Thursday, 30 June 2011

CCSVI Trial

Canadian Health Minister Leona Aglukkaq announced on Wednesday that federal funding will be made available for clinical trials of the so-called liberation therapy for MS'ers.

Read more in the Calgary Herald

"What will convince you that the treatment for CCSVI works or doesn't work?"

Are Pharma sponsored trials biased?

  • Drug companies produce most of the evidence we (neurologists) use for supporting our decisions for using disease-modifying therapies (DMTs).
  • There is no doubt that these companies have a conflict of interest when they conduct trials.
  • Pharma companies need positive trials to license and sell their products; therefore they want positive trials.
  • Pharma sponsored trials are more likely to be positive than non-Pharma sponsored trials.
"What should we do about it? Are you concerned? I am!"

Ben Goldacre, the author of Bad Science, argues that there is good evidence that this conflict of interest results in bad evidence, which distorts medical decision making and may harm patients.

Goldacre. Is the conflict of interest unacceptable when drug companies conduct trials on their own drugs? Yes. BMJ. 2009 Nov 27;339:b4949. doi: 10.1136/bmj.b4949.

Noble. Drug firm conflicting interests. Radical change, not tweaking, is needed. BMJ. 2009 Dec 31;339:b5656. doi: 10.1136/bmj.b5656.

Additional reading: Bad Science

Wednesday, 29 June 2011

A new remyelination target


The investigators found that a factor called Axin2 is essential for normal repair of nerves stripped of myelin. This is the process called remyelination. 

A small molecule XAV939, which stabilises levels of Axin2, accelerates remyelination. 

These findings indicate that Axin2 is an essential regulator of remyelination and that it might serve as a pharmacological target for drug development for MS'ers. 

"Another promising target for the Pharma industry to develop drugs to promote remyelination and recovery in MS'ers. The NMSS Promise 2010 delivers another target! Are you happy?"


[Epub ahead of print] Fancy et al. Axin2 as regulatory and therapeutic target in newborn brain injury and remyelination. Nat Neurosci. 2011 Jun 26. doi: 10.1038/nn.2855.

"Well done Steve and colleagues."

CoI: Nil

Further reading: myelin 

The highs and lows of cannabinoid drug development

"So as not to disappoint you (please see the following presentation by Professor David Baker); we are still trying to develop drugs for MS'ers. In this case we are targeting spasticity as the current drugs we have for spasticity are far from ideal and cause too many side effects; for example sedation, wearing-off spasms and the rag-doll effect (weakness)." 


CoI: Multiple

Rituximab: a possible treatment for SPMS?

Rommer et al. Rituximab for secondary progressive multiple sclerosis: a case series. CNS Drugs. 2011 Jul 1;25(7):607-13.

Treatment options are very limited for MS'ers with SPMS. In this observational study the investigators present clinical and spinal fluid findings in 3 patients with SPMS who were treated with rituximab, a drug that target the B-cell or the cell that produces antibodies, for at least 15 months. During the observation period, no severe adverse effects occurred and the disability score stabilised in all subjects after a dramatic increase over the previous years. Conclusion: The investigators concluded that Rituximab seems to be effective in active SPMS. 

"What is wrong with this study? Firstly, it is very small; only 3 MS'ers. Secondly, it may be biased by the design, i.e. it is an open study. Thirdly, the EDSS is a poor outcome measure and too insensitive for change over such a short period of time. Do you think this paper should have been published?"

"What is right with this study? The investigators should be complemented for trying Rituximab in SPMS. In the past this is how therapies evolved; you started with an idea or scientific rationale and you then test the drug in an individual with the disease. If it appeared to work in the individual you then test it in a few more cases; this is called a case series. If the results then look promising you do a trial. Unfortunately, the regulatory, ethical and financial constraints in the NHS means that this classical route of investigator-led drug development is now virtually non-existent. It is becoming increasingly difficult to get PCTs or Commissioners to pay for off-license use of drugs like Rituximab. The usual response to an individual funding request to a PCT is "NO"; particularly if it is the off-license use of an expensive drug. Ultimately, this will hamper medical discovery and staff in the NHS will drop down the league tables of innovation. It also means that drug discovery will become almost the exclusive reserve of the Pharma Industry; this is something we should try and avoid as the needs of Pharma are often at odds with the unmet needs of MS'ers (please see previous posts on oral cladribine). Any thoughts on this?"



Tuesday, 28 June 2011

Vitamin D: effects on immune cell function in MS'ers

Kimball et al. Cholecalciferol Plus Calcium Suppresses Abnormal PBMC Reactivity in Patients with Multiple Sclerosis. J Clin Endocrinol Metab. 2011 Jun 22. [Epub ahead of print]

The active metabolite of vitamin D is a potent modulator of immune cells. In this study the investigators' determined whether vitamin D, a sun-dependent nutrient can affect the cells athat are associated with the immune abnormalities in MS. Treated MS'ers received increasing doses of vitamin D (4,000-40,000 IU/d) plus calcium (1200 mg/d), followed by equilibration to a moderate, physiological dose of vitamin D of 10,000 IU/d (the amount you get from 20-30 minutes of sun exposure in mid summer). Control subjects did not receive supplements. Results: At 12 months, the average serum vitamin D concentrations were 83 nmol/liter and 179 nmol/liter in control and treated participants, respectively (P < 0.001). In treated MS'ers,  the abnormal immunological responses of lymphocytes (an important immune cell in MS) against components of nerve cells and myelin were suppressed. Interpretation: MS-associated, abnormal T cell responses that are believed to trigger MS were suppressed in subjects with vitamin D concentrations in their blood higher than 100 nmol/liter.

"This study would indicate that you would need to keep your serum vitamin D levels above 100 nmol/litre to have effects on the immune system; this would mean most of us taking 10,000U of vitamin D per day; in comparison we only need 400U per day to prevent bone  thinning. This is why we are trying to get public health officials to recognise this and increase the RDA of vitamin D."

"Interestingly, if you lived as a hunter-gatherer, i.e. out in the open as our ancestors did, your serum levels would be above 100nmol/litre. We know this from studies done on farmers, life guards and other groups of people who work outdoors. It makes you think about what we are doing to ourselves by changing, and continuing to change, our lifestyles so dramatically over the last 2 generations. Any thoughts about what the digital revolution is doing to our immune systems?"

CoI: Nil

Monday, 27 June 2011

Vascular aspects of multiple sclerosis: a review

D'haeseleer et al. Vascular aspects of multiple sclerosis. Lancet Neurol. 2011 Jul;10(7):657-66.

This review claims that there are potentially three types of blood vessel or vascular abnormalities in MS: 

(1) The study of diseases in the general population suggest that people with MS have a higher risk for stroke than people who do not have MS. The underlying mechanism of this unknown, but might involve damage to blood vessels secondary to brain inflammation that occurs in MS. Another proposed explanation is that MS'ers have a global reduction in blood flow to the brain.

