alexa An Improved Case of Autism as Revealed by PET CT Scan in Patient Transplanted with Autologous Bone Marrow Derived Mononuclear Cells | OMICS International
ISSN: 2157-7633
Journal of Stem Cell Research & Therapy
Like us on:
Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

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

Alok Sharma1, Prerna Badhe1, Nandini Gokulchandran1, Pooja Kulkarni2*, Priti Mishra3, Akshata Shetty3 and Hemangi Sane2

1Department of Medical Services and Clinical Research, NeuroGen Brain and Spine Institute, India

2Department of Research & Development, NeuroGen Brain and Spine Institute, India

3Department of NeuroRehabilitation, NeuroGen Brain and Spine Institute, India

*Corresponding Author:
Pooja Kulkarni
NeuroGen Brain and Spine Institute
SuranaSethia Hospital and Research centre
Suman Nagar, Sion-Trombay Road
Chembur, Mumbai-400071, India
Tel: 022-25281610/25283706
E-mail: [email protected]

Received date April 23, 2013; Accepted date May 18, 2013; Published date May 20, 2013

Citation: Sharma A, Badhe P, Gokulchandran N, Kulkarni P, Mishra P, et al. (2013) An Improved Case of Autism as Revealed by PET CT Scan in Patient Transplanted with Autologous Bone Marrow Derived Mononuclear Cells. J Stem Cell Res Ther 3:139. doi:10.4172/2157-7633.1000139

Copyright: © 2013 Sharma A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Journal of Stem Cell Research & Therapy

Abstract

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.

Keywords

Autism; Autologous; Bone marrow; Mononuclear cells; PET

Introduction

Autism is a neurodevelopmental, disorder with a multidimensional presentation. It isnoticeable by parents at the age of 3 years due to delayed or abnormal language development, deficits in social interaction, lack of eye contact, hyperactivity and repetitive behaviors and interests [1]. Autism is the most severe form of autism spectrum disorder (ASD), while other conditions along the spectrum include mild forms known as Asperger’s syndrome, childhood disintegrative disorder and pervasive developmental disorder. 1 in every 166 children is estimated to have autism [2]. Although outcomes are specific, behavioral characteristics change over time. Most autistic children remain within the spectrum as adults and continue to experience difficulty with independent living, employment, social relationships, and mental health. Since autism is incurable, chronic long term management is required and can become progressively difficult to handle for parents. The primary goal of the treatment is to improve the quality of life of the patient by minimizing the core features and associated deficits and maximizing functional independence. Facilitating development and learning, promoting socialization, reducing maladaptive behaviors, and educating and supporting families can help accomplish these goals [3-5].

Materials and Methods

Case presentation

Herein, we present a 14 year old boy with autism, who had birth history of Full Term – C – section delivery followed by normal motor milestones but delayed speech with lack of social interactions and emotional development. He was hyperactive with behavioral issues like engaging in self-injurious behavior, self-scratching and hyper aggression. He had normal vision and hearing with slurred speech. He was disoriented in time, but identified places and people. There was no history of seizures. Neurologically, he had normal muscle tone and power in trunk and limb muscles. Functionally, he was independent for most of the daily activities but needed assistance in fine motor activities. In spite of regular rehabilitation since the age of 6 years, he showed no improvements with respect to behavior and social interaction.

His intelligent quotient (IQ) was found to be 64 and Childhood Autism Rating Scale (CARS) score was 42.5 which is categorized as severely autistic.

The molecular diagnostic test of fragile X done using southern blot was negative. MRI Brain showed no significant intracranial abnormality and EEG showed bilateral episodic sharp and slow wave abnormalities. The brain PET scan showed moderately reduced metabolic activity in right broca’s, right insula, right lateral temporal pole, right calcarine, both basal ganglia and left medial prefrontal. It also showed mildly reduced metabolic activity in right parietal, right sensory motor and right Wernicke’s.

He underwent autologous bone marrow derived mononuclear cell transplantation. Our protocol is based on the inclusion criterion as per the World Medical Associations Helsinki declaration [6]. It has been reviewed and approved by the Institutional committee for Stem cell Research and Therapy (IC-SCRT). The patient’s parents were informed about the procedure and a duly filled informed consent form was obtained from them. 300 mcg of G-CSF injections were administrated 48 hours and 24 hours before bone marrow derived mononuclear cell transplantation, to stimulate CD34+ cells and increase their survival and multiplication. Bone marrow (100ml) was aspirated from the iliac bone. Mononuclear cells (MNCs) were obtained using density gradient separation method. Viable count of the isolated MNCs was taken and was found to be about 98%. The MNCs were checked for CD34+ by FACS analysis and was determined to be 1.92 %. Approximately 56 × 106 MNCs were immediately injected post separation, intrathecally in L4-L5 using a lumbar puncture needle and catheter. The patient was also given rehabilitation therapy which included occupational therapy and psychological therapy. Rehabilitation interventions seek to promote recovery & independence through neurofacilitation. During rehabilitation sessions, effective motor learning strategies with task oriented training, for real life environment were utilized & successful attainment of functional outcomes were achieved. He was evaluated at regular intervals of three and six months. He was reassessed by repeating CARS and PET scan of brain after 6 months.

