Author: Gavin Giovannoni

MS@thelimits 2018

Do you want to attend the MS@thelimits 2018 meeting?  This year the focus is on cellular therapies, comorbidities and trials in more advanced MS. 


Have a look at the programme. 



Following on the success of last year’s MS at the limits meeting in London we are holding a second meeting this November. 


The feedback we got from last year’s meeting was exceptionally good and I think it was due to the quality of the speakers and the format; i.e. 20-minute talk and 20-minute discussion. 


If you want to attend please register online.



ProfG    
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Prof G the feminist

Three things happened to me this week that made realise that I am a feminist.




Firstly, Alasdair Coles’ complimented me on the piece I wrote about ‘the MS Establishment‘ and the observation that so few women neurologists have made it onto trial steering committees. He has even asked some of his Cambridge medical students to track down the sex of all the author’s in his database so that we can do formal metrics on the male:female ratio of writing committee members of the pivotal phase 3 studies. I believe that highlighting the issue of a lack of women at the top may nudge the MS community to do something about it.

 At the MS Society Treatment Selection Workshop I attended on Tuesday, where I met Alasdair Coles, I was sitting next to a younger female colleague when Dr Richard Wyse, from The Cure Parkinson’s Trust, was presenting. He showed a slide of their expert advisory committee, which had a list of 18-20 names of eminent Parkinson’s Disease experts from around the globe. The sad thing was that not one of them was a woman. I nudged my female colleague and pointed out the total lack of women on this panel and she responded that men make more noise and hence are more likely to get invited to these sorts of things. That is not the issue. Without the diversity and different thinking, that women bring to committees like this, these committees are likely to underperform. And why shouldn’t women make it to the top in their fields of study? 

 Finally, I was teaching a group of Latin American Neurologists later this week when one of the female neurologists in the group said she supported everything I was doing to help women in neurology. ‘What I asked her?’ She said she viewed me as a feminist and followed me on Twitter and LinkedIn. To be honest with you I thought I was just being a good Dad standing up for his daughters’ future rights.  I have never thought about being a feminist in the past, but I suppose as a person who supports equal rights for women in society and in the workplace, I am one.

 I have just arrived in LaLa land to attend the AAN. I wonder how many of the attendees will be women? If you are reading this and are in a position of influence can you please try and support women in neurology, in particular academic neurology. There are far too few at the top. 

ProfG    
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Vaccines and Vaccinations: The Big Differentiator

I predict vaccines and the timing of vaccinations will in time become a major differentiator between the maintenance therapies and the immune reconstitution therapies (IRTs). 



What do you think? 

The systematic analysis below finds no link between human papillomavirus (HPV) vaccination and MS. This will be very reassuring for parents, public health doctors and the companies that manufacture and market these vaccines. 

What this study does not address is the issue of whether MSers should be vaccinated, or revaccinated, against HPV before starting DMTs. 

In the UK the Public Health England vaccination programme only covers girls with the quadrivalent HPV vaccine at 12-18 years of age. The quadrivalent vaccine only protects these girls and women against ~60% of the HPV strains and not against the HPV strains that cause vaginal or perineal warts. The newer HPV vaccine covers 9 strains, i.e. >90% of the strains that cause cervical cancer and many of the viral strains that cause warts and other cancers. Reassuringly, women who have previously been vaccinated with the earlier vaccine are able to respond to the newer vaccine. 

It is now clear that older women and men are also at risk from HPV infection. The sexual revolution in older life, that is being fuelled by social media and online dating sites, mean that the whole population is at risk of HPV infection and its consequences. HPV is not only linked to cervical cancer but causes penile, anal, throat and some oesophageal cancers so there is a strong argument for the whole population to be vaccinated with the newer 9-valent vaccine. 

