A Message From Our Research Coodinator: Joe Voros

May 19, 2012

Dear friends,

It’s an honor being the RE Children’s Consortium research coordinator and I wanted to share with everyone an overview of our progress.  Since joining this past January, we have been able to accomplish a great deal through the help of our experienced research teams and continued support from our RE Children’s Project community.   It is vital that we build-up our research infrastructure in order to find appropriate treatments and a cure for RE.  Creating a research infrastructure for a rare disease like RE is particularly tricky, but under Seth Wohlberg’s guidance we are making this a reality.  We are confident that if we can increase the supply of tissue, blood and cerebral spinal fluid (CSF) that is dedicated to research we can build a foundation that will advance RE research interest and get us many steps closer to a cure.   With this time-tested blueprint in mind, my main goals have been to: inventory our consortium’s resources, establish processes to collect and share biological research material for RE research, and strengthen our collaborations within the RE and epilepsy communities.

I’m  proud to say that through the collective efforts of our teams at Mattel’s Children’s Hospital UCLA, Children’s Hospital Boston, and Johns Hopkins University School of Medicine, led by Drs. Gary Mathern, Frances Jensen, and Carlos A. Pardo-Villamizar, respectively, we have been able to inventory what biological sample resources we have available at each consortium site.   This will allow us to best utilize these resources in current RE research projects within our consortium.  Our next step was to establish the legal and contractual framework necessary to allow our consortium sites to share and further collect research material.

Currently, we are finalizing our institutional review boards (IRBs) and material transfer agreements (MTAs) in order to allow research material to be shared between our consortium members for research projects.   An IRB is a committee designed to review research proposals.  In order to protect the rights of people who decided to participate in research projects, all institutions are required to send a research proposal to a review board for approval.  MTAs, on the other hand, define the legal contract that establishes the conditions of the transfer of tangible research materials between the owner and the recipient.  Basically, MTAs are contracts that allow institutions to share research material, which is usually de-identified to maintain the integrity of the original IRB that allowed it to be collected.   As discussed in previous blog entries, IRB boards can take considerable time and effort to gain approval.  Fortunately, our due diligence and hard work have allowed us to make excellent headway with our IRB and MTA processes.

To ensure that we have the material necessary to sustain and drive research, the RE Children’s Project is asking patients to please request that their doctors and surgeons contact us to arrange for the shipment of brain tissue to the research centers focused on RE.  Please contact me at joevoros@gmail.com or Seth Wohlberg at swohlberg@rechildrens.com and let us know that you are interested in participating in our research programs.   One’s ownership of his or her biological material following a surgery is not a cut-and-dry matter.  Legislative rulings and the institutional consent processes vary.   With a verbal request and the proper paperwork patients are well within their rights to request that their tissue be transferred after surgery.  We are working very hard to finalize the proper forms and processes to ensure your wishes are carried out.    This is a challenging task, since different sites have different collection processes and bureaucratic requirements.    We are here to help you through this process and have had success navigating these waters through our medical collaborations.  Thus far, we’ve been able to collaborate with New York University (NYU) and Children’s National Medical Center in order to transfer tissue samples to UCLA and Johns Hopkins.  This is a true testament of the support we’ve received from the RE and epilepsy communities as well as the strength of the RE Children’s medical collaborations.

The RE Children’s Project continues to receive strong support from medical and patient communities worldwide.  In order to build on this momentum and keep RE research at the forefront of the medical community’s mind, I’ve been working diligently to strengthen and build-out our collaborations.  With the help of National Institute of Health (NIH) Directors, Drs. Vicky Whittemore, and Brandy Fureman we have been able to gain valuable information on grant opportunities and rare disease resources, such as the Rare Diseases Clinical Research Network (RDCRN), and NeuroNEXT: Network for Excellence in Neuroscience Clinical Trials.  Through Drs. Whittemore and Fureman, I was able to reach out to Dr. Yaffa Rubinstein, Director of Patient Resources for Clinical and Translational Research Office of Rare Diseases Research and submit a Request for Information (RFI) to a pilot program to establish the Global Rare Diseases Patient Registry and Data Repository (GRDR).  If our RFI is accepted, we will have the opportunity to participate in the GRDR, which will allow our consortium’s patient registry to become part of NIH’s landmark program.   Additionally, I reached-out to Liz Donohue, Director of Coordination of Rare Diseases at Sanford (CoRDS) – a national rare disease registry designed to accelerate research into these rare conditions.  Liz was very eager to learn about The RE Children’s Project’s progress and shared potential partnership opportunities with us.  Most recently, I had the distinct pleasure of representing The RE Children’s Project at the American Epilepsy Society’s (AES) joint event with the Institute of Medicine (IOM), which launched their landmark study report on the public health dimensions of the different forms of epilepsy.

