Thursday, 31 January 2013

Research: excerise and MS

Asano et ak. Exercise barriers and preferences among women and men with multiple sclerosis. Disabil Rehabil. 2013 Mar;35(5):353-61. doi: 10.3109/09638288.2012.742574.

Purpose: The primary objective of this study was to estimate the extent to which women and men with MS present different exercise barriers. The secondary objective was to estimate the extent to which women and men with MS present different perceived-health, depressive symptoms, and current exercise routines or preferences. 

Methods: This was a cross sectional survey. 

Results: 417 people with MS completed a survey of exercise barriers and current exercise routines, perceived-health and depressive symptoms. The top three exercise barriers were: too tired; impairment; and lack of time, regardless of their gender. Regardless of their gender, three times/week and 60 min/session was identified as the most common current exercise structure among physically active participants. The top three currently preferred exercise by men included walking, strengthening/weights and flexibility/stretch exercise. Women reported the same three exercises but flexibility/stretch exercise were slightly more popular than other exercise. Similarities in perceived health status and depressive symptoms were seen between women and men; expect more men were diagnosed with progressive MS (20% higher) than women, leading to a higher rate of men reporting problems with mobility. 

Conclusion: Women and men with MS differed very little on exercise barriers and current exercise routines, perceived health and depressive symptoms. Even though MS is generally considered a woman's disease, this study did not find a strong need to develop gender specific exercise or physical activity interventions for this population.

 

Post on excerise you can read the conclusions!

Brain atrophy: what to do about it?

#MSBlog: Should we be measuring brain atrophy in routine clinical practice?

"I was asked by a colleague in Porto last week whether or not I let the presence or absence of brain atrophy on MRI affect my clinical decision making about DMTs and treatment? I had to think about the question and haven't stopped thinking about it since. The first problem is that our neuroradiologists don't routinely report brain atrophy, unless it is gross atrophy, i.e. easy to see with the naked eye. Although we know that brain atrophy occurs early in the disease course it is often very subtle and difficult to assess with the naked eye; it has to be assessed using post-acquisition data processing tools. In other words the neuroradiologist has to arrange for the images to be analysed off-line for atrophy and to then compare the results with a previous scans or to a normative data set. At the moment brain atrophy measurements are not a routine in our hospital, although we do collect the correct MRI sequences to measure atrophy."

"The brain atrophy discussion is timely, particularly in view of the recent poll result on this blog in relation to it being used as an outcome to monitor MS."


The generate discussion we came up with the following scenarios:

Scenario 1 - in a recently diagnosed person with MS with active MS has a low or moderate lesion load, would the presence of brain atrophy at baseline push you towards a more aggressive therapy, i.e. a drug that affects brain atrophy, or would you be comfortable with that person choosing interferon-beta or glatiramer acetate?

Scenario 2: A person with established MS who has been on an injectable 1st-line therapy for several years, with no relapses or focal MRI activity, but has evidence of ongoing brain atrophy above what you would expect for their age, would you change them to a DMT that has been shown to have an effect on brain atrophy?

"What these scenarios are testing is the concept of whether or not we should be incorporating brain atrophy measurements into routine MS clinical practice and whether or we should be incorporating brain atrophy into our definition of NEDA (no-evidence of detectable disease-activity). I suspect this may be premature, but I see no reason why we shouldn't start a debate on the issue."

"What does brain atrophy mean for you as someone with MS? Brain atrophy could mean a lot of things. In general it probably implies ongoing loss of axons and neurones. Brain atrophy cannot be a good thing and there is data that associates it with a poor prognosis."

Fisher E, Lee JC, Nakamura K, Rudick RA. Gray matter atrophy in multiple sclerosis: a longitudinal study. Ann Neurol. 2008 Sep;64(3):255-65. doi: 10.1002/ana.21436.

OBJECTIVE: To determine gray matter (GM) atrophy rates in MSers at all stages of disease, and to identify predictors and clinical correlates of GM atrophy.

METHODS: MSers and healthy control subjects were observed over 4 years with standardized magnetic resonance imaging (MRI) and neurological examinations. Whole-brain, GM, and white matter atrophy rates were calculated. Subjects were categorized by disease status and disability progression to determine the clinical significance of atrophy. MRI predictors of atrophy were determined through multiple regression.