The NHS currently covers the MSD vaccine called Gardasil, which protects against HPV types 6, 11, 16 and 18. It is generally given as using a 2-dose schedule with the 1st injection at any chosen date and the 2nd injection 6 months after the first injection. In comparison the newer and better Gardasil-9 vaccine, covers HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58.  Gardasil 9 can be administered according to a 2 dose schedule, with the second dose being administered between 5 and 13 months after the first dose. If the second vaccine dose is administered earlier than 5 months after the first dose, a third dose should always be administered. Another option is to use the 3-dose (0, 2, 6 months) schedule.


The issue with all of these schedules is that it means the starting of DMTs has to be delayed so that an adequate immune response can develop against the vaccine components. The delay in starting DMTs could have deleterious effects in relation to MS disease activity (‘Time is Brain’). Another issue is the question of what happens to patients who are already on agents that blunt the immune response? The latter is a particular problem for maintenance treatments such as fingolimod and ocrelizumab that inhibit vaccine responses. In comparison immune reconstitution therapies or IRTs, at least allow an effective immune response to occur once the immune system has reconstituted. 

Over the last few months whenever I give a talk on IRTs the above issues about vaccinations arises. I, therefore, predict vaccines and the timing of vaccinations will in time become a major differentiator between the maintenance therapies and the IRTs. What do you think? 


Mouchet et al. Human papillomavirus vaccine and demyelinating diseases-A systematic review and meta-analysis. Pharmacol Res. 2018 Apr 14. pii: S1043-6618(18)30288-3. 


BACKGROUND: Approved in 2006, human papillomavirus (HPV) vaccines were initially targeted for girls aged 9-14 years. Although the safety of these vaccines has been monitored through post-licensure surveillance programmes, cases of neurological events have been reported worldwide.


PURPOSE: The present study aimed to assess the risk of developing demyelination after HPV immunization by meta-analysing risk estimates from pharmacoepidemiologic studies.


DATA SOURCES: A systematic review was conducted in Medline, Embase, ISI Web of Science and the Cochrane Library from inception to 10 May 2017, without language restriction.


STUDY SELECTION: Only observational studies including a control group were retained. Study selection was performed by two independent reviewers with disagreements solved through discussion.


DATA EXTRACTION: This meta-analysis was performed using a generic inverse variance random-effect model. Outcomes of interest included a broad category of central demyelination, multiple sclerosis (MS), optic neuritis (ON), and Guillain-Barré syndrome (GBS), each being considered independently. Heterogeneity was investigated; sensitivity and subgroup analyses were performed when necessary. In parallel, post-licensure safety studies were considered for a qualitative review. This study followed the PRISMA statement and the MOOSE reporting guideline.


DATA SYNTHESIS: Of the 2863 references identified, 11 articles were selected for meta-analysis. No significant association emerged between HPV vaccination and central demyelination, the pooled odds ratio being 0.96 [95%CI 0.77-1.20], with a moderate but non-significant heterogeneity (I2 = 29%). Similar results were found for MS and ON. Sensitivity analyses did not alter our conclusions. Findings from qualitative review of 14 safety studies concluded in an absence of a relevant signal.


LIMITATIONS: Owing to limited data on GBS, no meta-analysis was performed for this outcome.


CONCLUSION: This study strongly supports the absence of association between HPV vaccines and central demyelination.

ProfG    
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Reflections on all things MS from Stornoway

We have just finished our 2018 Barts-MS Research Day on Stornoway with the Glasgow-MS team. The experience has been very humbling and quite and an eye-opener in terms of living with a chronic disease, such as MS, on a remote Island.


Barts-MS and Glasgow-MS hugging the Callanish Stones, Western Isles.




There are only 87 people with MS in the Isles with a denominator of ~26,000 people living on the Islands. The prevalence (all known existing cases) of MS in the Western Isles is, therefore, close to 340/100,000; this is very, very high. A recent MS incidence study in the Scottish Highlands puts the incidence (new cases per year) at ~15/100,000. The only figures that I am aware of that are worse than this are the Orkney and Shetland Islands at ~18/100,000 and Saskatchewan at ~17/100,000. In short, the Western Isles is in the top of the MS league table in terms of the MS epidemic. Please note my use of epidemic; as the incidence continues to increase we can’t call it endemic yet (stable incidence).