Important gains in research infrastructure, logistics and collaborations have been made, however none of this would have been possible without everyone’s support- thank you.   Your emails, calls and personal meetings truly demonstrate the strength and passion of our RE Children’s Project community.   We are building on our momentum and moving closer to a cure.

I look forward to our continued dialogue.

Kindest regards, Joe Voros

Joe Voros

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Human Tissue Continued

May 12, 2012

Last week I wrote about the issue of ownership of human tissue.  That blog elicited a few e-mails from individuals struggling to get a hold of medical records.  Additionally, Dr. Gary Mathern of UCLA weighed and corrected a few errors in my post. With his permission below is Dr. Mathern’s e-mail:

“In some states, such as California, by state law the title (ownership) of tissue removed from a person at surgery is automatically transferred to the pathologist (not the patient, family or researcher).  A state law mandated that the pathologist was required to make a histopathologic diagnosis of any tissue removed at surgery.   A patient sued to recoup their tissue and the matter went to the California Supreme Court which cited the state law indicating title of tissue belongs to the pathologist and corresponding hospital/institute.  The patient in California does not have rights to the resected tissue.  Hence, your blog site should correctly say that property rights related to tissue removed at surgery varies state by state in the US.

The second has to do with property rights:  For groups to conduct research with an approved IRB, one of the federal requirements (if the research is supported by federal funds) is that any intellectual property developed from a person’s tissue belongs to the researchers and institution and not the patient.  (this is in response to the Lacks case)  There is a clause in my research consent form put there by the IRB, for example, that indicates that any intellectual property is transferred to the researchers and in turn that property (because it is developed with public funds) should be readily available for general use.  Put another way, if a test were developed to diagnosis RE developed in part from patient’s brain tissue, the patients do not have financial rights.  The researchers and institution have the right to patent the finding and then either lease or sell those rights for the development of the diagnostic test for the public good. Hope that makes things clearer.”

For those of you in Fairfield County, Connecticut please be sure to check out the Darien Patch for my periodic blogs on everything to do with rasmussen’s and our local town of Darien.  We will touch on issues that I have covered in this blog, issues of a more local nature.

Joe Voros, our research coordinator continues to do a great job building the infra-structure necessary to ship tissue for RE research.  This is our focus and  will continue to be so for awhile as we cannot advance our understanding of RE without tissue to study.

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The Ownership of Human Tissue

May 6, 2012

In recent blogs we have been asking RE patients to request that their surgeons and doctors contact the RE Children’s Project to arrange for the shipment of brain tissue to the research centers focused on RE.  The need for the collection of tissue is of paramount importance for any rare disease and in the case of RE it is vital if we are to increase our understanding of RE.

The question has arisen who owns the tissue once it is removed from an individual.  Do the consent forms we sign relinquish our ownership of the tissue?  After some research we have learned that the signed informed consent agreements that govern this process are not based on statute and the human tissue donation process that is carried out at the local level is done so in an inconsistent manner.  The informed consent documents that we sign vary from institution to institution.  Although the use of human tissue is heavily regulated by the federal government, the question of who owns excised human tissue has been litigated under state property law.    There have been several court cases concerning the ownership of human tissue especially when the tissue was used for commercial purposes.

Contrary rulings have been reached in different cases.  The bottom line appears to be that we are well within rights to request/demand that our tissue be transferred after surgery, but the appropriate forms must be signed and they must reflect your interests.

We have been diligently working to harmonize the forms and procedures amongst UCLA, Boston Children’s Hospital and Johns Hopkins as well as the other organizations that have come forward to participate in our research efforts such as NYU.  This is not an easy task as each institution has its own legal framework to navigate.

