Monday, 30 September 2013

White knights back from their hols recharged

white Knight Smiling..Makes a change

Version 4 of ECTRIMS brain atrophy infographic

Version 4 brain atrophy infographic; comments please. #MSBlog #MSResearch

"The following is version 4 of my brain volume infographic that I will be using at the blogging session at ECTRIMS. I still have time for changes. Any more recommendations would be appreciated. Thank you."

Imaging the Spinal Cord

Bag AK, Patel BN, Osman S, Roberson GH. Clinico-radiologic profile of spinal cord multiple sclerosis in adults. Neuroradiol J. 2011;24(4):511-8.

MRI is extremely useful for the assessment of initial disease burden and to identify the dissemination of the multiple sclerosis (MS) in time and space. The spinal cord is frequently involved in this disease and there has been increasing emphasis of the spinal imaging in making clinical decision in the management of MS. 

We undertook a retrospective study of patients with diagnosed MS: 1) to identify radiologic pattern of spinal cord involvement in MS and 2) to correlate radiologic findings with clinical presentation. 

We reviewed radiologic records from 2004 to 2009 of patients with abnormal T2 signal intensity of the spinal cord with radiologic concern of demyelinating disease. Patients in this cohort who met the Revised McDonald MS Diagnostic Criteria (search blog for details) were included in this study. 166 patients were included in the study. There was preference for cervical spinal cord particularly posterior (back bit) aspect of the spinal cord. Enhancement of the lesions was rare (4.1%). Mean lesion length was 18.2 mm. The average number of lesions per patient was 2.04. 
Sensory (feelings) symptoms were predominating and most of the patients had relapsing-remitting course. Patients with sensory symptoms, bladder and bowel involvement and motor (movement) symptoms had almost equally distributed lesions among anterior (front bit), posterior and central spinal cord. However, all of the patients presented with posterior column signs and gait abnormality had involvement of the posterior spinal cord. Radiologic manifestation of spinal cord MS is extremely variable and can involve the entire length of the spinal cord. Clinical symptoms may or may not be associated with radiologic presentation of the lesions.
Maybe MRI can't spot spinal cord lesions but they are very important in mobility. Dr.Klaus would agree that lesions are concentrated in the cervical spinal cord. 

Trying to Distinguish from NMO

Huh SY, Min JH, Kim W, Kim SH, Kim HJ, Kim BJ, Kim BJ, Lee KH.The usefulness of brain MRI at onset in the differentiation of multiple sclerosis and seropositive neuromyelitis optica spectrum disorders.
Mult Scler. 2013 Sep  [Epub ahead of print]

BACKGROUND:Although neuromyelitis optica (NMO) is a central nervous system (CNS) autoimmune disease distinct from multiple sclerosis (MS). NMO and NMO spectrum disorder (NMOSD) sometimes show asymptomatic lesions on brain magnetic resonance imaging (MRI) at onset, and even present with symptomatic brain involvement.
OBJECTIVES:We investigated whether brain MRI at onset can be helpful for the differentiation of MS and NMOSD.
METHODS:We retrospectively analyzed initial brain MRIs, performed within three months of onset, in patients with MS (n = 51) and anti-aquaporin4-antibody-positive patients with NMOSD (n = 67).
RESULTS: NMOSD patients met the Paty (37%) and Barkhof (13%) criteria, and the criteria of the European Magnetic Imaging in MS (MAGNIMS) study group (9%), for MS. Ovoid lesions perpendicular to the lateral ventricle, isolated juxtacortical lesions in U-fibers and isolated ovoid/round cortical lesions were found only in MS patients, whereas longitudinal corticospinal tract lesions, extensive hemispheric lesions, periependymal lesions surrounding the lateral ventricle and cervicomedullary lesions were found only in NMOSD patients.
CONCLUSIONS: Our study suggests that it is difficult to differentiate MS from NMOSD by the fulfillment of the MRI criteria for MS on brain MRI at onset; however, the characteristic morphology of brain lesions is highly useful for the early differentiation of the two disorders.

NMO was originally called Devic's MS. This is characterized by lesions of the spinal cord and optic nerve, abit like EAE. More recently this has been shown to be associated with the production of antibodies against a water channel called aquaporin 4 and a few myelin proteins. It is important to distinguish this from more classical MS as the treatments are different. This study uses MRI and it cannot pigeon hole people into one or other of the diseases but it can aid in the decision making 

Fingolimod verses injectable 1st-line therapies

Dear doctor which is the most effective DMT? #MSBlog #MSResearch

"MSers are always asking me which is the best, most effective MS drug? It is not that simple to answer because we don't have many head-2-head studies that aren't biased. For example, even in the TRANSFORMS study that compared fingolimod to interferon-beta (Avonex) study subjects who were enrolled had to have active disease; i.e. they had to have had at least one documented relapse during the previous year or at least two documented relapses during the previous 2 years. As a large proportion (~50%) of them had failed, or had a suboptimal response, to prior interferon therapy the comparison was largely between Fingolimod and interferon failures. We therefore have to rely on so called 'real-life" data from registries and from insurance companies. Although these data sets are not ideal the give us a rough idea of comparative efficacy. This study below shows us that fingolinod is more effective than the injectable first-line therapies. So if you are on an injectable what should you do? This will depend on what country you live as treatment guidelines often dictate how these drugs are prescribed. In the UK you can only go onto fingolimod if you have failed interferon beta; you can't start fingolimod as a first-line therapy, nor can you switch from glatiramer acetate, or natalizumab, if you have not failed interferon-beta in the past. This is part of what I call the MS DMTs doughnut, that urgently needs filling."

"Let's say for argument sake that access to fingolimod is not a problem should you switch? This will depends on how well you are doing on IFNbeta or GA. If you are having relapses, or your MRI shows sub-clinical relapses, then the case for escalation therapy is relatively simple. If you have no evidence of disease activity (NEDA) then other factors will be more influential at an individual level; for example, injection site tolerability, other side effects, contra-indications, the risks of the more effective agents and other lifestyle issues. So there is no simple answer to the question of which is the more effective agent. This why you need to get yourself informed and discuss things in detail with your MS nurse and neurologist."

Epub: Bergvall et al. Comparative effectiveness of fingolimod versus interferons or glatiramer acetate for relapse rates in multiple sclerosis: a retrospective US claims database analysis. Curr Med Res Opin. 2013 Sep.

