Wednesday, 31 August 2011

Research: my lesion load has just gone up

Epub ahead of printde Graaf et al. Lesion detection at seven Tesla in multiple sclerosis using magnetisation prepared 3D-FLAIR and 3D-DIR. Eur Radiol. 2011 Aug 27. 

MRI scanners can be classified on the strength of their magnets. A typical diagnostic scanner is 1.5 Tesla with newer models being 3 Tesla. This study examined the feasibility and value of a 7 Tesla scanner in MS.  

Methods: High-resolution 3D images were obtained using a 7 Tesla scanner and compared with with conventional imaging in 10 MS'ers and 5 healthy controls. 

Results
  1. MR imaging at 7 T was safe. 
  2. Cortical and total lesion counts were 97/592 on the 7 Tesla scanner compared with 84/384 on the 3 Tesla scanner; a 15% and 54% increase in lesion number. respectively. 
  3. 205 juxta-cortical lesions were seen with 7 Tesla 3D imagingaing compared to 125 with 2D 3 Tesla imaging; a 64% increase. 
  4. Higher numbers of lesions were also found in the deep white matter using the 7 Tesla scanner:  196 vs. 155; a 26% increase. 
Conclusions: 7 Tesla MRI is safe and is more sensitive in detecting MS lesions compared to current technology. This is particularly important in detecting gray matter or cortical lesions.

"This confirms pathological studies that show that for every lesions seen with the naked eye there are many more lesions seen under the microscope; what is important about this study is that 7 Tesla scanners will allow us to focus on cortical pathology, the substrate that drives cognitive impairment in MS. Let's hope the newer technology will allow us to visualise B cell follicles on the surface of the brain. If we can do this then we can test the effectiveness of therapies that target such lesions."

Comment re laquinimod

Mr Giovannoni,

I don´t think it serious to refer to an analyst/equity researcher at an investment bank regarding laquinimods be or not to be. No offence, but should know that. Also, I think you are dismissing or press down the prospects of laquinimod wrongly.

NOT A PRETTY MS MARKET - DOG EAT DOG BEHAVIOUR Those investment bankers/analyst have loyalty to different MS-company´s (read: clients). For instance some investment bankers do big corporate and financial business with Novartis, Biogen or Merck and other promoters of specific MS-agents and have their loyalties to them and no other.

So their we have an explanation why this analyst and many others are NOT objective: they can simply discredit a competitors MS agent because the investment banker works for another company with another MS-agent. The investment banker business is a dirty business - it is a Dog Eat Dog business, as well as the Big Pharma business.

I know how the equity research and investment banker business works, because I worked 12 years in the city as an /Analyst Equity Researcher at an mayor investment bank That was before I caught the MS disease - I was diagnosed 8 years ago.

So, we know that the investment banker business is full of loyalties and ties to specific big pharma companys with MS-agents in their portfolio. So Mr Giovanni, referring to this analyst and investment banker Ori Hershkovitz is not so vice ... Belief me I have investment banker experience, and it is NOT a clean world … far from it. With all the ties and loyalties to different clients/companys.

An analyst working at an investment banker with Corporate finance departments, do not bite the hand that feeds them = their clients. That is just the way it works at an investment bank. Period!

And you should know, primary based on what I elaborated above, that I don´t use an analyst/Equity researcher at an investment bank as my MS-clinicians or adviser regarding the MS-disease and its course ...(!)

RELAPSES VERSUS DISABLITY AND LAQUINIMOD Also, I as a patient rather take a relaps once every third year or so, if I can stop the disablity progress. That is the main aim for me as a patient – not the relapses itself!

Also, laquinimod seems to have unique properties regarding the reduction of Brain Atrophy or tissue loss.

Also, the recently reported BRAVO study with laquinimod was imbalanced at baseline. The active laquinimod arm was in worse shape than the placebo arm, according to relevant MRI active disease markers at baseline.

At baseline, the percent of patients with gadolinium-enhanced lesions and the volume of T2 lesions at baseline were much lover in the placebo arm than than in laquinimod arm. Or another way to tell it: At baseline, the percent of patients with gadolinium-enhanced lesions and the volume of T2 lesions at baseline were much higher in the laquinimod arm than in placebo arm …

These metrics are, as you surely know, known to be important parameters of MS disease activity. It goes without saying, that laquinimod was behind placebo already at the start of the study, at baseline. I would be like having a hundred meters fast running at the Olympics, and let one person start 20 meters ahead of the other runners … Not fair play, to say the least …

And since you Mr. Giovanni, are so focused on MRI markers, you should acknowledge the reason for the pre-specified adjustment regarding the imbalance between laquinimod and placebo.

Also, if laquinimod would have had to positive above mentioned MRI markers at baseline for the MS-disease versus placebo, I would think it would be fair to say, that it would also be logic to adjust for such a imbalance ...(!) And if you acknowledge that, then logically you must see that it is intellectually honest and logic when the imbalance was the other way around, as with the Bravo study …

So all in all, of course it is logical to use the predefined adjustment, mentioned in the study protocol for the Bravo study, and of course, examined and granted by the FDA/EMA authorities.

Regardless how you angle things, at the end of the day it is to slow the progression of the disease which is priority number one for me as a patient: => stop/slow the disability.

Keep me as I am today as long as possible is my Top priority as a patient with MS. So slowing disablity is my prio number 1 and doing it in a safe manner.

Also, laquinimod has shown in human very promising elevation of BDNF, Brain-derived neurotrophic factor, treatment with laquinimod results in a significant increase in brain derived neurotrophic factor, a key protein responsible for the maintenance of mature neurons - up to 11 times elevation of BDNF in patients participating in phase IIb study with laquinimod. See references down below.

BRAIN ATROPHY – ITS IMPORTANCE FOR ME AS A MS PATIENT But the thing which makes me thrilled about laquinimod is that I think that we as patients has great hopes for laquinimod prospects for beeing an oral, safe agent with great NEUROPROTECTIVE properties.

Neuroprotective properties would explain the high score on disability reduction, measured accordingly to the established EDSS scale.

Also one must ask oneself this question:

At the severe MS-disease stage, SPMS, you don´t have any MRI markers regarding lesion, no relapses ... just a downhill degenerative destruction of the brain ... loss of brain volume or brain tissue loss.

And I belief I would make a real bet on, that laquinimod will be successful in this cruel segment of the MS-disease, SPMS, because of its neuroprotective properties.

So this focus on relapses is, according to me, as a 8 years diagnosed ms-patient, more or less a DEAD END. We must look after MS-agents with direct neuroprotective properties, which laquinimod definitely seems to have.

