Neural stem cell transplantation for the treatment of primary torsion dystonia: A case report.

Primary torsion dystonia (PTD) occurs due to a genetic mutation and often advances gradually. Currently, there is no therapy available that is able to inhibit progression. Neural stem cells (NSCs) are being investigated as potential therapies for neurodegenerative diseases, such as stroke and trauma. The present study evaluated the clinical effectiveness of NSC transplantation in an 18-year-old male patient with PTD, to assess the ability of this therapy to inhibit PTD progression. Genetic testing of the patient revealed a mutation in the torsion dystonia-1 (DYT1) gene (907-909 delGAG). NSCs were bilaterally implanted in the globus pallidus of the patient through stereotactic surgery. Prior to surgery, the patient's Burke-Fahn-Marsden dystonia movement score (BFMDMS) was 21, which progressively decreased after surgery to 18, 17, 15 and 13 at 1, 2, 3 and 4 postoperative years, respectively. BFMDMS was improved by 38.1% over the 4 postoperative years. Although computed tomography and magnetic resonance imaging examinations showed no significant changes prior to and following surgery, postoperative brain positron emission tomography scans revealed increased glucose metabolism in the transplanted region. The clinical efficacy of NSC transplantation in this patient suggests its potential for the treatment of DYT1-positive patients with PTD.

Extracellular α-synuclein--a possible initiator of inflammation in Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease involving the loss of dopamine-producing neurons of the substantia nigra and the presence of Lewy bodies which contain high levels of α-synuclein. Although the causative factors of PD remain unclear, the progression of PD is accompanied by a highly localized inflammatory response mediated by reactive microglia. Recently, attention has focused on the relationship between α-synuclein and microglial activation. This review examines the role of α-synuclein on microglia in PD pathogenesis and progression, we also discuss the way of α-synuclein induced microglial activation.

Clinical application of a vascular interventional robot in cerebral angiography.

BACKGROUND: Cardiovascular and cerebrovascular diseases have become the leading cause of death for people, and endovascular surgery has become the main therapeutic method. Robot technology would overcome some limitations of conventional surgery, and has good prospects. METHODS: A total of 15 patients received cerebral angiography assisted by a vascular interventional robot following preoperative examination, with approval from the hospital ethics committee and informed consent by the patients' families. RESULTS: Robot-assisted angiography was performed quickly and smoothly without surgical complications. The remote positioning accuracy was 1.05 ± 0.28 mm. The time staff were exposed to the digital subtraction angiography (DSA) machine was 0 min. The entire experimental process was mechanized and automated. CONCLUSION: This system achieved the preliminary purposes, including a reduction in radiation for the surgeons, facilitation of the application of interventional procedures, a decrease in operation time, and an improvement in operation quality.

[How to deal with cerebral palsy in 21st century--a new epoch in clinic treatment].

The aims of this paper were to define (1) criteria of cerebral palsy; (2) classification of cerebral palsy; (3) etiology, neuroimaging, and epidemiology of cerebral palsy; (4) different kinds of treatments of cerebral palsy. Data were drawn from an international survey of PUBMED (1994-2014) and CNKI (1994-2014). An expert panel used a consensus building technique. The10-point Jadad scale was used to assess the quality of the trials based on the following items, including allocation sequence generation, randomization concealment, methods of blinding, and descriptions of withdrawals and dropouts. Our clinical experience was also summarized. Below is a summary. (1) Further work is warranted to reach agreement for the classification of cerebral palsy. (2) A worldwide prevalence of 1.5-4.0 per 1 000 live births, with an average lifetime cost of 1 million dollars per person in the United States, while it is 1.8-6.0 per 1000 live births in China. (3) Comparison of clinical efficacy of different treatments. In this review, the current advances in different kind of treatments of brain injury are discussed with specific relevance to cerebral palsy.

Transplantation of human retinal pigment epithelium cells in the treatment for Parkinson disease.

