#T4TD Infected

Did you know that a third of relapses are triggered by infections, typically non-specific viral infections? 

The observation that a relapse is more likely to occur in the so-called ‘at risk’ period, typically 5-6 weeks after infection than at other times predates the disease-modifying therapy era of MS. The mechanism is thought to be that infection boosts the immune system non-specifically, which then trigger relapses. This observation was extrapolated to vaccinations, but most vaccine studies now show that vaccines in general, with the possible exception of the yellow fever vaccine*, are safe and are not associated with an increased risk of relapses nor MRI activity. 

* Please note recent data on the live yellow fever vaccine shows that it doesn’t trigger MS relapses. 

Once people are on an effective DMT the link between infections and relapses is not observed. This is another, albeit minor, reason to be on a DMT. However, there is an emerging field in basic science and clinical evidence to support it that recurrent infections drive some of the pathological processes that are responsible for smouldering MS. Systemic inflammation activates CNS microglia that then produce cytokines and inflammatory mediators that have a negative effect on neuronal function. This is why people with MS handle infections so poorly and often don’t get back to baseline after a severe systemic infection. 

Therefore as part of the holistic management of MS, it is a good idea to prevent chronic or recurrent infections. So if you have recurrent or chronic bladder infections, periodontitis (gum disease), chronic sinusitis or recurrent chest infections you need to do something about it. Don’t just accept recurrent infections as your lot in life ask your MS team for advice and help. 

#T4TD = Thought for the Day

CoI: nil in relation to this post

#T4TD Driving at night

Did you know that more than half of people with established multiple sclerosis (pwMS) have had an episode of optic neuritis (an MS lesion in the optic nerve)? Not all episodes of optic neuritis cause symptoms and can be subclinical. We detect the latter using visual evoked potentials that show slowed conduction in a particular optic nerve. 

When optic neuritis recovers the conduction speed of nerve impulses travelling through the recovered nerve rarely gets back to normal and is slower than the conduction speed in the unaffected eye. In addition, the conduction speed can change depending on fatigue or ambient temperature changes. The conduction in the affected, by remyelinated, nerves can even fail and this is can result in intermittent blurring or loss of vision called Uhthoff’s phenomenon. 

The brain is usually quite good at compensating for the signals coming from the eyes at different speeds, but the one thing it is poor at doing is adjusting for depth perception. The reason we have two eyes with overlapping visual fields or binocular vision is for depth perception. This is why pwMS with previous optic neuritis may have poor depth perception, which affects their ability to judge where for example a cup or glass is on the table and as a result of this they often spill drinks. PwMS will also have difficulty playing ball sports such as tennis, table tennis or any sport that requires accurate depth perception. 

One function that seems to very sensitive to this phenomenon is judging distances whilst driving at night; for example, estimating how far you are from the traffic intersection or a stop sign. Many of my patients don’t like driving at night because of this. Why? Well, the brain uses a process called parallax to compensate for the loss of depth perception; i.e. the brain uses the relative size of familiar objects to help make a judgment on how far something is away from you in the distance. By using parallax somebody who is blind in one eye can judge depth and distance relatively well. However, at night in the dark when images are not well illuminated and use of colour vision drops judgement by parallax fails and depth perception deteriorates. 

I would be interested to know if any of you have any of these problems with depth perception and driving at night. If you do the chances are that you have had optic neuritis in the past. 

Unfortunately, there is little we can do to treat this phenomenon, but knowing about and understanding why it occurs may help you compensate for this impairment, disability or handicap. 

Parallax: Have you ever wondered why the setting-sun and full-moon on the horizon look so big compared to it being smaller when it above us in the sky? It is actually not bigger; simply having a reference on the horizon (trees, mountains, buildings, the sea, etc.) makes your brain perceive it as being larger, i.e. closer. This is how parallax affects how the brain works and judges distance from you to an object in the distance. 

#T4TD = Thought for the Day

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#MSCOVID19 transient antibody responses

The MS community is panicking because a handful of pwMS on anti-CD20 therapy don’t seem to make antibody responses to SARS-CoV-2. The implications are that these patients are susceptible to reinfection. We can’t be sure of this as lasting long-term antiviral immunity may rely more on T-cell responses, in particular CD8+-T-cell responses, than antibody responses. Let’s hope this is the case. 