We are convinced that if we can increase the supply of tissue dedicated to research that we will be able to advance research interest for RE.  This is the blueprint that other rare diseases have followed to generate interest and funding.

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April 29, 2012

Dear Friends,

We are in need of rasmussen’s tissue.  We have been successful in attracting the interest of world class research scientists, but they are in need of brain tissue, spinal fluid, and blood to advance our understanding the disease’s causes and mechanisms.  As you know, rasmussen’s encephalitis is extremely rare and without the tissue on which to perform research our theories regarding treatment will remain untested without hard data to prove or disprove their validity.

We are aware of the despair and nightmare of dealing with the wrenching decisions regarding the hemispherectomy surgery, but if you are in this terrible situation we are asking that you inform your neurosurgeon that you would like your child’s tissue shipped to the RE Children’s Project.  Please contact either myself at swohlberg@rechildrens.com or our research coordinator, Joe Voros at joevoros@gmail.com and let us know that you are interested in participating in our research programs.

Please note that you are well within your rights to request that your surgeon ship the tissue.  The tissue is your property, not the property of the surgical institution and we will bear all of the costs associated with shipping the tissue.  New York University has already shipped brain tissue from a recent hemispherectomy to Johns Hopkins; pass this along information to your surgical institution.  We are also working on shipping tissue from overseas, regardless of your location we will be able to ship the tissue.

Many thanks for your support of our work to find a cure for rasmussen’s encephalitis.

Grace and friends in the beautiful waters off Captiva, Fla.

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April 21, 2012

There is an increasing body of research documenting the ill effects of a sedentary lifestyle.  All of the research is supporting the same conclusion:  less sitting is more important than increased exercise.  Watching your diet and exercising may not offset the medical hazards of prolonged sitting.  While increased weight gain is now universally recognized as a major health hazard, it is now becoming increasingly evident that the excessive sitting associated with post hemispherectomy surgery is also deleterious to health.

This topic is especially germane to the hemi individuals whose physical recovery and mobility post-surgery are severely limited or restricted.  With its wide of range outcomes, some hemis recover quite well and live active lives; it seems that the younger children under the age of 5 have an increased opportunity for a more active lifestyle vis-a-vis the older children and young teens that may experience a reduced inability to “rewire” following the surgery.  For some hemis, their lives are defined by a reduced physicality preferring to focus on the increased utilization of their remaining hemisphere.  It is now becoming clear that this focus on the mental aspects of the surgery may not be the best strategy.  The hope for independence that comes with a desk job and the use of computers may have a hidden downside.

The post hemi experience is an area that is ripe for additional research, however funds are sorely needed as most of the surgical centers lose track of their patients as time marches on, seizure control is achieved, and the return on investment in tracking these patients does not motivate these institutions into action.  While everyone agrees that post-hemi rehabilitative protocols are an essential area of research other topics include life expectancy and the long-term health ramifications of the hemispherectomy surgery.  We need to know if their are comorbidities, ie other diseases and conditions that are associated with the surgery as time passes and the hemi population ages into their 50s and beyond.

Vacationing in Captiva, Florida, a beautiful spot.

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Community support

April 8, 2012

Watch this video of a local fundraising event for the RE Children’s Project.  Grace is briefly interviewed.

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April 1, 2012

This past Friday the Institute of Medicine released its report on epilepsy, Epilepsy Across the Spectrum:  Promoting Health and Understanding.  The RE Children’s Project was a report sponsor.  Click here to see the joint press release that was issued by the patient advocate organizations that participated in the preparation of the report.  These groups all consist of wonderful individuals each with their own story of despair and tragedy, yet they are fighting to create awareness for the epilepsies and drive research dollars into finding  cures.  Under the leadership of Dr. Frances Jensen, the current President of the American Epilepsy Society and a member of our Scientific Advisory Board, this group of individuals is increasingly working together as part of Vision 20/20 to achieve their goals.  The report is worth perusing as it contains facts and figures, and touches on many important aspects of finding a cure.  Any attention paid to epilepsy is worthwhile and hopefully this report will create opportunities to advance medical research into the rare epilepsies.

