Hype or Hope? Much Touted Oral MS Drug Tecfidera (BG 12) Approved byFDA.

If you are currently taking Tecfidera, please take part in my Tecfidera patient poll (click here).

Last week, the FDA approved Biogen’s long-awaited oral MS drug, Tecfidera (formally known as BG 12). Naturally, the news was featured most prominently in the financial sections of newspapers/websites (click here), as an uptick in shareholder value is much more newsworthy than a potentially breakthrough drug that could help hundreds of thousands of patients suffering from a heinous disease. Much was also reported about the drug's yearly price of $54,900, which is actually considered reasonable in the demented world of MS drug pricing. Such are the priorities of our whacked out society. Okay, social commentary over…

Tecfidera’s active ingredient is dimethyl fumarate (DMF – click here), a derivative of fumaric acid, a naturally occurring substance that can be found in mushrooms, lichens, and moss. DMF was first used for medicinal purposes in a highly effective anti-psoriasis drug called Fumaderm, which has been marketed in Germany since 1994. It’s important to note that Tecfidera and Fumaderm are not identical compounds, which must be kept in mind when comparing the actions and side effects of the two drugs. Much might be inferred by reviewing the history of Fumaderm, but trying to make precise, direct comparisons could well in lead to erroneous conclusions. More on that later…

The release of Tecfidera has been much anticipated in the MS community, as clinical trials showed the pill to be significantly more effective in reducing relapses and slowing the progression of multiple sclerosis disability than the current frontline MS treatments (Copaxone, Rebif, Avonex, and Betaseron – all injectables), while its side effect profile appears to be quite mild when compared to many of the other MS disease modifying treatments.

Tecfidera joins Gilenya and Aubagio as the only MS treatments currently in pill form. In clinical trials, Gilenya was more effective in terms of reducing relapse rates, but concerns about potentially serious side effects (dangerously low blood pressure and pulse rates, potential for opportunistic infections) have kept the drug from reaching "blockbuster" status. There are some indications that Gilenya may have neuroprotective properties, and it is currently undergoing trials for use against Primary Progressive Multiple Sclerosis (click here). It is one of the few drugs being tested for the progressive forms of the disease. In trials, Aubagio proved to be just about as effective as the CRAB drugs in reducing relapses, and has exhibited some potential in inhibiting disease progression, but the drug comes with two black box warnings (the strongest issued by the FDA) concerning liver toxicity and the possibility that it can cause major birth defects (click here). Tecfidera’s comparatively mild side effect profile, which is comprised primarily of flushing of the skin and gastric disturbances, its high rate of efficacy, and oral dosing have led to the expectation that it will soon be a leader in the multiple sclerosis drug market.

Tecfidera’s mechanism of action, which is not fully understood (something that is not uncommon, the action of many pharmaceuticals are not fully understood), appears to be threefold. The drug exhibits immunomodulatory, anti-inflammatory, and antioxidant properties, the combination of which theoretically affords the compound its potency. In two large-scale studies, called DEFINE and CONFIRM, Tecfidera reduced relapse rates by approximately 50% over placebo, and reduced the progression of disability by about 30%. By comparison, the CRAB drugs reduce relapse rates by about 35%, and Tysabri cuts relapses about 65%. Whether these drugs impact disease progression has yet to be firmly established.

Much of the excitement surrounding Tecfidera involves the prospect that, in addition to its disease modifying characteristics, the drug may be neuroprotective. Neuroprotection is one of the holy grails of MS research. If the cells of the central nervous system can be protected from the ravages of multiple sclerosis, then the progression of the disease can be inhibited. The notion that Tecfidera may be neuroprotective is based on the fact that one of the drug’s supposed mechanisms of action is the activation of Nrf2 pathways in the human body. Nrf2 (click here) is simply a protein that exists within every human cell, inoperative until it is kicked into action by a Nrf2 activator (think of it like a bottle rocket – until lit, it sits there doing nothing, but once lit (activated) it zooms into action). Once activated, Nrf2 migrates into the nucleus of the cell and bonds to the DNA within, initiating the production of powerful antioxidants. If Nrf2 was a bottle rocket, it’s thought that Tecfidera could initiate the process that lights its fuse.

Antioxidants (the good guys) are the body’s defense against free radicals (the bad guys), cell damaging oxygen molecules that are released during the biological process of turning food into energy, much like noxious exhaust fumes are released by an automobile engine turning gasoline into energy. Once free radicals are released they act like wrecking balls, smashing through cell walls and inflicting injury. The process by which free radicals do damage to the body’s tissues is known as oxidative stress, which is believed to be one of the primary drivers of MS disease progression, as well as a factor in many other diseases (click here). Therefore, by combating oxidative stress through Nrf2 activation, Tecfidera may protect central nervous system tissues from damage by free radicals, which would be a very good thing.

Some Facebook pages and websites, including a previous post on Wheelchair Kamikaze (click here), have mistakenly equated Tecfidera with a nutraceutical product called Protandim (click here). In laboratory tests, Protandim has proven to be a powerful Nrf2 activator, a quality it does share with Tecfidera. However, Tecfidera’s mechanism of action appears to be much more complex and wide-ranging, and not confined only to Nrf2 activation. It also effects cytokines (chemical signals that influence the inflammatory process – click here), and down regulates the immune system. This down regulation of the immune system may in fact be the primary driver of Tecfidera’s effectiveness. According to the official report detailing the results of the DEFINE trial (click here), which appeared in the New England Journal of Medicine, “It is difficult to determine whether the therapeutic effect of BG 12 stems predominantly from immunomodulatory mechanisms or from neuroprotective mechanisms.”

Now back to Fumaderm, Tecfidera’s very effective German anti-psoriasis cousin. Fumaderm's efficacy in treating psoriasis, an autoimmune disease, is well documented, with 50% of the patients taking it achieving at least 70% improvement in their condition. Since Fumaderm’s primary component, like Tecfidera, is dimethyl fumarate, its side effect profile is similar to Tecfidera’s. Through 20 years of use, the most prevalent Fumaderm side effects have been gastric disturbances (stomach ache, vomiting, and diarrhea) and flushing of the skin, which, according to a paper prepared by Britain’s NHS (click here), can lead to discontinuance and/or noncompliance in 30% to 40% of patients. In the Tecfidera drug trials, though, dropout rates were negligible, with no significant difference between those patients taking the actual drug and those on placebo. Gastric disturbances and flushing of the skin were the most commonly reported side effects in the Tecfidera trials, but appeared to be manageable and diminished significantly after one month on the therapy. This discrepancy between the patient experience with Fumaderm versus Tecfidera is likely due to the different chemical makeup of the two compounds (Tecfidera is composed only of DMF, while Fumaderm includes DMF and some other derivatives of fumaric acid), and/or to differences in dosing, as patients on Fumaderm generally take a higher dose of DMF than will be given to Tecfidera users. Still, only real world experience will tell us how troublesome these side effects prove to be.

Another effect seen in both drugs is leukopenia, a reduction in white blood cell counts. This condition is accompanied by lymphopenia, a reduction in specific white blood cells, including B and T cells, which are the targets of many of the current MS drugs (Tysabri, Rituxan, Gilenya, Aubagio). This suppression of immune system cells may play a part in the two drugs' effectiveness, but can be problematic if the cell counts get too low, as this might open the patient up to opportunistic infections, although none were seen during the clinical trials. Tecfidera induced lymphopenia and leukopenia are reversible with cessation of drug therapy.

In its 20 years on the German market, comprising over 170,000 patient hours, Fumaderm has been linked to four cases of PML (click here), the opportunistic brain infection associated with Tysabri. While this may initially seem troublesome, it’s important to keep in mind that these cases occurred over a very long time period, and at least one of these patients was using other powerful immunosuppressive drugs. Generally, opportunistic infections are not seen in patients using Fumaderm.

During the Tecfidera DEFINE trial, white cell and lymphocyte cell counts dropped an average of 10% and 28% respectively, which could very well play a role in the drug’s efficacy. Importantly, though, over the two-year run of the trial, no instances of opportunistic infections were reported. It was noted, however, that 4% of trial patients experienced a more serious drop in cell counts (this info can be found on page 1106, paragraph 3 in the NEJM article – click here). In Germany, Fumaderm patients are required to have blood tests once a month for the first six months they are on the therapy, and then every other month thereafter, to keep an eye on cell counts The FDA guidelines for Tecfidera only call for yearly blood tests, and though I’m no doctor, this recommendation seems a bit questionable. Even though no opportunistic infections were noted in the two Tecfidera trials, why not err on the side of caution? We’re only talking about simple blood tests, which could head off potential problems before they get started.