"This is probably secondary phenomenon due to previous tissue damage as a result of MS. Whether this reduced blood flow predisposes MS'ers to stroke is not known."

(2) Data suggest that a subtype of focal MS lesions might originate from reduced blood flow. 

"This is very controversial and there is no consensus among card-carrying MS neuropathologists on this proposal."

(3) CCSVI: the pathology of MS might be the consequence of a chronic state of impaired venous drainage from the CNS, for which the term chronic cerebrospinal venous insufficiency (CCSVI) has been coined. A number of recent studies do not support the CCSVI theory, but some elements of CCSVI might be explained by slower cerebral venous blood flow secondary to the reduced cerebral perfusion in people with MS compared with healthy individuals.

"I agree with the latter and would add the possible con-founder of dehydration, please see my previous post (click here)."

"On balance I don't think the evidence is very strong that vascular abnormalities play a large role in MS. It is hard to explain a lot of what we know about MS with these vascular hypotheses or theories."

CoI: Nil

Potential health care cost savings associated with early DMTs

Curkendall et al. Potential Health Care Cost Savings Associated With Early Treatment of Multiple Sclerosis Using Disease-Modifying Therapy. Clin Ther. 2011 Jun 17. [Epub ahead of print]

This study assessed health care utilization and expenditures associated with treating MS'ers early  (CIS) with DMTs rather than delaying until MS'ers meet the full diagnostic criteria of MS (MRI evidence of dissemination in time or second clinical attack). It is important to note that this is a retrospective study from the United States using insurance claims data (2000-2008) of enrolled MS'ers before documented MS. The analysis indicated that early DMT treatment was associated with fewer hospitalisations than delayed treatment, and there was no statistically significant difference in annual health care expenditure. This suggests that the drug costs of early therapy were offset by savings in other medical expenditures. 

"I wouldn't be surprised if these findings were replicated under the NHS. Unfortunately, we don't have the data available to do this sort of analysis. This study suggest that we can't really use health economic arguments to delay therapy in early MS! In addition, the biggest savings from DMTs are yet to come; i.e from delaying the onset of SPMS, or hopefully preventing SPMS."

Research focus

In response to a anonymous comment: "Maybe one solution is to rethink the other research that is being undertaken. In your team there are researchers looking at the impact of neutralising anti-bodies) and others (Prof Baker - who referred to himself as the mouse doctor at the research day) looking at EAE (which you have noted in your blog is not MS). If EBV and Vit D looking so promising then it might be a case of ditching some of the research that is unlikely to significantly impact beneficially on the lives of people with MS and focussing on the more promising stuff...."


"(1) Neutralizing antibodies (NABs): we are using NABs as an autoimmune model to test immune tolerance strategies. NABs to interferon-beta are not found in normal healthy subjects; their presence represents an autoimmune disease. If we can work-out how to get rid of these antibodies safely then this will have implications for many other autoimmune diseases, including MS. Although MS may be triggered by vD deficiency and EBV, the possibility remains that it is an autoimmune disease, with the need to target this process with safe strategies. The immune tolerance strategy we are testing in relation to NABs was developed by David Baker in the 1990's using EAE; it is important for us to try and translate this. In fact we have an obligation to our generous funders to try and translate this strategy; it would be a great pity to give up on a promising lead at this stage.


(2) EAE: we are using our model at the moment mainly for testing drugs in progressive EAE and for symptomatic treatments. Having a progressive model of EAE is very valuable; several of the drugs that will go into clinical trial, including the STOP-MS trial, have come through our model. We also need the model to understand the delicate relationship between inflammation and progressive disease. The model is also being used for evaluating remyelination and neuro-restorative strategies. You may be interested to hear that we have invented a very exciting treatment for spasticity using this model. We now have funding from the Wellcome Trust to do a toxicology screen and hopefully get it into MS'ers in a phase 1 study withing 12 months. 


(3) vD and EBV: this is the main thrust of our research at present; we have both basic and applied clinical research projects at present. Please watch this space; we have ideas for both testing anti-EBV drugs as DMTs and as a potential MS preventative therapy in infectious mononucleosis or glandular fever. As for vD; this is a public health issue and we are part of the vD lobby that is trying to get public health officials to change the RDA. We are also collaborating with people doing clinical trials on vitamin D in MS. Unfortunately, the MRC and NIHR turned down the UK grant to do a vitamin D trial in CIS. You can help by lobbying for these studies to be done at a national level. 


In addition we are involved in several other MS-related research projects. One of the projects is a design project to improve the outpatient experience of MS'ers attending the Royal London Hospital. This may not seem important, but it is essential for us that MS'ers who come to see us leave with a sense that the consultation was worthwhile. I note that too many comments posted on this blog highlight the dissatisfaction MS'ers have with neurologists. 


Our group tries our best to have a holistic approach to MS research."


CoI: multiple 

Sunday, 26 June 2011

Cognitive impairment in MS

In response to the comment on memory impairment in MS. 

"Cognitive impairment is common in MS. Most cross-sectional surveys show that approximately 50% of MS'ers have cognitive problems. I hope you don't find this surprising."


"The MS Trust have produced a wonderful web-based programme to help MS'ers cope with this problem. I recommend it highly and MS'ers who have used it like it very much."


CoI: Nil

History of MS (2): St. Lidwina of Schiedam (1380-1433)

"I believe that studying or being aware of the history of MS is important; it may provide important insights into the origins of the disease and important clues to its cause."

Possibly the earliest known description of a case of  MS referred to the woman depicted in this woodcut, St. Lidwina of Schiedam. Lidwina lived in Holland in the 14th century and historical texts reveal that she was afflicted with a debilitating disease, sharing many characteristics that we now associate with MS. 


St Lidwina’s disease began at the age of 16 after a fall while ice-skating. From that time onwards, she developed walking difficulties, headaches and violent pains in her teeth. By the age of 19, both her legs were paralysed and her vision was disturbed. Over the next 34 years, Lidwina's condition slowly deteriorated. There is no indication that there were periods of remission. Lidwina eventually died at the age of 53. Lidwina's historical symptoms are consistent with those of MS, as is her age of onset, duration and course of disease. If this is correct then MS may date back to the 14th century.

"Why is this important? It is clear that MS was not common in until quite recently (middle to late 19th century), therefore there must be some message hidden in studying historical cases that can point to the environmental causes or triggers of this disease. Something must have emerged in the environment. If only we knew!" 

"Interesting or not?"

CoI: Nil

Saturday, 25 June 2011

CCSVI: could dehydration be a possible confounding variable?