Objective: Disease-modifying therapies, such as fingolimod, interferon (IFN) and glatiramer acetate (GA), have differing effects on relapse rates in MSers, but little is known about the real-world differences in relapse rates with these treatments. This retrospective study assessed relapse rates in patients with active MS initiating fingolimod, IFN or GA therapy in a real-world setting.
Methods: Using administrative claims data from the US PharMetrics Plus database, they identified previously treated and untreated MSers who initiated fingolimod, IFN or GA treatment between 1 October 2010 and 31 March 2011 and had experienced a relapse in the previous year. A claims-based algorithm was used to identify relapses over the persistence period in MSers with 540 days of post-index continuous enrollment. A logistic regression model assessed the probability of having at least one relapse and a generalized linear model estimated differences in annualized relapse rates (ARRs).

Results: The study enrolled 525 MSers (fingolimod, n = 128; combined IFN/GA cohort, n = 397) of the 31, 041 initially identified. Similar findings for fingolimod and IFN/GA were observed for the unadjusted proportion of MSers experiencing relapses (31.3% vs. 34.0%, respectively; p = 0.5653) and ARRs (0.50 vs. 0.55, respectively) while persistent to treatment. After adjusting for baseline differences, fingolimod was associated with a 52% reduction in the probability of having a relapse (odds ratio, 0.48; 95% confidence interval (CI), 0.28-0.84; p = 0.0097) and a 50% reduction in ARR (rate ratio, 0.50; 95% CI, 0.34-0.75; p = 0.0006) compared with IFN/GA.

Limitations: Identification of relapses is based on the claims in the database rather than on a clinical assessment.

Conclusions: In a real-world setting, fingolimod was shown to be associated with significantly lower relapse rates than IFN/GA in MSers who had a history of relapses.

CoI: multiple

Sunday, 29 September 2013

CCSVI is not a causal factor in the pathogenesis of multiple sclerosis.

#MSResearch: CSVI not causal or MS

Chambers B, Chambers J, Churilov L, Cameron H, Macdonell R. Internal jugular and vertebral vein volume flow in patients with clinically isolated syndrome or mild multiple sclerosis and healthy controls: results from a prospective sonographer-blinded study. Phlebology. 2013 Sep . [Epub ahead of print]

Objectives & Methods: We evaluated internal jugular vein and vertebral vein volume flow using ultrasound, in patients with clinically isolated syndrome or mild multiple sclerosis and controls, to determine whether volume flow was different between the two groups.
Results: In patients and controls, internal jugular vein volume flow increased from superior to inferior segments, consistent with recruitment from collateral veins. Internal jugular vein and vertebral vein volume flow were greater on the right in supine and sitting positions. Internal jugular vein volume flow was higher in the supine posture. Vertebral vein volume flow was higher in the sitting posture. Regression analyses of cube root transformed volume flow data, adjusted for supine/sitting, right/left and internal jugular vein/vertebral vein, revealed no significant difference in volume flow in patients compared to controls.
Conclusions: Our findings further refute the concept of venous obstruction as a causal factor in the pathogenesis of multiple sclerosis. Control volume flow data may provide useful normative reference values.

No need to say more. I forgot to Post Yesterday

Does eczema increase risk of MS....No.

 The aims of this overview are to synthesize the current evidence of published systematic reviews (SRs) on non-allergic comorbidities of atopic eczema (AE). EMBASE and MEDLINE were searched for SRs published from inception to November 2012. SRs were selected independently based on predefined inclusion criteria. Methodological quality of SRs included was assessed by two independent reviewers using the Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) checklist. Nine SRs met all inclusion criteria. Six reviews addressing the association between AE and cancer suggest a decreased risk of glioma, meningioma, and acute lymphoblastic leukemia in patients with current or previous AE. One SR reported a consistent positive association of AE with attention-deficit hyperactivity disorder (ADHD). Diabetes mellitus type 1 and multiple sclerosis (MS) were not significantly related to AE in reviews based on cross-sectional and case-control studies. Patients with AE appear to be at decreased risk of brain tumors. The relationship of AE with Th1- and Th17-mediated (auto-)inflammatory conditions such as diabetes mellitus type 1 and MS should be clarified in prospective observational studies. Children with AE are at increased risk of ADHD. SRs on the risk of depression and Th17-mediated disorders such as inflammatory bowel disease of patients with AE are missing.

Karimi P, Modarresi SZ, Sahraian MA, Shokouhi Shoormasti R, Mahlooji M, Kazemnejad A, Pourpak Z.The relation of multiple sclerosis with allergy and atopy: a case control study. Iran J Allergy Asthma Immunol. 2013; 12(2):182-9.

Multiple Sclerosis (MS) and Allergy are believed to up regulate T helper cell type 1 (Th1) and T helper cell type 2 (Th2) responses, respectively. It has been shown that disequilibrium in the ratio of Th1/Th2 activities may increase frequency of one disease and decrease the frequency of the other. The aim of this study was to investigate the relation of MS with allergy and atopy in new diagnosed MS patients. This case-control study was conducted on 40 new diagnosed MS patients and the same number of normal controls. All of the patients were diagnosed (according to McDonald criteria) at most 2 years prior to the study. Demographic data and clinical characteristics of both groups were recorded in a questionnaire. The total IgE and allergen specific IgE in the serum were measured in all the cases. Forty MS patients (female/male: 4.71) with mean age of 30.55±9.5 years and 40 healthy controls entered in this study. History of allergy was observed in 20(50%) of MS patients (including 15 (37.5%) rhinitis, 6 (15%) conjunctivitis, 3 (7.5%) urticaria and eczema, 1 (2.5%) asthma), and 20 (50%) of the controls (including 8 (20%) rhinitis, 4 (10%) conjunctivitis, 7 (17.5%) urticaria and eczema, 1 (2.5%) asthma). The differences between the two groups were not statistically significant. Neither the serum total IgE, nor the frequency of specific IgE against Weed mix, Grass Mix, Tree mix1, Tree mix 2, Dermatophagoides Farinae, Dermatophagoides pteronyssinus and Epidermal and animal proteins mix differed statistically between the two groups. There was also no significant relationship between MS clinical manifestations and allergy prevalence and also between MS and atopy. The results of this study as some other similar studies showed the same prevalence of allergy in MS patients and controls and also demonstrated no relation between MS and atopy.

