Neurologique

Gilenya scare and a reasoned approach

2012-01-24T01:26:00.007-05:00

By now most of you know that a woman with MS in the United States passed away within 24 hours of her first dose of Gilenya. This, along with 10 other reported deaths (not within 48 hours of the first dose), prompted the European Medicines Agency (EMA) to issue a press release concerning their review of Fingolimod (Gilenya) safety.

This has been picked up by mainstream media (not just on the Internet, but also in local newspapers) and people are bringing newspaper clippings to their neurologists. It is for this reason that we felt that it was necessary to speak directly to the MS community about what we do and don't know at this time. In the video below, I interview a patient (on Gilenya for a week) who came in with the newspaper clipping that was sent to her by her concerned friend. After I addressed her concerns, we discussed our making a video to help others understand what we do and don't know. Of the other 10 deaths, 3 were heart attacks and 1 was a cardiac dysrhythmia -- so this is 4 heart related deaths out of ~30,000 people treated with Gilenya worldwide (as opposed to what the news media implies, some of these deaths were in the U.S., as well).

So, bottom line, what do you do now?

Talk to your neurologist because there may be no cause for concern and the FDA and the EMA are looking into this to see if there are new risks associated with Gilenya.

- Dr. Daniel Kantor, MD
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

MS Town Hall Meeting in Valdosta, GA on 01/21/2012

2012-01-21T18:54:00.011-05:00

In this MS Town Hall Meeting, interactive topics include:

1. Disease modification -- newest research, currently approved medications and complementary and alternative medications (CAM). Emerging therapies:BG12, Lemtrada, Teriflunomide, Ocrelizumab, Daclizumab, Pegylated Interferon Beta-1a....

Factors include: Efficacy vs. Safety vs. Tolerability vs. Convenience (Route of administration vs. frequency).

2. Symptom control -- how to talk to your doctors and prioritize your issues. The use of NeuroFunctional Enhancers (NFEs). This does NOT necessarily mean medications.

3. Rescue treatments -- IV Solumedrol (Methylprednisolone), IM/SC ACTH, IVIG/IGIV, plasmapheresis). Only 2 FDA approved treatments (SOLUMEDROL and H.P. ACTHAR GEL).

Also, side effects of medications and how to deal with them. What to do when your insurance denies your needed medication.

Here are the flip chart notes:

- Dr. Daniel Kantor, MD
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Late 2012 is going to be great for MS

2011-11-14T19:12:00.005-05:00

Wow wow wow

It's an exciting time for MS drug development and an even more exciting time for our patients and future MS patients. In the past year, oral BG00012 was catapulted from a niche place in the MS treatment landscape to a highly prominent international position. DEFINE data presented at ECTRIMS 2011 highlighted BG00012 as a safe, effective and mostly tolerable oral medication for the reduction of MS relapses and disability. The enthusiasm generated at ECTRIMS was still spreading at the point when top line results from the second Phase III trial (CONFIRM) were released. In CONFIRM, BG00012 was not only compared to placebo, but there was also an additional arm of subjects treated with Glatiramer Acetate. BG00012's superiority over placebo in DEFINE was confirmed by CONFIRM, and while CONFIRM was not designed to compare BG00012 head-to-head to Glatiramer Acetate, it is difficult not to make the natural conclusion that BG00012 probably performed better than Glatiramer Acetate as well. While performing better than Glatiramer Acetate is a significant accomplishment, especially in light of the disappointing performance of the high-dose high-frequency interferons compared to Glatiramer Acetate in the BEYOND and REGARD studies. In CONFIRM, however, BG00012 did not have a significant effect on sustained disability as compared to placebo; this raises the question, not of whether BG00012 will be FDA approved for the treatment of MS, but rather whether it will be approved for delaying MS disability in addition to reduction of relapses. Further exploration of prespecified subgroups and post hoc analyses will be quite useful.

Race of the orals

While large amounts of new data on Terflunomide were not released, it remains in the running as an oral, mostly safe MS medication. The safety will be further characterized by release of more data from the expansive list of Sanofi sponsored trials for this medication.

Head-to-head

Alemtuzumab is the most exciting medication in the MS pipeline for the foreseeable future.The combination of a quantum leap in efficacy (50% better than Rebif) and the infrequent dosing schedule (only 5 days in a row in the first year and not again until the second year when it is given for 3 days, and then some perhaps it will not need to be re-dosed in most people), makes Lemtrada an attractive option for many physicians and patients. In the CARE--MS-1 study Alemtuzumab was found to be significantly better (55%) than Rebif in reducing relapses, but the results for disability were not significant -- probably because the Rebif treated subjects did better than in prior studies of Rebif. The results of CARE-MS-2 confirm this assumption as Alemtuzumab was superior in terms of reducing relapses (49%) as well as sustained disability (42%) as compared to Rebif (not to be mistaken for trials comparing medications to placebo). We look forward to Genzyme, a Sanofi company, releasing more information on the annualized relapse rates in the two groups and we suspect that further investigation of patient subgroups will help clinicians understand in which patients there will be ~50% reduction as compared to Rebif as opposed to ~70% reduction compared to Rebif (as suggested in prior Phase II trials).

The decision tree for newly diagnosed patients may evolve to a question of how risk averse the individual patient is. For those wanting a medication with a very long safety record (at least in psoriasis), BG00012 may be first line, while in others who want the medication with the strongest efficacy, but with some potential for the development of humoral autoimmune diseases, Alemtuzumab may be the right choice.

Beyond T cells

Ocrelizumab is a humanized version of Rituximab, a monoclonal antibody directed against B cells -- a fairly new treatment paradigm for MS. Ocrelizumab will be dosed 4 times a year with the goal of reducing relapses as well as disability. Roche is studying Ocrelizumab for relapsing MS in the mirror OPERA 1 and 2 studies, while also studying Ocrelizumab in primary progressive MS.

Daniel Kantor, MD
Medical Director
Neurologique

President
Florida Society of Neurology
----------------------------------------------------------------

Be a leader, help the network ... join neurologique@gmail.com

Multiple Sclerosis Team Approach Rule *** MS Patient Network

www.neurologique.org

Twitter, facebook, blogs and more.

Botox ... truth in advertising

2011-10-31T17:21:00.003-04:00

A local news story in Jacksonville had good intentions, but it missed the point with its editing -- it made it sound like Botox was experimental for chronic migraine!

For those of you following our tweets, we first reported on the FDA approval of Botox for chronic migraine (15 or more headache days a month) a year ago.

So, let's set the record straight -- Botox is FDA approved for many things -- my comments on experimental treatments were after the reporter asked about future uses -- and I mentioned that it was being tested for baldness (alopecia areata). I didn't want everyone running to their doctors demanding Botox for something still in experimental phases -- but I made it clear that Botox is FDA approved for chronic migraines ... and more.

In fact, at the recent ECTRIMS (European Committee for the Treatment and Research in MS), I reported in real-time with Ashley from MS World about the various (FDA approved) uses for Botox relevant to MS: cervical dystonia, blepharospasm, chronic migraine, urinary bladder and more):

Among treatments for spasticity (Tai Chi, Yoga, Baclofen, Arbaclofen Intrathecal Baclfen pump, Botox):

So what can we learn from all this?

Be wary of the news that you here -- go straight to the source ... Neurologique, your source for neurological news that matters.

- Dr. Daniel Kantor, MD
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Wow ... when enthusiasm is appropriate

2011-10-22T05:32:00.004-04:00

Wow!

Enthusiasm is important, even (or especially) at international scientific meetings.

If you are following our (MSWorld and Neurologique) real-time videos from ECTRIMS (European Committee for the Treatment and Research in Multiple Sclerosis) -- the biggest MS meeting of the year. On 10/21/2011, Prof. Ralf Gold presented data from the phase 3 DEFINE study (Determination of the Efficacy and safety of oral Fumarate IN rElapsing-remitting MS) and it was exciting.

While we still need to wait for the CONFIRM study (it compares placebo, two doses of oral BG-12 and subcutaneous Glatiramer Acetate/Copaxone) to ensure that oral BG-12 (dimethyl fumarate) is as exciting as it looks in DEFINE: safe, effective for MS relapses and disability, effective for MRI and mostly well tolerated.

At the end of the presentation by Prof. Ralf Gold, I said "I think that I speak for most people when I say wow." I then asked about pregnancies (no malformations) and 3 vs 6 month disability progression.

This has gotten me known as the "Wow Doctor" -- it has even been covered in the media by Medpage.

One day, I hope that I can say "wow" about many other new therapies.

- Dr. Daniel Kantor, MD
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Lack of focus and MS - Facebook Question and Answer

2011-09-12T16:02:00.002-04:00

Here is another great question (and, hopefully, answer) from Neurologique's open Facebook page.

Question:

Why do some MS people feel so unfocused in the head and what can be done to help this feeling?

Answer:

There are many potential reasons for this:

1. Related to medication side effects.
2. From the MS itself -- fatigue.
3. From the MS itself -- cognitive problems.
4. Something also called "MS brain fog"
5. Depression.
6. Not from MS, but something else.

In terms of how to approach treatment, it is going to depend on the cause. Non-pharmacologically we use meditation (especially mindful meditation), breathing exercises, visual imagery, acupuncture, yoga, tai chi, cooling, etc.

Pharmacologically, we maximize the MS disease modifying drugs and we choose appropriate symptomatic treatments, like medicines for fatigue (Amantidine, Provigil, Nuvigil, B12, Caffeine, Stimulants etc.). At Neurologique we are also looking at an Ayurvedic herb called Ashwagandha for MS -elated fatigue.

Interestingly, there are two medications that I call "NeuroFunctional Enhancers" because they enhance function in people with neurological diagnoses. Thus far the class is made up of:

1) Ampyra (dalfampridine) -- FDA approved for gait dysfunction in MS, but because it helps the nerves work better, it can help in lots of ways.

2) Nuedexta (dextromethorphan + quinidine) -- FDA approved for pseudobulbar affect (regardless of cause), which is, basically, problems with coordinating your emotions and how you display them to others (affect). It has an effect on blocking the effects of glutamate in the brain, and is an NMDA antagonist and Sigma-1 Agonist (scientific mumble jumble)

I hope that this was useful.
.

MS with a negative LP (lumbar puncture or spinal tap)

2011-09-09T19:16:00.002-04:00

As many of you know, I answer questions for the MS Foundation (MSF) and here is one that we thought would be interesting and useful to you.

