Degeneration and regeneration of the nervous system

Archives of disease in childhood. Fetal and neonatal edition

Cellular therapy is an emerging therapeutic modality with a great potential for the treatment of autism. Recent findings show that the major underlying pathogenetic mechanisms of autism are hypoperfusion and immune alterations in the brain. So conceptually, cellular therapy which facilitates counteractive processes of improving perfusion by angiogenesis and balancing inflammation by immune regulation would exhibit beneficial clinical effects in patients with autism. This is an open label proof of concept study of autologous bone marrow mononuclear cells (BMMNCs) intrathecal transplantation in 32 patients with autism followed by multidisciplinary therapies. All patients were followed up for 26 months (mean 12.7). Outcome measures used were ISAA, CGI, and FIM/Wee-FIM scales. Positron Emission Tomography-Computed Tomography (PET-CT) scan recorded objective changes. Out of 32 patients, a total of 29 (91%) patients improved on total ISAA scores and 20 patients (62%) showed decreased severity on CGI-I. The difference between pre- and postscores was statistically significant (P < 0.001) on Wilcoxon matched-pairs signed rank test. On CGI-II 96% of patients showed global improvement. The efficacy was measured on CGI-III efficacy index. Few adverse events including seizures in three patients were controlled with medications. The encouraging results of this leading clinical study provide future directions for application of cellular therapy in autism.

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Autologous Bone Marrow Mononuclear Cell Therapy for Autism: An Open Label Proof of Concept Study

Ventriculo-peritoneal (VP) shunting used in the treatment for hydrocephalus is associated with several complications. Mechanical failure of shunt is the commonest complication of all. Visceral/bowel perforation is an unusual but serious complication of VP shunting. This article reports our experience in the management of ten children who had VP Shunt catheter protrusion from anus. This is a retrospective study of ten patients who had VP shunt catheter protrusion from anus, admitted in the department of paediatric surgery between Jan 1996 and Dec 2005. The records of above ten cases were reviewed for their clinical presentation and management, etc. We had performed 398 VP shunt operations in the last 10 years. Two hundred and seventy one (68.09%) VP Shunts were done for congenital hydrocephalus of which 164 were done in infancy/neonatal period and 107 VP shunts were done in the age group of >1-12 years. One hundred and twenty-seven (31.90%) VP shunt operations were done for patients who had hydrocephalus as a complication following tubercular meningitis (TBM). Out of 398 VP shunts, ten patients (2.51%) had protrusion of the distal end of peritoneal catheter from anus without causing/leading to peritonitis. We observed a 08.29% mortality of all VP shunt operations. Protrusion of VP shunt catheter per rectum can occur without producing peritonitis. Formal exploration and localization of entry of VP shunt catheter in bowel is not mandatory. Mini laparotomy and revision of peritoneal part of shunt can be done if there is no shunt infection.

Trans-anal protrusion of ventriculo-peritoneal shunt catheter with silent bowel perforation: report of ten cases in children.

Biological cells are complex living machines that have garnered significant attention for their potential to serve as a new generation of therapeutic and delivery agents. Because of their secretion, differentiation, and homing activities, therapeutic cells have tremendous potential to treat or even cure various diseases and injuries that have defied conventional therapeutic strategies. Therapeutic cells can be systemically or locally transplanted. In addition, with their ability to express receptors that bind specific tissue markers, cells are being studied as nano- or microsized drug carriers capable of targeted transport. Depending on the therapeutic targets, these cells may be clustered to promote intercellular adhesion. Despite some impressive results with preclinical studies, there remain several obstacles to their broader development, such as a limited ability to control their transport, engraftment, secretion and to track them in vivo. Additionally, creating a particular spatial organization of the...

Engineering the Surface of Therapeutic “Living” Cells

The purpose of this multicenter observational clinical study was to evaluate the performance of a near-infrared (NIR)-based, non-invasive, portable device to screen for traumatic intracranial hematomas. Five trauma centers collected data using the portable NIR device at the time a computed tomography (CT) scan was performed to evaluate a suspected traumatic brain injury (TBI). The CT scans were read by an independent neuroradiologist who was blinded to the NIR measurements. Of 431 patients enrolled, 365 patients were included in the per-protocol population analyzed. Of the 365 patients, 96 were determined by CT scan to have intracranial hemorrhages of various sizes, depths, and anatomical locations. The NIR device demonstrated sensitivity of 88% (95% confidence interval [CI] 74.9,95.0%), and specificity of 90.7% (95% CI 86.4,93.7%), in detecting the 50 intracranial hematomas that were large enough to be clinically important (larger than 3.5 mL in volume), and that were less than 2.5 cm from the s...

