Prof G's MS Blog Archive

Gratitude

Barts-MS rose-tinted-odometer: ★★★★★

A problem in modern medical practice is the assumption that there is a pill for everything. The one eye-opener for me after my recent trauma has been how easy it is for medics to reach for the prescription pad. When I was first discharged from hospital I was on 14 different medications. About half of the medications were prescribed to manage or prevent the side effects of the primary medications. It is easy to rationalise the use of each of the 14 medications, but were they all necessary? It is quite astounding how we have ‘pharmaceuticalised medicine’.

Initially, when my head was muzzled by morphine and gabapentin, I had an elaborate system in place to make sure I didn’t miss or forget any of my medications. This experience has given me a profound appreciation for how difficult it must be for some of my own patients, particularly those with cognitive impairment, to manage their own polypharmacy. The other question, which is the elephant in the room, is are all these medications really necessary.

A good example in MS is the management of MS-related fatigue. MS neurologists prescribe a large number of different medications for MS fatigue when in reality none, yes zero, of these medications has been shown to make a difference in randomised controlled trials. A recent study from the US shows that amantadine, modafinil and methylphenidate make no difference. In comparison, mindfulness therapy has been shown to work in several MS fatigue trials. So why don’t neurologists prescribe mindfulness to more of their patients? There is also an expanding evidence-base that mindfulness therapy helps depression, anxiety and insomnia.

Maybe 2021 should be the year when the medical profession questions and challenges the ‘pharmaceutical-model of medicine’ and helps lobby the NHS so that all of our patients have access to mindfulness therapy.

If you have a moment can I suggest you watch Gratitude, on the ‘Mindfulness 360 – Center For Mindfulness’ channel on YouTube. Are you surprised that this is better than a tablet?

I would be very interested if you could share your thoughts on this blog post and your own experiences with tablets versus mindfulness therapy for managing your symptoms. There are a lot of cynical HCPs out there who question the benefits of mindfulness, which is just one of the main barriers that prevent the wide adoption of this complementary therapy into routine MS practice.

Nourbakhsh et al. Safety and efficacy of amantadine, modafinil, and methylphenidate for fatigue in multiple sclerosis: a randomised, placebo-controlled, crossover, double-blind trial. Lancet Neurol. 2021 Jan;20(1):38-48.

Background: Methylphenidate, modafinil, and amantadine are commonly prescribed medications for alleviating fatigue in multiple sclerosis; however, the evidence supporting their efficacy is sparse and conflicting. Our goal was to compare the efficacy of these three medications with each other and placebo in patients with multiple sclerosis fatigue.

Methods: In this randomised, placebo-controlled, four-sequence, four-period, crossover, double-blind trial, patients with multiple sclerosis who reported fatigue and had a Modified Fatigue Impact Scale (MFIS) score of more than 33 were recruited at two academic multiple sclerosis centres in the USA. Participants received oral amantadine (up to 100 mg twice daily), modafinil (up to 100 mg twice daily), methylphenidate (up to 10 mg twice daily), or placebo, each given for up to 6 weeks. All patients were intended to receive all four study medications, in turn, in one of four different sequences with 2-week washout periods between medications. A biostatistician prepared a concealed allocation schedule, stratified by site, randomly assigning a sequence of medications in approximately a 1:1:1:1 ratio, in blocks of eight, to a consecutive series of numbers. The statistician and pharmacists had no role in assessing the participants or collecting data, and the participants, caregivers, and assessors were masked to allocation. The primary outcome measure was the MFIS measured while taking the highest tolerated dose at week 5 of each medication period, analysed by use of a linear mixed-effect regression model. This trial is registered with ClinicalTrials.gov, NCT03185065 and is closed.

Findings: Between Oct 4, 2017, and Feb 27, 2019, of 169 patients screened, 141 patients were enrolled and randomly assigned to one of four medication administration sequences: 35 (25%) patients to the amantadine, placebo, modafinil, and methylphenidate sequence; 34 (24%) patients to the placebo, methylphenidate, amantadine, and modafinil sequence; 35 (25%) patients to the modafinil, amantadine, methylphenidate, and placebo sequence; and 37 (26%) patients to the methylphenidate, modafinil, placebo, and amantadine sequence. Data from 136 participants were available for the intention-to-treat analysis of the primary outcome. The estimated mean values of MFIS total scores at baseline and the maximal tolerated dose were as follows: 51·3 (95% CI 49·0-53·6) at baseline, 40·6 (38·2-43·1) with placebo, 41·3 (38·8-43·7) with amantadine, 39·0 (36·6-41·4) with modafinil, and 38·6 (36·2-41·0) with methylphenidate (p=0·20 for the overall medication effect in the linear mixed-effect regression model). As compared with placebo (38 [31%] of 124 patients), higher proportions of participants reported adverse events while taking amantadine (49 [39%] of 127 patients), modafinil (50 [40%] of 125 patients), and methylphenidate (51 [40%] of 129 patients). Three serious adverse events occurred during the study (pulmonary embolism and myocarditis while taking amantadine, and a multiple sclerosis exacerbation requiring hospital admission while taking modafinil).

Interpretation: Amantadine, modafinil, and methylphenidate were not superior to placebo in improving multiple sclerosis fatigue and caused more frequent adverse events. The results of this study do not support an indiscriminate use of amantadine, modafinil, or methylphenidate for the treatment of fatigue in multiple sclerosis.

Ulrichsen et al. Clinical Utility of Mindfulness Training in the Treatment of Fatigue After Stroke, Traumatic Brain Injury and Multiple Sclerosis: A Systematic Literature Review and Meta-analysis. Front Psychol. 2016 Jun 23;7:912. doi: 10.3389/fpsyg.2016.00912. eCollection 2016.

Background: Fatigue is a common symptom following neurological illnesses and injuries, and is rated as one of the most debilitating sequela in conditions such as stroke, traumatic brain injury (TBI), and multiple sclerosis (MS). Yet effective treatments are lacking, suggesting a pressing need for a better understanding of its etiology and mechanisms that may alleviate the symptoms. Recently mindfulness-based interventions have demonstrated promising results for fatigue symptom relief.

Objective: Investigate the efficacy of mindfulness-based interventions for fatigue across neurological conditions and acquired brain injuries.

Materials and methods: Systematic literature searches were conducted in PubMed, Medline, Web of Science, and PsycINFO. We included randomized controlled trials applying mindfulness-based interventions in patients with neurological conditions or acquired brain injuries. Four studies (N = 257) were retained for meta-analysis. The studies included patients diagnosed with MS, TBI, and stroke.

Results: The estimated effect size for the total sample was -0.37 (95% CI: -0.58, -0.17).

Conclusion: The results indicate that mindfulness-based interventions may relieve fatigue in neurological conditions such as stroke, TBI, and MS. However, the effect size is moderate, and further research is needed in order to determine the effect and improve our understanding of how mindfulness-based interventions affect fatigue symptom perception in patients with neurological conditions.

