Heat and MS

Now that the summer is sizzling hot (warmer up North than here in Florida), we received the following question:

Question

I live in NJ but our temps soared to 105 and 107 this week. I have had MS (diagnosed) for 5 years. We lost a/c at work this week, and I had a scary episode that almost put me into the emergency room. I drove home (and it's hotter in the car) and luckily my husband was with me.
I suddenly said "I don't feel well" and got instantly dizzy, almost blacking out and vomiting. I lay on the floor of the bathroom like that for a half hour. Called the doctor who said if I didn't improve in two hours to go to the emergency room.

I'm a patient at the Gimble center in Teaneck and my check up is in two weeks. I guess I will get a note stating that when we lose a/c or heat I need a phone call because i can't work under those conditions. I I immediately drank 5 or so glasses of juice and water.

Any other suggestions would be appreciated. I had some cool packs from my COPAXONE deliveries and I put them on my body especially on my wrists and under my armpits.

It was very scary for me, I hope it never happens again.

Answer

Thank you for the email.

As you are well aware, heat affects people with MS a lot and can cause an uncovering of older symptoms (this is called Uhthoff's phenomenon).

You made the right choice of using your COPAXONE cool packs, but there are more formal cooling vests, from such companies as Polar Products and Steel.

Two MS organizations work hand-in-hand have assistance program for people with MS who need these vests -- the MS Association of America (MSAA) and the MS Foundation (MSF). We work closely with both of these great trusted partners and Dr. Kantor serves as a member of MSF's Healthcare Advisory Panel and answers questions on their MS Forums:

http://bit.ly/9irjfl


MSAA - http://bit.ly/bb4poe
MSF -- http://bit.ly/c92L1l
Neurologique -- http://bit.ly/a9o5va

There are two main types of cooling vests: active and passive.

Active cooling involves a power source and are less common than
passive cooling. Passive cooling mostly mean evaporative cooling
(the vests or hats or scarves, etc.,which have beads inside,
that you dip into water) and ice pack cooling.

It is important to use the right cooling vest for your environment
and for YOU.
For example, in high humidity areas evaporative cooling is not the right
choice and ice packs (like you used are better).
Here is another source of information: http://bit.ly/bIRxo0 


I hope that this was useful.



Follow-up

I just spoke to my boss who knows now to call me if the a/c ever breaks. This is what my doctor recommended. He says it's not even a "reasonable accomodation" because it's simply the civil, correct way to go. When I go to Gimble next week however, I'll have my neurologist put it in writing that if the heat or a/c breaks, I need a phone call.

Has anyone else faced a similar situation? How did your employer react?

Post to Facebook: http://bit.ly/bCwjf2



- Dr. Daniel Kantor, MD BSE
Medical Director Neurologique

info@neurologique.org

www.neurologique.org

Happy days at the FDA

Happy Days are here again.

June 10^th 2010 is a big day for the MS community – the FDA (Center for Drug Evaluation and Research (CDER)) is having a Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee to discuss Gilenia (Fingolimod or FTY720) .

Although Novartis’s Gilenia, which is set to be the first oral disease modifying agent/drug/therapy (DMA/DMD/DMT) for Multiple Sclerosis (MS) had its priority review PDUFA (Prescription Drug User Fee Act) date pushed out to September 2010, this meeting is important because it will give us much clearer insight into what concerns the FDA may have.

The are 12 questions raised to the FDA Advisory Committee to discuss are:

1. Has the sponsor demonstrated substantial evidence of effectiveness of fingolimod for the treatment of patients with relapsing remitting multiple sclerosis to reduce the frequency of clinical exacerbations? [Voting Question]

2. Has the sponsor demonstrated substantial evidence of effectiveness of fingolimod for the treatment of patients with relapsing remitting multiple sclerosis to delay the accumulation of physical disability? [Voting Question]

3. If the answer to question #1 and/or question #2 is yes, should the sponsor be required to evaluate the effects of doses lower than 0.5 mg once daily? [Voting Question]

4. If the answer to question #3 is yes, should this be required prior to approval? [Voting Question]

5. If substantial evidence of effectiveness has been demonstrated, do you conclude that there are conditions under which fingolimod could be considered safe in use for this indication? [Voting Question]

