Update Provided on CCSVI Research Progress

The National Multiple Sclerosis Society provides a progress report on the seven research projects being conducted on various aspects of Chronic Cerebrospinal Venous Insufficiency (CCSVI) with $2.4 million society funding.  This is like mid-term grades.  It is good to know how you are doing, but better to know that there is still plenty of time to get down to business before the year (or project) is over. 

(Yes, the music students have all been bemoaning the dreaded mid-term deadline of tests and grades at school.  That's why the phrase is on my mind.)

These seven research projects do not represent the ONLY research being conducted into CCSVI in the United States or Canada.  For information regarding additional research studies, including treatment trials, visit the CCSVI Alliance 'Clinical Trials in the US' webpage.  CCSVI Alliance is a non-profit organization which "promotes education and research about CCSVI and its relationship to Multiple Sclerosis (MS) by providing objective information to the MS community, supporting medical investigations of CCSVI, and fostering collaboration among patients, advocates, and professionals."

In addition to the press release/progress report reprinted below, CCSVI Alliance patient advisory board member and MS blogger we know as the Wheelchair Kamikaze, Marc Stecker was heard on NPR's Morning Edition show this morning - "Doctor Challenges Cause of MS and Treatment."


Research Teams Report Progress from First Six Months of 2-Year Projects Focusing on CCSVI and MS 

National MS Society, January 31, 2011 - Six-month progress reports from seven multi-disciplinary teams investigating CCSVI (chronic cerebrospinal venous insufficiency) in MS indicate that they have established rigorous protocols, are successfully recruiting participants, and are on-track to evaluate and deliver important data when the two-year projects are completed. All seven studies are two years in length but will be closely monitored while in progress in order to expedite clinical trials should the data show it is warranted. The studies were launched on July 1, 2010 with a more than $ 2.4 million commitment from the MS Society of Canada [$700,000] and the National MS Society (USA).

Most of the teams have received approval to begin their studies from the required Institutional Review Boards in the U.S. or the Research Ethics Board in Canada, a required first step established by regulatory authorities to protect human subjects involved in research projects. (Read more about steps involved in conducting clinical research.)

Already more than 200 people have undergone scanning with various imaging technologies being used by the studies, including the Doppler ultrasound technology originally used by Dr. Paolo Zamboni and his collaborators, as well as magnetic resonance studies of the veins (MR venography), catheter venography, MRI scans of the brain, and clinical measures.

Owing to the significant interest in the MS community about CCSVI, we are providing 6-month updates rather than the more standard 12-month reporting cycle. Because the studies employ rigorous blinding and controls designed to attain objective and comprehensive data, the full results of the ongoing research will be available only after significantly more scans have been completed and evaluated. They will collectively involve more than 1300 people representing a spectrum of MS types, severities and durations, as well as individuals with other disease types and healthy controls.

“We are pleased with the progress reported by the research teams we have funded,” advised Dr. Tim Coetzee, chief research officer at the National MS Society, “and look forward to providing as quickly as possible the understanding and answers these projects reveal on the relationship between CCSVI and the MS disease process.”

Jon Temme, senior vice-president of research and programs for the MS Society of Canada concurs, “The grants were selected for having the greatest potential to quickly and comprehensively determine the significance of CCSVI in the MS disease process. It is very encouraging to see how effectively the work has advanced among all groups.”

Details: The funded investigators, which include an integration of both MS and vascular experts, report progress in establishing their teams, putting their protocols in place, recruiting participants and beginning their studies, as summarized below.

• Dr. Brenda Banwell, The Hospital for Sick Children, Toronto, Ontario: Her team received Research Ethics Board approval in the fall and has begun enrolling participants and studying vein abnormalities in children and teenagers who have MS, and healthy controls of the same age, using non-invasive MRI measures of vein anatomy and novel measures of venous flow, as well as ultrasound. The team’s ultrasound experts have received training in Dr. Zamboni’s original techniques. Read details of Dr. Banwell’s plan.

• Dr. Fiona Costello, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta: Her team received Research Ethics Board approval in the fall to begin recruiting a cross-section of people with MS compared to other neurological diseases and healthy volunteers. They also recruited two ultrasonography experts who have begun ultrasound scanning as originally used by Dr. Zamboni. Dr. Costello’s team slowed recruitment briefly to upgrade to a new 3T MRI machine (twice as strong as standard clinical MRI) that will be used to perform MR venography scans to compare against the ultrasound tests. Read details of Dr. Costello's plans.