The study below done in London shows that even in people from the general population with confirmed virus-positive COVID-19 rapidly lose their neutralizing antibody response to the virus. Are we surprised? No this is well described with both SARS-CoV-1, SARS-CoV-2 and other coronaviruses. 

What does this mean for the pandemic? It means that vaccine responses may need to be tracked with other immunological techniques outside of easy-to-develop and easy-to-do standard antibody assays. In short, we may not be able to rely on anti-SARS-CoV-2 antibodies to assess the effectiveness of a vaccine. 

The monitoring of  T-cell responses to viruses and other organisms is not trivial when you need to do it at scale. We will need to develop so-called T-cell proliferative-type response assay at speed. What this means is that we need to be able to measure if T-cells response to coronavirus antigens by dividing or activating themselves and producing cytokines. The latter is the easiest test to scale-up and is the method that is currently used in the Quantferon assay for latent or active TB. 

The challenges posed by SARS-CoV-2 for the world community is quite extraordinary and one has to wonder why coronavirus research funding was not continued and ramped-up after the SARS-CoV-1 epidemic in 2002-2003. Black swan events can be predicted; it is all about odds. I was pleasantly surprised to read the World Bank in 2017 had set the risk of a coronavirus pandemic in the next decade at 5.9%. They thought that the odds of a coronavirus pandemic was more than a 1 in 20 and this is only one of the risks that underpinned their catastrophic pandemic bonds issue; i.e. an insurance policy for low-income countries to deal with a catastrophic event. If the World Bank had the foresight to do this why didn’t politicians in high-income countries respond in a similar fashion? There will be many questions to answer when the dust settles post-COVID-19. I sincerely hope a few political heads roll. We need to take a hard look at whether or not market solutions are really the answer to dealing with existential threats and we need to stop bashing scientists and academics? If we as a society spend billions on academic/intellectual infrastructure we need to maximise its use.

Seow et al. Longitudinal evaluation and decline of antibody responses in SARS-CoV-2 infection. MedRxIV doi: https://doi.org/10.1101/2020.07.09.20148429

Antibody (Ab) responses to SARS-CoV-2 can be detected in most infected individuals 10-15 days following the onset of COVID-19 symptoms. However, due to the recent emergence of this virus in the human population, it is not yet known how long these Ab responses will be maintained or whether they will provide protection from re-infection. Using sequential serum samples collected up to 94 days post-onset of symptoms (POS) from 65 RT-qPCR confirmed SARS-CoV-2-infected individuals, we show seroconversion in >95% of cases and neutralizing antibody (nAb) responses when sampled beyond 8 days POS. We demonstrate that the magnitude of the nAb response is dependent upon the disease severity, but this does not affect the kinetics of the nAb response. Declining nAb titres were observed during the follow-up period. Whilst some individuals with high peak ID50 (>10,000) maintained titres >1,000 at >60 days POS, some with lower peak ID50 had titres approaching baseline within the follow-up period. A similar decline in nAb titres was also observed in a cohort of seropositive healthcare workers from Guy′s and St Thomas′ Hospitals. We suggest that this transient nAb response is a feature shared by both a SARS-CoV-2 infection that causes low disease severity and the circulating seasonal coronaviruses that are associated with common colds. This study has important implications when considering widespread serological testing, Ab protection against re-infection with SARS-CoV-2 and the durability of vaccine protection.

CoI: nil in relation to this post

Is exercise druggable?

Exercise is the most underrated and under-utilised DMT. Why? 

Ever since I ditched football, or soccer as it is called in the Americas, as a skinny 13-year old for long-distance running I knew intuitively that there was something extraordinary about aerobic exercise. Running is not only mindfulness, but it makes you think clearer in general and lifts your mood. Long-distance running is a philosophy and it adds true meaning to life. For those of you who are exercise-junkies, you will know what I am talking about. For those of you who haven’t experienced the uplifting benefits of exercise, I would suggest reading Haruki Murakami’s book ‘What I Talk About When I Talk About Running’. Murakami is an extraordinary writer and brings a wonderful and mystical Japanese philosophical twist to the task at hand.