Question:

I have 3 spots on my brain the doctor has tested me for MS even had a spinal tap it came up negative. I would like to know if I do have MS but just has not showed up yet sometimes I lose my balance and don't have much strength in my hands.

Answer:

Thank you for the question.

It is true that people with MS may have negative lumbar puncture's (LPs or spinal taps) and someone needs to explain your white spots on the brain, and more importantly, your symptoms. I strongly recommend that you see an MS specialist and that you consider (if not done already):

- Close Cervical spinal cord MRI with and without Gadolinium
- Close Thoracic spinal cord MRI with and without Gadolinium
- Visual Evoked potential (VEP)
- Somatosensory Evoked Potential (SSEP) of the upper and lower extremities
- Brainstem Auditory Evoked Potential/Response (BAEP/R)
- Optical Coherence Tomography (OCT)
- Lab work-up
- Repeat LP in a few years -- ut we don't want to wait that long!

MSF can help you find a neurologist near you ... they always help!!

I know that this means that you will need to be patient.

Thank you,

Daniel Kantor, MD
Medical Director
Neurologique

President
Florida Society of Neurology

----------------------------------------------------------------

Be a leader, help the network ... join neurologique@gmail.com

Multiple Sclerosis Team Approach Rule *** MS Patient Network

info@neurologique.org

www.neurologique.org

Q&A with Dr. Kantor: Numbness

2011-09-04T14:19:00.000-04:00

As many of you may know, I answer questions on multiple sites, including Avvo. I thought that this question and answer would be useful to many of you out there.

Question:

I have been experiencing numbness in my fingertips and toes. What could be causing this?

I have not injured my fingers or toes recently. I have had some numbness in some of my fingertips for awhile, but it seems to be getting more prevalent.

Answer:

I can understand why this is a concerning symptom. There are several possibilities, but remember that online discussions do not replace real life interactions with doctors -- especially neurologists.

The possibilities include that:

1. This is simply a variant of the weird things that we all feel.
2. This is not neurologic.
3. This is caused by a peripheral nerve problem -- like diabetes (diabetic neuropathy).
4. This is caused by a vitamin (like Vitamin B12) deficiency
5. This is caused by a spinal cord problem.
6. This is caused by something going on in the brain.

As you can see, there are a lot of possibilities and your best bet would be to see your primary care physician and then a neurologist.

Please try not to be worried until this is looked into (it may not be worth worrying about).

- Dr. Daniel Kantor, MD
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Exciting Advocacy News for FL: National Stage - Dr. Kantor appointed again to FMA Council on Lgislation

2011-08-27T13:43:00.002-04:00

From FMA:

TO: Daniel Kantor, M.D.

FROM: Miguel Machado, M.D., President

RE: Reappointment to the FMA Council on LegislationTO:

I would appreciate your willingness to accept reappointment to serve on the FMA Council on
Legislation as the Medical District B representative during my term as President of the FMA,
effective July 31, 2011. Attached is a list of those who have been asked to serve with you.

There are two FMA Board of Governors & Council Days scheduled during the appointed year.
This meeting format is intended to facilitate interaction between the various councils/committees while minimizing travel expenses. While I cannot confirm the specific date and time each group is meeting, every effort is being made to accommodate a Friday or Saturday meeting time concluding with the Board of Governors meeting on Sunday. I respectfully ask that you keep the dates open for scheduling. FMA staff assigned to each council/committee will distribute meeting details approximately 6-8 weeks in advance. Please keep in mind that there may be instances when a particular group may find it necessary to meet by conference call, rather than in person. Those details will be provided by appropriate staff as well.

Exciting Advocacy News for FL: National Stage - Dr. Kantor placed on AMA Reference Committee on Legislation

2011-08-27T13:39:00.001-04:00

From the AMA:

Dear Dr. Kantor

On behalf of the Speakers, it is my pleasure to invite you to serve the AMA House of Delegates at its Interim Meeting in New Orleans, Louisiana, November 12-15, 2011, as a member of Reference Committee B (Legislation).

As a member of a Reference Committee your responsibilities will include:

· Participation in the hearing on Sunday, November 13. (This open hearing will last as long as is necessary to receive comments on the business before you.)

· Participation in preparation of the report of the Reference Committee. (This includes an executive session of the full committee that immediately follows the conclusion of the open hearing as well as additional meetings, as needed, until the final report is complete. This often means being available throughout the night and the following morning.)

· Presence before the House during its consideration of the report of your Reference Committee.

In addition, virtual reference committees are planned for November as was done for Reference Committee E in June. Virtual (online) testimony will be accepted from approximately October 14 to October 30. Each reference committee will then have to meet by phone sometime the next week (October 31–November 4) so that a draft report can be prepared and posted on November 7 or 8, in time to allow the report to be reviewed by members of the House prior to the meeting. This process, although still in its trial phase, worked well in June, and in the end, resulted in a less harried experience for the reference committee members; we are hopeful for a similar experience at this meeting.

Your work on a Reference Committee is a service to American medicine and a very important contribution to the democratic process followed by the House of Delegates.

Outpouring of support for deceased neurologist, Jim Nealis, MD

2011-08-27T11:47:00.003-04:00

In response to our earlier obituary for the passing of Jim Nealis, MD - Past President, Florida Society of Neurology (see original obituary), we received the following message:

Thank you. When I first arrived at Harvard in 1976, Jim was a fellow at the Seizure Unit (where I was assigned) with Dr. Cesare Lombroso. I did not know a soul there and Jim became a good friend, even inviting me out for St Patrick’s Day. He was a caring doctor and a fun guy to work with. I will never forget him. My condolences to his family.

Herminio Cuervo

Your FSN ... Helping Neurologists help their patients.

Daniel Kantor, MD
Medical Director
Neurologique

President
Florida Society of Neurology

www.neurologique.org

FSN Distinguished Panel: Drs. Alternburger and Wilson and Senator Fasano

2011-08-21T16:11:00.010-04:00

Medicine 2011: Issues Facing Neurologists and Their Patients:

Local, State and Federal perspectives

Distinguished Guests:

Senator Mike Fasano -- Florida District 11

Karl Altenburger, MD – Past President, Florida Medical Association (FMA)

Cecil Wilson, MD --Immediate Past President, American Medical Association (AMA)

Schedule: September 17^th, 2011

12:00 – 12:15: Lunch preparation – FSN Business Meeting

12:15 – 12:20: Call to Order (Introduction of Board)

Daniel Kantor, MD

12:20 – 12:25: Introduction of distinguished panel

Daniel Kantor, MD

12:25 – 12:40: Pills Mills: How the Senate saved

FL Senator Mike Fasano

12:40 – 12:50: How the FMA works with specialists

Karl Altenburger, MD

12:50 – 1:10: Neurologists in the House of Medicine

Cecil Wilson, MD

1:10 – 1:20: Panel Discussion

Distinguished Guests

1:20 – 1:30 New Business and Concluding Remarks

Daniel Kantor, MD

FSN in Your Corner: Protecting you and your patients

2011-08-21T15:56:00.010-04:00

Dear Fl Neurologist,

Your FSN has been working hard for you – on the local, State and Federal levels and we are excited by the results.

Innovative Annual Meeting:

As you know, the FSNAnnual Meeting is fast approaching on Sept. 16 – 18, 2011. We are excited by the addition of a cognition & TBI (traumatic brain injury) program in the 37th Annual Course in Neuropsychology and Behavioral Neurology. Our Advances in Neurology Workshop promise to be innovative with Controversies in Neurology and Challenging Cases posed to and by our Neurology Chairmen. Your staff and primary care referring colleagues are sure to be enlightened by the Neurology for the Non-Neurologist: Localizing Neurologic Symptoms. Your family will be dazzled by the Disney Yacht Club pool and the proximity to the Disney parks … in short, everyone is sure to have an enlightening, productive and fun time at the FSN Annual Meeting at the Disney Yacht Club on September 16 – 18, 2011. If you haven’t yet, then please be sure to register and reserve your block of rooms online.

Unprecedented Distinguished Panel:

I am most proud of the distinguished panel that I will be introducing on Saturday September 17^th, 2011 at 12:00 – 1:20 PM. Cecil Wilson, MD – Immediate Past President of the AMA, Karl Altenburger, MD – Past President of the FMA (FL Medical Association) and Senator Mike Fasano will be addressing the topic of “Medicine 2011: Issues Facing Neurologists and Their Patients - Local, State and Federal perspectives.” The caliber of our panelists speaks volumes to the notoriety of your FSN and its place within the House of Medicine … with all the changes facing us, don’t be left in the dark!

Senator Mike Fasano	FL District 11
Karl Altenburger, MD	Past President, FL Medical Association (FMA)
Cecil Wilson, MD	Immediate Past President, AMA

Alert: West Nile Virus Outbreak:

There have been cases of Dengue Fever and neuroinvasive West Nile virus in different parts of the State. I have kept neurologists in Duval county abreast of the information disseminated by the FL Department of Health regarding the West Nile Virus cases. It is a privilege to represent you in discussions with the varied Public Health departments protecting the citizens of our great State. The FSN was the only State Specialty Society represented in these teleconferences and we are leading the way in both physician and Public education regarding this potentially dangerous outbreak … wherever there is an issue touching upon the nervous system, your FSN will be there representing YOU and your patients.

Value-added Membership benefits:

Your FSN recognizes that the economic downturn has affected each and everyone one of us, and we have developed a member benefits package to suit your needs:

1. Universal Waste Management (biomedical waste) -- 10% discount and lower price than competitors for FSN members Tel. (352)234-4BIO (4246)

2. TNP (The Neurologists’ Program) -- malpractice insurance and risk management

3. Long-term Care Insurance Program (Affinity)-- see below.

4. I.C. Systems Collection Agency

5. Medscape CMEs

6. The Southern Headache Society --we may do joint CME programs with discounts to FSN members (join the google group)

7. Discounts on medical books through Cambridge Publishing and Oxford Publishing (email fsneuro@gmail.com for your Promotional Code)

8. FSN lapel pins … get yours today!

9. Future pan-FL dinners

10. Regional pan-FL dinners -- stay updated and give your input.

Advocacy Victories … Finally Some Good News!