• Dr. Aaron Field, University of Wisconsin School of Medicine and Public Health, Madison: His team will be using MR venography and ultrasound techniques originally used by Dr. Zamboni to investigate CCSVI in people with early and later MS, controls with other conditions and healthy volunteers. A study coordinator is developing a recruitment list and an ultrasound expert has been hired and is slated to receive training in the Zamboni techniques. Dr. Field has been negotiating with the Institutional Review Board on issues related to study details and informed consent, and hopes to have these issues resolved to obtain IRB approval in the coming weeks so that scanning can begin. Read details of Dr. Field’s plans.

• Dr. Robert Fox, Cleveland Clinic, Cleveland: His team has received Institutional Review Board approval for using MR venography, ultrasound, MRI and clinical measures in people with MS or who are at risk for MS (CIS) and comparison groups, and recruitment is ongoing. Two ultrasound researchers underwent training in the technique originally used by Dr. Zamboni, and the team has obtained a new ultrasound machine previously used in other CCSVI studies. The ultrasound team found several aspects of the published methodology ambiguous, and they have standardized the protocol and analysis to achieve consistent results. To share ideas and solutions to these methodological challenges, Dr. Fox’s team has submitted an abstract for consideration for presentation at the American Academy of Neurology’s annual meeting in April. Read details of Dr. Fox’s plans.

• Dr. Carlos Torres, The Ottawa Hospital, University of Ottawa, Ontario: His team obtained Research Ethics Board approval in the winter and at once began the first phase of scanning using MR venography in people without MS, which will be used to compare with various scans in people with MS. Dr. Torres’s team has overcome several obstacles including negotiating with the Research Ethics Board over elements of the informed consent form used to explain the study’s procedures and potential outcomes to participants. Team members are slated to be trained using the ultrasound techniques originally used by Dr. Zamboni, and they are on track recruiting more participants for the study. Read details of Dr. Torres' plans.

• Dr. Anthony Traboulsee, UBC Hospital MS Clinic, UBC Faculty of Medicine and Dr. Katherine Knox, Saskatoon MS Clinic, University of Saskatchewan: The teams at both sites have received Research Ethics Board approval and have begun to recruit and scan participants. Their ultrasound technologists were trained by Dr. Zamboni, and they are also using catheter venography and MR venography to investigate the prevalence of CCSVI in people with MS and controls without MS. The radiologists on the teams of Drs. Traboulsee and Knox are meeting in February 2011 to ensure the consistency of their protocols across sites. The teams are on target for accrual of recruits and completion of the study. Read details of this team's plans.

• Dr. Jerry Wolinsky, University of Texas Health Science Center at Houston: His team applied in advance and obtained Institutional Review Board approval in the spring, and the team’s neurosonographer has received intensive training for intracranial and extracranial ultrasound scanning techniques. The team has already scanned a significant number of participants, which includes people with different types of MS, people with other conditions, and people with no known health problems. One obstacle Dr. Wolinsky’s team is addressing is the difficulty of recruiting non-MS control subjects who don’t have a personal interest in the purpose of the trial. The team is testing whether other imaging methods can confirm the ultrasound findings, while identifying the most reliable technique to screen for CCSVI. Read details of Dr. Wolinsky’s plans.

Going Forward: These seven teams were chosen by an international panel of experts that included specialists drawn from all key relevant disciplines including radiology, vascular surgery and neurology. The grants were selected for having the greatest potential to quickly and comprehensively determine the significance of CCSVI in the MS disease process.

The teams are now established and scanning procedures are underway at all but one of the study sites. Researchers have demonstrated a clear willingness to share technical advice and information so that projects can move forward as smoothly as possible. At this six-month milepost they are making significant progress on plans for these two-year studies.

The next update on the work of the seven grantees will be reported in six months.

What is the Romberg Test?

During each visit with the neurologist, I get to go through the steps of testing balance and gait.  The term gait refers to how you walk.  It’s fun getting to show off my abilities on any given day.  However, there is one particular neurological test which always gives me a chuckle.  It is the Romberg Test.

"What is the Romberg Test?"

The Romberg Test is a neurological test which detects poor balance and defects in proprioception.  The test involves standing with your feet together and closing your eyes.  The doctor will observe how you are able to maintain your balance and an upright posture.  The doctor may even push you slightly to see whether you are able to compensate and maintain an upright posture.

The very first time I underwent this testing, I thought that my neurologist had shoved me in the middle of the back.  He quickly told me to open my eyes.  My mother, who had come with me to the visit, told me later that he had caught me as I was quickly falling backwards.  I had no idea.  I had demonstrated a positive Romberg sign.

