Introduction

In this chapter, we have focused on stem cell therapy for Cerebral Palsy (CP) which is a heterogeneous group of neurological disorders mainly observed in infants. It results due to a static brain lesion at the time of pregnancy or early life. The survival of CP children has increased due to advanced modern medicine which has led to their growing population. CP involves impairment of movement, muscle function, and cognitive functioning and the effects range from mild to severe. [3] Chronic motor disability along with intellectual disability, epilepsy, behavioral disorders, and sensory and perceptual disturbances are few of the complications seen in these patients. No biological intervention has been effective for CP and the standard approach is limited to supportive management strategies which do not address the core issue of neural tissue damage. Currently, stem cell based strategies have garnered attention due to their ability of neuroregeneration and neuroprotection in CP. We have discussed the clinical aspects of stem cell therapy in cerebral palsy supported by various human case studies and clinical trials. We have also enumerated our experience and results wherein our subjects were administered autologous bone marrow mononuclear cells. In our study it was found to be safe, feasible and efficacious and may be used as a combinatorial strategy with the currently available standard treatments. Here, we try to summarize the current vast knowledge available for stem cell therapy in cerebral palsy. Read more...

Abstract

Cerebral palsy is defined as motor impairment that limits activity, and is caused by non-progressive disruption during cerebral development in fetus or infant. The standard treatment is focused on rehabilitation and symptomatic management, which does not address the underlying brain damage. Recently cellular therapy has been seen as promising  strategy to improve function of damaged areas of brain. Many mechanisms of action are postulated including cytokine  release, angiogenesis, activation of satellite cells, decrease inflammation decrease neuronal apoptosis; and neuronal  regeneration. We present a case of a two year old girl with spastic cerebral palsy, who was administered autologous  bone marrow derived mononuclear cells intrathecally. Six months after the therapy she showed significant functional  improvements along with correlating dramatic changes in Positron Emission Tomography-Computed Tomography scan. These changes provide objective evidence of functional restoration of affected areas of brain by cellular therapy. Read more...

Abstract

Cerebral palsy is a nonprogressive heterogeneous group of neurological disorders with a growing rate of prevalence. Recently, cellular therapy is emerging as a potential novel treatment strategy for cerebral palsy. The various mechanisms by which cellular therapy works include neuroprotection, immunomodulation, neurorestoration, and neurogenesis. We conducted an open label, nonrandomized study on 40 cases of cerebral palsy with an aim of evaluating the benefit of cellular therapy in combination with rehabilitation. These cases were administered autologous bone marrow mononuclear cells intrathecally. The follow-up was carried out at 1 week, 3 months, and 6 months after the intervention. Adverse events of the treatment were also monitored in this duration. Overall, at six months, 95%of patients showed improvements. Thestudy population was further divided into diplegic, quadriplegic, and miscellaneous group of cerebral palsy. On statistical analysis, a significant association was established between the symptomatic improvements and cell therapy in diplegic and quadriplegic cerebral palsy. PET-CT scan done in 6 patients showed metabolic improvements in areas of the brain correlating to clinical improvements. The results of this study demonstrate that cellular therapy any accelerate the development, reduce disability, and improve the quality of life of patients with cerebral palsy.

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Abstract

Cerebral palsy (CP) is a non progressive, demyelinating disorder that affects a child’s development and posture and may be associated with sensation, cognition, communication and perception abnormalities. In CP, cerebral white matter is injured resulting in  the loss of oligodendrocytes. This causes damage to the myelin and disruption of nerve  conduction. Cell therapy is being explored as an alternate therapeutic strategy as there  is no treatment currently available for CP. To study the benefits of this treatment we have  administered autologous bone marrow mononuclear cells (BMMNCs) to a 12-year-old  CP case. He was clinically re-evaluated after six months and found to demonstrate positive clinical and functional outcomes. His trunk strength, upper limb control, hand  functions, walking stability, balance, posture and coordination improved. His ability to  perform activities of daily living improved.  On repeating the Functional Independence  Measure (FIM), the score increased from 90 to 113. A repeat positron emission tomography-computed tomography (PET-CT) scan of the brain six months after intervention  showed progression of the mean standard deviation values towards normalization which  correlated to the functional changes. At one year, all clinical improvements have remained. This indicated that cell transplantation may improve quality of life and have a  potential for treatment of CP. Read more...

