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.