Some other rare but potentially serious side effects noted in the Tecfidera study were liver and kidney events, although most were mild and reversible. There were no reported incidences of kidney failure. Still, I would think, all the more reason for regular blood tests, especially since so many MS patients are on other drugs that can be liver or kidney toxic.

So, what do I make of all this, as an educated patient? Tecfidera seems to be a very promising new drug for MS sufferers, one which might even help those with progressive disease due to its antioxidant, neuroprotective potential. I will very likely begin Tecfidera therapy sometime in the near future, even though my diagnosis is still uncertain and none of the other MS drugs have helped me. I’m encouraged by the fact that Tecfidera is related to a drug that is very effective in treating psoriasis, and has also anecdotally been noted to have a positive effect on a host of other diseases, including sarcoidosis and alopecia. I definitely show signs of some sort of systemic autoimmune activity, a condition against which Tecfidera’s mechanisms of action suggest might make it effective.

Tecfidera’s clinical trials convincingly demonstrate it to be effective in treating RRMS. Whether you believe MS is an autoimmune disease or not, it’s indisputable that the immune system plays some significant role in the MS disease process, and Tecfidera’s combination of immunomodulation, anti-inflammatory action, and antioxidant activation should provide a potent mix to help tame the disease. We’ll have to see just how troublesome the gastric and skin flushing side effects turn out to be, although, as stated above, in the trials they appeared to drop off dramatically after the first month of therapy.

Personally, if and when I do go on Tecfidera, I am going to insist on blood tests every 4-6 weeks, based on the study data concerning leukopenia and lymphopenia, as well as renal and hepatic toxicity. I’m on so many drugs that I rattle when I move, and I’ve learned to take nothing for granted. I’d suggest patients sharing similar concerns print out the New England Journal of Medicine DEFINE trial article linked to above and show the pertinent sections to their neurologist. The 4% rate of serious lymphopenia has not been publicized, as far as I can tell, and that alone should be reason for regular monitoring of blood counts. Better safe than sorry, especially when using a drug new to the market. Of course, that’s just my humble “I'm not a doctor” opinion…

(Update: for more information on Tecfidera and PML, please see my latest post on the topic, by clicking here)

Related articles

• FDA Approves New Multiple Sclerosis Treatment: Tecfidera (fda.gov)
• UPDATED: Biogen Idec rolls up FDA OK for blockbuster multiple sclerosis drug Tecfidera (fiercebiotech.com)
• Biogen Prices New MS Pill At $55K, Prepares For Marketing Battle (forbes.com)

Bits and Pieces: Getting on with Life Edition

(Photo credit: davidyuweb)

(Please note: for those who receive these essays via email, this post contains videos which can only be viewed on the Wheelchair Kamikaze website)

The last couple of weeks have been tough. Losing my friend George, The Greek from Detroit, really hit hard. I’ve never before suffered the premature loss of someone with whom I’ve been so close. Of course I’ve lost loved ones, but they’ve either been elderly, in which case there’s solace in the thought that they lived full lives, or folks for whom I’ve felt affection for but not the extremely close bonds shared with someone in my “inner circle”. The fact that George and I bonded over our shared struggle with a debilitating disease, and that his death was directly related to that illness, only serves to focus the despondency.

Mourning is a strange process. For whom am I actually grieving? George is at rest, the despair he felt at the ravages of his multiple sclerosis ended. From that respect, at least, it would seem that those who knew him should be grateful that his long struggle is over. But I mourn for his life that was upended, and his life that could have been. I feel sorrow for all who will miss him, for all of those who held him dear. But most of all, if I’m completely honest, I mourn for me, for the fact that I’ll never again answer the phone and hear, “Kazmo, this disease fucking sucks!”

Of course, I have other friends to talk to, but George’s tremendously emotional manner was contagious, eliciting, at least in me, a license to let rip with all of the foul miseries and mindbending fears that helplessly watching a creeping paralysis devour your body brews in your brainpan. Yes, I still manage to find some good in (almost) every day, but there were days in the past few years when a significant portion of the good I found was talking to George.

Be that as it may, the world doesn’t stop spinning, the sun doesn’t stop rising, and life must go on. So here’s a collection of MS related items that aren’t too glum or weighty, but include a cause to rally around, some mindful artwork, a few helpful MS hints, and even a healthy dose of sex. What better to focus the mind back where it belongs, on the naughty bits. Believe me, George would approve…

♦ First up, a chance to help a fellow MSer and become a mini movie mogul, all in one fell swoop. Jason DaSilva is a young filmmaker whose work has been seen at film festivals around the world. About eight years ago, at the age of 25, he was struck with progressive MS and decided to turn his camera on himself. His new documentary, When I Walk, chronicles the first seven years of his struggle with PPMS in unflinching fashion, showing the effects of the disease warts and all even as it exposes the heart and soul of the man at the center of the storm. When the film opens, Jason is having some trouble walking; by its end he’s using a scooter full-time, his vision is increasingly affected, and the disease is attacking his hands. In between, we experience the physical and emotional roller coaster of MS as Jason searches for answers and possible cures, and though one might think this would make for gloomy subject matter, the film is an inspiring testament to Jason’s courage, the power of love, and the enduring nature of the human heart. Even as Jason’s body betrays him, he manages to find his soulmate, a woman special enough to love him despite all of the trepidation and uncertainties that come with MS. When I Walk had its premiere at the recent Sundance Film Festival, and received rave reviews (click here). Here’s the When I Walk trailer:


So, it would seem all is well in When I Walk land, right? Unfortunately, that’s not the case. Though the film got a big reception at Sundance, it really needs to be seen in cities around the country and around the world. It shows the side of MS that the public rarely sees, not the sanitized version most often portrayed on television and in the news media, but the Full Monty of ever advancing disability and its effects on the body and mind, capturing the jumble of emotions of the human being trapped inside an increasingly faulty body.

The realities of independent filmmaking today requires that filmmakers themselves raise the funds needed to get their works onto movie theater screens around the country, and Jason has started a Kickstarter campaign (click here) in an effort to do the necessary fund-raising. Kickstarter is a website allows individuals to contribute as little as one dollar to a wide variety of artistic, altruistic, or business endeavors. Jason’s goal is to raise $27,000 by April 3, and as of this writing has almost $19,000 to go. He’ll use the funds to do marketing, advertising, and promotion for the film, as well as pay for printing and duplication costs of the film and its trailer.

I don’t think I’ve ever before made a direct plea for financial donations of any kind on Wheelchair Kamikaze, but I was lucky enough to get a chance to preview this film, and it really struck a chord. So please, if you’re able, chip in as little as one dollar to help kickstart When I Walk into a theater near you (click here), and thus help a fellow MSer tell his story and show the world the realities of living with MS and the courage it takes to battle the disease day in and day out. Thanks.

♦ Check out the cover of the March issue of the journal Neurology, one of the top medical journals in the world:


Can you guess what lies at the heart of the striking piece of abstract art on the cover, called “Celebration”? I think you’ll be surprised to know that it’s (drumroll please)…

My brain!

Artist and MSer Elizabeth Jamison (click here to see a gallery of her work) uses MRI images to make her compelling etchings, and a few years ago I sent her several images from my MRIs and MRA’s (Magnetic Resonance Angiograms), one of which she transformed into the image that is right this moment gracing the cover of a journal sitting in the offices of neurologists all over the world. Pretty nifty, don’t you think?

Elizabeth is herself an inspiration, as the MS that she’s suffered from for over 20 years has progressed to the point that she is now a quadriplegic. Still, she continues making her art, using a surrogate as her hands as she choreographs the artistic process. Her work is gaining attention worldwide, and will be featured in an exhibit in Barcelona next month.

♦ Here in the northern hemisphere, it’s almost spring, and if things go as planned, summer will soon follow. That means the temperatures will be rising, and many folks suffering from MS will be wilting. Heat sensitivity is a hallmark of multiple sclerosis and for many people with MS, myself included, warm temperatures are like kryptonite. Once the temperatures get much above 80°, I can literally feel the energy being drained from my body, and I start losing whatever functionality I’ve so far managed to retain. Strangely, when the temperatures soar, I seem to be negatively affected even if I stay inside my air-conditioned apartment. Defies logic, but it’s the truth. Fun fact: before the advent of the MRI, one of the methods used to diagnose MS was to place the patient in a hot bath and see if their symptoms got worse.