BACKGROUND AND PURPOSE: To assess the clinical effect of transplantation of human retinal pigment epithelial (hRPE) cells into the unilateral postcommissural putamen for treatment for Parkinson disease (PD). METHODS AND RESULTS: Cells from postmortem human eye tissue (10-20 weeks of gestation) were cultured in vitro. Cells from -generation passage were implanted in PD postcommissural putamen with stereotactic operation in 12 patients with PD. All patients tolerated surgery well, and no major adverse events occurred. Eleven patients showed improvement in the primary outcome measure at 3 months post-treatment, particularly the Unified Parkinson's Disease Rating Scale-M score in the off state. Response reached a peak at 12 months and declined during the next 24 months. At the 36-month endpoint, there were eight patients who felt better than at baseline. Positron emission tomography (PET) showed a trend with increased dopamine (DA) release during the first 6 months. CONCLUSION: Human retinal pigment epithelial cells have the characteristics of neural progenitor cells and can be induced to differentiate into DA neurons. The results of this clinical trial suggest that the treatment of transplanted hRPE cells could improve symptoms of PD. These cells might serve as a useful source of DA neurons for neural graft in the treatment for PD.

[Experimental study of angiography using vascular interventional robot-2(VIR-2)].

OBJECTIVE: To verify the feasibility and safety of new vascular interventional robot system used in vascular interventional procedures. METHODS: Vascular interventional robot type-2 (VIR-2) included master-slave parts of body propulsion system, image navigation systems and force feedback system, the catheter movement could achieve under automatic control and navigation, force feedback was integrated real-time, followed by in vitro pre-test in vascular model and cerebral angiography in dog. Surgeon controlled vascular interventional robot remotely, the catheter was inserted into the intended target, the catheter positioning error and the operation time would be evaluated. RESULTS: In vitro pre-test and animal experiment went well; the catheter can enter any branch of vascular. Catheter positioning error was less than 1 mm. The angiography operation in animal was carried out smoothly without complication; the success rate of the operation was 100% and the entire experiment took 26 and 30 minutes, efficiency was slightly improved compared with the VIR-1, and the time what staff exposed to the DSA machine was 0 minute. The resistance of force sensor can be displayed to the operator to provide a security guarantee for the operation. No surgical complications. CONCLUSIONS: VIR-2 is safe and feasible, and can achieve the catheter remote operation and angiography; the master-slave system meets the characteristics of traditional procedure. The three-dimensional image can guide the operation more smoothly; force feedback device provides remote real-time haptic information to provide security for the operation.

Over-expression of BMPR-IB reduces the malignancy of glioblastoma cells by upregulation of p21 and p27Kip1.

BACKGROUND: In our previous study, we detected decreased expression of phospho-Smad1/5/8 and its upstream signaling molecule, bone morphogenetic protein receptor IB subunit (BMPR-IB), in certain glioblastoma tissues, unlike normal brain tissues. In order to clarify the functional roles and mechanism of BMPR-IB in the development of glioblastoma, we studied the effects of BMPR-IB overexpression on glioblastoma cell lines in vitro and in vivo. METHODS: We selected glioblastoma cell lines U251, U87, SF763, which have different expression of BMPR-IB to be the research subjects. Colony formation analysis and FACS were used to detect the effects of BMPR-IB on the growth and proliferation of glioblastoma cells in vivo. Immunofluresence was used to detect the differentiation changes after BMPR-IB overexpression or knocking-down. Then we used subcutaneous and intracranial tumor models to study the effect of BMPR-IB on the growth and differentiation of glioblastoma cells in vivo. The genetic alterations involved in this process were examined by real-time PCR and western blot analysis.ed. RESULTS AND CONCLUSION: Forced BMPR-IB expression in malignant human glioma cells, which exhibit lower expression of BMPR-IB, induced the phosphorylation and nuclear localization of smad1/5/8 and arrested the cell cycle in G1. Additionally, BMPR-IB overexpression could suppress anchorage-independent growth and promote differentiation of theses glioblastoma cells. Furthermore, overexpression of BMPR-IB inhibited the growth of subcutaneous and intracranial tumor xenografts and prolonged the survival of mice injected intracranially with BMPR-IB-overexpressing glioblastoma cells. Conversely, inhibition of BMPR-IB caused SF763 malignant glioma cells, a line known to exhibit high BMPR-IB expression that does not form tumors when used for xenografts, to show increased growth and regain tumorigenicity in a nude mouse model system, ultimately shortening the survival of these mice. We also observed significant accumulation of p21 and p27kip1 proteins in response to BMPR-IB overexpression. Our study suggests that overexpression of BMPR-IB may arrest and induce the differentiation of glioblastoma cells due to upregulation of p21 and p27kip1 in vitro and that in vivo and decreased expression of BMPR-IB in human glioblastoma cells contributes to glioma tumorigenicity. BMPR-IB could represent a new potential therapeutic target for malignant human gliomas.

