Researchers from across the U.S., as part of the Infantile Spasms Working Group (ISWG), established guidelines for the diagnosis and treatment of infantile spasms (IS). The goal of the ISWG is to improve patient outcomes by creating protocols that educate pediatricians on early diagnosis and treatment options. Full details of this study appear online in Epilepsia, a journal published by Wiley-Blackwell on behalf of the International League Against Epilepsy.
Infantile spasms — known also as West syndrome and named after Dr. William James West who provided the first account of the disease in his 1841 medical article — is a rare epileptic disorder that typically presents in infants between 3 and 7 months of age.
Symptoms of IS include spasms of the limbs and trunk (extending or stiffening of the arms, legs, neck or trunk) that occur in clusters, an electroencephalography (EEG) pattern of hypsarrhythmia, and psychomotor delay or arrest.
The IS incidence ranges from 2 to 3.5 per 10,000 live births, occurring in more boys than girls (60:40). Approximately 90% of all IS cases occur during the first year of life, but can affect children up to the age of 4. While some cases have unknown cause (cryptogenic IS), many experts cite tuberous sclerosis (benign growth of brain tumors) and lack of oxygen to the baby at birth as common causes of symptomatic IS.
As part of their investigation, the ISWG (led by John Pellock, M.D.) examined scores of related studies and reviewed current clinical practice. The goal was to establish criteria that target early diagnosis, timely treatment options, and support IS patients and their families. Dr. Pellock, commenting on the agreed protocols, said “We strongly recommend broad clinical evaluation, including: detailed clinical neurophysiology; continued use of vigabatrin (VGB) or adrenocorticotropic hormone (ACTH) as first-line treatment to suppress clinical spasms and abolish hypsarrhythmic EEG; a timely assessment of treatment efficacy (regardless of chosen medication), with prompt therapy modification to avoid serious adverse events and with a particular goal of establishing an ‘all-or-none’ response where effective IS treatment should produce cessation of spasms and resolution of hypsarrhythmia on EEG.”
To establish an IS diagnosis, a clinical evaluation is needed whereby doctors begin with a complete history and physical examination of the patient. Spasms observed by parents or physicians may vary from a cluster of as few as 2 to more than 100, lasting from less than 1 minute to more than 10 minutes. A full EEG evaluation is conducted to uncover any hypsarrhythmic pattern characterizing IS. Next, the etiologic diagnosis is made, aided by MRI, to understand the cause of the disorder. Such a diagnosis will aid in establishing the appropriate treatment strategy. “Following the completion of the history, physical, and neurological examinations, as well as EEG and MRI analysis, roughly 70% of patients will have an established diagnosis without the need for extensive metabolic testing” noted the ISWG team. “This saves valuable time to initiation of treatment and reduces evaluation costs.”
There was consensus in the ISWG that use of ACTH is effective as first-line therapy for IS. However, the team believed there was insufficient evidence to define precisely the optimum ACTH dose and duration of treatment for IS; in general, short duration was preferred (i.e., approximately 2 weeks followed by taper). The ISWG also agreed on the efficacy of VGB as a first-line treatment option, with a dose of 50 mg/kg/day up to 100-150 mg/kg/ day in patients requiring escalation. Since prior studies have established a risk of visual field loss with VGB treatment, the ISWG suggested that infants who respond to this therapy may continue for 6-9 months, with continued ophthalmic evaluation.
Raili Riikonen, M.D., from Children’s Hospital at the University of Kuopio in Finland, said in her commentary, “The goals of the ISWG are certainly worthwhile, but it should be appreciated that treatment approaches differ in Europe from the protocols described in this U.S. perspective.” In Europe there are differing opinions on first-line treatment options for IS. After two weeks of VGB therapy, seizure freedom was seen in 26% of patients (Granström et al., 1999), 23% of patients (Elterman et al., 2000), and 54% of patients (Lux et al., 2004). In the first two of these studies, the number of IS patients who were seizure-free increased to roughly 65% after 3 months. “These data suggested the response with VGB comes later than with ACTH,” Dr. Riikonen stated.
