our techniques, which are less invasive but provide successful decompression. CLINICAL PRESENTATION From September 2004 to April 2007, three consecutive patients with basilar invagination and instability in the craniovertebral junction were enrolled. The causes for the invagination and instability included rheumatoid arthritis in two patients and trauma in one patient, and all patients presented with myelopathy and quadriparesis before intervention. INTERVENTION All three patients underwent an endoscopic transnasal transclival approach for anterior decompression and resection of the displaced odontoid process and pannus to decompress the underlying medulla. Subsequently, they received occipitocervical fixation by lateral mass screws and bone fusion to ensure stability. Remarkable neurological recovery was observed after surgery in all patients, and no adverse effects were noted. CONCLUSION Compared with the standard transoral approach, the transnasal transclival endoscopic approach for decompressing basilar invagination is a feasible and effective alternative that avoids common disadvantages like prolonged intubation, excessive tongue retraction, and the need for palatal incision.

Screw loosening in the Dynesys stabilization system: radiographic evidence and effect on outcomes

OBJECT Dynamic stabilization systems are used to stabilize degenerative lumbar spondylosis. Loosening of the pedicle screws in such nonfusion implants is predictable. This retrospective study evaluated the incidence of screw loosening and its effect on clinical outcomes. METHODS Charts, radiographic films, and medical records of 71 consecutive patients who underwent decompression using Dynesys dynamic stabilization for 1- or 2-level lumbar spondylosis were reviewed. Radiographic films were evaluated and compared to detect screw loosening. A visual analog scale (VAS) for back pain and the Oswestry Disability Index (ODI) were used for measuring clinical outcome. Statistical analysis was conducted using the chi-square test and Student t-test. RESULTS The 71 patients in the study sample had a mean age of 59.2 +/- 11.65 years (range 23-80 years), with slight female predominance (39 women, 32 men). The mean follow-up duration was 16.6 months (range 8-29 months). There were loose screws in 14 of 71 patients (19.7%), for a rate of 4.6% per screw (17 of 368 screws). Most screw loosening occurred in patients >/= 55 years old (13 of 14 patients) although age and sex had no effect on screw loosening (p = 0.233 and 0.109, respectively). Both the loose screw and solid screw groups experienced significant improvement after the surgery in VAS and ODI scores. On the VAS, scores improved from 5.9 +/- 2.99 to 2.1 +/- 2.14 in the loose screw group (p = 0.003), and from 5.7 +/- 3.45 to 2.9 +/- 2.68 in the solid screw group (p < 0.001). For the ODI scale, scores improved from 43.5 +/- 16.78% to 28.0 +/- 18.18% (p = 0.006) in the loose screw group, and from 52.1 +/- 20.92% to 24.6 +/- 19.78% (p < 0.001) in the solid screw group. There were no significant differences between the 2 groups (p = 0.334 for VAS, p = 0.567 for ODI). CONCLUSIONS The preliminary study of this pedicle-based dynamic stabilization device for 1- and 2-level lumbar spondylosis shows radiographic evidence of screw loosening in 19.7% of patients and 4.6% of screws. Nonetheless, the loosening of screws has no adverse effect on clinical improvement.

Acid fibroblast growth factor and peripheral nerve grafts regulate Th2 cytokine expression, macrophage activation, polyamine synthesis, and neurotrophin expression in transected rat spinal cords.

Spinal cord injury elicits an inflammatory response that recruits macrophages to the injured spinal cord. Quantitative real-time PCR results have shown that a repair strategy combining peripheral nerve grafts with acidic fibroblast growth factor (aFGF) induced higher interleukin-4 (IL-4), IL-10, and IL-13 levels in the graft areas of rat spinal cords compared with transected spinal cords at 10 and 14 d. This led to higher arginase I-positive alternatively activated macrophage (M2 macrophage) responses. The gene expression of several enzymes involved in polyamine biosynthesis pathways was also upregulated in the graft areas of repaired spinal cords. The treatment induced a twofold upregulation of polyamine levels at 14 d, as confirmed by HPLC. Polyamines are important for the repair process, as demonstrated by the observation that treatment with inhibitors of arginase I and ornithine decarboxylase attenuates the functional recoveries of repaired rats. After 14 d, the treatment also induced the expression of neurotrophin nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), as well as M2 macrophages within grafted nerves expressing BDNF. IL-4 was upregulated in the injury sites of transected rats that received aFGF alone compared with those that received nerve grafts alone at 10 d. Conversely, nerve graft treatment induced NGF and BDNF expression at 14 d. Macrophages expressing polyamines and BDNF may benefit axonal regeneration at 14 d. These results indicate that aFGF and nerve grafts regulate different macrophage responses, and M2 macrophages may play an important role in axonal regeneration after spinal cord injury in rats.