Sitting here in Stornoway airport, as I am writing this post, I have just seen someone coming off the plane in a wheelchair. The reality of the MS epidemic on the Islands is that if I was a betting person the odds are that this person has MS. Sad but true.


At the end of my closing talk on Saturday Dr Niall Macdougall asked me a challenging question: “If I was to become the resident, or the advisory, neurologist to the Western Isles what would I do to improve MS outcomes on the Isles?”.

The following are some my initial thoughts:

  1. I would first spend time meeting people with MS, their families and the healthcare professionals on the Islands to understand their worldview and to get a feel for what is required to address their needs. I got a sense this weekend that a lot of the people with MS are quite accepting of their lot; it is as if this is the price you pay for living on the Islands. I am not sure if this impression is correct, but if it is I would spend time activating patients to demand more from the Scottish NHS. To do this they would need comparative data from other areas of Scotland to see if their access to treatments, etc. is inferior to the mainland. 
  2. I would start an MS register of family members of people with MS and try to contact people who have left the Western Isles and living on the mainland or elsewhere. I would want to educate these people about MS and the risk factors predisposing them to MS, in particular, smoking and low vitamin D levels and lifestyle factors such as obesity. The register could then be used as a platform for designing and piloting MS prevention studies. 
  3. I would help the MS Unit in Glasgow develop a business case to increase the amount of MSology cover for the Isles, including telemedicine clinics. This may include occasional visits to see patient to disabled to travel. 
  4. I would make sure Rachel Morrison, the local MS nurse specialist, has the necessary training to become a prescribing nurse specialist. This would help the neurologists in Glasgow and the GPs on the Island. 
  5. I would make the case for a mobile MRI scanner to visit the Isles for a few weeks at a time several times a year. This would save pwMS having to travel to Glasgow for their scans and would reduce the waiting times for MRI scans. The need for MRI scan is not limited to MS, but is clearly a problem for other specialities, for example, orthopaedics, surgery, etc. People with MS on the Isles need access to MRI to help with screening for MS, diagnosis of MS and for monitoring of their response to DMTs. 
  6. I would help Rachel expand her MS service to include group clinics to activate patients to self-monitor, self-manage and to expand the support network. It is quite clear that she is key to make any new services work. 
  7. I would create a risk register. As with all services that depend on a single practitioner they are at risk of a catastrophic breakdown in service provision in the event that person gets ill, leaves the Isles or is unable to work. A sustainability and succession plan is urgently needed. Rachel is a superwoman, but she is a mortal. I would, therefore, try include other HCPs in the new service structure, for example, by asking the neurology nurse specialists to cross-cover each other (maybe they do already). The latter may require investment in IT systems and common standard operating procedures to make sure that any urgent handovers are seamless. I would not be surprised if these are in place already. I am sure the Islanders have systems in place to cover any eventuality; they seem to be very resourceful. 
  8. As we were getting off the flight connecting flight in Glasgow, the Glasgow-MS team came up to me and said they had a solution to Western Isles’ problems. They felt a GPwSI (General Practitioner with a Specialist Interest) in MS would be the solution. I agree, but you would have to find a GP who was prepared to do an MS fellowship and be prepared to take on the care of all the patients on the Island. The GPwSI could then be supported by the Glasgow-MS team by telemedicine. It would also be important to make sure this GPwSI could prescribe and monitor DMTs; may be the introduction of newer DMTs such as oral cladribine and ocrelizumab will make this easier. 


I sincerely hope that Alison Thomson, our Scottish designer in residence, feels she has given something back to her homeland. Without her efforts, the weekend would not have happened. I would like to thank the other members of the Barts-MS and the Glasgow teams for making the weekend such a success. Thank you to Rachel and the Stornoway team for your hospitality; you made us feel very welcome.