6. First-dose effects of fingolimod include bradycardia and heart conduction abnormalities. Based on the data presented to you, should patients be required to receive the first dose in a monitored setting? [Voting Question]

7. If the answer to question #6 is yes, should that requirement apply to all patients or to a specific subset?

8. Fingolimod causes macular edema, including at the dose proposed for marketing (0.5 mg). Is routine ophthalmic examination sufficient to monitor patients treated with fingolimod? [Voting Question]

9. Fingolimod causes a gradual decline in pulmonary function that appears partially reversible. Do you believe that routine pharmacovigilance will be sufficient to mitigate the risks associated with the pulmonary toxicity of fingolimod? [Voting Question]

10. If the answer to question #9 is no, what additional monitoring or study do you recommend?

11. The sponsor has proposed to conduct a 5-year post-marketing safety study in 5000 patients to further explore the safety of fingolimod 0.5 mg under routine clinical care. Do you believe that such a study would be sufficient to address safety issues observed in this database, or do you believe that other safety studies should be required to assess specific safety concerns? If so, please identify these concerns.

12. Considering the risks and benefits, do you believe that fingolimod should be generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate MS therapy? [Voting Question]

To help us sort through these question, let’s go through the poster abstracts presented at the recent Consortium of MS Centers (CMSC) Annual Meeting in San Antonio, TX.

1. 1 1. TRANSFORMS – Oral fingolimod (FTY720) vs intramuscular (IM) interferon beta-1a (IFNB-1a) in relapsing-remitting multiple sclerosis (RRMS): clinical efficacy results.

In this trial patients received a daily oral pill and a weekly intramuscular injection, but it was double-blinded (both the patient and the team evaluating the patient) didn’t know whether she was receiving a real pill of fingolimod (at two doses – 0.5 mg and 1.25 mg) and fake (placebo) intramuscular injections or a placebo pill and real interferon beta-1a (Avonex) intramuscular injections.

The 3 arms of the study were well matched before the study and we saw a significant reduction in the annualized relapse rate (ARR) in this one year study: ARR for fingolimod 0.5 mg was 0.16 vs. fingolimod 1.25 mg at 0.2 and IM IFNB-1a at 0.33.

This means that we have a study population that looks similar to our more recent (“modern”) clinical trials in that it shows an ARR for the current injectables at about 0.33, yet we have an oral drug that beats active treatment (not simply placebo – this trial had no oral placebo + IM placebo arm) by 38 – 52%.

The data was further divided into the ARR for treatment naïve patients (0.15 vs. 0.17 vs. 0.31) and the ARR for participants who were previously treatment with a DMT (0.26 vs. 0.33 vs. 0.53). This makes a lot of sense – people who entered the study with 1 or more confirmed relapse during the previous year (or 2 or more confirmed relapses in the previous 2 years) and who had been on a DMT already, are more likely to have not responded fully to the DMT and, hence, be harder to treat with any medication, including fingolimod.

Now many patients (and neurologists) will say that an ARR of 0.33 (in patients treated with the current injectables) does not reflect the relapse rate they see in real life, so the investigators looked at he ARR for all relapses (not simply confirmed, but also unconfirmed) and that was 0.3 vs. 0.33 vs. 0.63. So, even if we liberalize the definition of a relapse, fingolimod still significantly beats Avonex in this one year trial.

Instead of looking at the relapse rate, we can also look at the proportion of participants relapse-free (after all, isn’t that what we want?) and that comes to 83% vs. 80% vs. 69%.

Not all relapses are created equally

While relapses are important, the disability they are accompanied with (not just left with) are important – so we care about the severity of the relapses as well. Although not approved by the FDA for these purposes, I believe that our DMTs not only reduce the number of relapses but also their severity. Looking at relapses requiring hospitalization, the ARR for the three groups (fingolimod 0.5 vs. fingolimod 1.25 mg vs. Avonex) was 0.022 vs. 0.039 vs. 0.077; this means that you are 71.4% less likely to need hospitalization for a relapse if you are on fingolimod 0.5 mg as compared to Avonex (49.4% for fingolimod 1.25 mg vs. Avonex).