RESULTS: Subjects included 17 healthy control subjects, 7 subjects with clinically isolated syndromes, 36 MSers with relapsing-remitting MS (RRMS), and 27 MSers with secondary progressive MS (SPMS). Expressed as fold increase from control subjects, GM atrophy rate increased with disease stage, from 3.4-fold normal in CISers converting to RRMS to 14-fold normal in SPMS. In contrast, white matter atrophy rates were constant across all MS disease stages at approximately 3-fold normal. GM atrophy correlated with disability. MRI measures of focal and diffuse tissue damage accounted for 62% of the variance in GM atrophy in RRMS, but there were no significant predictors of GM atrophy in SPMS.

INTERPRETATION: Gray matter tissue damage dominates the pathological process as MS progresses, and underlies neurological disabillity. Imaging correlates of gray matter atrophy indicate that mechanisms differ in RRMS and SPMS. These findings demonstrate the clinical relevance of gray matter atrophy in MS, and underscore the need to understand its causes.

"The following is a short survey to assess whether or not brain atrophy is being measured and discussed in routine MS practice. If you feel up to it I would appreciate it if you could answer the poll."



CoI: multiple

Other posts of interest:


26 Nov 2012
Poll results: outcome measures and brain atrophy. "The headline result is that MSers rate a delay in disease progression the most important outcome measures in relation to DMTs." "The problem with disability progression in ...
17 Nov 2012
"Data from several emerging DMTs now supports the natural history studies and the observation that there is a disconnect between relapses and disease progression and importantly an impact on brain atrophy. We have ...

29 Nov 2011
CONCLUSIONS: Serial magnetic resonance imaging revealed a low 2-year rate of brain atrophy in MS'ers with clinically benign MS, suggesting a less prominent degenerative component in its pathogenesis than in patients ...
23 Nov 2012
BACKGROUND: Brain size, white matter hyperintensity, and the development of brain atrophy are known to be highly heritable. The decrease of brain volume starts from the very onset of MS and is 10-fold compared with ...
21 Nov 2012
More relapses were associated with poorer recovery of neurological function and accelerated brain atrophy. CONCLUSIONS: Neurological impairment is more permanent, brain atrophy is accelerated and focal inflammatory ...
02 Nov 2012
Background: Cognitive dysfunction affects half of MSers. Although brain atrophy generally yields the most robust MRI correlations with cognition, significant variance in cognition between individual MSers remains unexplained ...

20 Nov 2012
Voxel-based analyses allow detection of regional atrophy throughout the brain and, therefore, may be sensitive to regional atrophy in CIS patients, and these changes may correspond with clinical disability. METHODS: This ...
09 Mar 2012
The relationship between inflammatory activity and brain atrophy in natalizumab treated patients.Eur J Radiol. 2012 Mar 3. [Epub ahead of print] OBJECTIVE: To assess the evolution of brain atrophy and its relationship with ...
31 May 2012
BACKGROUND: Brain atrophy (shrinkage) is a well-accepted imaging biomarker of multiple sclerosis (MS) that partially correlates with both physical disability and cognitive impairment. METHODOLOGY/PRINCIPAL ...
08 Jan 2012
In vivo scanning permitted us to evaluate brain structure volumes in individual animals over time and we observed that though brain atrophy progressed differently in each individual animal, all mice with EAE demonstrated ...

20 Mar 2012
Research: Brain Shrinkage. Riccitelli et al. Mapping regional grey and white matter atrophy in relapsing-remitting multiple sclerosis.Mult Scler. 2012 Mar 15. [Epub ahead of print] Objective: We aimed to investigate the regional ...

02 May 2011
The following diagram summarises the MRI data published on the impact of Fingolimod on brain atrophy over 2 years. Please see: Kappos et al. N Engl J Med. 2010 Feb 4;362(5):387-401. COI: Please note my previous COI ...
11 Oct 2012
Objectives: To assess whether high dose simvastatin can slow the rate of whole brain atrophy, and/or disability in secondary progressive multiple sclerosis SPMS. Methods: In a double-blind, placebo-controlled phase II trial, ...
18 Jun 2012
Methods: In 39 multiple sclerosis patients the area of corpus callosum in the sagittal plane, T(2) and T(1) lesion volumes, brain parenchymal fraction and brain atrophy were determined at baseline and 1 year after treatment ...
18 May 2012
Consistent with previous studies, associations were found between neuropsychological scores, and global brain atrophy and T2-lesion volumes (MS lesion volume). Critically, significant associations were found between ...