It is clear that running or exercise, in general, is one of the most underutilised treatments we have for multiple sclerosis and neurodegeneration in general. It is clear that exercise and diet have to be at the base of any brain health pyramid. As always there is biology that underpins the treatment effects of these simple lifestyle interventions. Most of us have assumed exercise works by simply stimulating growth factors and endorphins in the central nervous system. Growth factors are responsible for anti-ageing effects and endorphins for its mood-elevating effects and explain the runner’s high. However, the latest work just published in Science (see below) shows that the health benefits of exercise on ageing may be mediated by a hormone that is released from the liver. 

The circulating factor is glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (Gpld1), which increases after exercise and was shown to correlate with improved cognitive function in aged mice. Importantly blood levels of Gpld1 are increased in active healthy elderly humans. If this work is confirmed it means we may be able to hack exercise’s effects on this pathway and create a drug that you can take that will prevent you from ageing and if you have MS slow down your disease progression. Wouldn’t that be a remarkable innovation?

As always to create a viable market for anti-ageing drugs we need to classify ageing as a disease. This will create the incentive for Big Pharma to invest. If we don’t classify ageing as a disease antiageing medications will be confined to the consumer market, which makes it very difficult to study in diseases such as MS and get them licensed by the regulatory authorities as treatments for multiple sclerosis and other neurodegenerative diseases. If you interested in reading more on this issue please read my Medium post from three years ago where I make the case that ageing is a disease. 

Horowitz et al. Blood Factors Transfer Beneficial Effects of Exercise on Neurogenesis and Cognition to the Aged Brain. Science. 2020 Jul 10;369(6500):167-173. doi: 10.1126/science.aaw2622.

Reversing brain aging may be possible through systemic interventions such as exercise. We found that administration of circulating blood factors in plasma from exercised aged mice transferred the effects of exercise on adult neurogenesis and cognition to sedentary aged mice. Plasma concentrations of glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (Gpld1), a GPI-degrading enzyme derived from liver, were found to increase after exercise and to correlate with improved cognitive function in aged mice, and concentrations of Gpld1 in blood were increased in active, healthy elderly humans. Increasing systemic concentrations of Gpld1 in aged mice ameliorated age-related regenerative and cognitive impairments by altering signaling cascades downstream of GPI-anchored substrate cleavage. We thus identify a liver-to-brain axis by which blood factors can transfer the benefits of exercise in old age.

CoI: none in relation to this post

#MSCOVID19 Ding-dong round 2

A 15-round heavyweight boxing match is a good analogy when it comes to describing our fight against the coronavirus. We have spent the last 3 months sparring and looking for each other’s weaknesses as we land a few body blows but no knock-out punch. Although we have flattened the curve we have a long way to go. The ultimate aim will be to knock-out the virus with a strategically placed blow to the head in the form of a vaccine. However, before we get a vaccine there are many more rounds of boxing left in this pandemic and sadly many more deaths to come. 

It looks as if Israel has lost round 2. There has been a worrying rise in daily coronavirus infections in Israel. The failure to contain the virus has led to the resignation of the head of public health services, who said in his resignation letter that “the entire country is burning”. 

At one stage Israel was being held up as the poster child of how to control the pandemic at a countrywide level. Israel was one of the first countries to close down its borders and to lock down early. The strategy was so successful that by mid-May it only had a trickle of cases. Then Binyamin Netanyahu, the Israeli prime minister, relaxed the lockdown and urged Israelis to go out for a beer and “have fun”. Does this sound familiar? Boris Johnson and his cronies are even considering giving every adult in the UK a £500 voucher to spend on the service industries most hit by the economic fall-out of the COVID-19 to stimulate the economy.  Don’t you think this is a good idea? I don’t.

Based on the Israeli experience the UK is likely to have a second wave of coronavirus infections and the anticipated second surge in NHS hospital admissions and deaths. The one glimmer of hope has to be our contact-tracing system, despite its imperfections, which may be able to quell the outbreaks locally and prevent spillover into the wider population. 

