January 2010 Fact Sheet

Dolphin Assisted Treatment, Hyperbaric Oxygen Therapy and the Adeli Suit

Dr. Pedro Weisler, a child neurologist at the Nationwide Children’s Hospital in Columbus, OH just published a commentary in Clinical Pediatrics discussing 3 Complimentary and Alternative Medicine  (CAM) treatments for children with developmental disorders. The following are highlights from his paper.

1. )  CAM is defined as “ a group of diverse medical and health care systems, practices and products that are not presently considered to be part of conventional medicine”.

2. )  For the most part CAM treatments “ are based on anecdotal evidence and at times rather unusual ideas about the biology of the condition to which they are being applied”.
3. )  In 2002, Americans spent more than $34 billion for CAM treatments.
4. )  Dolphin- Assisted Therapy (DAT) for treatment of mental retardation

• A researcher has postulated that the ultrasound produced by dolphins has a ‘positive effect on the brain’s psycho-neuro-immunological alpha state’ and that the ultrasonic energy may cause neuronal migration and other cellular changes in living tissue.
• Studies to evaluate these claims don’t exist
• The cost of a 4-day DAT program is approximately $4,500.

5. )  Hyperbaric Oxygen Therapy (HBOT) for the treatment of cerebral palsy

• HBOT is the therapeutic use of oxygen at concentrations higher than normal air
• HBOT has proven efficacy for the treatment of carbon monoxide poisoning, decompression sickness and would healing
• The biological premise that HBOT is useful for the treatment of CP is based on the theory that exposure to high levels of pressurized oxygen can heal or reactivate damaged neurons.
• In most cases, the underlying cause for CP is periventricular leukomalacia, an injury of white matter in the brain. White matter is produced by oligodendrocytes, a glial cell, not a neuron, so the hypothetical basis for HBOT treatment is not defensible.
• No well-designed, controlled clinical study has shown that HBOT is more effective for the treatment of CP than exposure to pressurized air
• Reports of the benefits of HBOT on improving CP-related symptoms are from testimonials, single patient studies or poorly designed experiments from HBOT facilities
• The cost of a typical 40 session treatment is $4000.

6. )  Adeli Suit (AST) for the treatment of cerebral palsy

• The Adeli Suit was first designed for Russian Cosmonauts to counter the effects of weightlessness (loss of muscular fitness and decreased bone density)
• The AST technique uses an intensive exercise protocol paired with putting on the suit for 1 month
• The most recent clinical study comparing the Adeli suit with the use of a standard neurodevelopmental treatment found no difference in improvement of CP-related symptoms although both treatment groups did show greater than expected improvement
• The authors of the study concluded that the children with CP benefitted because they received intensive therapy, irrespective of type, for 1 month and because of the increased involvement of their families in their treatment.
• The cost of a 28 day AST treatment is $4000.00.

7. )  Conclusion: There is no good clinical evidence to support the use of these 3 alternative treatments for cerebral palsy. With regard to DAT and HBOT, there is no underlying biological basis that supports their use in the treatment of mental retardation and cerebral palsy, respectively. What is becoming clear, is that parental involvement, combined with intensive, physical therapy has beneficial effects on children with CP.

December 2009 Fact Sheet

Federal funding (National Institutes of Health) into the prevention and treatment of cerebral palsy is very low when compared to other childhood conditions. The disparity becomes readily apparent when examined on an annual funding per new case basis. For instance, NIH funding for cerebral palsy was $29 million dollars in FY 2009 and is projected to be $29 million in FY 2010  (NIH RePORT, 2009).  Estimates of CP prevalence in the western world range from 2 to 4.4 cases per 1000 live births; and is widely believed to be increasing.  Given that there were over 4 million lives births in the US in 2005 (CDC, 2006), a reasonable estimate of the number of new cases of cerebral palsy diagnosed each year is 12,000.  Thus, on an annual basis $2400 Federal research dollars are spent for every new case of cerebral palsy.  In comparison, $93 million Federal dollars were spent on cystic fibrosis research and it is projected that $94 million Federal dollars will be spent in FY10.  In the US, there were an estimated 0.3 new cases of cystic fibrosis per 1000 live births  (National Heart Lung and Blood Institute), resulting in 4000 new cases annually.  Thus, $23,000 Federal research dollars were spent for every new case of cystic fibrosis last year, a 10-fold difference over that spent for CP research.  Go to the NIH RePORT website to see Federal funding amounts for various conditions.  HYPERLINK “http://report.nih.gov/rcdc/categories/” http://report.nih.gov/rcdc/categories/

