Animal Studies On Role Of High Central Leptin In The Development Of Scoliosis And The Study On The Radiographic Characteristic And The Treatment Of Scoliosis Secondary To Chiari Malformation

Chapter1Role of high central leptin activity in a scoliosis model created in bipedal amputated miceObjective:To validate this hypothesis that leptin dysfunction might be involved in the etiopathogenesis of AIS.Method:In this study, a scoliosis model of bipedal amputated mice with high central leptin activity was established. Amputation of forelimbs and tails was performed at the age of3-week on50C3H/HeJ mice. Three days after bipedal amputation, the mice were randomly divided into two groups:then25mice were injected in the hypothalamus with lentivirus vectors which overexpressed leptin, whereas the remaining25were injected with lentivirus vectors expressing GFP (control vector). X-rays were obtained at20th week to determine the development of spinal deformity. After that all mice were sacrificed, and blood samples were collected. Then peripheral leptin levels were measured by an ELISA kit. Comparisons for the incidence of scoliosis and the severity of the curves were performed between groups. Results:The body weight was found to be slightly lower in the leptin-vector-treated C3H/HeJ mice when compared with control mice. Significantly higher peripheral serum leptin level was found in leptin-vector-treated mice than control mice. Scoliosis was observed in23/25of leptin-vector-treated mice with an average Cobb angle of29.9°, and in13/25of control with an average Cobb angle of18.3°. Both the incidence of scoliosis and curve severity was significantly higher in leptin-vector-treated mice than in control group.Conclusion:The results of this study indicated that the high central leptin activity might not only increase the risk of developing a scoliosis in bipedal mice but also contribute to the progression of scoliosis. The high central leptin activity might play an important role in the etiopathogenesis of scoliosis.Chapter2(section1) A morphometric analysis on the correlation between position of cerebellar tonsil and posterior fossa volume in the patients with idiopathic scoliosisObjective:To compare the posterior fossa volume of idiopathic scoliosis (IS) patients with that of age-matched controls and to determine the correlation between location of cerebellar tonsil and posterior fossa volume in IS patients.Methods:A retrospective radiographic study was performed on500patients with IS who received surgical treatment at our center between January2009to June2011. The recruited patients were selected with the following inclusion criteria:(1) age ranged from16to20years, and the Risser sign was5;(2) each patient had a posteroanterior standing X-ray and a combined head, cervical spine MRI scan. Age-matched healthy adolescents were recruited as controls. On sagittal MRI images, the position of the cerebellar tonsil was evaluated by the distance (d) between the inferior pole of cerebellar tonsil and the line connecting the basion and opisthion (BO line). And the anteroposterior diameter of the foramen magnum (AB), the length of supraocciput (BC), the anteroposterior diameter of the posterior fossa (CD) and the length of the clivus (AD) were measured on mid-sagittal MRI images to make a comparison of the posterior fossa volume between the IS patients and controls. Then a further analysis was performed to determine whether there was significant difference of the posterior fossa volume between IS patients with and without physiological tonsillar ectopia.Results:Totally,70IS patients were recruited with the mean age of17.2year. Of them, there were48males and22females.58normal adolescents were recruited with the mean age of17.3years. Of them, there were27males and31females. It was shown that the positions of cerebellar tonsils in IS patients were significantly lower than the positions in controls (p=0.009). The incidence of physiological tonsillar ectopia in IS was found to be22.9%. Significant increment in anteroposterior diameter of the foramen magnum (AB) was found in IS patients compared to the control group (p<0.001), while significant decrement were also found in the three remaining indexes (P<0.001). However, Cobb angles of the main curve in IS patients were found to be not correlated with positions of cerebellar tonsils. Significant difference in no index but the length of supraocciput (BC) was found in IS patients with physiological tonsillar ectopia compared to IS patients without physiological tonsillar ectopia.Conclusion:It was shown that the positions of cerebellar tonsils in IS patients were lower than the positions in controls. The incidence of physiological tonsillar ectopia in IS was found to be22.9%. It might be caused by the heteroplasia of posterior fossa in IS patients, indicating that abnormal growth kinetics of endochondral and membranous ossification could be found in the development of posterior fossa. Chapter2(section2) A morphometric analysis of the posterior fossa volume in patients with Chiari malformationsObjective:To determine whether posterior fossa volumes of patients with Chiari malformation type I (CMI) are smaller than those of the age-matched healthy adolescents through the measurement of linear distances between bony landmarks in posterior fossa and to document whether the small posterior fossa volume in CMI patient is a key point that leads to the aggravation of tonsillar displacement and syrinx formation.Methods:A retrospective radiographic study was performed on patients with CMI. The recruited patients