Tag: holistic management

What has my age got to do with having MS?

Barts-MS rose-tinted-odometer: ★★★ (some readers have asked for this feature to stay)

How old are you? It depends. You may be aware that there can be a disconnect between your chronological or actual age and your biological age. As ageing or senescence is a biological process driven by metabolic, genomic and environmental factors you can see how there can be a disconnect between the two. As a result, many of us in medicine are beginning to think about unhealthy or accelerated ageing as a disease process. Making ageing a disease will create incentives for pharmaceutical and nutraceutical companies to invest in ageing R&D with the hope of producing medications or dietary supplements to slow-down or reverse the effects of ageing. 

Ageing is important in MS as there is emerging evidence that MS causes premature ageing of the CNS (central nervous system), which means that pwMS are more likely to experience age-related neurodegeneration sooner than they have to and this almost certainly contributes to delayed disability worsening in pwMS. 

It is clear that ageing impacts one’s ability to recover from CNS damage. It has been known for some time from clinical and animal studies that remyelination and neuronal plasticity are less efficient as you get older, which is why older pwMS recover from relapses less well than younger people. The animal studies below show that there is real biology behind these observations. Oligodendrocyte (myelin-producing) progenitor cells (OPCs) isolated from the brains of neonate, young and aged female rats show an approximately 50% difference in the levels of proteins they make. Differences were noted in both myelin-associated proteins and proteins that control several metabolic pathways. This study has clinical implications and can act as a read-out for finding drugs that could be used as anti-ageing agents. 

There are several interesting biological targets and drugs that already exist for targeting ageing. Metformin, a drug for treating diabetes, is one of the lead compounds going in an MS clinical trial at the moment. It is believed that its antiageing effects of performing are mediated via the so-called NRF2 or programmed cell survival pathway. Interestingly, fumarates (e.g. dimethyl fumarate) and ketogenesis also activate this pathway. Could DMF, and the other fumarates, be the panacea antiageing drug we need for tackling progressive or more advanced MS? Yes, I think so but to convince Biogen to follow the money is proving more difficult than we anticipated. We approached them recently to do a combination DMF-plus trial with another class of drug to augment DMF’s response and they said no. Pity because I think they are missing a trick and an opportunity to create new intellectual property.

Physiological ketosis from caloric restriction, intermittent fasting or low-carbohydrate diets is another way of activating the NRF2 pathway. The biology behind this is probably via β-hydroxybutyrate, a ketone body, which works via the hydroxycarboxylic acid receptor 2 (HCA2). Interestingly, this is the same receptor DMF activates.

Other anti-ageing treatments and strategies include exercise and avoiding getting comorbidities, which accelerate ageing, in particular, the metabolic syndrome (obesity, hypertension, glucose intolerance or diabetes) and smoking. The driver of the metabolic syndrome seems to be hyperinsulinaemia and the diets referred to above are all very effective in suppressing or reducing circulating insulin levels. 

So in 2021 if you have MS you need to think seriously about what you can do to tackle early and accelerated ageing. Most of the things you can do now involve lifestyle changes, which are often hard to implement. My advice would be to implement the changes slowly and you may find over time that the behavioural changes you make will stick. There is a lot of evidence for this from the field of behavioural psychology.

The above advice is part of the holistic approach to the management of MS I have been pushing for several years and my adoption of the ‘marginal gains philosophy’ for managing MS. 

“If we break down everything we can think of that goes into improving MS outcomes, and then improving each by 1%, we will get a large improvement in MS outcome when we put them all together.”

“Ask not what your neurologist and HCP can do for you, but what you can do yourself to optimise your own MS management and long-term MS outcome.”

de la Fuente et al. Changes in the Oligodendrocyte Progenitor Cell Proteome with Ageing. Mol Cell Proteomics. 2020 Aug;19(8):1281-1302.

Following central nervous system (CNS) demyelination, adult oligodendrocyte progenitor cells (OPCs) can differentiate into new myelin-forming oligodendrocytes in a regenerative process called remyelination. Although remyelination is very efficient in young adults, its efficiency declines progressively with ageing. Here we performed proteomic analysis of OPCs freshly isolated from the brains of neonate, young and aged female rats. Approximately 50% of the proteins are expressed at different levels in OPCs from neonates compared with their adult counterparts. The amount of myelin-associated proteins, and proteins associated with oxidative phosphorylation, inflammatory responses and actin cytoskeletal organization increased with age, whereas cholesterol-biosynthesis, transcription factors and cell cycle proteins decreased. Our experiments provide the first ageing OPC proteome, revealing the distinct features of OPCs at different ages. These studies provide new insights into why remyelination efficiency declines with ageing and potential roles for aged OPCs in other neurodegenerative diseases.