Your FSN advocated diligently for you and your patients. We have made strategic partnerships with the FMA (we have two neurologists on the FMA Board of Governor’s and I sit on the FMA Council on Legislation and the FMA PAC [Political Action Committee]), the AMA (I was recently elected to the FMA delegation to the AMA), the AAN (through various leadership, including Advocacy) and other organizations, such as the FL Academy of Physician Assistants (I sat alongside the FMA and FOMA [FL Osteopathic Medical Association] Presidents). Additionally, we have ties to the FL Agency for Persons with Disabilities (APD) and I recently ha a productive meeting with the Medical Director of First Coast Service Options (the FL Medicare contractor) – I will present this information at the FSN Annual Meeting.

1, Pill Mills – Board-certified neurologist are not limited by this legislation and you are free to practice without registering with the State.

2. Gun bill – It is not a felony to talk to your patients about safety (even gun safety) … just document the reason.

3. Sports concussions – the FL High School Athletics Association recognizes (without the need for government intervention or legislation) that only MDs/Dos are qualified to return an athlete to play … Your FSN is leading the way in education and protecting our youth.

4. EMG/NCS – We are setting up a joint panel of 3 neurologists and 3 physiatrists with the FL PM&R Society to explore issues related to EMG/NCS and how they affect your practice (and your patients’ safety) – please let us know your local concerns.

5. Booster seats – FL has seatbelt laws but does not sufficiently protect our children, and the FSN is committed to supporting FL Pediatricians in their noble advocacy efforts.

6. Bicycle helmets – FL Academy of PAs (FAPA) Foundation is working to raise Public awareness regarding bicycle helmet safety and the FSN supports protecting our youth’s brains … get your family involved today.

7. IPAB (Independent Payment Advisory Board)- The FSN was the only State Neurology Society to sign the opposition letter (signed also by the AAN) – your Board is proactive and will not let you down. http://bit.ly/ppFWfA

Outreach: Nigeria Florida Neuroscience Partnership (NFNP):

Giving beyond our borders: FL has 6 Neurology residency programs, as does Nigeria, yet the population of Nigeria is ~10 times greater than FL. With the spirit of giving to others, the FSN has been instrumental in forming the NFNP and is proud to announce the 2^nd Annual NFNP Meeting in Abuja, Nigeria on October 10 - 14, 2011. Be a part of this unique program and see another side of Neurology. There are only 50 neurologists in Nigeria! For some stories on the NFNP, please see: Article 1, Article 2, Article 3.

You can make a tax-free donation to the FSN (a 501(c)3 not-for-profit) in the name of the NFNP. You are going to make tax-deductible charitable donations anyway, why not make it to a project that helps millions of people without proper neurological care? A $100 donation (less than a dinner for two at a nice restaurant) will cover the expenses of 1 Nigerian to this important conference … better yet, volunteer to join the Faculty and fly to Abuja (potential group discounts available through Delta).

Your FSN enters the 21^st Century:

Have you jumped on the Social Media wave? Want to follow issues important to

Have you jumped on the Social Media wave? Want to follow issues important to you and your patients? Follow your FSN on twitter at twitter.com/FLneurology or on facebook (search: florida-society-of-neurology). Want to pay your dues online? Visit fsn.aan.com

Developing Leaders:

Your FSN is there for you on the local, State and National levels.

We are currently accepting nominations for the FSN Board of Directors and for Officers. The positions open are: President-Elect (2011 – 2013), Secretary-Elect (2011 – 2013) and Treasurer-Elect. As of the upcoming FSN Annual Meeting, your current Secretary, Glen Finney, will have completed his term (2009 – 2011) and your incoming Secretary will be Rossitza Chichkova (2011 – 2013); your current Treasurer, Nestor Galvez-Jimenez, will have completed his term (2009 – 2011) and your incoming Treasurer will be David Decker (2011 – 2013).

Thank you Glen and Nestor for your service!

Please email us your nominations (including self nominations) to fsneuro@gmail.com.

Congratulations to Achraf Makki, MD – I have recommended him to sit on AHCA’s advisory group for a new utilization management program for Florida Medicaid’s Advanced Outpatient Diagnostic Imaging services. I would like to remind everyone who isn’t a PALFer, to go ahead and apply by Sept 18, 2011 for the January 12 – 15, 2012 Palatucci Advocacy Leadership Forum. Developed your leadership skills … make FL proud.

Welcome New Members:

Your FSN would like to welcome the following new members:

· Tetsuo Ashizawa, MD
· David Burks, MD
· Alfred Erontera, MD
· Gregory Hanes, MD
· Donna Hill, MD
· Roman Kesler, DO
· Ramon Lugo, DO
· Benjamin Moore, MD
· Donald Negroski, MD
· Steven G. Sable, DO
· Denise Taylor, DO

For your convenience, to pay your dues, you can use PayPal.

CME Corner:

The SouthernHeadache Society is hosting its 1st Annual Meeting in Asheville, NC

Do you have CME programs that you would like other FSN members to know about? Email us.

Your FSN is here for YOU.

Thank you,

Daniel Kantor, MD
Medical Director
Neurologique

President
Florida Society of Neurology

** Come to the FSN Annual Meeting: Sept 16 - 18, 2011. Register Today! **
----------------------------------------------------------------

Be a leader, help the network ... join neurologique@gmail.com

Multiple Sclerosis Team Approach Rule *** MS Patient Network

www.neurologique.org

Twitter, Facebook, Blogs, YouTube and more.

----------------------

The Florida Society of Neurology (FSN) has endorsed a discounted Long Term Care Insurance Program. This discounted program is now being made available to all FSN members and their families.

Considering the high cost for Long Term Care, this program is designed to help protect you, your family and your retirement security. Protection is available should you need care at home, in an assisted living or nursing home facilities.

To request information on this program click HERE.

This program offers special discounts not available to the general public for:

you
your family members including

Ø spouses

Ø parents

Ø grandparents

If you would like to forward this to a family member please feel free to do so.

Jacksonville Sharks: ArenaBowl XXIV World Champions

2011-08-14T23:16:00.004-04:00

They've done it again!

Yet another Jacksonville team has made us proud by winning a National Championship.

Last year the Jacksonville Axemen Rugby Team won the National Championship (although this year they were defeated in round one of the playoffs). This year, the Jacksonville Sharks Arena Football Team made all of Jacksonville proud by winning ArenaBowl XXIV.

The team returned to Jacksonville on Saturday August 13th, at around the same time that I was returning from lecturing at the FAPA (FL Academy of Physician Assistants) Summer conference on MS and how to perform a neurologic exam. At the airport, a reporter commented to me (I am the Jacksonville Sharks and the Jacksonville Axemen Team Neurologist) that no players had a concussion this past year -- this is inaccurate but understandable. The general Public mistakenly associates concussions with only glaring brain injury, however concussion are often more subtle. Tim Tebow's concussion in October 2009, helped raise some awareness regarding concussions (see the video), although it is very hard to believe that it was his first. To further raise awareness, Dr. Kantor joined the medical advisory board of the Seeing Stars Foundation.

We call concussions mTBI (or mild traumatic brain injury), but they are not always so mild.

- Dr. Daniel Kantor, MD
Medical Director
Neurologique

Board Certified, Headache Medicine

info@neurologique.org
www.neurologique.org

In Memoriam: James G. T. Nealis, MD

2011-05-09T02:47:00.002-04:00

IN MEMORIAM:

James G. T. Nealis, MD

March 7, 1945 - May 5, 2011

Jacksonville, FL

The Florida Society of Neurology is saddened by the news of the passing of Dr. Jim Nealis, past Secretary and President of the FSN (1982).

Dr. Nealis obtained his B.A. from Fordham University and his M.D. from the University of Miami. After residency training in Boston in Pediatrics and Neurology, Dr. Nealis served as an Instructor in Neurology at Harvard University School of Medicine and then returned to Florida, where he served as an Assistant Professor in both Clinical Neurology and Clinical Pediatrics at the Jacksonville campus of the University of Florida. He served patients in hospitals throughout the Jacksonville area and he contributed to the medical literature on pediatric seizures and EEG. His interests in Neurology were broad and he founded and directed the Jacksonville Alzheimer's Center (1987-1989).

Dr. Nealis is survived by his beloved wife Grace Arlene Kramer Nealis and the proud father of five sensational children Douglas and his wife Dawn, Gregory and his wife Melanie, James IV, Patrick, and Peyton. As well as four precious grandchildren, Cailyn, Austin, Sophia, and Madison. He is also survived by his sister Mary Farrell. A celebration of his life will be held at Southpoint Community Church at 7556 Salisbury Road at 10am Monday, May 9th. Burial will immediately follow at Oaklawn Cemetery. In Memory of Dr. Nealis, Contributions may be made to the American Center of Law and Justice PO BOX 90555, Washington DC 20090-0555. Dr. Nealis was a true humanitarian in the real sense. He was a man whose life was devoted to those unable to help themselves. HARDAGE-GIDDENS OAKLAWN CHAPEL, 4801 San Jose Blvd. is serving the family.

The loss of Dr. Nealis is a loss to the profession of Neurology and a loss to his patients. Our thoughts and prayers are with his family.

To sign the virtual Guest Book, please visit Legacy.com

Open Letter to FL neurologists

2011-04-10T02:45:00.005-04:00

Dear FL Neurologist,

Although Hawaii away, many FL neurologists have made the long flight to the AAN Annual Meeting as presenters, lecturers, leaders and attendees.

We hope that you will join your FSN at these events:

1. Joint breakfast – FSN and NFNP (Please welcome our Nigerian colleagues)

- Tuesday, April 12 from 7:30 AM - 9:30 AM at the Hawaii Convention Center – Room 308B. A light breakfast will be served at this event.

2. Current Practice Issues in Neurology – Daniel Kantor will be presenting on Accountable care organizations (ACOs) and neurologists

- Wednesday, April 13, 2011 from 5:30pm-7:00pm at the Hawaii Convention Center, Room 315

3. Awards Plenary Session

- Thursday April 14 4:30 p.m.-6:30 p.m. Hawaii Convention Center Kamehameha III

4. General Neurology Highlights in the Field (6SH.006) – Daniel Kantor will be presenting how healthcare reform affects neurologists

- Thursday April 14 Location: Hawaii Convention Center Kalakaua Ballroom C

Stay tuned – visit our Twitter account for updates on when you can support our own Michael Finkel as he wins the prestigious Kenneth M. Viste Patient Advocate of the Year Award (the 2007 inaugural Award was also won by a FL neurologist, Kamel Elzawahry).