Clinical evaluation of a portable near-infrared device for detection of traumatic intracranial hematomas.

Correspondence: Alok Sharma NeuroGen Brain and Spine Institute, Surana Sethia Hospital and Research Centre, Suman Nagar, Sion-Trombay Road, Chembur, Mumbai 400071, India Tel +91 022 2528 3706 Fax +91 022 2529 2250 Email alok276@gmail.com Background: Cell therapy is amongst the most promising treatment strategies in spinal cord injury (SCI) because it focuses on repair. There are many published animal studies and a few human trials showing remarkable results with various cell types. The level of SCI determines whether paraplegia or quadriplegia is present, and greatly influences recovery. The purpose of this study was to determine the significance of the clinical effects and long-term safety of intrathecal administration of autologous bone marrow-derived mononuclear cells, along with changes in functional independence and quality of life in patients with thoracolumbar SCI. Methods: We undertook a retrospective analysis of a clinical study in which a nonrandomized sample of 110 patients with thoracolumbar SCI underwent autologous bone marrow-derived mononuclear cell transplantation intrathecally and subsequent neurorehabilitation, with a mean follow-up of 2 years ± 1 month. Changes on any parameters were recorded at follow-up. The data were analyzed using the Wilcoxon’s signed-rank test and McNemar’s test. Functional Independence Measure and American Spinal Injury Association (ASIA) scores were recorded, and a detailed neurological assessment was performed. Results: Overall improvement was seen in 91% of patients, including reduction in spasticity, partial sensory recovery, and improvement in trunk control, postural hypotension, bladder management, mobility, activities of daily living, and functional independence. A significant association of these symptomatic improvements with the cell therapy intervention was established by the statistical analysis. Some patients showed a shift on the ASIA scale and changes in electrophysiological studies or functional magnetic resonance imaging. No major side effects were noted. Conclusion: In patients with thoracolumbar SCI, there were statistically significant beneficial effects, both symptomatic and functional, from intrathecal autologous bone marrow-derived mononuclear cell therapy and rehabilitation. This was a safe and viable therapeutic option with no long-term side effects at 2 years. This analytical study is an early documentation of cell therapy, and can be used as a guide to devise larger more refined clinical trials.

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Detailed analysis of the clinical effects of cell therapy for thoracolumbar spinal cord injury: an original study

Autism, the most severe form of autism spectrum disorder (ASD), is a complex neurodevelopmental disorder, characterized by language developmental delay, social skills impairment, communication problems, and restricted, repetitive, and stereotyped patterns of behavior. There is no cure for Autism; hence therapies and behavioral interventions are designed to remedy specific symptoms. We used autologous bone marrow derived mononuclear cells intrathecally in a 14 yr old boy with severe autism to improve the quality of life. At six months, follow up after therapy the general impression on clinical assessment showed mild autism. It is exciting to see symptomatic improvement with shift on Childhood Autism Rating Scale (CARS) from 42.5 (Severely Autistic) to 23.5 (Non Autistic), which was also visualized as enhanced PET scan brain function. All these improvements have led to improved quality of life of the patient as well as the family. Several incurable neurological disorders have shown benefits with cellular therapy thus, autism should be explored as an indication and nuclear imaging can be used to study its effects.

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An Improved Case of Autism as Revealed by PET CT Scan in Patient Transplanted with Autologous Bone Marrow Derived Mononuclear Cells

Abdominal cerebrospinal fluid (CSF) pseudocyst is an uncommon complication of ventriculo-peritoneal shunts. We report a case of a large lesser sac CSF pseudocyst in a 63-year-old male operated for fibroblastic meningioma of the cerebello-pontine angle ten years earlier. During the initial surgery a ventriculo-peritoneal catheter was inserted

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Alok Sharma

Papers

Clinical evaluation of a portable near-infrared device for detection of traumatic intracranial hematomas.

Detailed analysis of the clinical effects of cell therapy for thoracolumbar spinal cord injury: an original study

An Improved Case of Autism as Revealed by PET CT Scan in Patient Transplanted with Autologous Bone Marrow Derived Mononuclear Cells

Abdominal CSF pseudocyst in a pateint with ventriculo- peritoneal shunt

Orbital subperiosteal hematoma associated with subfrontal extradural hematoma.