were selected with the following inclusion criteria, including (1) age ranged from16to20years, Risser sign was5;(2)The diagnosis of CMI in each patient was confirmed by a combined head, cervical spine MRI scan. And age-matched healthy adolescents were recruited as controls. On mid-sagittal MRI images, the anteroposterior diameter of the foramen magnum (AB), the length of supraocciput (BC), the anteroposterior diameter of the posterior fossa (CD) and the length of the clivus (AD) were measured to make a comparison of the posterior fossa volume between CMI patients and controls. The severity of tonsillar descent was classified and the presence of syrinx was identified on the sagittal MRI image. Then a further analysis was performed to determine whether the posterior fossa volume in CMI patients was correlated with the severity of tonsillar displacement and syrinx formation.Results:37CMI patients were recruited with the mean age of17.2year. Of them, there were23males and14females.49normal adolescents were recruited with the mean age of17.5years. Of them, there were24males and25females. Significant decrement was found in terms of all four indexes in CMI patients compared to control group. CMI patients with tonsillar hernia of I degree were found to have longer clivus than those with tonsillar descent of Ⅱ or Ⅲ degree. No significant difference was found in terms of all four indexes between CMI patients with syrinx and those without syrinx.Conclusion:The results of the current study suggested that the bony components of posterior fossa were underdeveloped in CMI patients, supporting the current concept that CMI is caused by the underdevelopment of the para-axial mesoderm, leading to a small posterior fossa. Besides above, we found that the underdevelopment of clivus might lead to the aggravation of cerebellar tonsillar displacement and the small posterior fossa had no association with syrinx formation.Chapter2(section3) The radiological features and clinical relevance of pediatric population with scoliosis secondary to Chiari malformation Type I.Objective:To analyze the clinical and imaging features of scoliosis secondary to Chiari malformation Type I in pediatric population and to discuss their clinical significance.Methods:We reviewed the records of children(age<10years old) diagnosed as scoliosis secondary to Chiari malformation Type I from2001to2008.These indexes were measured as follow:thoracic kyphotic angle, lumbar lordotic angle, degree of cerebellar tonsillar descent, configuration, length of syrinx, the maximal ratio of syrinx to cord (S/C ratio). The correlation among them were investigated.Results:In this study,40pediatric patients with Chiari I malformation were included. There were23male and17female patients with a mean age of7.4years (range:4-10 years). In these patients, there were37(92.5%) children who had a thoracic curve,2with a thoracolumbar curve and1(2.5%) child with a lumbar curve. The overall frequency of atypical curve patterns was47.5%(19/40) in our series. Left-sided thoracic curve patterns occurred in22.5%patients(9/40). Sixteen of twenty-one (72.7%) patients had typical curve patterns with atypical features in this study. The average thoracic kyphotic angle was25.4°. A total of60%of patients had a normal to hyperkyphotic thoracic spine. The average lumbar lordotic angle was53.1°. A total of36(90%) patients were identified to have a syrinx.Conclusion:Thoracic curve,atypical curve patterns, atypical features in typical curve patterns and a normal to hyperkyphotic thoracic spine are usually found in pediatric population with scoliosis secondary to Chiari malformation Type Ⅰ. We suggest it is necessary for scoliotic children with the above features to have a MRI scan.Chapter2(section4) Syrinx resolution after posterior fossa decompression in patients with scoliosis secondary to Chiari malformation type ⅠObjective:to investigate the outcome of PFD in patients with scoliosis secondary to CMI and to identify potential predictive factors for better outcome after PFD.Methods:Patients with scoliosis secondary to CMI and SM, who had undergone PFD during the period2000through2009. were recruited. Inclusion criteria were (1) age≤18years,(2) diagnosis of SM associated with CMI,(3) scoliosis as the first complaint,(4) having undergone preoperative and follow-up magnetic resonance imaging (MRI). Patients with acquired CMI anomalies or who had received syringosubarachnoid shunting were excluded. The maximal S/C ratio and syrinx length were measured to evaluate syrinx resolution after PFD. A20%decrease in S/C ratio or length at the latest follow-up was defined as a significant radiographic improvement and complete resolution was used to describe the syrinx disappearing after PFD.Results:44patients were recruited. Follow-up MRI was conducted for all44patients at6±3months postoperatively, for37patients at2years±3months, for26patients at4years±3months, and for15patients at6years±3months.97.7%(43of44) of patients showed significant radiographic improvement by MRI. The distance of tonsillar descent (mm) was correlated significantly with the surgical outcome (r=0.116, P=0.013). Significant improvement was observed within6months postoperatively, with continued slow improvement after that.Conclusion:Syringes showed significant improvement after PFD in most patients with scoliosis secondary to CMI. Resolution generally occurred within6months follow-up and continued at a slow rate for several years. In addition, the severity of tonsillar descent is a potential predictor for better improvement after standard PFD.