The FSN will also be represented by Drs. Kantor and Elzawahry at the State Society Leadership Roundtable and the Payment Policy/NeuroCAC Representatives/State Society Leaders

Throughout the week, we will be accepting your information about when you are presenting posters/lectures – please add it as a comment on our Facebook page and we will then spread the word on Twitter as well!

Our promoting your presentations is just another way how your FSN is here for you.

1. Membership

Membership benefits keep expanding.

a. Universal Waste Management (biomedical waste) -- 10% discount and lower price than competitors for FSN members,
b. TNP (The Neurologists’ Program) -- malpractice insurance.
c. Medscape CMEs
d. The Southern Headache Society --we may do joint CME programs with discounts to FSN members
e. Discounts on medical books through Cambridge Publishing and Oxford Publishing (email fsneuro@gmail.com for your Promotional Code)

If you have paid your 2011 FSN dues then you have already received a lapel pin to wear proudly on your blazer or white coat. If you pay your dues at the AAN, you will receive a pin at the FSN-NFNP breakfast on Tuesday.

Don't forget to pay your 2011 dues online or we can discuss this with your office manager -- please have them contact us. Also, your ARNPs, PAs and nurses can join the FSN as well.

Our Pan-FL Dinner Meeting on March 10th 2011 was a great success and the presentation can be found online on our website.

2. Education/Annual Meeting -- The schedule looks great so save the date: Orlando, FL: 09/16-18/11 -- FSN Annual Meeting (Disney Yacht Club)

3. Website/Communications -- The FSN has entered the 2010s and we have a social media presence that you can sign up for at Twitter and Facebook

Also, everytime we send out the 'FSN in Your Corner' emails, they get added to the website. We are considering having a members only section of the website for content (including CME and practice management seminars).

4. Outreach -- The Outreach Committee is doing an amazing job along with our Nigerian colleagues applying for an American Board of Internal Medicine Foundation grant.Come and meet your Nigeria colleagues all the way in Hawaii -- The Nigeria Florida Neuroscience Partnership will be joinging the FSN on Tuesday, April 12 from 7:30am-9:30am at the Hawaii Convention Center – Room 308B. A light breakfast will be served at this event.

5. Advocacy/Legislation -- Your FSN continues to get media coverage, for example in Neurology Reviews. To summarize:

a. Pill Mills -- This is becoming even more complicated, with the Senate and the House pitted against each other and the Governor weighing in against the PDMP (Prescription Drug Monitoring Program). Representative Scheck wants to get rid of all physician dispensing. To make this even more confusing, the Department of Health is finally launching the PDMP, (the vendor bidding battle has been settled) but the whole program may be shut down.

On much better notes, we have 2 victories for our patients and for your practice:

b. Sports concussion -- These bills HB 301 / SB 730 are gliding through their committees (currently in Education in the House and Rules in the Senate). It looks like MDs/DOs will be the final arbiters of return to play, but they may delegate parts of their responsibilities to ARNPs, PAs and athletic trainers. Neuropsychology reports and computerized testing may be used as supportive documentation. This is a major improvement over allowing other practitioners to clear our youth athletes -- this is a victtory for our patients.

c. Gun bill -- The NRA was pushing for doctrs to be punished by up to 5 million dollars in fines and 5 years in prison simply fr asking if their patients own guns. This is a patient safety issue but it is being disguised as an affront on the 2nd Amendment. Our 1st Amendment rights and the doctor-patient relationship. In another victory, HB 155 was amended to allow physicians to ask the gun question if it related to health and safety. Doctors also can record the information in their records (they were trying to bar this). In a nod to the NRA, doctors would not be allowed to discriminate against gun owners.

Can you see now why you should pay your dues online

This is going to be a very difficult session because almost nothing that adds to the budget or increases any fees/taxes to citizens will be passed.

On a frustrating note, Senator Mike Bennett on 04/04/11 lashed out at the Florida Medical Association (FMA), calling it a "greedy" group whose political agenda was about ensuring doctors salaries, not improving access to health care. "The FMA, the doctors, are greedy," said Bennett. "They want to continue to be able to double bill, they want to be able to continue to restrict access to health care for greed."

We have been educating and advocating for FL neurology needs, but since we are a 501(c)3, we have not lobbied and so I have been asked to not only continue to sit on the FMA Council on Legislation but also to join the Board of the FMA PAC (political action committee).

I accepted this position on the condition that FL neurologists would be recognized when donations are made so that FL neurologists can have their voices heard. Those of you that have already been contributing to the FMA PAC, can either do so through me or simply write “Neurology” on the check that they send it to the FMA PAC. Please do not direct any of the donations to the FSN, as we are a 501(c)3 tax exempt organization, instead make your checks out to the Senator Gaetz Campaign (maximum donation $500) and write “Neurology” on the memo line and email me.

Lastly, don’t forget that because the FSN is a tax-exempt 501(c)3 nonprofit, you can make tax free charitable donations (beyond your dues) to the FSN.

Your FSN is committed to serving your needs, so you will be receiving regular emails from me.

CME Programs in FL:

Orlando, FL: 09/16-18/11 -- FSN Annual Meeting (Disney Yacht Club)

If you have CME announcements, please email me at fsneuro@gmail.com

Daniel Kantor, MD
Medical Director
Neurologique

President
Florida Society of Neurology

Your FSN is here for you.

Parkinson's Event: "10 Mountains 10 Years" screening at the Palm Beach Film Festival

2011-03-25T16:19:00.005-04:00

Attention: Patient, carepartners, healthcare professionals and the Public, please take note of the great event this weekend:

"10 Mountains 10 Years" screening at the Palm Beach Film Festival

PRESS RELEASE

Contact:
Elizabeth K. Barber, PhD, Advocate
Parkinson’s Action Network and PALF, American Academy of Neurology
Tel: 331-452-3530; Fax: 630-665-3940
Email: ekbarber2@aol.com

Winfield Resident To Attend Parkinson’s Action Network
Event in Washington, DC to Put Education and Advocacy in Action

February 25, 2011 – Residents of Illinois will join members of the Parkinson’s disease community from across America in Washington, DC for the Parkinson’s Action Network (PAN) Research & Public Policy Forum, from February 28 through March 2, 2011.

At the PAN Forum, people living with Parkinson’s, their families and caregivers, and others working toward finding a cure for Parkinson’s come together in the Nation’s Capital to:

 Receive updates on the latest Parkinson’s disease research;
 Learn about where they can be most effective in helping educate elected officials about Parkinson’s;
 Attend grassroots advocacy workshops; and
 Meet with Members of Congress and their staff to talk about ways in which the government can support efforts to find better treatments and a cure, as well as improve the quality of life for people living with Parkinson’s

During the Forum, Dr. Elizabeth Barber, PhD, Parkinson’s Advocate from Winfield, Illinois and member of the American Academy of Neurology and the American Parkinson’s Disease Association will join/lead a team of advocates from Illinois to meet with Illinois Senators and Representatives and/or their staff to educate them about Parkinson’s disease, and why their vote on certain issues matter to people with Parkinson’s.

“The PAN Forum is an incredible opportunity to join forces with other advocates from across the country and let our voices be heard in Washington,” said Dr. Barber. I am excited to represent the people of Winfield, Illinois in our nation’s capital, particularly since the American Parkinson’s Disease Association, Midwest Chapter has just relocated to Winfield, and will work hard to make a difference for people with Parkinson’s and their families. “I am particularly excited to share the promising research results I have achieved in working with my mother, using supplements complementary to her prescribed Parkinson’s drugs which I am seeking support to have them studied in a larger clinical trial. I will also share the importance of an ordered environment in addition to a regular medication, dining, and exercise regime. I will also highlight the necessity of warning Parkinson’s patients of complications with accidental falls if they are prescribed anticoagulants.”

# # #

The Parkinson’s Action Network is the unified voice of the Parkinson’s community advocating for better treatments and a cure. In partnership with other Parkinson’s organizations and our powerful grassroots network, PAN educates the public and government leaders on better policies for research and an improved quality of life for people living with Parkinson’s. For more information, go to www.parkinsonsaction.org.

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

President
Florida Society of Neurology

info@neurologique.org
www.neurologique.org

Finger contractures and MS

2011-02-05T14:44:00.001-05:00

I received the following question on the MSF African-American forum:

Question:

Dear Doctor,

Are finger contractures a MS symptom? If so, what is the remedy?

Thanks.

Answer:

Thank you for the excellent question -- we need to approach your question as three separate ones:

1. Is what you are describing called finger contractures?

2. Can MS be the cause of the symptom?

3. How can you treat the symptom?

Before we go onto "1," let's describe for everyone what you mean by finger contractures:

Finger contractures are when the fingers are more than simply tight (spasticity), but actually shortned muscles or tendons from being contracted for too long. This makes the fingers look like they are tight and abnormal.

1. One should not simply assuming that every tight finger muscles is a contracture. For example, dystonia ("dys" -- "abnormal" or "bad" muscle tone) may appear to you as a contracture, but it is completely different and has different treatments.

Your neurologist can help you with this.

2.Yes, MS can cause spasticity, that if left for a long time, could turn into contractures. However, there are any other reasons for contractures.

So, once again -- speak to your neurologist.

3. Your treatment plan, is just that -- YOUR treatment plan and should be individualized and personalized in a partnership between you and your neurologist.

For actual contractures (not simply spasticity, which may be treated with stretching, yoga, oral muscle relaxants, injectable botulinum toxin and intrathecal baclofen pumps etc.), surgical release is sometimes considered.

I hope that this was useful.

Thank you,

Daniel Kantor, MD
Medical Director
Neurologique

President
Florida Society of Neurology
----------------------------------------------------------------

Be a leader, help the network ... join neurologique@gmail.com

Multiple Sclerosis Team Approach Rule *** MS Patient Network

www.neurologique.org

Twitter, Facebook, Blogs, YouTube and more.

Dr. Kantor Goes to Tallahassee OR What is a Neurologist Anyway?

2011-01-13T18:44:00.004-05:00

- Dr. Daniel Kantor, MD
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Triad Alcohol Swab Recall and How it Affects YOU

2011-01-13T17:47:00.030-05:00

This notice affects almost everyone, whether you have MS, Migraines (40 million Americans) or almost anything (1 in 5 Americans has a disability).

If you are a doctor or other health professional, please read this as you may use alcohol swabs in your offices.