So, what can a patient do to combat these summertime blues? There are many forms of cooling garments, from vests to headbands to scarves, available from a variety of manufacturers (click here). If you are an American person with MS who is in financial hardship, both the Multiple Sclerosis Association of America (click here) and the Multiple Sclerosis Foundation (click here) have programs offering cooling equipment to qualifying clients, free of charge. Don’t be shy, both groups do terrific work, and the heat of the summer will soon be upon us.

♦ Now, finally, the subject you’ve all been waiting for, sex. The Sexuality and Disability webpage (click here) is a comprehensive resource for all things having to do with, well, sexuality and disability. From information on sexual morality to the actual mechanics of sex when dealing with a disabled body to relationship issues to sexual violence, this site is a veritable almanac on sex, sexuality, and relationships for the disabled person. I especially love the modified handicapped icons that grace the site’s front page, which depict a person in a wheelchair and their partner in all sorts of imaginative hijinks. Must’ve been fun coming up those, although some look to be a bit treacherous…

“Don Juan in a Wheelchair” (click here), an article from Salon.com, was written by a man with cerebral palsy, and explores his determination to lose his virginity. The article brought to mind two recent films that deal with similar subject matter, The Sessions and Scarlet Road.

The Sessions is a terrific, touching film starring John Hawkes and Helen Hunt, which tells the real-life story of Mark O’Brien, a severely disabled man who was afflicted with polio in childhood. Because of the weakness in his muscles, Mr. O’Brien had to spend most of his time in an iron lung, except for stretches of three or four hours at a time when he could survive with the aid of a portable oxygen unit. His entire life was spent lying on his back; despite this, he was able to earn a degree in English, and worked as a writer and poet, managing to get out and about on a gurney wheeled around by an aide. The film takes up his story in 1988, when, at the age of 38, he decided he wanted to lose his virginity and contacted a registered sex therapist. The Sessions deals with its delicate subject in a frank, matter-of-fact manner, and is infused with humanity, humor, and beauty. Though hardly pornographic, the film doesn’t dance around the sexual nature its narrative, so if glimpses of nudity and straightforward talk of sexual subjects aren’t for you, this movie probably isn’t your cup of tea. Everyone else, though, can watch The Sessions on Amazon.com’s streaming video-on-demand service for $3.99 (click here). I recommend this film highly. It’s one of the best I’ve seen in a while. (Please note: I have a raging dislike for 90% of American films made after 1980, so this is high praise indeed. BTW, I’m not a snob, but I do have a degree in Film… Okay, maybe I’m a snob…)


Scarlet Road is an Australian documentary that has received much acclaim, but, as far as I can tell, is so far not available for viewing in the USA. The film profiles a sex worker who specializes in catering to the disabled, and looks to be provocative and entertaining. I only wish I could see it. Here’s the trailer…


With that, I’ll bid you a sweet adieu. The show must go on… RIP George Bokos

The Greek, In Memoriam

About two and half years ago I was hospitalized with very high fevers. It turned out I had a bizarre case of meningitis, which of course was extremely debilitating and terribly frightening, greatly exacerbating my very heat sensitive creeping paralysis. A short time after I returned home from the hospital, I was greeted with a great big gift basket, filled with all kinds of delicious goodies. To my immense surprise, the basket came from a man in Detroit that I had met only a few months earlier, and had exchanged several emails and phone calls with. He was a fellow MS sufferer, and I had little inkling at the time that we would soon develop a long-distance connection that would eventually transcend friendship and approach something akin to brotherhood.

The man who sent that basket was George Bokos, the self-described “Greek From Detroit”, who died early last Sunday morning. Although it seems almost de rigueur to offer such platitudes in this kind of essay, in George’s case the following are the absolute truth: he was one of the kindest, gentlest, most generous and good-natured people that it’s ever been my privilege to know. He was smart and funny, a master of sarcasm. In his own way, for better or worse, he was a force of nature, a tremendously emotional man whose heart was his guiding beacon. His friendship was a gift, his loss a heartbreak, and I will miss him as long as I draw breath.

The burdens and constraints imposed by the miserable beast called multiple sclerosis simply became too much for George to bear, and he exited this life on his own terms. The farewell note he left on his blog (click here), though quite forthcoming, only hints at the anguish he suffered. The disease and its wicked gravity robbed him of all he held dear, leaving him bereft of joy, a man whose sense of self was too enmeshed with his physicality to submit to an existence spent bedridden. The ravages of multiple sclerosis broke his tremendous heart and shattered his beneficent spirit. His decline was precipitous, a cruel freefall that proved impossible to break.

I first met George almost exactly 3 years ago, in the office of the Interventional Radiologist who performed both of our CCSVI procedures. I was there with my wife for pre-procedure testing, and George, having had his procedure the previous day, was awaiting his follow-up examination, accompanied by his mom, Hilda. The doctor, who is an avid amateur photographer, hadn’t yet arrived, and I was talking to the office manager, telling her of my photographic efforts using a camera mounted to the arm of my wheelchair. I’d been writing this blog for about a year, and when Hilda overheard my conversation with the office manager, she exclaimed, “Oh my, are you the Wheelchair Kamikaze?” Stunned, I stammered “Yes”, and in a blink Hilda was upon me, showering me with hugs and kisses, thanking me for writing about my life with MS and whatever part I played in helping to bring CCSVI to the attention of the MS population. The four of us had a brief but lively conversation, and then we were on our respective ways. I was tickled by the encounter, thinking it one of those strange bits of serendipity that life sometimes bestows upon us, completely unaware of the bond that George and I would eventually form.

Unfortunately, neither of us benefited from CCSVI treatment. At the time, my disease was fairly advanced and had already forced me to rely on a wheelchair, but George’s MS was far less noticeable, in fact, almost invisible. In the relatively short three years since, MS delivered an unrelenting series of hammer blows to George. It seemed the more he fought, the worse things became, like a man frantically struggling to free himself from a pit of quicksand only to find his every effort resulting in his getting dragged further down. He was tortured by terrible spasticity in his torso, and spasms so painful that at the end he all he could do was lie in bed on his side. He tried to find relief by getting a baclofen pump implanted, but this, like all of his other efforts to save himself, only resulted in a cascade of increasingly dire problems, a grueling saga he powerfully recounted on his blog (click here) Please note, I know many patients who have had fantastic success with the baclofen pump, and George's experience with it shouldn't be considered the norm.

Through it all, George and I became a two-person support group, usually speaking on the telephone at least once a week, sometimes more. We shared some tears, but much more often laughter, both of us marveling at the mind-boggling absurdities of the hand the fates had dealt us. George had a keen sense of humor, and a quick and sharp wit. Together, we would pick apart our miseries as only can be done by those who share them, reveling in the freedom of not needing to maintain a stiff upper lip in each other’s company. Life with MS is filled with irony and paradox, and though many of our conversations began with a recounting of tales of woe, they almost always ended with us joined in a catharsis of fitful laughter, the two of us trading quips and throwing verbal barbs at MS and all its attendant indignities. He called me “Kazmo”, and it seems incredible that I’ll never again hear that voice on the other end of the line. I will miss him so.

Was George perfect? Of course not, none of us are. At times that big heart of his proved a detriment, and overruled his head. His emotions could get the better of him and effect his decision-making, especially when it came to treatment choices. But who could blame him when faced with so frightening a foe, when so little is known about the progressive forms of MS, and when so many alternative treatments are promulgated and overhyped on the Internet? Fear plays a large role in the life of every MS patient, and George's MS was especially aggressive. Over many years I've learned the hard way that discretion is often the better part of valor, a notion that my friend George had a difficult time putting into practice. But he always meant well and acted with the best of intentions, with malice towards no one.

Unlike me, a man who spent much of my lifetime wrestling with neurotic existential angst despite whatever successes I achieved, George was a man with relatively simple needs and desires, incredibly content with the basic pleasures of a happy family life thriving on the fruits of the prosperous business he worked hard to build. As he says in his farewell note, he was in his bliss mowing the lawn, shoveling the snow, or washing his truck, three activities which I would be only all too pleased to pay someone else to do, and if he was still here I’m sure we’d share a chuckle over that one. As is far too common, George’s long marriage tragically fell victim to his disease, and though he battled to remain productive, eventually he had to give up work as well. Losing his family and business, the very anchors of his life, tore his heart out, and inflicted more pain than the disease alone ever could. He loved his children dearly, and his mom Hilda, herself a delight and my treasured friend, was among the brightest lights of his life. She was with him when he died, and says that “he was so happy to finally give MS a kick in the ass that he had a beatific glow and a smile on his face at the last breath.”