Finally, to Roche, Merck and Sanofi-Genzyme for the educational grants that allowed us to host the weekend. It is much appreciated I am sure the event will be remembered for many years to come. We have several action points to follow-up on and I think that MSers living in the Western Isles will now get more attention. For example, I definitely want to study the epidemiology of MS on the Isles in more detail. I suspect the cause of MS is to be found in Western Scotland and the Scottish Isles. DrK hinted at tweaking his off-label cladribine protocol so that it can be used safely on the Islands; dare I suggest he call it ‘The Island Cladribine Protocol’?

I am convinced that doing research days away from London is a way to reach many more pwMS and their families. We will let you know when our Stornoway talks go live on YouTube. If you have any suggestions where you think we should hold our Barts-MS day in 2019 please let us know.



ProfG    
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What is so special about Stornoway?

A post to celebrate some of the MS Champions who help make the MS-World go around.


Stornoway, Lewis, Western Isles of Scotland


A few years ago Dr Niall MacDougall came down from Glasgow to spend 3 months at Barts-MS MS as a visiting fellow. This was just prior to him getting his first consultant job as an MSologist in Lanarkshire, Scotland. It was during this visit that he made me appreciate the scale of the MS crisis in Scotland and the burden it was placing on a clearly under-resourced Scottish Health Service. It also made me realise that in comparison MSers in London have it relatively good. Londoners have a choice; there are 6 regional neuroscience centres and MSers can vote with their feet. This is not the case in Scotland.

When Niall started his new job he was thrown into the deep end and immediately had a crisis with the loss of his MS nurse specialist. She was forced to leave because she could not cope with the workload. She has subsequently been replaced by two nurse specialists, but based on their caseload even two nurses is not enough. Niall, who is an incredibly caring neurologist, his MS nurses and their extended team of allied healthcare professionals are true MS Champions and are making a real difference to their Lanarkshire patients’ lives.

 Shortly after Niall’s visit Alison and I were approached by Rachel Morrison, the MS Nurse Specialist who covers the Western Isles of Scotland, at the MS Trust meeting in Windsor in 2016. Rachel asked us if we would consider visiting the Islands and hosting an MS Research Day for her patients on the Island. After a false start in 2017, we have finally managed to get our acts together and will be spending three days on Lewis. The Western Isles does not have a resident neurologist and, therefore, all the patients have to travel to Glasgow to seek a neurological opinion. This can make it difficult for patients as trips from the island are often cancelled due to bad weather, but the fact that they have a rather exceptional caring MS nurse specialist in Rachel makes the real difference. For example, I have just written a letter of support for Rachel to the Western Isles Hospital to help set-up a new rehabilitation service for young people with disabilities. Rachel is clearly an MS Champion extraordinaire. 

Stornoway on the Isle of Lewis is one of the highest MS incidence and prevalence areas in the world. Based on recent estimates the incidence of MS in this region of Scotland is about 2.5x the incidence of MS in the SouthEast of England. The Glasgow MS Team and the other Scottish MS teams are doing their bit to manage the avalanche of patients, but the Scottish MS epidemic is very concerning and needs to be addressed. This is one of the reasons why we have launched our preventive neurology initiative to start working on preventing MS.  Dr Ruth Dobson will be rejoining Barts-MS in May; her brief to set-up the infrastructure to do MS prevention trials. MS is almost certainly a preventable disease, or at least partly preventable and we can’t leave it to the next generation of researchers to sort out. We have to #ActNow to #PreventMS.

 The good news is that at least five of the Glasgow MS team (Niall MacDougall, Pushkar Shah, Sarah-Jane Martin, Stewart Webb and Mhairi Coutts) will be partnering with Barts-MS over the next few days to run three separate educational activities on the Island. One for the healthcare professionals, a second for MSers and a third for the children of MSers. We plan to record the talks and will put them online for the wider community to watch. 

 You may know that Alison Thomson, our designer in residence, is Scottish and she has always wanted to give something back to her home country. The Stornoway MS Research weekend is one of the many activities Alison is involved in to help Scottish MSers. She has done an enormous amount of work organising this weekend, which makes Alison our super MS Champion. 