On January 5^th, 2011 the FDA announced that Triad Alcohol Swabs have been voluntarily recalled due to potential contamination with bacteria.

Dr. Daniel Kantor has spent the last few days tirelessly clarifying for the MS community what this means in terms of the injectable therapies:

Here are the responses from 3 of the medications:

· Bayer’s Betaseron

· Teva’s Copaxone

· Novartis's Extavia

According to Biogen Idec, their Avonex is packaged with Dukal Alcohol Swabs, which we have clarified (with Dukal and Biogen Idec) that it is not a Triad product and is NOT part of the recall.

EMD Serono and Pfizer’s Rebif is not packaged by the company with alcohol swabs, and any alcohol swabs included in the shipment of this medication, is put in there by the specialty pharmacy distributors.

Neurologique always attempts to be your trusted source for timely MS news, and as such, Dr. Kantor has prepared a video demonstrating the Triad Alcohol Pads as compared to three of the others (the Dukal pad was not shown).

Since these alcohol swabs get rebranded by different companies, it is important to clarify which company produced your alcohol swab. If you are uncertain, do not use the alcohol swab and use other methods (as described in the press releases above) to clean the area before injection.

- Dr. Daniel Kantor, MD
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

MS Residential Center (ALS and CP too)

2010-11-26T06:58:00.001-05:00

MS Residential Center

- Dr. Daniel Kantor, MD
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

MS Town Hall Meeting: Dothan, AL on 11/04/10

2010-11-05T09:20:00.002-04:00

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Support Non-Mainstream MS Research ... Vote today!

2010-11-01T13:46:00.003-04:00

We are applying for a grant to support a non-mainstream MS Research Institute to support funding for research that wouldn't otherwise have much funding -- CCSVI (chronic cerebrospinal venous insufficiency), LDN (low dose naltrexone) etc.

Vote daily and spread the word at: http://pep.si/dniprs

Please VOTE today and every day:

&amp;amp;amp;amp;amp;amp;lt;br /&amp;amp;amp;amp;amp;amp;gt;&amp;amp;amp;amp;amp;amp;lt;br /&amp;amp;amp;amp;amp;amp;gt;&amp;amp;amp;amp;amp;amp;lt;br /&amp;amp;amp;amp;amp;amp;gt;&amp;amp;amp;amp;amp;amp;lt;br /&amp;amp;amp;amp;amp;amp;gt;&amp;amp;amp;amp;amp;amp;lt;br /&amp;amp;amp;amp;amp;amp;gt;&amp;amp;amp;amp;amp;amp;lt;br /&amp;amp;amp;amp;amp;amp;gt;&amp;amp;amp;amp;amp;amp;lt;br /&amp;amp;amp;amp;amp;amp;gt;

- Dr. Daniel Kantor, MD BSE Medical Director Neurologique info@neurologique.org www.neurologique.org

ECTRIMS 2010 (Goteborg, Sweden): Living longer with disease modifying treatments

2010-10-17T03:18:00.003-04:00

Well, another year has past since our historic first time ever (in any medical conference) live video bloggingat ECTRIMS 2009 in Dusseldorf, Germany. This year, ECTRIMS (European Committee for Treatment and Research in Multiple Sclerosis) was held on October 13 - 16, 2010 in Goteborg, Sweden and once again I filmed video blogs directly to you.

What made this year special was that aside from interviewing other MS professionals (Dr. Gary Cutter at the Consortium of MS Centers or CMSC Annual Meeting), we had other neurologists make videos with MSWorld, as well. The excitement is spreading and this can only be a good think for people with MS and their families.

For the next few postings, I will highlight important abstracts and presentations.

It is very difficult t wrap our heads around the concept of disease modification, but living longer is something that we can all understand. As Daniel Defoe first wrote in The Political History of the Devil, 1726:"Things as certain as death and taxes, can be more firmly believed." Benjamin Franklin coined the phrase n a letter to Jean-Baptiste Leroy, 1789, which was re-printed in The Works of Benjamin Franklin, 1817: "'In this world nothing can be said to be certain, except death and taxes." In an abstract by Reder et al. entitled: Survival analysis 21 years after the initiation of the pivotal interferon beta-1b trial in patients with RRMS, the authors compared the survival of those originally randomized to Betaseron/Betaferon to those initially placed on placebo; people with MS who were originally placed on Interferon ß-1b had increased survival.

This is significant because no longer do we have to say that this medication may modify the disease course, but that it may actually make you live longer.

This is another reason to start treatment early.

- Dr. Daniel Kantor, MD BSE Medical

Director Neurologique

info@neurologique.org

www.neurologique.org

Ex-U.S. access to Ampyra

2010-09-23T23:19:00.002-04:00

On the MSF Focus Ask-the-Doctor forum, I received the following question:

Question

Dear Doctors,

May I ask, when you prescribe the compounded 4-AP for an MS patient, what makes you decide this patient will need a sustained release not an instant release form, and vice versus?

My second question is, suppose a patient is taking Ampyra, if they have to switch to 4-AP, should they take 4-AP SL 10mg/capsule which is very much like Ampyra, or what dose should they start?

I’m a wheelchair MS patient in Vietnam. After a lot of efforts, a friend of mine living in the states managed to buy me one month supply of Ampyra with the cost of $1,271 (Almost all my income last year, the average income in Vietnam is less than $100/month. But I think if I can walk again, it worths it).

As suggested by my neuro, to play safe, I took 1 tablet/day for the first week. My walking ability improved, and so did my bladder problem. However, when I increased dose to 2 tablets/day, everything was getting worst. Now I’m back to 1 tablet/day and in good shape again.

I’m very happy with the effect, however I cannot afford another month of Ampyra and really want to switch to 4-AP. My neuro refused to write a prescription for it, though, saying it’s illegal in Vietnam, also he can’t prescribe for something he’s not sure about quality. He promised to talk to the authorities about having a GMP, GSP… (I’m not sure about this bit) pharmaceutical company here compounded it for MS patients. I know my neuro is a man of his words, but it will take several years before they can make their decision, and I can’t wait that long…

Fighting with MS is hard enough, it’s even harder for me in Vietnam with limited MS medication and experience. I feel so lonely and abandoned joining forums here and see people discussing about a wide range of medication they can choose

Sorry I didn’t mean to moan. It’s just pouring out.

I’m appreciated for your inputs.

Answer

We certainly all feel for your situation. Was it your doctor who has been corresponding with me? If so, I can attest to the amount of time that he has invested in helping you. We worked with Biogen Idec (they handle Ampyra globally, ex-U.S., for Acorda), but unfortunately the "named" program is not available in Vietnam.

Ampyra is a pharmaceutical grade product and there are several reasons to choose it over Compounded 4-Aminopyridine, including the potential for compounding/dosage errors with potential for overdose and resultant seizures. Please see my discussion: http://bit.ly/dzVLcP

You are right (as most patients are) that some people feel worse on 10 mg every 12 hours than 10 mg once a day. Patients with kidney problems need to watch out for reduced renal clearance of Ampyra, which can cause an increase in the amount of Ampyra in the body, and result in seizures. The FDA has asked Acorda to study 5 mg pills, but it may not be that easy to make. Compounded 4-Aminopyridine can, of course, be made in 5 mg capsules.

You are not moaning, you are frustrated, but hopefully people with MS in the U.S. and Europe can learn from you that, in some ways, things are easier in the Western World (that might not be a consolation to many) -- but, rest assured, your neurologist and I are in contact.

Stay strong.

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Gilenya vs. Cladribine: Differences and similarities in regulatory review

2010-09-22T21:03:00.002-04:00

Pharmawire covered our comment, see below:

Novartis: Recent Gilenya decision best-case scenario; cladribine receives two-year label restriction in Australia - physicians Pharmawire

Novartis' (NYSE:NVS) Gilenya is expected to take more market share than previously expected in multiple sclerosis, due to labeling that was a "best case scenario" for the company, neurologists said.

Gilenya (fingolimod) 0.5 mg daily received approval today, making it the first oral multiple sclerosis drug approved in the US. Competitor Merck-Serono is awaiting an FDA ruling on their competing oral compound cladribine, later this year.

Under the label restriction in Australia, Merck-Serono's Movectro (cladribine) is indicated for the treatment of relapsing-remitting multiple sclerosis for a maximum duration of two years.

Elmar SchNee, Head of Pharma at Merck KGa, said at a recent investor conference that cladribine faces an upcoming EU decision, and the regulators might be "more restrictive" there, following on from comments about the recent 2-year Australian label restriction. Cladribine tablets will be registered in Australia under the trade name Movectro.

"I am extremely pleased Gilenya got approved, and pleased that the FDA didn’t put a lot of restrictions on it, as those decisions are best left to physicians," said Dr Anne Cross, a professor of neurology at the Manny and Rosalyn Rosenthal – Dr. John Trotter MS Chair in Neuroimmunology at Washington University in St. Louis.

Cross said she will initially use Gilenya in patients who have failed the front-line therapies, but expects to use the drug in other patients after the drug has been on the market for awhile. "I'm a conservative person, so I tend to not use new drugs in a lot of patients until after a few months," she said.

However, while Cross is excited about the potential of cladribine due to its more convenient dosing schedule relative to Gilenya, she said the drug is "a problem if you need to reverse it." She explained that cladribine is long acting, therefore if patients develop infections, "you’re in a bind. It isn’t reversible. That worries me a little bit about cladribine, moreso than Gilenya," Cross said.

There are some individual things that will be “ironed out” with Novartis' drug, such as how closely to monitor heart rate, but this issue should “sort itself out over time,” Cross noted.

"There is a lot of demand for Gilenya. Novartis really got a deal from the regulators. It’s going to do a lot for their market share," said Dr Samuel Hunter, a neurologist and President of the Advanced Neurosciences Institute in Franklin, Tennessee. He added that he was surprised that the drug did not receive a blackbox warning due to several malignancies that were observed in clinical trials.

Still, Gilenya was likely spared such a warning since while there was an increased risk for the development of malignancies in the Phase II TRANSFORMS study, which tested the 0.5 mg and 1.25mg doses of Gilenya, in the larger Phase III trial, involving over 1,000 patients, there was no increased risk, noted Dr Douglas Jeffery, a neurologist at Wake Forest University School of Medicine. In addition, there was also no increase in cancer risk in patients who entered into the long term extension study, he said.

