Sunday, 31 July 2011

Exposing the Failure of EAE

You wrote “I would like someone to expose the greatest fraud in MS research - EAE and other mouse models that bear no resemblance to human MS……The complete failure to identify any effective treatments form this model is the biggest scandal/ fraud, unfortunately no one is prepared to rock the boat and own up to this”.

Do not kid yourself there are always people who are prepared to rock the boat and state their opinions about animal studies, notably EAE

There are more than 100 compounds of proven efficacy in EAE, and we believe that it is pointless to add anymore to this list” (Sriram & Steiner)

“It is now possible to conduct a Phase II trial for anti-inflammatory MS drug candidates within a few months… is not useful to pre-screen potentially effective drugs using the EAE model” (Ransohoff)

It is true that there are only a few treatments that were found to be active in EAE, which have been translated into new drugs for MS. However, it is wrong to say that there have been no treatments that have resulted from work in EAE. The new breed of MS drugs such as Tysabri and Gilenya have their foundation firmly rooted in ideas from EAE or other animal studies.

This is likely to increase as drugs are being targeted at common causes of disease that occur both in both animal models and human disease. Therefore although EAE is not MS, if used sensibly it can be used to address some questions that will lead to "tomorrows therapies". Indeed there would probably be no drugs for MS without animal studies, as they have been essential in providing the basis of knowledge and the tools that have been required to provide drugs for MS.

There is a constant, ever evolving debate about the relevance of animals in research. As times change, so do practices, including banning of animal research where it is no longer considered useful. As you probably know animal use for cosmetic testing has been banned for many years and this too has become the way of animal testing of food products. However, for many medical aspects, we are not yet at that stage. If all such animals studies were considered futile, then because of the great human and financial costs involved in under taking such work, it would not be supported and would not be undertaken.

All animal studies within the United Kingdom must go through an independent ethical review process and permission to undertake this work is controlled by UK Government, Home Office via the Animals (Scientific Procedures) Act. These panels have the power to stop work with animals and these processes involve debates about the merits of EAE with regard to the research and MS and justifications for each line of research must be made.

There are many reasons for this slow-development in translating drugs towards the clinic, and one aspect is that indeed human MS is more complex than the simple experiment using EAE. However, there are many other reasons for this slow progress Furthermore you must also appreciate that it takes 10-15 years to develop a drug from animal studies to get a drug suitable for human use. Many will fail not because they could not work, but because they will not be sufficiently safe.

Some people (EAEologists) study EAE because they are more interested in the disease mechanisms, rather than treating MS. Some "ThEAEologists" convince themselves that EAE is MS, without really ever understanding what MS is. We try to use our animal models in a context that is useful for MS and we are committed to the Refinement, Reduction and Replacement principles of animal use in research.

The public including MSers, scientists and clinicians continue to rock the boat, and we are not adverse to a bit of rocking ourselves.

Todays research is tomorrows progresss.

Cognitive deficits correlate with MRI changes in normal appearing brain tissue

Background:  The disease load in MS often is based on the visible lesion volume on MRI. The subtle changes in the  normal appearing brain tissue are rarely considered.

Study objectives: This study investigated whether MRI changes in the normal appearing brain tissue explained part of the cognitive impairment seen in MS'ers  

Results: In this study a significant correlation was found between total lesion volume (normal and abnormal appearing tissue) and general cognitive dysfunction, verbal intelligence, mental processing speed, visual problem solving and complex motor speed.

Conclusion:  These results show that even in the normal appearing brain tissue MRI detects changes likely to be associated with an underlying pathology and contributes to the cognitive impairment in MS.

"This study confirms several other studies in that MRI lesion load correlates with cognitive impairment." 

"Some studies have shown that DMTs, which reduce the burden of disease, also slow the rate at which cognition is affected in MS'ers. Unfortunately, not all trials have collected relevant outcome data on cognition."

"I sincerely hope that the more effective DMTs that are emerging will have a greater impact on this hidden disability (very few neurologists check for cognitive impairment)."

Saturday, 30 July 2011

Alemtuzumab - risks of developing other autoimmune diseases

Study objectives: To define the rate, timing, and clinical risk factors for the development of autoimmune disease after alemtuzumab treatment in MS'ers.