Many childhood health conditions have been able to obtain support from the general public to support research activities.  The US Cystic Fibrosis Foundation provides $85 million annually in research support, and the Juvenile Diabetes Foundation, $156 million.  Our foundation, the Cerebral Palsy International Research Foundation is the only Foundation in the US entirely devoted to research for the prevention and treatment of cerebral palsy. Unfortunately, our  entire research budget in FY09 was only $1.6 million. Clearly, for advances in prevention and treatment of one the most common disabling conditions of childhood, cerebral palsy, more money is needed to fund the research that must to be done to decrease the number of new cases of cerebral palsy, to develop early treatments that might prevent or lessen the disability associated with brain injury and to improve motor and cognitive function in children and adults with CP.  So what can YOU do? Write your Congressman and alert them to this funding disparity! Donate to CPIRF what you can so that we can continue to fund more and better research for CP! We are the only private foundation in the US solely devoted to CP research.

October 2009 Fact Sheet

Human periventricular white matter injury (PWMI) is the predominant form of brain damage and the leading cause of life-long neurological disability from cerebral palsy in survivors of premature birth. The two major causes of PWMI are thought to be: chorioamnionitis, which can induce fetal inflammatory response, and hypoxia/ischemia (H/I), which both can cause acute degeneration of oligodendrocyte progenitors resulting in chronic myelination disturbances of neuronal axons and subsequent loss of motor control.

Recently , there has been much discussion of how cell-based therapies may used for regeneration of damaged neuronal tissue. In particular, cell based therapies may help repair/regenerate damaged neurological tissue by becoming neurons or glial cells (oligodendrocytes and astrocytes) and integrating into the neuronal network, restoring tissue by promoting activation of endogenous stem cells or by preventing tissue damage by changing body’s immune response.

Neural stem cells (NSCs) are found in the subventricular zone (SVZ) of the brain and give rise to three major cell types: neurons, astrocytes and oligodendrocytes. In development, neuroblasts from the SVZ migrate to the olfactory bulbs and a separate lineage of glioblasts migrate throughout the forebrain. While the neuroblast marker Doublecortin (Dcx) is necessary for embryonic cortical migration, it is unknown whether it is necessary for migration towards neonatal H/I lesions. Scientists are currently studying how neural stem cells respond to neo-natal hypoxia/ischemia and their potential role in repairing tissue resulting tissue damage. The researchers hypothesize that the SVZ derived stem cells redirect their migration toward brain areas injured by H/I; that SVZ NSCs expand lineage restrictions following H/I; and that Doublecortin is necessary for SVZ neuronal migration in response to H/I. This study may provide an important understanding of SVZ cell behavior in response to neonatal H/l and serve as a starting point for developing strategies to harness endogenous NSCs for repair/regeneration of damaged nerve tissue.

In addition, scientists are evaluating the role of vascular endothelial growth factor (VEGF) on neural progenitor cell proliferation and differentiation after a perinatal H/I injury. Previous research indicates although the SVZ expands in size after H/I injury, there is a shift in the production of astrocytes and oligodendrocytes. VEGF, a key mediator of tissue repair after ischemia, is rapidly induced after H/I injury and increases the specification of astrocytes rather than oligodendrocytes from bipotential glial progenitors in vitro. These researchers hypothesize that VEGF isoforms cause an aberrant shift in the proliferation and differentiation of SVZ progenitors towards astrocytic phenotypes instead of a more appropriate oligodendrocyte lineage after H/I injury. They propose to evaluate a particular isoform of VEGF that they believe will stimulate mainly oligodendrocyte production in response to a perinatal H/I injury and perhaps lead to a therapy that will stimulate endogenous neural stem cells to expand the production of oligodendrocytes for myelin repair.

