Post-resection Cavity Lavage of High Grade Glioma With a Novel Drug Combination: A Case Report.

BACKGROUND: High grade gliomas are the most common and most lethal primary cancers of the central nervous system. CASE REPORT: We herein present a case report of a long-term surviving 36-year-old female diagnosed with high grade glioma, for which she underwent neurosurgery with a gross total removal of the tumor. Shortly thereafter (<3 months) she was readmitted in a desolate state due to a large recurrence. After Ethical Committee approval, proper explanation, and consent from spouse, she was subjected to a reoperation involving a post-operative infusion into the excised tumor cavity, containing a mixture of a non-physiological amino acid in millimolar concentration and a proapoptotic drug in micromolar concentration. The patient tolerated the treatment well and was discharged in a stable state thereafter. A series of follow ups revealed successive clinical improvements and after 4-6 months, she had recovered with mild left hemiparesis, meaning that she was able to carry out activities of daily living independently. Now, 5.5 years later, after the recurrence and the infusion therapy, she continues to have a mild left hemiparesis and her MRI with contrast shows no evidence of tumor. CONCLUSION: Continuous intratumoral infusion therapy with an artificial amino acid combined with a proapoptotic drug results in complete glioma cell lysis both in vitro and in vivo.

Indian Society of Pediatric Neurosurgery Consensus Guidelines on Preventing and Managing Shunt Infection: Version 2020-21.

BACKGROUND: Shunt infection is the most significant morbidity associated with shunt surgery. Based on the existing literature for the prevention and management of shunt infection, region and resource-specific recommendations are needed. METHODS: In February 2020, a Guidelines Development Group (GDG) was created by the Indian Society of Paediatric Neurosurgery (IndSPN) to formulate guidelines on shunt infections, which would be relevant to our country and LMIC in general. An initial email survey identified existing practices among the membership of the IndSPN, and eight broad issues pertaining to shunt infection were identified. Next, members of the GDG performed a systematic review of the literature on the prevention and management of shunt infection. Then, through a series of virtual meetings of the GDG over 1 year, evidence from the literature was presented to all the members and consensus was built on different aspects of shunt infection. Finally, the guidelines document was drafted and circulated among the GDG for final approval. Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to grade the evidence and strength of recommendation. RESULTS: The guidelines are divided into eight sections. Level I and Level II evidence was available for only five recommendations and led to a moderate level of recommendations. Most of the available evidence was at Level III and below, and hence the level of recommendation was low or very low. A consensus method was used to provide recommendations for several issues. CONCLUSIONS: Although most of the recommendations for the prevention and management of shunt infections are based on a low level of evidence, we believe that this document will provide a useful reference to neurosurgeons not only in India but also in other low and middle income countries. These guidelines need to be updated as and when new evidence emerges.

Functional recovery after transplantation of bone marrow-derived human mesenchymal stromal cells in a rat model of spinal cord injury.

BACKGROUND AIMS: Spinal cord injury (SCI) is a medically untreatable condition for which stem cells have created hope. Pre-clinical and clinical studies have established that these cells are safe for transplantation. The dose dependency, survivability, route of administration, cell migration to injury site and effect on sensory and motor behavior in an SCI-induced paraplegic model were studied. METHODS: A spinal cord contusion injury model was established in rats. Bone marrow (BM) mesenchymal stromal cells (MSC) were tagged to facilitate tracing in vivo. Two different doses (2 and 5 million cells/kg body weight) and two different routes of infusion (site of injury and lumbar puncture) were tested during and after the spinal shock period. The animals were tested post-transplantation for locomotor capacity, motor control, sensory reflex, posture and body position. Stem cell migration was observed 1 month post-transplantation in spinal cord sections. RESULTS: The overall results demonstrated that transplantation of BM MSC significantly improved the locomotor and sensory behavior score in the experimental group compared with the sham control group, and these results were dose dependent. All the infused stem cells could be visualized at the site of injury and none was visualized at the injected site. This indicated that the cells had survived in vivo, were probably chemoattracted and had migrated to the lesion site. CONCLUSIONS: MSC transplanted with a lumbar puncture method migrate to the site of injury and are the most suitable for SCI healing. These cells demonstrate a dose-dependent effect and promote functional recovery when injected during or after the spinal shock period.