"What is alemtuzumab? You may know the drug as Campath-1h. This is a powerful immuno-modulator that is given as a course of intravenous infusions. It depletes the immune system and allows it to recover. I refer to it as an immune system rebooter. Short of bone marrow transplantation it is probably the most effective MS disease-modifying therapy in late stage development."

"What is an autoimmune disease? Autoimmunity refers to a family of related diseases in which the body's immune system goes awry and attacks itself. For every organ system in the body there is an autoimmune disease. Please see Wikipedia's article on the subject for more information; autoimmunity"

Methods: The data on 248 MS'ers treated with alemtuzumab, with a median follow-up of 34.3 months (range 6.7-107.3), was analysed.
  1. Novel autoimmune disease developed in 22.2%. 
  2. Thyroid autoimmune disease was the most frequent (15.7%). 
  3. A range of blood, kidney, and skin autoimmune disease were also observed as was the development of asymptomatic autoantibodies. 
  4. Autoimmune disease was seen from 2 weeks after initial treatment and was most frequent 12-18 months after first treatment. 
  5. No new cases of autoimmune disease were identified after 60 months after initial treatment. 
  6. The risk of autoimmune disease was not linked to the dose or interval of alemtuzumab treatments. 
  7. Established risk factors for autoimmune diseases including sex and age had no impact on autoimmune disease frequency. 
  8. In this study MS'ers with a family history of an autoimmune disease were 7.3x more likely to develop an autoimmune disease, compared to MS'ers without a family history. 
  9. MS'ers with a personal smoking history were 3x more likely to develop autoimmune disease, compared to non-smokers. 
Conclusions: Individual risk of autoimmune disease post-alemtuzumab is modified by smoking and family history, which should be incorporated into the counseling process prior to treatment. 

"This is a very useful study and allows us to assess the risk of developing autoimmunity after alemtuzumab therapy. Some MS'ers may find this risk too high and others may find the risk acceptable. The good news is that the risk falls off after 5 years. This will help us as it means we may not need to monitor for these complications beyond this time."

"More data on how bad smoking is for MS'ers; time to give up?"

"Are you prepared to take the risk?"

Conflicts of interest: multiple

Additional reading: autoimmunity, autoantibody, alemtuzumab

Please see other posts on this blog in relation to Alemtuzumab:

18 Jul 2011
"This was not a negative study; Alemtuzumab is still a very promising disease-modifying therapy! The patients in this trial were less active than previously therefore the trial lacked power to detect a difference in ...
12 Jul 2011
More on the Alemtuzumab trial. The previous post is simply the headline results; we need to wait for the full results that will be presented at the ECTRIMS/ACTRIMS meeting from the 19 – 22 October 2011, in Amsterdam, ...
11 Jul 2011
A press release on the headline results of the Alemtuzumab vs. Interferon-beta-1a trial: "Sanofi said Lemtrada worked better than an older drug, Rebif, in preventing relapses, as patients treated with Lemtrada were 55 ...
17 Jan 2011
Wow! Let's hope it is not too expensive for the NHS. Click here to read the press release!

Etc. Please use search term "alemtuzumab"

Friday, 29 July 2011

Shoddy Media Reporting

You may have noticed stories about stem cell trials funded by the Multiple Sclerosis Society and the UK Stem Cell foundation

MS Society Press Release

Please ingnore much of the rubbish that has been appearing on some media websites. Queen Mary is not undertaking a trial of stem cells from aborted foetues, in fact the study is only a study in mice. This is another example of shoddy reporting by the media. 

CCSVI: Zamboni should have declared his conflicts of interest

In response to a previous comment and my response.

"I only realise now that most MS'ers are not aware of some very important background information in relation to CCSVI."

"The worrying and most upsetting thing about the whole CCSVI saga is the fact that Zamboni had, and still has, massive conflicts of interest. He has patents in relation to CCSVI and received money from a company that sells the equipment for diagnosing CCSVI."

Read about it in the National Post and The Globe and Mail.

"If he had declared these conflicts of interest early on I suspect we, the scientific community and MS'ers, would have been much more critical of his claims."

