Slow onset vs. sudden onset ME/CFS - numbers anyone?

[Hip]

This paper comparing sudden to gradual onset CFS is interesting: they studied 36 CFS patients, who were self referred. Out of this 36, 25 were sudden onset, and 11 were gradual onset, suggesting that sudden onset is more common.

So in this study they found:
31% of CFS patients are gradual onset
69% of CFS patients are sudden onset

Sudden onset was defined as a viral-like illness with a specific date of onset from which subjects did not recover. Gradual onset was defined as a slow progression of symptoms over a period of weeks to several months or greater.

They found that CFS patients with gradual onset are more likely to have comorbid psychiatric disorders (such as major depression and anxiety) than patients with sudden onset of symptoms.

They also note that in another study, CFS patients with gradual onset had a significantly greater incidence of stressful life events occurring in the year just prior to symptom onset, relative to CFS patients with sudden onset.

Analysis of level of fatigue and illness severity showed no significant differences between the sudden vs gradual CFS groups.

CFS subjects with sudden onset tended to experience more difficulties in memory (particularly verbal memory) than subjects with gradual onset of symptoms.

 

[alex3619]

Once we have a diagnostic test (Griffith University expects to have one in the next 5 years)

Ron Davis might have one very much sooner. However its always good to have multiple tests, particularly if one comes back negative. False negatives may still occur. As might false positives.

 

[Forbin]

Sudden onset was defined as a viral-like illness with a specific date of onset from which subjects did not recover.

In my case there was an interval of a few days between when I felt fully recovered from a really bad flu and when I experienced the sudden onset of M.E. Although I certainly link my onset to that "flu" (which may have been strep throat), it felt like I had recovered from it (though I did experience a couple of momentary, "fish eye" visual distortions during that "well" period).

On the other hand, my WBC count was hanging just outside of the normal range immediately following onset, presumably still due to that "flu" that began 3-4 weeks earlier. Anyway, it's not like I went to bed with the flu and never felt OK again prior to the onset of M.E. It's possible that feeling "well" while my immune system was still fighting something may have compounded the problem by making me think it was OK to exert myself fully again.

At any rate, I think that a delay between the flu and ME onset may suggest that it can take time for something like Fluge and Mella's "x-factor" to reach critical mass and initiate M.E. People may reach that point at different speeds, some quickly enough to feel like they never recovered from the flu at all.

 

[arewenearlythereyet]

This paper comparing sudden to gradual onset CFS is interesting: they studied 36 CFS patients, who were self referred. Out of this 36, 25 were sudden onset, and 11 were gradual onset, suggesting that sudden onset is more common.

Sudden onset was defined as a viral-like illness with a specific date of onset from which subjects did not recover. Gradual onset was defined as a slow progression of symptoms over a period of weeks to several months or greater.

They found that CFS patients with gradual onset are more likely to have comorbid psychiatric disorders (such as major depression and anxiety) than patients with sudden onset of symptoms.

They also note that in another study, CFS patients with gradual onset had a significantly greater incidence of stressful life events occurring in the year just prior to symptom onset, relative to CFS patients with sudden onset.

Analysis of level of fatigue and illness severity showed no significant differences between the sudden vs gradual CFS groups.

CFS subjects with sudden onset tended to experience more difficulties in memory (particularly verbal memory) than subjects with gradual onset of symptoms.

thank you @Hip this is really interesting. Looks like staged/gradual onset are a minority within a minority then?

Interesting. I wish there was more though. It seems that there is definitely a whole subset of people that have the staged/gradual and from what Alex is saying there seems to be 3 levels (sudden, gradual, staged). It would be great to understand whether there are biochemical/immunological commonalities and differences between the 3 groups other than psychiatric symptoms.

 

[arewenearlythereyet]

Found this

(Ray et al. (1998) interviewed 60 adults out of a larger subset of 147 adults who met the Oxford Criteria (Sharpe et al., 1991) for CFS and asked them to describe their illness onset. Ray et al. (1998) prompted participants by asking whether they had a gradual or sudden onset and asked them to describe in detail their onset duration as well as perceived contributory factors. Additionally, they interviewed participants with the shortest illness durations as well as individuals with the longest illness durations to investigate how illness length impacts their perception of onset and contributory factors. Interviews were coded for perceived contributory factors as well as how participants perceived the early development of their illness. The authors reported that the designated coders focused on how participants described their initial illness progression and they did not limit their coding to the terms “sudden” or “gradual.” Three separate groups of participants were identified when coding for CFS onset. One group was characterized by a gradual onset of CFS in which there was a slow, worsening of symptoms over time, culminating into the attribution that the illness was serious (n=15). A second group was identified as having an acute onset, which was characterized by a sharp increase in symptoms (n=31). Lastly, a third group was identified as having a two-phase illness onset, which began with a sharp deterioration and subsequent improvement in phase one, that was then followed by another deterioration of symptoms in phase two (n=14).