Wednesday, 30 January 2013

CCSVI Research: Now Pigs! Should we save them for bacon?

EpubHabib et al. MR imaging of the yucatan pig head and neck vasculature. J Magn Reson Imaging. 2013 Jan 24. doi: 10.1002/jmri.24003.
 

PURPOSE: To evaluate the cerebral venous drainage system of the swine as a probable model to test whether extracranial venous abnormalities may play a role in neurodegenerative diseases as reported recently in multiple sclerosis.

MATERIALS AND METHODS: Three Yucatan micropigs, 5 to 7 months old, were scanned with a comprehensive MRI protocol at 3 Tesla. The vascular anatomy of the head and neck was imaged using conventional and angiographic MR sequences. Phase-contrast MR images were collected at multiple levels of the neck and intracranial space to monitor flow.


RESULTS: Three large cervical veins were observed; the external jugular vein draining the olfactory and gustatory tissues; the internal jugular vein (IJV) draining the cavernous sinus as well as surrounding soft tissues in the neck; and the ventral vertebral venous plexus (VVVP) surrounding the dural sac and paraspinal region. The majority of the cerebral blood flow in the pig appears to drain through the VVVP. Flow through the IJV comprised a nondominant component. Anastamoses were observed connecting the major veins of the neck bilaterally.


CONCLUSION: The dominance of outflow from the brain to the VVVP may be analogous to the typical dominance of the IJVs in humans in the supine position.




First we had mice.....next pigs for animal experiments? Do we need research in this area?, if so should we study animals? or should we concentrate on humans?

Given the recent Italian study on the lack of good indications for efficacy of venoplasty maybe we should Save the Pigs. 

I suspect their use in food will be far more useful.

CCSVI treatment: no major effect

#MSBlog: Venoplasty for CCSVI appears not to work! Do we need more data?

Epub: Ghezzi et al; The MS Study Group-Italian Society of Neurology. Endovascular treatment of CCSVI in patients with multiple sclerosis: clinical outcome of 462 cases. Neurol Sci. 2013 Jan 25.

Background: Although it is still debated whether chronic cerebro-spinal venous insufficiency (CCSVI) plays a role in MS development, many patients underwent endovascular treatment (ET) of CCSVI. 


Objective: The objective of the study is to evaluate the outcome and safety of ET in Italian MSers. 

Methods: Italian MS centers that are part of the Italian MS Study Group were all invited to participate to this retrospective study. A structured questionnaire was used to collect detailed clinical data before and after the ET. Data from 462 patients were collected in 33 centers. 

Results: ET consisted of balloon dilatation (93 % of cases) or stent application. The mean follow-up duration after ET was 31 weeks. Mean EDSS remained unchanged after ET (5.2 vs. 4.9), 144 relapses occurred in 98/462 cases (21 %), mainly in RR-MS MSers. Fifteen severe adverse events were recorded in 3.2 % of cases. 

Conclusion: Given the risk of severe adverse events and the lack of objective beneficial effects, our findings confirm that at present ET should not be recommended to patients with MS.



"The results of this study are self-explanatory and mirrors our experience with the few MSers from our centre who have had treatment, typically abroad. The results are clear; it is no miracle treatment. What we also need is some symptomatic outcome data and an economic analysis." 

"Whilst we are waiting for the results of prospective blinded trials we do not recommend that any MSer have this procedure outside of a clinical trial protocol. In addition, MSers should not be paying to have the procedure either."