"May be the unnecessary deaths due CCSVI procedures and the unnecessary diversion of valuable research funds into CCSVI research could have been avoided ."

"The moral of the story; transparency, transparency, transparency."

Professor David Baker: not just a pretty face

The fraud case he saw coming; well done Prof DB!

Read all about it in Nature News & Science Insider.

The paper David spotted: Van Parijs et al. Role of interleukin 12 and costimulators in T cell anergy in vivo. J Exp Med. 1997 Oct 6;186(7):1119-28.

"Another one of our day jobs is to expose research fraud; unfortunately it is not always this obvious. Fraud not only sends people down the wrong track in terms of scientific discovery, but it makes the general public lose faith in the scientific process. This can't be a good thing. Biases and conflicts of interest are also a problem, but are hopefully not as big a problem to deal with as fraud, provided there is transparency." 

Van Parijs L, Refaeli Y, Lord JD, Nelson BH, Abbas AK, Baltimore D.

Immunity. 2009 Apr 17;30(4):611. No abstract available.
PMID: 19382300 [PubMed - indexed for MEDLINE]

Van Parijs L, Refaeli Y, Abbas AK, Baltimore D.

Immunity. 2009 Apr 17;30(4):612. No abstract available.
PMID: 19378495 [PubMed - indexed for MEDLINE]

Van Parijs L, Peterson DA, Abbas AK.

Immunity. 2009 Apr 17;30(4):611. No abstract available.
PMID: 19378493 [PubMed - indexed for MEDLINE]

Additional reading: Luk van Parijs

MS pathology is more extensive than previously thought

Background: The 'normal appearing white matter' in MS,  i.e. the areas without visible lesions, is known to be diffusely abnormal using special MRI techniques. 

Results: Using a new stronger high-field MRI the investigators identified numerous lesions that were not detectable in areas of 'normal appearing white matter' as seen using conventional MRI. 

Conclusions: Focal MS lesions contribute to the abnormalities known to exist in the 'normal appearing white matter'.

"This study shows that using better technology MS pathology is more widespread than what we can see using conventional MRI. This is not surprising as this has been known for decades from pathological studies; i.e.  many more MS lesions are found using a microscope than can be seen with the naked eye."

Natalizumab risk stratification update

The following is an update of the natalizumab risk stratification figures based on:
  1. Prior use of immunosuppression; for example mitoxantrone. azathioprine, etc. 
  2. Treatment duration (months); please remember that the risk of PML within the first 12 months of therapy is very low.
  3. Anti-JCV antibody status (positive or negative); if you have not been tested for these antibodies you need to ask your neurologist to arrange the test, which is available within the UK. 

The figures in this diagram are based on data from Biogen-Idec presented at the following meetings:
  1. Sandrock, et al. Presented at: ENS; May 28-31, 2011; Lisbon, Portugal. O212. 
  2. Sandrock, et al. Presented at: CMSC; June 1-4, 2011; Montreal, Quebec, Canada. S92
CoI: multiple

Additional reading: please see other posts on this blog using the search term "natalizumab"

Natalizumab PML incidence estimates by treatment period

There are now 145 confirmed PML cases as of July 5, 2011. Please note there has now been over 165,000 years of exposure to Natalizumab. Therefore the number of PML cases has to be seen in the context of the number of MS'ers receiving the drug. 

The following graph provides the risk by treatment period. 

*Yousry TA, et al. N Engl J Med. 2006;354:924-933. This is the observed rate of PML in clinical trials in MS'ers who received a mean of 17.9 monthly doses of natalizumab.

The post-marketing PML 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 period are calculated based on natalizumab exposure through June 30, 2011 and 145 confirmed PML cases as of July 5, 2011. 

The incidence for each period is calculated as the number of PML cases divided by the number of patients exposed to natalizumab. For example for 25 to 36 infusions all PML cases diagnosed during this period is divided by the total number of MS'ers ever exposed to at least 25 infusions and therefore having risk of developing PML during this time. 

Source: Biogen Idec, data on file.