During the past couple of years, I don’t even need to close my eyes when I’m standing with my feet together before I begin to sway and wobble.  I can’t feel my feet which makes feeling their positioning more difficult.  As a result, I hardly ever stand with my feet together and I definitely don’t close my eyes in the shower.  My physical therapist even has a nifty testing device which can map the amount of swaying I do under different circumstances.


Read this post in its entirety:

MS Signs vs. Symptoms: What is the Romberg Test?

Removing the Synovium in an Inflammed RA Joint

In the previous post, we discussed different types of surgeries which are used in patients with rheumatoid arthritis.  This week I’d like to talk more about surgeries involving soft-tissue, specifically synovectomy, tendon repair, and carpal tunnel release.

What is a Synovectomy?

The synonium is a membrane surrounded a joint, usually only one or two cell layers thick, which produces synovial fluid to help lubricate the joint.  In rheumatoid arthritis, the synovium becomes inflamed and may grow excessively, producing too much synovial fluid containing an enzyme that can eat away at the cartilage on the joint surface.  Disease-modifying anti-rheumatic drugs (DMARDs) are used to control the abnormal growth of synovium.

If DMARDs do not work, a patient’s rheumatologist may suggest steroid injections into a joint or a needle aspiration of excess synovial fluid.  If these strategies do not work, then the patient may be referred to an orthopedic surgeon to discuss the removal of the synovium.  This surgery is called a synovectomy and can be done as an open surgical procedure or through arthroscopic surgery.

Synovectomies are performed are knees, elbows, wrists, finger joints, and hips.  The surgery typically produces better results when the patient’s cartilage has not been eroded, thus it is recommended for patients who are in earlier stages of their disease.  Note that over time the synovium may grow back and require repeat surgery.


Read this post in its entirety:


Soft-Tissue Surgery in Rheumatoid Arthritis: Synovectomy, Tendon Repair, Carpal Tunnel Release

"I want to play by my lonely."

That's what my youngest nephew said to me a few days after Christmas.  The house had been full of activity and "J" had kept up with his two older brothers in all of the festivities and rough and tumbles.  I had managed to keep up with each of them (mostly).

"J" gave up his big boy bed so that Aunt Lisa could stay over during the week.  Each morning I had awakened before the boys, except for the last day.

"It's morning time!!" said J as I lingered in bed without an alarm going off.  He was my alarm clock that morning, however I played 'dead' to get a few more winks.

When I finally did get up (at around the late hour of 9am, lol) and went to take a shower, J took back his bedroom to play.  I came back after the shower to gather a few things to take downstairs.

"I want to play by my lonely," says J. 

Wow, a little boy of my own heart.  Of course he has two older brothers and probably cherishes the few moments he might get to play "by his lonely" without interference or competition.

I love my alone time.  I need my alone time.  If I don't get some every week, I'm a cranky mess.  (In other words, watch out!!)

Solitude is a beautiful thing when you know that you will never truly be lonely.  Having the security to allow yourself to enjoy loneliness, when it really is just the opposite, has got to be one of life's little blessings.

So I hope that you are able to enjoy playing "by your lonely" too.

What is the Hoffmann Reflex?

During one of my early visits with the neurologist, he conducted a test of which I didn’t understand the significance.  He’d already asked me to squeeze his fingers in my fists - “oh come on, squeeze harder” - and now he is ‘thumping’ my fingers.

“What is the neurologist looking for when he is tapping my finger?”

The neurologist is looking to see if there is a finger flexor response.  The finger flexor response is demonstrated by a sudden flexing of the thumb and/or index finger.  There are two ways to cause this response: 
     * The doctor snaps or flicks the nail of the middle or 4th finger.  A positive finger flexor response elicited in this manner is known as the Hoffmann reflex or sign.
     * The doctor holds the middle finger while partially flexing it between his/her finger and thumb, then taps or flicks the underside of that finger.  A positive finger flexor response elicited in this manner is known as the Trömner sign.

To view two videos of a positive Hoffmann sign, visit the website of the University of Washington Neurological Surgery Spine Center.

“What causes the thumb to flex?”

The finger flexor response (Hoffmann relex or Trömner sign) is somewhat similar to the Babinski sign in that it is suggestive of a lesion or impingement along the corticospinal track.


Read this post in its entirety:

MS Signs vs. Symptoms: What is the Hoffmann Reflex?

European Medicines Agency recommends Gilenya (fingolimod), but rejects Fampyra (fampridine) and Movectro (cladribine)

Today was a big day for news of new Multiple Sclerosis medications in Europe.