The tragedy of a potential second, third and subsequent wave of infections is that it prevents the NHS from getting back to a relative state of normality and recommencing routine services again. The longer the tail wags the dog more of our patients with MS and other chronic diseases are suffering from a suboptimal service. Although we are providing a remote MS service, that I am actually quite proud of, it is not ideal. Many patients are trapped in limbo on a stalled diagnostic pathway or waiting for routine monitoring MRI scans and/or lumbar punctures and the list goes on. 

The following is the summary of the recent survey we completed in relation to remote MS services in the UK. I think the results are self-explanatory and there is clearly room for improvement. I want to thank you for taking the time to fill out the survey; you will be surprised that we do take on board your feedback and just maybe we can improve things going forward.

Any additional thoughts or comments from yourself? They are much appreciated.

CoI: none in relation to this post

#MSCOVID19: summertime

To me three swallows make a summer; one from Sweden, a second from Iran and now a third from Italy. I have little doubt more will emerge soon.

A few weeks’ ago I explained that having asymmetrical information is never a good thing. Tragically I have known about the data published yesterday on the Lancet’s pre-publication archive for several weeks.

The new data shows that ocrelizumab-treated Italian pwMS were more likely to get COVID-19 and severe COVID-19 compared to other DMTs. This now supports the Swedish rituximab data presented by Jan Hillert on the iWiMS COVID-19 webinar in May and the Iranian survey data on rituximab (see Safavi et al. below). The message across these three data sets is now quite consistent; anti-CD20 therapies affect the biology of COVID-19 differently to other DMTs. 

How anti-CD20 therapy increases your chances of getting COVID-19 suggests it either (1) increases your exposure to the SARS-CoV-2 virus, which to me is not plausible unless it is due to increased exposure to the virus as a result of attending hospitals for infusions, or (2) it reduces your chances of having an asymptomatic infection. To me, the latter seems most likely and is meanable to study.

The immune responses to other human coronaviruses, the ones that cause the common cold, may cross-react with SARS-CoV-2 and help keep the virus in check and explains why some people get asymptomatic or mild infections. Having had a common cold in the recent past has given you some built-in protection against getting COVID-19 and severe COVID-19.  

I hypothesise that if you were B-cell depleted from being on an anti-CD20 when you had that common cold your immune system doesn’t make the necessary high-quality or high-affinity cross-reactive antibodies that you now need to protect yourself from getting symptomatic COVID-19 and potentially severe COVID-19. 

Should this data on anti-CD20 therapy change clinical practice? If you are already on an anti-CD20 therapy there is little you can do about your preexisting immunity to community-acquired coronaviruses; you either have immunity or you don’t. Similarly, you can’t simply revere the action of anti-CD20 therapies as it takes months to years to reconstitute your peripheral B-cell pool. Therefore I would simply recommend that if you are on an anti-CD20 therapy being extra-vigilant when it comes to trying to avoid being exposed to SARS-CoV-2 (social isolation, personal hygiene and avoiding high-risk environments). 

What about starting an anti-CD20 therapy? The decision to do this must be individualised and weighed against the risk of getting COVID-19. In countries where this risk is very low anti-CD20 therapies will be safe. 

The issue of vaccine readiness may affect your decision to be treated with anti-CD20 therapy.  People who are B-cell depleted, as a result of anti-CD20 therapies, make blunted vaccine responses. This is not surprising because anti-CD20 treated patients lack germinal centres in their lymph nodes and spleen. Germinal centres are the immunological equivalent of a university. It is in the germinal centres that T-cells help B-cell mature, class switch their antibodies, i.e. go from IgM to IgG for example, and to then undergo affinity maturation of the antibody genes to produce high-quality antibodies. Without germinal centres, your immune system can’t educate your B-cells to make high-quality antibodies and hence vaccine response are poor. 

For people on anti-CD20 therapies, if they want to maximise your chances of responding to a vaccine you are going to have to pause your treatment to allow your immune systems to recover before receiving a coronavirus vaccine. When should you do this? Not now. I would not recommend this until an effective vaccine emerges. Only cross bridges when they are built and only if you need to cross them. 