[Magnetic resonance spectroscopy-guided stereotactic biopsy for brain lesion].

OBJECTIVE: To study the clinical value of magnetic resonance spectroscopy (MRS) image in stereotactic biopsy for brain lesion. METHODS: From April 2008 to April 2010, 126 cases (72 male and 54 female, aged from 10 to 82 years, mean 45 years) of brain lesion which were difficult to diagnose were divided into two groups by random number table, 62 cases were executed for MRI-guided frameless stereotactic biopsy (MRI group), 64 cases were executed for MRI and MRS-guided frameless stereotactic biopsy (MRS group). Operation used MRI and Three-dimensional MRS image to locate, and used frameless CAS-R-2 robots to carry out the positioning operating. RESULTS: No surgery-related deaths and infections. Pathological diagnosis was 106 cases of brain tumors, 6 cases of inflammatory disease, 4 cases of tumor-like demyelinating disease and multiple sclerosis, 3 cases of neurodegenerative disease, 7 cases failed to obtain positive pathological diagnosis. The total rate of positive diagnosis was 94.4%, the positive rate in MRS-guided stereotactic biopsy group was 98.4% (63/64), the positive rate of conventional MRI-guided biopsy group was 90.3% (56/62), and there was statistically significant difference between the two groups (χ(2) = 3.92, P = 0.047). Four cases presented with postoperative complications, the complication rate was 3.2% (4/126); the complications were cerebral hemorrhage associated with aphasia, epilepsy, subcutaneous hematoma, gastrointestinal bleeding, which were improved after treatment. CONCLUSIONS: MRS-guided stereotactic biopsy group has a higher positive rate than MRI-guided stereotactic biopsy group, indicating that this method can improve the positive rate of diagnosis, and thus will help to formulate treatment plan for brain lesion.

Application study of medical robots in vascular intervention.

BACKGROUND: Based on the background of minimally invasive surgery and applications of medical robots, a vascular interventional robotic system has been developed that can be used in the field of vascular intervention. METHODS: The robotic system comprises a propulsion system, an image navigation system and a virtual surgery training system. Integration of the three systems constitutes a vascular intervention prototype robotic system used to carry out in vitro vascular intervention and animal experiments. RESULTS: On a transparent glass vascular model, a catheter was shown to enter an arbitrary branch of the vascular model with catheter motion meeting the requirements of clinical vascular intervention surgery (VIS); i.e. error band of catheter motion < 0.5 mm. In the animal experiments, 1.33-2.00 mm (4F-6F) diameter catheters were selectively inserted successfully into predefined targets in the animal, such as the renal, cardiovascular and cerebrovascular artery. Compared with conventional manual surgery, the time for robotic surgery is a little longer. There were no operative complications in the animal experiments. CONCLUSIONS: These simulation and animal study results demonstrate that this vascular interventional robotic system allows doctors to perform angiography remotely and prevents them from radiation exposure. The system may be the basis for further clinical applications of vascular intervention.

[Clinical experience of stereotactic biopsy for the brain lesions].