Abstract

PET CT scan is one of the most sensitive neuroimaging techniques used to study brain metabolism. We used this technique to map changes occurring in the brain at a cellular level after intrathecal transplantation of autologous bone marrow mononuclear cells (BMMNCs) combined with neurorehabilitation in Cerebral Palsy (CP). CP is a group of non-progressive heterogeneous neurological disorders resulting in damage to the brain at or around birth. This damage leads to neurological deficits. The pathophysiology of CP is multifactorial. Hence, the management of CP should be multidisciplinary. Cellular transplantation has gained popularity in the treatment of CP. We administered a one and half year old female of dystonic CP with autologous bone marrow mononuclear cells (BMMNCs) twice in the period of 1 year and followed her up for 3 years. A comparative PET CT scan was performed af which showed significant improvement in periventricular areas which are typically damaged in cerebral palsy. This further led to functional improvements in oromotor skills, speech, balance, fine and gross motor activities and cognition. In the duration of 3 years, her GMFCS score improved from Level 5 to Level 4 and GMFM score improved from 3.92% to 9.24%. No adverse events were recorded in this period of follow up. The outcome of this case indicates that cellular therapy along with neurorehabilitation improves neuronal function and enhances functional recovery in CP patients. PET CT scan can also be used effectively to map the changes occurring after intervention. Read more...

Abstract

Cerebral palsy (CP), group of permanent nonprogressive clinical disorders inchildren, is caused by damage to the immature brain. Conventionally available treatments for CP are mainly targeted toward management of its symptoms. With the upcoming field of neurorestorative strategies, we are now able to repair the core brain damage in CP. There are various drugs, stem cells, etc, which have been implicated to have neurorestorative properties. Autologous bone marrow stem cells, umbilical cord stem cells, neural stem cells, and olfactory ensheathing cells have shown the safety and efficacy in preliminary studies. Here, we review the different medicines and cell types that have shown beneficial effects in clinical studies. We propose that combination strategies may be the future of neurorestoration.  Read more...

Abstract

Aims: Cerebral palsy (CP) is an umbrella term including a group of permanent disorders of development of movement and of posture causing activity limitation. Oxidative stress and glutamate mediated excitotoxicity are important mechanisms of injury to both the white matter and neurons in the developing brain resulting in motor deficits. No treatment measures are available that can repair the existing damage. Use of bone marrow stem cells for the treatment of CP has shown promise owing to their capacity for self-renewal, differentiation with a potential of neuroregeneration and secretory paracrine effects. Methods: To study the efficacy of cell transplantation in CP, we administered autologous bone marrow mononuclear cells intrathecally to a 2.2-year-old female patient. She was followed up at 9 months and a repeat transplantation was administered. A second follow up was done 5 months after second transplantation. Gross Motor Function Classification System-Expanded & Revised (GMFCSE&R), Gross Motor Function Measure-88 (GMFM-88) and Functional Independence Measure for children (WeeFIM) were used as outcome measures to assess therapeutic efficacy. Results: 9 months after first transplantation, symptomatic improvements such as reduced spasticity, ability to crawl with reciprocal pattern, independent walking with Walker, independent transfer from bed to floor, improved biting and chewing and cognition were observed. On GMFCS-E&R she improved from level III to level II, GMFM-88 improved from 36.36% to 38.62% and WeeFIM improved from 34 to 38. These improvements were well supported by positron emission tomography-computed tomography which showed improved metabolism in bilateral cerebellum and medial temporal cortex. All these improvements were maintained even at 5 months' follow up post second transplantation. No adverse events were reported after the procedures or at follow ups. Conclusion: Intrathecal administration of autologous bone marrow mononuclear cells are safe and an effective therapeutic strategy in the management of CP.  Read more...

Abstract

Cerebral palsy (CP) encompasses a group of non- progressive disorders of movement and posture causing activity limitation or disability. Presently, the treatment options are limited with primary focus being on rehabilitation of the patients. Cellular therapy is being considered as an alternative therapeutic strategy. Our patient is11-year-old girl diagnosed as a case of mixed cerebral palsy with both spastic and dystonic components. She presented with complaints of poor sitting and walking balance, incoordination and faltering school grades. Autologous bone marrow derived mononuclear cells were administered intrathecally along with extensive neurorehabilitation.   Read more...

Abstract

Cellular therapy has gained acknowledgement as a novel modality for the treatment of Cerebral Palsy (CP) due to its neuro-regenerative and neuroprotective characteristics. CP affects movement and posture in childhood causing severe neuro-disability in children. The standard therapeutic approaches are seldom effective as they do not address the underlying neural damage.  In this case of 4 years 10 months old boy with diplegic dystonic CP, we administered autologous bone marrow mononuclear cells intrathecally. The patient underwent two cellular therapies at an interval of seven months. The follow up assessment was conducted at 3,7 and 13 months after the first cellular therapy. Improvements in voluntary control, muscle tone (spasticity and dystonia), balance, weight bearing of the upper limbs, oromotor skills and cognition were noted over the follow up period of 13 months. Gross motor function measure (GMFM) improved from 30.59 to 69.87 %, and Wee-Functional Improvement Measure (Wee-FIM) improved from 45 to 84. No adverse events were reported post cellular therapy. This case study highlights the clinical benefits of cellular therapy with corroborative improvements in the outcome scales in a unique case of diplegic dystonic CP. We recommend that its effectiveness should be established in a more comprehensive randomised controlled study.   Read more...