This week the first shipment of brain tissue was shipped from New York University to Johns Hopkins under the auspices of the RE Children’s Research Consortium.  This is a huge breakthrough as we have previously documented the difficult issues associated with transferring human tissue among research institutions.  Our Research Coordinator, Joe Voros is working with several surgical institutions to ensure that the blood and brain tissue of RE patients ends up in the hands of individuals that are conducting RE research.  Many thanks to Dr. Orrin Devinsky at NYU and Dr. Carlos Pardo at Johns Hopkins for making this happen, as well as Dr. Carol Kruse at UCLA for her important input.

E-mail of the week:

Hello my name is Barbara and my son was diagnosed with Rasmussen’s Encephalitis last summer.  He is now 12 years old and will be 13.  In April when we have his surgery, it is his left hemisphere which controls language and speech I am more afraid because of his age. Are you aware of any kids close to his age having this surgery today,  I know there were a couple in the past, they have made tremendous recoveries.  I read about your daughter Grace, what a blessing.  I have been reading on the Hemispherectomy website and the RE Children’s website over and over to help find answers…. I hope I am making the right decision for my son.  I could really use some support and prayers at this very difficult time.

Left hemispherectomies are tricky business as the left side of the brain contains the speech center and its transfer to the right side is not a foregone conclusion following surgery.  At times the left hemispherectomy is performed in stages to facilitate the rewiring of the speech center in the healthy right hemisphere.  The Wada Test is performed to identify the location of the speech center in the brain to evaluate the likelihood that the individual will be verbal following left-sided hemispherectomy.

Although RE is incredibly rare I am amazed at the e-mails I am receiving from around the globe regarding new patients with rasmussen’s.  We are fortunate to live in an age where families impacted by RE have the power of technology to reach out and help one another.  Please continue to donate to the RE Children’s Project.  Rare disease research is underfunded, yet the benefits of finding a cure for a disease such as RE are not well understood.  The RE Children’s Project is making a difference, but we need your help.  Many thanks for your support.

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March 25, 2012

This week the Institute of Medicine will be releasing its report on epilepsy entitled, “Epilepsy Across The Spectrum.”  The release is an important event as the IOM’s reports become source documents for the development of public policy.  This report provides a general overview of epilepsy and is a blueprint on how to advance our understanding of the disease and find a cure.  The report is full of interesting statistics and information.

The report states that epilepsy is the fourth most common neurological disorder in the US after migraine, stroke, and Alzheimer’s disease with 2,200,000 people in the US with epilepsy (as compared to 349,000 with Parkinson’s.)  Rasmussen’s encephalitis is not specifically addressed in the report, while disappointing it is not unexpected due to its extreme rarity.  The RE Children’s Project, however, is acknowledged.  With its public release this Friday the report will receive lots of media and will focus attention on the relative lack of public and private resources that are addressing epilepsy.

Here is an e-mail I received this week from some friends with a 5 year old son wrestling with rasmussen’s.

During the trip Sam was already seizing a lot and when we got home unfortunately his seizures increased and Tuesday we wound up back at NYU and by Wednesday he was in the PICU again in status epilepticus.  They’ve got Sam somewhat stabilized on Versed right now and the surgeon has managed to get Leo on the OR schedule for tomorrow.  Unfortunately, reducing his Depakote has caused him to destabilize and the docs here won’t put him back on Depakote because they are afraid it might cause bleeding during surgery.

Status epilepticus is serious business, an unending seizure requiring hospitalization.  It’s frustrating that rasmussen’s is such a devastating and severe disease, but because it is not common the medical and research communities do not see the benefits of investing resources in finding non-invasive treatments.  The choice of unrelenting epilepsy or the removal of your half your brain is the definition of despair.

Please click on this link to watch the television segment that was produced around the Lifting Grace event, the local fundraiser in our town sponsored by the Darien Varsity football team.  The event raised close to $10,000 and we are grateful to the coaches, players, and their sponsors for supporting our mission.  Please continue to support our efforts to advance medical research into rasmussen’s.  Thank you.