In the RECLAIM (Relative Efficacy of repeat Course of intravenous methyLprednisolone and intramuscular ACTH in the treatment of acute relapse of multiple sclerosis after sub response to Initial course of intravenous Methylprednisolone), we (this is a Neurologique specific trial written by Dr. Kantor) are trying to see how we can reduce the need for additional courses of steroids for the treatment of MS and in the TRANSFORMS trial, taking fingolimod meant that even if you had a relapse, it was less likely that you needed steroids (ARR of 0.084 vs. 0.115 vs. 0.176).

So, of the 429 participants on fingolimod 0.5 mg vs. 420 on fingolimod 1.25 mg vs. 431 on IFNB-1a, 17.5% vs. 19.5% vs. 29.9% had a relapse and 11.2% vs. 13.1% vs. 18.3% required steroids with no hospitalization and 1.9% vs. 3.1% vs. 7% required hospitalization.

In summary, the efficacy data from TRANSFORMS (Trial Assessing Injectable Interferon vS FTY720 Oral in Relapsing-Remitting Multiple Sclerosis), demonstrated that in a one year trial, fingolimod significantly beat a currently available injectable in terms of measures of relapses. The results for fingolimod 0.5 mg vs. 1.25 mg, has led us topursue the lower 0.5 mg dose rather than 1.25 mg.

2. 2. Oral fingolimod (FTY720) vs placebo in relapsing-remitting multiple sclerosis (RRMS): 2 year efficacy results of the phase III FREEDOMS trial.

While TRANSFORMS [2302] was a one year global (including U.S.) trial comparing two dose of fingolimod to active treatment (Avonex), FREEDOMS was a two year global (ex-U.S.) trial comparing two doses of fingolimod to placebo.

As we have discussed in the past (http://bit.ly/98pGyk and http://bit.ly/dBWxrH), FREEDOMS [2301] (FTY720 Research Evaluating Effects of Daily Oral Therapi in Multiple Sclerosis) confirmed in a longer (2 year) trial that fingolimod has robust efficacy. Compared to placebo, fingolimod 0.5 mg and 1.25 mg reduced ARR by 54 – 60% (and it did so whether participants had been previously treated with a DMT or no). Compared to placebo, fingolimod 0.5 mg and f

Fingolimod 1.25 mg increased the proportion of participants who were relapse free (46% vs. 70% vs. 75%).

It’s not all about the relapses – what about disability?

Fingolimod significantly reduced the risk of disability progression by 30% – 40% (we look at 3 or 6 month confirmed Expanded Disability Status Scale or EDSS progression and the Multiple Sclerosis Functional Composite or MSFC).

3. 3. Oral fingolimod in relapsing-remitting multiple sclerosis (RRMS): MRI findings from TRANSFORMS and FREEDOMES phase III trials

So, now that we have seen the robust clinical efficacy (in terms of relapses and also some disability data) from TRANSFORMS (fingolimod vs. IM IFNB-1a) and FREEDOMS (fingolimod vs. placebo), we move on to the best (yet imperfect) surrogate marker we have, MRI.

When using MRI to compare the efficacy of treatments, we look at several aspects of the MRI – inflammatory lesions (there is Gadolinium enhancement of white matter spots when there is active breakdown of the blood brain barrier; T2 lesions are the white spots we see that do not necessarily have enhancement at this point in time, but must have at some point) in terms of number and volume, as well as loss of brain volume (atrophy).

New/newly enlarged T2 lesions (‘white spots’):

In TRANSFORMS, there was a 31% - 42% reduction on the mean lesion count as compared to IFNB-1a and in FREEDOMS it was 74% as compared to placebo.

Gadolinium enhancing (Gd+) lesions:

In TRANFORMS, after 12 months, there was a mean of 0.5 Gd+ lesions in the IFNB-1a arm vs. 0.2 in fingolimod 0.5 mg and 0.1 in fingolimod 1.25 mg.

In FREEDOMS, after 24 months, there was a mean of 1.1 Gd+ lesions in the placebo arm vs. 0.2 in both fingolimod arms.