Other posts on this blog concerning Natalizumab:

24 Jul 2011
“The expectation of Natalizumab therapy is to prevent future attacks; it does little to repair previous damage. In MS'ers with early disease suppressing on-going disease activity allows endogenous repair to occur; ...
23 Jul 2011
Background: Natalizumab is a biological therapy; that is it is a protein and therefore you immune system can reject it as being foreign and make antibodies against the drug. This is what we aim to achieve with vaccines. ...
21 Jul 2011
"This video blog is response to a query from one of the readers for more information on this topic and in response to an audit we performed on this subject among the MS'ers on Natalizumab at the Royal London Hospital." ...
17 Jun 2011
The observed clinical trial rate was in PwMS who had received a mean of 17.9 monthly doses of natalizumab. In comparison, the post-marketing rate is calculated as the number of PML cases since reintroduction in PwMS who ...

Etc. search term "natalizumab"

Thursday, 28 July 2011

CCSVI - NICE to review the procedure

NICE has been notified about CCSVI and will consider it as part of the Institute’s work programme.

The Interventional Procedures Advisory Committee (IPAC) will consider this procedure and NICE will issue an Interventional Procedures Consultation Document about its safety and efficacy for 4 weeks public consultation.

 IPAC will then review the consultation document in the light of comments received and produce a Final Interventional Procedures Document, which will be considered by NICE before guidance is issued to the NHS in England, Wales, Scotland and Northern Ireland.

If you wish to be alerted to developments regarding this procedure, including the release of the consultation document, please express your interest on the NICE website.

"Some action at last! Good news for all you CCSVI'ers, at least the relevant professional bodies are taking notice and will provide an objective overview of the field, free of any conflicts of interest."

"Hopefully, the safety of MS'ers considering undergoing an intervention for the condition will be NICE's top priority. We don't want any deaths from CCSVI procedures done in the UK."

Additional reading: please see other posts on this blog using the search term "CCSVI"

Slowed nerve conduction: fatigue and heat sensitivity

As a follow-up to my post yesterday.

"Roshni was correct; well done!"

The main consequence to slowed conduction is fatigue. The commonest example is exercise-induced fatigue. For example you may find that as you walk or exercise it becomes more difficult; your leg begins to drag, your vision may blur or your thought processes seem to slow. The reason for this is that those demyelinated segments in the nerve stop conducting due to conduction block. Why this happens is complex, but could be related to an energy deficit, a rise in body temperature, or both. The molecules that transmit the electrical signal down a nerve fibre, are little pumps (ion pumps) and require energy to work. In addition, these ion pumps are optimised to function at a certain temperature, this is why some MS'ers are heat sensitive.

"Have you heard of Uhthoff's phenomenon?"

Wilhelm Uhthoff (1853-1927) was a famous German Professor of ophthalmology who described temporary visual loss associated with optic neuritis linked to physical exercise. This was later found to be caused by a rise in body temperature. This phenomenon is now known to affect other neurological systems as well, for example the motor system when walking, balance and sensory pathways and even the cognitive centres. 

Up until recently, apart from cooling, we have not had a treatment for Uhthoff's phenomenon. More recently the drug Fampridine has been licensed to improve walking speed in MS'ers; I suspect that MS'ers with heat sensitivity or fatigue-related conduction block will be more likely to be fampridine responders (see figure below).

Goodman et al. Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial. Lancet. 2009 Feb 28;373(9665):732-8.

"Symptomatic treatments remain the mainstay of MS therapies; having drugs to treat fatigue due to conduction block are welcomed. However, I remain sceptical about their long-term effectiveness which is why we need effective remyelination therapies." 

"Remyelination therapies, should be neuroprotective preventing or slowing down the degeneration of nerve fibres that have been left vulnerable by demyelination."

Animal use rises

The number of genetically modified (GM) animals, particularly mice, being bred for research in the UK rose by 6% from 2009 to 2010.

"I wonder how many of them were being used for MS-related research? I suspect a lot."

Additional reading: Nature 21 st July 2011

Vitamin D intake during pregnancy is associated with a lower risk of MS in offspring

Objective. Vitamin D may have a protective role in the aetiology of MS, but the effect of vitamin D in pregnancy on adult onset MS has not been studied.