Other posts on CCSVI on this blog:

28 Jan 2013
Chronic cerebro-spinal venous insufficiency (CCSVI) has been proposed as a "congenital malformation" implicated in the pathogenesis of multiple sclerosis (MS). However, numerous studies failed to confirm its presence in ...
26 Jan 2013
SUBJECTS AND METHODS: We assessed flow variables in the ophthalmic artery, central retinal artery, and central retinal vein and measured the diameter of ONe in 46 relapsing-remitting MS patients and 37 healthy controls ...
09 Jan 2013
Google Trends and CCSVI. "Google Trends as an epidemiological tool to study social phenomena continues to fascinate me! The following is the latest update on CCSVI. What do you think?" ...
29 Dec 2012
OBJECTIVE: Chronic cerebrospinal venous insufficiency (CCSVI) was recently described in patients with multiple sclerosis (MS). The hypothesis of the vascular aetiology provides a new approach in the investigation and ...

24 Nov 2012
CCSVI monthly November. Epub: Simka et al. Internal jugular vein entrapment in a multiple sclerosis patient. Case Rep Surg. 2012;2012:293568. doi: 10.1155/2012/293568. Epub 2012. We describe a multiple sclerosis ...
21 Dec 2012
Complications from CCSVI. #MSBlog: complications from jugular vein stenting in MS. Doležal et al. Serious Complication of Percutaneous Angioplasty with Stent Implantation in so Called "Chronic Cerebrospinal Venous ...
27 Oct 2012
CCSVI Monthly October. As the nonsense arrives, whenever there is a contentious post on CCSVI, to keep some balance for those interested, we will go back to the last Saturday of the month with no comments taken.
08 Oct 2012
Background: Chronic Cerebro-Spinal Venous Insufficiency (CCSVI) has been proposed to be associated with Multiple Sclerosis (MS). Zamboni et al reported significant improvement in neurological outcomes in MS patients ...

27 Oct 2012
CCSVI survey results. BLOG readers are sceptical. The survey results on CCSVI have been interesting. When asking Prof G to the post survey, I would have predicted that if all trials were positive the majority of people would ...
17 Oct 2012
In response to someone's comment re comparing CCSVI to Tysabri or Natalizumab. I have embedded the graph. It is clear the trends are very different; Tysabri/Natalizumab dwarfs that of CCSVI. In epidemiological terms we ...
06 Oct 2012
Introduction. An alternative etiology of MS named chronic cerebrospinal venous insufficiency (CCSVI) has recently been proposed by Zamboni et al. By venous ultrasound (US) and venography they found venous stenosis ...
08 Oct 2012
Zamboni P, Bertolotto A, Boldrini P, Cenni P, D'Alessandro R, D'Amico R, Del Sette M, Galeotti R, Galimberti S, Liberati A, Massacesi L, Papini D, Salvi F, Simi S, Stella A, Tesio L, Valsecchi MG, Filippini G. Efficacy and safety ...

17 Oct 2012
Google trends: CCSVI a waning social phenomenon. "These latest Google trend figures are reassuring and continue downward. I sincerely hope the off-license use of procedures to treat CCSVI are waning as fast." "CCSVI .
14 Oct 2012
This is one of the trials by protagonists of CCSVI. It appears that the Canadian Government has pledged to do a trial of 100 MSers, but this trial is being led by a CCSVI sceptic. Will the results be definitive. If positive, will we ...
8 minutes ago
CCSVI Research: Now Pigs?-Save the Pigs! Habib CA, Utriainen D, Peduzzi-Nelson J, Dawe E, Mattei J, Latif Z, Casey K, Haacke EM MR imaging of the yucatan pig head and neck vasculature. J Magn Reson Imaging.
16 Sep 2012
Research: CCSVI papers back after the Summer holiday. After 2 months of essentially nothing in terms of papers published nothing, now the periodical "Neurological Research" gives the journal over to CCSVI topics. Morovic ...

12 Sep 2012
Only one subject, a control, satisfied the Zamboni definition of CCSVI; however, 19 patients and 13 controls had abnormalities as defined by Zamboni, the difference largely caused by a higher prevalence in patients of internal ...
25 Aug 2012
This study looks at MSers and finds some with criteria compatible with the theory of CCSVI and some that do not. Likewise there are healthy individuals with CCSVI and some without. Where there is ultrasonic CCSVI there can ...
28 Aug 2012
The graph below compares the search volume index of alemtuzumab to CCSVI. To make the graphs readable I had to do a log conversion of the search volumes, which are given by week. To do the log conversion I simply ...
10 Aug 2012
RESULTS: CCSVI was present in 28 (18.9%) of the MS patients, in 2 (10%) of CIS patients, in 11 (6.4%) of the controls, and in 2 (5%) of the OND patients. A significant association between MS and CCSVI was found with an ...