Another way of looking at this, is that in TRANSFORMS, the percentage of patients free from Gd+ lesions was 80.8% on IFNB-1a, 90.1% on fingolimod 0.5 mg and 91.2% on fingolimod 1.25 mg. There was no statistical difference in the percentage of participants free from new/newly enlarged T2 lesions (45.&% vs. 54.8% vs. 48%). In FREEDOMS, 65.1% of participants on placebo were Gd+ free compared to 89.7% on fingolimod 0.5 mg and 89.8 on fingolimod 1.25 mg. There was also a statistical difference in the percentage of participants with new / newly enlarged T2 lesions – 21.2% in placebo vs. 50.5% in fingolimod 0.5 mg and 51.9% in fingolimod 1.25 mg.

Looking at the data together, it argues how similar TRANSFORMS and FREEDOMS were and it explains why there was no statistical difference in the percentage of participants with new / newly enlarged T2 lesions in the three arms of the TRANSFORMS trial: namely, because the IFNB-1a arm also had an almost 50% of participants with no new or newly enlarged T2 lesions (as compared to 21.2% in the placebo arm of FREEDOMS).

It is not surprising, then, that there was less change (accumulation) of T2 lesions from baseline in the fingolimod arms as compared to placebo (in FREEDOMS) and not as compared to IFNB-1a (in TRANSFORMS).

Not just accumulation, but loss

We are not only interested in T2 lesions, but in T1 hypointense lesions (unfortunately termed ‘black holes’) and brain volume.

In FREEDOMS, the mean change from baseline in T1 hypointense lesion volume was 50.7 in placebo vs.8.8 in fingolimod 0.5 mg and 12.2 in fingolimod 1.25 mg. In TRANSFORMS, there were only nonsignificant trends in favor of fingolimod over IFNB-1a.

In terms of brain volume, all of our brains lose volume (0.2-0.4% per year) over time (just as the rest of our body shrinks), but this can be accelerated in MS. One of our goals is to slow down any loss of brain volume. In TRANSFORMS, the percentage change in mean brain volume from baseline was -0.45 for placebo vs. -0.31 in fingolimod 0.5 mg and -0.3 in fingolimod 1.25. Probably since FREEDOMS was one year longer, the numbers are higher and the change for fingolimod 0.5 mg was -0.84; for fingolimod 1.25 mg it was -0.89 and for placebo it was -1.31. In FREEDOMS, fingolimod significantly reduced brain volume loss at 6, 12 and 24 months, compared to placebo.

Now, let’s move on to the elephant in the room: safety.

4. 4. Oral fingolimod (FTY720) in relapsing-remitting multiple sclerosis (RRMS): safety findings from TRANSFORMS and FREEDOMS trials.

When choosing a disease modifying agent with your neurologist, we usually consider efficacy (how strong it is), safety, tolerability, convenience and whether the medication will fit into your lifestyle (i.e. whether you will actually take it). The strongest medication in the world is of little use if it is not actually getting into the body.

When TRANSFORMS came out, many of us were concerned with the possibility of safety issues. We clearly have a drug that is effective (it beat one of our current injectables), but the question was the side effect profile. Then FREEDOMS came out and looked more promising. In this poster, we look at the combined safety information.

Firstly, overall less people discontinued the study who were on fingolimod 0.5 mg (8% in TRANSFORMS and 13% in FREEDOMS) than on fingolimod 1.25 mg (13% in TRANSFORMS and 23% in FREEDOMS), or the control arms (IFNB-1a in TRANSFORMS at 11% and placebo in FREEDOMS at 21%).

In clinical trials when you look at the percentage of people who have any adverse event (AE) it is always high, but the serious AEs (SAEs) are what concern are much more.

The overall incidence of AEs were similar for all the groups (91 – 94 %), except the TRANSFORMS fingolimod 0.5 mg where it was 86%.

AEs that led to discontinuation were more likely in the fingolimod 1.25 mg group (10% in TRANSFORMS and 14.2% in FREEDOMS). Of the IFNB-1a group in TRANSFORMS, 3.7% had any AE that led to discontinuation and in FREEDOMS the placebo arm had 7.7% while the fingolimod 0.5 mg arm had 7.5%. The reason for the higher percentages of those who discontinued in FREEDOMS as compared to TRANSFORMS was that it was one year longer.

