Prediction of pyramidal tract side effect threshold by intra-operative electromyography in subthalamic nucleus deep brain stimulation for patients with Parkinson's disease under general anaesthesia.

Introduction: In DBS for patients with PD, STN is the most common DBS target with the sweet point located dorsal ipsilaterally adjacent to the pyramidal tract. During awake DBS lead implantation, macrostimulation is performed to test the clinical effects and side effects especially the pyramidal tract side effect (PTSE) threshold. A too low PTSE threshold will compromise the therapeutic stimulation window. When DBS lead implantation is performed under general anaesthesia (GA), there is a lack of real time feedback regarding the PTSE. In this study, we evaluated the macrostimulation-induced PTSE by electromyography (EMG) during DBS surgery under GA. Our aim is to investigate the prediction of post-operative programming PTSE threshold using EMG-based PTSE threshold, and its potential application to guide intra-operative lead implantation. Methods: 44 patients with advanced PD received STN DBS under GA were studied. Intra-operative macrostimulation via EMG was assessed from the contralateral upper limb. EMG signal activation was defined as the amplitude doubling or greater than the base line. In the first programming session at one month post-operation, the PTSE threshold was documented. All patients were followed up for one year to assess clinical outcome. Results: All 44 cases (88 sides) demonstrated activations of limb EMG via increasing amplitude of macrostimulation the contralateral STN under GA. Revision tracts were explored in 7 patients due to a low EMG activation threshold (<= 2.5 mA). The mean intraoperative EMG-based PTSE threshold was 4.3 mA (SD 1.2 mA, Range 2.0-8.0 mA), programming PTSE threshold was 3.7 mA (SD 0.8 mA, Range 2.0-6.5 mA). Linear regression showed that EMG-based PTSE threshold was a statistically significant predictor variable for the programming PTSE threshold (p value <0.001). At one year, the mean improvement of UPDRS Part III score at medication-off/DBS-on was 54.0% (SD 12.7%) and the levodopa equivalent dose (LED) reduction was 59.5% (SD 23.5%). Conclusion: During STN DBS lead implantation under GA, PTSE threshold can be tested by EMG through macrostimulation. It can provide real-time information on the laterality of the trajectory and serves as reference to guide intra-operative DBS lead placement.

Non-mitotic proliferation of malignant cancer cells revealed through live-cell imaging of primary and cell-line cultures.

INTRODUCTION: Anti-mitosis has been a key strategy of anti-cancer therapies, targeting at a fundamental property of cancer cells, their non-controllable proliferation due to overactive mitotic divisions. For improved anti-cancer therapies, it is important to find out whether cancer cells can proliferate independent of mitosis and become resistant to anti-mitotic agents. RESULTS: In this study, live-cell imaging was applied to both primary-cultures of tumor cells, and immortalized cancer cell lines, to detect aberrant proliferations. Cells isolated from various malignant tumors, such as Grade-III hemangiopericytoma, atypical meningioma, and metastatic brain tumor exhibit distinct cellular behaviors, including amoeboid sequestration, tailing, tunneling, nucleic DNA leakage, as well as prokaryote-like division such as binary fission and budding-shedding, which are collectively referred to and reported as 'non-mitotic proliferation' in this study. In contrast, benign tumors including Grade-I hemangiopericytoma and meningioma were not obvious in such behaviors. Moreover, when cultured in medium free of any anti-cancer drugs, cells from a recurrent Grade-III hemangiopericytoma that had been subjected to pre-operation adjuvant chemotherapy gradually shifted from non-mitotic proliferation to abnormal mitosis in the form of daughter number variation (DNV) and endomitosis, and eventually regular mitosis. Similarly, when treated with the anti-cancer drugs Epirubicin or Cisplatin, the cancer cell lines HeLa and A549 showed a shift from regular mitosis to abnormal mitosis, and further to non-mitosis as the dominant mode of proliferation with increasing drug concentrations. Upon removal of the drugs, the cells reversed back to regular mitosis with only minor occurrences of abnormal mitosis, accompanied by increased expression of the stem cell markers ALDH1, Sox, Oct4 and Nanog. CONCLUSIONS: The present study revealed that various types of malignant, but not benign, cancer cells exhibited cellular behaviors indicative of non-mitotic proliferation such as binary fission, which was typical of prokaryotic cell division, suggesting cell level atavism. Moreover, reversible transitions through the three modes of proliferation, i.e., mitosis, abnormal mitosis and non-mitosis, were observed when anticancer drug concentrations were grossly increased inducing non-mitosis or decreased favoring mitosis. Potential clinical significance of non-mitotic proliferation in cancer drug resistance and recurrence, and its relationship with cancer stem cells are worthy of further studies.

Phase I/II randomized controlled trial of autologous bone marrow-derived mesenchymal stem cell therapy for chronic stroke.

AIM: To examine the safety and efficacy of mesenchymal stem cell (MSC) therapy for intracerebral haemorrhage with neurological dysfunctions for a year. METHODS: MSC were ex vivo expanded from 29 mL (17-42 mL) autologous bone marrow. Patients were randomized to have two intravenous injections of autologous MSC or placebos in four weeks apart. Neurological functions and clinical outcomes were monitored before treatment and at 12th, 16th, 24th, 36th and 60th week upon completion of the treatment. RESULTS: A mean of 4.57 × 107 (range: 1.43 × 107-8.40 × 107) MSC per infusion was administered accounting to 8.54 × 105 (2.65 × 105-1.45 × 106) per kilogram body weight in two occasions. There was neither adverse event at time of administration nor sign of de novo tumour development among patients after monitoring for a year post MSC therapy. Neuro-restoration and clinical improvement in terms of modified Barthel index, functional independence measure and extended Glasgow Outcome Scale were evident among patients having MSC therapy compared to patients receiving placebos. CONCLUSION: Intravenous administration of autologous bone marrow-derived MSC is safe and has the potential of improving neurological functions in chronic stroke patients with severe disability.