"Way back in 1996 we wrote a letter to the Annals of Neurology highlighting the possibility of dehydration being a confounding factor when assessing MS'ers with progressive disease."

Giovannoni et al. Urinary myelin basic protein-like material as a correlate of the progression of multiple sclerosis. Ann Neurol. 1996 Jul;40(1):128-9.

"What we had found in our own studies is that the concentration of particular substance in urine correlated with disability. Why? We subsequently showed that the reason for this was voluntary dehydration; MS'ers  with urinary symptoms often restrict their fluid intake to control troublesome urinary frequency, especially when quick access to toilet facilities may be limited, for example during hospital visits. 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, which will result in a higher chance of finding collapsed veins when doing ultrasound or doppler studies as part of a work-up for CCSVI. This may explain why it is more common in MS'ers with progressive disease; they are more likely to have bladder problems and hence more likely to dehydrate themselves."

"I wonder if the CCSVI investigators' have considered this? Do you dehydrate yourself to control your bladder?"

CoI: nil

MS Frontier's Meeting

In response to the comment "Did you attend MS Frontiers? Any positive news?": 


"Yes, I attended and enjoyed it very much. Unfortunately, because of parallel sessions I could not attend all the talks I wanted to.  The following are my highlights:


1. Dr Jeremy Chataway; good news the MS Society's clinical trial network is well advanced in their plans to start a neuroprotection trial in progressive MS. The trial will be called the MS-STOP trial and will hopefully start late 2012 or early 2013, 
2. Professor Siddharthan Chandran; University of Edinburgh, presented the phase 1 results of the MRC-funded mesenchymal stem cell trial. It is safe and feasible to do a trial of this nature. 
3. Dr Stephen Sawcer, Professor George Ebers and Prof. Gavin Giovannoni; all spoke on gene-environment interactions. We all agreed that MS is complex disease and we are getting  closer to defining the causal pathway. This is important to target therapies and more importantly to prevent MS. 
4. Katie Lidster presented a new animal model of optic neuritis. This will be very important in testing strategies to target focal inflammation and its consequences. 
5. Inocencio Maramba presented an update on the MS Register; there are close to 5,000 subjects registered. This is excellent news. 
6. Giulio Disanto presented a paper on infectious mononucleosis (IM), sex ratios and MS in the UK. Interestingly, there was significant correlation between MS and IM sex ratios and latitude and MS Sex ratio. More data to support the link between MS and EBV, which causes IM."

Is the treatment of CCSVI safe?

Petrov et al. Safety profile of endovascular treatment for chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Endovasc Ther. 2011 Jun;18(3):314-23.

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 venous lesions during 495 procedures. Although balloon angioplasty was preferred, 98 stents were implanted in 76 patients for lesion recoil, restenosis, or suboptimal dilation. There were no deaths, major bleeding events, or clinical deterioration of MS. Complications at the site of venous access included limited groin hematoma (5, 1.0%); there were no arteriovenous fistulas or puncture site infections. Systemic complications included cardiac arrhythmias (6, 1.2%). Procedure-related complications included vein rupture (2, 0.4%), vein dissection (15, 3.0%), acute in-stent/in-segment thrombosis (8, 1.6%), and acute recoil (1, 0.2%); there was no stent migration or fracture or distal embolization. The average x-ray or fluoroscopy time was 22.7 minutes, and mean contrast volume used was 136.3 mL. The investigators concludes that endovascular therapy appears to be a safe and reliable method for treating CCSVI. 

"Do you think it is safe?"

"I am amazed that so many patients are undergoing this procedure; particularly when CCSVI has yet to be established as a disease entity or cause of MS and that endovascular treatment has yet to be shown to work in appropriately designed randomised controlled trials."

CoI: nil

Some insight into the mechanisms of memory in MS'ers

Kooi et al. Cholinergic imbalance in the multiple sclerosis hippocampus. Acta Neuropathol. 2011 Jun 21. [Epub ahead of print]

MS affects the part of the brain that is involved in memory called the hippocampus; when this part of the brain is affected it is associated with memory impairment. In this post-mortem study, the researchers studied the hippocampus in people with MS and Alzheimer's disease and compared these to control subjects. They detected substantial alterations in the systems the brain uses to activate the programs that control memory; this system is called the cholinergic neurotransmitter system. The system was affected in both MS and Alzheimer's disease, but differed from each other. These findings reveal an MS-specific imbalance of the cholinergic system in the hippocampus.



"These findings are very important and will be helpful in designing treatment options for MS-related memory impairment in the future. Unfortunately, to date we do not have a drug that treats this symptom in MS and the Alzheimer's drugs have failed in recent trials after showing promise in earlier studies."

"Memory impairment is another one of the massive unmet needs in MS. Does it affect you?"

CoI: Nil

Click here to read more about the hippocampus

Friday, 24 June 2011

CCSVI is not the cause of MS

Zivadinov et al. Prevalence, sensitivity, and specificity of chronic cerebrospinal venous insufficiency in MS. Neurology. 2011 Apr 13. [Epub ahead of print]

CCSVI = Chronic cerebrospinal venous insufficiency

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 ultrasound technique called echo-color doppler. This was a large study in 499 subjects. Results: CCSVI was diagnosed in 63% for MS, 46% for other neurologic diseases, 42% for clinically isolated syndrome, and 26% of health controls. CCSVI was commoner in patients with progressive compared to non-progressive MS. Conclusions: The findings argue strongly against CCSVI having a primary or causative role in the development of MS.

"I am not surprised by the results of this study. These results are beginning to confirm my position that CCSVI is not a disease entity and that CCSVI is not the cause of MS. We now need to wait and see if the other studies currently being undertaken confirm these results."

Please see some previous posts on this entity:


Thursday, 23 June 2011

History of MS (1): Russell Brains Monologue

Murray T. Russell Brains Review of MS. Int MS J. 2011 May;17(2):50-3.

In 1930 there were many conflicting views on the cause, incidence, precipitating factors, inheritance and treatment of MS. A young, London neurologist summarized the state of understanding of the disease with his personal view of many of the uncertain areas, and clarified the thinking for the neurological community at that time. Although his later career was influential in many fields of medicine, and his personal influence was extraordinary in many areas as an author, educator, administrator, opinion leader and historian, his review was an important milestone in the history of MS.

"Lord Brain was one of predecessors at The Royal London Hospital. His monograph on MS is remarkable considering when it was written. I would recommend it if you are interested in the history of MS."

Brain, W.R. Critical review: disseminated sclerosis. Q J Med 1930, 23: 343-391.


What bladder drug are you on?

van Rey and Heesakkers. Solifenacin in multiple sclerosis patients with overactive bladder: a prospective study. Adv Urol. 2011;2011:834753. Epub 2011 May 5.