Death:

In FREEDOMS, 2 participants died in the placebo arm.

In TRANSFORMS and FREEDOMS, 3 participants in the fingolimod 1.25 mg groups:

A. Disseminated varciella zoster virus infection (chickenpox all over the body)

B. Herpes simplex encephalitis (brain infection with herpes)

C. Suicide

Neoplasms

In TRANSFORMS, there were 10 localized skin cancers (8/10 diagnosed at the first on-study examination by a dermatologist 4 - 12 months after enrollment) and all were successfully excised. Breast cancer was reported in 2 patients in each fingolimod groups (3 cases were diagnosed within 4 months of starting study drug and one after 11 months on-study). In the IFNB-1a group, one patient had basal cell carcinoma and one had squamous-cell carcinoma.

After these results, neurologists were concerned and we waited with (a)bated breath for the neoplasm safety data from FREEDOMS.

In FREEDOMS, malignant neoplasms were observed in 4 patients receiving fingolimod 0.5 mg (4 basal cell carcinoma), 4 receiving fingolimod 1.25 mg (1 basal cell carcinoma, 1 malignant melanoma, 1 Bowen's disease [squamous cell carcinoma in situ] and 1 breast cancer) and 10 receiving placebo 3 basal cell carcinoma, 1 malignant melanoma, 3 breast cancer, 1 endometrial cancer and 1 cervical carcinoma in situ).

Other adverse events of special interest: macular edema, bradycardia, first and second degree AV (heart) block, increased blood pressure, liver abnormalities, pulmonary function and infection.

5. Oral fingolimod (FTY720) vs placebo in relapsing-remitting multiple sclerosis (RRMS): baseline data from a 2-year phase III trial (FREEDOMS II [2309]).

This mostly North American study has more safety monitoring than FREEDOMS and is also a two-year trial (last patient completing the trial should be March 2011) and there was intensive safety monitoring for the first several hundred participants and this has been presented to the FDA.

This poster demonstrated that the baseline demographics and characteristics of the three arms in this trial (placebo, fingolimod 0.5 mg and fingolimod 1.25 mg) are similar to each other. This means that we have a well designed population with a good study population, so the results should be valid ... we will wait until after March 2011 ...

... but will this be relevant if Gilenia is FDA approved before the conclusion of FREEDOMS II?

Is it still ethical to continue the trial once Gilenia is FDA approved?

- Dr. Daniel Kantor, MD BSE

Medical Director

Neurologique

info@neurologique.org

www.neurologique.org

Virtual SecondLife MS Town Hall Meeting on Sun May 16 with Dr. Kantor

For the latest Virtual MS Town Hall Meeting at SecondLife.com:

Topics included: CCSVI, LDN. Bee stinging, progressive MS, Gilenia (Fingolimod), Cladribine, Campath (Alemtuzumab) and the autonomic nervous system.

- Dr. Daniel Kantor, MD BSE

Medical Director

Neurologique

info@neurologique.org

www.neurologique.org

CCSVI (chronic cerebrospinal venous insufficiency)

Dr. Daniel Kantor and Clay Walker discuss CCSVI (chronic cerebrospianl venous insufficiency) and the importance of Hope.

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Clay Walker and Dr. Daniel Kantor

- Dr. Daniel Kantor, MD BSE

Medical Director

Neurologique

info@neurologique.org

www.neurologique.org

Emotional Lability, Pseudobulbar Affect and Hope for Zenvia

There was a great and timely question on the MSFocus Forum that I wanted to bring to everyone's attention. See the question and my answer, below:

Question:

I have RR - diagnosed in 1996, and has been getting much worse lately. I am in a family dynamic that is highly stressful - and I read something about emotional lability? I have had some very tough days with being unable to control emotions, grumpy, crying, laughing at anything. I recently started Betasaron again, and wonder if that might help the symptoms. My wife and I are close to breaking up, as she says she can not live with the MS symptoms anymore. Do you know of other people that have these kinds of difficulties with relationships and stress? And, do you know of anything that might help?