I know the “right to die” is a controversial issue, but let nobody ever say that George ended his life rashly, or on a whim. He was simply done suffering the indignities that the disease piles on, the relentless gnawing away of the man he once was. Suffice it to say that the exit he chose was not an easy one. George Bokos was a man who was true to himself, and he took control of his ultimate fate, one of the few things he still had any control over. Proud of his Greek heritage, George remained a Spartan to the end, but it is not that end for which he will be remembered. Though I write this through tears, I know that in time it is only the laughter we shared that will remain. George was one hell of a guy, a unique individual, a true and dear friend, and my comrade in arms. This world is a richer place for having had George in it; it owed him a better fate.

Rest in peace, you crazy Greek, Kazmo will always love you.

Entering the Twilight Zone

A memory arrived in the mail the other day. It wasn’t unexpected, as I had ordered the item on eBay about a week earlier. My wife helped me open the package, and as its contents emerged my eyes fell upon an object that seemed like a long-lost piece of myself, a relic long consigned to the mists of remembrance suddenly made real once again. There in my one working hand was a nearly 32-year-old copy of “The Twilight Zone” magazine, dating back to August, 1981, its cover as instantly familiar to me as the face of a rediscovered old friend.

I opened the magazine and flipped through the first few pages until I found the publication’s masthead, the long column of titles and names of the people who worked to publish each issue. Scanning the list, my heart jumped a bit as my eyes landed on a name that I knew would be there but which somehow managed to surprise me nonetheless. There it was, under the names of the Editor and Managing Editor, just as I remembered: “Editorial Assistant: Marc Stecker”. Me. Suddenly I was 17 years old again, as excited to see my name in print as I was the first time around over three decades past, back when all of life was still in front of me, and my current Twilight Zone like circumstances were beyond imagination.

I worked at The Twilight Zone magazine during the spring semester of my senior year of high school. Because I attended what is considered to be New York City’s best public high school, Stuyvesant High, the school's bulletin board listing afterschool jobs attracted more than the usual busboy and supermarket positions most kids worked at in those days to earn their weekend money. I was lucky enough to be the first to respond to a new posting looking for a proofreader to work at a publishing company uptown.

When I nervously arrived for my interview, I learned that the publication I was applying to work for was a magazine dedicated to The Twilight Zone, one of my all-time favorite TV shows. Back then, before the advent of cable television, when we had to make do with (gasp!) all of seven TV channels, The Twilight Zone was a syndicated staple of local non-network television broadcasts. I can’t speak for the rest of the country, but in New York City the show was televised seven days a week, usually with back-to-back half-hour episodes airing late at night in glorious black and white. Even before working on the magazine, I was already familiar with virtually every episode of The Twilight Zone, having viewed most of them numerous times. I was far from alone in this expertise; in those days before video games, my friends and I would sometimes while away the time recounting the diabolically clever plot lines of Twilight Zone episodes, even though we all knew most of the shows by heart.

The original Twilight Zone series was produced in the late 50s and early 60s, the brainchild of creator Rod Serling, who introduced each episode dressed in a suit with skinny lapels and tie, a cigarette usually dangling from his fingers. The show featured off kilter tales with a very human touch that almost always ended with a mindbending twist, most episodes falling into the sci-fi/fantasy realm. In The Twilight Zone nothing was quite what it seemed, and you’d better be careful what you wished for, because wishes would often come true in unexpected and sometimes – but certainly not always – unpleasant ways. The episodes were deftly produced and directed, and were written by some of the top TV and film wordsmiths of the day. Several episodes starred actors who were already well known, or who soon would be, including Robert Redford, Jack Klugman, Burgess Meredith, and Agnes Moorehead, to name a few.

Much to my surprise, after a brief interview with the magazine’s Managing Editor, I was hired on the spot. My daily tasks were devoted to assisting the very small staff of The Twilight Zone, which was primarily a two-person operation, with responsibilities split between an Editor and a Managing Editor, who were tucked away in a small office at a large publishing company. The company's primary product was a second-tier “adult” magazine (yes, the kind featuring naked ladies – a definite perk as far as this 17-year-old was concerned), with a large staff devoted to publishing it and some sister publications. The Twilight Zone magazine itself turned out to be not some cheesy fanzine, but an impressive, very literate publication, featuring not only information about The Twilight Zone and other science fiction and fantasy movies and TV shows, but also original fiction in the Twilight Zone tradition. As such, every month it featured half a dozen or so new short stories by known and unknown writers, including some very famous authors such as Stephen King and Joyce Carol Oates, stories whose typewritten pages I not only got to lay hands on but help copy edit, making sure the typeset “galleys” for publication were free from mistakes such as misspellings and misplaced punctuation. For a kid with literary ambitions, this was intoxicating stuff.

As I sat in my wheelchair leafing through the yellowed pages of the old magazine, a steady stream of long dormant memories roused from hibernation. My job at the publishing house was my first foray into the everyday world of working adults, and I remember how surprised and amused I was at the controlled chaos around me. Though older and allegedly more mature, these folks seemed as full of foibles and quirks as my teenage friends and classmates. Did anybody ever really grow up?

One of the big bosses at the publishing company was a man with a hair-trigger temper, who was plagued by physical tics that worsened the angrier he got. The editor of the magazine was a fellow named T.E.D Klein (who would later become a not very prolific but well-respected horror author), a man in his mid-30s with a sharp mind and dry wit. I vividly remember the big boss once flying into our office in a blind rage over some relatively minor transgression, screaming wildly as his tic ridden body Increasingly took on a mind of its own, his anger manifesting itself physically in the form of his uncontrollably pounding himself rhythmically in the center of his chest with his right forearm. I of course was horrified, but I could see T.E.D desperately trying to suppress his bemusement, his face weirdly puckered as he bit the inside of his lip in an attempt to not break down in uproarious laughter at the sight of the lunatic in front of him. So, this was life in the working world of adults. How strange.

Although I only worked at the magazine part-time for six months or so before going off to college, those days were brimming with teenage drama and angst, and my time at the magazine was a heady source of pride. Not only did I get to work with the hand typed manuscripts of famous authors, but I also took part in helping choose photos and illustrations for the magazine (developing the deep crush on one of the freelance illustrators in the process), met a variety of interesting people (including Carol Serling, Rod’s widow), and generally felt very much a part of the team.

Holding that old magazine, dating back to a time when I was about to embark on a defining new chapter of my own life story, I wistfully recalled that peculiar teenage mix of omnipotence and insecurity, the future rushing at me filled with prospects both exhilarating and terrifying. Life itself beckoned, and the preview reel that played in my mind featured visions of fame and fortune, romance and adventure, success and recognition, tempered liberally by fears of abject failure and disappointment. Despite occasional flashes of bravado, I was a bundle of neuroses back then, more Woody Allen than Mick Jagger, but still, my visions of a grand future seemed tantalizingly possible.

The notion that my life would be upended by a creeping paralysis certainly never entered my mind, even though I was an accomplished hypochondriac. I feared cancer, brain tumors, even leprosy, but the prospect of paralysis never really occurred to me. Now, with my disease continuing to progress, all of those teenage notions of what was to be are painfully bittersweet, the decades old magazine that sat in my lap their physical encapsulation. Viewed from certain angles, my current circumstances could be fodder for one of the stories contained within its pages, and it has often occurred to me that in some ways I could very well take my place as a character in a Twilight Zone episode.

I’m the wannabe writer who strayed from his path, his literary aspirations forever lingering as a painful reminder of dreams unfulfilled, until he contracted a dread disease and suddenly found his written ruminations reaching a worldwide audience through a medium that didn’t even exist when his dreams were first formed. I’m the lifelong neurotic and hypochondriac who spent countless hours and dollars on psychotherapy, whose inner demons were only put to rest through the realization of one of his greatest fears. I’m the disquieted seeker of wisdom always searching the arcane for glimmers of truth, only to grasp that which is truly important when forced to the sidelines of life, unable to apply the lessons learned to the existence he once led, the life interrupted.

I’ve written this before, but in this context I think it bears repeating. If a fortune teller had told the 17-year-old me that at age 49 I would live with my beautiful wife in a skyscraper next to Lincoln Center, that I’d sleep and wake to my own schedule, that my writings and photos would be read, viewed, and valued by people all around the world, and that I’d spend my days free from the constraints of having to work for a living, I’d have been ecstatic, convinced that all of my dreams would be realized. Of course, that seer would have left out one little detail, one slight wrinkle, an asterisk attached to the story that would make all the difference between dream and nightmare.