I would like to thank the other members of the Barts-MS team (David/MouseDoctor, Gareth/MouseDoctor2, Sharmilee/NeuroDocGnanapavan, Klaus/DrK and Beki) for taking time-out over a weekend and for making the effort to help MSers on a relatively remote, but important, group of Islands on the Western tip of Scotland. You are all MS Champions. 

 As for me, I am in the doghouse. Today is my 54th Birthday and instead of spending it with my family and our dog relaxing I will be travelling to Stornoway. I am sure we will have a tipple (Harris Gin), or two, tonight to celebrate my birthday and contemplate what the next few days hold for us. 


ProfG    
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Brain damage in MS predicts long-term unemployment

Do you love your brain? 



After reading this post you will love it even more. 



In this 12-year follow-up study of a trial cohort of MSers, brain volume loss, T1 lesion volume (black holes) and T2 lesion volume (white blobs) were the best MRI predictors of worsening employment status over the 12-year follow-up period. Amazingly having just one extra millilitre of T1 lesion volume was associated with a 53% greater risk of worsening employment status. Similarly, a brain volume decrease of 1% increased the risk of worsening employment status by 22%. 

To remind you T1 black holes are the more destructive lesions and result in the so-called  Swiss cheese brain; i.e. peppered by holes left behind by the more destructive MS lesions. 

Please remind yourself that preventing end-organ, or brain, damage should become the primary therapeutic target in MS. It is a no-brainer. 


Please note that biomarkers of brain damage come after the event, i.e. they are a consequence of unchecked MS disease activity. Once you have acquired the damage it can’t be fixed. This is why we need to prevent the damage from occurring in the first place. This is why it is so important to treat MS early and effectively. 

We need to view the use of DMTs in MS as a preventive strategy to protect the brain so that we maximise the brain health of the person with MS for their whole life. We have to make sure we get you, our patients, to old age with a brain that has enough reserve to cope with the ageing process. Quality of life in old age is what it should be about. Do you agree? You can disagree.



Kadrnozkova et al.  Combining clinical and magnetic resonance imaging markers enhance prediction of 12-year employment status in multiple sclerosis patients. J Neurol Sci. 2018 May 15;388:87-93.


BACKGROUND: Multiple sclerosis (MS) is frequently diagnosed in the most productive years of adulthood and is often associated with worsening employment status. However, reliable predictors of employment status change are lacking.



OBJECTIVE: To identify early clinical and brain magnetic resonance imaging (MRI) markers of employment status worsening in MS patients at 12-year follow-up.


METHODS: A total of 145 patients with early relapsing-remitting MS from the original Avonex-Steroids-Azathioprine (ASA) study were included in this prospective, longitudinal, observational cohort study. Cox models were conducted to identify MRI and clinical predictors (at baseline and during the first 12 months) of worsening employment status (patients either (1) working full-time or part-time with no limitations due to MS and retaining this status during the course of the study, or (2) patients working full-time or part-time with no limitations due to MS and switching to being unemployed or working part-time due to MS).


RESULTS: In univariate analysis, brain parenchymal fraction, T1 and T2 lesion volume were the best MRI predictors of worsening employment status over the 12-year follow-up period. MS duration at baseline (hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.03-1.18; p = 0.040) was the only significant clinical predictor. Having one extra milliliter of T1 lesion volume was associated with a 53% greater risk of worsening employment status (HR = 1.53, 95% CI 1.16-2.02; p = 0.018). A brain parenchymal fraction decrease of 1% increased the risk of worsening employment status by 22% (HR = 0.78, 95% CI 0.65-0.95; p = 0.034).


CONCLUSION: Brain atrophy and lesion load were significant predictors of worsening employment status in MS patients. Using a combination of clinical and MRI markers may improve the early prediction of an employment status change over long-term follow-up.

ProfG    
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Are you about to be treated with Alemtuzumab?

If you are about to be treated with alemtuzumab you may want to know about acute acalculous cholecystitis?  