Scientists are also evaluating the effects exogenous neural stem cells implanted into the SVZ of a developing brain after H/I injury. They propose to implant adult neural stem cells into the lateral ventricle or injured cortex at 24 hours and 7 days post injury. The location, cell type, and degree of differentiation of the transplanted stem cells will be analyzed 7 to 14 days post transplant. Axonal tracing studies will also be performed to begin to understand the physiologic activity of the implanted cells.

Finally, researchers are evaluating transplantation of oligodendrocyte precursors (OPCs) as a potential repair strategy in both acquired (CP) and congenital disorders of myelination. They propose to transplant genetically engineered oligodendrocyte precursors (pre OLs) into a model of congenital leukodystrophy, a condition characterized by progressive degeneration of the myelin sheath. Their previous work has demonstrated that Dlx homeobox transcription factors act as repressors of oligodendrocyte formation and maturation during embryogenesis. Cells for transplantation will be generated by using conditional Dlx2 knockout mice with loss of Dlx2 function in postnatal SVZ progenitors. The researchers hypothesize that the loss of Dlx function in the pre OLs will result in enhancement of their maturation and increased myelination of axons, and possibly a new therapeutic strategy for treatment of white matter pathology.

These studies demonstrate that, while in its infancy, cell therapies for the treatment of cerebral palsy hold great promise for a condition that has proven very difficult to prevent or cure.

October 2009 Fact Sheet

Under the Food and Drug Administration Amendments Act of 2007 (FDAAA), gave FDA authority to require safety labeling changes.  The FDA review for safety of BOTOX started February 2008, the conclusion of this review was introduced by implementation of a Risk Evaluation and Mitigation Strategy (REMS) that includes a BOTOX®/BOTOX® Cosmetic Medication Guide to provide to patients being administered BOTOX. The REMS has been implemented to ensure that the benefits of BOTOX®/BOTOX® Cosmetic treatment outweigh the potential risks of BOTOX®/BOTOX® Cosmetic treatment.  The goals of the BOTOX®/ BOTOX® Cosmetic REMS are to:

• Minimize the risks of medication errors related to the lack of interchangeability of BOTOX®/ BOTOX® Cosmetic Units with those of licensed botulinum toxins of other manufacturers
• Inform prescribers and patients about the potential occurrence of spread of toxin effect beyond the injection site

The strategy requires that an FDA-Approved Patient Medication Guide for BOTOX® be sent to health care providers who are administering Botox and to patients each time Botox is administered.

Non-Interchangeability of Botulinum Toxin A products
Because the potency units of BOTOX®/BOTOX® Cosmetic Units are specific to the preparation and assay method utilized, it is not interchangeable with other Botulinum Toxin A products such as DYSPORT ^TM manufactured by the Ipsen Group.  To address this issue, Allergan, in conjunction with the FDA and the United States Adopted Names Council, has adopted the established the name onabotulinumtoxinA that is specific to BOTOX® . This uniquely established nonproprietary name replaces the previous common terms Botulinum Toxin Type A and differs from the established name for DYSPORT™ (abobotulinumtoxinA) .

Distant Spread of Toxin Effects
Postmarketing reports indicate that the effects of  BOTOX®/BOTOX® Cosmetic and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These may include asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and breathing difficulties. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life threatening and there have been reports of death. Therefore patients, care-givers, and/or parents must be vigilant about be on the alert for these symptoms. The risk is probably greatest in children treated for spasticity but symptoms can also occur in adults treated for spasticity and other conditions, particularly in those patients who have underlying conditions that would predispose them to these symptoms. In unapproved uses, including spasticity in children and adults, and in approved indications, cases of spread of toxin effect have occurred at doses comparable to those used to treat cervical dystonia and at lower doses. The REMS requires a periodic evaluation on its’ effectiveness. The timeline for evaluation is 18month, 3years, or 7 years. FDA may eliminate the REMS requirement if after 3 years if it is managed well.