This study assessed the efficacy and the effect on Qol of solifenacin (Vesicare) for overactive bladders in MS'ers. Solifenacin resulted in a significant decrease in number of micturitions and number of continence pads used per day compared to baseline. The severity of urinary urgency prior to passing urine decreased significantly and there was an increase in the volume of urine passed. Two thirds of MS'ers chose to continue solifenacin therapy after completion of the study. The majority of MS'ers reported an improvement in their QoL.

"Is this study important? Yes. Bladder problems are one of the curses of having MS; effective treatments are very helpful. Please note another intervention that improves quality of life."

"Solifenacin is one of the new generation drugs that has been designed not to penetrate the brain and to work in the periphery; i.e. on the bladder where its action is needed. Why is this important? One of the most commonly prescribed drugs for overactive bladders is oxybutynin; this drug is an old generation drug that penetrates into the brain and affects cognition. Oxybutynin has been been shown consistently to impact on cognitive function; in a disease such as MS that already affects cognition this is simply a no-no. I personally stopped using oxybutynin over 5 years ago and only prescribe the newer generation agents. If you are an MS'er and are on oxybutynin you should speak to you GP, MS clinical nurse specialist, continence nurse or neurologist about changing you onto a newer drug that are associated with less of this particular side effect; for example tolterodine (Detrusitol), solifenacin (Vesicare) or others."


"I can't stress the importance of symptomatic therapies to improve the QoL of MS'ers. I spend most of time in clinic doing this. This is contrary to what people think; i.e. prescribing and monitoring DMTs."

CoI: Nil

Wednesday, 22 June 2011

Bad news: regulatory update on cladribine

The following are the headline results of a press release from Merck-Serono:
  1. Following recent feedback from FDA and previous feedback from EMA Merck Serono has decided to no longer pursue the global approval process of Cladribine Tablets 
  2. Merck Serono will focus resources on other projects bringing benefit to patients with MS 
  3. The benefit/risk profile of Cladribine Tablets is unchanged - Ongoing clinical trials will continue 
  4. One-time charge of EUR 20 million to be recorded in the second quarter
"What does this mean for PwMS? In essence oral cladribine will not become available for treating MS'ers."

"Don't underestimate the implications of this decision. What about other MS drugs in the pipeline with undefined or even defined risks?"

"How did cladribine fail? Some initial thoughts: (1) the drug development programme was designed in the pre-natalizumab-PML era; once PML emerged potential undefined risks of new drugs became the big issue and the cladribine development programme was not sufficiently large enough to satisfy, the insatiable, appetite of regulators for safety data. (2) Cladribine has an oncology legacy; oncology drugs are simply perceived as being toxic. (3) Emergence of potentially safer competitors; notably BG12 (see previous post). (4) Patent issues; I assume cladribine will have needed to be tested in another pivotal phase 3 trial, this would delay its launch by several years, eating up valuable time on the patent clock. This would make it difficult or impossible for Merck-Serono to recoup the development costs and turn a profit on the drug for its shareholders. At the end of the day the pharma industry is a business and is shaped by the market. Unfortunately, the market rarely, if ever, prioritises unmet medical need."

"Undefined risk; at present we simply don't know what the long-term safety profile of cladribine is. Is this a good reason to kill a drug with so much promise? In every set-back lies an opportunity. I wonder if the NHS would be prepared to take-up the baton and run a national study to compare cladribine (the cheaper generic version) against established DMTs? Some food for thought!"

"Finally if there are any other amateur of professional hacks out their with relevant information or opinions please feel free to join the debate. It may yet become the 'SAVE CLADRIBINE FOR THE NHS' campaign."

Article of interest (4): Parent of origin effects

Ebers et al. Parent-of-origin effect in multiple sclerosis: observations in half-siblings. Lancet. 2004 May 29;363(9423):1773-4.

MS can be viewed as a complex genetic trait in which occurrence rates in offspring are 20 to 50x greater than in the general population. In this very clever study the investigators studied the recurrence risk of MS in half-siblings with respect to their parent in common, i.e. mother or father. The risk of MS to full-siblings was 3.11%. By contrast, half-sibling risk in the same families was significantly lower at 1.89%, but higher than expected if familial risk was simply polygenic (due to multiple genetic factors). For maternal half-siblings (mother in common), the risk was 2.35%, and 1.31% for paternal half-siblings (father in common). Conclusions: the difference in risk suggests a maternal parent-of-origin effect in multiple sclerosis susceptibility.

"This is a very important study and suggests that a mother is more likely to transmit the risk of MS to her offspring than a father. This could be due to epigenetics, i.e. the imprinting on the genome that is known to occur (see previous post), or the possible vertical transmission of a virus from mother to child. Vertical transmission is well described with several viruses the most analagous being HTLV-1 a retrovirus that causes a progressive spinal cord syndrome called HTLV-1 associated myelopathy (HAM) or tropical spastic paraparesis (TSP). Whatever the reason for the parent-of-origin effect it needs to be explained by any MS causation theory."

CoI: Nil

For more information on epigenetics click here
For more information on HAM or TSP click here

Tuesday, 21 June 2011

Hot topic: a new animal model of MS trumps all others and supports the viral causation hypothesis of MS

Axthelm  et al. Japanese macaque encephalomyelitis: A spontaneous multiple sclerosis-like disease in a nonhuman primate. Ann Neurol. 2011 Apr 7. doi: 10.1002/ana.22449. [Epub ahead of print]

Japanese macaque encephalomyelitis (JME) is a spontaneous inflammatory demyelinating disease occurring a colony of Japanese macaques. This JM colony was established in 1965 and no cases of JME occurred until 1986. Since 1986, 57 JMs spontaneously developed a disease characterized clinically by paresis or weakness of one or more limbs, unsteadiness of gait, or weakness of eye movements. Most affected animals were humanely euthanised during their initial episode. However, three recovered, later relapsed, and were then euthanised. MRI of 8 cases of JME revealed multiple gadolinium-enhancing (inflamed) lesions in the white matter of the brain and cervical spinal cord. The pathology contained multiple plaque-like demyelinated lesions of varying ages, including acute and chronic, active demyelinating lesions with macrophages (scavenger cells) and lymphocytic infiltrates around veins, and chronic, inactive demyelinated lesions. A previously undescribed gamma-herpesvirus was cultured from acute JME white matter lesions. Cases of JME continue to affect 1% to 3% of the colony per year. Interpretation: JME is a unique spontaneous disease in a nonhuman primate that has similarities with multiple sclerosis (MS) and is associated with a novel simian herpesvirus.

"One of the criteria for causation is reasoning by analogy. A spontaneous relapsing MS-like disease in a non-human primate with MRI and pathological features similar to MS ticks this box. I am still in the camp that thinks MS is due to an infection; EBV. Interestingly, EBV is a human gamma herpesvirus. Any supporters out there?"