We must not be naive, the big pharma industry will never accept a competitor with a new agent with unique features. They will use the all the power they have to play down its importance. Not for the best of the patients, but for the best of their shareholders interest. MS is right now a 10 billion US dollar market ... So they have all reasons to be greedy.

So the Big Pharma business will play down this new agent, using spin-doctors, lobbyists etc to discredit a new unique agent. That is the way it works. The patient is just a revenue soldier for the industry - we as patients must remember that!!

A new agent in MS or another devastating disease, and its prospects, its not mainly to do with its power to treat the disease in a safe manner, it is to do with marketing and lobbyist network within the big Pharma industry against doctors and other opinion leaders.

MS - A DEGENERATIVE BRAIN DISEASE

Nevertheless, I personally view the MS-disease as a pure degenerative brain disease, where the reduction of relapses will not have any impact on this degenerative brain disease. It can´t have by definition.

I am not alone with that view, several key MS opinion leaders have also aired that view in science artichles and at conferences. So I am not alone ...

So having said the above, I have great faiths in laquinimods ability to reduce brain tissue loss or brain volume, formally called Brain Atrophy.

No matter what MS-clinicians would say to me, to remain the brain volume intact, with exception for normal brain Atrophy, which is related to ageing, I prefer to go on a future oral MS-agent like laquinimod, that will halting or slow the Brain Atrophy on me as an MS-patient, and thereby slowing the progression of this degenerative brain disease.

To be noted Laquinimod had very good scores on brain atrophy: In the Allegro study, laquinimod reached 33% reduction of brain Atrophy vs placebo. In the BRAVO study, laquinimod reached 27.5%, and this figure was statistically significant both before and after adjustment for imbalances at baseline between laquinimod and placebo.

Apart from the immunosupressive agent Gilenya, which in the FREEDOM study showed 30% recution in Brain Atrophy (only one study), the immunmodulator, non-immunsupressive agent laquinimod, is the only agent which has shown profound results in halting Brain Atrophy. Laquinimod has showned it in two pivotal studies, Allegro and Bravo. Gilenya only in the Freedom study.

But Gilenya has also safety problems, so it will not be my first choice. Laquinimod has none safety problem and a very benign profile, so it will therefore be my first choice, when if it will be approved by the drug authorities, FDA (US) and EMA (EU).

MY WAY IN FUTURE MS TREATMENTS …

If you add the score on disability for laquinimod, ut reached 36% reduction in the Allegro study. In the Bravo study it reached 33.5%. As mentioned earlier above, the Bravo study was adjusted for umbalance at baseline.

So for me, who has been on injections since diagnosis, Avonex, and now are offered to use the immunosupressive agent Gilenya, I will say no to gilenya and other agents and wait for the promising agent laquinimod to be approved and to be available on the market late 2012.

The story about a successful MS-agents for me as a patient, is to stop this degenerative brain disease and doing so in a safely manner.

I will be on treatment for the rest of my life, so safety is extremely important for me. And I think therefore laquinimod will be an unique new option of treatment for MS patients, who wants to fight the degenerative side of this disease.

Hope this comment not will be deleted by you Mr Giovanni, because my view on several issues regarding MS is not in line with your views. But then again, if everyone would always agree with each other, then we will have less development or progress. And we want progress, don´t we … :-)

All the best

PGC now living in Stockholm. Before my diagnosis in London.

Disclaimer: I have no ties or loyalties to the industry. I am only loyal to myself as an MS-patient.

REFERENCES:

BDNF and laquinimod: W. Brück ”Journal of the Neurological Sciences” JNS - 11705; No of Pages 7

BRAVO study: Audio webcast: http://phx.corporate-ir.net/phoenix.zhtml?p=irol-eventDetails&c=73925&eventID=4168607







Research: clinical scales in progressive MS

Epub ahead of printBosma et al. Clinical scales in progressive MS: predicting long-term disability. Mult Scler. 2011 Aug 25.

Background: The aim of this study was to determine which short-term changes on clinical scales including the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg test (9HPT) and Guy's Neurological Disability Scale (GNDS) are most predictive of long-term outcome of disability as rated by the EDSS in progressive multiple sclerosis (MS). 

"This is a subject close to my heart; we don't really have scales that measure disability progression with enough accuracy to use in progressive clinical trials of a practical duration to make phase 2 or exploratory trials feasible."

Methods: From a longitudinal database, all progressive patients, both primary (PP) and secondary (SP), were selected on the basis of at least two complete examinations being available within a time interval of 1-2 years (short-term change). All patients who fulfilled the selection criteria were invited for a third visit after an interval of at least 3 years (long-term outcome). 

Results: 181 patients fulfilled the selection criteria. Early change on EDSS and T25FW were the best predictors of long-term EDSS. 

Early EDSS change was a slightly stronger single predictor compared with early T25FW change. 

Adding early T25FW change to early EDSS change in a 'combined predictor' model improved prediction.

Conclusion: Both early change on EDSS and T25FW predict long-term EDSS with comparable strength. Therefore the investigators recommend the use of early T25FW examinations in future clinical trials in progressive MS.

"By definition this study excludes MS'ers who are already in a wheelchair; this is not good for their psyche. Is my disease too advanced to be included in clinical trials? Not necessarily if you are prepared to volunteer for the trial design with repeated lumbar punctures."

"The other problem with recommending these scales is that MS'ers are unable to measure their own EDSS; you have to be examined by a trained neurologist to be given an EDSS score. A typical EDSS takes about 20 minutes to perform and sometimes longer. We are trying to address this by evaluating a patient related outcome measure that gives you an estimated EDSS. If this works it will empower MS'ers with data that can then be used to calculate their disease courses using tables, etc."

Tuesday, 30 August 2011

Research: antibody production and cortical lesions

Epub ahead of printCalabrese et al. The association of intrathecal immunoglobulin synthesis and cortical lesions predicts disease activity in clinically isolated syndrome and early relapsing-remitting multiple sclerosis. Mult Scler. 2011 Aug 25.

Background: The production of immunoglobulin by B cells and plasma cells within the brain and spical cord is a major biological feature of MS. Studies have suggested a primary role of the B cell and immunoglobulin response in causing irreversible brain damage. 

Objective: To evaluate whether, in the early phases of MS, immunoglobulin synthesis within the nervous system correlates with the presence of cortical lesions and if their association could predict the clinical course of MS. 

Methods: 86 patients presenting with symptoms and signs suggestive of MS underwent a diagnostic work-up that included MRI and cerebrospinal fluid examination. 