CPIRF Scientific Advisory Council member, Dr. Nigel Paneth will lead a statewide team of researchers from Michigan who will utilize the state’s archive of newborn blood spots to help them uncover causes of cerebral palsy. The research team’s work is being funded by a $1.9 million grant from the National Institute of Neurological Disorders and Stroke as part of the federal American Recovery and Reinvestment Act. Partners include the Michigan State University, University of Minnesota, the University of Michigan and Helen DeVos Children’s Hospital and the Mary Free Bed Hospital in Grand Rapids.

Read more about the study here

Recent Developments in Healthcare for CP: Implications and Opportunities for Orthotics

A conference convened by the International Society for Prosthetics and Orthotics (ISPO) reviewed the evidence for the physical management of cerebral palsy (CP). Papers presented at the meeting included a global health perspective, definition and classification of CP, classification of gait in CP, and reviews of physiotherapy, occupational therapy and medical, surgical and orthotic management. Small group and plenary discussions resulted in wide ranging conclusions and recommendations.

The report of the conference, titled Recent Developments in Healthcare for Cerebral Palsy: Implications and Opportunities for Orthotics, is available free of charge at www.ispoweb.org The report contains the background to the conference, manuscripts of all the papers, and the conclusions and recommendations. Notwithstanding the focus on implications for orthotics, the content provides a valuable resource for anyone providing or researching health services for people with CP.

The ISPO intends to use the report as an educational resource for further instructional courses and disseminate the information as broadly as possible with the aim of improving the health care of people with CP worldwide.

Nathan Baker is proof positive that kids with disabilities can compete in sports.

Nathan Baker and Coach Mike Miragliuolo :

Nathan Baker was a participant in a study conducted by Dr. Deborah Thorpe at the University of North Carolina at Chapel Hill and funded by the Cerebral Palsy International Research Foundation. Dr. Thorpe’s study compared the efficacy of treadmill training versus aquatic therapy in improving quality of life and motor function in children with cerebral palsy aged 12-19 years of age.

From Nathan’s Mom…

We are so thankful for the research funds that the Cerebral Palsy International Research Foundation contributed to Dr. Deborah Thorpe of the University of North Carolina School of Medicine, Division of Physical Therapy. Nathan’s physical therapist, Cathy Howes (also UNC Hospitals), recommended us for the study. We soon discovered that Nathan would be in the treadmill portion of Dr. Thorpe’s study and this meant that he would be on the treadmill for 3 times a week for 40 minutes at each session. Nathan decided to combine this study participation with physical fitness work he needed to do for his Boy Scout Personal Fitness merit badge.

Dr. Thorpe, Nathan, and I were amazed at Nathan’s progress on the treadmill as he participated in this study. He increased his speed to 4 mph and higher and was able to sustain this pace for the two 20 minute sessions. As Nathan’s participation in this study was coming to completion, Dr. Thorpe began to educate us on how important it is for individuals with CP to exercise throughout their lives so they can ward off loss of function as they age. She also inspired Nathan to inquire about Cross Country or Track opportunities at his school.

Nathan inquired about Track at his middle school and was not enthusiastically received. We found some coaches are unwilling or fearful to include those with disabilities in physical endeavors. Other coaches will embrace the idea and know the benefit it can bring to all members of the team as they learn lessons of perseverance and “heart” from those with disabilities.

We decided to be persistent and inquired about Cross Country as Nathan was making plans to enter High School. Coach Mike Miragliuolo urged Nathan to join his team at Green Hope High School. He promised Nathan that if he was willing to attend practices and put in the effort, he would be part of the team. Nathan began his workouts with the team that summer. North Carolina is gruelingly hot and humid in the summer and the municipal park where the high school team often trains has some challenging terrain for a person with motor disabilities to navigate.

Coach’s first goal for Nathan was to be able to run 3 miles without stopping to walk. The first two weeks were daunting. Nathan grew discouraged. Coach began to reconsider what was possible and offered Nathan the opportunity to remain as part of the team in a support role(help with water/towels, etc.). Nathan “dug in” and founded it within his character to continue to try and by the time the team was ready for its first meet, Nathan could run 3 miles. He ran this first 5 K with a time of 33:55. The lead runner’s time was 19:08. Nathan’s current personal record for the 5K has improved to 24:18.