CoI: multiple

Twitter: @gavinGiovannoni                                              Medium: @gavin_24211

Self-diagnosis

Dear Neuro,

You see me once a year for 15 minutes, you look at my MRI report and blood results, you ask me a lot of questions, you examine me and then you tell me that everything is fine. At my last visit, you said my MS was stable, you mentioned to me that I was NEDA, because I had had no relapses, no new lesions on my MRI and my EDSS was static at 3.0. 

I have now looked up and read about NEDA (no evident disease activity) and I disagree with your assessment. I am clearly getting worse. The Christmas before last I remember going for a 5-mile walk with my family after lunch and managed it fine. When I tried the same walk last Christmas I had to turn back after a mile because my right leg was dragging. 

I also have other problems that you didn’t pick up on during the consultation. I now have to get up 2 or 3 times at night to pass urine. My memory is much worse than it was last year. My head feels foggy all the time as if I have a permanent mild hangover. I now avoid any social occasions with colleagues after work. The truth is I am too tired to at the end of the day to do anything else than get home. I feel exhausted most of the time. I have stopped gardening. 

I think I have developed secondary progressive MS. Do you agree? Would it be possible to see you sooner to discuss this? Is there anything you can do about my deterioration in functioning?

Yours sincerely

Patient Y

Does this story sound familiar? 

At first glance, it is easy to say this person has SPMS. But do they? 

Based on the definition of SPMS it seems likely, i.e. objective worsening of function for at least 6-12 months independent of relapse activity. Based on the latter it seems Patient Y is not having relapses. As for the objective worsening of function the interpretation is in the eye of the beholder. As far as the neurologist is concerned the patient is not deteriorating because the EDSS is stable. In comparison, the patient has documented, albeit rather crudely, a drop if in functioning. Who do you believe? 

The scenario illustrates what will happen when MSers begin to self-monitor and prepare for clinic appointments in advance, i.e. they will potentially be self-diagnosing secondary progressive or worsening MS. 

However, I want you to take a step back and ask could the deterioration be due to something else, something reversible? If it is due to something else it may be treatable and potentially reversible. 

Does this patient have any reversible comorbidities that could be responsible for the deterioration? Smoking, hypertension, diabetes, metabolic syndrome, obesity, underactive or overactive thyroid function, renal, liver, heart or lung disease? If a woman, is she menopausal? What about mental health issues; depression and anxiety? Is this patient drinking too much alcohol? Is the patient malnourished? They may be eating a diet of toast and tea.

Is this patient sleeping well? Getting-up 2 or 3  times a night to pass urine means their sleep hygiene is very poor. Just improving this patient’s bladder problems will have a major impact on their daytime fatigue and work performance.

What about a chronic infection? Could this patient have a low-grade urinary tract infection? What about their oral health; could they have gingivitis or periodontitis? Sinusitis?

Is this patient exercising enough? I suspect not. The drop off in the walking distance could be deconditioning, i.e. losing fitness because of lack of exercise. In this particular patient, I suspect this, however, is unlikely because deconditioning is unlikely to result in a dragging leg on walking a mile.

What medication is this patient on? Are they are on an anti-spastic medication or anticholinergics for their bladder problems? Both these class of drugs affect cognition and may explain the memory loss and brain fog. I have commented on baclofen being particularly problematic in the past.

How well is patient Y? Patient Y seems to have become socially isolated and withdrawing from having social interactions with their work colleagues. The patient has stopped gardening, which helps improve mental health. What about the home environment? Is patient Y’s relationship with the family stable, etc? What are this patient’s finances like? Are they in debt? Are they struggling economically? 

Could this patient have smouldering MS? Does this patient need an MRI of the spine and a lumbar puncture to measure CSF neurofilament levels? We know that brain MRI will not pick-up all disease activity. Does this patient need to start a DMT or have a DMT switched and escalated? I would be very interested to know how this patient’s cognitive function is and whether or not they have a swiss cheese brain (lots of black holes) and brain volume loss. Having this information makes a diagnosis of SPMS and/or smouldering MS more likely.

How old is patient Y? If they are over the age of 50 we may be seeing early ageing. 

Making a diagnosis of SPMS is not simple and most neurologists would prefer not to do it. However, if we are to improve the lives of our patients we need to take a holistic approach to the management of MS. Clinical practice must not be a box-ticking exercise. We need to provide our patients with the tools to self-monitor, self-diagnose and self-manage. We need them to become partners on a life-long MS journey that will result in better outcomes and happier and more content MSers and HCPs. 

To reiterate the philosophy of marginal gains “if you break down everything we can think of that goes into improving MS outcomes, and then improving it by 1%, we will get a significant increase when we put them all together”. This case vignette illustrates this very well. 

I hope this post motivates you to start self-monitoring and to start preparing for your consultations with your HCP. You need to have a list of questions to ask. Don’t let your neurologist or HCP fob you off. You know yourself better than they do; please don’t forget this.

CoI: multiple

Exit mobile version
%%footer%%