22 Jul 2012
I sincerely hope the off-license use of procedures to treat CCSVI are waning as fast." "CCSVI remains predominantly an Italian and Canadian phenomenon. The UK and USA don't make the top 10." "Once the dust has settled ...
31 Aug 2012
Research: Clinical Improvement after Venoplasty of CCSVI. Epub: Hubbard D et al. Clinical Improvement after Extracranial Venoplasty in Multiple Sclerosis. Journal of Vascular and Interventional Radiology Epub online 28 ...
28 Jul 2012
CCSVI Monthly July. Yet again nothing! Do you think it is time to wind-up this monthly post? Reactions: Posted by MouseDoctor at 02:00 · Email ThisBlogThis!Share to TwitterShare to Facebook · Newer Post Older Post Home ...
11 May 2012
FDA Safety Communication CCSVI. FDA Safety Communication: Chronic Cerebrospinal Venous Insufficiency Treatment in Multiple Sclerosis Patients The FDA today issued a safety communication about CCSVI ...

31 May 2012
BACKGROUND AND PURPOSE: CCSVI has been reported to occur at high frequency in MS. Its significance in relation to MR imaging parameters also needs to be determined, both in patients with MS and HCs. Therefore ...
16 Jun 2012
Twenty-nine patients with clinically definite relapsing-remitting MS underwent percutaneous transluminal angioplasty for CCSVI, outside a clinical relapse. All the patients were regularly observed over at least two years before ...
30 Jun 2012
Yes. beside the couple of offerings that Prof G has served up there is nothing to report this month. Maybe people just want to see what the clinical studies show. Maybe the scientific interest is waning. Maybe it is time to kick ...
02 Jun 2012
To systematically review the ultrasonographic criteria proposed for the diagnosis of chronic cerebrospinal venous insufficiency (CCSVI). The authors analyzed the five ultrasonographic criteria, four extracranial and one ...

11 Nov 2009
Recently, evidence has emerged – and widely publicised – that a condition called “chronic cerebro-spinal venous insufficiency (CCSVI)” may play a role in the pathogenesis of multiple sclerosis (MS). Paolo Zamboni ...
17 May 2012
It's amazed me from the beginning that even skeptics of the theory of ccsvi agree to the need for clinical trials when the crucial point of the entire situation is that not long ago shared total obscurity along with the thousands of ...
10 Jun 2012
CCSVI: News of Negative trial. You may be have heard that trial data is emerging from Canada..in the press (ugh this is not where we should be hearing about this, science using the media for publicity is normally bad ...
21 Mar 2012
Search volume index. Region, Ranking. Italy, 1. Canada, 0.755. Serbia, 0.58. Croatia, 0.35. Norway, 0.275. Denmark, 0.245. Netherlands, 0.205. Ireland, 0.19. Finland, 0.155. Sweden, 0.135. City, Ranking. Cagliari (Italy), 1 ...

4th MS Research Day - 2nd Febuary 2013

If you can't make the research day on Saturday you can follow the event on Twitter. We will be using the following hashtag(#): #msresearchday.


For those of you new to Twitter:

YOU CANNOT “FOLLOW” A HASHTAG DIRECTLY THROUGH YOUR TWITTER ACCOUNT. This is generally a confusing point for those of you who are new to Twitter and hashtags (#). A hashtag is not a source of tweets; it is simply a way of labelling or tagging tweets so they can be easily pulled together as a group. Hashtagging is the mechanism used for trending.

TWITTER SEARCH: An easy way to track hashtags is through your web browser or twitter App: go to Twitter Search. Search for a hashtag you want to track. Include the “#” in your search query, for example #MSBlog. Keep the page open in your browser and refresh it to see the latest results. 


TRACKING TOOL: You can also use a third-party tool for using and monitoring Twitter. The one I use is Tweetdeck; there are great Tweetdeck and Chrome Apps for your smart phone and chrome browser. 