Methods: In 2001, 35,794 mothers of participants of the Nurses' Health Study II completed a questionnaire inquiring about their experiences and diet during pregnancy with their nurse daughters. This allowed these investigators to study  the association of maternal milk intake, maternal dietary vitamin D intake, and predicted maternal serum vitamin D during pregnancy and their daughters' risk of developing MS.

Results: MS was diagnosed in 199 women. The relative risk of MS was lower among women born to mothers with high milk or vitamin D intake during pregnancy. The relative risk of MS was 0.62 (38% lower) for nurses whose mothers consumed 2 to 3 glasses of milk per day compared with those whose mothers consumed <3 glasses per month. The predicted vitamin D level in the pregnant mothers was also inversely associated with the risk of MS in their daughters. 

Conclusions: Higher maternal milk and vitamin D intake during pregnancy may be associated with a lower risk of developing MS in offspring. 

"This supports my current recommendation that all woman should be taking physiological doses of vitamin D supplements during pregnancy. In fact we all should be supplementing our dietary intake all the time. I currently recommend 5,000U of vitamin D3 per day."

Other posts on this blog in relation to Vitamin D:

17 Jul 2011
In Australia and New Zealand, the number of people with vitamin D deficiency varies, but is acknowledged to be much higher than previously thought. One study found marginal deficiency in 23% of women, and another frank ...
16 Jul 2011
The vitamin D-lemma. A must read news article for all of you following the vitamin D debate. Amy Maxmen, The vitamin D-lemma. Nature 2011;475:23-25. Some extracts to wet you appetite: A vociferous debate about vitamin-D ...
10 Jul 2011
This study compared vitamin D status in 200, free-living, woman, aged between 20 to 55 years, from Tehran, a high-polluted area, and Ghazvin, a low-polluted area. Level of UVB (ultra-violet B - the part of the light ...
05 Jul 2011
Vitamin D - some facts. Vitamin D is a misnomer; it was incorrectly classified as a vitamin. Vitamins: are nutrients that are required in tiny amounts; cannot be synthesised in sufficient quantities by our bodies ...

11 Jul 2011
"This study provides a hint that vitamin D supplementation that results in higher blood vitamin D levels many suppress EBV within the body. Interesting? We think very interesting and trying to work out how EBV and ...
05 Jul 2011
"This study is another reason to make sure that you are vitamin D replete. There is not enough good quality sunshine in the UK to do this so you need to take supplements. I advocate 5000U of vitamin D3 per day." ...
24 Jul 2011
EBV viral load was lower at higher serum vitamin D concentrations in controls subjects. Conclusion: Past infection with EBV, but not current EBV viral load in whole blood, is significantly associated with increased CIS ...
05 Jul 2011
Vitamin D websites. You may find these websites helpful: Vitamin D Council & Vitamin D3 World CoI: Nil. Posted by Gavin Giovannoni at 09:38 · Email This BlogThis! Share to Twitter Share to Facebook Share to Google Buzz ...

Etc. Search term "Vitamin D"

Wednesday, 27 July 2011

CCSVI does not predict MS risk or severity

Background: It is unclear whether chronic cerebrospinal venous insufficiency (CCSVI) is associated with MS, because substantial methodological differences have been claimed by Zamboni to account for the lack of results of other groups. Furthermore, the potential role of venous malformations in influencing MS severity has not been fully explored. This information is particularly relevant, because uncontrolled surgical procedures are increasingly offered to MS patients to treat their venous stenoses.

Methods: In the present study, CCSVI was studied in 84 MS'ers and in 56 healthy subjects by applying the Zamboni method for CCSVI identification.

Results: The investigators found no differences in CCSVI frequency between MS'ers and control subjects. Furthermore, no differences were found between CCSVI-positive and CCSVI-negative MS'ers in terms of relevant clinical variables such as disease duration, time between onset and first relapse, relapsing or progressive disease course, and risk of secondary progression course. 

ConclusionsCCSVI has no role in either MS risk or MS severity.

Centonze et al. Proposed chronic cerebrospinal venous insufficiency criteria do not predict multiple sclerosis risk or severity. Ann Neurol. 2011 Jul;70(1):52-9. doi: 10.1002/ana.22436.