Answer:

Family dynamics can be difficult at times, and having a lifetime diagnosis often makes things worse (but I see plenty of couples whose relationship has been tried and strengthened through the diagnosis).

It seems like there are two questions here:

1. Can tress make your MS symptoms worse?
2. Can stress make a person have emotional lability?

The answer to the first question is that it seems that stress can make everything worse. MS symptoms can be affected by heat, and stress can increase core body temperature.

The answer to the second question is that people with MS may have something called emotional lability (pseudobulbar affect), meaning that there may be dramatic changes in emotions without a clear cause for the dramatic nature of the emotional outbursts. This can be socially disabling, such as when a person starts laughing at a funeral or crying at a funny joke (interestingly, all of us have this a littl ebit, like when we cry at a wedding).

Besides psychological counseling, doctors sometimes prescribe SSRIs (selective seretonin reuptake inhibitors), one of the classes of antidepressants. A company named Avanir is developing a medication called Zenvia ( a combination of dextromethorphan and quinidine) for emotional lability in MS patients, so there will be another treatment option available to you (hopefully) soon.

Thank you,

- Dr. Daniel Kantor, MD BSE

Medical Director

Neurologique

info@neurologique.org

www.neurologique.org

LIVE Video Blogs from the AAN (American Academy of Neurology) Annual Meeting in Toronto

Please visit http://www.youtube.com/Neurologique

For LIVE video blogs direct to you from the American Academy of Neurology (AAN) Annual Meeting in Toronto, Canada.

Please post your questions at http://facebook.com/Neurologique or email neurologique AT gmail.com

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Options ... alway more

I received this excellent question on the MSF forum, that I thought would interest a lot of you:

Question:

I have been diagnosed for 9 years now and am running out of options for treatments. I was on Avonex for the first 5 years until my antibody count went to 121 which was way above the high count of 60. I was switched to copaxone and was on it for 1 year but had to stop due to severe allergic reactions. I was on pulse steroids for a short time during transition to Tysabri. I have been on Tysabri now for 16 treatments but was just told I have to get off due to my Dr., whom I respect whole heartedly, does not want any of her patients to go past 14 treatments due to the PML starting to show up after 14 treatments, not before but after. I am being retested for antibodies to avonex to see if I can go back on it but other that that as far as I am aware there is only a daily pill left and it is not ever FDA approved yet. I have also been told that the pill is not a disease modifying treatment.

Is there anything else you are aware of that I can ask about or would I be just as well off to go back to pulse steroids quarterly?

Answer:

Thank you for the excellent question, which I am sure resonates with a lot of people in this online community.

[Thank you to the MS Foundation for encouraging and hosting such a forum]

Since your neurologist seems quite aware of the latest data, I am just going to give broad treatment strategies, and you can discuss those with your doctor:

The FDA disease modifying agents for MS are:

1. Beta Interferons:

a. Avonex (interferon beta-1a in the muscle)

b. Rebif (interferon beta-1a under the skin)

c. Betaseron / Extavia (interferon beta-1b under the skin)

You have already been on Avonex, which is the medication least likely to cause neutralizing antibodies, so we may presume that Rebif and perhaps Betaseron / Extavia would also (as these neutralizing antibodies are often cross-reactive to both types: 1a and 1b).

The problem is that there isn’t consensus about what these “neutralizing” antibodies actually mean: do they actually neutralize the effect of the medication or do they just go up and down.

2. Glatiramer Acetate (Copaxone):

You have already been on it and had some sort of reaction, the question is whether it was an actual allergic reaction or if it was the hive-like skin bumps that we see with Copaxone use.

3. Natalizumab (Tysabri):

You have already been on it, and your doctor feels strongly that you should stop. The question is whether she wants you to stop indefinitely or whether she is suggesting a drug “holiday.” Many neurologists presume that stopping for (usually) 6 months may reduce the risk of PML back down. The problem is that we don’t know if that is true (one of the original people with Crohn’s disease and PML had been on and off the medication) and the question of what you should be on in the meantime.

4. Mitoxantrone (Novantrone):

This is usually used for worsening RRMS (relapsing-remitting MS) or for SPMS (secondary-progressive MS). The issue with this medication is that it is a chemotherapy and there are potential side effects of infection, blood cancers and there is a lifetime limitation because of the risk of congestive heart failure.