Increased risk of stroke after spinal cord injury A nationwide 4-year follow-up cohort study

Objective: Spinal cord injury (SCI) is associated with a higher risk of cardiovascular diseases but whether or not the risk of cerebrovascular disease also increases remains unclear. This study aimed to evaluate the incidence of stroke in patients with disability caused by SCI. Methods: Study subjects were identified from a nationwide cohort of 18,690,066 people from 1998 to 2002 that was divided into an SCI group (n = 2,806), who were disabled from SCI, and a comparison group (n = 28,060), composed of age-, sex-, and propensity score– matched control subjects. Every subject was followed up for 4 years, unless they died or had a stroke by December 31, 2006. Kaplan-Meier and Cox regression analyses were performed. Results: The incidence rate of stroke in the SCI group (5.96 per 1,000 person-years) was higher than that of the comparison group (p < 0.001). Stroke was more likely to occur in the SCI group than in the comparison group (crude hazard ratio 2.93, p < 0.001; adjusted hazard ratio 2.85, p < 0.001). In the SCI group, the incidence of ischemic stroke was higher than that of hemorrhagic stroke (incidence rate ratio 3.42, p < 0.001). Conclusions: SCI patients with disability are at a higher risk of stroke, especially the ischemic type. Strategies to prevent stroke are therefore suggested for them.

Pedicle screw loosening in dynamic stabilization: incidence, risk, and outcome in 126 patients

OBJECT The long-term outcome of lumbar dynamic stabilization is uncertain. This study aimed to investigate the incidence, risk factors, and outcomes associated with screw loosening in a dynamic stabilization system. METHODS The authors conducted a retrospective review of medical records, radiological studies, and clinical evaluations obtained in consecutive patients who underwent 1- or 2-level lumbar dynamic stabilization and were followed up for more than 24 months. Loosening of screws was determined on radiography and CT scanning. Radiographic and standardized clinical outcomes, including the visual analog scale (VAS) and Oswestry Disability Index (ODI) scores, were analyzed with a focus on cases in which screw loosening occurred. RESULTS The authors analyzed 658 screws in 126 patients, including 54 women (42.9%) and 72 men (57.1%) (mean age 60.4 ± 11.8 years). During the mean clinical follow-up period of 37.0 ± 7.1 months, 31 screws (4.7%) in 25 patients (19.8%) were shown to have loosened. The mean age of patients with screw loosening was significantly higher than those without loosening (64.8 ± 8.8 vs 59.3 ± 12.2, respectively; p = 0.036). Patients with diabetes mellitus had a significantly higher rate of screw loosening compared with those without diabetes (36.0% vs 15.8%, respectively; p = 0.024). Diabetic patients with well-controlled serum glucose (HbA1c ≤ 8.0%) had a significantly lower chance of screw loosening than those without well-controlled serum glucose (28.6% vs 71.4%, respectively; p = 0.021). Of the 25 patients with screw loosening, 22 cases (88%) were identified within 6.6 months of surgery; 18 patients (72%) had the loosened screws in the inferior portion of the spinal construct, whereas 7 (28%) had screw loosening in the superior portion of the construct. The overall clinical outcomes at 3, 12, and 24 months, measured by VAS for back pain, VAS for leg pain, and ODI scores, were significantly improved after surgery compared with before surgery (all p < 0.05). There were no significant differences between the patients with and without screw loosening at all evaluation time points (all p > 0.05). All 25 patients with screw loosening were asymptomatic, and in 6 (24%) osseous integration was demonstrated on later follow-up. Also, there were 3 broken screws (2.38% in 126 patients or 0.46% in 658 screws). To date, none of these loosened or broken screws have required revision surgery. CONCLUSIONS Screw loosening in dynamic stabilization systems is not uncommon (4.7% screws in 19.8% patients). Patients of older age or those with diabetes have higher rates of screw loosening. Screw loosening can be asymptomatic and presents opportunity for osseous integration on later follow-up. Although adverse effects on clinical outcomes are rare, longer-term follow-up is required in cases in which screws become loose.

New nerve regeneration strategy combining laminin-coated chitosan conduits and stem cell therapy

Nerve regeneration remains a difficult challenge due to the lack of safe and efficient matrix support. We designed a laminin (LN)-modified chitosan multi-walled nerve conduit combined with bone marrow stem cell (BMSC) grating to bridge a 10 mm long gap in the sciatic nerve of Sprague-Dawley rats. The repair outcome was monitored during 16 weeks after surgery. Successful grafting of LN onto the chitosan film, confirmed by immunolocalization, significantly improved cell adhesion. In vivo study showed that newly formed nerve cells covered the interior of the conduit to connect the nerve gap successfully in all groups. The rats implanted with the conduit combined with BMSCs showed the best results, in terms of nerve regrowth, muscle mass of gastrocnemius, function recovery and tract tracing. Neuroanatomical horseradish peroxidase tracer analysis of motor neurons in the lumbar spinal cord indicated that the amount and signal intensity were significantly improved. Furthermore, BMSCs suppressed neuronal cell death and promoted regeneration by suppressing the inflammatory and fibrotic response induced by chitosan after long-term implantation. In summary, this study suggests that LN-modified chitosan multi-walled nerve conduit combined with BMSCs is an efficient and safe conduit matrix for nerve regeneration.