"CCSVI falls down on the first criterion proposed by Sir Austin Bradford-Hill (see post below)."

CoI: Nil

Other posts on CCSVI on this blog:

30 Jun 2011
CCSVI is simply a placebo effect. MS'ers are so desperate they're willing to try anything resembling effective treatment. I sometimes think that MS'ers are holding back progress by jumping on unproven bandwagons. ...
25 Jun 2011
The purpose of this study was to evaluate the safety of endovascular treatment of chronic cerebrovascular insufficiency (CCSVI) in patients with MS. In a 1-year period 461 MS'ers underwent endovascular treatment of 1012 ...
25 Jun 2011
Why is this important for CCSVI? The venous system is a capacitance system; i.e. it stores blood. When MS'ers dehydrate themselves they will almost certainly reduce the amount of blood in the venous system, ...
24 Jun 2011
This study was performed to determine how common CCSVI is in a large group of patients with MS, clinically isolated syndrome, other neurologic diseases, and healthy controls, using specific diagnostic criteria using an ...

20 May 2011
The following are the results of our survey on CCSVI that has just closed. Surprisingly only 10% of respondents thought that CCSVI is the cause of MS. Almost a quarter of people think it is an established disease. ...
21 Jun 2011
Klaus' annual CCSVI stand-up routine is fast becoming an institution. Maybe next year he'll even do some proper research rather than just Googling for some 'hilarious' images… Thursday, June 23, 2011 2:28:00 PM ...
04 May 2011
CCSVI - The rise of people power. Italy and Canada bare the brunt of the CCSVI lobby (please see link and picture below). Is this the way to prioritize research? Chafe et al. Nature 472, 410–411 (28 April 2011). ...
15 Apr 2011
CCSVI - time for Sir Bradford-Hill's criteria for causation. Did you know that there is a whole science behind causation? It started way back in the later 1800's when Robert Koch formulated his postulates to persuade his ...

14 Apr 2011
Those with results suggestive of CCSVI underwent selective venography (the gold standard for diagnosing diseases of blood vessels). Fifty healthy age- and gender-matched controls were studied. ...
22 Apr 2011
If any one is interested in CCSVI they should read "Bad Science" by Ben Goldacre; the book provides the social context to the CCSVI phenomenon. Please see
14 Apr 2011
CCSVI: value of MR venography for detection of internal jugular vein anomalies in MS: a pilot longitudinal study. Zivadinov R, et al. AJNR Am J Neuroradiol. 2011 Apr 7. [Epub ahead of print] ...
11 Nov 2009
The “big idea” underlying the presumed link between CCSVI and MS is that narrowing in large veins outside the central nervous system (CNS) leads to stagnation of venous blood in small veins within the CNS and, ...

Etc. Search term "CCSVI"

Slow nerve conduction in MS: are there consequences?

As a follow-up to the post from yesterday.

The top video shows how nerve fibres conduct electricity within the nervous system; the scientific term for this is saltatory conduction; i.e. the electrical impulses jump from one gap in the myelin to the next. The conduction is very rapid.

The video below shows conduction in a demyelinated nerve that has restored conduction by a process called axonal plasticity; a big word for describing the process by which the nerve fibre recovers its ability to conduct electricity without a myelin sheath; this is called non-saltatory conduction. It is very slow.

"The conduction of electricity by nerve fibres takes energy*; clearly the amount of energy it takes to send an electrical impulse down a demyelinated nerve (bottom) is substantially more than a normal nerve (top). This has major consequence for MS'ers. Any guesses what?"

"So please imagine what the result would be if your brain had to receive electrical information from your left and right eyes at different speeds? This is something that happens to MS'ers who have had optic neuritis."

"More on this tomorrow."

*One of the reasons, if not the only reason, why myelin evolved was to save energy. In nature evolution tends to optimise systems that save energy; myelin is one of these. You may be interested to know that nature has evolved at least 7 different systems of myelination in different animal species. This process is called convergent evolution. Myelin must have therefore given our ancestors a major survival advantage; unfortunately, it also primed us to develop a whole host of diseases that target myelin.