Ready to Work? Meeting the employment and career aspirations of people with Multiple Sclerosis


We had a successful outing to the Houses of Parliament yesterday for the launch of the Work Foundation's report into working life years and MS. Here's a link to the report: click here 

And here are the main findings:
  • On average, 37 per cent of people with mild MS are employed, however, many have to change or quit their jobs due to fluctuating functional capability; 
  • More than 75 per cent of people with MS report that the condition has impacted their employment and career opportunities;
  • Up to 80 per cent of people with MS stop working within 15 years of the onset of the condition;
  • At the same time 30 per cent of individuals with a significant level of disability remain in employment; 
  • Up to 44 per cent of people with MS retire early due to their condition – a higher percentage than the European average (35 per cent);
  • As a result of reduced availability of social services, a considerable burden of the costs associated with MS falls on those with the condition and their carers;
  • Professional careers of 57 per cent of relatives are adversely affected by MS of a family member;
  • People with MS lose an average of 18 working years, assuming a retirement age of 60. 
  • If one worker with MS draws Employment Support Allowance (ESA) for 18 years the total cost (at 2011 prices) will be £61,000. If 20,000 people are on ESA benefits for 18 years the cost to the welfare system is over £1.2 billion. This takes no account of the income tax which these workers would be paying;
  • The annual costs of MS may vary from £12,000 for those with low disability scores to £60,000 for those with severe disability stage. One estimate suggests that MS costs UK society about £2.3 billion per year.
Be interested to know your thoughts on this report.

Posted on behalf of Beki Hawes (beki@shift.ms) 

"This post is for those of you who need reminding of what the socioeconomic impact of MS is for the individual and the UK. Quite staggering! What do you think?"

Impact on QoL of cystectomy with ileal conduit urinary diversion for neurogenic bladder dysfunction

Guillotreau et al. Neurourol Urodyn. 2011 Jun 14. doi: 10.1002/nau.21121. [Epub ahead of print]

Bladder dysfunction in MS has a negative impact on QoL. Removal of the bladder (cystectomy) with the insertion of a piece of bowel, or ileal conduit, to divert the urine flow into a bag is a treatment option in PwMS who fail conservative treatment. This study evaluated the impact of ileal conduit urinary diversion on the QoL in people with neurogenic bladder dysfunction. Methods: QoL was assessed by self-administered questionnaire scores before and after surgery. Results: After surgery, subjects had a significant reduction in limitations and constraints. There was no significant change in SF36 scores, QoL measure, postoperatively. Conclusions: Ileal conduit urinary diversion improves the urinary QoL of patients with neurogenic bladder dysfunction by decreasing limitations and constraints induced by urinary disorders, but has no impact on general QoL. 


"Another QoL study; I blogged this to say that QoL data is important when making the case to Commissioners about the need for these sorts of operations. Fortunately, urinary diversion procedures are seldom necessary these days, but when they are rarely done they have a big impact on the quality of someone's life. We need to remember this!"


CoI: Nil.

CCSVI - Big Idea Little Evidence


Monday, 20 June 2011

Neuroimmunology Fundraising - "The Big Bake"

Thank you! The neuroimmunology team at Barts and The London have just raised £372 for the MS Society with their cake sale.


From left to right: Priya, Monica, Sarah, Alison, Katie, Alicia, Adriana, Ruth and Beki

CoI: I love cake!

Vitamin D metabolic pathway genes and risk of MS

Orton et al. J Neurol Sci. 2011 Jun 15;305(1-2):116-20. Epub 2011 Mar 26.

Previous studies have shown that serum vitamin D levels are genetically influenced. Therefore variations or polymorphisms in vitamin D pathway genes are candidates for association with MS susceptibility.Surprisingly, no there was significant association of vitamin D pathway genes with MS susceptibility after correction for multiple comparisons. The findings fail to directly connect vitamin D metabolism genes to MS susceptibility, despite a large sample size and comprehensive gene coverage.

"Negative papers are as important as positive ones in science. Despite the size of this study (1364 MSers and 1661 unaffected first-degree relatives) the study is still not large enough to look at rare variants as susceptibility genes for MS. So we still need to keep an open mind about the possibility of genes involved in vitamin D metabolism being involved in MS disease susceptibility. Watch this space!"

CoI: Sreeram Ramagopalan a co-author on this paper works in our group. 


 

Sunday, 19 June 2011

Top of the Pops: Dr Giles Elrington

Since making a selection of our talks from the "2nd Barts and The London MS Research Day" available on-line, Dr Giles Elrington's talk on "Emerging Therapies for Multiple Sclerosis" has been a run away success with the most viewings. Well done Giles!


More on Quality of Life (QoL) Research

Re comment from anonymous and others: "Nothing annoys me more that the money wasted on quality of life type research."

QoL research has to be done; in fact it is critical if we want to get drugs licensed for use in the UK. NICE assesses drugs based on their impact and this includes their impact on QoL; they need to know this to be able to assess their cost effectiveness. NICE do this by assessing what the direct costs of the drug are to NHS and use the cost of the quality-adjusted life year (QALY) for this purpose. The QALY is the measure of disease burden that health economists have developed; the QALY includes both the quality and the quantity of life lived. In relation to MS DMTs we think that NICE set the threshold at £30,000 to £36,000 per QALY to approve DMTs. Interferon beta and glatiramer acetate did not pass this threshold, which is why we have the Department of Health's risk-sharing scheme. This latter scheme was meant to assess the impact of these drugs over time and if they did not deliver the necessary effectiveness the cost of the drugs would need to be reduced. In comparison, natalizumab was considered to be cost-effective in MSers with highly-active disease. Without QoL data we would not be able to prescribe natalizumab.

"Love it or hate it QoL research is essential, in fact vital and underpins all our work on DMTs. Take Sativex for example, the trials that got the drug licensed in the UK did not include QoL outcomes, making it impossible for NICE to assess its cost-effectiveness. Without approval by NICE the PCTs (not many of these left) and the new GP Commissioners are reluctant to fund its use. That's fine if you don't have severe spasticity but it makes it difficult for us neurologists' on the firing line when MSers want and need the drug. I must point out that only ~50% of MSers respond to Sativex, so it is not a magic bullet. It helps spread the hope, something we rely on to make peoples lives more comfortable."