OBJECTIVES: To investigate the methodology of diversified advanced image-guided stereotactic biopsy for the brain lesions, and its diagnostic significance and experience in nervous system diseases. METHODS: Retrospectively reviewed 1187 cases of brain lesions underwent image-guided stereotactic biopsy from December 1987 to January 2009. There were 694 male (58.5%) and 493 female (41.5%) patients, aged from 1 to 85 years (average 39.7 years). There were 607 cases in CT-guided, including positron emission computed tomography (PET) guided stereotactic biopsy; 580 cases in MRI-guided, including proton magnetic resonance spectroscopy ((1)H-MRS) guided stereotactic biopsy. Routine frame was used in 726 cases and frameless stereotactic biopsy in 461 cases, including neuroendoscopic biopsy in 28 cases, guided by computer assisted surgery (CAS) computer-assistant robot. In the early 450 cases, CT/MRI images films were employed to measure the coordinates of the target by hand, while in the late 737 cases, computer-assistant planning software rebuilt the CT/MRI images and figured out the optimal neurosurgical path for biopsy. RESULTS: The positive diagnosis rate of biopsy was 97.4%, 983 (82.8%) cases were diagnosed pathologically as brain tumors, and 173 (14.6%) cases as non-tumor diseases. The tumors mainly including neuroglioma, metastatic tumor, primary central nervous system lymphoma and germ cell tumors. In non-tumor diseases, mainly including multiple sclerosis, tumefactive demyelinating lesion, neurodegenerative disease, inflammation and parasite. The biopsy operation caused small hematoma without neurological deficits in 20 cases (1.7%), and caused large hematoma (> 10 ml) which need neurosurgical treatment (catheterization or craniotomy evacuation of hematoma) in 9 cases (0.8%). Hemorrhage associated with biopsy caused 3 cases (0.3%) death. There were no severe intracranial infection cases. CONCLUSIONS: The stereotactic biopsy with advanced image-guided technique represents a safe, reliable and minimally invasive method for pathological diagnosis of intracranial lesions. Moreover, the developments of biochemical imaging gives a new concept to the stereotactic biopsy.

[Experimental study of angiography using vascular interventional robot].

OBJECTIVE: To assess the feasibility and safety of vascular interventional surgery by using vascular interventional robot system (VIRS). METHODS: VIRS included image navigation systems and body propulsion systems, and adopted a master-slave structure. The surgeon sat at the master site, sending controlling instructions to the robot fixed at the slave site, and then the robot translated these instructions into catheter motion. A 3D vascular model was reconstructed so that the surgeon can perform surgical planning easily. In glass model and animal experiments, the surgeon remotely controlled VIRS, which inserted a catheter into predefined targets, and the catheter positioning error and robotic surgery time were measured. RESULTS: The robot was initially tested on a glass vascular model. Under robotic manipulation, the catheter could enter an arbitrary branch of the vascular model. The catheter positioning error was less than 1 mm. Then robotic interventional surgery was performed successfully in ten adult dogs. The renal artery and the vertebral artery angiography carried out smoothly without complication. Experiment took 35 minutes, and the time what staff exposed to the digital subtraction angiography (DSA) machine was 0 minute. CONCLUSION: Vascular interventional surgical robot system is safe and feasible, and can achieve the catheter remote operation, meet the requirements of angiography basically.

Clinical study of transplantation of neural stem cells in therapy of inherited cerebellar atrophy.

OBJECTIVE: To study the clinical effect of neural stem cell transplantation in the treatment of inherited cerebellar atrophy (CA). METHODS: The cells from human fetal cerebellum (8-10 weeks of gestation) were grown and expanded in vitro. The cultured neurospheres were then planted into the dentate nuclei of patients by stereo tactic operation. Totally, 12 patients (7 males and 5 females with age ranging 22-62 years, mean 43 years) were treated by this operation from August 2006 to August 2008. RESULTS: The cells of fetal cerebellum were expanded by 10(7) folds in undifferentiated state in the culture. After the operation, no rejection was detected. Follow up, the effective rates were 58.3% after 3 months, 75.0% after 6 months, and 66.7% for 12-24 months (mean 18 months). CONCLUSION: The transplantation of in vitro cultured neural stem cell is a feasible and effective treatment for inherited CA, but the long term effectiveness need to be taken in consideration.

[The expressional alterations of CSF-1R after ischemic injury of cerebral cortex].

AIM: To observe the expressional alterations of colony stimulating factor-1 receptor (CSF-1R) after ischemic injury of cerebral cortex, and study the function of colony stimulating factor-1 (CSF-1)/CSF-1R signal during the process of ischemic injury and repair of central nervous system (CNS). METHODS: We examined the distribution and expression of CSF-1R in normal brain tissues and ischemic brain tissues by immunohistology and Western blot analysis. RESULTS: The expression of CSF-1R in neurons could be up-regulated by ischemic injury in CNS. CONCLUSION: CSF-1/CSF-1R might take part in the process of ischemic injury and repair.

[Diagnosis and radiotherapy of germinomas arising in basal ganglia and thalamus].