There is a risk management program, and both the company and physicians will continue to evaluate the safety of Gilenya, Jeffery noted.

Jeffrey also cautioned that despite Novartis' seemingly easy approval process and label for their oral MS drug, Merck-Serono's cladribine and its side-effects are at a different order of magnitude in regards to malignancy risk. Based on the literature in hairy cell leukemia, patients who received lower doses of cladribine than those used in MS trials, reported secondary malignancies. "This is a whole different order of magnitude, which the FDA will have to look at very carefully," he said.

Hunter added that despite the ease for Novartis in securing approval, he also believes that the FDA will follow guidelines from the EU and Australian regulators with regards to cladribine and its label restriction. "The agency is going to be cautious, since the drug is too similar to other immunomodulators that have had problems in MS," he said, referring to Biogen’s Tysabri. However, a risk management program is easier to follow for an oral drug, he noted.

The risk management plan for Gilenya is very benign, said Hunter, who has the in-house skills to handle those tests internally at his clinic. "We have a retinal scanner that can do the job for the eye test. Most neurologists have an EKG machine. That’s manageable for most people who are treating MS," he said.

The risk management program for Gilenya requires that patients receive a medication guide, and a letter and safety information guide for healthcare providers. Novartis will also be initiating a five-year, international post-authorization safety study to monitor selected safety-related outcomes and a voluntary pregnancy registry.

Dr Daniel Kantor, a neurologist and Medical Director of the Neurologique Foundation in Florida, said the label for Gilenya was the best possible outcome for Novartis. The addition of an indication for disability is probably the most important indication for MS in a long-time, he said. That combined with the fact that it is an oral drug for delaying disability progression is sure to increase market share, he noted.

The REMS program for Gilenya was also very beneficial to Novartis, and will be clarified further in the upcoming weeks, Kantor said.

by Kimberly Ha

- Dr. Daniel Kantor, MD BSE

Medical Director

Neurologique

info@neurologique.org

www.neurologique.org

Pharmawire quotes Dr. Kantor on Gilenya launch

2010-09-22T16:06:00.002-04:00

You heard it here first.

Please see the Pharmawire article below:

Novartis' new oral MS drug Gilenya official US launch date 4 October, company confirms Pharmawire

Novartis (NYSE:NVS) plans to launch its new oral multiple sclerosis (MS) drug Gilenya (formerly Gilenia) on 4 October, according to Dr Daniel Kantor, Medical Director, Neurologique Foundation in Florida.

A spokesperson for Novartis confirmed that in the US, physicians will be able to prescribe Gilenya starting on 4 October 2010.

Gilenya is the first oral disease-modifying therapy for the treatment of relapsing remitting multiple sclerosis (MS).

The company will be hosting an upcoming internal launch meeting in Orlando, Kantor said. Novartis also plans to host a web conference with physicians to discuss this new treatment on 7 October, he noted.

by Kimberly Ha

- Dr. Daniel Kantor, MD BSE

Medical Director

Neurologique

info@neurologique.org

www.neurologique.org

Rocking MS: First Big News since Betaferon, GA and Tysabri hit the market: Open Letter to Novartis CEO

2010-09-22T02:33:00.003-04:00

Open Letter to Joe Jimenez, CEO, Novartis:

Dear Joe,

CONGRATULATIONS!

The FDA Approval of Gilenya(TM) is a milestone in the MS community.

Novartis (NVS) heard the outcry from MS patients, care partners, nonprofits and neurologists; Novartis heard the outcry and listened carefully.

What makes the approval even more exciting is that Gilenya(TM) [FTY720, Fingolimod, Gilenia] is approved for reduction in relapses and in slowing disability progression. While Gilenya is approved for relapsing MS, we are excited about the potential that Gilenya may hold in progressive forms of MS as well (and we await the conclusion of the PPMS trial).

The REMS (Risk Evaluation and Mitigation Strategy) is gentler than we ever could have expected, but this will of course be further clarified in the future.

Novarti's press release was at 7:00 AM CET (GMT +1) and we first broke the news less than 30 minutes later:

http://bit.ly/cOemMl

http://bit.ly/cwMe4W

http://bit.ly/cSNqey

- Dr. Daniel Kantor, MD BSE

Medical Director

Neurologique

info@neurologique.org

www.neurologique.org

Brave New World: Oral Medicines in MS

2010-09-21T00:08:00.002-04:00

In a few hours, the U.S. FDA (Food and Drug Administration) is set to make history by approving the first oral medication for the reduction of annualized relapse rate in Relapsing forms of MS.

It is unlikely that the FDA will delay this milestone in MS therapeutics, and so Novartis's FTY720 (Fingolimod) will be welcomed to our growing MS armamentarium. It is unclear what the name of this medication will be -- please see: http://bit.ly/aqTrsz (will Gilenia be spelled "Gelenia" or "Gelinia" or "Gelenea" or "Gelinea").

Of course predictions of how MS specialists and general neurologists will use this medication, are usually discussed in private consultations with Wall Street analysts/investors, but I thought that it would be useful to discuss different patient types and where FTY720 may be positioned in their care:

1. Clinically Isolated Syndrome (CIS) -- FTY720 has not been systematically studied in CIS, and so there will be no FDA indication for its use in the first demyelinating event suggestive of MS. In the future, however, FTY720 may be studied, just as EMD Serono's Cladribine is (ORACLE MS - Oral Cladribine in Early MS). Novartis will probably wait some time before initiating a large scale CIS trial, just as the other DMD companies did (CHAMPS, ETOMS, BENEFIT, PreCISe).

2. Early MS -- Patients and their physicians will weigh the benefits of an oral medication as well as the patients' desire to not be on injectable medications, against the long term safety data of the currently approved injectable MS treatments.

3. Newly diagnosed -- When faced with options of an oral medication or injectables/intravenous (IV) medications, patients may be swayed to choose the oral treatment because of fears concerning the older medications and a perception that oral means safer (this is not necessarily borne out by the safety data).

4. Active RRMS -- People with active inflammatory MS will need an additional option to control the demyelinating lesions, and FTY720 will afford another option. Patients and their neurologists will choose between Biogen Idec's and Elan's Tysabri (natalizumab) and FTY720. Other patients who have been on every DMD, will only have FTY720 to choose from.

5. MS patients who have not tolerated other MS medications -- FTY720 will allow an additional medication option for those who cannot be on the other DMDs because of tolerability issues.

6. Early secondary progressive MS -- Although not studied in TRANSFORMS or FREEDOMS, there is an ongoing trial of FTY720 in PPMS (primary progressive MS). If the suggestive animal data translates into human beings, then FTY720 could be effective in both RRMS and PPMS, which would make it an attractive drug for SPMS.

7. Later secondary progressive and primary progressive MS -- Although not studied in TRANSFORMS or FREEDOMS, there is an ongoing trial of FTY720 in PPMS (primary progressive MS). If the suggestive animal data translates into human beings, then FTY720 could be effective in PPMS (and perhaps later SPMS).

8. Patients in the FREEDOMS II trial -- Patients who are enrolled in the ongoing placebo-controlled trial of FTY720, may be tempted to drop out and initiate FTY720, instead of taking the risk of placebo. This drop-out rate plus the approval of FTY720 may cause the Data Safety Monitoring Board (DSMB) to cut FREEDOMS II short.

9. Patients in other MS clinical trials -- Patients may choose to start this new oral medication instead of taking the risk of placebo in other trials. This could have a chilling effect on ongoing MS research.

As you can see, there are many potential uses for FTY720, but most importantly it will be AVAILABLE.

- Dr. Daniel Kantor, MD BSE

Medical Director

Neurologique

info@neurologique.org

www.neurologique.org

Open Letter to Dr. Zorba Paster -- Dangerous Assumptions and RLS

2010-09-20T05:11:00.000-04:00

Dear Dr. Zorba Paster,

While I appreciate your patient-centered approach to medical queries on your radio show, as a neurologist I was very concerned to hear how you answered a question regarding nonspecific nighttime leg symptoms. On September 12, 2010, a caller asked about her uncomfortable leg sensations. Without a complete history or physical examination, you informed her that she has restless legs syndrome (RLS) and should ask her doctor to place her on Requip(R) (Ropinirole). Not only is this favoring one medication over others. You did not encourage the patient to look for the source of her symptoms, for example if this is truly RLS, iron deficiency should be looked for.

Most concerning, it is unclear that this patient even has RLS. There are many other causes of nonspecific nighttime symptoms, such as spasticity, peripheral neuropathy, skin disorders etc.

I am concerned because this patient may have then gone primary care physicians and told her that she has RLS and needed to be on Requip(R). This unexpecting physician, may have taken the diagnosis as an established one and not investigated it fully, nor treated it appropriately. This patient may have then had the rare side effect of suicide, all because she was on an unneeded medication.

Once again, I implore you to stick to your excellent expertise and comingling of CAM (complementary and alternative medications) and approaches because whenever you make an assumption and recommendation outside your specialty area, it raises doubt over all your other answers.

Please remember, Primum Non Nocere (First Do No Harm).

Thank you,

Daniel Kantor, MD BSE
Medical Director
Neurologique

President-Elect
Florida Society of Neurology

CCSVI and the MSF

2010-08-09T23:38:00.006-04:00

As many of you know, I answer questions on the MSF forums (Ask the Doctor and African Americans with MS), and I wanted to share a recent question and answer.

Question:

I am 45 year old American woman with rr ms. i am pretty stable, have drop foot, fatigue. I read that the CCSVI could block the illness and improve symptoms. Of course I am curious. My family urges me to wait until there is more solid evidence of success. How long should I wait? If I can find a doctor here in Italy (I live in Italy) who is willing to do the angioplasty I think I would do it tomorrow. It seems to be helping the many who have done the procedeure. Isn't this evidence enough? What are the major cons?

Answer:

Thank you for the question.

CCSVI (chronic cerebrospinal venous insufficiency) is the name of the proposed condition, not the procedure -- which has been termed the Liberation Procedure, and is venoplasty with or without stenting.

A few previous blogs of mine on this, can be found at:

So, what does this all mean?

The testimonials and videos of people with MS undergoing venoplasty are impressive, but so is the response of people in clinical trials, of medications which may ultimately found to not be effective overall.

On the other hand, people with MS don't want to wait until the procedure is either proven or disproven; this is why we are designing research where everyone still gets the procedure, but at least we collect useful information that will help the entire MS community in the future ... so stay tuned for the research.