Simpson et al. Effects of Mindfulness-based interventions on physical symptoms in people with multiple sclerosis – a systematic review and meta-analysis. Mult Scler Relat Disord. 2020 Feb;38:101493.

Background: Physical wellbeing is commonly impaired in people with multiple sclerosis (PwMS). This study aims to update our previous systematic review (2014) and conduct a meta-analysis on the efficacy of Mindfulness-based interventions (MBIs) for improving physical symptoms in PwMS.

Methods: In November 2017 we carried out systematic searches for eligible randomised controlled trials (RCTs) in seven major databases, updating our search in July 2018. We used medical subject headings and key words. Two independent reviewers used pre-defined criteria to screen, data extract, quality appraise, and analyse studies. The Cochrane Collaboration risk of bias tool was used to determine study quality. Physical wellbeing was the main outcome of interest. We used the random effects model for meta-analysis, reporting effect sizes as Standardised Mean Difference (SMD). This study is registered with PROSPERO: CRD42018093171.

Results: We identified 10 RCTs as eligible for inclusion in the systematic review (including 678 PwMS), whilst seven RCTs (555 PwMS) had data that could be used in our meta-analyses. In general, comorbidity, disability, ethnicity and socio-economic status were poorly reported. MBIs included manualised and tailored interventions, treatment duration 6-9 weeks, delivered face-to-face and online in groups and also individually. For fatigue, against any comparator SMD was 0.24 (0.08 – 0.41), I2=0%; against active comparators only, SMD was 0.10 (-0.14 – 0.34), I2=0%. For pain SMD was 0.16 (-0.46 – 0.79), I2=77%. Three adverse events occurred across all studies.

Conclusions: MBIs appear to be an effective treatment for fatigue in PwMS. The optimal MBI in this context remains unclear. Further research into MBI optimisation, cost- and comparative-effectiveness is required.

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CoI: multiple

Twitter: @gavinGiovannoni Medium: @gavin_24211

Christmas

Barts-MS rose-tinted-odometer: ★

My name is Laura Smith, I am 54 years old and have progressive MS. I am divorced with a grown-up son who is 32 years old and lives with his partner in the North of England. I am medically retired and live alone in a small bungalow in a rural village close to the Essex-Suffolk border. I am disabled and need a stick to walk indoors. I use a wheelchair and/or scooter for outdoor mobility. I rarely go out because of bladder problems. Despite this, I had planned to travel to London to spend the Christmas break with my sister and her family. These plans have now been cancelled. I will therefore be spending Christmas alone. I don’t enjoy Christmas as it reminds me of a time before I had MS, before my divorce, of a time when I had a successful career as a lawyer, a lovely home and a fulfilling family life. I am dreading waking-up this Friday alone. Help!

Is this short story familiar?

Yesterday morning on the Andrew Marr show Justin Welby, the Archbishop of Canterbury, made it clear that Christmas was not cancelled, only the celebration of Christmas was being downsized or put on hold. He urged people to reflect on Christmas and what it means if you are a Christian and to delay the need for celebration to a time when it more appropriate and the mood of the nation less sombre.

The Archbishop then discussed the epidemic of loneliness that COVID-19 has caused and gave some general advice to people spending Christmas alone. The following are things you can do if you are home alone this Christmas.

If you are religious reconnect with the true meaning of Christmas and try and get to a Church service; either in person or one of the TV, radio or online Christmas services. Pick-up the phone and call people; friends, family or one of the many charitable organizations who provide telephone companions. Watch Christmas TV. Listen to Christmas carols. If you can practice mindfulness please do. Get out if you can for exercise and fresh air. Make sure you fill your day with as many activities as you can.

If you can I would recommend reading or listen to a reading of the Charlie Mackesy book ‘The Boy, The Mole, The Fox and The Horse’. My wife bought all of us a copy of the book at the beginning of the pandemic and whenever I feel low I pick it up from the pile of books next to my bed and read it (it only takes 5 minutes to read). I know it can easily be dismissed and labelled bedside philosophy, but there is something very therapeutic and uplifting about its tempo and messages.

My favourite quote in the book is “What’s the best thing you have learnt about storms?” “That they end”, said the horse. Yes, this storm will end.

If you know someone who is alone this Christmas can you please take some time-out on Christmas day to give them a call and if you have any other suggestions to help the many people who are alone this Christmas please let us know.

I hope you are all holding up and I want to use this opportunity for us at Barts-MS to wish you a different, but merry, Christmas or happy holidays.

Crowdfunding: Are you a supporter of Prof G’s ‘Bed-to-5km Challenge’ in support of MS research?

CoI: multiple

Twitter: @gavinGiovannoni Medium: @gavin_24211

PTSD-2

My recent post on PTSD (post-traumatic stress disorder) and the resulting comments were an eye-opener to me and many of our readers. If you haven’t read the post and the comments I would urge you to do so as it provides context for the following survey we are doing in partnership with Shift.ms a social platform for people with MS.

We understand that this survey may be upsetting or distressing to some members of the community so you are welcome to skip any questions that you do not want to answer.

The purpose of the survey is to see how common PTSD is in pwMS and then in collaboration with Shift.ms to develop an awareness and training programme for MS Healthcare Professionals to (1) prevent pwMS developing PTSD when they are diagnosed as having MS, (2) to screen for the condition in routine MS practice and (3) to develop the skills to treat PTSD so as to mitigate its impact of PTSD on the lives of pwMS.

Please click here to take the Shift.ms survey; thank you.

As you can see this blog has become more than a soapbox and occasionally we try to address important issues to improve the lives of people, and their families, living with MS.

CoI: multiple

#MSPrevention: air pollution

Barts-MS rose-tinted-odometer: ★★

As MS is highly likely to be a preventable disease we should be doing everything we can to reduce our exposure to modifiable risk factors. Smoking, passive smoking, solvent exposure and air pollution have all been linked to an increased incidence of MS. It has always been argued that air pollution may work by acting as a filter for ultraviolet light and hence increases one’s risk of getting MS by reducing UVB exposure, which is important for vitamin D synthesis in the skin. However, I am not sure this is the case as common to all these exposures, including air pollution, is inflammation in the lungs.

The current hypothesis is that inflammation in the lungs changes or alters proteins via a process called post-translational modification, which converts normal proteins in highly immunogenic autoantigens that trigger autoimmune disease. There is good support for the latter hypothesis in rheumatoid arthritis, but to the best of my knowledge outside of animal models, the evidence in MS remains speculative. Saying this who wouldn’t want to breathe clean air if one of the benefits is a lower risk of MS?