Results: MS'ers with clinically isolated syndromes (CIS) having cortical lesions and nervous system synthesis of immunoglobulin had a 3.4x greater risk of conversion to MS; whereas CIS patients without cortical lesions and immunoglobulin had the lowest risk of conversion to MS (0.1X). 

Conclusion: The investigators observed that the association of nervous system immunoglobulin synthesis and cortical lesions was highly predictive of an earlier CIS conversion to MS as well as of a higher disease activity.

"This study supports pathological studies that B cell activity within the nervous system correlates with cortical disease or superficial gray matter pathology. Another reason to target B cells to try and prevent progressive gray matter pathology and hopefully prevent or delay the acquisition of cognitive dysfunction in MS." 

Previous, related, posts of interest:

16 Aug 2011
Background: Inflammation of the coverings layers of the brain and spinal cord, in the form of lymph node like structures, has been suggested to play an important role in the development of grey matter pathology in MS. ...
07 Jun 2011
Grey Matter (5) & B Cells: Baminercept in SPMS. The immune system forms and maintains the ectopic B-cell follicles in the brain & spinal cord by producing a cocktail of immune messengers called cytokines. One of these ...
08 Jun 2011
This study is also targeting the B cell within the central nervous system (CNS) in the hope of disrupting the ectopic B cell follicles and thereby trying to stop progressive cortical or grey matter disease progression. Rituximab is a ...
06 Jun 2011
Grey matter (4) - Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Magliozzi et al. Brain. 2007 Apr;130(Pt 4):1089-104. In MS the ...
05 Jun 2011
Methods: In this study specialist MS pathologists analysed global brain involvement in MS focusing on the normal-appearing white matter (NAWM) and the cortex (grey matter). Findings: (1) New and active focal inflammatory ...
05 Jun 2011
"This and other studies show that grey matter involvement is there from the start. I use this as argument for aggressive early treatment. It is better to protect the brain, particularly the grey matter, than to compensate for the ...
05 Jun 2011
In this study the investigators were able to relate cortical or grey matter lesions and tissue loss or atrophy to cognitive impairment in patients with RRMS. "This study adds to the growing body of evidence that grey matter ...
02 Jun 2011
"Grey matter pathology is an increasing important area of MS research and an important target for both DMTs and symptomatic therapies. I am sure that grey matter pathology is responsible for the cognitive issues PwMS ...

Monday, 29 August 2011

Digesting Science

There seems to be some misunderstandings in relation to the "Digesting Science" series of post. I would strongly recommend that you look at Alison Thomson's site, which explains her work and the motivation behind it. Her work was not done for the blog. From our perspective it has been great collaborating with her; not only is it interesting and engaging, but a fresh look at the way we communicate with the public. The fact that it is generating conversation and debate means it is achieving something we have difficulty doing with our daily posts. Any ideas and help in communicating science and MS to the wider public would be much appreciated.

Somehow Related

Other topics Alison has covered that are worth looking at are "The Anatomy of Multiple Sclerosis" and her degree show work on the "The Chronic Facility"

Sunday, 28 August 2011

Reporting about the blog

Hello Prof G,

I follow your blog, the articles about CCSVI treatment seem to appear ever so often. I think enough has been said this form of treatment for the time being. The publication of the NICE document seems to be a good opportunuty to put the whole issue to bed for a while.

Another thing, I think it would be interesting to see a name against a reply that is made to an entry or piece of news that you publish. Would it worth making it perfectly clear how to ensure this.

Lastly I would undergo 3 lumber punctures if there is a chance that the progress of MS can be stopped even only for a few months.

Patrick

Disease course of PPMS

In response to the previous comment from the MS'ers with PPMS, who needed a walking aid within 4years of disease onset and malignant MS. 

The following is the survival curve in relation to PPMS. As you can see only ~8% of MS'ers with PPMS need a walking stick within 4 years (red); this is twice the progression rate of the average, i.e. 50% require a walking aid within 8 years (blue).


Source: Cottrell et al. The natural history of multiple sclerosis: a geographically based study. 5. The clinical features and natural history of primary progressive multiple sclerosis. Brain. 1999 Apr;122 ( Pt 4):625-39.

This study reports the natural history of 216 MS'ers with PPMS defined by at least 1 year of attack-free progression at onset. This represents 19.8% of a largely population-based patient cohort having a average follow-up of 23 years.

This subgroup of PP-multiple sclerosis patients had a average age of onset of 38.5 years, with females predominating by a ratio of 1.3:1.0. 

Disease course:
  1. The rate of deterioration from disease onset was substantially more rapid than for RRMS, with a median time to EDSS 6 (cane) and EDSS 8 (restricted mobility) of 8 and 18 years, respectively
  • EDSS 6.0 = Intermittent or unilateral constant assistance (cane, crutch or brace) required to walk 100 meters with or without resting.
  • EDSS 8.0 = Essentially restricted to bed, chair, or wheelchair, but may be out of bed much of day; retains self care functions, generally effective use of arms.
Examination of the early disease course revealed two groups with adverse outcomes
  1. A shorter time to reach EDSS 3 (moderate disability, though fully ambulatory) from onset adversely influenced time to EDSS 8. 
  2. Involvement of three or more neurological systems at onset resulted in a median time to EDSS 10 (death) of 13.5 years in contrast to PPMS patients with one system involved at onset where median time to death from MS was 33.2 years. 
  3. Age, gender and type of neurological system involved at onset appeared to have little influence on prognosis. 
Life expectancy:
  1. Cause of death and familial history profile were similar in PPMS and relapse-onset MS. 
PPMS vs. SPMS:
  1. From clinical onset, rate of progression was faster in the PPMS than in the SPMS. 
  2. However, when the rates of progression from onset of the progressive phase were compared, SPMS had a more rapid progressive phase. 
Relapses:
  1. A substantial minority (28%) of the PPMS'ers had a distinct relapse even decades after onset of progressive deterioration. 
"Apologies, if some of you find these figures grim reading. Unfortunately, as you know, MS is a bad disease, particularly PPMS, and these figures make that very clear. This why we are spending a large amount of time working on progressive disease; how to stop or slow it down or in the case of relapse-onset MS prevent it from starting in the first place."