In regards to "evidence enough," sadly the answer is no. Scientific evidence is a process that has rules and processes. Suggestive - possibly, hopeful - definitely, but evidence has a very specific meaning.

Thank you,

Daniel Kantor, MD BSE

Medical Director

Neurologique

President-Elect

Florida Society of Neurology

----------------------------------------------------------------

Be a leader, help the network ... join neurologique@gmail.com

Multiple Sclerosis Team Approach Rule *** MS Patient Network

www.neurologique.org

Twitter, facebook, blogs and more.

Virtual Second Life MS Town Hall Meeting

2010-08-01T15:07:00.003-04:00

Virtual Second Life MS Town Hall Meeting:

- Dr. Daniel Kantor, MD BSE

Medical Director

Neurologique

info@neurologique.org

www.neurologique.org

Heat and MS

2010-07-13T23:54:00.006-04:00

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

2010-06-10T08:08:00.005-04:00

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

2010-05-17T01:25:00.001-04:00

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)

2010-05-12T22:51:00.002-04:00

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

2010-05-12T16:21:00.003-04:00

- Dr. Daniel Kantor, MD BSE

Medical Director

Neurologique

info@neurologique.org

www.neurologique.org

Emotional Lability, Pseudobulbar Affect and Hope for Zenvia

2010-05-03T09:21:00.003-04:00

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

2010-04-12T23:08:00.002-04:00

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

2010-04-09T17:24:00.002-04:00

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

2010-03-15T09:46:00.000-04:00

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

2010-03-11T16:18:00.001-05:00

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

2010-03-09T20:24:00.004-05:00

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

2010-03-05T17:38:00.006-05:00

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

2010-03-03T22:52:00.002-05:00

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

2010-02-27T01:01:00.001-05:00

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

2010-02-26T17:32:00.002-05:00

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

2010-02-22T15:33:00.003-05:00

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

It's a tough time to have migraines

2010-02-20T01:45:00.003-05:00

As if it's not bad enough having the pain of migraines, all these medical articles are coming out suggesting that people with migraines have a higher risk of heart attacks, stroke, claudication (peripheral artery disease), diabetes, hypertension, high cholesterol.

Migraines with aura were even associated with smoking.

So, how do we understand this paper: Bigal ME, et al "Migraine and cardiovascular disease: A population-based study"Neurology 2010; 74: 628-35. ?

Could migraine be an actual risk factor for these other problems?

Like always, let's look at several possibilities:

1. The association is incorrect -- this seems unlikely since multiple studies seem to show similar results, but there is always that problem of case ascertainment (how do you know who does and who doesn't have something).

2. The association is correct and there is something else that causes both the migraines and the other problems -- this is fairly likely.

3. The association is correct and migraines and cardiovascular disease/risk factors share a common genetic link (the genes contributing to them are close to each other in our DNA) -- this is also fairly likely.

4. The association is correct and migraines are caused by cardiovascular disease/risk factors -- so even though it seems that the migraines happened first, there could have been an underlying risk for the cardiovascular disease. This may be less likely since many people start having migraines very young and they don't (supposedly) have heart disease at that time, but couldn't there be something about their underlying genetic/environmental makeup that makes them destined for cardiovascular disease?

This is much more likely in the whole discussion of migraines and MS -- see:

http://neurologique.blogspot.com/2010/02/migraine-and-ms-lessons-for-ccsvi.html

Our analysis made WebMD and Medscape Neurology interested, see:

http://www.medscape.com/viewarticle/717267?src=emailthis

5. The association is correct and migraines cause cardiovascular disease/risk factors -- is it that the actual migraine disease process (inflammation on the covering of the brain [meninges]) causes cardiovascular disease? Alternatively, could it be that having migraines makes you more likely to have other (as of yet, immeasurable) habits that could predispose you to cardiovascular disease/risk factors? It would be difficult to explain the smoking association otherwise. Do we really think that migraine pathophysiology causes smoking? Couldn't it be that being a person with migraine (with aura) makes you want to smoke (maybe it relaxes you)? This is an example of how migraine can be associated with something but not cause it in the way we usually understand it.

So, we are stuck with more questions (as always), so what are our lessons?

Instead of focusing on how worried you should be about your migraines causing future health problems, you should take control over your own health and modify the cardiovascular risk factors that you can (you can't change age, sex or your family), such as smoking, blood sugar control, weight loss, cholesterol management.

The central principle of the Migraine and MS Team Approach Rule (M*STAR) is that YOU are the center of your own health team. That means you control your own destiny, but that also gives you great responsibility.

What can your doctors / neurologists learn from this?

When we see a patient with migraine, we should be sure to ask about cardiovascular risk factors and encourage you to modify them in order to maximize your potential and to work with you as a consultant for your M*STAR health team.

We need to keep this open dialogue among people with migraines and between people with migraines and their doctors. Don't forget your doctors probably have migraines too (especially neurologists and headache specialists). This is what My Grrr AYN (Migraine Association of Young Networkers) is all about.

Interestingly, establishing the association of migraine and cardiovascular disease raises the issue of our treatments and the potential for heart complications. Merck (MRK) is developing Telcagepant), a CGRP (calcitonin gene related peptide) antagonist, that we hope will be able to be used in people with migraines who have heart disease as well.

The real advance will be if treating and preventing migraines will actually reduce cardiovascular disease/risk factors.

In the meantime, remember ... an apple a day ....

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Revisiting the past: Neck pain in migraine

2010-02-19T17:23:00.003-05:00

Medical media reporting confuses me sometimes.

Medscape Neurology reported on February 16th 2010 a study by Dr. Anne Calhoun looking at the percentage of migraine patients who reported neck pain and how that compares to those who have nausea.

See: http://www.medscape.com/viewarticle/717025?src=mpnews&spon=26&uac=88627FN

Is this surprising?

No.

Look to: Kaniecki et al. Poster presented at: 10th IHC; June 29-July 2, 2001; New York, NY.
Where they found that in a retrospective chart review of 144 patients with migraine, 75% reported neck pain with their migraines; 43% described bilateral neck pain and 57% unilateral (one-sided). 69% described the neck pain as "tightness" and 17% as "stiffness." The neck pain occurred 61% of the time in the prodrome (you just have a feeling that something isn't right and that a migraine is going to come on), 92% of the time during the headache and 41% during the postdrome (the yucky period you feel after the migraine).

In Cady et al. Poster presented at: 10th IHC; June 29-July 2, 2001; New York, NY, nausea is only present 63% of the time, while in Schreiber et al. Poster presented at: AHS June 21-23, 2002: Seattle, WA, nausea was present 70% of the time.

So, is anything new?

No.

We already knew this, as Dr. Calhoun pointed out: "...when we first presented these findings at the American Academy of Neurology meeting, the response from headache specialists was almost universal: vigorous nodding and assent,”

It is good, however to raise awareness to this and all the other common features of migraine, such as sinus stuffiness, pressure and drainage. Schreiber found prospectively in 2,524 patients without a prior migraine diagnosis that 82% of people reporting "sinus" headaches met the International Headache Society (IHS) criteria for migraines.

So, what does this mean?

1. Migraine is not just about the head pain and it is probably a lot more common than we think.

2. Not having a migraine diagnosis (yet) doesn't mean that your headaches aren't migraines.

3. Labels are important because they help with reassurance and they direct therapeutic options.

[see: http://neurologique.blogspot.com/2010/02/migraine-and-ms-lessons-for-ccsvi.html]

and ...

4. Take studies into their historical context. Maybe there really is nothing new under the sun.

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Tragic Luger death: neurological lessons

2010-02-19T12:17:00.002-05:00

I have been asked to weigh in on the potential causes of death of Olympic luger Nodar Kumaritashvili's.

As neurologists (and doctors in general), we think in terms of a differential diagnosis. We think in terms of what could potentially cause a given problem.

Here are some potential causes for his tragic death (at over 90 mph):

1) Subdural hematoma -- unlikely to kill so fast.
2.) Intracerebral hemorrhage.

3.) Epidural hematoma.

4.) Axonal shearing injury.

5.) Cervical (neck) fracture with damage to the sympathetic fibers to the heart.

6.) Voodoo death (death by fright) as we know he expressed fear the day before -- remember our discussion surrounding Michael Jackson's death:

http://neurologique.blogspot.com/2009/06/michael-jackson-voodoo-death-and.html

7.) Direct trauma to the chest -- stopping the heart.

For a full version of the interview I gave, please see:

http://www.associatedcontent.com/article/2708371/exact_cause_of_lugers_death_doctor.html?cat=70

Our hearts and thoughts are with the family of this great Georgian athlete.

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Daclizumab -- how does it fit in

2010-02-16T21:50:00.003-05:00

Why did Facet Biotech Corporation (FACT) shareholder's reject Biogen Idec's (BIIB) unsolicited tender offer ($17.50)?

Maybe they were waiting for the release of the CHOICE data ($16.71).

The Lancet Neurology released Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase 2, randomised, double-blind, placebo-controlled, add-on trial with interferon beta online in advance of print publication in April 2010

(http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(10)70033-8/fulltext#article_upsell).

So, how does the data on this subcutaneous (under the skin) anti-CD25 monoclonal antibody (which causes an increase in CD56bright natural killer cells) compare to data from other MS disease modifying agents?

In this study, participants wither received high dose Daclizumab plus interferon beta, low dose Daclizumab plus interferon beta or placebo plus interferon beta -- this reminds of the study design of the phase III AFFIRM study of Tysabri plus Avonex vs. Avonex alone. The endpoint in the 6-month phase II CHOICE study of new or enlarged Gadolinium enhancing lesion on brain MRI is different from the enfpoints in the AFFIRM (and other) studies. There was a mean of 4.75 in the interferon alone group and 1.32 in the high dose Daclizumab plus interferon group. This is a fairly active group of relapsing MS patients since there are so many new (or enlarged) Gadolinium enhancing lesions despite all patients being on interferon beta.