The study below from Padua Province in Italy shows quite a strong correlation (r-0.89) between exposure to particulate matter in the air greater than 2.5 micrometres (PM2.5) and the prevalence of MS. Some epidemiologists say that when you start seeing R-values close to 0.9 it is hard to ignore them and suggest the relationship could be causal. I am not sure about this, but it is clear that we need to more interventional studies, to reduce air pollution, and track what happens to MS incidence.

In relation to the issue of air quality, there was a landmark ruling from an inquest yesterday that linked the tragic death of a nine-year-old girl, Ella Adoo-Kissi-Debrah, who died following an asthma attack 9 years ago to air pollution. Legal pundits have stressed the importance of this case, which will now create the legal precedent for the UK to modify its clean air act. The importance of the latter cannot be ignored as it may lead to a drop in the incidence of many diseases linked to air pollution including MS.

The question we also need to ask ourselves is there anything we can do to address the problem of air pollution in low- and middle-income countries that are all seeing a rise in MS incidence? Let’s hope as we transition from a carbon-energy economy to other cleaner forms of energy we will see this problem improve across the world.

Arianna et al. Association of Multiple Sclerosis with PM 2.5 levels. Further evidence from the highly polluted area of Padua Province, Italy. Mult Scler Relat Disord. 2020 Dec 6;48:102677. doi: 10.1016/j.msard.2020.102677. Online ahead of print.

Background: Fifty years of epidemiological survey and intra-regional differences in prevalence suggest that environmental factors may be associated with increased multiple sclerosis (MS) risk in Northern Italy. Based on the findings of a previous study carried out in the highly polluted Padan Plain, we further explored the relationship between PM2.5 levels and MS prevalence by comparing bordering areas characterized by quite different environmental conditions, namely the Municipality of Padua and the special protected zone (SPZ) of the Euganean Hills Regional Park, located 15 km from the City.

Methods: Three territories were identified; 1) the SPZ, extending over an area of 15.096 hectares and having a total population of 23,980 inhabitants, 2) the urban area of Padua, with a total population of 210,440 inhabitants and repeatedly recognized by the European Environmental Agency as one of the most polluted cities of Europe, 3) the Intermediate Zone (IZ), i.e., the area in between the previous two, including part of the urban territories of eight villages adjacent to the SPZ. Demographic and socio-economical data were obtained from official government sources (www.istat.it and http://www.regione.veneto.it). All Italian MS patients residing in these three areas on December 31, 2018, were registered. PM2.5 concentrations (annual average 1998-2018, μg/m3) were measured by satellite. The correlation between PM2.5 concentrations and MS prevalence was analysed.

Results: MS prevalence was significantly higher in Padua City (265/100.000) compared to both the SPZ of the Euganean Hills Park (160/100,000; p < 0.0001) and the IZ (194.4/100,000). Prevalence strongly associated with the annual average concentration of PM2.5 (r = 0.89 p < 0.00001).

Conclusion: In the Province of Padua, one of the most polluted areas of Europe, MS prevalence is strongly associated with PM2.5 exposure. Our findings suggest that air pollutants may be one of the possible environmental risk factors for MS in the Veneto Region of Italy.

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CoI: multiple

Twitter: @gavinGiovannoni Medium: @gavin_24211

#MSCOVID19: CATCH-22

Barts-MS rose-tinted-odometer: ★

I know it sounds like a cliche but Catch-22 would definitely be on my list of most impressionable books I read as a teenager. I liked it because of its dark satirical humour, it was written in the third-person and it taught me how absurd war actually is. Catch-22 (and the Great Gatsby) also taught me if you love a book you should never watch the movie; the screenwriters, actors and directors can never do your imaginary characters justice.

The book has become so influential that ‘Catch-22’ has become a noun and refers to a dilemma or difficult circumstance from which there is no escape because of mutually conflicting or dependent conditions.

Although I am meant to be at home recovering from injuries I am doing some emails. Over the last few days, I have received numerous emails from patients and neurologists asking for advice about COVID-19/SARS-CoV-2 vaccines and DMTs and what am I telling my patients. One patient tells me that her neurologist referred her the excellent MS Society webpage for advice, but the site then referred her back to her neurologist for definitive advice. A Catch-22?

Some US neurologists have picked-up that my advice and position on vaccines and vaccine readiness has changed since I first started talking about this issue on the blog. They are correct, my position has changed. I always took the position that we should continue to manage MS the way we managed it before COVID-19 with certain caveats* around the risk of being exposed to SARS-CoV-2 and whether or not individuals could self-isolate or not, and that we should cross the vaccine bridge when it arrives. Now that the vaccines are arriving and the ambitious national roll-out suggests the whole country will be vaccinated within the next 6 months, advice has to be given and given quite quickly.

In my opinion, all the COVID-19 vaccines that the UK Government has purchased can be used in people with MS regardless of whether or not they are on a DMT. This advice is based on the fact that the MHRA and other regulatory bodies have licensed or will license these vaccines because of their safety and efficacy profile in the general population.

Importantly none of these vaccines is likely to be a ‘live viral vaccine’. There is some confusion around the Oxford-AstraZeneca vaccine that does use a chimpanzee adenovirus vector to deliver the immunogen to our cells so that the immunogen can be expressed. The virus in this vaccine is able to infect cells and express its relevant proteins, but because some of its genes for replication have been mutated it cannot replicate itself and cause ongoing infection. I am not sure how this vaccine will be classified by the MHRA or other regulatory authorities, but in my opinion, it is likely to be safe to use in pwMS.

I say these vaccines are likely to be safe in pwMS. However, none of the COVID-19 vaccines has specifically been tested in pwMS so we have to extrapolate data from the general population data. There may be something we don’t know about having MS that predisposes pwMS to some rare complications. However, based on other vaccines that have been used in MS this is very unlikely.

It is clear that being on some immunosuppressive DMTs may reduce your chances of responding adequately to the vaccine and hence being fully immune to infection from wild-type SARS-CoV-2. Until we do detailed immunological studies in pwMS on each DMT we won’t be able to answer specific questions about each DMT with certainty.

Interferon-beta , glatiramer acetate and immune reconstitution therapies

In general being on interferon-beta and glatiramer acetate, immunomodulatory DMTs, are unlikely to interfere with vaccine responses. Similarly, if you have had one of the immune reconstruction therapies, such as alemtuzumab, cladribine, mitoxantrone or HSCT in the past and have reconstituted your peripheral immune system you should respond to the vaccines. If on the other hand, you have not had completely reconstitution of your immune system you may still consider having the vaccine, but the immune response may be blunted. Waiting for immune reconstitution or having the vaccine now will be a trade-off between wanting to protect yourself now or waiting months when the pandemic may be almost over. Please note vaccination is not only about you, but slowing and preventing transmission of the virus in the general population, which is a factor you may want to consider. This may relevant, for example, if you want to see unvaccinated vulnerable relatives or if you want to travel to parts of the world with a delayed vaccination programme.