Yes, in The Twilight Zone you must be careful to read all of the fine print and consider every nuanced possibility. My life has seen me go from working at The Twilight Zone to living in my own private version of it, which in itself might make for an interesting episode. As Rod Serling might have said in an introduction to that episode, “Presented for your inspection, a man watching himself disappear, one side of his body paralyzed, and the other desperately trying to hold on. He finds himself oddly off-balance, his right leg immobile and his left firmly planted in The Twilight Zone…”

So, has this Twilight Zone life delivered it’s final twist, or might there be one more to come, a happier one in my future unwritten? One can only hope, and hope is the precious legal tender of The Twilight Zone.

Cue spooky music…



Here’s a classic old episode of The Twilight Zone, enjoy…

Big Pharma, Bad Medicine

(Photo credit: Mike Licht, NotionsCapital.com)

Given the importance of rigorous, verifiable research in the practice of modern medicine, it seems a natural assumption that the doctors who treat us base their actions and recommendations on solid, irrefutable evidence. Evidence-based medicine, is, after all, the mantra that we as patients hear over and over again, especially when it comes to our inquiries into the implementation of alternative therapies that fall outside of the medical mainstream. More often than not we are told that there is simply no evidence for the effectiveness of this or that alternative therapy, and that rather than waste our time and energy on unproven and possibly dangerous unconventional remedies, we should stick to the tried-and-true, which almost always come in the form of pharmaceutical products produced by one of the giant multinational pharmaceutical firms, known collectively as “Big Pharma”.

The logic behind such thinking isn’t necessarily faulty. Untold millions of dollars are spent developing drugs and putting them through laborious clinical trials, the result of which is the evidence upon which “evidence-based medicine” thrives. Absent the data produced by this research model, the practice of medicine would be largely reduced to educated guesswork, based solely on the experiences and impressions of individual medical practitioners, which by definition would be limited in scope and might easily be skewed by subliminal prejudices and statistical aberrations physicians could encounter during the course of their careers. Relying instead on evidence amassed through years of rigid research encompassing thousands of patient hours makes deciding which medicine to prescribe or procedure to recommend an exercise in logic and intellectual reasoning, the cornerstones of all disciplines of modern science.

This all makes perfect sense, and indeed this very reasoning has fueled the rapid advances seen in many fields of medicine over the last half-century. However, if the evidence which is the foundation of evidence-based medicine becomes unreliable, or downright misleading, the entire edifice that is modern medicine stands in danger of collapse. To an extent that is almost incomprehensible, this is the very environment in which patients and physicians now find themselves operating, as the research published in scholarly journals and presented at medical symposiums appears to be increasingly biased in favor of the drugs being researched, to the point that physicians are now basing their treatment decisions on woefully incomplete data sets and trial results that conveniently leave out the negative while emphasizing the positive.

As is documented by British psychiatrist Dr. Ben Goldacre in his book “”Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients”, which was recently excerpted at Salon.com (click here), the trial evidence upon which doctors base their most important decisions is often misleading at best, and outright dishonest at worst. As more and more medical research is funded by the drug companies themselves, rather than by independent concerns such as foundations or government agencies, the results of that research appear to be becoming less and less reliable. Dr. Goldacre cites studies which show that research funded by pharmaceutical companies is far more likely to favor the drug being tested than studies funded by independent organizations.

One such study, conducted in 2007, looked at every published study investigating the effectiveness of statin drugs, which are commonly prescribed to lower cholesterol. The studies either compared an individual drug to another kind of treatment, or to a competing statin drug. In all, 192 studies were surveyed, and researchers found that pharmaceutical company funded studies were 20 times more likely to give results favoring the test drug than similar trials funded by independent concerns. Other studies looking at different bodies of research found discrepancies that weren’t quite so dramatic, but invariably found that industry funded studies were far more favorable to the drug being researched.

The reasons for this bias are many. Trial results can be manipulated by testing a drug against another drug given at a sub optimal dosage. Patient populations can be manipulated, so that only patients most likely to get better are used in the research. The researchers themselves, even those conducting studies that are properly designed, may be subconsciously biased by the knowledge that their paycheck is being funded by the pharmaceutical company whose drug is being tested. Whatever the reasons, the evidence appears to be irrefutable: the trial results upon which doctors base their treatment decisions are very often biased in favor of the treatment being tested.

To make matters worse – much worse – drug companies routinely fail to report negative research outcomes, never allowing them to see the light of day. The companies conduct many studies on a single drug, and only publish those studies whose findings are positive for the drug in question. Dr. Goldacre writes about a situation in which he did the very best he could as a doctor, only to later find that he had been misled by the very act of doing his due diligence. In deciding on an antidepressant drug on which to put a patient for whom other drugs had proven ineffective, Dr. Goldacre read every published study he could find on a new drug he was considering, which all showed it to be better than placebo, and as good if not better than competing antidepressant drugs. Later, Dr. Goldacre learned that, though he had read all of the available studies, he’d only received a tiny glimpse into the true research record of the drug he was investigating, Reboxetine.

Some time after Goldacre prescribed Reboxetine for his patient, researchers did a comprehensive survey of all the trials that had ever been conducted on the drug, including those that had not been submitted for publication in academic journals by the drug company, collecting their data through numerous requests to manufacturers and regulating agencies. They found that seven studies had compared Reboxetine to placebo. Of those seven studies, only one found the drug had a positive result, the other six found Reboxetine to be no better than a dummy sugar pill. Only the positive study was published for review by physicians. The six failed studies were never submitted for publication. Trials comparing the drug to competing drugs showed a similar pattern. Three trials, totaling 507 patients, found Reboxetine to be more effective than a rival drug. However, other trials, which used data derived from 1657 patients, found that Reboxetine treated patients fared worse than those on other drugs. These findings were again left unpublished, shielded from the view of the physicians.

Tragically, this situation is typical of the industry. The fact that pharmaceutical companies can fund their own studies and decide to only publish positive data is unfathomable. Would we let, say, automobile manufacturers conduct their own safety tests, and without question accept their claims that the cars they make are the safest in the land? Of course not, yet this same practice has been allowed to flourish in an industry upon which the health of the world has come to rely. The situation is outrageous, but is so endemic that remedies are difficult to come by.

The British Medical Journal, a highly respected academic journal better known these days as BMJ, has, as of January of this year, announced that it will only publish studies that allow access to patient data from all of the studies conducted on the drug in question. The editors of the BMJ lay out their case for this action in a hard-hitting editorial published last October (click here). If only other academic journals would follow suit. The pharmaceutical giant GlaxoSmithKline announced in October 2012 that it will open up all research data for investigation by physicians and scientists (click here). While this is an admirable step, it comes only after GlaxoSmithKline was forced to pay $3 billion to the Federal Drug Administration to settle three charges of fraud levied against it (click here), one of which included holding back data and making unsupported claims regarding its diabetes drug Avandia.

Another of the charges in the GlaxoSmithKline settlement was that the pharmaceutical giant used inappropriate tactics to influence physicians to prescribe their drugs, tactics which included paying large speaking fees to doctors and providing them free access to high-priced entertainment. Couple the reality that pharmaceutical companies have been allowed to bury negative trial data with the fact that these companies routinely use their huge sales forces to court practicing physicians with offers of all-expenses-paid trips to “educational symposiums” in exotic locales, free gifts and lunches, and sponsored lectures, and we have what some cases amounts to a completely rigged system.

As circumstances currently stand, physicians find themselves faced with a situation in which they can’t trust the research published in academic journals (often their only resource for such vital information), and many find themselves subject to conflicting influences offered by pharmaceutical companies, the success of whose products lies completely in the hands of these same physicians. The end result can only be that patients in general, who trust their very lives to doctors, can only wonder about the motivation and correctness of the treatment decisions made on their behalf. For MS patients, whose drugs can cost tens of thousands of dollars a year and some of which carry potentially deadly side effects, the gravity of these questions is only multiplied.

It’s a situation that truly boggles the mind.

The below video is a presentation given by Dr. Ben Goldacre on some of these very same issues. It's really a must watch…
 

Related articles

• 5 prescription drugs doctors had no idea could hurt their patients (ted.com)
• What is known - and not known - about your flu medication (macleans.ca)
• Profits over your dead body (arstechnica.com)

Changes, Inside And Out

Change (Photo credit: mbgrigby)

For many individuals, change is an unpleasant proposition. Most folks generally strive to maintain stability in their personal and professional lives. Major life changes, such as switching jobs, suffering the breakup of a romantic relationship, or moving to a new location can cause tremendous amounts of anxiety and stress, and studies have shown that some major life events, such as divorce, can have a lasting negative effect on mental and physical health. The simple fact is, though, that a certain amount of change is inevitable, and quite often changes once feared turn out, in retrospect, to have been for the better.