In the world view of T cell biology, MS and allergies are on the opposite ends of the spectrum. What is thought to be good for MS is bad for allergy and vice versa. I was asked if the risk of eczema and MS are related and as can be seen from these post-there is no direct relationship. Therefore if you have eczema it does not increase you risk of MS. However other conditions like thyroid problems are more associatied

Parkinsons Disease and MS. No increase risk

Nielsen NM, Pasternak B, Stenager E, Koch-Henriksen N, Frisch M. Multiple sclerosis and risk of Parkinson's disease: a Danish nationwide cohort study.Eur J Neurol. 2013 Sep 19. doi: 10.1111/ene.12255. [Epub ahead of print]
BACKGROUND AND PURPOSE:Case reports have observed a co-occurrence of multiple sclerosis (MS) and Parkinson's disease (PD) and it has been hypothesized that MS lesions could affect dopaminergic pathways causing parkinsonism. Our aim was to examine the association between MS and PD in a historically prospective cohort study using Danish nationwide register data.
Multiple sclerosis patients identified in the Multiple Sclerosis Registry were followed for PD from 1977 to 2011 in the National Patient Register. As measures of relative risk, ratios of observed to expected incidence rates of first hospitalization for PD amongst persons with MS were used, i.e. standardized incidence ratios (SIRs) with 95% confidence intervals (CIs).
RESULTS:Amongst 15 557 MS patients 26 cases of PD were observed versus 26.51 expected, reflecting no overall increased risk of PD (SIR 0.98, 95% CI 0.67-1.44). Similar estimates were seen for female (SIR 0.99, 95% CI 0.58-1.67) and male MS patients (SIR 0.97, 95% CI 0.55-1.72). Likewise, no increased risk of PD amongst MS patients was observed in a robustness analysis backdating the date of diagnosis of PD by 5 years to account for the time lag between disease onset and first hospital contact with PD (SIR 0.57, 95% CI 0.32-1.00).
Our data do not suggest an increased risk of PD amongst patients with MS.

conclusions say it all

Saturday, 28 September 2013

Re-investigating TNF antagonism likely or not?

Dendrou CA, Bell JI, Fugger L. A clinical conundrum: the detrimental effect of TNF antagonists in multiple sclerosis.Pharmacogenomics. 2013 Sep;14(12):1397-40

Although TNF antagonists are efficacious in treating a range of autoimmune conditions, they exacerbate or even promote multiple sclerosis (MS) - a clinical finding that has been a conundrum for over a decade and has been a source of debate regarding the role of these drugs and of TNF signaling in the development of demyelinating disease. Recent work investigating the functional consequences of MS-associated genetic variation in the gene encoding TNFR1 has demonstrated that genetic risk drives the production of a novel, endogenous TNF antagonist. This mirrors the clinical experience with the drugs and indicates that the net effect of TNF function in MS development is a protective one, warranting a re-evaluation of the studies that have contributed to our understanding of TNF signaling in inflammation, immunoregulation and neuroprotection, to determine how future research can be directed towards targeting this pathway for therapeutic benefit.

Based on previous studies that an MS risk gene causes blockade of TNF it is suggested that TNF has a protective one...This may indeed the case but it may also be context dependent and could be a good or bad thing...Would you risk it to take TNF block, given the rocky history?

Measuring mobility in MSers

Your legs are made for walking. Lose leg function and it correlates with the impact of MS on your life in general. #MSBlog #MSResearch

"Who thought you could relate the social and occupational impact of MS to mobility as determined by the number of steps you take in a single day? So called real-life anchors (unemployment, divorce, assistive device use) resulted in a mean minimal clinically important difference MCID of 2,580 steps/day, which was only 45% of mean score for MS group as a whole. Put in another way MSers who were unemployed, divorced or needed a assistive device took 55% fewer steps on average than the whole MS group. Are you surprised? The question that this study raises is whether or not the regulators will accept steps per day as a surrogate, or indicator, for the impact that MS has on the life of someone with the disease?"

Motl et al. Clinical Importance of Steps Taken per Day among Persons with Multiple Sclerosis. mPLoS One. 2013 Sep;8(9):e73247. 

BACKGROUND: The number of steps taken per day (steps/day) provides a reliable and valid outcome of free-living walking behavior in MSers.

OBJECTIVE: This study examined the clinical meaningfulness of steps/day using the minimal clinically important difference (MCID) value across stages representing the developing impact of MS.

METHODS: This study was a secondary analysis of de-identified data from 15 investigations totalling 786 MSers and 157 healthy controls. All participants provided demographic information and wore an accelerometer or pedometer during the waking hours of a 7-day period. Those with MS further provided real-life, health, and clinical information and completed the Multiple Sclerosis Walking Scale-12 (MSWS-12) and Patient Determined Disease Steps (PDDS) scale. MCID estimates were based on regression analyses and analysis of variance for between group differences.

RESULTS: The mean MCID from self-report scales that capture subtle changes in ambulation (1-point change in PDSS scores and 10-point change in MSWS-12 scores) was 779 steps/day (14% of mean score for MS sample); the mean MCID for clinical/health outcomes (MS type, duration, weight status) was 1,455 steps/day (26% of mean score for MS sample); real-life anchors (unemployment, divorce, assistive device use) resulted in a mean MCID of 2,580 steps/day (45% of mean score for MS sample); and the MCID for the cumulative impact of MS (MS vs. control) was 2,747 steps/day (48% of mean score for MS sample).

CONCLUSION: The change in motion sensor output of ∼800 steps/day appears to represent a lower-bound estimate of clinically meaningful change in free-living walking behavior in interventions of MS.

Headline ECTRIMS. CCSVI is not that effective

#MSResearch #MS Blog CCSVI not that effective

Kipp et al. British Columbia chronic cerebrospinal venous insufficiency (CCSVI) registry: early self-reported benefits are not sustained at follow-up interview. ECTRIMS 2013 Thursday, October 03, 2013, 15:45 - 17:00.

Background: Venoplasty with or without intravascular stents (the “liberation” treatment) has been proposed as a treatment for multiple sclerosis (MS) patients with radiologic findings suggestive of Chronic Cerebrospinal Venous Insufficiency (CCSVI). The purpose of the British Columbia (BC) CCSVI Registry is to gather information on safety and efficacy from MS patients in BC, Canada who have received the “liberation” treatment abroad.

Methods: A standardized telephone survey is used to interview volunteer MS patients up to 4 times - initial, 6-month, 12-month and 24-month follow-up. Participants are asked to rate their general health (GH), fatigue level (FL), mobility (M), exercise level (EL) and procedure rating (PR) on a scale of 5 (1= much better, 2= somewhat better, 3= same, 4= somewhat worse and 5= much worse).

Results: As of April 23, 2013, 76 patients completed the first 2 interviews. Patient-reported outcomes at initial interview (average 15.5 months post-treatment) and 6-month follow-up (average 21.5 months post-treatment) will be presented. 