In Japan, treatment strategies for IS also differ from the recommended U.S. protocols. “The dosage of ACTH administered in Japan is strikingly different than prescribed amounts in the U.S.,” commented Yukio Fukuyama, M.D., Ph.D., from the Child Neurology Institute in Tokyo, Japan in his commentary on the study by Pellock et al. A 6-month old infant with 8 kg body weight and 0.4 m2 body surface, would be administered a daily dose of ACTH of 60 IU/day (0.6 mg/day) in the U.S. versus 5 IU/day (0.05 mg/day) in Japan. The dosage difference between the U.S. and Japan is likely due to the different preparation forms (simple natural vs. prolonged synthetic). “Despite this large difference in dosage, the rate of seizure disappearance and EEG amelioration appears to be similar. Since the introduction of this low dosage scheme in Japan, it has been rare to observe serious side effects of ACTH (e.g., obesity, hypertension, hypertrichosis, electrolyte imbalance, manifest immunodepression, cardiac dilation, brain shrinkage on CT/MRI) in our daily practice,” noted Dr. Fukuyama. VGB is currently not commercially available in Japan.
Oliver Dulac, M.D. and colleagues stated in their commentary, “Pellock et al. provide an excellent overview of IS in the form of a consensus report by a reliable panel of experts.” This European team emphasized that IS is not a disease per se, but a common denominator of several conditions, mainly determined by etiology. Patients with different IS etiologies experience different disease courses, requiring different and specific treatment strategies and durations. Both Pellock et al. and Dulac et al. agree that length of IS therapy is one of the most challenging current questions in effectively and safely treating IS patients. VGB treatment, in particular, needs a balanced approach to curb retinal toxicity. “Patients with no cortical lesion (e.g. Down syndrome, leukodystrophy, or cryptogenic cases) usually require no chronic treatment following the control of spasms — ACTH treatment may be stopped after only one month, and VGB after 6 months,” said Dr. Dulac.
While IS is a rare condition, the outcomes for patients with the disorder include higher mortality, ongoing development of additional seizure disorders as the patient matures, and often severe cognitive and developmental delay. A 2003 study by Hrachovy and Frost reviewed 67 published studies, with an average follow-up period of 31 months, and found only 16% of patients with IS had normal development. Additional studies indicated that severe learning difficulties may be present in 70% to 90% of IS patients. An IS study in an Atlanta birth cohort (1975�) found that 15% of patients died by age 11 and 35% died by age 25 (Trevathan et al., 1999).
“The establishment of an IS patient registry, and the development of a continuum of care for patients with this disorder are critical for improving outcomes,” added Dr. Pellock. The ISWG suggested the need for a comprehensive approach for optimal management of children with IS, including access to and evaluation by a variety of professionals, including child neurologists, pediatricians, psychiatrists, rehabilitation services (physical, occupational and speech therapy), nurses, vocational rehabilitation counselors, neuropsychologists, social workers, and pharmacists. “Further studies are needed to determine ideal treatment strategies for IS; carefully controlled comparative studies or patient registries will allow a standard format for gathering important clinical data (e.g. IS recurrence rates, administered therapy details, developmental outcomes) from a large patient sample,” concluded Dr. Pellock.
This study is published in Epilepsia. Media wishing to receive a PDF of the articles may contact [email protected].
Full Citations:
Article: “Historical Infantile spasms: A U.S. consensus report.” John M. Pellock, Richard Hrachovy, Shlomo Shinnar, Tallie Z. Baram, David Bettis, Dennis J. Dlugos, William D. Gaillard, Patricia A. Gibson, Gregory L. Holmes, Douglas R. Nordli, Christine O’Dell, W. Donald Shields, Edwin Trevathan, and James W. Wheless. Epilepsia; Published Online: July 1, 2010 (DOI: 10.1111/j.1528-1167.2010.02657.x). Print Issue Date: October 2010.
Commentary: “A European perspective — Comments on Infantile Spasms: 2009 U.S. Update.” Raili Riikonen. Epilepsia; Published Online: September 3, 2010 (DOI: 10.1111/j.1528-1167.2010.02704.x). Print Issue Date: October 2010.
Commentary: “The Japanese scheme of ACTH therapy in West syndrome.” Yukio Fukuyama. Epilepsia; Published Online: September 3, 2010 (DOI: 10.1111/j.1528-1167.2010.02718.x). Print Issue Date: October 2010.
Commentary: “The Infantile spasms: toward a selective diagnostic and therapeutic approach.” Oliver Dulac, Thomas Bast, Bernardina Dalla, Eija Gaily, Brian Neville. Epilepsia; Published Online: September 3, 2010 (DOI: 10.1111/j.1528-1167.2010. 02657.x). Print Issue Date: October 2010.