Determinants of Quality of Life in MSers

Fernández et al. Patient characteristics and determinants of quality of life in an international population with multiple sclerosis: Assessment using the MusiQoL and SF-36 questionnaires. Mult Scler. 2011 Jun 13. [Epub ahead of print]

Background: MS has psychological and socioeconomic consequences that affect quality of life (QoL) as much as physical disability. This study was performed to determine the clinical and sociodemographic factors affecting QoL in a large international study using the MS International QoL (MusiQoL) questionnaire and SF-36. Results: In total, 1992 patients from 15 countries were enrolled with an average age of  42yrs. The analyses identified (1) lower educational level, (2) higher EDSS score, i.e. disability, (3) cognitive impairment, (4) being single and (5) shorter time since last relapse as significant predictors of lower QoL. In comparison (1) older age, (2) female sex, (3) higher EDSS score, (4) shorter time since last relapse and (5) receiving current MS treatment were significant predictors of lower QoL on the physical component of the SF-36. The SF-36 mental component summary score was linked to (1) occupational status, (2) inpatient/outpatient status, (3) time since last relapse, and (4) whether the patient was receiving MS treatment. Conclusion: Sociodemographic and clinical factors are linked to QoL in patients with MS. Interventions that affect these factors might be expected to influence QoL.

"No surprises here; common sense if you ask me. Being aware of these factors may help MSers focus on improving their QoL. As healthcare professionals we can help by asking about these factors, bringing in help when necessary and most of all treating aggressively in the hope of preventing disability. The latter underpins a lot of the factors linked to poor QoL. Does anybody disagree?"

CoI: Nil

Saturday, 18 June 2011

The positive effect of CBT on fatigue in patients with MS

Knoop et al. Psychol Med. 2011 Jun 15:1-9. [Epub ahead of print]

Chronic fatigue is a major problem in MS; it's the commonest symptom PwMS complain about (~85%) and in patients with fatigue ~50% claim it be their most disabling symptom. A randomized controlled trial has shown that cognitive behavioural therapy (CBT) is more effective in reducing MS fatigue than relaxation training (RT). This study analysed additional data from this trial . Results: avoidance behaviour and three cognitive variables (symptom focusing, believing symptoms are a sign of damage and a negative representation of fatigue) improved significantly more in the CBT than the RT group. Changing negative representations of fatigue mediated the decrease in severity of fatigue. Conclusions: Change in beliefs about fatigue play a crucial role in CBT for MS-related fatigue.

"If you suffer from severe MS-related fatigue you should look into CBT; some of my patients have had good responses. This paper attempts to define which patients are likely to respond to CBT. I wish we knew more about MS-related fatigue; I would rate the treatment of MS-related fatigue as one of the biggest unmet needs in MS. Do you agree?"

Friday, 17 June 2011

Latest PML risk estimate on natalizumab


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 have had at least 1 dose of natalizumab. Incidence estimates by treatment epoch are calculated based on natalizumab exposure through 31st May 2011 and and 133 confirmed cases as of 1st June 2011. The incidence for each epoch is calculated as the number of PML cases divided by the number of patients exposed to natalizumab (e.g. for 25 to 36 infusions all PML cases diagnosed during this period is divided by the total number of patients ever exposed to at least 25 infusions and therefore having risk of developing PML during this time). This data has been provided by Biogen-Idec.

"The data is becoming much clearer in relation to the risk of PML on natalizumab. Please see earlier post on new data in relation to risk profiling in relation to duration of exposure, JCV seropositivity and previous exposure to chemotherapy; click here for post on risk stratification."  

My MS Manager

Do any of you use "My MS Manager" an iPhone App to monitor your disease? If yes, can you please let us know how good it is and does it meet your needs. An MS smartphone App is something we have been thinking about doing ourselves and I am involved with a consortium that is developing a suite of Apps to track the impact of your disease on your life; the aim being is to use it as an outcome measure in clinical trials.

Click here for the link to download "My MS Manager"

CoI: nil

Results of the EBV survey


"Wow, I am surprised. Finally something must be getting through. THANK YOU!!!"

Thursday, 16 June 2011

Genetic Testing: Can We Predict Multiple Sclerosis?

After the human genome project was completed in 2003 it was predicted that “predictive genetic tests will exist for many common conditions”, but nearly 10 years on how close are we to being able to predict disease risk from a person’s DNA?

Multiple sclerosis does not result from something wrong in a single gene, but is instead subtly influenced by a combination of many different genes, as well as environmental factors such as vitamin D, smoking and EBV. In the 1970s, a form (allele) of the HLA-DRB1 gene, called HLA-DRB1*15, was shown to increase the risk of MS by 3-fold (300%). Only recently has further understanding of the genetics of MS been made as genome-wide association studies (GWAS) have identified approximately 50 locations in the human genome which also influence risk. The gene variants discovered by GWAS barely nudge someone’s overall risk, typically increasing it by a factor of 1.1–1.3 (10 to 30%).

It is now possible to perform a GWAS on yourself in attempt to work out your individual risk for developing disease. Being a geneticist particularly interested in risk prediction, I signed up to a genetic test from 23andme (note we are not advising for anyone to do this). I received my results yesterday and the first thing I did was to look at my disease risks.

23andMe gives calculates my risk according to my genes and then compares to this the population risk. Based on my genotype data I am at “decreased risk” for MS 0.2% as compared to the average risk of 0.3%.




Looking in more detail, this is based on the risk associated with two genetic markers, HLA-DRB1 and a gene identified by GWAS, called IL7RA which codes for an immune molecule called interleukin 7 receptor alpha. I have the risk allele for IL7RA but not HLA-DRB1*15. Because HLA-DRB1*15 is the key genetic locus in MS, not having this risk allele has a major impact on my risk.



How robust are these risk estimates? The risk associated with each genetic variant can vary across different populations, environments and age groups and, as a consequence, affect disease risk estimates and thus anything provided by 23andme needs to be taken in context. These caveats aside, it is a bit disappointing that 23andme only look at two genetic markers- there are now more than 20 genes associated to MS (De Jager et al. Nat Gen 2009), and so if I had all the other risk alleles what then would be my risk?

However, because the genetic risk loci are common in the general population (i.e. 20% of everyone in the UK carry HLA-DRB1*15 but will never develop MS), the question remains whether by studying just genetics will MS be predictable? A study to address this by Phil de Jager and colleagues at Harvard (De Jager et al.) has shown the predictive power of 16 MS risk loci together is generally not great.

So will it ever be possible to predict who will develop MS? As the previous post discusses, the environment can alter the risk associated with a genetic marker (called a gene-environment interaction). Combining HLA and smoking increases MS risk by more than 1000%- a huge effect. By including other data (e.g. EBV antibody levels, vitamin D levels) it might be possible to develop a model with strong predictive power and to identify individuals in which preventative measures could be studied.

One of the major goals of the Giovannoni group is to see if MS is predictable and therefore preventable. Watch this space.