Conclusions: The majority of participants’ self-reported benefits in general health, fatigue level, mobility and exercise level following CCSVI “liberation” treatment are short term and decline the longer the time period from treatment. Interestingly, while this self perception of impact of the therapy declines over time, this perception is less true when patients are asked to rate the overall procedure (PR). This may reflect psychosocial and interpersonal issues rather than be a true measure of treatment outcome.

This study is to be presented next week at ECTRIMS and proably we should not comment until then but it has slipped out.

This short term benefit has been a consistent feature of reports, but it is not sustained. Therefore as the trials are much longer term the chances of finding a success is reduced. If we look at some of the the placebo effects in some trials, this lasts around three months.

You have been pressing Prof G on his beliefs about this aspect of MS, but if you take a step-back and look at the accumulating data. 

This is the suggestion as far as I read it.

The original idea that there is 100% concordance of CCSVI and MS and that it is causal in MS is not supported. Therefore, the original view was fundamentally flawed.

Arguments that more recent studies can not support this because they are not using the right new methods of detection seem like goalpost shifting and the original view was not based on newer methods of detection.

Where the radiographic markers attributed to CCSVI are found.
  • It does not occurring all MSers.
  • It occurs in non-MSers.
  • However they occur in more MSers than non-MSers
This indicates it is not causal next
  • The markers of CCSVI increase with disease duration and is therefore likely to be a consequence rather than a cause...        
  • Many neurologists are sceptical about the validity of the outcome measure. Non-CCSVI protagonists find no evidence of the condition.
What is the therapeutic effect?

  • People claim remarkable improvements on social media.          
  • Remarkable improvements are not universal and no effect is not uncommon.                                                                             
Therefore if the effect was so obvious it would be easy to detect in small well-controlled studies. Trials would be halted because of the obvious benefit. However so far it appears
  • Short term-benefit from venoplasty may be gained but it is often not sustained. Is it a placebo effect? However, there are many testimonies on the web.

  • Class I evidence or the value of treatment is lacking
  •  One clinical US trial (by CCSVI protagonists) was stopped due to apparent worsening
  • Second trial halted due to lack of interest (this reason is unbelievable)
  •  Three other trials ongoing reporting hopefully Soon.
As CCSVIers are gathering in Canada for a meeting this weekend, I am sure some venom may be mentioned about this site but the data is what it is and this is where the body of evidence is leading us. 

If CCSVI was working I would say great it matters not to me.  I would dust myself down and try to move on. If MS is cured, which I hope it will be,  there are plenty of neurological problems to adapt ones skill set to

If something dramatic changes, we can change our world view but until then, sceptical is the order of the day. 

This is what the weight of data is saying to me, so there you have it. You asked and pushed for opinions and one has now been given, it may be wrong, if it is, I am big enough (literally) to accept this,you may not like it but it is, what it is.

You may have your head in another worldview..but I say "show me the evidence"


Well before the research, I guess you have heard the the US trial on CCSVI by Dr. Gary Siskin has been apparently cancelled, because they could not get enough willing participants from the US, despite the promise of some Health Tourists from Canada.

Were people really unwilling to have the risk of placebo?
Or were people just not sufficiently interested?

Anyway you can debate that amongst yourselves, I am sure all travellers to CCSVI convention in Canada today will be talking about it.

The sad part is there is not answer and so we will these posts so another 1 down 3 to go. 

Zwischenberger BA, Beasley MM, Davenport DL, Xenos ES.Meta-Analysis of the Correlation Between Chronic Cerebrospinal Venous Insufficiency and Multiple Sclerosis.Vasc Endovascular Surg. 2013 Sep 4. [Epub ahead of print]

Purpose: To determine whether a correlation exists between chronic cerebrospinal venous insufficiency (CCSVI) and multiple sclerosis (MS). 

Materials and Methods: A meta-analysis of the current literature was performed to evaluate the frequency of CCSVI, diagnosed by echo color Doppler criteria, in patients with MS and in normal controls. 

Results: In all, 19 studies were identified from January 2005 through February 2013; however, 3 studies were excluded due to duplicate data and 3 additional studies because 0 patients fulfilled CCSVI criteria in both MS and control groups. In order to improve homogeneity, 4 outlier studies were also removed from the analysis. Analysis of the remaining 9 studies demonstrated a significant correlation between CCSVI and MS (odds ratio 1.885, P < .0001) with no significant heterogeneity of the studies (I2 = 18, P = .279). Conclusions: The meta-analysis demonstrated a correlation between CCSVI and MS. However, there was no evidence that CCSVI has a causative role in MS.

So people with MS can have features consistent with CCSVI it is not causal. I guess we now know this, so the original hypothesis I was likely to be incorrect.

Comi G, Battaglia M, Bertolotto A, Sette MD, Ghezzi A, Malferrari G, Salvetti M, Sormani M, Tesio L, Stolz E, Zaratin P, Mancardi G; the CoSMo Collaborative Study Group.Observational case-control study of the prevalence of chronic cerebrospinal venous insufficiency inmultiple sclerosis: results from the CoSMo study. Mult Scler. 2013 Sep . [Epub ahead of print]

BACKGROUND:Chronic cerebrospinal venous insufficiency (CCSVI) has been proposed as a possible cause of MS.
OBJECTIVES:The CoSMo study evaluated the association between CCSVI and MS.
METHODS:The primary end-point of this multicentric, case-control study was to compare the prevalence of CCSVI between patients with MS, patients with other neurodegenerative diseases (ONDs) and healthy controls (HCs). Colour-coded duplex sonography was performed by a sonologist and the images were sent to one of three central sonologists for a second reading. Agreement between local and central sonologists or, in case of disagreement, the predominant judgment among the three central readers, was required for a diagnosis of CCSVI. All readings, data collection and analysis were blinded.
RESULTS:The study involved 35 MS centers across Italy and included 1874 subjects aged 18-55. 1767 (94%) were evaluable: 1165 MS patients, 226 patients with ONDs and 376 HCs. CCSVI prevalence was 3.26%, 3.10% and 2.13% for the MS, OND and HC groups, respectively. No significant difference in CCSVI prevalence was found amongst the three cohorts (MS versus HC, OR = 1.55, 95%CI = 0.72-3.36, p = 0.30; OND versus HC, OR = 1.47, 95%CI = 0.53-4.11, p = 0.46; MS versus OND, OR = 1.05, 95%CI = 0.47-2.39, p = 0.99). High negative and low positive agreement was found between the local and centralized readers.
CONCLUSIONS: CCSVI is not associated with MS.