Fumarates, teriflumide and natalizumab

If you are fumarates (DMF, diroximel fumarate), teriflunomide or natalizumab, based on other vaccine studies, COVID-19 vaccine responses are likely to be reasonably preserved. Therefore there is no need to stop these DMTs or delay getting a vaccine if you are on these treatments.

S1P modulators

For the so-called S1P modulators (fingolimod, siponimod, ozanimod and ponesimod) vaccine responses are likely to be blunted, but whether or not the blunted responses will be sufficient to prevent SARS-CoV-2 infection is a moot point. However, I would not recommend stopping these treatments to have a vaccine as these therapies are associated with MS rebound activity. My advice would be that if you are on these therapies to go ahead with the vaccine when it is offered to you.

Anti-CD20 therapies

When I initially wrote about vaccine hesitancy I suggested that pwMS on an anti-CD20 therapy (rituximab, ocrelizumab, ofatumumab) may have to delay their next infusion or miss one or two infusions to allow B-cell reconstitution before they have a coronavirus vaccine. Since making this statement more immunological data has emerged and there really is no definitive evidence to support this position.

Yes, I agree that in general people on anti-CD20 therapies have blunted antibody responses to wild-type SARS-CoV-2 infection and to other vaccines including vaccines with containing new antigens that the immune system has not seen before. However, this doesn’t mean these people haven’t developed immunity to the infection or vaccine that is long-lasting. For one the vast majority of pwMS on an anti-CD20 therapy who get COVID-19 make an uneventful recovery. Why? Almost certainly this recovery is due to cellular and not humoral (antibody) immunity and this immunity won’t vanish and is likely to persist longterm.

Even normal people who have had COVID-19 and who lose their antibody responses still have detectable cellular immunity. My interpretation of this data is that pwMS who are on an anti-CD20 therapy should simply go ahead and have the coronavirus vaccine when it is offered to them and not to worry about whether or not they mount an antibody response.

I am aware that some pwMS are planning to delay their next infusion regardless of what I or their HCP says. The question I ask is for how long? One, two, three or more months? Some pwMS plan to wait for peripheral B-cell reconstitution that can take months to years to occur and even then there is no consensus of what normal B-cell reconstitution looks like. You need to weigh the lack of evidence that delaying your next anti-CD20 therapy or waiting for B-cell reconstitution will make any difference to your vaccine response against the time-sensitive nature of the vaccine to protect you during the high-risk period of the pandemic. If you wait too long and the pandemic is over the benefits of the vaccine will be reduced.

The only evidence base we have at the moment is the recently published VELOCE study that delayed vaccination until 12 weeks after an initial course of ocrelizumab. This study showed blunted, but not absent, antibody responses to recall and new vaccines. Based on this study if you have just had a recent course of ocrelizumab you may want to delay getting the COVID-19 vaccine for 12 weeks after the last infusion. However, as 12 weeks is a long time to wait in the current climate I have been recommending at least 4 weeks; a pragmatic compromise.

In my opinion, it is more important for pwMS on anti-CD20 therapies to be vaccinated than to not be vaccinated. This is because vaccination policy is really about population, or subpopulation, health and stopping the spread of the virus and protecting the individual is a secondary aim.

MS relapses

Will the COVID-19 vaccines trigger MS relapses? This hypothesis is based on extrapolating data on two non-peer-reviewed cases of CNS demyelination in the Oxford-AstraZenca (Ox-AZ) trial and several cases of transverse myelitis in patients who have had COVID-19. One case on in the Ox-AZ trial, who received the vaccine, had an initial attack or relapse and was subsequently diagnosed as having MS; i.e. I assume because they had pre-existing lesions and were now shown to have a second attack or new lesions consistent with dissemination in time. The other case had an episode of vaccine-related transverse myelitis (TM), which is relatively common with vaccines in general. Please note that vaccine-related TM is not MS. The only vaccine that has been reported to potentially trigger MS relapse is the live yellow-fever vaccine and this is based on one report that has subsequently not been replicated. Therefore, there is no current evidence that coronavirus infection or coronavirus vaccines trigger MS relapses. In my opinion, there is no reason to avoid the COVID-19 vaccine based on this hypothesis. Clearly, my opinion may change if new data emerges to the contrary.

Summary

If you have not had COVID-19 having a vaccine will offer you the opportunity of preventing getting COVID-19 or at least if you do get it, of having milder disease. All the licensed vaccines, which have been shown to be safe in the general population are likely to be safe in pwMS. Although some people on immunosuppressive therapies, in particular, S1P modulators and anti-CD20 therapies, may have blunted antibody vaccine responses these may still be sufficient to protect you against infection or at least severe COVID-19. There is no evidence that stopping or delaying treatment, in the hope of boosting vaccine responses will work and may result in you missing out on being protected when your risk of infection is highest. Please be aware that stopping some DMTs, in particular, natalizumab and S1P modulators, is associated with a rebound of disease activity and is not recommended. Hopefully, the pharmaceutical industry and the wider MS community will collect data and do specific studies to answer the many questions we have around vaccination and vaccine responses in pwMS on specific DMTs.

* The caveats refer to alemtuzumab and HSCT, which affect both innate (monocytes and/or neutrophils) and adaptive (particularly cytotoxic CD8+ T lymphocytes), which are required for fighting SARS-CoV-2. My advice for the other DMTs has not to self-isolate, but to simply stick to the current government guidelines in relation to social distancing and personal hygiene.

Bar-Or et al. Effect of ocrelizumab on vaccine responses in patients with multiple sclerosis: The VELOCE study. Neurology October 06, 2020; 95 (14)

Objective: The phase IIIb VELOCE study (NCT02545868) assessed responses to selected vaccines in ocrelizumab (OCR)-treated patients with relapsing multiple sclerosis.

Methods: Patients were randomized 2:1 into Group OCR (n=68; OCR 600mg); or Control (n=34;interferon-β or no disease-modifying therapy). All received tetanus toxoid (TT)-containing vaccine, Pneumovax® (23-PPV) and keyhole limpet hemocyanin (KLH). Group OCR was subdivided into OCR1 (n=33) and OCR2 (n=35) at randomization. OCR1 received Prevnar® (13-PCV) 4 weeks after 23-PPV; OCR2 and Control received influenza vaccine. Vaccinations started 12 weeks after OCR initiation (Group OCR) or on Day 1 (Control).

Results: Positive response rate to TT vaccine at 8 weeks was 23.9% in OCR vs 54.5% in Control. Positive response rate to ≥5 serotypes in 23-PPV at 4 weeks was 71.6% in OCR and 100% in Control. Prevnar® did not enhance response to pneumococcal serotypes in common with Pneumovax®. Humoral response to KLH was decreased in OCR vs Control. Seroprotection rates at 4 weeks against five influenza strains ranged from 55.6–80.0% in OCR2 and 75.0–97.0% in Control.