Acalculous cholecystitis with pericholecystic fluid collection as demonstrated by abdominal computed tomography scans (G). (Figure from ResearchGate)
This is a relatively new complication that occurs early after starting alemtuzumab infusions. I can hear you all saying ‘Oh no, not something else to consider when making a decision to go high-efficacy high-risk’.



 Acalculous cholecystitis is inflammation of the gallbladder without evidence of gallstones or bile duct obstruction. It can be a severe illness that is a complication of various medical or surgical conditions, including the administration of alemtuzumab. The condition causes approximately 5-10% of all cases of acute cholecystitis and is usually associated with more serious morbidity (sickness) and higher mortality (death) rates. It is most commonly observed in the setting of very ill patients; e.g. patients on ventilators, with sepsis or burn injuries and after severe trauma. Acalculous cholecystitis is associated with a higher incidence of gangrene and gallbladder perforation compared to calculous (gallstone/s) disease. 

I recall looking after a patient with acalculous cholecystitis when I was a house officer. She had an acute abdomen and had to have an emergency cholecystectomy. At surgery, she had a gangrenous gallbladder. She managed to pull through but she spent many weeks in ITU.

 The usual presentation is of sudden onset right upper quadrant abdominal pain. Imaging studies typically reveal a distended acalculous gallbladder with thickened walls (>3-4 mm) with or without pericholecystic fluid (that is fluid around the gallbladder, see picture above). 

When you search the EMA’s EudraVigilance Database (3-April-2018) there are quite a few case reports under Lemtrada that could be due to acalculous cholecystitis. 

Biliary tract disorder = 1
Cholecystitis = 8
Acute Cholecystitis = 11
Gall bladder enlargement = 3
Gallblader edema = 2

Total = 25 cases

 If you are about to be treated, or retreated, with alemtuzumab please take abdominal pain seriously in the first few days and weeks after being treated. 

Croteau et al. Acute acalculous cholecystitis: A new safety risk for patients with MS treated with alemtuzumab. Neurology. 2018 Mar 30.

 OBJECTIVE: To evaluate acute acalculous cholecystitis (AAC) as a potential safety risk for patients treated with alemtuzumab.


RESULTS: Eight spontaneously reported cases meeting the case definition of AAC in close temporal association with alemtuzumab use were identified. 

 CONCLUSIONS: AAC represents a new and potentially life-threatening adverse event associated with alemtuzumab use in relapsing-remitting multiple sclerosis. In cases seen to date, early and conservative treatment resulted in good clinical outcomes, Awareness of this safety risk by general and speciality neurologists is important for prompt recognition and optimal management.

ProfG    
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How does your socioeconomic status affect your MS?

Does socioeconomic status predict outcomes in MS?



This rather startling paper shows that people with low socioeconomic status have reduced life expectancy that is predicted by slowed walking speed. As MS clips walking speed can these results be extrapolated to MS? I am sure they can, but we need MS-specific data. Let’s hope the ‘big-data’ miners will help replicate these findings in a population of MSers. 


The EDSS, the gold-standard MS disability scale, goes from zero (normal physical neurological function) to 10 (death). Along this scale walking speed drops off from being normal to being unable to walk. The message here is that if you can maintain your walking speed you are less disabled and hence further away from EDSS 10. This study also indicates that we must think of MSers being outside of the ‘normal population’. If we think like this then our treatment goals for MS change. This is why we are aiming beyond MS. The treatment target in MS is to ‘Maximise Lifelong Brain Health’. If we adopt this target it should revolutionise the way we treat MS. 


Please note that it is not only low socioeconomic status that predicts poor life outcomes but comorbidities (hypertension, diabetes, obesity) and low physical activity. Therefore if we are serious about treating MS and life then we need to proactively be screening and treating these comorbidities and prescribing exercise as a DMT.


Stringhini et al.  Socioeconomic status, non-communicable disease risk factors, and walking speed in older adults: multi-cohort population-based study. BMJ 2018;360:k1046.


