Neuroregenerative-Rehabilitative Therapy for Spinal Cord Injury

Spinal cord injury is one of the leading causes of disability worldwide. Current mainstay treatment strategies consist of surgical and medical management in acute and subacute stage. Rehabilitative management in the chronic stage. None of the existing strategies can repair the damage to the spinal cord and recover neurological functioning. Stem cells have promising results in pre-clinical and clinical studies. Various pre-clinical studies have evidenced neuro-regenerative capabilities of stem cells and shown neural recovery. Clinical studies have also shown improvements in neurological functions and quality of life. This chapter discusses about different types of cells available, routes of administration available to transplant these cells, dosages of cell and optimum time after injury at which cells should be transplanted based on world-wide literature. We have also discussed results following our protocol of intrathecal transplantation of autologous bone marrow mononuclear cells. Although, not a cure, stem cell therapy further improves quality of life, functional independence and reduces secondary complications when combined with existing treatment strategies; neuroregenerative rehabilitative therapy

Stem Cell Therapy in Motor Neuron Disease

Motor neuron disease (MND) is an insidious, fatal disorder that progresses with the selective loss of anterior horn cells of the spinal column. Over 150 years since it was first described, various therapeutic approaches have been tested in the quest of a cure but with little success. Current standard therapy only improves lifespan by a few months; palliative care is the only option available for patients. Stem cell therapy is a potent approach for the treatment of this devastating disease. A multitude of vitalizing effects, both paracrine and somatic, a robust safety profile, as well as ease of availability make a strong case for using these cells for therapeutic purposes. Coupled with rigorous rehabilitation, this powerful treatment modality has been shown to slow disease progression, improve quality of life, and increase survival, along with being well tolerated by amyotrophic lateral sclerosis (ALS)/MND patients. Compelling preclinical as well as clinical evidence abounds that stem cells hold great potential as a therapy for ALS/MND. Although not a definitive solution yet, stem cells have been verified to have slowed and/or halted disease progression in a subset of ALS/MND patients

Stem Cell Therapy in Pediatric Neurological Disabilities

Pediatric neurological disorders represent a major part of the disabilities worldwide. In over 10 decades of research to find a cure for these disorders, medical science has not been able to repair the underlying brain injury. This chapter focuses on recent advances in the application of stem cells as a therapeutic tool for some of the common neurodevelopmental disorders (cerebral palsy, autism, intellectual disability and muscular dystrophy). The mechanism of action of stem cells in each disorder has been explained. A review of clinical data has been described giving a clear understanding of current status of stem cell therapy in these disorders. Various factors influencing the outcome of stem cell therapy such as different types of cells, different routes of administration and dosage and frequency of transplantation have also been discussed. Our experience of treating these disorders is exhibited in the form of our published data. Use of novel monitoring tools such as MRI MSK and PET‐CT scan brain to track the changes occurring at cellular level after stem cell therapy are described. We also highlight the importance of a multidisciplinary approach of combining rehabilitation with stem cell therapy

Cell Therapy for Muscular Dystrophy

Muscular dystrophy is a major unmet medical need associated with an inevitable progressive muscle damage and loss of function. Currently, treatment is only symptomatic and supportive. This chapter focuses on cell therapy as a potential treatment approach for muscular dystrophy. Mechanism of action of cell therapy and its ability to alter disease pathology have been discussed. A review of preclinical and clinical studies has been presented with the advantages and shortcomings of various cell types. Rationale for our treatment protocol and experience of treating muscular dystrophy patients has been discussed. Our published results have shown the efficacy of the intrathecal and intramuscular administration of autologous bone marrow mononuclear cells in different types of muscular dystrophy patients. The scores on outcome measures such as 6-minute walk distance, North star ambulatory assessment, Brooke and Vignose scale, Functional independence measure, and manual muscle testing either improved or were maintained suggestive of slowing down disease progression. Efficacy and safety of the treatment was also studied using comparative MRI-MSK and EMG showing decreased fatty infiltration in various muscles post-cellular therapy. Thus, it was found that autologous BMMNC transplantation is a safe and effective treatment option and improves the quality of life of MD patients

Cerebellar glioblastoma multiforme with non-contiguous grade 2 astrocytoma of the temporal lobe in the same individual

Multicentric Gliomas, both supratentorial and infratentorial, with varying histopathological picture is extremely rare. We report a unique occurrence of such a combination in a 50-year-old man who presented with features of elevated intracranial pressure, ataxia and vertigo. Magnetic resonance imaging showed a diffuse non-enhancing lesion in the temporal lobe and insula and another non-contigous well defined enhancing lesion in the cerebellum. Both the lesions had mass effect. The lesions were decompressed; first the temporal lesion and then the cerebellar lesion. Histopathology revealed grade II astrocytoma in the temporal lobe and glioblastoma multiforme in the cerebellum. He recieved whole brain radiotherapy with which he showed symptomatic improvement and survived for 1.5 years

Comparison of methylprednisolone with dexamethasone in treatment of acute spinal injury in rats

476-480Effect of methylprednisolone sodium succinate (MPSS) and its comparison with dexamethasone in experimentally induced acute spinal cord compression in adult rats was studied. The rats were divided into group A (control) and group B, which was subdivided into B1, B2, B3 where MPSS was given after 1, 8 and 24 hr and B4 where dexamethasone was given after 1 hr of cord injury respectively. Proper neurological evaluation was done with mobility, running and climbing score. Recovery index was evaluated for 7 days. After sacrificing the rats, spinal cord was observed histopathologically. Mean recovery index and microscopic findings based on hemorrhage in gray and white matter, neuronal degeneration, hematomyelia and edema in white matter were recorded. The results suggested that MPSS was effective in promoting posttraumatic clinical and histological recovery and to a greater extent, when given 1 hr after trauma. MPSS is more effective than dexamethasone in reducing edema when both are given after interval of 1 hr

Brainstem gliomas – A clinicopathological study of 45 cases with p53 immunohistochemistry

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

Neuroprotective effects of vitamin E in cold induced cerebral injury in guinea pigs

180-184Significant reduction in hemorrhage (10 v/s 13), necrosis (2 v/s 4), cavitations (7 v/s 13), neuronal degeneration, perivascular and parenchymal inflammatory infiltrate (7 v/s 11) were observed in Vitamin E treated cold induced head injury in guinea pigs, evaluated post injury using the modified Benderson’s scale. The results suggest that Vitamin E is highly effective in promoting clinical and histopathological recovery in cold induced head injury in guinea pigs