Are you an Ostrich?

We have invented some fun terms on the blog like a Shania
Today we have the "Ostrich". This is someone, who is stuck in the world of Dogma. They just stick their head in the ground and ignore the real world.


Science is full of Ostriches, and they talk to a mirror everyday to say how great they.......eventually they believe themselves.


They ostrich convinces the real world to follow their world view like lemmings, such that they conform and do everything to conform to the the dogma without question. They spawn a new generation of Ostriches.



We scientists are very dogmatic, you don't need to be an Ostrich. 

Research Early MS lesion not around Blood Vessels

Singh S, Metz I, Amor S, van der Valk P, Stadelmann C, Brück W. Microglial nodules in early multiple sclerosis white matter are associated with degenerating axons. Acta Neuropathol. 2013 Jan 26. [Epub ahead of print]

Microglial nodules in the normal-appearing white matter have been suggested as the earliest stage(s) of multiple sclerosis (MS) lesion formation. Such nodules are characterized by an absence of leucocyte infiltration, astrogliosis or demyelination, and may develop into active demyelinating MS lesions. Although the aetiology of MS is still not known, inflammation and autoimmunity are considered to be the central components of this disease. Previous studies provide evidence that Wallerian degeneration, occurring as a consequence of structural damage in MS lesions, might be responsible for observed pathological abnormalities in connected normal-appearing white matter. As innate immune cells, microglia/macrophages are the first to react to even minor pathological changes in the CNS. Biopsy tissue from 27 MS patients and autopsy and biopsy tissue from 22 normal and pathological controls were analyzed to determine the incidence of microglial nodules. We assessed MS periplaque white matter tissue from early disease stages to determine whether microglial nodules are associated with altered axons. With immunohistochemical methods, the spatial relation of the two phenomena was visualized using HLA-DR antibody for MHC II expression by activated microglia/macrophages and by applying antibodies against damaged axons, i.e., SMI32 (non-phosphorylated neurofilaments) and amyloid precursor protein as well as neuropeptide Y receptor Y1, which marks axons undergoing Wallerian degeneration. Our data demonstrate that the occurrence of microglial nodules is not specific to MS and is associated with degenerating as well as damaged axons in early MS. In addition, we show that early MS microglial nodules exhibit both pro- and anti-inflammatory phenotypes.



This study looks at the white matter around the lesion (perplaque) and finds evidence of microglial cell activation and link this to nerve damage. This can be seen by looking for blebs of amyloid precursor protein, which is shuttled down nerves and blebs out like a water droplet where the nerve is cut. Then below the cut the next degenerates by a process called Wallerian degeneration. This type of early lesion has been reported before on the blog and is subject to much debate about what it tells us about the cause of MS. This lesion is associated with nerve damage rathher than oligodendrocyte damage. What comes first the microglial activation and then the nerve damage or the do they become activated because of nerve damage?

However, before you start bleating that this is yet more evidence against the autoimmune hypothesis, think again. It can and already has been incorporated into an autoimmune hypothesis by the authors. You can hear about this at the research day when DoctorLove presents the early MS lesion. You could of course make the case that this argues against the autoimmune hypothesis as there is not a T cell in sight. Will the Ostriches need to change their world view? However, why would you expect T cells to be central to lesions of the nerve, as they seldom express MHC antigens that are vital for T cell recognition, activation and function? 

Importantly if these are the early MS lesions, it does argue against a vascular cause of MS as these nodules are not centred around blood vessels!!!.


Are they independent of demyelination? or is this just nerurodegeneration? Do they reflect the consequences of lesional events occurring elsewhere in the nerve some distance from the nodule? Is this what drives immune attacks or is this what drives progressive MS. The MSers studied with largely be progressive MSers. As these are not specific to MS are these part of an ageing process, that is exaggerated in progressive MS?

What a lot of questions, why not ask DoctorLove them at the Research Day on Saturday. If you can't make it, then why not ask them here and maybe someone can ask the question for you. The talks are being filmed and will be put on the blog.


Sorry the tickets are all gone but email us for returns.

If you can not make it, sorry to hear that but please, please let us know if you can't make it, such that we can allocate your place/lunch to someone else.