Epilepsia is the leading, most authoritative source for current clinical and research results on all aspects of epilepsy. As the journal of the International League Against Epilepsy, subscribers every month will review scientific evidence and clinical methodology in: clinical neurology, neurophysiology, molecular biology, neuroimaging, neurochemistry, neurosurgery, pharmacology, neuroepidemiology, and therapeutic trials. For more information, please visit http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1528-1167
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My name is David Summers of Murfreesboro, TN and I have had MS for 16 years. I am 37 years old and as of January 2012, was effectively an 8.0 on the EDSS scale. Originally RRMS, my disease progression had become SPMS (very progressive) within 4 years of onset. Normally anyone in my position and with my bleak diagnosis is limited to a short future, absolutely no quality of life and a painful end…possibly prior to my 40th birthday if the current progression of the disease continued (without the slightest hesitation or glimmer of hope, my Neurologist just told me: “ Prepare to deteriorate”). But after I heard about Dr. Zamboni’s ‘liberation therapy hypothesis’ in 2010, I began my search for the vein-widening therapy. This put me into a clinic in Duluth, Georgia where they were doing the liberation procedure. I received immediate positive results post-procedure…along with the surgeon’s warning that 50% of the MS patients who undergo the liberation therapy suffer a re-narrowing of the jugular veins within a year or so. Sure enough, within 3 months I knew that I was going to be among the unlucky 50%; all of the original improvements disappeared as I relapsed.
I felt the only way forward was to get it done again, hopefully this time with more enduring results. But where would I go to get this done again and how would that be possible? If my neck veins restenosed after the first treatment, what was to prevent that from happening again…and again? I began to read the Internet blogs and forum chats placed on the many new CCSVI sites by MS patients about where to go and what their experiences were. In this respect, the Internet became a valuable educational tool for me. On several of the blogs, I discovered a New York clinic where they placed a stent during the procedure to keep the jugular veins open, and that positive results were being seen. Grimly, I also discovered that although rare, the prospect of death as a result of this procedure was also a risk. At least one person in a recent study had died when the stent migrated to his heart. But I was willing to put those thoughts and the risks aside. What did I really have to lose? I was dying a slow death. As long as someone was able to treat me there was a chance to hope, and I was down for it. But that wasn’t the main question I was asking myself.
As my disease rapidly progressed and my disabilities became more overwhelming, the question I was asking myself was, was it too late for me? Although I was happy with the fact that my original liberation therapy had diminished most of the symptoms above my waist, I had to ask myself if getting stents was merely settling for a compromised improvement. Having had some success, if I had this done again, I wanted more! Don’t get me wrong, I think the liberation therapy is a miracle discovery from God. As soon as I had my first procedure my cog fog lifted, the vision in my right eye improved greatly, the numbness in both hands dissipated by a few degrees, my ability to taste food returned, my energy levels were ’off the charts’, and my sleep was so sweet. Also, because MS had robbed my body of the ability to regulate body temperature by sweating, I had not been able to handle the hot, humid Southern summers where I live, except to blast cold AC non-stop as a survival method during those sickly ‘dog days’. After the procedure this changed too. I knew it when deodorant suddenly became necessity for my personal hygiene once again!
But it ended by the 90-day point and I was right back where I started. Immediately following the procedure I had dreams of rising from the wheelchair I’d been confined to for ten years and walking like a real man; but even with the incredible improvements overall, it seemed that the only healing occurred above the waist. Perhaps I would just have to accept that even if I could improve to what the full extent of the liberation therapy would allow, I would always be in a wheelchair. While researching the New York clinic and other places, my parents and I came upon CCSVI Clinic through a Google search. We discovered that they are essentially a research clinic operating under an IRB but with a major difference. For the past year, having seen even better results than just doing the liberation therapy alone, they have also been transplanting adult autologous stem cells, cultured and re-injected into the body shortly after the neck venoplasty. If I chose to go there instead of New York, the procedure would be done at CCSVI Clinic at Noble Hospital in Pune India and I would have to get there essentially as a partially paralyzed patient transported in a wheelchair. There would also be a requirement to stay in the hospital for 10-12 days. But after researching the improvements demonstrated in MS patients in stem cell clinical trials, I simply decided that as long as they would take me, nothing was going to stop me from making that trip. On calls with the clinic, it was also explained that stents were not necessary as the stem cells injected intravenously could be enough to keep my veins from restenosing. My confidence in their method increased when I discovered that Dr. Gupte, the neurosurgeon, had been transplanting autologous stem cells for 4 years for a number of different neurodegenerative conditions, including MS and based his therapies on completed stem cell trial methods done in a number of hospitals and universities outside of the US (to be absolutely sure, I confirmed this through searches on Google Scholar). He had already done over 2000 successful transplants! Regarding my communications with CCSVI Clinic, I need to confess here that we did not tell the doctors the truth originally. My mother, who arranged the treatments, told them that I was an EDSS 6.5 in order to qualify. Basically she knew that they wouldn’t accept me into the program if she said I was higher. But if they saw my actual physical condition could they refuse me on the clinic steps? I hoped not.