Conclusion: Peripherally B-cell depleted OCR recipients mounted attenuated humoral responses to clinically relevant vaccines and the neoantigen, KLH, suggesting use of standard non-live vaccines while on OCR treatment remains a consideration. For seasonal influenza vaccines, it is recommended to vaccinate patients on OCR, as a potentially protective humoral response, even if attenuated, can be expected. Classification of evidence This study provides Class II evidence confirming that the humoral response to non-live vaccines in patients with RMS following ocrelizumab treatment is attenuated compared with untreated or interferon-β–treated patients, though can still be expected to be protective.

Twitter: @gavinGiovannoni Medium: @gavin_24211

R-squared

Barts-MS rose-tinted-odometer: ★★★★★

R-squared = resilience x reciprocity

Resilience = the capacity to recover quickly from difficulties; toughness.

Reciprocity = the practice of exchanging things with others for mutual benefit, especially privileges granted by one country or organization or person to another.

Health and wellness can’t be taken for granted. For the body and mind to navigate life as best it can it needs to be prepared for its eventualities, which in some cases are a certainty. At the beginning of the COVID-19 pandemic, I actively promoted the concept of prehabilitation, i.e. doing everything you can do to improve your general health so that if you got COVID-19 you could deal with it and hopefully prevent yourself from getting severe COVID-19 and thereby reduce your chances of dying from the infection and/or its complications.

Another way of looking at this concept is building ‘biological resilience’, in other words, maximising your ability to recover quickly or cope with difficult situations be they infections, trauma (falls and fractures), MS relapses or even disease worsening.

Prehabilitation is preventive medicine. Prehabilitation is undertaking a health & wellness programme to deal with a known stressor in the near future. In surgery, this is typically a planned or an elective surgical procedure, such as a hip or knee replacement or cardiac surgery. However, widening the concept to medicine, for example, to include so-called known-knowns, unknown-knowns and known-unknowns in relation to immune therapies make sense.

Known-knowns = these are adverse events that are known to occur in relation to specific immunotherapy, for example, hypogammaglobulinaemia from prolonged treatment with anti-CD20 therapy. In terms of a specific prehabilitation programme, you could check and manage hypogammaglobulinaemia as it develops or develop a new treatment paradigm (induction-maintenance) that derisks patients when they develop hypogammaglobulinaemia.

Unknown-knowns = adverse events that have not been described yet, but based on scientific principles are likely to occur in the future, for example, meningococcal septicaemia and meningitis in patients on anti-CD20 therapy. This prediction based on the observation that people who have had a splenectomy or have low IgM levels from other causes are more susceptible to infections with so-called encapsulated bacteria such as meningococcus. In terms of incorporating this into a prehabilitation programme would be to offer patients the meningococcal vaccine if they are at high risk of being exposed to meningococcus (army recruits, university students, etc.).

Known-unknowns = adverse events in people with other diseases on a particular treatment that has yet to be described in people with MS on the same treatment. For example, people with rheumatoid arthritis and lupus treated with ocrelizumab were more likely than control subjects to get pneumococcal pneumonia. Therefore, we can assume that pwMS on ocrelizumab are increased risk of pneumococcal infections. Part of the prehabilitation programme, to derisk this, would be to ensure all pwMS have the pneumococcal vaccine prior to starting an anti-CD20 therapy and to then have their boosters every 5 years.

The examples I give above should be relatively easy to understand but are passive in that they rely on the HCPs to have systems in place to derisk specific MS DMTs. However, when it comes to optimising your general health so that you have biological resilience the story is different. Here you as pwMS need to engage with the general principles of prehabilitation and prepare yourself, for example, to help make sure the infections you acquire are mild and to maximise your chances of making an uncomplicated recovery.

This is when reciprocity applies, i.e. the practice of exchanging knowledge with your HCP for mutual benefit. In other words, by you entering into a well-defined partnership with your HCP you will hopefully maximise your outcome and at the same time to reduce healthcare expenditure. In this partnership, your HCPs (neurologist, MS nurse, GP, etc.) will inform you of the aims of the programme, which may include some healthcare intervention, for example, vaccinations to prevent specific infections, an exercise programme to prevent falls, dietary advise to lose weight, medication to help you stop smoking, a social prescription for a personal trainer, which then it requires you to adhere to the programme. Reciprocal agreements are based on trust and only work if you trust each other (I wonder if the British and EU politicians understand this?).

These concepts of resilience and reciprocity go well beyond the management of MS and apply to health in general and other social and political interactions. For example, in the UK the NHS will always look after you if you develop a disease, but the NHS or greater society are asking you to be more careful with your life choices so as to reduce your risk of getting certain diseases in later life. Unfortunately, the behavioural interventions that public health bodies and the NHS promote are not always backed-up by the actions of our politicians, for example, an adequate sugar tax or minimal pricing of a unit of alcohol to act as disincentives for obesity and its associated ills and alcohol misuse, respectively.

Saying this I think we need to start activel working into our thinking ways to include R-squared into healthcare. What can we do to make the MS population more resilient? What do we need to do to remind both HCPs and pwMS that the optimal management of MS is based on reciprocity?

Having suffered a catastrophic loss of wellness with my recent accident makes me realise that my relatively rapid recovery has something to do with my general health and fitness (physiological resilience) and my determination to remain positive (mental resilience). However, my recovery back to a new normal now requires me to stick to my rehabilitation programme. The surgeons did what they were trained to do, i.e. fix and stabilise my fractures, and the next phase of my recovery is up to me. I have been given an exercise programme by my physiotherapists and medication to help deal with the pain. My part of the relationship is to take the medication and stick to my exercise programme.

To paraphrase John F. Kennedy’s historic quote in his inaugural presidential lecture, “Ask not what your country can do for you – ask what you can do for your country”. “Ask not what the NHS or your MS team can do for you – ask what you can do to manage your own MS”. What can you do to build physical and mental resilience and how can you optimise the reciprocal relationship with your MS team to make this happen?

In reality, the concepts of r-squared (resilience x reciprocity) are what we are really trying to achieve via our Raising-the-Bar initiative as part of the MS Academy. The only difference is there is another tier above the HCP-Patient relationship in that we need to interact with the NHS or healthcare system to make sure that the necessary resources or infrastructure are in place to implement r-squared.

As people with MS do you think the issues raised in this post are relevant to you? How would you feel if we developed a formal agreement or contract for both parties to sign in relation to the HCP-patient partnership? The latter is not a new concept and is used widely in psychiatry.

Crowdfunding: Please note I manage to walk over 3 km yesterday and it is looking likely I will be able to walk 5 km before the 31st of December. It is not a done deal yet so if you haven’t supported my challenged there is still time 😉 We are getting very close to our fund-raising target so hopefully, this will be the final push and I can stop promoting fundraising. For those who have given already, thank you. Click on the link to support Prof G’s ‘Bed-to-5km Challenge’ to support MS research.