Abstract

Cerebral palsy (CP) is characterized by a non-progressive motor impairment related to brain injury early in development. It may be associated with other deficits such as intellectual disability, speech and language and oromotor problems. In many cases, the cause of CP may not be apparent. So, the current treatment options are mostly focused on the symptomatic management. Herein, we present a case of an eight year old child diagnosed as cerebral palsy with intellectual disability. He was administered with autologous bone marrow derived mononuclear cells intrathecally. Eight months after intervention, Gross Motor Function Measure (GMFM) scale score changed from 1.9 to 3.077 depicting improvement in movement. On follow up improvements were noticed in oromotor functions, neck control and sitting balance, awareness, understanding of surrounding. These functional improvements correlated with the improved brain metabolism in basal ganglia, cerebellum, hippocampus and thalamus as observed in Positron Emission Tomography-Computed Tomography (PET-CT) Scan. No major side effects were recorded after intervention. The results suggest that autologous bone marrow derived mononuclear cells have a significant potential as a therapeutic strategy for CP.   Read more...

Abstract

Cerebral palsy (CP) represents a group of developmental disorders leading to neurodisability in the pediatric population. The 2008 Autism and Developmental Disabilities Monitoring Network (ADDM) CP Network revealed that nearly 7% of children with CP co-existed with autistic disorders. Here we present a case report of a six and a half year old child who presented with CP coexisting with autistic features. She underwent two cellular therapies with autologous bone marrow mononuclear administered intrathecally, followed by intensive neurorehabilitation. Over the span of 15 months post cellular therapies, improvements were seen in the walking balance, sitting tolerance, eye contact, clarity of speech, social interaction and voluntary control of the left upper limb with increased weight bearing capacity. There was a decrease from 96 to 82 on the ISAA scale. CARS score reduced from 30.5 to 25 after the two cellular therapies. GMFM score showed an improvement from 64.31% to 79.96% and FIM increased from 40 to 49. No adverse events were observed. This case report supports the evidences suggesting that cellular therapy along with rehabilitation augments the recovery processes in patients with CP coexisting with autistic features. Further clinical studies are required to establish the therapeutic potential of cellular therapy taking into consideration the multifaceted symptomatic presentations in CP.   Read more...

Abstract

Background: Cerebral palsy (CP) is a non-progressive disorder. The global incidence of neonatal CP is 1-5 per 1000 live births where 45% of children with CP have a comorbid intellectual disability (ID). This affects the quality of life and reduces life expectancy of affected individuals.

Methods and findings: With an aim to study the efficacy and safety of autologous bone marrow mononuclear cells (BMMNCs) transplantation in CP with ID, we administered a 17-year-old boy with BMMNCs along with neurorehabilitation. On follow up after 6 months, clinical improvements were recorded in speech, fine motor skills, ambulation, oromotor skills, social awareness, cognitive skills, memory and attention. Comparative Positron Emission Tomography- Computer Tomography scan of brain before and six months after cell transplantation revealed improved metabolism in the anterior cingulate cortex, left caudate head, thalamus, medial temporal cortex, cerebellum. Intelligent Quotient improved from 21 to 29. Social age according to the Vineland Social Maturity Scale was increased by 1 year. Functional Independence Measure and Gross Motor Functional Measure increased from 22 to 26 and 74.65 to 76 respectively. On Gross Motor Functional Classification System, he improved from IV to III.

Conclusion: These changes suggest that BMMNCS transplantation along with neurorehabilitation was effective for this child suffering from CP with ID.

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Abstract

The safety and efficacy of cellular transplantation has been established in pediatric cerebral palsy (CP). However, not many studies have been performed to determine its efficacy in adult CP. Adults with CP are at a higher risk of  secondary complications. They have an overall lower tness level, reduced muscle mass, neuromuscular inefficiency, and limited physical activities. Effects of long-term rehabilitation also eventually plateau in these individuals. To study the effect of cellular transplantation in adult CP, we administered a 27-year-old female, diagnosed as spastic triplegic cerebral palsy, with autologous bone marrow mononuclear cells intrathecally followed by neurorehabilitation. The patient was followed up after 4 and 6 months of transplantation. She was then administered a second transplantation and later followed up after 5 months.  Improvements were noted in voluntary control, spasticity, balance and gait. PET CT scan brain was performed before and 6 months after intervention to monitor the outcome of intervention at a cellular level. On the comparative PET CT scan, metabolic improvements were recorded in bilateral paracentral lobule, thalamus, medial temporal and cerebellum regions. No major adverse effects were noted after both the interventions. The results suggest that BMMNC transplantation is potentially safe and effective therapy for adults with CP. Hence, cellular transplantation in adult CP may help address the complications and improve their quality of life.   Read more...