We have reported on this before, the conclusions say it all. 

Friday, 27 September 2013



12.30 for 13.00-14.00 (CET, Copenhagen), 2 October.


MS Roadshow - Basildon, 30th Sept 2013

Annual MS Roadshow season. #MSBlog #MSResearch

"We group start our annual round of MS Roadshows this weekend and next week. MouseDoctor will be speaking in South London and Prof Gold and I at the MS Chilterns Centre on Saturday. We then go to Basildon on Monday night, followed by Southend the following Monday. If this is the first you have heard of these events please contact your local MS nurse specialists for more details. The purpose of thee regional meetings is for us to meet MSers and  to update you on our research and to ask you to help us. Most of our research needs volunteers."

Time to Improve Standards in Animal Use

Today Universities were asked by the National Centre of Refinement, Reduction and Replacement of Animals in Research to pull their finger out and encourage their employers to perform and importantly report animal studies in a more rigorous fashion.

This is a movement that is coming, if not in its present format in another guise, so better to embrace now than face rejection later on

The failing in animal experiments into human drugs is a cause for concern. Poorly designed and executed studies is part of this. This error rate can be improved by reducing bias in the system to find and report positive effects when there aren't any. 
Journals are likewise failing in their duty to enforce there own policies concerning reporting standards

Stressed oligos activate microglia

Bsibsi M, Holtman IR, Gerritsen WH, Eggen BJ, Boddeke E, van der Valk P, van Noort JM, Amor S.Alpha-B-Crystallin Induces an Immune-Regulatory and Anti-viral Microglial Response in PreactiveMultiple Sclerosis Lesions. J Neuropathol Exp Neurol. 2013 Sep 13. [Epub ahead of print]Microglial nodules are frequently observed in the normal-appearing white matter of multiple sclerosis (MS) patients. Previously, we have shown that these clusters, which we call "preactive MS lesions," are closely associated with stressed oligodendrocytes and myelin sheaths that contain markedly elevated levels of the small stress protein alpha-B-crystallin (HspB5). Here, we show that microglia in these lesions express the recently identified receptors for HspB5, that is, CD14, Toll-like receptor family 1 and 2 (TLR1 and TLR2), and several molecular markers of the microglial response to HspB5. These markers were identified by genome-wide transcript profiling of 12 primary human microglial cultures at 2 time points after exposure to HspB5. These data indicate that HspB5 activates production by microglia of an array of chemokines, immune-regulatory mediators, and a striking number of anti-viral genes that are generally inducible by type I interferons. Together, our data suggest that preactive MS lesions are at least in part driven by HspB5 derived from stressed oligodendrocytes and may reflect a local attempt to restore tissue homeostasis.
Oligos express a stress marker and microglia get called-in and they produce factors that pull in  other cells (chemokines) and anti-viral molecules.Is this because the oligos are infected with a virus and is this the start of the MS lesion? 

It is thought that there are too many pre-active lesions so some of them may resolve.

CoI DrLove is part of Team G

The story of campath-1h, now known as alemtuzumab

"Some of you may find this video interesting."

"The key take home messages are: (1) how long it takes to develop a drug for MS, (2) how important scientists, researchers and neurologists are in the process of drug development and (3) you need the pharmaceutical industry to get it to market."

CoI: multiple

Thursday, 26 September 2013

ECTRIMS Question Time

Our final member of the ECTRIMS Question time panel is the Chair and Head of Research at the National Multiple sclerosis Society Tim Coeztee

Remember to get a twitter account to tweak #MSQT



Cladribine works in rodents Should it?

Musella A, Mandolesi G, Gentile A, Rossi S, Studer V, Motta C, Sepman H, Fresegna D, Haji N, Paolillo A, Matarese G, Centonze D. Cladribine interferes with IL-1β synaptic effects in experimental multiple sclerosis. J Neuroimmunol. 2013 Aug. doi:pii: S0165-5728(13)00230-0. 10.1016/j.jneuroim.2013.08.009. [Epub ahead of print]
Alterations of glutamate-mediated synaptic transmission occur in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), the animal model of MS. Here we investigated whether intracerebroventricular (icv) administration of cladribine has effects on EAE. Icv infusion of cladribine reduced the clinical deficits of EAE mice and reversed EAE-induced enhancement of excitatory postsynaptic current (sEPSC) frequency, a neurophysiological measure of glutamatergic synaptopathy associated with central inflammation. Cladribine failed to interfere with EAE-induced microglial and astroglial activation, but blocked EAE synaptic alterations by interfering with interleukin-1β effects. Cladribine possesses neuroprotective properties in experimental MS that are independent of its peripheral immunosuppressant action.

This study says cladribine has beneficial activities independent of immunosuppressant action. However does it matter? 

Cladribine is the drug that has been thrown down the toilet by pharma, 

This is sad when you think is probably as least as effective as any other DMT  and probably safer than many.... if only the placebo group had behaved normally in the trial, Lemtrada would be having a run for its money...Generic version is a fraction of the cost. 

However big question is does cladribine work really work in rodents,? Aren't their immune cells resistant to the effects of Cladribine, in contrast to the effects in humans? Anyone for Merck care to comment as they sponsored the study. 

MS Reporting Finding Milstones

The next question from Shift MS

The next in a fortnight


Twitter Feed for the Live event this week #MSQT
 Social Media Session 12.30-14.00 
(UK Time 11.30-13.00
Question Time.13.00-14.00
Pop-up window will be on the ECTRIMS website
we will post Link

EBV in Childhood MS

More data to support EBV as being involved in the causal pathway of MS. #MSBlog #MSResearch

"This study fingers EBV again, only this time in children MSers. Children with MS are more likely to be seropositive for EBV and shed EBV in  their saliva. Why? Is it because they have a more virulent strain of the virus? This looks unlikely as no specific EBV variant was associated with MS. You need to realise that EBV is not one virus but a family of viruses. Could it be that there is something faulty in the immune systems of these children allowing the virus to replicate unchecked? I suspect this is the most likely explanation. Unfortunately, we don't know what is wrong with the immune systems of MSers that allows EBV to be more active."