Although we are looking at slightly different MRI outcomes and certainly different time periods, let's look at a few of the Tysabri, Fingolimod and Cladribine trials:

2-year AFFIRM (Tysabri plus Avonex vs. Avonex alone):

Number of Gadolinium enhancing lesions:

0.1 vs. 0.8

Number of new or enlarging T2 hyperintense lesions:

0.5 vs. 2.4

1-year TRANSFORMS (Fingolimod/Gilenia [here low 0.5 mg dose only] vs. Avonex):

Number of Gadolinium enhancing lesions:

0.23 vs. 0.51

Number of new or enlarging T2 hyperintense lesions:

1.7 vs. 2.6

2-year CLARITY (Cladribine [here low 3.5 mg/kg dose only] vs. placebo):

Number of Gadolinium enhancing lesions:

0.12 vs. 0.91

Number of Combined Unique lesions:

0.43 vs. 1.72

Number of Active T2 lesions:

0.38 vs. 1.43

6-month CHOICE (Daclizumab [here high 2 mg/kg dose] plus INF vs. INF alone):

Number of new or enlarged Gadolinium enhancing lesion:

1.32 vs. 4.75

So, no matter how you look at it, the patients in the CHOICE study had more active MRIs (albeit, this is only a 6-month study).

So, were the FACT shareholders right in rejecting BIIB's bid?

What do you think?

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

Migraine and MS: Lessons for CCSVI

2010-02-16T19:29:00.004-05:00

Migraine and CCSVI have a lot to learn from each other.

Dr. Zamboni (and Dr. Zivadinov preliminarily) thinks that there is more CCSVI in people with MS than in those without Multiple Sclerosis.

[See our other blogs on CCSVI (chronic cerebrospinal venous insufficiency) at:

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

]

Does that mean that CCSVI causes MS or that fixing the CCSVI will fix/cure/treat the MS?

Well, does a recent study, to be presented at the upcoming AAN (American Academy of Neurology) annual meeting in Toronto, which raises the possibility that there is more migraine in women with MS than in those without MS, also mean that migraines cause MS or that treating the migraine will cure the MS?

No.

In the abstract (http://www.eurekalert.org/pub_releases/2010-02/aaon-mmc020210.php) to be presented by Dr. Ilya Krister, they found that by looking at participants in the Nurses' Health Study II, more people who were diagnosed with MS at the end of the 16-year study period had an initial diagnosis of MS than those who were not diagnosed with MS.

So, of the 116,678 women, 18,000 had an initial diagnosis of migraine, of which 82 went on to be diagnosed with MS by the end of the study; of the 98,678 without an initial diagnosis of migraine, 293 were diagnosed with MS by the end of the study.

This information has been picked up and spread around the internet by WebMD, U.S. News and World Report (HealthDay), MSN etc., but before striking fear in the 18 - 20 million American women with migraines, we need to analyze this further (in anticipation of the actual presentation):

This means that 15.427073% of the study population had an initial diagnosis of migraine, which is reasonable considering different prevalence rates depending on age (what is the age distribution in this study?) of approximately 18%. If someone went on to be diagnosed with MS, the prevalence of an initial migraine diagnosis was 21.866…% (which means that 78.133…% of the women who were eventually diagnosed with MS did not start out with a migraine diagnosis). Of the women who started out with an initial migraine diagnosis, 82 (0.455…%) went on to be diagnosed with MS, as opposed to 293 (0.29692535%) who were later diagnosed with MS and who did not have an initial migraine diagnosis.

This suggests that maybe women with MS have an earlier diagnosis of migraine – this can be for several hypothetical reasons, including that women who eventually get diagnosed with MS are more likely to go see a doctor as they may be having other early symptoms and when they see the doctor, they may be diagnosed with migraine at that time.

Looking at epidemiology alone also suggests that neurologists and especially headache specialists have a higher rate of migraine than the general population – in Neurology 2003;61:1271-1272, Evans, Lipton and Silberstein reported that 1-yearand lifetime prevalences of migraine in the 220 respondentswere as follows: male neurologists, 34.7%, 46.6%; male headachespecialists, 59.3%, 71.9%; female neurologists, 58.1%, 62.8%;and female headache specialists, 74.1%, 81.5%.

The idea that migraine precedes the MS, and not vice versa assumes that MS comes on at a certain defined point, like a car accident, instead we believe that MS is diagnosed well after the disease process starts (even prior to the initial symptoms), so it could be that the women who had migraines and then went on to be diagnosed with MS, actually had the MS first.

Epidemiology and prevalence rates can be tricky – in a 1995 meta-analysis by Stewart et al. in the Journal of Clinical Epidemiology, 36.1% of the variation in prevalence estimates among studies was explained by case definitions/. Thus, the largest source of variation in prevalence estimates of migraine has to do with how you decide who does and who doesn’t have migraines. In the Nurses’ Health Study II, the definition of migraine was based upon the participant having gone to a doctor and that doctor having given them a diagnosis of migraine. This makes the data more difficult to interpret.

As some of you may know, a special interest of mine is the intersection between migraine and MS. With that in mind, we looked at a big series of neurology office visits by people with MS and found that neurologists underreported their patients’ migraines. A possible reason for this is that if a neurologist is less familiar with MS, she may focus on the disease process itself (the medications can be frightening) and not on the individual symptoms. This is why it is very important to write down three major issues you want to discuss with your neurologist at each office visit, so it will focus the visit on the symptoms and issues important to YOU.

Let’s delve deeper into the numbers in the press release of Dr. Krister’s study/ At the end of the study, 375 out of 116,678 women had an MS diagnosis. This makes a prevalence of 321.397835 per 100,000. This is extremely high and raises questions about the data. If we take the prevalence of MS in the U.S. as 450,000 and we assume that two-thirds of people with MS are women, then there are 300,000 women with MS in the United States out of a population of 154,938,000 women in the U.S. (2008 census of U.S. population is 303,800,000 of whom ~51% are women). This means that in the U.S. there are 193.61584 women with MS per 100,000 and if we took the very high number of 321.397835 per 100,000 as in the Nurses’ Health Study II, there should be ~497,967 women with MS in the United States!

So, how does this all related to CCSVI?

Well, looking at associations can be confusing and even looking at large numbers of people doesn’t always answer the question.

But we can keep trying, can't we?

P.S. Think about the name of a diagnosis that affects women more than men; young more than old; has a genetic component; normal appearing white matter may not be so normal; has white spots (T2 hyperintensities) on brain MRI in a quarter of people in some series; and involves inflammation on the meninges (covering of the brain, optic nerves and spinal cord).

Give up?

Clue: It's not MS.

It's migraine.

- Dr. Daniel Kantor, MD BSE

Medical Director

Neurologique

info@neurologique.org

www.neurologique.org

CCSVI: Does it hold up?

2010-02-10T11:27:00.002-05:00

CCSVI: Fact or Fiction?

When I saw Robert Zivadinov, MD PhD 2 weeks ago he was excited. He may have even have a greater reason to be excited.

When they looked at the preliminary data (first 500 patients) from the University of Buffalo Combined Transcranial and Extracranial Venous Doppler Evaluation (CTEVD) study, they found that when the 10.2% of subjects in which results were border line were excluded, the percentage of affected MS patients rose to 62.5%, compared to 25.9 percent of healthy controls.

These are promising results, but remember a few things that we discussed on previous blogs:

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

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

We need to prove the association (although 500 is a large number of patients) and then see whether association is equal to causation and then whether causation means that we can fix it after the fact.

I know it is hard, but patience is key ...

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

The more information, the better

2010-01-24T20:46:00.002-05:00

Screening out?

Biogen Idec (BIIB) has been forced to learn the importance of disseminating information, quicker and better than any other MS company.

That's what having a side effect, such as PML (progressive multifocal leukoencephalopathy) in what was supposed to be a blockbuster MS drug.

PML occurs when the JC virus is reactivated and crosses the blood-brain barrier. The thinking is that if a person who goes on Tysabri (Natalizumab) has not been exposed to the JC virus in the past, then they should not be at risk for developing PML.

The first scientific question is whether this holds true -- if you do not acquire JC virus in childhood or adolescence are you really not at risk for developing PML with Tysabri? Could being exposed to Tysabri make someone more likely to even get infected in the first place with a virus that is thought to be acquired when we are younger?

For the moment we will leave that question behind, as well as the question of what percentage of people in the general population have the latent JC virus : is it 80% as we previously thought, or 50% as new data has suggested?

Will developing a JC virus antibody screen be beneficial to Biogen Idec and Elan?

Firstly, Biogen Idec has prided itself on returning so much of its revenues back into R&D, nd this should be applauded -- so advancing science is always beneficial.

But on a sales point-of-view, I actually think that knowing who does not have the JC virus in their system ill aide the sales of Tysabri. Assuming the test is perfect and that the JC virus is only acquired in younger ages, this would mean that 50% of MS patients are not at risk for PML, even when placed on Tysabri.

This is 50% of the MS market that could [potentially be taken over by Tysabri -- not only in switches as second- or third-line choices, but even as a first-line agent (as it was projected to be back before it was originally voluntarily pulled from the market due to PML. This is a lot larger market share than Tysabri has right now and it can be justified based on the good efficacy data (that looks even better when taking the CLARITY, TRANSFORMS and FREEDOMS studies into consideration -- see:

http://neurologique.blogspot.com/2009/07/merck-kgaa-not-to-be-confused-with.html )

The other 50% of MS patients (those who have been exposed to the JC virus in the past) would be at a potential risk for PML. This doesn't mean that they wouldn't necessarily be placed on Tysabri, but that they are the ones who are at risk -- just as now we think of everyone on Tysabri as being at risk for PML, yet many neurologists and patients choose to be on the medication. So, assuming the 1:1000 risk for PML (simply for demonstrative purposes), then the patient population at risk for PML is actually 500 and so the risk in JC virus antibody positive patients is 1:500 and in JC virus antibody negative patients it is 0:500.

So overall, just as Tysabri patients are willing to assume the risk of PML, the true at-risk MS population of JC virus antinody positive patients will include patients who will be placed on Tysabri despite the risk.

So, the JC virus antinody test will increase the Tysabri market share.

Screening out? No, screening in.

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org

The two Fs

2010-01-24T20:06:00.003-05:00

Better late than never.

Novartis's press release may have been a month after filing the NDA for Fingolimod with the FDA, but it was before something else:

With all the excitement surrounding the imminent Fampridine-SR or Ampyra (Acorda) PDUFA on January 22nd, 2010, Novartis may have used the quiet before the storm of Ampyra to excite analysts and investors about its own big (no, HUGE) news.

Or, maybe it was the JPMorgan Healthcare Conference and the NEJM.

- Dr. Daniel Kantor, MD BSE
Medical Director
Neurologique

info@neurologique.org
www.neurologique.org