So in late March it was off to India with my father who is a strong man, and my capable assistant. We arrived on March 26, 2012, and met Surjo Banerjee, CCSVI Clinic’s Managing Director at the airport. He drove us from the airport to Pune, a surprisingly modern city just south of Mumbai. I was amazed to see that the hospital and the CCSVI Clinic itself, (a full wing of suites within the hospital complex) was as clean and modern as any hospital here in the States. After checking in with a number of other patients, I was triaged for the procedures. However, based on my new assessment, it was determined that I would need about twice the amount of stem cells that they had originally programmed, figuring my EDSS scale requirement of 6.5. But paying more was out of the question. We are not rich and had basically ‘sold the farm’ to get here in the first place, and the recommended additional stem cells were going to cost another $12,000 that we had not planned for. Not their fault…I didn’t tell them the extent of my condition in the first place. So the first miracle happened when CCSVI Clinic management offered to personally cover these additional costs. I had never even met some of them, but as a result of their generosity, I received an additional 50,000,000 mesenchymal stem cells and I cannot thank them enough for the difference they have made to my life.
On Tuesday March 27
, I once again had the liberation therapy followed by the harvesting of red bone marrow cells from my hip bone. The clinic has strict aftercare protocols around each type of procedure with regard to position control and movement. It didn’t much affect my activity because I was unable to move much anyway. I was supine positioned, tilted slightly head high for two days following my venoplasty and then laid out supine again, in just the opposite tilt…head-lower-than-the-body for several days following the transplants of the stem cells. I was told that this would allow the newly transplanted stem cells to filter through the full length of the nervous system and locate to the points of injury. A Doppler ultrasound of my neck veins was done every day for 10 days following my liberation procedure. This was to check for any clotting or re-narrowing of the veins which had been widened. If they clotted or restenosed at any time I was in the clinic, they would take me back into the cathlab for a re-do. Happily this wasn’t necessary.
Following the liberation therapy, the changes within my body were just as immediate and dramatic as in my first procedure in 2010, hopefully without the fear of re-stenosis; but my ‘headspace’ almost didn’t accept it. The first time with my liberation therapy in the US, the IR found one narrowing in each jugular, the right side being more severe. This time around, two blockages were found on my right side, and again one on the left. I have heard that second and third procedures for venous angioplasty are more difficult for the surgeons because there is more build up of scar tissue in the interior of the veins, but the medical team took their time and did a perfect job. Words cannot express the emotional joy in getting the blood flowing again and getting those symptomatic improvements back a second time!
Four days later I underwent a lower lumbar puncture, but this time not simply to gather information on whether I have MS. This time, stem cells cultured from my own body were on their way to do what God designed them to do, and that is to heal. For all of you that might be skeptical about this, I am here to tell you that is exactly what they are doing. The positive changes were noticed as soon as I returned to my suite in the clinic and anyone who is paralysed below the waist will understand this next part. To manoeuvre myself as I usually do, I went to pick my leg up from a sitting position and throw it in front of me. The hope here is that the ‘dead-weight’ of the leg will land just right and in a position where I can best situate myself to haul my body into a position where I can further awkwardly throw my whole body into my wheelchair. If you’ve ever seen a spinal patient do this or are unlucky enough to have to do this yourself, you know what an ugly, uncomfortable process this is. But this time the ‘throw’ of the leg proved to be an over-compensation. To my absolute shock and delight my leg lifted itself just as it’s supposed to work…without aid from my helpful hands and placed itself exactly where my brain told it go! At first I didn’t think much of it…this was a fluke, maybe my imagination, but it was something sure not to last. But it has to this day without any hint of regression as I work out and get stronger. This was the first sign of any recovery whatsoever that has occurred below the waist in over ten years, and it happened only hours after the stem cell transplant!
Upon returning home on April 14, 2012, I closely followed the Clinic’s physiotherapy program. Since then I have been working out at levels I had been told by my doctors here in the states would not be possible again. When exercising before I had stem cell therapy, I always had to be careful not to overdo it because I would get a sickness that sometimes lasted 2 days, completely wiping me out. This even occurred after the first liberation therapy, but no more. I’ve been working myself silly and have not yet felt sick. Real strength has returned and muscles have been popping out in places on my body where I haven’t seen them in many years. As of this writing today, and for about the last two weeks my right hand has been functioning normally in every respect. I’m not saying it has improved some, I’m saying it is now completely NORMAL! I can hardly believe it myself.