There is still a relatively high chance that all of the 150+ SARS-CoV-2 vaccine candidates will fail; vaccine development for respiratory viruses is notoriously difficult.

These data is likely to be relevant to ofatumumab and other anti-CD20 therapies. 

Not surprisingly interferon-beta which is an antiviral protects you from COVID-19 and exposure to high-dose methylprednisolone in the last 4 weeks increased your chances of severe COVID-19. The latter supports our current policy of asking patients to shield for 2 weeks after steroids and to be extra-vigilant. 

Interestingly, there is a strong trend in the Italian data suggesting that natalizumab-treated patients may be at increased risk of COVID-19. Whether this is a real signal or not waits further data, but again the Swedish data supports this. This observation would not be surprising as we know natalizumab reduces trafficking of lymphocytes to mucosal membranes, which may be relevant in early anti-coronavirus immunity.

I suspect these observations will have implications for other infectious diseases. I would not be surprised when we study the immune responses and outcomes to other viral infections, for example, seasonal influenza the same patterns will emerge. Now that we have set-up COVID-19 registries I would urge the MS community to keep them open so that we can study what happens with the next influenza epidemic emerges, which is only months away. 

Sormani et al. Disease-Modifying Therapies and COVID-19 Severity in Multiple Sclerosis. The Lancet Preprint 8-Jul-2020.

Background: Immunosuppressive and immunomodulatory therapies are a major issue during the current coronavirus disease 2019 (Covid-19) pandemic, and in anticipation of possible next waves. 

Methods: In a nationwide study we retrospectively collected data of persons with Multiple Sclerosis (PwMS) with suspected or confirmed Covid-19. We assessed the association of therapies for MS with Covid-19 by comparing their observed frequency with the one expected in non-pandemic conditions (expressing the association by Odds Ratios [OR]). We evaluated baseline characteristics and MS therapies associated to a severe Covid-19 course by multivariate logistic models.

Findings: Of 784 PwMS with suspected (n=593) or confirmed (n=191) Covid-19 and a median follow-up of 84 days (range=30-135), 13 (1·66%) died: 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-three (4·2%) were admitted to an Intensive Care Unit; 90 (11·5%) had a radiologically documented pneumonia; 88 (11·2%) were hospitalized. We found an excess of patients treated with Ocrelizumab (OR=1·84,95%CI=1·31-2·56, p<0·001) and a reduction of patients treated with Interferon (OR=0·47,95%CI=0·33-0·67, p<0·001) as compared to the frequency of use of these DMTs in the Italian MS population. After adjusting for region, age, sex, progressive MS course and recent methylprednisolone use, the therapy with an anti-CD20 agent (Ocrelizumab or Rituximab) was significantly associated (OR=2·59,95%CI=1·43-4·67, p=0·002) with an increased risk of severe Covid-19 course. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR=6·0,95%CI=2·2-16·5, p=0·007).

Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, the study detected elements of risk and protection with respect to Covid-19 in MS. These will need to be considered in countries where the pandemic is persisting and in preparation for post-pandemic scenarios.

Funding: Roche donated the web-Platform and funded a fellowship to the University of Genoa.

Safavi et al B-cell depleting therapies may affect susceptibility to acute respiratory illness among patients with multiple sclerosis during the early COVID-19 epidemic in Iran. MSARDS Published:May 12, 2020.

Objective: To determine whether the course of COVID-19 is more severe in patients with MS and if MS disease-modifying treatments (DMTs) affect the risk of contracting the disease.

Methods: In a cross-sectional survey, data were collected by sending a questionnaire to 2000 patients with a demyelinating disease through an online portal system. Collected data included the current MS DMT and patient-reported disability level, history of recent sick contact, recent fever, respiratory symptoms, diagnosis with COVID-19, and the disposition after the diagnosis. We defined a COVID-19-suspect group as patients having fever and cough or fever and shortness of breath, or a presumptive diagnosis based on suggestive chest computed tomography. We calculated the proportion of COVID-19-suspect patients and compared their demographics, clinical characteristics, and DMT categories with the rest of survey-responders, using univariable and multivariable models.

