Do you smell like someone who has MS?

D

Barts-MS rose-tinted-odometer: ★★★★★

Did you know that because you have MS you are likely to have different odours on your breath compared to someone who doesn’t have MS? In other words, you have a characteristic MS smell

Multiple sclerosis is usually referred to as a complex disease, i.e. it is caused by an interaction between genetic factors and the environment and bad luck. Some people have difficulty getting their heads around this relatively simple concept. 

Now I want to take it one step further. MS must be a metabolic disease, i.e. MS must have a characteristic metabolic signature that differentiates it from other diseases and from ‘normality’. The reason I say this that metabolism is the great integrator of your genome and how your genes interact with the environment (microbiome, diet, season, stress, medications, etc.). If MS is a complex disease it must manifest metabolically with a unique profile.

If the MS metabolome has a characteristic metabolic signature and some of the metabolites are likely to be volatile and released in your breath, it may be possible to train a nose, either a dog’s nose or an electronic nose to detect the presence of this metabolic signature in your breath that can then be used to diagnose MS. Science fiction or not?

This may sound like science fiction but this approach is being evaluated in neurodegenerative diseases such as Parkinson’s disease and the data looks very compelling. I even know a few Parkinson’s disease experts who say they can smell if someone has Parkinson’s disease or not.

The MS study below, although a pilot, shows promising results. Using an eNose or electronic nose the investigators first taught an AI engine to what people with MS smell like. The taught AI engine, using a new cohort of study subjects, was then able to identify who has MS from healthy controls with a sensitivity of 0.75 or 75%, which to me is very good as a starting point. Imagine how this will improve as eNose technology improves and the AI engine is given more people with MS to smell and learn from.

I see a future when we use devices such as the eNose or metabolic profiling and artificial intelligence to identify people at risk of MS or with asymptomatic MS for MS prevention studies. Smell or eNose technology will become more sophisticated with time. I see a future when it will become mainstream and be part of the new healthcare environment we work in. Patients attending their GPs or an emergency department with a diagnostic problem will be sent for an eNose evaluation as part of the diagnostic work-up. This routine screening may open a window into the early detection of MS and other diseases. Watch this space!  

The Aeonose device or eNose

Ettema et al. Detecting Multiple Sclerosis via breath analysis using an eNose, a pilot study. J Breath Res. 2020 Dec 3. doi: 10.1088/1752-7163/abd080. Online ahead of print.

Objective: In the present study we investigated whether Multiple Sclerosis (MS) can be detected via exhaled breath analysis using an electronic nose. The AeonoseTM (an electronic nose, The eNose Company, Zutphen, The Netherlands) is a diagnostic test device to detect patterns of volatile organic compounds in exhaled breath. We evaluated whether the AeonoseTM can make a distinction between the breath patterns of patients with MS and healthy control subjects.

Methods: In this mono-center, prospective, non-invasive study, 124 subjects with a confirmed diagnosis of MS and 129 control subjects each breathed into the AeonoseTM for 5 minutes. Exhaled breath data was used to train an artificial neural network (ANN) predictive model. To investigate the influence of medication intake we created a second predictive model with a subgroup of MS patients without medication prescribed for MS.

Results: The ANN model based on the entire dataset was able to distinguish MS patients from healthy controls with a sensitivity of 0.75 [95% CI: 0.66-0.82] and specificity of 0.60 [0.51-0.69]. The model created with the subgroup of MS patients not using medication and the healthy control subjects had a sensitivity of 0.93 [0.82-0.98] and a specificity of 0.74 [0.65-0.81].

Conclusion: The study showed that the AeonoseTM is able to make a distinction between MS patients and healthy control subjects, and could potentially provide a quick screening test to assist in diagnosing MS. Further research is needed to determine whether the AeonoseTM is able to differentiate new MS patients from subjects who will not get the diagnosis.

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Twitter: @gavinGiovannoni                             Medium: @gavin_24211

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

22 comments

  • I’m sure I remember reading about a woman (in US, think) who had been identified as having a super-developed sense of smell and was then enrolled in a trail involved in a trial about detecting Parkinson’s. This was after she had convinced doctors that she had diagnosed her own husband with it because his smell had changed.

    • Yes and I remember raising that on this blog a long time ago and questioning MD1 if it could be used in diagnosing MS.

  • I could notice that my late Dad’s smell changed when early onset Alzheimer’s was diagnosed.

    I also notice my own smell (don’t judged everyone has our own unique smell!) changed, especially the smell (quite distinctive) of any congestion of my nose!

    I feel breathe too – but I eat way too much spicy food for me to really comment! My other half says I can smell things really well & always have been able to – this seems to have not changed, since diagnosis.

    I hope you’re getting there & I wish you well with your recovery.

    All the best,

  • It makes a lot of sense but it needs a lot of efforts for standardization and specificity is to be verified. Also the training set would be quite large to ensure adequate specificity. But if the system is simple it will be a great thing. It would be even better if it could be used to predict/detect relapses and if a therapy is effective or not.

  • This might sound weird, but I knew I smelled different after both rounds of alemtuzumab. Thankfully it only lasted for a couple of weeks before I returned back to normal (I think…).

  • This shouldn’t come as a surprise. EBV chronically infects B-cells, some T-cells and oromucosal epithelial cells. I suspect this is detecting the latter.

  • “Multiple sclerosis is usually referred to as a complex disease, i.e. it is caused by an interaction between genetic factors and the environment and bad luck. Some people have difficulty getting their heads around this relatively simple concept.”

    Is it a relatively simple concept? I can get my head around the genetic factors (my aunt died of MS in her late 40s) and the environment (I had a bad case of glandular fever / mono), but the issue of bad luck is way more complicated. Was the bad luck the combo of having the susceptibility genes and getting EBV infection at the wrong time? Was the bad luck being born in 1969 (c.4 billion years after the earth was created) in a time period where I may live to see strategies to prevent MS or repair MS damage, but which I am unlikely to benefit from? Was the bad luck getting a disease which fell to the one specialism where limited progress has been made against the very worst diseases? Or was my bad luck a punishment from above for transgressions in a previous life ie it was my fate? The reason why some people get ‘bad luck’ and others get ‘good luck’ is even beyond your intellectual abilities.

    • Luck is all too often the excuse for all the factors that we don’t yet understand. It might be solar vitamin D, stress from factors beyond our control, genetics, exposure to EBV, inherited retroviruses or some other factor. One day, probably a long way in the future, everybody will stop talking about luck. Maybe before then, we’ll be honest and admit, “we don’t know”, or maybe we’ll carry on calling it luck/superstition.

    • Most Neurologists are at a stage of unconscious incompetence (The BAN). This blog demonstrates conscious incompetence. https://en.wikipedia.org/wiki/Four_stages_of_competence It is probably wrong to think that we’ll completely understand everything about MS in our lifetimes. Equally, MS treatment demonstrates a flaw in this model because some neurologists are doing the right thing for the wrong reasons like AHSCT – they actually believe they’re rebooting the immune system!

  • Haven’t read other peoples’ comments but haven’t dogs had a significantly higher success rate, say 90+%? Cheaper and cuddlier too.

  • That would be cool but it can open fire to misdiagnosis and unnecessary workup if used in low likelihood of having MS in the ED or PCP setting. I can also imagine the psychological burden of patients have this quick screening test in the ED until they get in to see a neurologist . I think MS is way complicated than a simple nose test and clinical judgment and exam will always be key.

      • I’d love to but if I’m thinking prevention, I’d put more weight on modifying environmental risk factors or dig into/discover new environmental risk factors rather than a screening test to improve diagnostic accuracy.

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