COI: I have a pen from 23andme

Posted on behalf of Sreeram Ramagopalan (our vD Champion)

Yellow Fever Vaccination and Increased Relapse Rate in Travelers With MS

Farez and Correale. Arch Neurol. 2011 Jun 13. [Epub ahead of print]

A small study that investigated the effect of yellow fever immunization on the subsequent risk of MS relapse in 7 PwMS. Result: The annual exacerbation rate during risk periods following immunization was 8.57, while the relapse rate outside the risk period was only 0.67 (rate ratio = 12.778; P < .001). Three and nine months after immunization, the PwMS showed a significant increase in MRI activity compared with 12 months prior to vaccination. Conclusions: For patients with MS traveling to endemic yellow fever areas, vaccination should be recommended on the basis of carefully weighing the risk of exacerbation against the likelihood of exposure to the yellow fever virus.

"This is a small study but confirms my predictions of live vaccinations to PwMS. It is well established that infections are a potent trigger of MS relapses. It is therefore not surprising that a live vaccine does the same. The good news is that the development of  an inactivated yellow fever vaccine is well advanced. Another issue for PwMS to consider is the risk of exotic infections whilst taking immunosuppressive agents."

Smoking and two human leukocyte antigen genes interact to increase the risk for MS


Hedström et al. Brain. 2011 Mar;134(Pt 3):653-64. Epub 2011 Feb 8.

As you know from previous postings both genetic and environmental factors are associated with MS. Gene-environment interactions may exert stronger effects. 

In this study, the investigators studied potential interactions between genetic risk factors and smoking in relation to risk of developing MS. Results: a significant interaction between two genetic risk factors was found; smokers who had inherited a particular human leukocyte antigen DRB1*15 were less likely to inherit another leukocyte antigen A*02; the interaction between these two genetic factors was absent among non-smokers. Importantly, compared with non-smokers with neither of the genetic risk factors, smokers with both genetic risk factor were 13.5x more likely to get MS. For smokers without the genetic risk there chances were only 1.4x. For non-smokers with both genetic risk factors there risk was 4.9x greater than the background risk. Conclusion: The risk of developing MS associated with specific human leukocyte antigens is strongly influenced by smoking status. 



Please see previous smoking posts on this blog: "smoking and MS risk" and "young girls and smoking".

"How these interactions lead to an increased risk of MS is unknown. Clearly we need to explain this if we want to understand the cause of MS." 

Wednesday, 15 June 2011

Another target identified to promote remyelination


In response to Graeme W's comment from the 14th June:

Wang et al. An oligodendrocyte-specific zinc-finger transcription regulator cooperates with Olig2 to promote oligodendrocyte differentiation. Development. 2006 Sep;133(17):3389-98.

These investigators identified a transcription factor called Zfp488 in oligodendrocytes (the cells that make myelin) that appears to be important in stimulating the oligodendrocytes to mature and make myelin. Transcription factors are proteins that enter the nucleus of cells and turn on specific genes that control the function of the cell. An analogy will be a specific icon on the desktop of your PC that controls a specific program; when you click on the icon a specific programme is launched. Hopefully this work will be confirmed by others and the pathway shown to be important in humans and MS. It may be also be a "druggable" target, i.e. pharma companies may be able to develop drugs to activate the pathway to promote myelination in MS.

"Interesting things continue to happen in the laboratory that may in the future lead to treatments for progressive MS. No recent news regarding this transcriptional factor could be interpreted as bad news. A trawl through the patent literature will be necessary to see if any new patents have been filed on this target. Any volunteers?"

Pseudobulbar affect: an under-recognized and under-treated neurological disorder

Work et al. Adv Ther. 2011 Jun 6. [Epub ahead of print]

Some of you may recognise a "pseudobulbar affect"; it is a syndrome of emotion that comprises disinhibition, characterised by uncontrollable, exaggerated, and often inappropriate emotional outbursts, which may cause severe distress, embarrassment, and social dysfunction. MS is a common cause of a pseudobulbar affect and typically occurs in patients with progressive disease that are disabled. The presence of pseudobulbar affect occurs when MS lesions involve the frontal lobes or the pons in the brain stem (see figure below). In this large online survey ~10% of subjects had pseudobulbar affect; this high figure indicates that the condition is under-recognised. This is important as there are effective treatments that can reduce the frequency and intensity of these emotional outbursts. If this affects you and has not been recognised, you may want to bring it to the attention of your medical team. 





CoI: None

Author defends film of assisted dying as BBC fields complaints

I make no apologies for discussing death on a MS Blog. MS is a serious disease and the topic needs airing. Did you watch the BBC documentary on assisted suicide with Terry Pratchett? For those of you living the UK, who missed it, you can see it on the BBC iPlayer: Choosing to Die.

Death and assisted suicide in the context of MS a difficult subject to discuss. We are trying to get some data on this issue to guide us with our clinical service development. If you are involved in MS in any way we would appreciate 5 minutes of your time to complete the following survey: end-of-life survey. We promise to publish the headline results of the survey on this blog in the near future. Thank you. 

If you don't have access to BBC iPlayer you may find the The Richard Dimbleby Lecture delivered by Terry Pratchett called "Shaking Hands with Death" in 2010, of interest. It covers similar ground.


CoI: none

Tuesday, 14 June 2011

Article of interest (3): month of birth and risk of MS

Willer et al. BMJ. 2005 Jan 15;330(7483):120. Epub 2004 Dec 7.

In Canada significantly fewer patients with MS were born in November compared with controls from the population census and unaffected siblings. These observations were confirmed in a dataset of British patients. A pooled analysis of datasets from Canada, Great Britain, Denmark, and Sweden showed that significantly fewer (8.5%) people with MS were born in November and significantly more (9.1%) were born in May. The month of birth and risk of MS are associated, more so in familial cases, implying that there is some interactions between genes and environment that may be related to climate. Such interactions may act during gestation or shortly after birth in individuals born in the countries studied.


"The finding that your month of birth affects your risk of MS is very interesting and tells us something about the causal pathway in MS. The current hypothesis is that if your mother was pregnant during winter ( and you were born in April), a time when she is more likely to be vitamin D deficient, it affected the development of your immune system making you more likely to develop MS in later life. On the other hand if you mother was pregnant in summer ( and you were born in November), this lowers your chances of getting MS. This study supports another Prevent MS strategy we are promoting, i.e. high-dose physiological supplementation of vitamin D in pregnancy. If only the British public health officials will take this on board; they have in France."

Symptomatic liver injury associated with complementary and alternative products (Ayurveda-AP-Mag Capsules(®) ) in a beta-interferon-treated PwMS

Tremlett et al. Eur J Neurol. 2011 Jul;18(7).

Liver damage or hepatotoxicity due to an complementary medicine in combination with IFN-beta.

"There dangers associated with taking alternative medicine in combination with IFN-beta and other DMTs with the potential to affect liver function. Please be careful; if in doubt don't or at least ask." 

