ABSTRACT
BACKGROUND: Chronic Traumatic Brain Injury (TBI) is one of the common causes of longterm disability worldwide. Cell transplantation has gained attention as a prospective therapeutic option for neurotraumatic disorders like TBI. The postulated mechanism of cell transplantation which includes angiogenesis, axonal regeneration, neurogenesis and synaptic remodeling, may tackle the pathology of chronic TBI and improve overall functioning. METHODS: To study the effects of cell transplantation, 50 patients with chronic TBI were enrolled in an open label non-randomized study. The intervention included intrathecal transplantation of autologous bone marrow mononuclear cells and neurorehabilitation. Mean follow up duration was 22 months. Fifteen patients underwent second dose of cell transplantation, 6 months after their first intervention. Percentage analysis was performed to analyze the symptomatic improvements in the patients. Functional independence measure (FIM) was used as an outcome measure to evaluate the functional changes in the patients. Statistical tests were applied on the pre-intervention and post-intervention scores for determining the significance. Comparative Positron Emission Tomography- computed tomography (PET CT) scans were performed in 10 patients to monitor the effect of intervention on brain function. Factors such as age, multiple doses, time since injury and severity of injury were also analyzed to determine their effect on the outcome of cell transplantation. Adverse events were monitored throughout the follow up period. RESULTS: Overall 92% patients showed improvements in symptoms such as sitting and standing balance, voluntary control, memory, oromotor skills lower limb activities, ambulation, trunk & upper limb activity, speech, posture, communication, psychological status, cognition, attention and concentration, muscle tone, coordination, activities of daily living. A statistically significant (at p ≤ 0.05 with p-value 0) improvement was observed in the scores of FIM after intervention on the Wilcoxon signed rank test. Better outcome of the intervention was found in patients with mild TBI, age less than 18 years and time since injury less than 5 years. Ten patients who underwent a repeat PET CT scan brain showed improved brain metabolism in areas which correlated to the symptomatic changes. Two patients had an episode of seizures which was managed with medication. They both had an abnormal EEG before the intervention and 1 of them had previous history and was on antiepileptics. No other major adverse events were recorded. CONCLUSION: This study demonstrates the safety and efficacy of cell transplantation in chronic TBI on long term follow up. Early intervention in younger age group of patients with mild TBI showed the best outcome in this study. In combination with neurorehabilitation, cell transplantation can enhance functional recovery and improve quality of life of patients with chronic TBI. PET CT scan brain should be explored as a monitoring tool to study the efficacy of intervention.
ABSTRACT
BACKGROUND: Autism spectrum disorders [ASD] is a lifelong disability mainly affecting the development, communication, social interaction and behavior of an individual. Cell transplantation is emerging as a potential therapeutic strategy for ASD. Our previously published proof of concept study showed beneficial effects of cell transplantation in ASD. This study shows effect of cell transplantation in a larger sample size of ASD patients. METHODS: 254 patients diagnosed with ASD on DSM V criteria were enrolled in this open label non-randomized study. The intervention included intrathecal transplantation of autologous bone marrow mononuclear cells and neurorehabilitation. On mean follow up of 7.50 months, percentage analysis was performed on all symptomatic changes. Changes in outcome measures, Indian Scale for Assessment of Autism [ISAA] and Childhood Autism Rating Scale [CARS], were analyzed statistically using Wilcoxon Signed-Rank Test. Comparative analysis of Positron Emission Tomography [PET CT] scan brain, performed before and 6 months after intervention, was done in 86 patients to monitor the outcome at cellular level. Change in the standardized uptake values was statistically evaluated using T-Test [P≤0.05]. RESULTS: Improvements were observed in eye contact, attention and concentration, hyperactivity, sitting tolerance, social interaction, stereotypical behavior, aggressiveness, communication, speech, command following and self-stimulatory behavior. Statistically significant improvement was observed in scores of ISAA and CARS after intervention. A significantly better outcome of the intervention was found in patients at younger age and with shorter duration of disease [<5 years from time of diagnosis]. 86 patients who underwent a repeat PET CT scan showed improved brain metabolism after intervention in areas which correlated to the symptomatic changes. No major procedure related adverse events were recorded. However, 5 patients, with history of seizure and abnormal EEG, had an episode of seizure which was managed using medications. Outcome of intervention in these patients was not affected by seizures as improvements were observed in them. CONCLUSION: The results of this study indicate that autologous bone marrow mononuclear cells in combination with neurorehabilitation are a safe and effective treatment modality for ASD. It improves the quality of life of patients and helps them to integrate in mainstream lifestyle.
ABSTRACT
Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive neurodegenerative disorder with fatal prognosis. Cellular therapy has been studied for ALS in various animal models and these advances have highlighted its potential to be a treatment modality. This is a retrospective controlled cohort study of total 57 patients. Out of these, 37 patients underwent autologous bone marrow mononuclear cell transplantation in addition to standard rehabilitation and Riluzole. Control group consisted of 20 patients who did not receive cell transplantation. The survival duration since the onset of the disease for both the groups was computed using a Kaplan-Meier Survival analysis and compared using log-rank test. Effect of age at onset, type of onset and lithium on survival duration in the intervention group was analyzed. Mean survival duration of patients in intervention group was 87.76 months which was higher than the control group mean survival duration of 57.38 months. Survival duration was significantly (p = 0.039) higher in people with the onset of the disease below 50 years of age. Limb onset and lithium also showed positive influence on the survival duration. Mean survival duration of the intervention group was also higher than the survival duration of ALS patients in previous epidemiological studies. In addition to the standard treatment with Riluzole, early intervention with combination of BMMNCs transplantation and Lithium may have a positive effect on the survival duration in ALS. Prospective randomized controlled studies with a larger sample size and rigorous methodology are required for conclusive findings.
ABSTRACT
BACKGROUND: Brainstem tumors represent 10% of central nervous system tumors, accounting for 30% of pediatric posterior fossa tumors. AIMS: The aim of this study was to clinicopathologically correlate 45 cases of brain stem gliomas and determine the occurrence and prognostic significance of p53 expression. MATERIALS AND METHOD: 45 cases of brain stem gliomas encountered during a 19-year period. 30 were diagnosed by surgical biopsy and 15 at autopsy. In 25 cases p53 immunohistochemistry (Avidin Biotinylated technique) was performed. The WHO brain tumor classification and Stroink's CT classification were applied. STATISTICAL ANALYSIS USED: Chi square test. RESULTS AND CONCLUSIONS: 51 % of gliomas were observed in the first decade of life. The female to male ratio was 1.04: 1. The commonest presenting features were cranial nerve palsies (33%) and cerebellar signs (29.8%). 55.55% of cases were located in the pons, 31.01% in the medulla and 13.33% in the midbrain. Diffuse astrocytomas were seen in 40 cases (5% were Grade I, 47.5%Grade II, 32.5% Grade III and 15% Grade IV) and pilocytic astrocytomas in 5 cases. Grade IV patients had 2- 3 mitoses /10 high power fields and had a poorer survival rate. Grade II astrocytomas were treated with excision and radiotherapy, while grade III and IV tumors were treated with radiotherapy and chemotherapy (CCNU). Improvement was noted in 20% of patients postoperatively. The outcome was better in patients who were treated surgically. p53 is a frequently mutated gene in brain stem astrocytomas. It was found in 50 % of glioblastoma multiforme, 28.57% of grade III astrocytoma and 12.5% of grade II astrocytoma, while grade 1 astrocytomas failed to express p53 protein. p53 positivity was more in high grade lesions, decreasing significantly in lower grade lesions.