Objective: To assess the association of low socioeconomic status and risk factors for non-communicable diseases (diabetes, high alcohol intake, high blood pressure, obesity, physical inactivity, smoking) with loss of physical functioning at older ages.


Design: Multi-cohort population-based study.


Setting: 37 cohort studies from 24 countries in Europe, the United States, Latin America, Africa, and Asia, 1990-2017.


Participants: 109 107 men and women aged 45-90 years.
Main outcome measure: Physical functioning assessed using the walking speed test, a valid index of overall functional capacity. Years of functioning lost was computed as a metric to quantify the difference in walking speed between those exposed and unexposed to low socioeconomic status and risk factors.


Results: According to mixed model estimations, men aged 60 and of low socioeconomic status had the same walking speed as men aged 66.6 of high socioeconomic status (years of functioning lost 6.6 years, 95% confidence interval 5.0 to 9.4). The years of functioning lost for women were 4.6 (3.6 to 6.2). In men and women, respectively, 5.7 (4.4 to 8.1) and 5.4 (4.3 to 7.3) years of functioning were lost by age 60 due to insufficient physical activity, 5.1 (3.9 to 7.0) and 7.5 (6.1 to 9.5) due to obesity, 2.3 (1.6 to 3.4) and 3.0 (2.3 to 4.0) due to hypertension, 5.6 (4.2 to 8.0) and 6.3 (4.9 to 8.4) due to diabetes, and 3.0 (2.2 to 4.3) and 0.7 (0.1 to 1.5) due to tobacco use. In analyses restricted to high-income countries, the number of years of functioning lost attributable to low socioeconomic status by age 60 was 8.0 (5.7 to 13.1) for men and 5.4 (4.0 to 8.0) for women, whereas in low and middle-income countries it was 2.6 (0.2 to 6.8) for men and 2.7 (1.0 to 5.5) for women. Within high-income countries, the number of years of functioning lost attributable to low socioeconomic status by age 60 was greater in the United States than in Europe. Physical functioning continued to decline as a function of unfavourable risk factors between ages 60 and 85. Years of functioning lost were greater than years of life lost due to low socioeconomic status and non-communicable disease risk factors.


Conclusions: The independent association between socioeconomic status and physical functioning in old age is comparable in strength and consistency with those for established non-communicable disease risk factors. The results of this study suggest that tackling all these risk factors might substantially increase life years spent in good physical functioning.

ProfG    
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Brain damage and the Black Dog

MSers are often depressed. Depression leads to poor quality of life, the breakdown in relationships, a sense of hopelessness, social isolation, unemployment and suicide. It is important that MSers are regularly screened for depression and treated.



 Are you interested in knowing more about depression in MS?




 The study below suggests that depression in MS may occur as a result of damage to the temporal and frontal regions of the brain, which may lead to a disconnection between the frontal and limbic systems of the brain. If this is the case then depression, at least in some MSers, is due to end-organ or brain damage. Is this not another reason to treat MS early and effectively to prevent this damage from occurring in the first place? 


If you have MS and are depressed you should seek help from your family doctor, MS nurse or neurologist as soon as possible. If you are not sure that you are depressed you can use the Beck’s Depression Inventory and score and self-diagnose yourself. 
Please note that depression rarely occurs in isolation and is usually accompanied by fatigue, anxiety and cognitive problems (difficulty concentrating, poor memory and inability to think clearly and efficiently). Depression may be associated with ‘sickness behaviour’, which in MS may be due to ongoing inflammation in the brain. Therefore if you are depressed your MS should be assessed to see if it is active. The latter would involve being seen by a neurologist and examined for new clinical signs and almost invariably include a new MRI scan to see if you have new or enlarging MS lesions. In some centres, such as Barts-MS, you may be offered a lumbar puncture to have your neurofilament levels measured in your spinal fluid. If the neurofilament levels are raised it indicates that your MS is active. If you are not on a disease-modifying therapy (DMT) and your MS is active you should be offered a DMT. The latter is not universal and will be determined by local and regional treatment guidelines and whether or not your neurologist accepts depression as a clinical marker of possible disease activity. If you are on a DMT already and have evidence of disease activity this may prompt a switch in your treatment.