Monday, 13 June 2011

Direct conversion of human fibroblasts to neurons

Pfisterer et al. Proc Natl Acad Sci U S A. 2011 Jun 6. [Epub ahead of print]

In this study investigators converted fibroblasts, a cell found in the skin, into functional neurons by the overexpression of three transcription factors (Ascl1, Brn2, and Myt1l). Transcription factors are the messages the cell uses to turn certain genetic programs on or off; in this case the program to make a cell become a neuron. When the expression of the three conversion factors was combined with the expression of two genes involved in dopamine neuron generation (Lmx1a and FoxA2) they converted the cells into dopaminergic neurons (the cells that are lacking in Parkinson's disease). They concluded that subtype-specific induction of neurons from human skin cells could be potentially valuable for cell replacement therapy in Parkinson's disease and by analogy MS.

"Exciting stuff; if the technology wheel keeps turning we will have the material to test neuronal sub-type specific therapeutic strategies in PwMS."

Relationship between MRI lesion activity and response to IFN-beta in RRMS

Rio et al. Mult Scler. 2008 May;14(4):479-84.

Aims: This study evaluated whether brain MRI performed at the start of IFN-beta and after 12 months of treatment could allow one to identify PwRRMS who would develop an increase in disability within the first 2 years of treatment. Results:  Subjects with active lesions on MRI at 12 months. i.e. non-responders on MRI,  were 8.3x more likely to have an increase in disability after 2 years of IFN-beta  therapy compared to patients without MRI activity (95% confidence interval* 3.1-21.9; p < 0.0001). 

"There are a host of other studies like this showing the approximately the same result. In other words if you are on IFN-beta treatment and have evidence of ongoing disease activity on MRI or clinically you are more likely to progress in the future. Good or bad news? I would say good news as we now have a one way, albeit rather a crude way, to assess response or non-response to IFN-beta treatment."

Sunday, 12 June 2011

The Mechanism of Action of Interferon-β in RRMS

Kieseier, CNS Drugs. 2011 Jun 1;25(6):491-502. 

The mechanism of action of IFNβ is complex: 
  1. Increases the expression and concentration of anti-inflammatory agents and downregulates the expression of proinflammatory cytokines (messenger molecules that the cells of the immune system use to communicate with each other). 
  2. Reduces the trafficking of inflammatory cells across the blood-brain-barrier.
  3. Increases nerve growth factor production, which may lead to an increase in neuronal survival and repair. 
  4. Increases the number of natural killer cells in the peripheral blood; these cells are efficient producers of anti-inflammatory mediators, and may have the ability to curb inflammation. 
IFNβ's actions manifest clinically as reduced MRI lesion activity, reduced brain atrophy, increased time to reach clinically definite MS after the onset of neurological symptoms, decreased relapse rate and reduced risk of sustained disability progression. 

"The one action that did not make this list and should have is its effect on viruses, both external viruses for example flu and internal or persistent viral infections such as EBV and other herpes viruses. By reducing reactivation of the viruses that live within our bodies interferon-beta may reduce MS disease activity. This is something we are studying at present in relation to EBV."

CoImultiple

Saturday, 11 June 2011

Smoking in young girls

Smoking is an important risk factor for MS (see previous post) and almost certainly interacts with other risk factors. Therefore getting young people to not start, or to stop smoking, is an important message of our "Prevent MS" campaign.

If you are a child or a sibling of someone with MS and have first hand experience of the disease how could you consider smoking or continuing to smoke?

A worrying trend is the apparent increase in smoking in young girls, relative to boys. The reasons for this are complex and need to be addressed if we want to reduce the incidence of MS in the next generation.


Click here to read the report on "Smoking among young people in England in 2009"



"I get very depressed when I see young people, particularly woman, smoking; smoking increases your chances of getting MS by ~50%."

Article of interest (1): change in sex ratio of MS

Over the next few months I will blog about a series of MS articles that I consider very important; important enough to shift or even change the paradigm*.

Orton et al. Lancet Neurol. 2006 Nov;5(11):932-6.

This study showed that the female to male sex ratio by year of birth has been increasing for at least 50 years and now exceeds 3.2:1 in Canada.


"The incidence of MS is increasing; particularly in woman. Why?"

* Paradigm: a worldview underlying the theories and methodology of a particular scientific subject.

Friday, 10 June 2011

New MS journal: Multiple Sclerosis and Related Disorders

Good news a new MS journal that will include "summaries of key articles written for a lay audience" that will "be provided as an on-line resource".

Click here for journal

CoI: I am one of the Chief Editors

MS the Big Knit: did you guess correctly?

The Bottle Neck in MS Drug Development

I would like to stress that there is no shortage in potential drugs for treating MS; this includes both the relapsing and progressive phases. The problem in my opinion are the costs associated with drug development, the lack of a tried-and-tested rapid phase 2 trial for assessing neuroprotective therapies and  the lack of focus on preventative strategies. The following is a figure demonstrating the current bottle-neck in MS drug development:


Thursday, 9 June 2011

Society's perception of MS: how bad is it?

In response to your comments about the prognosis and severity of MS. There is no doubt in my mind that MS is a disabling disease and leads to disability in the majority of subjects given sufficient time. However, this statement refers to the prognosis from natural history studies done in the the pre-DMT era. I believe that in the current era with aggressive treatment early on the prognosis has improved. 

The following figure demonstrates UK Society's perspective on the disease. On the y-axis is utility an index of quality of health used by health economists; 1 is perfect quality of health and 0 is death. Your utility on the day you are born is 1 and gradually drops to 0 when you die. A value less than 0 is considered a quality of life worse than death. It is alarming that in the UK a PwMS with an EDSS of 8.0 or 9.0 (weakness in all 4 limbs and/or bed-bound) is considered to have a quality of life worse than death. I am told that no other chronic disease scores this low. Alarming?



"I use this figure as the backbone of my argument to support early aggressive treatment. How can we not treat this disease aggressively? Despite the poor Societal perspective of MS, MS does not fulfill contemporary criteria for being a terminal illness. Would you agree? If not we can continue the debate."

Wednesday, 8 June 2011

Design in Healthcare

Some of you may already be aware that about 10 months ago we employed Alison Thomson, a designer, to review our outpatient services with the view of improving the experience for PwMS attending Barts and The London. It has been a very interesting exercise for us and made us see ourselves in a different light. The good news is that Alison has had her work accepted for a platform presentation at the inaugural Design4Health Conference at Sheffield Hallam University.
click here for more details

The following is some of Alison's work in relation to MS:

1. The chronic facility (please watch the video)
2. Anatomy of MS

"The purpose of incorporating good design into healthcare service provision is a no-brainer for me; hopefully PwMS attending our hospital will notice a difference in the next 6-12 months."