"You will note that not all childhood-onset MSers are positive for EBV, which is a strong argument against the virus causing the disease. I agree that this is one hole in our EBV  theory. IF EBV causes MS there are two possible explanations for this observation. Firstly, not all these are EBV negative; the assays used to test for antibodies against EBV are not 100% specific. Secondly, these MSers may not have 'classic MS'. It is more difficult to make a diagnosis of MS in childhood due to more MS mimics and other non-MS like demyelinating diseases presenting as MS. The only way to assess this is to follow the EBV negative MSers to see if they behave like adult-onset disease in the future or turnout to have anothe disease."
"I am still firmly in the camp that believes EBV is thc cause of MS and may be involved as a driver of the ongoing inflammatory activity. To test these hypotheses we need to EBV vaccine trials to prevent children getting EBV or at least infectious mononucleosis and we need to do clinical trials of drugs that target EBV replication and reactivation in MSers with active MS. Why active MS? We need to have an outcome to assess whether or not an antiviral drug is active in a relatively short period of time. This is why we use relapses and MRI activity as an outcome measure."

OBJECTIVE: To investigate Epstein-Barr virus (EBV) oral shedding frequency and EBV genetic diversity in pediatric patients with MS.

METHODS: This was a prospective case-control study. We used PCR-based assays to detect viral DNA in the monthly mouth swabs of 22 pediatric MSers and 77 age- and sex-matched healthy controls. EBV-positive samples were further analyzed for sequence variation in the EBV BCRF1 (ebvIL-10) gene using direct DNA sequencing methods, and in the EBV LMP1 gene by mass spectrometry.

RESULTS: Nineteen of the 22 (86.4%) children MSers were seropositive for remote EBV infection compared to 35 out of 77 (45.5%) healthy controls (p = 0.008). Baseline analysis of mouth swabs revealed a higher proportion of EBV-positive samples from EBV-seropositive MSers compared to EBV-seropositive healthy controls (52.6% vs 20%, p = 0.007). Longitudinal analysis of monthly swabs revealed average EBV detection rates of 50.6% in MSers and 20.4% in controls (p = 0.01). The oral shedding frequencies of Herpesviruses herpes simplex virus-1, cytomegalovirus, human herpesvirus (HHV)-6, and HHV-7 did not differ between groups. Changes in the predominant EBV genetic variants were detected more frequently in MSers; however, no specific EBV genetic variant was preferentially associated with MS.

CONCLUSION: Children with MS demonstrate abnormally increased rates of EBV viral reactivation and a broader range of genetic variants, suggesting a selective impairment in their immunologic control of EBV.

Eye thinning an outcome for MS studies

Winges KM, Werner JS, Harvey DJ, Cello KE, Durbin MK, Balcer LJ, Calabresi PA, Keltner JL.Baseline Retinal Nerve Fiber Layer Thickness and Macular Volume Quantified by OCT in the North American Phase 3 Fingolimod Trial for Relapsing-Remitting Multiple Sclerosis.J Neuroophthalmol. 2013 Sep 18. [Epub ahead of print]

BACKGROUND::Patients with multiple sclerosis (MS) demonstrate thinning of peripapillary retinal nerve fiber layer (RNFL) and decreased macular volume as measured by optical coherence tomography (OCT). To our knowledge, there are no previous reports from a large MS OCT database with strict quality control measures that quantitate RNFL and macula in patients with relapsing-remitting multiple sclerosis.
METHODS:: The University of California Davis OCT Reading Center gathered OCT data at baseline as part of the North American phase 3 trial of fingolimod (Gilenya). Average RNFL thickness (RNFLT) and macular volume (TMV) were measured using time domain OCT (TD-OCT). RNFL quadrants, clock hours, and macular subfields were included. With strict quality control and accounting for signal strength differences, scans were categorized as "reduced" or "not reduced" for each field, based on being less than 5th percentile for age-matched controls derived from the normative database in the scanner software. Patients were deemed "abnormal" if at least 1 eye had reduced values for a given parameter. Patients with abnormalities in corresponding RNFL and macular subfields were compared by cross-tabulation.
RESULTS:The TD-OCT data were prospectively collected from 939 of the 1,083 trial patients, 712 of whom met all final quality and data inclusion criteria. Of the final cohort, 242 (34.0%) demonstrated reduced (less than 5th percentile) average RNFLT in at least 1 eye. One hundred seventy-eight (25.0%) patients had reduced TMV. One hundred twenty-eight (18.0%) demonstrated both reduced TMV and RNFLT in the same eye, whereas 42 (5.8%) had reduced TMV and RNFLT in both eyes. Of the 242 patients with reduced average RNFL thickness, 128 (52.9%) also had reduced TMV. Fifty patients had reduced TMV in the absence of reduced RNFLT in at least 1 eye, a cohort prevalence of 7.0%. Quadrant and subfield analysis showed a predominance of temporal and inferior RNFL thinning, with inferior macular thinning corresponding best to RNFL thinning.
CONCLUSION:RNFL and macular thinning/volume loss is common at baseline in relapsing-remitting multiple sclerosis, as measured by TD-OCT. When the RNFL is thin, the macular volume is reduced in more than half of the patients. There is a population of reduced TMV without any reduction in RNFLT. Documenting the prevalence and distribution of these structural abnormalities supports recent reports and suggests new retinal areas to probe for functional vision changes in MS.

Wednesday, 25 September 2013

Free up your diary

I had posted about keeping you diary free for a special event in November 28th to be held a Barts, but unfortunately we have not been able to get any Members of Parliament to attend, which we wanted.

The main reason is that it is being held on a Thursday night when parliament is in session (I suspect they are all too chicken). ProfG therefore wants to postpone the event until the New Year

Maybe we can actually get the MS select Committee to actually do something.

How Not to Win an Award

We (Giovannoni & Team G) have been nominated for the MS Society 2013 Awards in the category of MS Digital Media of the Year.

After outburst (below), I would just like to say congratulations to or Barbara as Prof G blows our chance.

Anyway should be a fun day.

I wonder who will attend? JLS split this year!

What is the evidence that public partners make a difference when setting research priorities?

How did we miss the elephant in the room? #MSBlog #MSResearch

"Last week I got a lot of behind the scenes stick for taking the MS Society to task for delegating the setting of research priorities to the James Lind Alliance (JLA). It was particularly galling when research into MS causation did not make it into the top 10, when clearly this is the most important and pressing issue in MS; it's the elephant in the room. I would like to thank many of you who took the time to comment on my post for your support."

"The article below is very timely and explains a lot about the JLA process and why the results confound common sense. I note the JLA  excludes the pharmaceutical industry and pure researchers. Why? If they had included Pharma I am sure a half , or maybe three-quarters, of the top 10 priorities would have moved off the MS Society's list and on to a Pharma list. Put bluntly the MS Society does not have the resources to develop drugs. All it can do is fund small proof-of-concept studies, lobby Pharma and support academics in lobbying Pharma, to develop drugs for MS and helping get its members behind treatment paradigms and strategies."