Additional reading: EDSS

Saturday, 27 August 2011

CCSVI - NICE Consultation Document


Provisional recommendations

1.1 Current evidence on the efficacy and safety of percutaneous venoplasty for chronic cerebrospinal venous insufficiency (CCSVI) in multiple sclerosis (MS) is inadequate in quality and quantity. Therefore, this procedure should only be used in the context of research.
1.2 NICE encourages further research on venoplasty for CCSVI in MS. Clinical trials should be controlled, ideally comparing venoplasty against sham. Technical success should be clearly defined and should include measurement of pressure gradients across treated vein segments before and after venoplasty. Outcomes should include clinical and quality of life measures.

Espresso clinical tutorial (1): Fulminant MS or Marburg's variant

In response to a comment yesterday:

Marburg's variant of MS, which is also known as fulminant MS, is quite rare.

It was initially described by the Austrian neurologist Otto Marburg

The term fulminant is a carry-over from the pre disease-modifying therapy era. Most cases presenting with Marburg's variant of MS who treated promptly with appropriate therapies, respond to treatment, and can do very well. 

In the modern-era Marburg's variant of MS is rarely fatal and responds to the more aggressive therapies such as, mitoxantrone, cyclophosphamide and alemtuzumab. These are usually given in combination with high dose steroids. In some MS centres they also use plasma exchange. 

I have personal experience of using natalizumab in 37-year old male presenting with Marburg's variant of MS; apart from some persistent weakness in his right leg and some unsteadiness of gait he is well and fully independent 3 years after starting natalizumab. 

"This is no humbug! For the cynics out there does this not represent a major advance in the treatment of MS? In the pre-DMT era he would not be alive."

Marburg's variant of MS is diagnosed using MRI. It typically occurs in the form of a single large demyelinating lesion that can be indistinguishable from a brain tumor (see figure below; taken from radiopaedia). You may see the term tumefactive (tumour-like) used to describe these lesions. Such lesions are often biopsied to exclude other diagnoses in particular brain tumours. It is important to stress that the pathology of Marburg-variant MS is indistinguishable from 'classic MS'; i.e. Marburg MS is MS. 


Marburg's variant of MS, should also not be confused with neuromyelitis optica, Balo's concentric sclerosis and Schilder's disease. These are distinct clinico-pathological or disease entities, that overlap with MS, and can also present with a malignant or fulminant course.

"I will prepare separate posts on these diseases. I suggest you register yourself as a member or subscribe to email updates not to miss these posts."

The term malignant MS also needs clarification in this context; we us the term malignant MS to describe rapid progression of disease with substantial disability within 5 years of disease onset (typically needing a walking aid). Marburg's variant may be classified as being malignant if it results in significant and sustained disability within 5 years. Patients with Marburg's variant of MS may respond to treatment and recover from their initial presentation to then do well over the next 5 years. It is important to note that most cases of malignant MS will not be due to Marburg's variant of MS. 

"I hope this post clarifies your questions regarding fulminant MS." 

Team G & 5min Meal..Dr.A

Dr. A talks about Nerve Impulses

Based on these Unhelpful sorts of Posts....
You probably will Enjoy GQ more than G Blog.
Video Removed (MD)






Friday, 26 August 2011

Fulminant MS

Epub ahead of printRohani & Ghourchian. Fulminant multiple sclerosis (MS). Neurol Sci. 2011 Aug 24.

Fulminant MS is the most malignant form of MS which usually leads to death with in a few weeks.

Fulminant MS  can be accompanied by optic neuritis (ON); however a long interval between ON and the fulminant phase has not been reported. 

This is a case report of 30-year-old woman with a history of ON that occurred 1 year ago; who tragically developed rapid deterioration in her MS. She went into to a unresponsive or vegetative state followed by a seizure. All investigations were compatible with a diagnosis of MS. 

"We don't usually present case reports on this blog, however, this case illustrates that MS can be very severe."

Thursday, 25 August 2011

Team G-Who Are they?

Anonymous comments or Not Anonymous comments I hear you say.
"Who is the Mouse Doctor? you ask again"

He's just part of Team G (see some of them below). They are just a bunch of Guys and Gals doing their bit to do something positive about MS............Oh and wanting World Peace!

Do they hide....Well not really the information on their identities is to be found on the blog. So Home Work, Home Work, Home Work.

Is it a co-incidence that Dr Ruth (Not Westheimer) is next to Dr VD (that's Vitamin D not VD)

P.S. If you are a Nutter, Anti-Vivisectionist (non-nutter AV's are OK......we can have a conversation), then Don't Do Your Homework cos then I'ld rather be anonymous. More serious stuff to follow. Have a good weekend!


Your cognitive state impacts on your memory complaints

Demers et al. Impact of the Cognitive Status on the Memory Complaints in MS Patients. Can J Neurol Sci. 2011 Sep;38(5):728-33.

Objective: Despite the evidence of cognitive deficits in MS'ers, evaluation of their cognitive integrity is often limited to the use of clinical interviews and questionnaires. However, the consensus in the literature is that MS'ers under- or overestimate their deficits and repercussions. The objective of this study was to clarify why some patients overestimate while others underestimate their memory deficits.

Method: Fifty-four participants (30 MS, 24 controls) completed a prospective and retrospective memory questionnaire  and were tested on a battery of neuropsychological tests. Based on the test results, MS'ers were categorised as having either mild or moderate/severe cognitive deficits. 

Results: The moderate/severe MS group differed from the two other groups on an auditory verbal learning test but did not differ from the control group on the prospective and retrospective memory questionnaire. 

Conversely, the mild MS group did not differ from the control group on the auditory verbal learning test  but did report significantly more problems than this group on the prospective and retrospective memory questionnaire. 

Conclusion: The results explain the contradiction in the literature. It is the mild group who overestimates, maybe because they are overly concerned by their deficits, whereas the cognitive impairments of the moderate/severe group lead them to underestimate and may make their self-assessment unreliable.

"An interesting observation that may affect how we perceive and investigate cognitive problems in MS." 

"What do you think?"

Complications associated with the treatment of CCSVI

Burton et al. Complications in MS Patients after CCSVI Procedures Abroad (Calgary, AB). Can J Neurol Sci. 2011 Sep;38(5):741-6.

Background: The "chronic cerebrospinal venous insufficiency" or "CCSVI" hypothesis, namely that MS is caused by abnormalities in the azygous and internal jugular veins with subsequent alterations in venous hemodynamics in the central nervous system, has been a dominant topic in MS care in Canada over the past year.

Although there is no methodologically rigorous evidence to support this hypothesis presently, a considerable number of MS patients have undergone endovascular CCSVI procedures. Such procedures include angioplasty or stent placement in jugular and azygous veins. The safety and efficacy of these procedures is unknown, but not without risk. 

