Japan epicentre of an Asian MS epidemic

J

I am about to return from a short MS meeting in Tokyo. This was my first exposure to Japan and Japanese culture. It is everything and more than I expected.

I am beginning to get a sense of what ikigai means. Ikigai translates ‘to a reason for being, encompassing joy, a sense of purpose and meaning and a feeling of well-being’. Ikigai derives from iki, meaning life and kai, meaning the realisation of hopes and expectations.

I first learnt about ikigai from the ‘Blue Zones’, a book by Dan Buettner, on the secrets of the world’s ‘happiest places’, where people are super-agers. One of the blue zones is Okinawa, a subtropical Japanese island to the South of Japan. Some of the philosophy underpinning happiness and super-ageing is cultural and is specific to the Japanese culture.

The lessons of the blue zones are applicable to our Brain Health initiative and I would urge you to read the book. Who knows it may change the way you want to live your life regardless of whether or not you have MS.

It is clear that MS is a problem in Japan and the incidence and prevalence is rising. Why? Japan is now one of the epicentres of the global MS epidemic; i.e. an area of the world where MS has gone from a low to a medium incidence area, similar to Iran, and will quite soon become a high incidence area. The clue to this is the rapidly increasing sex ratio of females to males that is now over 3:1.

As an MS community, we need to study these epicentres to see if we can pin down the cause of MS and put in place robust prevention trials. Japan has rapidly westernised and the Japanese neurologists I spoke to think this is the reason why the incidence of MS is increasing in Japan. Not sure I buy this at face value. What is it about the Western lifestyle that is causing MS? Could it be childhood obesity? Processed carbohydrate/sugar consumption? Smoking? Change in the epidemiology of EBV infection; a different strain, later infection, more infectious mononucleosis? Less sunshine and lower vitamin D levels?

It is interesting that Japanese neurologists think MS is more benign in Japan than elsewhere. I am not sure why they think this. All the evidence I saw this weekend points to Japanese MS being identical to Western European MS. Unfortunately for Japanese MSers, they have access to fewer DMTs and there are only two highly effective DMTs licensed in Japan, i.e. fingolimod and natalizumab. There is also a much higher JCV seroprevalence rate in Japan of close to 80% with a higher proportion of people with a high anti-JCV index. This makes the risk of PML potentially much higher in Japan. For example, there have been 4 cases of non-carryover PML on fingolimod, which equates to a PML rate of about 1 in 1,000 to 1,500 per fingolimod-treated MSer. This is an order of magnitude higher than the non-carryover PML rate on fingolimod outside of Japan and clearly needs further study.

Another factor is the reluctance of Japanese neurologists to use off-label treatments, for example, subcutaneous cladribine and rituximab. The reasons for this are multiple but mainly relate to lack of reimbursement and cultural factors. It was also clear that the Japanese neurologist, similar to British neurologists, are quite conservative and prefer a step-care approach. The Japanese are particularly concerned that because of their ancestry they may respond differently to DMTs, which have been tried and tested in other populations. In other words, they need data on the safety and efficacy of specific DMTs in their own Japanese MS population. To get a drug licensed in Japan Pharma has to trials in Japan.

As a result of the JCV problem extended interval dosing of natalizumab, also referred to as EID, and PML surveillance (3-monthly MRI monitoring) is very important for natalizumab-treated Japanese MSers. In fact, Japan is the one country that the derisking of PML for natalizumab is critical. Until other high-efficacy DMT arrive the Japanese are going to have to make do with fingolimod and natalizumab. In comparison, we are spoilt for choice in the UK and other high-income countries; we have forgotten what it was like to manage MS before the avalanche of new DMTs.

I have uploaded my slides from Japan on my slideshare site; you are welcome to download them and repurpose the slides for your own uses. I presented our #AttackMS study as a way to illustrate how important time matters in MS. I am not sure the Japanese neurologists agreed with such an active approach to treating MS. Do you?

Houzen et al.  Consistent increase in the prevalence and female ratio of multiple sclerosis over 15 years in northern Japan. Eur J Neurol. 2018 Feb;25(2):334-339.

BACKGROUND AND PURPOSE: The prevalence of multiple sclerosis (MS) is considered to be lower in East Asia than in Western countries. An increasing trend has been reported globally for the prevalence of MS. We investigated the changes in the prevalence and clinical characteristics of MS in the Tokachi province of Hokkaido, northern Japan from 2001 to 2016.

METHODS: Prevalence was determined on 31 March 2016. Data-processing sheets were collected from all MS-related institutions in Tokachi province. We applied Poser’s diagnostic criteria for MS as used in our previous three studies. Cases of neuromyelitis optica spectrum disorders were excluded.