 In conclusion, depression like other hidden symptoms of MS should not be ignored. Depression, or the black-dog, is a red-flag and indicates that something is going on inside your brain.

 van Geest et al. Fronto-limbic disconnection in patients with multiple sclerosis and depression. Mult Scler. 2018 Mar 1:1352458518767051.

 BACKGROUND: The biological mechanism of depression in multiple sclerosis (MS) is not well understood. Based on work in major depressive disorder, fronto-limbic disconnection might be important.


 OBJECTIVE: To investigate structural and functional fronto-limbic changes in depressed MS (DMS) and non-depressed MS (nDMS) patients.

 METHODS: In this retrospective study, 22 moderate-to-severe DMS patients (disease duration 8.2 ± 7.7 years), 21 nDMS patients (disease duration 15.3 ± 8.3 years), and 12 healthy controls underwent neuropsychological testing and magnetic resonance imaging (MRI; 1.5 T). Brain volumes (white matter (WM), gray matter, amygdala, hippocampus, thalamus), lesion load, fractional anisotropy (FA) of fronto-limbic tracts, and resting-state functional connectivity (FC) between limbic and frontal areas were measured and compared between groups. Regression analysis was performed to relate MRI measures to the severity of depression.

 RESULTS: Compared to nDMS patients, DMS patients (shorter disease duration) had lower WM volume ( p < 0.01), decreased FA of the uncinate fasciculus ( p < 0.05), and lower FC between the amygdala and frontal regions ( p < 0.05). Disease duration, FA of the uncinate fasciculus, and FC of the amygdala could explain 48% of variance in the severity of depression. No differences in cognition were found.

 CONCLUSION: DMS patients showed more pronounced (MS) damage, that is, structural and functional changes in temporo-frontal regions, compared to nDMS patients, suggestive of fronto-limbic disconnection.

ProfG    
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Invitation to Future-proofing Healthcare: NeuroSense

I have been invited to speak this Thursday evening at a meeting in London. There are still free places if you want to attend. As usual, I will post my slides online.


People continue to be intrigued by the mysteries of the brain, but many areas of neuroscience remain unexplained. Will we ever be truly able to solve these puzzles? What does the future of neuroscience look like? Which innovations will improve daily life for people living with neurological conditions? Will big data and better brain measurement lead to improved outcomes?


Future-proofing Healthcare: NeuroSense, the second in a series of non-promotional events exploring the answers to these questions, following the launch of the series in November 2017.

To view the full agenda and to book your place, please register here by Monday 2 April as places are limited.

What can I expect if I attend?


Experts, innovators and professors from across the neuroscience space will discuss advances in understanding neurological conditions, the role of technological innovations in improving the lifestyle of people with these conditions and what we can expect from the field of neuroscience.

Speakers include Dr David Reynolds from Alzheimer’s Research UK; Professor Gavin Giovannoni, Chair of Neurology at Barts Health; Neuroscientist & BBC presenter Dr Jack Lewis; innovative University of West England student & founder of Walk to Beat Neha Chaudhry; and leading British neurosurgeon and top-selling author, Henry Marsh. The event will be facilitated by Top 100 UK Scientist Dr Hannah Critchlow.

There will also be the opportunity to view an array of fascinating cutting-edge developments in our exhibition, including: VR experiences that simulates some symptoms of MS and dementia, robotic inventions from cats to walking sticks designed to support individuals living with Alzheimer’s and Parkinson’s, human-centred activity products and games to help people lead active lives, and interactive EEG experiences looking at brain activity through gaming and art.

What & Where?


The event will take place 6:30-9:45pm on Thursday 5 April at Studio Spaces, Warehouse Studio, Unit 2 110 Pennington Street, St Katharine‘s & Wapping, London, E1W 2BB.

Refreshments will be provided as part of the meeting.


For information and to register please click here.

Please note that this event is being sponsored by Roche.