Results

After the procedure, the patient had no side effects. The patient showed some immediate improvements within a week and significant improvements over a period of six months to one year.

Within a week, there was improvement in his eye contact and attention. His hand-writing and fine motor activities like buttoning had improved significantly. On follow up after six months, further improvements were observed in his behavior with respect to social interaction and emotions. Aggression in activities and hyperactivity had reduced by 45 to 50%. Improvements in impulse control, reading skills, tracing, recognition of all shapes and following commands were noted. His score on CARS reduced from 42.5 (Severely autistic) to 23.5 (Non-Autistic) but the general impression on clinical assessment showed mild autism.

On repeating brain PET scan after 6 months, there were improvements recorded in comparison with previous report. Comparative study of previous and post stem cell therapy PET CT scan showed markedly increased uptake in bilateral temporal lobes and bilateral calcarine cortices with mild increased uptake in left medial pre-frontal cortex. All the views; saggital, transverse and coronal views (Figure 1) showed the improvements.

stem-cell-research-therapy-Pre-Post-cell-therapy

Figure 1: A, B, C: The Pre and the Post cell therapy PET CT scans. Comparative study of pre and post cell therapy PET CT scan shows increased FDG uptake in bilateral temporal lobes and bilateral calcarine cortices with mild increased uptake in left medial pre-frontal cortex as visualized below in the post scans.

At one year follow up, he was found to interact more with his peers. Peer activity had increased significantly. New task learning abilities had improved which was noticed due to increased participation in household work. Comprehension and ability to follow commands had improved significantly. He had developed self insight and appropriate emotional response.

Discussion

The exact etiology of autism is not known, but it is likely to result from a complex combination of genetic, environmental, and immunological factors [7]. Current available treatments for autism can be divided into behavioral, nutritional, and pharmacological options, in addition to individual and family psychotherapy and other nonpharmacologic interventions [8]. However, there is no defined standard approach [9]. Currently, numerous clinical trials are being conducted with interventions ranging from hyperbaric oxygen, to administration of zinc, to drugs exhibiting anti-inflammatory properties.

Stem cell therapy offers great promise for the treatment of autism. Although several neurophysiological alterations have been correlated with autism, immune dysfunction and neural hypoperfusion appear to be broadly consistent. The association of altered inflammatory responses and hypoperfusion with symptology is reported, which suggests its causative role [10]. The BMMNCs are comprised of a variety of cells which includes mesenchymal stem cells (MSCs), hematopoietic stem cells, tissue specific progenitor cells and stromal cells. Mesenchymal stem cell have an ability to modulate the immune system and restore the altered brain organization with unique property of homing, wherein the cells migrate to the site of injury and carry out the repair process [11]. The various stem cells in MNC enhance angiogenesis by producing signaling molecules such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF2). They also promote tissue remodeling, prevent apoptosis, decrease inflammation and activate the satellite cells [12]. We have previously published data wherein autologous mononuclear cell transplantation was carried out in children with various incurable neurological disorders including autism, cerebral palsy and mental retardation. Improvements were reported in quality of life of these patients [12-14]. On repeating and comparing the PET scan of brain after six months post therapy, significant changes were recorded and correlated to symptomatic improvements. In numerous studies the areas affected by hypoperfusion seem to correlate with regions of the brain that are responsible for dysfunctions in autism. For example, specific temporal lobe areas associated with face recognition, social interaction, and language comprehension, have been demonstrated to be hypoperfused in autism [10]. The functions of insulae include emotional processing, empathy, perception, motor control, selfawareness, cognitive functioning, and interpersonal experience. In our case these areas showed improvements on PET scan of brain. So the clinical and radiological improvements are well correlated.

Hence, we hypothesize that the cumulative effect of various cells in MNCs showed significant clinical improvements in this case and has altered the course of disease. We conclude, though single case, that intrathecal transplantation of autologous bone marrow derived mononuclear cells is safe, feasible; and may be beneficial in autism. The large clinical studies are an immediate need to fully explore its potential in autism and nuclear imaging can be used to study its effects.