RESULTS: In 2016, the crude MS prevalence was 18.6/100 000 (95% confidence interval, 14.3-23.8) in northern Japan. Over the last 15 years, the prevalence of MS in the same area was 8.1, 12.6 and 16.2 in 2001, 2006 and 2011, respectively. The female:male ratio was 3.57, which increased from 2.63 in 2001. The ratios of primary progressive, relapsing-remitting and secondary progressive MS types were 2%, 84% and 14%, respectively.

CONCLUSION: Our results demonstrated a consistent increase in MS prevalence among the northern Japanese population, particularly in females, and relatively lower rates of progressive MS in northern Japan than in Western countries.

CoI: multiple

About the author

Gavin

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

14 comments

Leave a Reply to Jay G Cancel reply

  • Hi Gavin, what a fantastic article you see unless we had the likes of yourself tirelessly researching and trouble shooting, to go through a proses of so called elimination, we would be none the wiser.

    Just this weekend I stumbled upon an article referring to Dirty Electricity, when you read into this more thoroughly there are some very valid points.

    Keep up the good fight
    Warmest wishes
    Sophia X

  • But they do have a history of Ibudilast use in Japan? For the treatment of asthma? Any data on effects on those taking the drug who also have MS?

  • Very interesting, thank you. You do get around. I’ve never been abroad. My plan had been to have treatment this year, I was expecting Lemtrada unless I could talk my way into HSCT, and then I was going to try go abroad with my girlfriend. And then move to London next year.

    But I fell at the first hurdle, didn’t manage to get treatment, so everything’s fallen apart and I’m looking at suicide clinics in mainland Europe.

    I’m a big fan of Japan, so it was on my bucket list of places to go. I’m an autistic geek, and Japan’s our spiritual home. I’m also a horror geek and japan makes great horror movies. Also Yuri, Yaoi… I like Japan.

    As for why MS is increasing in Japan… I still wonder whether MS is really increasing, or is it just that diagnoses are increasing?

    I imagine people have always had MS here in the UK? They just didn’t have diagnoses or treatment.

    Awareness of MS is no doubt increasing in Japan, both among doctors and patients. And the people of Japan are very much on the internet.

    I diagnosed myself with MS from Googling, and also as autistic with Hypernycthemeral Syndrome.

    ‘We have forgotten what it was like to manage MS before the avalanche of new DMTs.’ For me that’s a very interesting statement for you to make. I understand that you’ve forgotten. I certainly haven’t. I spent decades managing severe, disabling MS, from being an adolescent, with no treatment for symptoms, or DMT’s, or support. I won’t forget the hell of it till I die.

    I have lived as an autistic person with MS the same way as someone would have in medieval times.

    Is it just that people with MS in Japan were experiencing what I did, that no one believed them? MS effects women more, and Japan like everywhere is misogynist, did they just dismiss those people as ‘hysterical’ and lazy women? Japan in particular struggles with the concept of mental illness, not that MS is in any way a mental illness, but if people were persevered that way then the shame of it could have kept them hidden.

    I realise that, as always, I’m a complex case. My MS, my autism, my sleep disorder, my abusive family, being queer and trans and working class in Yorkshire… It all bled into each other and resulted in what happened to me. Those things can’t be separated.

    I became a Hikikomori, from being a child, legally, though I was never really a child. Which is a Japanese term for people, usually young men, who withdraw from society and are shut away. Usually in their bedroom in their parents’ house. Who disappear.

    I wasn’t just similar to a Hikikomori. I was literally 100% a very extreme Hikikomori.

    People would say that couldn’t happen in Yorkshire. It can and it did. In the west people like me can end up on the news, when they’re discovered. Someone, no one ever cared what happened to me.

    It’s interesting that people think it’s only boys. The reality is, there’s more social pressure on boys in Japan to excel in school and then in work.

    If a girl becomes a Hikikomori, that’s probably easier to ignore. Do any of them have MS? Possibly.

    Not that I think MS is a common occurrence amongst Hikikomoris. Autism is probably more common. But it’s an interesting question. Especially in Japan.

    A woman who, due to fatigue, pain, etc, withdraws from the world, could be perceived as modest, reserved, a homebody. It could almost be perceived there as admirable. And Japan is a reserved and polite society, it would be even harder there to fight the system, fight the doctors, fight one’s family, and I did a bad enough job of it here.

    And as for neurologists there perceiving MS as having fewer devastating symptoms, could that be them not taking the patients and symptoms seriously enough? Which is very much what happened to me for decades in the UK. It might not be what’s happening in Japan: but it might be. MS, like many diseases, is an invisible disability.

    How many people there are going through what I went though? No doctor believing them or caring.

    It is entirely possible to be completely disabled by MS, even here, even now, and the medical profession completely dismissing one and brainwashing one into believing that one is mentally ill and making it all up.