Once, while working for a large corporation, I attended a three day symposium that focused entirely on how to deal with change from a business point of view. Since change is inescapable, the symposium leaders told us, rather than fearing and trying to avoid it, workers and organizations are much better served by anticipating and embracing the shifting circumstances that are sure to come. Sticking rigidly to the tried-and-true will sooner or later find a business, no matter how large or successful, facing an existential crisis.

Patients dealing with progressively disabling diseases like Multiple Sclerosis are often forced to navigate lives riddled with change. Some of these changes, the physical, are often abundantly obvious to the outside world. Others, the changes that occur within, which are necessitated by the patient’s need to cope with their changing physical circumstances, are often only perceived by the patient themselves, or those closest to them.

From the moment of diagnosis, change becomes a constant way of life for the stricken, and the uncertainties associated with a disabling disease only serve to amplify the anxieties felt by the patients suffering from it. The physicians call MS a heterogeneous disease, meaning that it can present quite differently from patient to patient. Be that as it may, no matter how the disease presents itself physically, psychologically all patients share a fear of the physical destruction that can be wrought by the disease, and the resulting life changes that may be forced upon them.

I can quite clearly remember the haze of confusion that engulfed me in the days and weeks following my diagnosis, a sense of befuddlement heightened by the fact that the simple act of diagnosis had forced a sudden, irrevocable change in my reality, a permanent alteration to my sense of self. Although my symptoms at that point were largely invisible, I knew that I now stood apart from the crowd, that the so-called problems that I grappled with pre-diagnosis were dwarfed by a larger one that lurked within me, one that had the potential to change my life in ways that were almost too terrible to contemplate.

Though my knowledge of MS at that time was quite limited, I knew from the moment of my diagnosis forward that my life would never be the same. Even as I vowed to fight the disease with everything I had, and consciously told myself that this hurdle needn’t be an insurmountable wall, the research I was obsessively doing to educate myself didn’t paint quite so confident a picture. Yes, many patients were able to fend off significant disability for years and sometimes even decades, but others found themselves caught in the jaws of an insatiable monster, their lives twisted in ways they once thought impossible. Deep inside I knew that waves of changes were coming; it was just a matter of how destructive they would be and how fast they would crash ashore.

Indeed, my life now, just about 10 years later, bears little resemblance to the one I lived on the day I first noticed my right knee buckling ever so slightly with every step I took. A snapshot of my existence taken just before my diagnosis compared to one taken at this very instant would reveal changes so dramatic as to be almost surreal. The path from then to now is paved with incremental changes, each following a logical progression, but as I travel down that path the sum total of those changes seems anything but logical.

Through conscious effort I’ve managed to find a measure of solace and sometimes even contentment despite the effects of the disease, but not a day goes by that I don’t find myself at least once experiencing a terrific moment of shock at the toll the disease has thus far exacted. And then the knowledge that further changes are surely coming briefly crystallizes and compounds that shock, like a sudden chill stabbing through a drafty window frame, until with effort I force myself back into the relative safety of present. There is no getting used to the situation, rather, one learns to live with it largely because there is simply no other choice..

The physical changes inflicted by my disease (which now may or may not be MS, depending on which doctor you ask) that impact my day-to-day existence result from a toxic brew of symptoms. Muscle weakness, spasticity, fatigue, and a storm of other symptoms subtle and possibly nameless combine to grip me in their own diabolical custom-made vise. The progressive nature of the illness makes mentally coming to terms with any current state of disability a difficult proposition, since without some form of intervention it’s almost certain that more losses are to come.

Some patients are fortunate in this regard, and their disease plateaus at a certain point, stabilizing their state of disability, at least for a while. My disability, though, has thus far shown itself to be a constantly moving target. Trying to throw a psychological net around it so that it can be assimilated into at least a semi-permanent sense of self has proven to be an exercise in futility, like attempting to collect soap bubbles momentarily floating through the air. Change, then, has become a constant, and my life over these last 10 years can be charted by the mental and physical adjustments made to accommodate an ever transforming new normal.

Starting at day one and plotting my course to the present, walking with a limp progressed to walking with an ankle brace, and then to walking with a cane, as the distances I was able to travel grew ever shorter. Soon after came a power wheelchair, at first only used outside of my apartment, but eventually inside as well, much to the chagrin of my apartment’s walls, doorframes, and certain pieces of furniture. Walking is now reserved for the few clumsy and increasingly difficult steps between my chair and the bed, or my chair and my computer, or my chair and wherever else my chair can’t quite reach.

Of course, mobility issues are only part of the physical damage done by the disease. These myriad physical changes have made necessary alterations to my very definition of who I am and the qualities with which I define myself, as the disease methodically stripped away layer after layer of the superficialities that, over time, I had come to believe were the building blocks of “me”. The impermanence of what once seemed to be the foundational elements of my life speaks loudly of the tenuous fragility of what most consider their reality. In fact, the only permanence I can now count on is change, and living life in a state of constant physical flux requires ongoing psychological adaptation as well.

Unlike the changes to my physical self, which have been decidedly negative, many of the psychological changes that I’ve undergone have been surprisingly positive. I’ve certainly gained a sense of perspective, as many of the problems that vexed the healthy me have been revealed to be mere trivialities. Since the disease itself appears to delight at taking whacks at me, I’ve compensated by trying to be easier on myself, though self-criticism sometimes still does get the best of me. I’ve gained a tremendous amount of empathy for the downtrodden, victims not only of disease but also of circumstance, especially if those circumstances are not of their own doing.

Above all, I’ve learned the immense value of striving to stay rooted in the present, as the now, this very moment, is all we ever truly possess. The past is but a collection of memories filtered through a veil of years, and the future a place populated, courtesy of the disease, by some potentially very real monsters. Even if the now isn’t ideal, you do yourself a tremendous disservice by not attempting to fully occupy every moment. Far more than platinum, gold, or diamonds, time is the most precious of commodities, as it is irreplaceable and grows scarcer with each passing second. Used properly, the past is a tool that can best inform us how to make the most of the present, but it’s so very easy when faced with a present that is wrought with hardship to instead use the past has a sanctuary, attempting to blot out what is with memories of what was.

Though this may provide some temporary and sometimes much-needed comfort, ultimately one must find the resolve to seek the nugget of good that always hides somewhere in the present, even if finding it requires digging through layer after layer of psychological and spiritual pain. For each of us the composition of that glimmer of good might be quite different, but reason to hope, I think, is an essential ingredient. Once this labor is done, and the nugget of good uncovered, it must be held tightly and nurtured, and carried through the next moment, and then the moment after that.

Change is never easy, and the sea of change engendered by a crippling disease can be especially cruel. It can be tremendously difficult to not get caught in its currents and dragged under, and often the more one struggles the tighter gets the grip of its tides. Rather than wasting precious energy fighting the pull of the roiling ocean within, practicing kindness to self and making some effort to accept what is allows one to let go and float along the crests of the turbulent waves of distress, instead of fruitlessly struggling while being pulled under by them. This can be the key to finding respite amidst a raging storm, and ultimately making your way to calmer waters.

Attempting action through inaction is of course easier said than done, especially when the changes are coming hard and fast and it seems that there is no time to even take a breath, but taking charge of the raging elements within to create your own internal reality is the only way I know to soothe the savage psychological goblins of progressive illness. We must never stop fighting the disease, but in order to properly do so we must consciously give up the fight we sometimes wage against ourselves, and focus our efforts instead on the very real beast at hand.

A Potentially Effective Treatment for Progressive MS: Hiding in Plain Sight?

Methotrexate (Photo credit: Wikipedia)

While all of the varieties of Multiple Sclerosis are vile, especially troublesome are the progressive flavors of the disease. Over the last two decades, strides have been made in understanding and treating Relapsing Remitting MS, the most common form of the illness. While the available treatments for RRMS are far from universally effective, don’t address the still unknown root cause of the disease, and some carry with them downright frightening side effect profiles, they do significantly improve the quality of life for many of the patients taking them. No such strides have been made in the fight against progressive MS. Patients suffering from Secondary Progressive MS (SPMS) or Primary Progressive Multiple Sclerosis (PPMS) are left with few if any treatment options, and their care often amounts to nothing more than aggressive attempts at symptom management. The reasons for this are many, including the relatively small patient population, and the difficulty in designing cost-effective treatment trials with readily measurable endpoints.