Methods: Chart and patient review of five patients with confirmed MS followed in Calgary were undertaken after patients came to medical attention by referral or admission secondary to complications believed to be associated with CCSVI procedures. 

Results: Complications upon investigation and review included internal jugular vein stent thrombosis, cerebral sinovenous thrombosis, stent migration, cranial nerve injury and injury associated with venous catheterization. 

Conclusions: As the debate about CCSVI and its relationship to MS continues, the complications and risks associated with venous stenting and angioplasty in jugular and azygous veins are becoming clearer. As increasing numbers of MS patients are seeking such procedures, these five cases represent the beginning of a wave of complications for which standardized care guidelines do not exist. Our experience and that of our colleagues will be used to develop guidelines and strategies to monitor and manage these patients as their numbers increase.

"I suspect these 5 cases, the Charing Cross case reported on this blog and the two deaths that have been widely publicised are only the tip of the iceberg." 

"Unless collected in a rigorous and prospective way complications and serous adverse events are always under reported."

Natalizumab PML Update - 150 cases worldwide

Natalizumab PML Incidence Estimates by Treatment Duration


 *Yousry TA, et al. N Engl J Med. 2006;354:924-933.

Observed clinical trial rate in patients who received a mean of 17.9 monthly doses of natalizumab. The post-marketing rate is calculated as the number of PML cases since reintroduction in patients that have had at least 1 dose of natalizumab.

Incidence estimates by treatment duration are calculated based on natalizumab exposure through July 31, 2011 and 150 confirmed cases as of August 4, 2011. The incidence for each time period is calculated as the number of PML cases divided by the number of patients exposed to natalizumab (e.g. for ≥24 infusions all PML cases diagnosed with exposure of 24 infusions or more divided by the total number of patients exposed to at least 24 infusions). 


As of August 4, 2011:

  • 29 patients have died (19%); most of the deaths have occurred within approximately 2 months after PML diagnosis
  • 121 patients are alive (81%) 
Approximate incidence of natalizumab-associated PML by 
prior immunosuppressive (IS) use and treatment duration**


**Based on natalizumab exposure data as of February 28, 2011; PML incidence data based on 102 confirmed PML cases as of March 4, 2011; prior IS data in overall natalizumab-treated patients based on proportion of patients with IS use prior to natalizumab therapy in TYGRIS study as of November 23, 2010; and prior IS data in PML patients as of March 4, 2011 (with 102 confirmed PML cases of which only 88 had known prior IS status available and had natalizumab exposure between 1 and 48 doses).

Source: Biogen Idec, data on file.

CoI: Multiple

Survey results of cognition vs. physical disability


"It is clear that this poll was quite divisive with some favouring cognition and others physical disability."


"The issue here is that early in MS when the accumulation of physical disability is too slow to be used in clinical trials we should seriously consider using a cognitive outcome. Let's hope the regulatory authorities agree."

New survey: genetic testing

DO YOU THINK MS'ERS SHOULD ENCOURAGE THEIR RELATIVES TO HAVE GENETIC SCREENING TESTS DONE TO SEE WHAT THEIR RISK OF DEVELOPING MS IS?

"Recent posts have highlighted genetic risk factors for developing MS. So we think this question is very relevant." 

"In addition, a new industry has sprung-up to provide these services independent of your usual healthcare providers. So this is a real-life issue that is accessible to you now."

"You may want to see the previous post on this topic from the 16th June 2011, when Ram in our group tested the services of 23andme himself." 

16 Jun 2011
Being a geneticist particularly interested in risk prediction, I signed up to a genetic test from 23andme (note we are not advising for anyone to do this). I received my results yesterday and the first thing I did was to ...

"If you are using email alerts or mobile blogger to follow this blog please log onto the web version to complete this survey."

Thank you.

Team G & 5 Minute Meal...KT

KT talks about how the the Eye and Multiple Sclerosis



If you can't see the video visit our website (using a real computer?)
Don't watch more now it'll spoil the fun!

Director: Alison Thomson, Cinematographer: Maja Zamojda,
Funded by UnLtd Awards

Wednesday, 24 August 2011

Genetics-Prof G....No Speak Ingrish!

The Hunt for the genetic links to Multiple Sclerosis is confusing. But in simple English, whilst Beanz meanz Heinz, Jeanz meanz who you are!

Your genetic code, which is found in essentially every cell in the body, defines who you are. Half of this code comes from your Mum and half from your Dad. This code is in your DNA and contains has about 30,000 genes and this is called the genome. This zip-like structure is unzipped to reveal the gene. The gene is made of a sequence of nucleiotide "zipper teeth" (often many thousands of zipper teeth). To date, variants of about 50-100 of these 30,000 genes have been shown to increase your risk of developing MS.

How do the genes influence the development of MS?

The translation of the genes into making proteins and how these proteins function it central to this effect. The codes from three zipper teeth in the gene are read and tell the cell to make an amino acid. These are building blocks (bricks) of life. There are about twenty different amino acids and these are joined (about 300-2000) to make proteins.
The amino Acids (bricks) are joined together according to the information given by the genes to make proteins, These are an essential part of of the building fabric of our bodies (Buildings). These proteins can be simple or highly complex (a house a bridge can be all made out of bricks) .
The structure of these proteins (walls) often determines the function of the protein. They can do many different things (e.g. below is a wall for playing football or a climbing wall).
However, the protiens (walls) may not be identical between different people and this gives variation. Therefore, some people have blue eyes, others brown others green eyes. This is because they have different variants of the genes, which encodes a slightly different amino acid sequence, which makes a slightly different protein. Some of these variatons appear to be of little consequence. But this variation ( seen below as easy climbing verse hard climbing) allows us to adapt better to where we live. Some people have long eyelashes, others have short eyelashes, but in a sandy dessert there is an advantage to having long eyelashes which keeps sand out of your eyes. In a climate with little sunlight it helps to have a fair skin so that you can make more vitamin D than highly pigmeneted skin.

One set of genes in a place called the Major Histocompatibility Complex are very variable between different individuals (walls of flags). This is used by CSI (Crime Scene Investigation) and the Poeleece to DNA fingerprint you!. So we can call them Identity Proteins (there are six major ones and a numer of others), cos it tells us who you are. The chances of you having an identical match to someone else, you are not related to is very slim and because of this, it is difficult to get a match for an organ transplant.
The above flags were made out of red and white bricks there are many more, now add a blue brick and see how many more flags you can make. This can give a clue how varied the major histocomplatibility complex can be


This set of genes is very variable because it is designed to allow your white blood cells to determine who you are and distinguish who you are not. Your white blood cells are trained to recognise our own major histocompatibility complex proteins (flags on your own cells). This flag allows them to distinguish your own cells from unwelcome guests such as viruses, bacteria, fungi, parasites and even cancers. However one of these variants, which is common in Northern Europeans is associated with an increased risk of MS. This is because it helps to trick the white blood cells to either recognise something it should not recognise or miss something is should not miss. Animals studies suggest the former occurs, such that the white blood cells attacks the myelin-producing oligodendrocyte as if it were a virus/bacteria. This is the beginning of MS.