"I feel sorry for pure researchers. The fact that the JLA excludes pure researchers means that the days of blue sky basic science research in specialist fields are over. Blue sky research today has always been  the economic engine of tomorrow. What MS research needs is cross-disciplinary researchers and some out-of-the-box thinking. Sitting in a room with a lot of other people who are researching MS, or who have MS, is not the way forward. We need to sit in the room with immunologists, microbiologists, virologists, molecular biologists, system biologists, IT superstars, medical physicists, medical sociologists, psychologists, heath economists, etc."

"It is interesting that the article below states that the JLA process results in 'patients' pushing for research into causes. This is clearly not the case with regard to the top 10 MS research priorities."

"Has the JLA given us a camel? How did the process miss the elephant in the room?"

If you simply focus on the white swans you won't see the black ones!


.... Involving patients and the public as partners in medical research - from deciding what to study to influencing how results are used - is an emerging force. For some, the approach is based on common sense and justice. Others, such as the chief medical officer for England, Sally Davies, feel that the advice of patients and the public “invariably makes studies more effective, more credible and often more cost efficient”....

..... PPI is a prerequisite for much UK government research funding and it is spreading among funders, health-care organizations and charities. The James Lind Alliance (JLA).... enables patients, carers and clinicians to agree on what research matters most. It explicitly excludes the pharmaceutical industry and pure researchers ...... 

...... This international growth of PPI is rightly paralleled by unease at the paucity of evidence for its impact.....

...... And the evidence there is, including the findings that PPI improves recruitment to studies and changes what is researched is weak. As Simon Denegri, the United Kingdom's first national director for public participation and engagement in research, put it: “The evidence-base for PPI's impact is meagre, patchy and largely observational.”.....

..... A key element of reporting PPI is to make clear who was involved, in part to allow us to gauge when it matters to distinguish between public and patient input......

...... We must also probe whether PPI is valuable for all research types. Will it ever, for example, have a place in basic science? Anecdotal evidence suggests that it might, in part because patients push for research into causes. The UK Alzheimer's Society, the only funder that works with people with dementia and their carers to select research projects, backs work from the lab bench to the clinic. And priorities in sight-loss research, identified through the JLA approach, revealed patient interest in causation, as well as treatments using stem cells and gene therapy......

...... One of the knottiest problems in PPI is how to best weigh up anecdotes and evidence. How are the patients involved chosen? Do they bring more than their own views? Are diverse voices heard, or just those that are loudest? ....... Ignore such questions, and PPI might unwittingly perpetuate power imbalances...... 

...... The most well-meaning approaches can simply extend input from educated, middle-class professionals to input from educated, middle-class patients....... 

....... Yet we must also avoid double standards. Just as people will always want the best researchers or clinicians, we must not exclude the most informed or articulate patients........

Other posts to read:

12 Sep 2013
Ignore the black swan at your members peril. #MSBlog #MSResearch "I received the email below from the MS Society. You may find the research priorities interesting, or not! My one criticism is the priorities make no mention ...
12 Sep 2013
The James Lind Alliance (JLA) is a non-profit making initiative which was established in 2004. It brings patients, carers and clinicians together to identify and prioritise the TOP 10 uncertainties, or 'unanswered questions', ...

Sex the Mental Problem

Schairer LC, Foley FW, Zemon V, Tyry T, Campagnolo D, Marrie RA, Gromisch ES, Schairer D.The impact of sexual dysfunction on health-related quality of life in people with multiple sclerosis.Mult Scler. 2013 Sep. [Epub ahead of print]

BACKGROUND:Sexual dysfunction is a prevalent symptom in multiple sclerosis (MS) that may affect patients' health-related quality of life (HrQoL).
OBJECTIVE:The objective of this paper is to examine the impact of sexual dysfunction on HrQoL in a large national sample using The Multiple Sclerosis Intimacy and Sexuality Questionnaire
METHODS:Participants were recruited from a large MS registry, the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry.
RESULTS & CONCLUSION:The study population included 6183 persons (mean age: 50.6, SD = 9.6; 74.7% female, 42.3% currently employed). In patients with MS, sexual dysfunction has a much larger detrimental impact on the mental health aspects of HrQoL than severity of physical disability.

Last time we had a post on this subject I was accused of being insensitive, so I will not say anything except to say the results may be as predicted.

Neural Components as targets for autoimmuntity

Puentes F, van der Star BJ, Victor M, Kipp M, Beyer C, Peferoen-Baert R, Ummenthum K, Pryce G, Gerritsen W, Huizinga R, Reijerkerk A, van der Valk P, Baker D, Amor S.Characterization of immune response to neurofilament light in experimental autoimmune encephalomyelitis. J Neuroinflammation. 2013 Sep ;10(1):118. [Epub ahead of print]

Autoimmunity to neuronal proteins occurs in several neurological syndromes, where cellular and humoral responses are directed to surface as well as intracellular antigens. Similar to myelin autoimmunity, pathogenic immune response to neuroaxonal components such as neurofilaments may contribute to neurodegeneration in multiple sclerosis.
METHODS:We studied the immune response to the axonal protein neurofilament light (NF-L) in the experimental autoimmune encephalomyelitis animal model of multiple sclerosis. To examine the association between T cells and axonal damage, pathology studies were performed on NF-L immunized mice. The interaction of T cells and axons was analyzed by confocal microscopy of central nervous system tissues and T-cell and antibody responses to immunodominant epitopes identified in ABH (H2-Ag7) and SJL/J (H2-As) mice. These epitopes, algorithm-predicted peptides and encephalitogenic motifs within NF-L were screened for encephalitogenicity.
RESULTS:Confocal microscopy revealed both CD4+ and CD8+ T cells alongside damaged axons in the lesions of NF-L immunized mice. CD4+ T cells dominated the areas of axonal injury in the dorsal column of spastic mice in which the expression of granzyme B and perforin was detected. Identified NF-L epitopes induced mild neurological signs similar to the observed with the NF-L protein, yet distinct from those characteristic of neurological disease induced with myelin oligodendrocyte glycoprotein.
CONCLUSIONS: Our data suggest that CD4+ T cells are associated with spasticity, axonal damage and neurodegeneration in NF-L immunized mice. In addition, defined T-cell epitopes in the NF-L protein might be involved in the pathogenesis of the disease.