Given the confusion regarding the subtypes of MS that I see on Internet forums, it seems that a quick rundown of the subtypes may be in order. Relapsing Remitting Multiple Sclerosis, RRMS, is marked by distinct disease relapses, during which a patient suffers a significant onset of symptoms, followed by periods of remission, when those symptoms subside and the patient returns to their former physical state, albeit sometimes with additional accumulated disability. After a period of years, the disease of many RRMS patients transitions into Secondary Progressive Multiple Sclerosis, SPMS, at which point they stop having relapses and remissions, and instead suffer a steady accumulation of symptoms. Primary Progressive Multiple Sclerosis, PPMS, is much like SPMS, in that patients experience a steady increase in symptoms and disability, without the peaks and valleys that signify RRMS. The difference between SPMS and PPMS is that, by definition, all SPMS patients must have had RRMS first, whereas PPMS patients experience progressive illness from the onset of their disease. If a patient has ever experienced relapses and remissions then they cannot have PPMS. If such patients find themselves, over time, suffering from a strictly progressive course of the disease, they would fall into the SPMS category. As mentioned above, both SPMS and PPMS, though distinct subtypes of the disease, unfortunately share the same lack of effective treatment options.

There is, though, one treatment, called intrathecal methotrexate, that has shown promise in limited real-world implementation when used to treat progressive MS, both in anecdotal patient reports and retrospective studies conducted by the one MS clinic that makes extensive use of the treatment. Unfortunately, most MS neurologists are unaware of the potential benefits of intrathecal methotrexate for progressive MS patients, and many who are aware of the protocol are often too dubious of the treatment to give it serious consideration.

The intrathecal methotrexate treatment protocol involves injecting the drug methotrexate directly into the spinal fluid of progressive MS patients, via a lumbar puncture. The treatment is typically given every eight weeks, using a very thin needle to inject the medication into the lumbar region of the spine. While many patients may be understandably queasy about the prospect of having a lumbar puncture every eight weeks, when done by experienced medical personnel the procedure should cause minimal discomfort with few side effects. When weighed against the insidious nature of progressive MS left untreated, periodic lumbar punctures, as unsavory a prospect they may be, certainly are preferable to an inexorable slide towards significant disability.

Used extensively by the International Multiple Sclerosis Treatment Center of New York (where I am a patient), the use of intrathecal methotrexate has been shown to be widely effective in limited studies published by the clinic’s researchers and practicing physicians, led by Dr. Saud Sadiq. In one such study of 121 patients, disability scores were found to be stable or improved in 89% of SPMS patients and 82% of PPMS patients one year after their last treatment (click here). A longer-term study (click here) found that 48% of patients experienced no increase in disability after treatment periods ranging from 3 to 6 years. As noted, both studies looked at small patient populations, and did not include a placebo group for comparison, but their findings do offer some intriguing evidence of the efficacy of this treatment in a notoriously hard to treat group of patients. It is thought that intrathecal methotrexate, which has known anti-inflammatory properties, also may inhibit the progression of MS by interacting with astrocytes, cells that are associated with the formation of MS lesions (click here).

When given orally or intravenously, methotrexate’s side effects are typical of many chemotherapy drugs, and include hair loss and nausea. In the tiny doses used in intrathecal injections, though, the side effects are negligible. I experienced absolutely no side effects from the treatment, and neither has any patient I’ve met have has also undergone the protocol.

In my time under Dr. Sadiq’s care (since 2004), I have tried the treatment on two occasions, totaling eight intrathecal injections of methotrexate. Unfortunately, the treatment did me no benefit, but I am a very poor example upon which to base any opinions, since my disease is highly atypical, if it is even MS at all (click here). Another popular MS blogger, my good friend Mitch, who writes the terrific MS blog “Enjoying the Ride”, suffers from classic PPMS, and recently happily announced that after five spinal injections of methotrexate, the progression of his disease has slowed to a trickle, and may have even stopped (click here for all of Mitch's methotrexate posts). As documented in his blog, Mitch had to do a bit of heavy lifting to get his neurologist to agree to treat him with intrathecal methotrexate, but he eventually got his neurologist to agree after providing him with research documentation linked to in the above paragraph. Mitch's experiences with the treatment haven't always been easy, but have been well worth it if indeed the progression of his illness has been beneficially impacted.

Why has the use of intrathecal methotrexate for the treatment of progressive MS not been studied more extensively? You’d think that a treatment as potentially effective as this would attract researchers and pharmaceutical companies like flies to honey. Unfortunately, the sad truth is that it all comes down to money. Methotrexate is a very old drug (click here), first developed in the 1950s to treat certain forms of leukemia. It has since been shown to be effective in treating other kinds of cancer, as well as lupus and a variety of other autoimmune diseases. It was granted FDA approval for use in treating rheumatoid arthritis in 1988. Because the drug is so old, any patents held on it have long since expired, and it’s available as a cheap generic compound. In the extremely small doses used to treat MS intrathecally, each shot costs about five dollars. Therefore, there is very little profit to be derived from marketing methotrexate, and so it receives no attention from the pharmaceutical companies, which at this point fund the vast majority of medical research conducted in the USA. Many other potentially effective treatments, such as low dose naltrexone (LDN), also fall into this same trap, left largely untested and unheralded simply because facilitating robust trials would not be cost-effective. Forget about patient well-being, the financial bottom line has become THE bottom line in medicine as it is now practiced, oftentimes to the detriment of the very people the system supposedly exists to benefit. When patients are viewed first as consumers, something is very wrong.

Based on what I know about this treatment, I’d suggest that any patient with progressive MS at least discuss intrathecal methotrexate with their MS neurologist. Be prepared for pushback. As noted previously, most neuros are reticent to try this approach. This is where the importance of patient education and self advocacy comes in. When talking to your doctor, bring back up materials, such as printouts of the research linked to in this post, and some of Mitch’s blog entries from Enjoying the Ride. With other treatment options limited if not nonexistent, and the long-term prognosis of those suffering from progressive multiple sclerosis so daunting, all options need to be put on the table.

Although having a chemotherapy drug injected directly into the spinal fluid may sound a bit radical, when broken down to its individual bits the protocol really isn’t all that scary. Methotrexate has been used safely and effectively for decades, and in the tiny doses used in this protocol presents very little risk. Lumbar punctures, while no joyride, are routine for most neurologists, and the use of very fine needles minimizes the chance of postprocedure complications. Many neurologists are willing to try the new generation of powerful immunosuppressant drugs now used to treat RRMS on their progressive patients, with no proof whatsoever of their efficacy in treating the progressive forms of MS. Given the potentially dire consequences of leaving progressive MS untreated, shouldn’t a potential therapy that has already helped hundreds of patients be given serious consideration, regardless of its "outside the box" designation?

On the day of my diagnosis, I vowed that if this disease was going to take me down, I was going to go down swinging, both fists battered and bloodied, all guns blazing. Progressive MS (or whatever it is that I’ve got) isn’t very likely to show much mercy, and as a guy who grew up on the streets of New York City I know that when faced with such an adversary, all bets are off. You do what you have to do, throw any rules right out the window, and meet fire with fire. Like it or not, this is mortal combat, and if getting a spike in the back every couple of months provides even the slightest chance of beating this thing back, I was, and am, willing to take it. Treatment with intrathecal methotrexate did not work for me, but it has worked for some, and that alone should give all engaged in the struggle reason enough to give it serious consideration. Talk to your doctor, and pay close attention to their advice, but always remember that in the fight against your disease, the doctor-patient relationship should not be a dictatorship, but a partnership. Treatment with intrathecal methotrexate may be unconventional, but, as it stands now, the conventional modality for treating progressive MS has been nothing but an abject failure. Hopefully, with ongoing research, this situation will turn, but in the meantime I say self educate, agitate, and take an active role in mapping the attack on your illness.

Bits and Pieces: Doomsday/Happy Holidays Edition

English: An engraved illustration of Santa Claus and what may be Mrs. Santa Claus from the 1878 book "Lill's Travels in Santa Claus Land and Other Stories", by Ellis Towne, Sophie May and Ella Farman. Artist unknown. (Photo credit: Wikipedia)

Well, if the Mayans are correct, this might be one of my least read posts ever. Yup, as I write this, the doomsday allegedly predicted in the Mayan “Long Count” calendar, December 21, is only 2 ½ hours away. According to end of the world aficionados across the planet, the Mayan calendar ends on Friday, December 21, 2012. The ancient Mayans were remarkably expert astronomers, and their calendar was able to predict celestial events, such as eclipses, centuries in advance. Even more incredibly, they also predicted that their prophecy would provide cable television’s History and Discovery Channels with fodder for an endless amount of doomsday programming. If it weren’t for the Mayan doomsday, ancient aliens, and Nazis, these two media outlets would be forced to put up a test pattern 24 hours a day. Not that I’m complaining, because there’s nothing I like to watch more than Nazi aliens causing doomsday (much to Karen’s dismay). If the Mayans were correct, tomorrow should be interesting.