Many of the other gene variants, such as that found in the gene for CD6, which increase the risk of developing MS, also help stimulate the white blood cell response. We know this is a problem because if we block the white blood cell response it can control some aspects of MS.

Genetic studies by post

Tung et al. Efficient Replication of over 180 Genetic Associations with Self-Reported Medical Data. PLoS One. 2011;6(8):e23473.

While the cost and speed of generating genetic data have come down dramatically in recent years, the slow pace of collecting medical data for large numbers continues to hamper genetic research.

In this study the investigators evaluated a novel online framework for obtaining large amounts of medical information from people by assessing their ability to replicate genetic disease associations using these data. 

Using web-based questionnaires, they gathered self-reported data on 50 medical phenotypes (diseases and traits) from a generally unselected group of 20,000 individuals. 

Of a list of genetic associations they successfully replicated about 75% of the diseases associations that they expected to. 

Altogether they replicated over 180 previously reported associations, including many for type 2 diabetes, prostate cancer, cholesterol levels, and MS. 

They also demonstrated that we could improve the replication success by taking advantage of their ability to recontact the subjects, offering more in-depth questions to refine self-reported diagnoses. 

Their data suggest that online collection of self-reported data from a recontactable cohort may be a viable method for both broad and deep phenotyping in large populations.

"This is a amazing study; we need to jump on the band wagon."

"It helps to have money; the founder of 23andme is the partner of Sergey Brin, one of the founders of Google."

Tuesday, 23 August 2011

Kid and Adolescent Vaccine Query

From: Brenda Banwell [mailto:************]
Sent: 23 August 2011 02:03
To: 'g.giovannoni@qmul.ac.uk'
Subject: Re: [Multiple Sclerosis Research] New comment on Inflammation ...

I do not give any vaccine within 6 mos of acute attack. After this, we use all routine vaccines normally. I always ensure that children have varicella vaccine (if they did not have natural infection) before immunosuppression. Hope this helps! Brenda

Sent from my BlackBerry device

 
From: Gavin Giovannoni [mailto:g.giovannoni@qmul.ac.uk]
Sent: Sunday, August 21, 2011 07:38 PM
To: Brenda Banwell
Subject: FW: [Multiple Sclerosis Research] New comment on Inflammation on the surface of brain drives grey m....
 
Brenda

I hope you are well. Is there a consensus regarding routine vaccinations in kids and teens with MS? I need to respond to this query on our blog.

Thanks

With best wishes

Gavin

  
From: Anonymous [mailto:noreply-comment@blogger.com]
Sent: 21 August 2011 23:32
To: g.giovannoni@qmul.ac.uk
Subject: [Multiple Sclerosis Research] New comment on Inflammation on the surface of brain drives grey m....

Anonymous has left a new comment on your post "Inflammation on the surface of brain drives grey m...":

Many parents believe their child's MS was triggered by a vaccination and have decided to avoid the HPV vaccine. Should kids & teens with MS get all the usual vaccines?

Posted by Anonymous to Multiple Sclerosis Research at Sunday, August 21, 2011 11:31:00 PM

Shared genetic risks across several autoimmune diseases

Cotsapas et al. Pervasive Sharing of Genetic Effects in Autoimmune Disease. PLoS Genet. 2011 Aug;7(8):e1002254.

Genome studies have identified numerous genetic associations between common genetic variants (small changes in the DNA code) and risk of other autoimmune diseases; some of these genetic variants are shared between two diseases.

Along with clinical evidence, this suggests that some genetic risk factors may be shared across several diseases. 

In this study the investigators evaluated the extent of this sharing for 107 immune disease-risk variants in seven diseases: celiac disease (gluten sensitivity), Crohn's disease (inflammatory bowel disease), MS, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes

They found evidence that 47/107 (44%) immune-mediated disease risk variants are associated with multiple, but not all-immune-mediated diseases. 

They also showed that distinct groups of interacting proteins are encoded near these variants in our genomes, which predispose to the same subsets of diseases. 

They propose that common genetic risks and mechanisms underlie several related autoimmune diseases. The mechanisms are inferred from the proteins that occur near these genetic variants. 

"Why is this important?"

"It may provide us with clues to the cause of MS and provide common treatment targets for several diseases. If we can identify an important pathway common to several disease we may be able to design a drug to target this pathway."

"Please let me know if this post is easier to understand than yesterday's on immunology?"

"This paper is a theoretical paper based on data already published. The term we use for this type of analysis is 'in silico'; i.e. data mining done a computer. What this paper needs is some hard core lab work on MS'ers and control samples to see if these variants have functional consequences on the way their immune systems function." 

Monday, 22 August 2011

MS susceptibility gene affects immune function

Epub ahead of printKofler et al. The CD6 Multiple Sclerosis Susceptibility Allele Is Associated with Alterations in CD4+ T Cell Proliferation. J Immunol. 2011 Aug 17.

"Up until now I have tried to avoid giving you too much immunology on this site. Now for something completely different."

Genetic studies have revealed a large number of genetic associations with MS. Despite this progress, the mechanisms underlying the contribution of the genetic variants to the onset of MS remain mostly unknown. A recent analysis of all the genome-wide association studies of MS identified a new susceptibility locus that is found close to a gene called CD6. 

CD6 plays an important role in the maintenance of T cell activation and proliferation. 

T cells are thought to be the main immune cell that orchestrates the damage in MS. 

In this study the researchers examined the biologic effects of the risk-associated genetic variant in CD6.

They report that the MS susceptibility variant in CD6 is associated with decreased expression of the full-length version of CD6 in the two major types of T-cells called CD4(+) and CD8(+) T cells. 

As a consequence of this, proliferation of T cells is diminished during long-term activation of CD4(+) T cells from subjects with the risk allele. 

These findings indicate that the MS risk variant in the CD6 gene is associated with altered proliferation of T cells and demonstrates the possible influence of a disease-related variants on immune function.

"Wow, what a mouthful!"