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March 18, 2012

This week we received an e-mail from Portugal printed below:

I am a doctor in Lisbon, Portugal. I am an Internist, having special interest in autoimmunity.  My 6 year old started, 5 months ago, showing a focal epilepsy which proved resistant to treatment, as well as a focal atrophy in the right hemisphere on the MRI. One month later a left hemiparesis developed. He has criteria to RS.  Epilepsy is going better with therapeutics having two/three partial crises per week. He started two months ago with prednisolone (high dose, IV) and immunoglobulins, and is showing sign of of improvement. Reading about rituximab, it seemed quite a good promise… But the results are not clear. I could not find good reports, neither was it clear how the subsequent administrations were carried – every 6th months like in other autoimmune diseases?I would much appreciate your kind attention, and, hopefully, also your opinion on the best course of treatment. At this moment, since epilepsy is under control, surgery appears to not be an immediate course of action, but, as is known, the later the surgery, the harder the recovery. It is a hard decision, and a dilemma; search for a treatment, or take that monumental step…Also, I would like to congratulate you on the initiative, it is a godsend for both patients and parents!

This e-mail captures the dilemma faced by all parents dealing with RE, run the gamut of treatments in the hope that something will work, but face the eventuality of hemispherectomy surgery or just remove half your child’s brain despite their temporary reprieves from the disease.  As a parent it can only be summed up as despair.

This e-mail makes reference to rituximab.  I posted on facebook this week the only study that I have seen on the drug regarding its use for rasmussen’s.  The study was provided to me by Dr. Ken Laxer; there was no follow-up that I am aware of and I know from discussions with RE families that rituximab has help some, while ineffective in others.  We are in touch with some families that are trying the drug today and will keep you posted.

This week I watched an inspiring documentary, The Announcement, about Magic Johnson and his personal journey with the AIDs virus.  Fortunately, today it is a period piece that documents a past era characterized by fear and misunderstanding.  We forget that back in the mid 80s AIDs was a death sentence and when Magic Johnson announced he was HIV positive he was considered a dead man walking.  It is a testament to the power of medical technology and the human intellect that Magic Johnson today is living a worthwhile and productive life.

As I watched the documentary I could not help but be a little selfish and think about how the “cure” for RE, a radical brain surgery that removes half the brain has not changed at all since the 80s, and in fact has not changed since the 50s when the surgery was first introduced.  We understand so little about this disease, but with resources and focus as with AIDSs we can make a difference.  That difference is a non-invasive, effective treatment for this disease.

My favorite social media obsession this week is Pinterest.  Like all social media there is a lot of fluff and junk, but what appeals to me is its simplicity and its ability to increase awareness among the general public.

Many thanks to Steve Levy (right) and Shawna Ryan of the MSG Varsity Channel for their Lifting Grace segment. We will be posting the video.

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March 11, 2012

We are often asked when is the appropriate time to perform the hemispherectomy surgery once a rasmussen’s encephalitis diagnosis is confirmed.  The short answer according to most RE families is the sooner the better.  This question along with other frequently asked questions by parent of RE children is addressed in a new piece we have compiled that is on the front page of the website.  This advice may not be warranted in each case, but unfortunately most treatment institutions prefer to try different drug regimens that invariably do not stem the seizure activity.

There was a new study published recently by UCLA about the effectiveness of brain surgery on epilepsy patients and it superior outcome versus anti-seizure medicines.  The study concludes that individuals with temporal lobe epilepsy that is not controlled with medicine should be evaluated for surgical intervention not after decades of poor response to medicine but within two years. Temporal lobe epilepsy is the most common drug resistant form of epilepsy.  While the study does not focus on the hemispherectomy surgery, it does highlight that the benefit of early intervention in seizure management.

Grace is now 2 years out from her redo surgery at UCLA and her recovery is accelerating.  At 10 years of age during her first surgery at Johns Hopkins, Grace’s brain plasticity or resiliency was not as strong as younger children and her recovery was slow to take hold.  We learned for older kids such as Grace the recovery “switch” gets thrown anywhere from 6 months to 2 years after the surgery when the brain has sufficiently healed.  Grace’s physical recovery has recently accelerated which goes against conventional wisdom which states that 90% of what is physically recoverable after the surgery occurs during the first year of surgery.  This is not the case as plasticity is a permanent feature of life and the brain continually rewires to adapt to change.

This past Friday we attended the 4th annual Lifting Grace event at Darien High School.  It was great to see all of the young athletes turn out to raise funds for our cause while at the same time preparing for the upcoming football season.  Thanks to Coach Trifone and the extended football family.

Grace with Coach Rob Trifone and Michael.

MSG Varsity Channel covered the event and interviewed Grace.

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