Results: Out of 712 patients, 34 (4.8%) fulfilled our criteria for being in the COVID-19-suspect group. Only two patients required hospitalization. No patient required intensive care. In a multivariable model, disease duration (p-value=0.017), DMT category (p-value=0.030), and history of sick contact (p-values<0.001) were associated with the risk of being in the COVID-19-suspect group. Being on B-cell depleting antibodies (as compared to non-cell depleting, non-cell trafficking inhibitor DMTs) was associated with a 2.6-fold increase in the risk of being in the COVID-19-suspect group. (RR: 3.55, 95%CI: 1.45, 8.68, p-value=0.005).

Conclusions: The course of infection in patients with MS suspected of having COVID-19 was mild to moderate, and all patients had a full recovery. B-cell depleting antibodies may increase the susceptibility to contracting COVID-19.

Shen et al. Delayed Specific IgM Antibody Responses Observed Among COVID-19 Patients With Severe Progression. Emerg Microbes Infect. 2020 Dec;9(1):1096-1101.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly worldwide since it was confirmed as the causative agent of COVID-19. Molecular diagnosis of the disease is typically performed via nucleic acid-based detection of the virus from swabs, sputum or bronchoalveolar lavage fluid (BALF). However, the positive rate from the commonly used specimens (swabs or sputum) was less than 75%. Immunological assays for SARS-CoV-2 are needed to accurately diagnose COVID-19. Sera were collected from patients or healthy people in a local hospital in Xiangyang, Hubei Province, China. The SARS-CoV-2 specific IgM antibodies were then detected using a SARS-CoV-2 IgM colloidal gold immunochromatographic assay (GICA). Results were analysed in combination with sera collection date and clinical information. The GICA was found to be positive with the detected 82.2% (37/45) of RT-qPCR confirmed COVID-19 cases, as well as 32.0% (8/25) of clinically confirmed, RT-qPCR negative patients (4-14 days after symptom onset). Investigation of IgM-negative, RT-qPCR-positive COVID-19 patients showed that half of them developed severe disease. The GICA was found to be a useful test to complement existing PCR-based assays for confirmation of COVID-19, and a delayed specific IgM antibody response was observed among COVID-19 patients with severe progression.

CoI: multiple

#T4TD when it comes to Anti-CD20 therapy body size counts

Did you know that if you are a large person standard dose ocrelizumab is not as effective as it is in a small person? 

When looking at the efficacy of anti-CD20 therapies such as ocrelizumab you shouldn’t bother looking at relapses and focal MRI activity (Gd-enhancing lesions or new T2 lesions) when comparing effectiveness between doses and competing products. Relapses and MRI lesions are ultrasensitive to the effects of anti-CD20 therapies and are suppressed, to almost zero, at relatively low doses. In scientific measurement-speak we refer to this as a floor effect; in other words, you can’t go lower than zero or near-zero. 

However, when you look at disability progression (the real MS) there is clearly a dose effect, i.e. the higher the dose of ocrelizumab relative to body size, the greater the B-cell depletion and the less likely you are to progress. Most commentators miss this insight and are lulled into a false sense of security by seeing the relapse and MRI data when the real MS may be smouldering away and shredding your brain unabated. 

For this reason, we really need to do studies with higher doses of ocrelizumab and almost certainly higher doses of rituximab and ofatumumab. The observation that rituximab, at relatively low doses, doesn’t prevent the majority of pwMS becoming secondary progress is not surprising when it seems we need more intensive and not less intensive B-cell depletion. 

There are two hypotheses that could explain the dose-effect of ocrelizumab: (1) CNS penetration and the need to scrub the brain free of B-cells, or (2) really deep tissue B-cell depletion. Higher doses of ocrelizumab may achieve both of these. The real question is what is it about B-cells that is driving MS?

Those of you who are up to speed with safety and vaccine readiness data will argue that higher dose ocrelizumab will come with a price. Yes and no. Until we do the studies we won’t know. In relation to vaccine responses, I suspect there will be little difference between low and high dose ocrelizumab as both will almost certainly ablate germinal centre function. 