"In short, one of the many genetic variants that increase one's risk of getting MS has functional effects on the immune system. If you happen to be a carrier of this genetic variant a subtype of your T cells is unable to proliferate (divide and increase in numbers) when activated." 

"I wonder how this affects your risk? You would expect that anything that increases your risk would result in an increase in proliferation of autoimmune T cells. Unless these T cells are responsible for controlling the immune system or are fighting a virus."

"Another fact about science is that most new findings result in more questions being asked. For example the identification of a new 'at risk genetic variant' opens up a whole new avenue of research and results in many more questions."

"Please let me know if this post was too complex for you."

Phase 2 trial targeting JC virus is cleared by the FDA

Inhibikase Therapeutics has received the go-ahead from the US Food and Drug Administration (FDA) to begin a phase II proof-of-concept trial of IkT-001, an inhibitor, targeting JC human polyomavirus (JCV) infection.

JCV infection, which is very common in the general populace, is a causative agent of Progressive Multifocal Leukoencephalopathy (PML). 

In MS'ers on Natalizumab, PML is fatal in more than 50 per cent of patients, as the JCV virus creates lytic infection of the brain. 

In pre-clinical models, however, IkT-001 was shown to be able to block JCV viral entry into host cells, suppressing the development of PML.

The phase II trial will be a four-week, open-label, multicentre, sequential dose-ranging study of the safety and pharmacokinetic profile of IkT-001 against JCV in 48 at-risk patients: those with relapsing multiple sclerosis (MS) who receive Tysabri (natalizumab) infusion therapy. 

The study will also examine the compound’s antiviral effect as measured by the urinary excretion of JCV.

PML currently has no approved treatment, meaning that IkT-001 will be eligible for orphan drug status if it continues to progress through trials to market. Additionally, as IkT-001 utilises a common mechanism of action that enables treatment for bacterial and viral infectious disease, an efficacious outcome in this phase II study could clear a path for multiple indications using the same pharmaceutical approach, according to Inhibikase.

Source: PMLive News

Sunday, 21 August 2011

EBV & Bradford-Hill

Re: Curious Orange's post on "An EBV controversy":

"Hello, in a previous thread you mentioned that in adult MS, EBV is found in 99.9% of cases. This struck me as an amazing statistic, then I googled a bit and read that over 95% of the general population also show evidence of EBV infection. Now it seems a bit less amazing…

Can anyone out there help me understand why this small difference is so significant?
Also, how well does the EBV theory fit into Bradford-Hill's 9 criteria for causation? Thanks"

"I agree that at first glance this seems less amazing; however the negative predictive value is very high. In other words if you don't have EBV you are virtually protected from getting MS; your risk is close to zero! This is one of the strongest arguments that I keep putting forward when making the claim that  EBV is the cause of MS."


"Regarding Bradford-Hill criteria. I recently gave a talk at the MS Frontiers meeting at Heathrow Airport and concluded my talk with the following slide."


"EBV ticks between 2 and 6 of Bradford-Hill criteria; it depends on how strong the evidence is and if you are willing to accept the evidence." 


"There is debate on the strength of the EBV-MS association; with a relative risk of between 2 and 3. A low relative risk of developing MS due to EBV is to be expected as it would be a rare manifestation of a common exposure. High relative risks are only found with common manifestations of uncommon or rare exposures."  

"What is essential for causation is experimental evidence. If we prevent (vaccination) or suppress EBV  (anti-viral drugs) to we prevent or cure people of MS? These are strategies high-up on our research agenda."


"In isolation the conclusion slide is difficult to understand. I will therefore make a video and post it on YouTube to explain it in more detail."

Other posts of interest:


01 Jun 2011
I am giving a debate at the MS Frontiers meeting taking place 23-24 June 2011 at Sofitel , Heathrow. The following is my abstract. "Multiple Sclerosis is caused by Epstein Barr virus" ...

An EBV controversy

Epub ahead of printLassmann et al. Epstein-Barr virus in the multiple sclerosis brain: a controversial issue--report on a focused workshop held in the Centre for Brain Research of the Medical University of Vienna, Austria. Brain. 2011 Aug 16. 

Recent epidemiological and immunological studies provide evidence for an association between Epstein-Barr virus (EBV) infection and multiple sclerosis, suggesting a role of EBV infection in disease induction and disease course. 

A key question in this context is whether EBV-infected B lymphocytes (the immune cells that make antibodies) are present within the central nervous system and the lesions of MS'ers. 

Previous studies on this topic provided highly controversial results, showing EBV reactivity in B cells in the vast majority of MS'ers and lesions, or only exceptional EBV-positive B cells in rare cases. 

In an attempt to explain the reasons for these divergent results, a workshop was organized under the umbrella of the European Union FP6 NeuroproMiSe project, the outcome of which is presented. 

This report summarizes the current knowledge of EBV biology and shows that EBV infection is highly complex. There are still major controversies, how to unequivocally identify EBV infection in pathological tissues, particularly in situations other than EBV-driven lymphomas (a type of cancer due to EBV) or acute EBV infections. 

It further highlights that unequivocal proof of EBV infection in MS lesions is still lacking, due to issues related to the sensitivity and specificity of the detection methods.

"And you thought only CCSVI was controversial."

"This issue is only in relation to whether or not EBV infection has a direct role within the brain and spinal cord of MS'ers."

"The controversy does not extend to strong epidemiological association between EBV and MS. With regard to the latter the data is unequivocal."

"I still believe EBV causes MS. What I don't know is how it does this and where the virus acts. That is the million dollar question."

Red flags and atypical symptoms

"The following study is very timely in view if the recent debate on the diagnosis and misdiagnosis of MS."


Background: Red flags and atypical symptoms have been described as being useful in suggesting alternative diagnoses to MS and clinically isolated syndrome (CIS); however, their diagnostic utility has not been assessed. 

Aim: The aim of this study was to establish the predictive value of red flags and the typicality/atypicality of symptoms at presentation in relation to the final diagnosis of patients referred with suspected MS. 

Methods: All patients referred with suspected MS over a 3-year period were assessed by the typicality of the clinical presentation and the occurrence of red flags in relation to the eventual diagnosis. The extent of agreement of trainee and consultant neurologists as to typicality of clinical presentations was determined. 

Results: Of 244 patients referred, 119 (49%) had MS/CIS and 125 (51%) did not. 41 patients were referred because of an abnormal MRI. Of 203 with clinical symptoms, 96 patients had atypical symptoms of whom, 81 (84%) did not have MS and 15 (16%) had MS/CIS. Typical symptoms occurred in 107 patients; 10% did not have MS/CIS. 