More many years EAEologists soley focused on myelin as a potential target.This study shows that immune responses to nerve proteins can cause a disease that is comparable to that induced  myelin although grey matter lesions can occur and the clinical disease can be abit different. Is this relevant to MS well maybe we see that is often antibodies against neurofilament light in the tissues from MSers. Are these harmless well I am sorry to say no but that's another story. 
CoI This is work by Team G

ECTRIMS Question Time

The Question time panel has now been disclosed

We are will have a Live Webfeed with Twitter (#MSQT).

Get yourself a twitter account and join the fun

If you are a Neuro/Scientist/Pharma Rep come join us in Hall C and show us your tweeting skills so sign up before the big day
If you can't make it join us for For Question Time Live 13.00-14.00 Central European time 12.00 UK time (Web feed details to follow)

Our final neurologists on the panel is Robert Fox,USA

Dr. Robert Fox is the Medical Director at the Mellen Center for Multiple Sclerosis at the Cleveland Clinic, USA.

His research interests are development of novel imaging modalities and the generation of treatments of MS and monitoring of repair.

He serves as an advisory committee member and principal site investigator for many clinical trials and is Managing Director of the MS Patient Registry in the USA and was the global lead investigator for trials on tecfidera. 

He has been listed in the Best Neurologist Category in the Cleveland Magazine for the past decade.

Questions to BartsMSBlog(at)

Please note email addresses will not be disclosed or associated with a question. 


You can post questions Anonymously (or with names) below. 

These will be removed and posted to BartsMS Blog on your behalf.
We will not Respond to Anything Posted Here. 

Likewise please refrain from commenting on any questions posed.

This is your Last chance!

Tuesday, 24 September 2013

Save the Grey!

Grey Matter Matters

Will the ProgressiveAlliance 
find a Solution?

ECTRIMS 2013: Brain atrophy infographic version 1

Version 1 of ECTRIMS 2013 brain atrophy infographic. #MSBlog #MSResearch

"The following is the first version of my brain atrophy infographic for the ECTRIMS blogging session. My aim is to get across what brain atrophy is, how common it is, its consequences and its relationship to inflammation and neuronal loss in small digestible sound bites. I would appreciate your feedback on whether it achieves this; if not let me know. I still have a week or so to improve on it."

"Please note that I have chosen the title based on your voting."

Team G in the News

Team G in the News

Virtual Exercise improves balance

Gutiérrez RO, Galán Del Río F, Cano de la Cuerda R, Alguacil Diego IM, González RA, Page JC. A telerehabilitation program by virtual reality-video games improves balance and postural control in multiple sclerosis patients. NeuroRehabilitation. 2013 Sep. [Epub ahead of print]

Balance and postural control (PC) disorders are frequent motor disorder symptoms associated with multiple sclerosis (MS).
OBJECTIVE:To demonstrate the potential improvements in balance and PC among patients with MS who complete a virtual reality telerehabilitation program that represents a feasible alternative to physical therapy for situations in which conventional treatment is not available.
METHODS: 50 patients was recruited. Control group (n = 25) received physiotherapy treatment twice a week (40 min per session). Experimental group (n = 25) received telerehabilitation treatment using the Xbox 360® console monitored via videoconference. Experimental group attended 40 sessions, four sessions per week (20 min per session). The treatment schedule lasted 10 weeks for both groups. A computerised dynamic posturography and clinical outcomes were used at baseline and at the end of the treatment.
Results showed an improvement over general balance in both groups. Visual preference, the contribution of vestibular information(from the ear where balance is controlled), mean response time and Tinetti test yielded significant differences in the experimental group. An ANOVA revealed significant between-group post-treatment differences 
CONCLUSION:We suggest that our virtual reality program enables anticipatory PC and response mechanisms and might serve as a successful therapeutic alternative in situations in which conventional therapy is not readily available.

As ProfG has maintained we need to embrace technology in todays medicine , this study uses a physiotherapy session via xbox. Having wasted a morning travelling to the physio, a virtual session sounds appealing

The Tinetti balance test

Symptoms in MS

The vicious cycle of MS symptoms. #MSBlog #MSResearch

"This study shows that MS-related cognitive impairment is more related to clinical disability and disease duration than depression and anxiety. This may be the case when you look at a group of MSers, but in my experience in individual MSers fatigue, depression and anxiety go with poor cognitive functioning. Mental fatigue is a manifestation of cognitive impairment and the brains compensatory mechanisms. MSers use a lot more mental energy to complete the same cognitive task as normal people; this is how the brain compensates when it is damaged. When you ask MSers to describe their mental fatigue it is way and above the levels of fatigue normal people feel when completing complex and prolonged mental tasks, for example a school or university examination paper. I don't think we appreciate how severe this fatigue can be."

"If MSers have depression this results in low motivation and exacerbates fatigue. Similarly, anxiety consumes unnecessary mental energy with rumination about negative things. Both anxiety and depression affect sleep, for example early morning waking or an increased sleep latency (the time it takes to get to sleep), which exacerbates daytime fatigue. All these symptoms create a vicious cycle, which is why we need to take detailed histories and manage MSers holistically."

Epub: Karadayi et al. The relationship of cognitive impairment with neurological and psychiatric variables in multiple sclerosis patients. Int J Psychiatry Clin Pract. 2013 Sep 19.

Objective: Cognitive impairment (CI) in MS can develop any time. CI is associated with degree of neuronal loss but disease duration, fatigue, comorbid affective disorder and drug dose may also affect cognition. 

Aim: To assess which cognitive domain was disturbed primarily in mild MSers and to see if CI was related with clinical and psychiatric features. 

Method: Neurological and psychiatric evaluation of 31 MSers and 31 age-sex-education matched healthy controls were done with SCID-I. Depression, anxiety, functionality, fatigue, disability scoring was done with Hamilton Depression-Anxiety scales, Global Assessment of Functionality, Fatigue Severity and Expanded Disability Status Scales. Cognitive functions were assessed by Mini Mental, Serial Digit Learning, Verbal and Nonverbal Cancellation, Stroop and Rey Auditory Verbal Learning tests. 

Results: Retrieval from long term memory and psychomotor speed were significantly worse in MS group. CI was correlated with disease duration, number of attacks and physical disability but not correlated with depression and anxiety severity. Disease duration predicted disturbances in recall and psychomotor speed, whereas fatigue and disability predicted depression. 

Conclusion: Psychomotor speed and memory were primarily impaired in MSers and CI was closely associated with clinical aspects of MS rather than depression and anxiety.