Nathan discovered a fountain of inspiration:
1) others inspire him to run his best with their cheering and 2) he inspires others to run because “if I can run, so can others with CP”. Nathan became an advocate for people with disabilities to exercise and he challenges those without disabilities to join him as well.

Read more about Nathan Baker and the Green Hope, NC running team in an article in USA Today.

http://www.usatoday.com/sports/preps/xcountry/2008-10-14-big-teams_N.htm

The New England Journal of Medicine just published a study on the medical and social problems of adults (20-36 years old) who were born alive (and without congenital anomalies) in Norway between 1967 and 1983. The authors state:

“Advances in perinatal care have increased the number of premature babies who survive. There are concerns, however, about the ability of these children to cope with the demands of adulthood.”

Here are some of the most important points:

1.The risk of serious medical disabilities such as cerebral palsy, mental retardation, and disorders of psychological development, behavior, and emotion, as well as of other major disabilities such as blindness or low vision, hearing loss, and epilepsy increased markedly with decreasing gestational age. We also observed a significant association of autism-spectrum disorders with very low gestational age, but these findings were based on a very small number of cases in the lowest gestational-age groups.

2. At 19 to 35 years of age, nearly 1 of 9 persons who had been born at 23 to 27 weeks of gestation received a disability pension, as compared with 1 of 12 who had been born at 28 to 30 weeks, 1 of 24 born at 31 to 33 weeks, 1 of 42 born at 34 to 36 weeks, and 1 of 59 born at term.

3. There were progressively higher risks of cerebral palsy, mental retardation and autism with decreasing gestational age.

4. Among those who did not have medical disabilities, the gestational age at birth was associated with the education level attained, income, receipt of Social Security benefits, and the establishment of a family, but not with rates of unemployment or criminal activity.

5. Babies born between 23-27 weeks were 78 times more likely to have CP than those born at term.

6. Babies born <28 weeks were 9.7 times as likely to develop Autism Spectrum Disorder.

Moster D, Lie RT, Markestad T. Long-Term Medical and Social Consequences of Preterm Birth. NEJM 359:262-273.

Cerebral Palsy International Research Foundation comments on FDA Public Notification concerning adverse events reported in child

Concerns about the safety of Botox injections to treat spasticity in individuals with CP have recently been raised. It has not been established whether these adverse events are causally related to Botox treatment. Serious adverse events have been reported in children with cerebral palsy. The FDA is currently reviewing safety data from clinical studies submitted by the drug’s manufacturers, as well as post-marketing adverse event reports and medical literature. The FDA is not advising health care professionals to discontinue prescribing these products.

After completing a review of the data, the FDA will communicate to the public its conclusions, resulting recommendations and any regulatory actions. In the interim, the FDA is not advising health care professionals to discontinue prescribing these products. CPIRF is closely monitoring this situation and will alert the CP community of any new developments.

Background

The severe adverse events resulting in death reported in the United States occurred in three children with CP. All involved some degree of aspiration, respiratory infections, and other breathing complications; all 3 children had a history of respiratory compromise and dysphagia prior to treatment with Botox. It is unknown if treatment with Botox was causal in their deaths.

Botox use has been approved for the treatment of limb spasticity in individuals with CP in approximately 60 countries since 1995. While not approved in the US by the FDA for this use, highly trained physicians have been effectively treating spasticity (severe arm and leg muscle spasms) with Botox over the last 15 years.

The FDA is aware of the body of literature describing the use of botulinum toxins to treat limb spasticity in children and adults with CP.

Comments

Botox has been a very helpful and effective method for treating children and adults with disabling spasticity and dystonia for many years. Those being treated by a qualified and experienced physician should discuss their concerns with their physician, but there is no indication that treatment should be discontinued, and the product is not being “recalled”.

It is critical that Botox only be administered by highly trained physicians who understand and fully explain the risks to patients and their care-givers. It is also important that physicians make patients and care-givers fully aware of the signs and symptoms of botulism. The symptoms include difficulty in swallowing, weakness, difficulty in breathing, difficulty in speaking. Patients and care-givers should also understand that these side effects can occur as early as one day and as late as several weeks after a Botox injection and that if they have any of these symptoms they should seek medical attention immediately.