The average percentage agreement between consultants and trainees was 73% with a range of 32-96%.

Conclusions: Atypical features at presentation are more sensitive and specific and have a higher positive predictive value than red flags to refute a diagnosis of MS/CIS.

Q: "What are red flags?"
A: "Red flags are clinical features that alert neurologists to potential other diagnoses and MS mimics."

Q: "What are atypical presentations?"
A: "These are presentations of MS that are rare and are more common with other diseases. For example presenting with a seizure."

"I hope the figures presented in this study highlight the difficulty we have making a diagnosis of MS and that things are not black-and-white." 

"Remember the artist with a palette who paints in various shades gray."

Saturday, 20 August 2011

Drug-The game-Back Again!

Drug the Game Part I , Part II, Part III, Part IV

You said " Actual game? Who'll play a game you can almost never win "

Well first thing to say is ask the San Marino Football Team!

However we can increase the odds of completion by increasing the number of "proceed cards" within the "Decks of risk". Secondly if I were to offer a real wad of cash to people who completed the game in the minimum number of moves, or say to the player who wins with the least number of moves within one year, then I am sure some of you would play!. The more the cash prize the more players.

The fastest you can get round is about 50 turns, just think of incentives, the darts player with the nine dart finish or the 147 break in snooker or the hole in one form the golfer. Likwise there is an incentive for the pharmaceutical industry to get round the board and they get a cash prize, with a limited amount of time to spend it.

This prize pays for the success and the loses. In the real world it is not all a game of chance and we learn from our mistakes. I am sure that there will be more finishers in the near future!


CCSVI - another negative independent study

Epub ahead of printTsivgoulis et al. Extracranial venous hemodynamics in multiple sclerosis: A case-control study. Neurology. 2011 Aug 17.

Objectives: These investigators performed a color-coded Doppler sonography case-control study to externally validate the CCSVI criteria.

Results: The investigators recruited 42 MS'ers with MS and 43 control individuals 

There was no evidence of stenosis or nondetectable Doppler flow in cervical veins in patients and controls. 

Reflux in internal jugular vein (IJV) was documented in 1 MS'er (2%) and 1 control subject (2%), both in sitting and supine posture during apnea. 

Conclusions: Their data argue against CCSVI as the underlying mechanism of MS. Without further independent validation of CCSVI, potentially dangerous endovascular procedures, proposed as novel therapy for MS, should not be performed outside controlled clinical trials.

"No comment!"

CCSVI - another study; dare I say negative or independent?

Epub ahead of printBaracchini et al. Progressive multiple sclerosis is not associated with chronic cerebrospinal venous insufficiency. Neurology. 2011 Aug 17. 

Objective: CCSVI could represent a late phenomenon of MS or be associated with progression of disability. Thus, these investigators studied CCSVI prevalence in primary progressive (PP) and secondary progressive (SP) MS, to clarify whether CCSVI characterizes the progressive forms of this disease.

Methods: A total of 35 MS'ers with SPMS, 25 patients with PPMS, and 60 age- and gender-matched normal controls (NC) were enrolled into a cross-sectional study. Extracranial and transcranial high-resolution venous echo color Doppler sonography (ECDS-TCDS) was performed in all MS'ers and NC. Those MS'ers having any abnormal ultrasound finding were asked to undergo selective venography (VGF).

Results:
TCDS was normal in all MS'ers. 

ECDS showed one or more abnormal findings in 9/60 (15.0%) MS'ers (7/35 [20.0%] SPMS, 2/25 [8.0%] PPMS) and in 14/60 (23.3%) NC (p not significant for all comparisons). 

CCSVI criteria were fulfilled in 0 NC and 4 (6.7%) patients with MS: 3 SPMS and 1 PPMS. 

VGF, performed in 6/9 patients, was abnormal only in one case who had bilateral internal jugular vein stenosis.

Conclusion: Their findings indicate that CCSVI is not a late secondary phenomenon of MS and is not associated with disability.

"This study's findings are self-explanatory; no commentary is necessary."

Friday, 19 August 2011

Neonatal outcome in MS

van der Kop et al. Neonatal and delivery outcomes in women with multiple sclerosis. Ann Neurol. 2011 Jul;70(1):41-50.

Objective: To determine (1) whether the risk of adverse neonatal and delivery outcomes differs between mothers with and without multiple sclerosis (MS) and (2) whether risk is differentially associated with clinical factors of MS.

Methods: Comparisons were made between births to women with MS (n = 432) and to a frequency-matched sample of women without MS (n = 2,975) from 1998 to 2009. 

Results: Babies born to MS mothers did not have a significantly different average gestational age or birth weight compared to babies born to mothers without MS. MS was not associated with an increase assisted vaginal delivery or Caesarean section rate. There was a slightly elevated risk of adverse delivery outcomes among MS mothers with greater levels of disability, although findings were not statistically significant. Disease duration and age at MS o
nset were not significantly associated with adverse outcomes.

Interpretation: This study provides reassurance to MS'ers that maternal MS is generally not associated with adverse neonatal and delivery outcomes.

"Woman with MS planning to start, or expand, their families will find this study results reassuring."

"Please note this was a study done in Canada and the results may not necessarily be applicable in other healthcare systems." 

Fatigue, cognitive functioning and depression in paediatric MS

Epub ahead of printGoretti et al. Fatigue and its relationships with cognitive functioning and depression in paediatric multiple sclerosis. Mult Scler. 2011 Aug 15.

Background: There is limited information on fatigue and its clinical and psychosocial correlates in children and adolescent MS'ers.

Objective: To assess the relationships between fatigue, cognitive functioning and depression in paediatric MS.

Results: In total, 57 patients with RRMS were compared with 70 healthy controls.

Percentages of fatigued patients ranged from 9% to 14% according to self-reports, and from 23% to 39% according to parent reports.

Fatigue was significantly related with higher scores on the Children's Depression Inventory.

Higher levels of self-reported cognitive fatigue were associated with impaired performance on a problem-solving test, whereas higher levels of parent-reported cognitive fatigue were associated with impairment on tests of verbal learning, processing speed, complex attention and verbal comprehension.

Conclusions: Our data show that fatigue can affect a sizeable proportion of paediatric MS'ers, and confirm the association between fatigue and depressive symptoms in MS.

"Interesting that fatigue is less common in paediatric MS; in adults ~80% of MS'ers will complain of fatigue. I wonder if the perception of fatigue is learnt?"


"Fatigue, cognitive impairment and depression are also a massive problem in paediatric MS."