While online publications have been excited about the recommendation by the American Academy of Neurology that plasmapheresis (plasma exchange) can be used to treat MS relapses which do not respond to high-dose steroids (something which I was under the impression neurologists already had in their tool belt), the European Medicines Agency's or EMA Committee for Medicinal Products for Human Use (CMPH) has made decisions regarding the newer pills designed for use in MS treatment (both disease-modifying and symptomatic).

GILENYA/Novartis

The Committee adopted a positive opinion recommending the grant of marketing authority for Novartis' drug Gilenya (fingolimod).  Gilenya is a an oral (pill) disease-modifying drug which received FDA approval in September 2010.  Patients in the US have more recently been able to gain access to the drug.  In the summary of opinion, the Committee mentions that the benefits with Gilenya are its ability in reducing the number of relapses in patients with relapsing-remitting multiple sclerosis.

The most common side effects (seen in more than 1 patient in 10) are influenza viral infections, headache, diarrhoea, back pain, cough and elevated liver enzyme (known as ALT). Other common side effects (seen in between 1 and 10 patients in 100) that could be or could become serious are herpes virus infection (shingles or herpes zoster), lymphopenia, leucopenia (reduced white blood cells), bradycardia (slow heartbeat), atrioventricular block (irregular heart rhythm), bronchitis and gastroenteritis.

FAMPYRA/Biogen Idec

A negative opinion was delivered to Biogen Idec regarding Fampyra (fampridine) which is marketed in the United States as Ampyra (dalfampridine) by Acorda Therapeutics.  The Committee recommends that marketing authority should not be granted to Biogen for Fampyra, which is intended to be used to improve the walking ability of adult patients with multiple sclerosis.  The Committee was not convinced that Fampyra’s small effect on the walking speed was a meaningful benefit for patients. The effect on speed could not be linked to meaningful improvements such as better coordination, balance or stamina or increased range of action.

The Committee was of the view that the medicine’s uncertain benefits did not outweigh its side effects which included pain, dizziness, paraesthesia (unusual sensations like pins and needles) and problems with balance, as well as symptoms similar to those of multiple sclerosis that could impair the patient’s ability to walk. The Committee also noted the lack of adequate long-term data on the medicine’s benefits and safety as well as data on some groups of patients, such as the elderly and patients with epilepsy or heart problems.

As of September 30, 2010, Ampyra has been prescribed to 31,000 patients with MS in the US since it's FDA approval on January 22, 2010 and commercial launch in March 1, 2010.  Biogen Idec plans to appeal the Committee's decision.  Biogen owns the rights to market Fampyra/Ampyra outside of the United States.


MOVECTRO/Serono

Merck/Serono received greater bad news in that the Committee confirmed its previous negative opinion and adopted a final negative opinion regarding Movectro (cladribine).  Serono shall not be granted the authority to market Movectro (cladribine) as a disease-modifying therapy in relapsing remitting multiple sclerosis.

Previously, Merck/Serono had presented the results of one main study that compared Movectro with placebo (a dummy treatment) in 1,326 patients with relapsing-remitting MS.  The Committee was concerned that an increased number of patients with cancer were observed patients treated with Movectro compared to the control group in the clinical trial. The Committee also noted that the benefits and the most appropriate dosage for treatment had not been fully established in patients who were expected to use the medicine. Therefore, the Committee is of the opinion that the benefits of Movectro do not outweigh its risks.

According to Reuters, Merck said it remained committed to completing ongoing clinical trials with cladribine tablets. It can re-apply for approval of the tablets in 2012 at the earliest, when trial results are due.

I personally have no opinion regarding any of these medications for my own use.  I am highly unlikely to use any of them due to my history of methotrexate use (for fingolimod and cladribine) and due to insurance coverage for Ampyra (dalfampridine).

However, I am disappointed that these treatment options will not be made available to patients for whom they may benefit.  I know that many MS patients in Europe have been eager to try Fampyra as we have received many questions at HealthCentral asking when it will be made available.  Those patients will have to wait a while longer now.

More information about the Committee's decisions is available in separate question-and-answer documents on the Agency's website.  PDF's can be found in the right-hand sidebar of the website.

UPDATE: A good compilation of information and links to relevant press releases can be found at FiercePharma.  Read MS drugs get yeas, nays and price increases.

UPDATE #2: Biogen announces updated Tysabri/PML statistics.  The total number of cases is now at 85 patients with the addition of 6 new cases reported in January 2011.  The number of deaths holds at 16 patients.  Of the total PML cases, 36 were in the U.S., 44 were in the European Union and five in other areas.

Disclosure: The website for which I provide video and written blogs, HowIFightMS.com, is sponsored by EMD Serono.