Ex vivo-expanded autologous bone marrow-derived mesenchymal stromal cells in human spinal cord injury/paraplegia: a pilot clinical study.

BACKGROUND AIMS: Spinal cord injury (SCI) is a medically untreatable condition for which stem cells have created hope in the last few years. Earlier pre-clinical reports have shown that transplantation of bone marrow (BM) mesenchymal stromal cells (MSC) in SCI-simulated models can produce encouraging results. In a clinical pilot study, we investigated the growth kinetics of BM MSC from SCI patients, their safety and functional improvement post-transplantation. METHODS: Thirty patients with clinically complete SCI at cervical or thoracic levels were recruited and divided into two groups based on the duration of injury. Patients with <6 months of post-SCI were recruited into group 1 and patients with >6 months of post-SCI were included into group 2. Autologous BM was harvested from the iliac crest of SCI patients under local anesthesia and BM MSC were isolated and expanded ex vivo. BM MSC were tested for quality control, characterized for cell surface markers and transplanted back to the patient via lumbar puncture at a dose of 1 x 10(6) cells/kg body weight. RESULTS: At the time of writing, three patients had completed 3 years of follow-up post-BM MSC administration, 10 patients 2 years follow-up and 10 patients 1 year follow-up. Five patients have been lost to follow-up. None of the patients have reported any adverse events associated with BM MSC transplantation. CONCLUSIONS: The results indicate that our protocol is safe with no serious adverse events following transplantation in SCI patients. The number of patients recruited and the uncontrolled nature of the trial do not permit demonstration of the effectiveness of the treatment involved. However, the results encourage further trials with higher doses and different routes of administration in order to demonstrate the recovery/efficacy if any, in SCI patients.

Innovative approach for prevention and treatment of post subarachnoid hemorrhage vasospasm: A preliminary report.

More than one third of patients with subarachnoid hemorrhage (SAH) develop clinically significant vasospasm, as a leading morbidity and mortality factor for these patients. It is widely accepted that a) Degradation products of blood are the causative factors of vasospasm b) The amount of subarachnoid blood seen on admission CT is correlated to the risk of vasospasm c) Reducing the subarachnoid clot burden at the time of surgery reduces the risk of vasospasm. But there is no existing method to clear the blood from subarachnoid spaces satisfactorily. We have evaluated safety and feasibility of fluid exchange catheter system in SAH, to achieve this goal. We were successful in clearing cisternal blood in three patients with aneurysmal rupture with fluid exchange catheter system. Baseline CT scan of brain was performed immediately after the surgery and then at the end of irrigation. The amount of subarachnoid blood was evaluated. This innovative, fluid exchange catheter system infuses and aspirates micro volumes of drug solution in a cyclic mode, ensuring isobaric exchange of fluids. The result is good clearance of blood in subarachnoid spaces were seen in all the patients. Also, significant improvement in neurological deficits secondary to vasospasm was seen. We conclude that the fluid exchange catheter system is safe and adoptable in neurosurgical practice.

Diffusion tensor imaging in spinal cord injury.

BACKGROUND AND PURPOSE: To assess the feasibility of spinal tractography in patients of spinal cord injury vs a control group and to compare fractional anisotropy (FA) values between the groups. MATERIALS AND METHODS: Diffusion tensor imaging (DTI) was performed in the spinal cord of 29 patients (18 patients and 11 controls). DTI was done in the cervical region if the cord injury was at the dorsal or lumbar region and in the conus region if cord injury was in the cervical or dorsal region. FA was calculated for the patients and the controls and the values were compared. RESULTS: The mean FA value was 0.550±0.09 in the control group and 0.367±0.14 in the patients; this difference was statistically significant (P=0.001). CONCLUSION: Spinal tractography is a feasible technique to assess the extent of spinal cord injury by FA, which is reduced in patients of spinal cord injury, suggesting possible Wallerian degeneration. In future, this technique may become a useful tool for assessing cord injury patients after stem cell therapy, with improvement in FA values indicating axonal regeneration.

Fulminant hepatic failure after repeated exposure to isoflurane.