CoI: multiple

Twitter: @gavinGiovannoni Medium: @gavin_24211

Epidemic

Barts-MS rose-tinted-odometer: ★

Do you live in Scotland? Thes latest MS incidence (new cases) and prevalence (all cases) figures from the Scottish Highlands should make Scottish public health officials shiver.

In the Scottish Highlands, there are now over 18 people diagnosed with MS every year per 100,000 population with a total of 376 people with MS per 100,000 population. These figures may be artificially low as a lot of people born in the highlands may move away, for example to University or to work, and don’t get counted or included in these figures.

This is one of the highest, if not the highest, MS incidence rates in the world and about 30% higher than the figure from about a decade ago. This would indicate that we are still living through an MS epidemic and something needs to be done about it as urgently as possible.

What can be done? If MS is preventable the Scots should be setting-up and testing various MS prevention strategies to see if they can lower the incidence or at least stop its continual rise. This may be an opportune time to look into vitamin D prevention trials and campaigns to get first and second degree relatives to sign-up for more targeted MS prevention studies.

Francisco Javier Carod-Artal. The epidemiology of multiple sclerosis in the Scottish Highlands: Prevalence, incidence and time to confirmed diagnosis and treatment initiation. Mult Scler Relat Disord. 2020 Nov 28;47:102657.

Introduction: Although multiple sclerosis (MS) is frequent in the northern hemisphere, there have not been recent epidemiological studies in the Scottish Highlands about MS.

Objectives: To get updated data regarding MS prevalence, incidence and mortality in the Highlands. Time between symptom onset and MS diagnosis was also evaluated in incident MS cases and the pattern of use of disease-modifying therapies (DMTs) was analysed.

Methods: Study population was people with MS under the care of the Highland Health and Social Care Partnership. The catchment area included North area (Wick, Thurso, Brora, Invergordon), Center (Inverness, Aviemore, Nairn, Fort William), and West coast (Ullapool, Skye). Data were obtained from the MS database at Raigmore hospital (prevalence, midyear 2017) and the prospective hospital-register based study (diagnosis) that was carried out over a 12-month period, in 2016. The 2010 McDonald criteria for diagnosis of new MS cases were used. Crude prevalence and incidence and 95% confidence interval (CI) were calculated for the MS adult onset population, and data was standardised to the European standard population 2013; cause-specific mortality rate was analysed. Pattern of use of DMTs during the first year of diagnosis was also registered.

Results: 745 patients were registered in the MS database. 75.4% (562 cases) were females, and female/male ratio was 3:1. Mean age of population was 54.1 ± 14.1 years (range: 15-95 years). Mean number of years since diagnosis was 8.5 ± 4.6 years. Estimated prevalence for the population aged 15 and older was 376 cases per 100,000 inhabitants (95% CI: 354-399). 36 incident MS cases were registered in 2016 (88.8% females; mean age 40.4 ± 12.1 years). Annual incidence in Highlands was 18.2 per 100,000 inhabitants (95% CI: 14-24). The mean period of time from symptom onset to diagnosis was 38.8 ± 43.2 months. 47.2% (17/36) did not take any DMT during the first year after the diagnosis.

Conclusion: Prevalence and incidence of MS in the Scottish Highlands is high. Although the gap period between symptom onset and diagnosis is moderate, a significant proportion of recently diagnosed MS patients were not keen to start a DMT the first year after the diagnosis.

Crowdfunding: Are you a supporter of Prof G’s ‘Bed-to-5km Challenge’ in support of MS research?

CoI: multiple

Twitter: @gavinGiovannoni Medium: @gavin_24211

PTSD

Barts-MS rose-tinted-odometer: zero ★s

I look after a patient with MS who is now in her late 60’s. She was diagnosed with MS almost 30 years ago in the early ’90s. She has done very well and has by definition benign MS. Apart from mild unsteadiness of gait, a weak right leg that causes a mild limp when she is tired and back pain, she is fully functional. She was treated with interferon-beta for 14 years and after having no relapses for over 10 years she decided to stop taking interferon-beta. She made the decision to stop interferon-beta treatment when she retired in her early 60s. Her only ‘MS medication’ is 300mg of gabapentin at night; this helps dull the back or myelopathic pain so she can get a good nights sleep.

Despite having MS and a good prognosis she suffers from PTSD (post-traumatic stress disorder) in relation to how her MS was diagnosed by a private neurologist in London. She had a prior history of vertigo and unsteadiness of gait and had developed weakness of her right leg, presumably from a spinal cord attack. This was before the world-wide-web and DMT era so most people in the general population did not know a lot about MS; their knowledge of MS was based on a billboard advertising campaign of the MS society showing young pwMS in wheelchairs. The idea of the MS Society’s campaign at the time was to scare the general public to donate money for research. In addition, to this, the poster child of MS at the time was Jacqueline du Pré, the celebrated British cellist, who had tragically died at the age of 42 from MS. Jacqueline du Pré had died quite recently in 1987 and as her death had been extensively covered on TV and in the newspapers. The general public’s view of MS in the late ‘80s and ‘90s was not a very good one; MS was a disease that struck you down when you were young and invariably caused disability and early death. How things have changed!

The private neurologist who saw my patient was not an MS expert and had not prepared my patient for the diagnosis. When she returned for her follow-up or diagnostic appointment he simply walked up to an old backlight x-ray box on which he had pre-arranged her MRI scans and said without looking at her that she had a large number of white blobs on her MRI, which confirmed his suspicions that she had MS. He then turned around and said that he will write to her GP with the details. And that was the end of the consultation; no time for questions, no information on MS its treatment or prognosis. My patient recalls having to walk out of the consultation with a cold panic enveloping her. Tragically on catching the tube home she ended-up opposite one of the MS Society’s posters of a young person with MS with a zip down their spine; the implication that the damage MS had done to the spinal cord was responsible for causing the disability. My patient recalls this person in the poster, leaning forward in a wheelchair. This is clearly not the kind of poster you would want to see minutes after you have been told that you have MS.

To this day my patient gets regular (almost daily) and intrusive flashbacks of this experience. These flashbacks are associated with a feeling of anxiety or panic, palpitations, hyperventilation, hot flushes, sweating and a feeling of doom. The flashbacks can come on spontaneously, but typically happen when she needs to come to the hospital and particularly when she has an MRI scan. In fact, MRI is such a problem that she has now refused to have repeat MRI studies. The white blobs have become a bogeyman and she imagines them expanding and suffocating her. Her GP has diagnosed her as having PTSD or post-traumatic stress disorder and had prescribed an SSRI (selective serotonin reuptake inhibitor), which did help reduce the frequency and intensity of the flashbacks. However, as the SSRI caused weight gain the patient decided to stop taking it. She has subsequently found CBT (cognitive behavioural therapy) and mindfulness or meditation helpful, but clearly not a cure.