With that said, there are experimental medications and off-label medications we use.

A few of these trials may allow you to be on them, despite your exposure to Tysabri, but usually not. In terms of off-label medications, we generally use lower dose chemotherapy medications, which your neurologist can discuss with you.

Now, the question of oral medications. One of those medications (FTY720 or Fingolimod or Gilenia) has been submitted to the FDA for possible approval, but it is not yet approved or available. The issues with the newer medications, are just that: they are new. This means that we don’t yet know what all the possible side effects may be (such as cancer and infections).

You mentioned that there is an oral medication that is not a disease modifying agent. I presume that you are referring to Dalfampridine (Ampyra). This medication is not a disease modifying agent, but it is FDA approved and available for improvement in walking speed. See: http://bit.ly/a8yB0a

In terms of steroids, some people use pulse IV Solumedrol (or oral Prednisone or into the muscle/under the skin ACTH), and there was a recent study published about adding monthly pulse steroids to Avonex, but it is not clear that steroids alone are enough and there are potential side effects (bone health problems, insomnia, agitation, psychosis, acne, blood sugar elevation etc.).

So, the options that your neurologist may be considering are:

1. Pulse steroids and a beta interferon while waiting to restart Tysabri.

2. Beta interferon with or without pulse steroids.

3. Retrying Copaxone (depending on what that reaction was).

4. Novantrone.

5. An off-label use of a chemotherapeutic medication, such as Cyclophasphamide (Cytoxan), Rituximb (Rituxan), Alemtuzumab (Campath), etc.

As you can see, there are a lot of options that you and your neurologist may want to consider in your partnership in your MS care.

We will soon be releasing online video presentations concerning such strategies, which you will hopefully find useful. When these are ready, we will be sure to let everyone on this forum know.

All the best and please let us all know (if you are comfortable doing so) what you decide on.

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

CCSVI Heats up

Neurologique has launched its Facebook page at www.facebook.com/Neurologique and the discussions are advancing.

One member wrote the following:

There may be a cure for Multiple Sclerosis!Dr Ashton Embry President, Direct-MS says it best in this open letter, http://www.direct-ms.org/magazines/Embry%20Open%20Letter%20to%20Khan%20et%20al%20regarding%20CCSVI.pdf I say,”CCSVI is a known condition in the legs and has been treated for years! Why then can't CCSVI in the neck be treated? Regardless of whether or not a person has MS or not. Let research continue to figure out what came first MS or CCSVI, in the mean time it only makes sense the doppler scanning become a part of ruling out MS or CCSVI and the the Liberation Treatment become a part of MS therapy.”


My answer was:


Thank you for sharing this. While I understand the anger here, it is not clear on what basis the author states: that there is "little doubt that CCSVI is an important factor in the MS disease process in many cases (definitely not all cases)."

Throughout mose of the 'open-letter' Ashton Embry takes a measured approach, but that quotation is unclear to me. If MS itself may be congenital, then once again how do we know if CCSAVI preceded it or not.

I was not an author on the Annals of Neurology piece, but I think it is fair to point out that the CCSVI data is preliminary, because although Dr. Zamboni's paper does not say it is definitive, hundreds (or thousands) of patients are treating it as if it is. They are taking real health risks by having an unestablished semi-surgical (endovascular) procedure. Patients have gone so far as to created Facebook pages with titles such as 'Dr. Zamboni for Nobel Prize.' Websites, such as www.ccsviForMS.com, www.ccsviLiberation.com and www.ccsviCuresMS.com, have crept up as well.

In terms of experts in MS and pharmaceutical company relationships, Mr. Embry writes: "Naturally your advice is going to be “Don’t use the non-drug treatment. Use only the drugs”. How can it be otherwise and that is why advice from those with obvious conflicts of interest is self-serving and worthless." and "...your Point of View is completely out of date and your advice regarding CCSVI testing and treatment is totally compromised and of no value." If he truly feels this way, then I would suggest not seeing a specialist neurologist for MS. Nothing forces patients to seek allopathic and osteopathic physician consultations. If doctors are not to be trusted, then why do patients come to see us? "How can it be otherwise?" The Hippocratic Oath and our dedication to our patients is how it can be otherwise.