In terms of long-term safety, I suspect we may not need to use high-dose or very high-dose anti-CD20 therapy long term; we may get away with using it as an induction therapy followed by a maintenance therapy. 

Does this have implications for you as an individual? Yes, don’t accept your neurologist saying your disease is under control simply because you are relapse and MRI activity free; remember smouldering MS is the real disease. There are now compelling reasons why we need to do the double-dose ocrelizumab trial or DODO study and other add-on studies to target smouldering MS. Do you agree?

#T4TD = Thought for the Day

CoI: multiple

#T4TD falls and fractures

Did you know that people with MS have a six times higher risk than age-matched controls of having a long bone fracture of the lower limb?

The reason for this is that pwMS often have balance problems, unsteadiness of gait (ataxia), lower limb weakness (dropped foot) and are maybe excessively sedated from their medications. All these factors increase your chances of falling. In addition, pwMS are at high risk of poor bone health (osteopaenia or osteoporosis) due to inactivity, reduced outdoor activity, low vitamin D levels, steroid treatment and comorbidities such as smoking. 

falls + poor bone health = increased long bone fractures

Why is this so important? A lower limb long bone fracture is one of the events that can tip someone with MS from being independent into becoming dependent and is often the trigger for needing a wheelchair. In addition, people with advanced MS don’t rehabilitate very well because they have reduced reserve and are usually quite disabled. 

How do you know if you are at risk of falls and fractures? We have shown that the best predictor of falls is the need for a walking aid (splint, stick, crutch, frame, functional electrical stimulator, etc.). If you are using a walking aid and are having falls, or near falls, you need to see a physiotherapist to be enrolled in a falls prevention programme and you will also need to have your bone density checked. This latter can be assessed via several methods, but the commonest is called a DEXA scan (dual-energy X-ray absorptiometry scan). If you are found to be osteopaenic or osteoporotic you may need treatment. 

Falls and fracture prevention is another self-management task; please don’t ignore it!

Prevention is better than treating the consequences of falls and fractures. For example, one of my patients with MS tragically fell going to the toilet at night. She crashed into a mirror that shattered and lacerated her arm and severed her brachial artery. She tragically bled to death as she lived alone, did not have an alert dongle around her neck and was unable to get herself up off the floor. Ever since she died I have taken falls prevention very seriously. Can you please do the same? You never know it may even save your life. 

Long bones of the lower limbs = femur, tibia and fibula

#T4TD = Thought for the Day

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#T4TD vascular comorbidities

Did you know if you have MS and vascular comorbidity you are likely to need a walking stick approximately 6 years earlier than if you did not have vascular comorbidity?  Importantly this 6-year difference in reaching EDSS 6.0 (requiring a walking stick) is larger than the treatment effect of a platform DMT.

As vascular comorbidities are largely preventable are you doing anything to prevent or optimally treat your own comorbidities? If not, you need to ask yourself why not? Self-management and taking responsibility for your own health is the order of the day; this has become the new normal. 

Vascular comorbidities = diabetes, hypertension, heart disease, hypercholesterolemia, peripheral vascular disease and smoking.

#T4TD = Thought for the Day

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#T4TD menstruation

Women with MS may notice increased fatigue and intermittent symptoms in the second half of their menstrual cycle and during menstruation. Why?

After ovulation, a woman’s body temperature rises by ~0.4℃ (range = 0.3 to 0.6℃) which in someone with MS is enough to cause temperature-dependent conduction block. In addition, the process of menstruation involves a mild systemic inflammatory reaction that may exacerbate fatigue. I refer to this as catamenial fatigue. 

Catamenial = relating to or associated with menstruation

Over the years I have had several female patients with MS who have reported using aspirin or non-steroidal anti-inflammatories or paracetamol (acetaminophen) to self-manage these two periods of their cycle. Interesting? 

If you suffer from catamenial fatigue you may want to try one of these agents that almost certainly work by lowering body temperature.

#T4TD = Thought for the Day

CoI: none in relation to this post

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