Tuesday, 26 July 2011

Evoked potentials in early MS correlate with disability

Evoked potentials (EPs) is a technique that allows us to test the electrical conduction in a particular pathway within the nervous system. If the conduction is slow it tells us the particular pathway being tested is demyelinated. 

EPs can be very helpful in making a diagnosis of MS; EPs can be used to show sub-clinical or asymptomatic involvement of a particular pathway.

Aim: This study assessed combined EPs as a marker and predictor of the disease course of early MS over 3 years.

Methods: 50 MS'ers in the early phase of RRMS prospectively underwent visual, sensory and motor EPs and disability (EDSS) assessments at baseline and at 6months intervals for 3years. 

Results: EDSS correlated with the sum of the EPs. The change in the sum of the EPs correlated with the change of EDSS

Conclusions: EPs correlate well with clinical disability in cross-sectional and longitudinal comparison in early MS and allow prediction of disease evolution over a period of 3 years.

Epub ahead of printSchlaeger et al. Combined evoked potentials as markers and predictors of disability in early multiple sclerosis. Clin Neurophysiol. 2011 Jul 19.

"Why is this study important? Firstly, it confirms that EPs can be useful in the diagnosis of MS. More importantly, however, this study shows that EPs may be suitable as a marker of remyelination. If for example you have a delayed visual EP, for example instead of conduction at 100 milliseconds your left optic nerve conducts at 120milliseconds, an effective remyelination therapy would have to reduce this delay."

"EPs will almost certainly be used to assess remyelination thearpies."

"Do you know what the clinical effects of delayed conduction speed in an the visual pathway?"

Additional reading: evoked potential

Monday, 25 July 2011

Do you have a problem with walking?

This review article highlights another big problem in MS; problems with gait or walking.

Gait problems in MS'ers is characterised by reduced walking speed, walking endurance, step length, cadence (how smooth your gait is) and joint motion, as well as increased energy requirements of walking and increased variability of gait.

Standardised clinical, timed, and patient-based measures can identify MS'ers with gait problems. 

Observational gait analysis, instrumented walkways, or 3D gait analysis can help determine which problem underlie gait dysfunction to help direct effective treatments. 

Exercise may ameliorate some or all types of gait dysfunction.

Gait dysfunction due to weakness may be helped by orthoses or functional electrical stimulation. 

Gait dysfunction due to spasticity may be relieved by oral, intrathecal, or intramuscular medications targeting spasticity. 

Assistive devices and balance training may reduce gait dysfunction from imbalance. 

The use of dalfampridine or fampridine may increase walking speed in selected MS'ers where this is a problem.

"This article highlights another problem MS'ers have as a result of becoming disabled and discusses ways to assess and manage the gait problems."

Are you having falls?

Aims: This study investigated the incidence, associated factors and health care provider response to falls in 474 MS'ers.
Methods: The study was done via a postal survey questionnaire 

Results: A total of 265 (58.2%) MS'ers reported one or more falls in the previous 6 months. 
58.5% of falls resulted in injuries. Tripping or slipping while walking accounted for 48% of falls. 

The following factors increased the risk of falls:
  • Use of a cane or walker by a factor of 2.6
  • Annual income of less $25,000 by a factor of 1.85
  • balance problems by a factor of 1.28
  • leg weakness by a factor of 1.26 
Only 51% of those who fell (135/265) reported to speaking to their health care provider about their falls. Recommended management strategies from their health care provider to reduce falls included: 
  • safety strategies (53.2%)
  • use of gait assistive devices (42.1%)
  • exercise/balance training (22.2%)
  • home modifications (16.6%)
Conclusions: Factors associated with falls in MS'ers are similar to those in other populations with neurological diseases. Despite the high incidence of falls, fewer than 50% of MS'ers receive information about prevention of falls from their health care providers (neurologists, clinical nurse specialists, general practitioners).

"Again this article highlights a neglected problem in MS'ers; falls. Worryingly it appears as if there is a disconnect between the neurologists and the problems their patients are having."

"If they don't ask, which they should, it is very important that if you are having falls or near falls that you let your neurological team know about it. There is a lot of simple things that can be done to prevent falls and reduce the risk of injuries associated with them."