Interestingly, as I make a slow physical recovery from my injuries, I have started to have flashbacks about my recent accident. These are not intrusive and are typically triggered by crossing and traffic intersection or when I hear a motorcycle in the distance. These flashbacks are fleeting and not associated with any systemic symptoms. I, therefore, suspect flashbacks are a normal phenomenon for people who have just suffered a traumatic experience, but simply experiencing them provides a context and a deeper understanding of how traumatic it can be for someone to be diagnosed with MS or for that matter any chronic disabling disease.

My patient above may be an extreme example, but when asked a large number of pwMS tell me the worst part of MS is being told you have MS. In the Italian study below a quarter of pwMS have symptoms of PTSD and more than 1 in 20 have a confirmed diagnosis of PTSD. This is way more common than I expected this phenomenon to be. The question I ask is why are we HCPs so bad at communicating the diagnosis of MS? Is there anything that HCPs can do to improve the experience?

Nowadays most people who turn out to have MS already suspect the diagnosis because they have asked Dr Google. Is this a good or bad thing? Does it cause more or less anxiety going into a consultation suspecting the outcome?

George Pepper, one of the cofounders of shift.ms talks about his diagnostic experience as being a very poor one in that there was no support for people like him. This is why he started shift.ms, to create an online resource centre and supportive community to help people, particularly young people, come to terms with the diagnosis of MS. The Shift.ms YouTube movie Gallop is almost autobiographical and captures some of George’s experiences before and during the diagnostic phase of MS. If you haven’t watched the video before I would recommend it.

What were your experiences like? Have any of you developed PTSD as a result of being diagnosed with MS? Do you have any advice for other people with MS?

Carletto et al. Prevalence of Posttraumatic Stress Disorder in Patients With Multiple Sclerosis. J Nerv Ment Dis. 2018 Feb;206(2):149-151.

Chronic and life-threatening illnesses, such as multiple sclerosis (MS), have been identified as significant stressors potentially triggering posttraumatic stress disorder (PTSD). The study aims to investigate the prevalence of PTSD according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria in a large sample of patients with MS. A total of 988 patients with MS were screened with the Impact of Event Scale-Revised, and then assessed with the PTSD module of the Structured Clinical Interview for DSM-IV and with the Clinician-Administered PTSD Scale to confirm PTSD diagnosis. Posttraumatic symptoms were reported by 25.5% of the sample. A confirmed diagnosis of PTSD was found in 5.7% of patients, but prevalence could reach 8.5%, including also dropout patients. Further studies are needed to evaluate if adjustment disorder could better encompass the frequently encountered subthreshold posttraumatic stress symptoms and how clinicians can deal with these symptoms with appropriate interventions.

Crowdfunding: Are you a supporter of Prof G’s ‘Bed-to-5km Challenge’ in support of MS research?

CoI: multiple

Twitter: @gavinGiovannoni Medium: @gavin_24211

Women

Barts-MS rose-tinted-odometer: zero ★s

As I gradually drift into health-related politics I realise that it is not enough just to measure something to trigger a change in behaviour. Information and data don’t change behaviour; carrots and sticks or incentives do. The US study below shows that women in academic medicine are no better off than they were 35 years ago. Women physicians are less likely than men to be promoted to the rank of associate or full professor or to be appointed to the department chair. I wouldn’t be surprised if the same situation exists in the UK and other high-income countries and it no doubt applies to academic neurology and the field of MS.

The discrimination against women and other segments of our population has a pernicious effect on outcomes. If there is no level playing field it affects motivation and performance in the workplace and ultimately the kind of research that gets done, MS services we provide and clinical outcomes of our patients with MS.

We have highlighted gender bias in relation to MS research activities many times before on this blog. In relation to the make-up of MS trial steering committees, speakers at conferences, authors on publications and the faculty of important MS conferences, etc. Unconscious bias is all around us and unless you have an active process in place to address gender imbalances they don’t go away.

My wife who is a feminist is adamant that nothing is going to change regarding gender inequality unless men start to engage and actively promote women in their spheres of influence. I agree with her and more importantly as a father-of-daughters, I have a vested interest in making this happen. In the UK we have the so-called Athen Swan initiative, by which academic institutions have to show that they are addressing the gender gap and depending on how well they are doing they get a rating. This rating was used by the funding agencies to effect change; to apply for research funding from the MRC and NHIR you had to have a gold or silver Athena Swan award, which meant that women were getting a better deal from these Institutions.

This Athena Swan policy was the stick and carrot to make change happen. However, the Athena Swan requirement for funding applications has now been dropped in the UK. As a result, I predict there will be a gradual slide back down the hill and the next generation of women in academic medicine will be let down. I hope I am wrong.

The cynics reading this blog post will ask what thas this got to do with MS? I would suggest you think about the answer to this question and make a comment. Discussing how broader societal issues impact on MS research, MS management and the MS workforce underpins what happens in the field.

Richter et al. Women Physicians and Promotion in Academic Medicine. N Engl J Med. 2020 Nov 26;383(22):2148-2157.

Background: In 2000, a landmark study showed that women who graduated from U.S. medical schools from 1979 through 1997 were less likely than their male counterparts to be promoted to upper faculty ranks in academic medical centers. It is unclear whether these differences persist.

Methods: We merged data from the Association of American Medical Colleges on all medical school graduates from 1979 through 2013 with faculty data through 2018, and we compared the percentages of women who would be expected to be promoted on the basis of the proportion of women in the graduating class with the actual percentages of women who were promoted. We calculated Kaplan-Meier curves and used adjusted Cox proportional-hazards models to examine the differences between the early cohorts (1979-1997) and the late cohorts (1998-2013).

Results: The sample included 559,098 graduates from 134 U.S. medical schools. In most of the cohorts, fewer women than expected were promoted to the rank of associate or full professor or appointed to the post of department chair. Findings were similar across basic science and clinical departments. In analyses that included all the cohorts, after adjustment for graduation year, race or ethnic group, and department type, women assistant professors were less likely than their male counterparts to be promoted to associate professor (hazard ratio, 0.76; 95% confidence interval [CI], 0.74 to 0.78). Similar sex disparities existed in promotions to full professor (hazard ratio, 0.77; 95% CI, 0.74 to 0.81) and appointments to department chair (hazard ratio, 0.46; 95% CI, 0.39 to 0.54). These sex differences in promotions and appointments did not diminish over time and were not smaller in the later cohorts than in the earlier cohorts. The sex differences were even larger in the later cohorts with respect to promotion to full professor.

Conclusions: Over a 35-year period, women physicians in academic medical centers were less likely than men to be promoted to the rank of associate or full professor or to be appointed to department chair, and there was no apparent narrowing in the gap over time. (Funded by the University of Kansas Medical Center Joy McCann Professorship for Women in Medicine and the American Association of University Women.).