Inhalational agents are used routinely for maintenance of anaesthesia. Post anaesthesia hepatic failure has been documented following exposure to halothane. However, there are very few reports of such complications following isoflurane anaesthesia. A 6-year-old child developed fulminant hepatic failure 2 days following craniotomy under general anaesthesia. There was no evidence of viral, autoimmune, or metabolic causes of hepatitis. No other medications known to cause hepatitis, except low dose paracetamol, were administered. The clinical and histological picture of our case is similar to that of halothane hepatitis, which has a significant mortality rate. We report this as a possible fulminant hepatic failure resulting from exposure to isoflurane anaesthesia.

Establishment of a brain tumor tissue repository in India: maintaining quality standards.

Tumor tissue repositories (TTRs) play a pivotal role in both basic and translational research by acting as a conduit to facilitate innovative research, thereby providing solutions to treat the incurable disease--'Cancer'. One of the fundamental requirements to achieve this goal would be the acquisition of high quality tumor tissue specimens that are stored in such a manner that its integrity is preserved. Further, a quality system should be in place that assures the compliance of procedures that are the key to a smooth functioning of all the inter-related departments that play a key role in the entire operations. To address this, we have initiated an effort to build a tumor tissue repository of brain tumor tissues in the Southern part of the Indian sub-continent. One of the cardinal features of brain tumors is the heterogeneity, both phenotypically and genotypically. Moreover, significant gaps exist in current understanding of the molecular pathways involved in the genesis, progression, and biological and clinical behavior of brain tumors. We hope that our initiative will provide researchers accessibility to a reserve of high quality tissues in this part of the globe. We have created and validated a complete histology service including tissue processing, embedding, sectioning and H&E staining for fixed tissues, in addition to creating and staining frozen sections. To our knowledge, such a structured initiative to store brain tumor samples is the first of its kind in the India.

Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease for which stem cell research has created hope in the last few years. Seven PD patients aged 22 to 62 years with a mean duration of disease 14.7+/-7.56 years were enrolled to participate in the prospective, uncontrolled, pilot study of single-dose, unilateral transplantation of autologous bone-marrow-derived mesenchymal stem cells (BM-MSCs). The BM-MSCs were transplanted into the sublateral ventricular zone by stereotaxic surgery. Patients were followed up for a period that ranged from 10 to 36 months. The mean baseline "off" score was 65+/-22.06, and the mean baseline "on" score was 50.6+/-15.85. Three of 7 patients have shown a steady improvement in their "off"/"on" Unified Parkinson's Disease Rating Scale (UPDRS). The mean "off" score at their last follow-up was 43.3 with an improvement of 22.9% from the baseline. The mean "on" score at their last follow-up was 31.7, with an improvement of 38%. Hoehn and Yahr (H&Y) and Schwab and England (S&E) scores showed similar improvements from 2.7 and 2.5 in H&Y and 14% improvement in S&E scores, respectively. A subjective improvement was found in symptoms like facial expression, gait, and freezing episodes; 2 patients have significantly reduced the dosages of PD medicine. These results indicate that our protocol seems to be safe, and no serious adverse events occurred after stem-cell transplantation in PD patients. The number of patients recruited and the uncontrolled nature of the trial did not permit demonstration of effectiveness of the treatment involved. However, the results encourage future trials with more patients to demonstrate efficacy.

Differential responses of tumors and normal brain to the combined treatment of 2-DG and radiation in glioablastoma.

2-Deoxy-D-glucose (2-DG), an inhibitor of glucose transport and glycolysis, enhances radiation damage selectively in tumor cells by modulating damage response pathways resulting in cell death in vitro and local tumor control. Phase I and II clinical trials in patients with malignant glioma have shown excellent tolerance to a combined treatment of orally administered 2-DG and hypofractionated radiotherapy without any acute toxicity and late radiation damage. Phase III efficacy trials are currently at an advanced stage. Re-exploratory surgery performed in 13 patients due to persistent symptoms of elevated ICP and mass effect at different follow-up periods revealed extensive tumor necrosis with well-preserved normal brain tissue adjoining the tumor included in the treatment volume as revealed by a histological examination. These observations are perhaps the first clinical evidences for differential effects of 2-DG on tumors and normal tissues in conformity with earlier in vitro and in vivo studies in normal and tumor-bearing mice.