If, on the other hand, the Mayans weren’t correct, and the world doesn’t end in a terrifying cataclysm of meteor showers, catastrophic Earth changes, floods of biblical proportions, alien invasions, magnetic polar shifts, or a lack of cable programming, then Ho Ho Ho, Happy Holidays! Hope you were nice and not naughty this year, otherwise jolly old St. Nick will leave nothing but a lump of coal in your stocking. I can think of a few less savory lumps he might leave, but I suppose coal is disappointing enough to get the point across. Besides, if the Mayans were right, and doomsday strikes but you actually survive it, that lump of coal might come in pretty handy. So, this year you may be better off having been more naughty the nice.

To my mind, though, being really nice includes a prerequisite bit of naughtiness, so I’m not quite sure how Santa Claus actually divvies up his list. The naughty/nice divide is surely not black and white, but I guess that’s why Santa Claus gets paid the big bucks. Please, though, don’t tell me that stuck way up there in the North Pole with just Mrs. Claus and the elves that no naughtiness ensues. For Santa’s sake, I hope that Mrs. Claus makes liberal use of the Victoria’s Secret catalog…

Be that as it may, here’s this month’s selection of mostly MS related news tidbits that caught my eye over the last several weeks. Hope you find them entertaining and/or informative. If you don’t, feel free to pelt me with your lumps of coal, because I’m pretty sure that naughtiness is pandemic among the Wheelchair Kamikaze readership.

♦ I'd like to give a shout out Healthline.com (click here), which recently named Wheelchair Kamikaze the "Best MS Blog of 2012". Healthline is an extremely valuable patient resource, whose mission is to “improve health through information”, by providing readers with “objective, trustworthy, and accurate health information guided by the principles of responsible journalism and publishing.” One of the site’s unique features is an interactive, multimedia “MS Assessment Tool” (click here), which allows patients to objectively assess the state of their disease, and thereby make more informed treatment decisions. It’s really pretty cool. Actually, it would be cooler to have no need to use an MS Assessment Tool, but we can only play the cards we’re dealt. Healthline's Facebook page (click here) offers patients a rich social media experience for learning and interacting with others.

♦ At the risk of appearing like a gluttonous blog award whore, Wheelchair Kamikaze has also been nominated for a “Best in Show” award by Wegohealth. If you’d like to endorse that nomination, you can do so by using the badge located on the upper left-hand column of this page.

Okay, shameless self-promotion over.

♦ On the clear as mud MS research front, we have two interesting studies that looked at whether or not the interferon drugs effectively delay the progression of MS disability. The answer is a resounding “No” (click here). Also, a resounding “Yes” (click here). That’s right, two studies, two entirely different conclusions.

Okay, to be fair, the studies didn’t look at quite the same parameters. In the first study, the interferons (Avonex, Rebif, and Betaseron) showed no efficacy in delaying progression of disability to EDSS score 6, which basically translates into needing a cane to walk 100 m. This study compared contemporary treated patients, contemporary untreated patients, and an historical group of patients derived from older patient histories tracked before the interferon drugs were available. The results of the study are actually a little bit confusing, as the untreated contemporary patients time to EDSS 6 was 4.0 years, while treated patients took 5.1 years to reach the same level of disability, which would seem to indicate that treatment did have a beneficial effect on disability progression. The historical group took 10.8 years to reach the same EDSS score. However, more than twice the number of treated patients than untreated patients eventually reached EDSS 6, and four times as many reached that point in the historical group. When researchers mixed all of this data together, their conclusion was that the interferon drugs showed no beneficial effect in delaying progression. Confused? Me too.

The second study looked at whether or not the interferon drugs delay the transition from RRMS to SPMS. As all diligent MS patient should know, transitioning from RRMS to SPMS is not a good thing, as progressive MS has few if any effective treatments, and progressive patients generally experience a slow and steady increase in disability, without the benefit of any remissions. This study, conducted in Sweden, compared contemporary patients treated with DMDs with a historical group of patients from 1950-1964, decades before the DMDs were available. Although the abstract does not provide concrete numbers, the researchers conclude that the DMDs do delay the onset of SPMS, which, if true, is a very good thing.

So, what to make of these studies? I think that the only real conclusions that can be drawn are that no conclusions can be drawn. It appears that the CRAB drugs are more effective than many anti-drug advocates would have it, and less effective than mainstream neurology would like patients to believe. In the end, each patient must make their own decisions based on their own experiences. There does seem to be a growing body of evidence that shows a “window of opportunity” early in the RRMS disease process, when nearly all treatments are most effective. Once this window closes, it seems that the beneficial effects of the current MS treatments fall off dramatically. Personally, if I were a newly diagnosed RRMS patient, or a patient early in a course of relapsing remitting disease, I would opt to go with treatment. But again, that’s just me; each patient, in conjunction with their doctors, must assess their own situation, which, as the above shows, can be no easy task given all of the conflicting information.

♦ As patients, we must never forget how wonderful our caregivers are, if we are lucky enough to have good ones. It’s very easy for the strain on the caregiver to take a backseat to the problems of the patient, but the disease takes a terrible toll on all it touches. A study out of Mexico (click here) attempted to examine the impact of MS on the emotional health of caregivers. Researchers found that 40% of the caregivers they studied met the criteria for “probable major depressive disorder”. They furthermore found that the symptoms most likely to cause distress in caregivers were patient depression, difficulty talking, difficulty hearing, becoming upset easily, and upsetting other people. Patient symptoms causing the lowest average level of distress for caregivers included difficulty learning, seizures, trouble reading, difficulty eating, and difficulty writing. I found this surprising, as it seems that the symptoms that might be most troublesome to patients were found least troublesome to caregivers. This just illustrates the complexity of the patient/caregiver relationship, and the fact that 40% of caregivers were found to be clinically depressed speaks volumes of the hideous nature of multiple sclerosis. If you’ve got someone who cares for you in a loving, supportive manner, please take this holiday season to make sure they know just how much they are loved and appreciated.

♦ A while back I posted an essay that talked about how hard a job it can be just to be sick (click here), with seemingly constant battles with insurance companies and other organizations and individuals in the medical industrial complex. This opinion piece (click here) from the New York Times, written by a prominent business journalist who found himself in a mindbending skirmish with his insurance company when he simply tried to find out how much the pill that controls his blood cancer would cost, is a terrific example of just how maddening the “job” of being a patient can be. The article is really a must-read for anybody caught in the lunatic web of modern medicine as it is now practiced.

♦ The Scottish island of Orkney one of the highest rates of MS in the world, with one in 170 women on the island suffering from the disease. Researchers now think that the Viking ancestry of Orkney residents may be to blame (click here). Studies have shown that half the general population of the Orkneys originates from Scandinavia, and other studies show that areas colonized by those with Viking ancestry have higher incidences of MS as well. For example, in Canada the provinces colonized by the English and Scots have higher rates of MS than does Québec, which was colonized by the French. This would obviously point to a genetic link to the disease, although other factors must be in play as well, such as a lack of vitamin D (the places studied afforded their residence very limited sun exposure), as well as environmental elements. Furthermore, researchers found that even within Orkney there were “hotspots and cold spots. Some isles and parishes and villages had much increased rate and in other parts there were hardly any residents who had it.”

And all along I’ve been thinking that the worst thing about the Vikings was all the raping and pillaging. Now I can add MS to my list of Viking grievances. In the Vikings favor, though, is the fact that one of their kings was named Ivar the Boneless (click here), which is one of my favorite names in all of history. If there is anything to his name, good old Ivar may have been disabled (there are other interpretations, including that he might have been impotent), but that didn’t stop him from leading a brutal invasion of England. And this was way before there were any laws mandating the rights of the disabled.

So, with cheerful visions of Ivar the Boneless pillaging and plundering with his apparently wet-noodle like appendages dancing in your head, I bid you all the happiest of holiday seasons. May the coming year bring you copious amounts of good health and an abundance of happiness. May your fondest holiday dreams come true, and always remember that the greatest gift of all is love shared between family and friends.

Here’s a classic Christmas tune, sung by the always alluring Eartha Kitt, with some, um, unusual accompanists. I believe that this video proves that Boy George is a time traveler. Happy holidays!…

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