Serious adverse events should be reported to FDA’s MedWatch reporting system by completing a form on line at http://www.fda.gov/medwatch/report/hcp.htm, by faxing (1-800-FDA-0178), by mail using the postage-paid address form provided online (5600 Fishers Lane, Rockville, MD 20853-9787), or by telephone (1-800-FDA-1088).

By Dr. Mindy Aisen

The field of stem cell research offers enormous promise for the treatment of human disease. Stem cells are “undifferentiated” cells; they have the potential to develop into virtually any specialized type of cell in the body. So theoretically, stem cells might be used to regenerate human tissue or organs damaged by disease. There is hope that some day stem cells may provide effective restorative therapy for many human conditions, including those caused by damage the nervous system such as stroke, Parkinson’s Disease, spinal cord injury and cerebral palsy. At the present time, however, the field of stem cell research is in its infancy, and there are few effective uses of this type of therapy.

Stem cells can be derived in several ways. Embryonic stem cells (removed from early stage embryos) can be maintained in the laboratory and coaxed into differentiating into various cell types. Fetal cord blood contains human stem cells that can also be grown in the laboratory or frozen for later use. A recent technique for generating human stem cells involves obtaining cells from skin biopsies and “deprogramming” them into stem cells that can then be differentiated into various human cell types. The adult human brain contains viable neural stem cells; it may be possible to use medications to stimulate these natural stem cells into regenerating damaged brain tissue.

Stem cell scientists are currently working on the optimal conditions to maintain stem cells in the laboratory, the precise methods necessary to convert stem cells into the specific cells that might reconstitute damaged human tissues, and the techniques required to direct such cells to function effectively together. At the present time, much work remains to be done before the practical application of stem cells to the treatment of human disease becomes feasible.

In cerebral palsy, brain tissue is damaged at a very early stage of development: in utero, at or around the time of birth, or up until the age of 2 years. The brain is, of course, the most incredibly complex of all human organs. The brain consists of many different cell types interacting in a precisely organized fashion to produce the different aspects of thought and behavior in different brain regions. Before stem cells can be used to repair damaged brain tissue in cerebral palsy or any other brain disorder, scientists will have to discover how to turn stem cells into various specific types of brain cells, and induce them to form the precise connections and organization necessary for meaningful brain function. It is likely that stem cells converted into brain cells will have to be implanted in the precise areas that they are needed in order to provide effective treatment.

Specific Types of Approaches: Cord Blood Infusions

It is extremely unlikely that the administration of stem cells by peripheral infusion of cord blood can effectively treat cerebral palsy. Such cells have not been “taught” to form the necessary types of brain cells, and they will not be able to enter the brain, because there is an anatomic and physiological barrier which prevents certain medications and cells from reaching the brain, known as the blood brain barrier.

How can one explain the reports of improvements in the symptoms of cerebral palsy (CP) following cord blood infusions? Medicine is filled with such “anecdotal” reports of improvements when novel treatments are applied to chronic conditions. The symptoms of all chronic conditions fluctuate, and subjective factors, including the optimistic expectations that accompany novel therapies, often seem to alleviate disease manifestations. But in almost all cases, the underlying disease remains unchanged, and there is no meaningful long-term benefit. Indeed, in most cases, the risk of harm outweighs the chance of benefit when unproven novel therapies are used.

CPIRF strongly supports research into the use of stem cells to treat CP. But at present, CPIRF, in consultation with leading stem cell scientists, has reached the firm conclusion that use of cord blood or other forms of stem cell treatments for CP is inadvisable. Basic and applied research into various approaches to stem cell neural regeneration therapy must be vigorously pursued, and CPIRF will continue to fund such efforts. But at present, administration of cord blood to people with CP offers no meaningful chance of benefit.

Furthermore, the long term risks of cord blood infusions have not been studied, receiving infusions in other countries from donated cord blood may have significant risk and certainly present substantial financial strain for the families of those being treated.

We strongly endorse an organized scientifically rigorous initiative focused on rapidly identifying the most effective methods for using stem cell treatments to help repair the damaged brains of children and adults with developmental brain conditions.