Crowdfunding: Are you a supporter of Prof G’s ‘Bed-to-5km Challenge’ in support of MS research? The project being funded is being led by Dr Ruth Dobson; yes, a woman researching MS. So every pound raised will be addressing the gender issue indirectly.

CoI: multiple

Twitter: @gavinGiovannoni Medium: @gavin_24211

Alison

Barts-MS rose-tinted-odometer: ★★

As you know we have had a designer, who is now a design researcher, embedded in our Barts-MS group for over a decade. Her name is Alison Thomson. In my opinion, Alison is worth her weight in gold in terms of the added-value she brings to the table. Alison’s work has been instrumental in many of our research projects and themes. For example, Alison was behind the design and validation of our cardboard 9-hole peg test that was part of our #ThinkHand campaign. Alison extended this to her project designing the Under&Over rehabilitation tool to maintain hand and arm function in people with more advanced MS. Alison is now leading a web-based study to see how effective the Under&Over activity is in maintaining and preserving hand-function in people with advanced MS. This is a very exciting project that is underpinned by the philosophy of ‘use it or lose it’.

After my accident and my thoughts on what needs to be done to improve healthcare design, Alison emailed me to ask the following questions.

“I’m thinking about how we can best support people to stick to the 12-week rehab programme. From what you are going through, what is keeping you motivated to continue with your rehab? Is it external factors like support from family, friends, colleagues etc. or seeing yourself physically improve? Or is it more internal, based on your personality as a self-motivated person? I’m looking for things we could incorporate into our digital programme – maybe not for the study, but for delivering digital programmes in the future.”

I delayed responding to this question because I had to think about it. I am not sure I have one definitive answer and I suspect my answers, or at least their emphasis will change over time.

I think first and foremost is that I have taken a positive position after my accident. I have refused to take a glass-half-empty approach. I am focusing on how lucky I am. Firstly, to be alive, yes to live another day and secondly not to have had a more severe head injury or spinal cord injury. I am not depressed. I now wake up each morning and look forward to living each day; one day at a time. My recovery is a form of mindfulness therapy; a time to reflect on the bigger picture.

I can’t overstate the role my family, friends, colleagues, acquaintances, blog readers etc. have also played. Being valued and appreciated makes such a difference. Never underestimate the role and value that a sense of self-worth plays in motivation. The experience has also taught me how important social capital is. For example, just getting kudos from strangers and friends via my Strava (a sports-related social media application) for my very slow rehab walks helps. So if we could socialise rehabilitation, i.e. use Strava or a similar application, to allow people to share their activities will be highly motivating and help engagement with rehabilitation.

Making rehab competitive is another lever that should be explored. I don’t mean beating each other at the 25-foot timed walk, but setting personal goals that are realistic. I did this by setting myself the ‘crutches-to-500m challenge’, which I subsequently changed to the ‘bed-to-5km challenge’ when I realised the former was too easy. Making this public, by linking this to a fund-raising initiative, which has its own target, is another nudge factor that helps me get-up and exercise every day. The one downside of this is I suspect I have been overdoing it a bit, i.e. trying to walk too far too quickly, which may actually be slowing down the pelvic fracture healing process. However, the feedback you get from measuring your progress shouldn’t be underestimated. Seeing that I am walking faster and further is highly motivating and makes me want to recover quicker.

Self-motivation is important and I am not sure this is any different to other things in life. I have always been intrinsically motivated and love personal challenges. I love reading and discovering new things even if they are not necessarily related to any specific goals or ambitions. Designing and implementing a self-rehabilitation programme has been great. I started by going back to basics and re-learning about all the muscles in the shoulder and hip girdle; their insertion sites, which nerves and nerve roots innervate them and how to exercise each muscle. What I wasn’t sure about was whether I had to exercise my weak muscles to exhaustion (anaerobic exercise) or should I just do slow repetitions (aerobic). Another issue was isometric (a muscle contraction in which the muscle doesn’t change in length) vs. isotonic (muscle changes in length) contractions. I searched and read the rehabilitation literature and there were no clear answers to these questions. What I didn’t get right is how to prepare your body posture to isolate the muscle action to prevent compensatory muscles taking over the action of the weak muscles. Fortunately, a good friend and neurorehabilitation colleague recommended I see a specialist rehabilitation neuro-physiotherapist who has identified the flaws in my DIY programme and has given me a much more targeted exercise programme. This is an example of why experts, in particular deep experts, matter.

I have to admit that I have had to go the private physiotherapy route because the NHS route would have taken too long (10-12 week wait) and I had already achieved all the objectives set by the inpatient therapy team at King’s College Hospital; i.e. being independent in terms of activities of daily living, climbing stairs and walking outdoors unaided. What the inpatient therapy team should have done is to ask me what I wanted to achieve with a bespoke rehab programme? I would have taken their objectives for granted, as the minimal baseline on which to build on. In reality, I want to get back to normal as quickly as possible, i.e. back running and potentially running another marathon. If I do run another marathon I promise to do it to raise money for either the MS Society or the MSIF. I also want to get back to work; i.e. being able to complete a 12 hour day sitting or standing at my desk.

I am also a bit of an exercise junkie. If I don’t exercise I get low and feel that something is missing in my life. My addiction to exercise, in particular, running goes back to my teenage years. Doing my daily rehab exercise programme makes me feel good; self-reward for a job well done. I also enjoy doing it. If you do regular exercise you will know what I am talking about. If on the other hand, you don’t like exercise, which is about 40% of the population, you won’t relate to this aspect of self-motivation.

I think Alison also needs to appreciate that I am coming to my rehab from a very privileged position. I have had trauma, which is a monophasic or one-off insult to my body and hence my injuries will improve spontaneously, provided I have no complications. If I had MS this would not necessarily be the case; particularly if I had advanced or progressive MS. Just having MS, or another chronic progressive disease may impact on motivation. I am highly educated and have medical knowledge. I also have financial resources and was able to purchase home gym equipment and pay for private physiotherapy. Being employed with a good income must count a lot. I am married and don’t live alone. Being lonely will impact on your mood and motivation. What I am getting at is that my personal circumstances make it so much easier for me to optimise my rehab compared to other people who are in very different positions. This is why the social determinants of health are likely to be as important in determining rehab outcomes as they are in determining mortality or other health outcomes.

So in summary, I think the following is a list of factors that are motivating me to stick to my rehab programme:

Positive attitude; not depressed
Education and knowledge
Access to resources
Self-directed objectives
- Feedback
Social support
- Family, friend and colleagues
- Social media apps, e.g. Strava
Competitive
- Goal-orientated rewards
- Gamify or make addictive
- Fund-raising
Make it fun and enjoyable

Crowdfunding: Are you a supporter of Prof G’s ‘Bed-to-5km Challenge’ in support of MS research?

CoI: multiple

Twitter: @gavinGiovannoni Medium: @gavin_24211