Heterotopic ossification after cervical total disc replacement: determination by CT and effects on clinical outcomes

OBJECT Heterotopic ossification (HO) after cervical total disc replacement (TDR) has been reported to impede artificial disc motion. In all previously reported cases of HO, assessment was based on plain radiographs. The authors hypothesized that CT scan is a more sensitive and accurate detector. The aims of this study were to assess the actual incidence of HO and its effect on outcome in a cohort of patients undergoing cervical TDR with the Bryan disc and to compare HO detection by means of plain radiographs and CT. METHODS The authors retrospectively assessed data from medical records, radiological studies, and clinical evaluations of patients who underwent 1- or 2-level cervical TDR with the Bryan disc and were followed up for more than 12 months. The presence and grading of HO according to the McAfee classification were assessed by CT scan, and these findings were compared with findings on plain radiographs. Thirty-six patients (mean age 46.61 ± 7.24 years; range 29-60 years; 21 men and 15 women) who underwent Bryan TDR at 52 levels were included in the study. The mean duration of CT follow-up was 19.03 ± 4.64 months; the mean duration of clinical follow-up was 26.78 ± 7.20 months. RESULTS On the basis of CT, HO was identified in 18 (50%) of 36 patients and 25 (48.1%) of 52 levels treated. Grade 1 HO was present in 9 of the levels treated (17.3%), Grade 2 in 13 levels (25.0%), Grade 3 in 2 levels (3.8%), and Grade 4 in 1 level (1.9%). Nineteen (76%) of the 25 affected levels were in patients who had undergone 2-level TDR. There was no significant association with patient sex or disc pathology. There was a tendency for HO development among older patients, but this finding was not statistically significant (mean age 48.8 ± 6.8 in patients with HO vs 44.4 ± 7.2 in those without HO, p = 0.065). Although HO was found in 25 levels, 96.2% of the treated levels (50 of 52) had segmental range of motion on dynamic (flexion and extension) radiographs. The concordance between HO grading by CT and radiography was high, with an intraclass correlation coefficient of 0.822 (lower limit of 95% CI: 0.710, p < 0.001). Patients who had HO had the same clinical success rate as those who did not (94.4% vs 94.4%, p = 1.00). The visual analog scale scores for neck and arm pain were significantly improved in both the HO and the non-HO group. CONCLUSIONS The rate of HO detected by CT scan in this cohort of patients undergoing cervical TDR with a Bryan disc was 48.1% per level treated and 50% per patient with minimal limitation of segmental motion (96.2% of levels remained mobile), but plain radiograph is an acceptable detection tool. Two-level surgery has a higher risk of HO, although development of HO does not affect clinical outcome.

Recovery of neurological function of ischemic stroke by application of conditioned medium of bone marrow mesenchymal stem cells derived from normal and cerebral ischemia rats

BackgroundSeveral lines of evidence have demonstrated that bone marrow-derived mesenchymal stem cells (BM-MSC) release bioactive factors and provide neuroprotection for CNS injury. However, it remains elusive whether BM-MSC derived from healthy donors or stroke patients provides equal therapeutic potential. The present work aims to characterize BM-MSC prepared from normal healthy rats (NormBM-MSC) and cerebral ischemia rats (IschBM-MSC), and examine the effects of their conditioned medium (Cm) on ischemic stroke animal model.ResultsIsolated NormBM-MSC or IschBM-MSC formed fibroblastic like morphology and expressed CD29, CD90 and CD44 but failed to express the hematopoietic marker CD34. The number of colony formation of BM-MSC was more abundant in IschBM-MSC than in NormBM-MSC. This is in contrast to the amount of Ficoll-fractionated mononuclear cells from normal donor and ischemic rats. The effect of cm of BM-MSC was further examined in cultures and in middle cerebral artery occlusion (MCAo) animal model. Both NormBM-MSC Cm and IschBM-MSC Cm effectively increased neuronal connection and survival in mixed neuron-glial cultures. In vivo, intravenous infusion of NormBM-MSC Cm and IschBM-MSC Cm after stroke onset remarkably improved functional recovery. Furthermore, NormBM-MSC Cm and IschBM-MSC Cm increased neurogenesis and attenuated microglia/ macrophage infiltration in MCAo rat brains.ConclusionsOur data suggest equal effectiveness of BM-MSC Cm derived from ischemic animals or from a normal population. Our results thus revealed the potential of BM-MSC Cm on treatment of ischemic stroke.

Epidemiology of cervical spondylotic myelopathy and its risk of causing spinal cord injury: a national cohort study

OBJECT 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). METHODS 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. RESULTS 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. CONCLUSIONS 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.

Acidic fibroblast growth factor for repair of human spinal cord injury: a clinical trial

OBJECT 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.