    My brother, with his PhD and who is the head of department at a university, told me that I should have succeeded in killing myself when I was 14, I did try, because ‘at least that’s taking responsibility.’ That I’m no use to anyone. And he didn’t believe I was really sick, he believed I was lazy and not trying hard enough, because the NHS said I was mentally ill with Chronic Fatigue Syndrome.

    I, eventually, diagnosed myself, went private, saw the doctors the NHS wouldn’t let me see, had the neurological tests the NHS said I wasn’t worth, put it all on credit card, and was proved right about everything.

    But I’ve led a Japanese life, in Yorkshire. I tell doctors that I was a Hikikomori, and they have no idea what I’m talking about, admittedly. But we have no word for it in English. The Japanese have a word for everything, it’s great the Japanese language.

    But I think it always has to be considered, that rates of MS, or anything else, aren’t increasing, just people managing to fight for the correct diagnosis and treatment are increasing.

    One always has to look at the culture. And the prejudices that the patients are going up against. And the prejudices of the doctors.

    Mental illness is a social construct. Most things are. We have to look at what social constructs exist and how long they’ve existed. Some things we have to fight to change.

    The reality is, the NHS didn’t believe I had MS, because I was autistic, and it didn’t believe I was autistic, because I had MS. It didn’t believe anyone could be that unlucky, to have that many rare conditions. And it was easier and cheaper to chuck me on the rubbish heap as mentally ill. Which is also a terrible way to treat the mentally ill, even though I’m not mentally ill. After I went private, I was in the Royal Papworth Hospital, and they called me an ‘anomaly.’ I get called ‘complex’ and ‘vulnerable’ by professionals all the time. And I am. But I wonder: how many people are out there, living lives of quiet desperation, as I did? How many people are being refused help by the NHS and other medical bodies in other countries? I should be dead, and it’s remarkable that I’m not. And were it not for my autistic gift for research, my spite, and my credit card with a £9000 credit limit, you wouldn’t be reading this.

    Whilst I was misdiagnosed as being mentally ill with CFS, I was under the CFS team from Hull Royal Infirmary. I used to get home visits from the lead, a consultant liaison psychiatrist, because I was too sick to get there. She told me that, ‘At least you have your health.’ I’d already gone blind from Optic Neuritis, couldn’t feel my feet anymore from repeated bouts of loss off feeling in my body, the fatigue and pain were overwhelming, and I was incontinent. She said that I had CFS, and I would totally recover if I just got rid of my ‘illness beliefs’ and did what the CFS team told me to do. I hated myself for being a failure, because I tried to be good and do what they told me to do, but I just sicker. She told me that CFS was what they used to just call ‘hysterical women,’ though I’m not a woman. I’m nonbinary.

    Point is, one has to look at what happens to people culturally. That happened to me in Yorkshire, and I was autistic with Hypernychthemeral Syndrome and MS, so what is happening to people in Japan?

    Part of the problem is that neurologists only ever see the winners. The people who get as far as you. So, I, for instance, had paediatric MS originally, then decades of MS as an adult, and you never knew I existed. The NHS would never have diagnosed me. I already had every symptom of MS for decades. I got myself a diagnosis. Most people, in my circumstances, couldn’t have done that. So, it has to be considered, that some people were/are just failing to get a diagnosis and treatment and support. How many people are killing themselves, are being told that they’re just failures, I certainly tried.

    The only thing that would really be indicative, is looking at people who get as far as a neurologist, who have an MRI scan, evoked potential tests, and a lumber puncture. What percentage of those people are diagnosed with MS? And even then, one has to look at who can get that far. What groups of people are being prevented from it? I was prevented from getting an MS diagnosis because I’m autistic. What chance does someone schizophrenic have? One has to look at race, class, poverty, gender, sexual orientation, culture, nationality, age, level of education, other disabilities, etc.

    One has to look at the difference between correlation and causation.

    I’m glad you had a good time in Japan.

  • Gavin your air miles and carbon emissions must be off the Richter scale! But thanks for sharing everything and making it worthwhile, saves lots of others needing to make the trip.

    So, MS is on the rise everywhere. Or at least awareness and diagnosis is. Another reason for centres around the world to meet and learn from each other. Thanks for continuing to do this.

  • OK. But does this imply the spread of ebv virus or more likely. People idea of beauty has changed a d fair skin is sought after by avoiding the sun? Same reason for the epidemics in India, Iran etc.

  • Thanks very much for this Gavin. I am curious to know if the gender ratio for MS in Japan is the same as it is in the rest of the world – with women getting it much more often then men?
    Rachel

  • Amazon has almost a series of ‘Blue Zones’
    related books by Dan Buettner.
    Which one should one start with?

By Gavin

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