OBJECTIVE: To summarize the clinical characteristic and radiotherapeutic effect of germinomas arising in basal ganglia and thalamus. METHODS: The clinical data of 13 cases were reviewed retrospectively. All cases were pathologic diagnosis through stereotactic biopsy. Gamma-knife or ordinary irradiation were 2 cases respectively and the combined therapy with interstitial brachytherapy as foundation were 9 cases. RESULT: All cases were male, median age of 16.1 years. Hemiparesis and ataxia were major symptoms, some cases were accompanied with precocious puberty. Imaging manifested intratumoral cystic components represented 76.9% of all lesions, calcification represented 30.8%, ipsilateral cerebral and brain stem hemiatrophy represented 46.2%, cerebral white matter invasion through internal capsule or corpus callosum represented 30.8%. One case died because of late complication and 12 cases had achieved satisfied therapeutic effect (the mean followed-up period was 40.6 months). Tumor-control were effective. CONCLUSIONS: The clinical manifestation and imaging characteristics are helpful to diagnosis. Stereotactic biopsy make the affirmatory diagnosis. Operative total-removal is impossible because of deep location, neighbour of vital structure and invasion. The combined therapy with interstitial brachytherapy was effective.

[Clinical analysis of 1434 cases of frameless stereotactic operation].

OBJECTIVE: Stereotactic operations were performed using a frameless stereotactic instrument manufactured by CAS-R-2 instead of traditional stereotactic frame. The aim of this study was to assess the clinical usefulness, accuracy and safety of frameless stereotactic instrument. METHODS: The clinical data of 1434 patients was retrospectively reviewed. The mean age was 30.7 years (from 0.2 to 89.0 years). Each patient underwent frameless CT/MRI image-guided stereotactic surgery by this robot system from January 1997 to January 2006. The accuracy of position and improvement of symptom were observed. The averaged period of followed-up was 24 months (from 3 to 48 months). RESULTS: The surgical procedures were performed successfully in all cases. All targets were pointed accurately at first time during the operation. The total effective rate was 93.3% without serious operation related complications. CONCLUSIONS: Compared with the traditional stereotactic operations, this method has some advantages, such as releasing the patient's pain, convenience the doctors, extending the range of indications and increasing the safety and effective of operation.

[Identification of novel genes related to glioma by oligonucleotide microarray].

OBJECTIVE: To identify the genes differentially expressed in development of human glioma, and to study the expression of some genes in different grade gliomas. METHODS: Oligonucleotide microarray (including 218 genes related to neural system development) was adopted and hybridized with probes which were prepared from the total RNAs of glioma specimens and normal brain tissues. Differentially expressed genes between the normal tissues and glioma tissues were assayed after scanning oligonuceltide microarray with ScanArray 4000, and some of these genes such as smad1, Hmp19 and TRIP3 were verified by real-time quantitative PCR(real-time-Q-PCR) method. RESULTS: In comparison with the genes in the normal brain tissue, 5 down-regulated and 5 up-regulated genes in glioma specimens were revealed by means of microarrays, and the expression of smad1, Hmp19 and TRIP3 were verified by real-time-Q-PCR assay. CONCLUSION: Multiple genes play important roles in development of glioma. cDNA microarray technology is a powerful technique in screening for differentially expressed genes between glioma tissues and normal brain tissues. This study is helpful for judgement of invasion and prognosis of gliomas, and provides more target genes for targeted therapy.

[Clinical application of robotic tele-manipulation system in stereotactic surgery].

OBJECTIVE: To assess the clinical usefulness, accuracy, and safety of tele-manipulation for frameless stereotactic surgery using the CAS-R-5 robot system. METHODS: We prospectively evaluated 32 patients underwent tele-manipulation of frameless stereotactic operations from Sep. 2005 to Sep. 2006. Tele-manipulations were performed via a digital data network by a neurosurgeon in Beijing while the patients were located in Yan'an. The distance is 1300 kilometers away. The accuracy of location and improvement of symptom were observed after operation. The period of follow-up was from 3 to 14 months (the average was 12 months). RESULTS: The surgical operations in 32 cases were successful. Remote fiducial registration was performed with a mean accuracy of 1. 50 mm and the standard difference were 0.32 mm between the planned and actual target. There were no complications. CONCLUSIONS: Diagnosis and treatment for intracranial disease by tele-manipulation frameless stereotactic surgeries are reliable and safe.