Since I returned, and after only one month, the positive changes have been happening regularly and most every day. Most significantly, I think, my incontinence has completely improved and I am now able to almost totally control my urinary and elimination functions. All other disabilities aside, I think that this is one of the most important deficits that anyone with MS wishes they could get back! Incontinence is so embarrassing and not having control of that particular function somehow makes you feel lesser as a person. So I’m very happy to see the improvements there. My speech is back to normal. Although I never slurred my words, the thought process was oh-so-slow. Now my words come so quickly that I sometimes find myself stumbling over them…trying to say too much at once. I can’t complain about that!
I am convinced that CCSVI Clinic is on to important discoveries about MS. They have figured this out and are doing the sequence of therapies correctly and the addition of the stem cells completes the need to repair the nerve damage that’s been done by the disease. In retrospect what they are doing suddenly makes complete sense to me. It’s still early yet and I guess time will tell to what extent my motor functions will come back, but if the last month is any indication, it could be everything, which excites me so much. I don’t know if that’s too much to hope for, but it’s the first time in 10 years that I’ve even really allowed the thought to cross my mind. The first fleeting thoughts of this after the original liberation therapy 2 years ago weren’t realistic. The good changes didn’t last. And consider this; a few months ago, I was in a wheelchair, in a permanent brain fog losing more of my independence and quality of life on a daily basis. All I had to look forward to was a deteriorating condition where others would have to take care of my every bodily function. Now I can’t wait to wake up every morning to check myself out. If anything I’m too impatient and working out too hard. But at least I can! Given my current state of health and ability to live and function on my own, the thing that is very certain is that I have a much better quality of life back and that wouldn’t have even been possible if it hadn’t been for the lucky discovery of CCSVI Clinic through an Internet search. My family and I will be eternally grateful for what has happened no matter how this turns out. Thanks to Dr. Gupte, the other doctors, the medical team and staff at the Clinic who made this all happen for me, I’m looking forward to each day with new health and optimism! May God Bless them all!
I have a long way to go, but as long as my jugular veins are wide open and the stem cells continue to clean up the mess those narrowed veins left behind, and damaged nerves continue to regenerate, I believe the sky is truly the limit! My main focus at this point is not only to rebuild muscle but to get my legs to work together, which will restore my balance.
Every day is a new gift that allows me more recovery. I can hardly wait for each morning to see the next improvement! There’s so much more happening in my body than I’ve even mentioned in this writing but I hope I’ve related the main message here…MS was my previous diagnosis.
I will be starting a blog on my progress in a week or two if anyone wants to contact me or follow my improvement. I’m sure there are many of you out there who are skeptical or would want to know how this is going for me. I’ll post the site information back here once I have it up.The first fleeting thoughts of this after the original liberation therapy 2 years ago weren’t realistic. The good changes didn’t last. And consider this; a few months ago, I was in a wheelchair, in a permanent brain fog losing more of my independence and quality of life on a daily basis. All I had to look forward to was a deteriorating condition where others would have to take care of my every bodily function. Now I can’t wait to wake up every morning to check myself out. If anything I’m too impatient and working out too hard. But at least I can! Given my current state of health and ability to live and function on my own, the thing that is very certain is that I have a much better quality of life back and that wouldn’t have even been possible if it hadn’t been for the lucky discovery of CCSVI Clinic through an Internet search. My family and I will be eternally grateful for what has happened no matter how this turns out. Thanks to Dr. Gupte, the other doctors, the medical team and staff at the Clinic who made this all happen for me, I’m looking forward to each day with new health and optimism! May God Bless them all!
I have a long way to go, but as long as my jugular veins are wide open and the stem cells continue to clean up the mess those narrowed veins left behind, and damaged nerves continue to regenerate, I believe the sky is truly the limit! My main focus at this point is not only to rebuild muscle but to get my legs to work together, which will restore my balance.
Every day is a new gift that allows me more recovery. I can hardly wait for each morning to see the next improvement! There’s so much more happening in my body than I’ve even mentioned in this writing but I hope I’ve related the main message here…MS was my previous diagnosis.
I will be starting a blog on my progress in a week or two if anyone wants to contact me or follow my improvement. I’m sure there are many of you out there who are skeptical or would want to know how this is going for me. I’ll post the site information back here once I have it up.For more information visit our site http://davidsmsstemcelljourney.blogspot.in/