References

Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Relevant Topics

Recommended Conferences

  • 3rd World Bio Summit & Expo December 11-12, 2017 Dubai, UAE
    December 11-12, 2017 Dubai, UAE
  • 20th Global Congress on Biotechnology March 5-7, 2018 London, UK
    March 5-7, 2018 London, UK
  • 7th International Conference and Exhibition on Cell and Gene Therapy March 15-16, 2018 London,UK
    March 15-16, 2018 London, UK
  • 10th World Congress and Expo on Cell & Stem Cell Research March 19-21, 2018 New York, USA
    March 19-21, 2018 New York, USA
  • 4th World Congress on Human Genetics and Genetic Diseases April 19-20, 2018 Dubai, UAE
    April 19-20, 2018 Dubai, UAE
  • 3rd International Conference on Molecular Medicine and Diagnostics April 19-20, 2018 Dubai,UAE
    April 19-20, 2018 Dubai, UAE
  • 11th World Congress on Cell & Tissue Science May 09-10, 2018 Tokyo, Japan
    July 19-20, 2018 Dubai, UAE
  • 11th World Congress on Cell & Tissue Science May 09-10, 2018 Tokyo, Japan
    May 09-10, 2018 Tokyo, Japan
  • 6th International Conference on Integrative Biology May 21-23, 2018 Barcelona, Spain
    May 21-23, 2018 Barcelona, Spain
  • 10th International Conference on Genomics and Molecular Biology May 21-23, 2018 Barcelona, Spain
    May 21-23, 2018 Barcelona, Spain
  • 12th Annual Conference on Stem Cell and Regenerative Medicine June 04-06, 2018 Prague, Czech Republic
    June 04-06, 2018 Prague, Czech Republic
  • 4th International Conference on Bioscience July 2-3, 2018 Vienna, Austria
    July 2-3, 2018 Vienna, Austria
  • 22nd World Congress on Biotechnology July 10-11, 2018 Bangkok, Thailand
    April 16-18, 2018 Amsterdam, Netherlands
  • 9th International Conference on Tissue Science and Regenerative Medicine July 13-14, 2018 Sydney, Australia
    April 23-24, 2018 Las Vegas, USA
  • 10th Annual Conference on Stem Cell and Regenerative Medicine August 13-14, 2018 London, UK
    August 13-14, 2018 London, UK
  • World Congress on Stem Cell Biology and Biobanking September 3-4, 2018 Tokyo, Japan
    September 3-4, 2018 Tokyo, Japan
  • 2nd Annual summit on Cell Metabolism and Cytopathology September 19 - 20, 2018 Philadelphia, Pennsylvania, USA
    September 19 - 20, 2018 Philadelphia, USA
  • 2nd Annual summit on Cell Signaling and Cancer Therapy September 19 - 20, 2018 Philadelphia, Pennsylvania, USA
    September 19 - 20, 2018 Philadelphia, USA
  • 6th Annual Congress on Biology and Medicine of Molecules September 20-21,2018 Kuala Lumpur, Malaysia
    September 20-21,2018 Kualalumpur, Malaysia
  • 5th International Conference on Human Genetics and Genetic Disorders September 21-22,2018 Philadelphia, Pennsylvania, USA
    September 21-22,2018 Philadelphia, USA
  • 11th International Conference on Genomics and Pharmacogenomics September 21-22, 2018 Philadelphia, Pennsylvania, USA
    September 21-22, 2018 Philadelphia, USA
  • 5th World Congress on HUMAN GENETICS SEPTEMBER 24-25, 2018 BERLIN, GERMANY
    SEPTEMBER 24-25, 2018 Berlin, Germany
  • 21st Euro Biotechnology Congress October 11-12, 2018 Moscow, Russia
    October 11-12, 2018 Moscow, Russia
  • 11th International Conference on Tissue Engineering & Regenerative Medicine October 18-20, 2018 Rome, Italy
    October 18-20, 2018 Rome, Italy
  • 24th Biotechnology Congress: Research & Innovations October 24-25, 2018 Boston, USA
    October 24-25, 2018 Boston, USA
  • International Conference on Human Genome Meeting October 25-26, 2018 Istanbul, Turkey
    October 25-26, 2018 Istanbul, Turkey
  • International Congress & Expo on Genomics and Bioinformatics November 2-3, 2018 Columbus, Ohio, USA
    November 2-3, 2018 Columbus, USA
  • 12th International Conference & Exhibition on Tissue Preservation and Biobanking November 9-10, 2018 Atlanta, Georgia, USA
    November 9-10, 2018 Atlanta, USA
  • 2nd Annual Summit on Cell Therapy and Stem Cell Research November 9-10, 2018 Atlanta, Georgia, USA
    November 9-10, 2018 Atlanta, USA

Article Usage

  • Total views: 11862
  • [From(publication date):
    May-2013 - Dec 12, 2017]
  • Breakdown by view type
  • HTML page views : 8073
  • PDF downloads : 3789
 

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

[email protected]

1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]ne.com

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

 
© 2008- 2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version