Please note, I am not defending either viewpoint and I have made that clear in my blogs:

http://neurologique.blogspot.com/2009/11/going-to-other-side.html

http://neurologique.blogspot.com/2009/12/on-other-hand.html

http://neurologique.blogspot.com/2010/02/ccsvi-does-it-hold-up.html

There is no "war" as Mr. Embry suggests -- the front-line of facing MS is made up of patients, carepartners and doctors. We are the only ones who are sworn to have no other interest (as opposed to all the other 'stakeholders.'


The question is whether testing for CCSVI has utility. What will you do if it shows CCSVI? Would you then take real health risks? Your doctors are sworn to protect your health and we don't know whether performing the Liberation procedure will cause more harm than good.

What do you think?


- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Open letter to NPR's Morning Edition

Dear NPR, On 03/10/2010 I was disturbed to hear the story on physicians prescribing medications based on limited study data, but rather on years of clinical experience. Instead of NPR offering a balanced view of this issue, the speaker stated that doctors write prescriptions "in the dark." The tone used when referring to the thousands of caring physicians was unfair and unwarranted.

No one forces patients to seek allopathic or osteopathic care, but the Public does need to recognize that "evidence-based medicine" also means clinical experience. In these times of the Public's confusion over the role of health insurers vs. providers (i.e. doctors), NPR should educate their listening audience in a more fair and well-balance manner.

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

MuSic to our ears

MuSic

We will hopefully be having an MS jam session with the Lee Boys in May at Freebird Live in Jacksonville, FL

See: http://bit.ly/b85Dxk

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

MS Town Hall Meeting: Jacksonville, FL - Jax Beaches MS Support Group

Even if you couldn't be there, catch the latest MS Town Hall Meeting, filmed on LIVE WebTV.

Cupping -- old treatment for age old problem

Pain.


Cupping is usually performed by heating up the edges of a glass cup, which is then placed on the skin. The heating up is what helps cause the vacuum, which causes the skin/fat/muscle to be raised a little into the cup. Traditional Chinese medicine uses cupping, almost like how it uses acupuncture -- by applying the cups to certain area, it is supposed to relieve pain. Often cupping is not used alone and is used with other forms of therapy. There is growing medical evidence that cupping does wotk in certain types of pain, such as lower back pain. One of the problems lies in the difficulty in really 'blinding' someone to whether they receive the cupping or not (sham cupping or placebo). In a drug trial, we use placebo pills (commonly called 'sugar pills') that look exactly like the pills being studied. This is a lot more difficult in a cupping study.

Most people associate cupping exclusively with Traditional Chines Medicine, but many other cultures use it -- such as the Bedouins. Cupping can be performed with suction and without heating the cup, but this is less traditional. It is also possible that cupping work by sucking blood into the area to which it is applied.

Pros:

- Low cost alternative way to treat pain, especially since there aren't that many alternatives.
- Has a long tradition and is relatively safe

Cons:

- Often needs to be used in conjunction with other treatments, so unclear how much it adds
- The fire may leave burns or marks
- Some practitioners may charge a lot for this treatment, which is not proven to be effective.


What do you do for your pain?


- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Brain games

Low tech vs. hi-tech.

See the story on brain games:

- What do you think?

- What do you use?

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Recordings of LIVE Web TV

Recordings of LIVE Web TV: MS Town Hall Meetings and more at http://ustream.com/neurologique and http://www.neurologique.org and http://facebook.com/Neurologique

First Oral for MS: New idea, new leader

Congratulations Novartis AG (NVS), but more importantly:

Congratulations MS community.

As expected and anticipated, the FDA has granted priority review for Novartis's Gilenia (Fingolimod or FTY720) -- see:

http://neurologique.blogspot.com/2010/01/filing-and-timing.html

That leaves EMD Serono / Merck KGaA's Cladribine (Movectro/Mylinax) behind in refuse-to0file limbo. Of course, Gilenia leads Laquinimod (Teva), Teriflunomide (Sanofi-Aventis), and BG0012 (Biogen Idec).

So, let's countdown and wait for approval!

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org