So looks like:

Half have sudden onset
A quarter have gradual onset
A quarter have staged

It's on page 36 of

http://via.library.depaul.edu/cgi/viewcontent.cgi?article=1117&context=csh_etd

 

[arewenearlythereyet]

Also on page 100

Ray et al. (1998) found that a portion of participants attributed their illness development to their immune system “breaking down.” A subset (36%) of participants in the current study also endorsed an immune component to their illness cause. These individuals typically described a series of infections (one individual described infections in combination with a physical trauma) that negatively impacted the immune system over time. These findings are consistent with an immune component theory posed by Hyde et al. (2007) who asserts that ME often follows multiple, minor infections in individuals with susceptible immune systems or immune systems that are weakened by severe stressors (e.g. contact with infectious persons, exhaustion, trauma, immunizations, epidemic disease, travel and exposure to virulent agents). Additionally, prior research has evidenced immune dysfunction and damage to the CNS in individuals with CFS (Broderick et al., 2010).

 

[arewenearlythereyet]

I think reading through all this that 50% seem to have sudden onset and then there is a difference in how researchers interpret the rest of us. It's interesting that on this forum it appears that most do seem to be sudden onset?

Perhaps us gradual onset "ers" are less visible. I know I am quite shy and retiring and very rarely state my opinion

 

[purrsian]

Ron Davis might have one very much sooner. However its always good to have multiple tests, particularly if one comes back negative. False negatives may still occur. As might false positives.

Oh yes I just learned about him and his family the other day, so wonderful to have such a talented man so personally involved but it's so sad that his son is in such a terrible state (I cried a lot while watching his mum talk about it!). Imagine the feeling though if he personally figures something out that significantly helps his son - that would feel incredible. Multiple tests would be great, in case there are some subsets who don't get a positive with one test but might with another.

And great searching @arewenearlythereyet ! I think the graded onset is definitely something that's been overlooked in the past. I think I fit in to that category, although I always used to say gradual onset. To me, it felt like each major stressor (infection, overworking) just broke my system that little bit more. I'd recover from each one and assume all was fine, but in retrospect, I can see I was actually declining each time and was just struggling with life so much that I never really noticed the overall decline. It was probably a 2-3 year decline before I started to get PEM.

 

[sleepingbeautyxxx]

My staged onset was like this:

1. VZV and never completely regained energy, mild fatigue, daytime sleepiness
2. one year after, blatter-, kidney-, tonsil infections, fatigue worsened, brain fog worsened, but still very mild symptoms
3. a few viral infections in addition and stress in school due to exams, all the symptoms worsened, heart pounding and "adrenaline kicks" all the time, sleep problems
4. flu shot, since then cold/flu like symptoms, aching joints all the time (mild though), brain fog and concentration problems worsened a lot, burning sensation under skin after waking up, problems falling asleep, very fatigued and heavy all the time (this was the stage that gave me a lot of new symptoms)

I feel like it's a progressing type for me @purrsian. I might get a little little bit better, but overall it got worse over the timespan of 3 years. This might be caused bc I can never rest very long after a "new stage" hits me (because of school).

 

[arewenearlythereyet]

And great searching @arewenearlythereyet ! I think the graded onset is definitely something that's been overlooked in the past. I think I fit in to that category, although I always used to say gradual onset. To me, it felt like each major stressor (infection, overworking) just broke my system that little bit more. I'd recover from each one and assume all was fine, but in retrospect, I can see I was actually declining each time and was just struggling with life so much that I never really noticed the overall decline. It was probably a 2-3 year decline before I started to get PEM.[/QUOTE]

Yes similarly mine was:
First 6 months
fatigue first (easily overlooked because I was working hard)
Followed by chronic skin infections and poor wound healing
Noravirus 1 (week off work)
A significant worsening of my existing creeping peripheral neuropathy (from carbamazepine prescription)
Worsening fatigue and lack of physical strength

Next 6 months
Cognitive decline/ memory problems
Muscle and joint pain (chronic)
Noravirus 2
PEM after very little activity

The first 6 months were a slow creeping but the second 6 months everything picked up speed. It's difficult to pin down whether it was 8 months or 12 in total since the symptoms were so slow to develop and my memory isn't what it was, especially towards the end.

It's good to know that I'm not alone...I was beginning to doubt my diagnosis with so many people so sure about it being sudden.

 

[arewenearlythereyet]

My staged onset was like this:

1. VZV and never completely regained energy, mild fatigue, daytime sleepiness
2. one year after, blatter-, kidney-, tonsil infections, fatigue worsened, brain fog worsened, but still very mild symptoms
3. a few viral infections in addition and stress in school due to exams, all the symptoms worsened, heart pounding and "adrenaline kicks" all the time, sleep problems
4. flu shot, since then cold/flu like symptoms, aching joints all the time (mild though), brain fog and concentration problems worsened a lot, burning sensation under skin after waking up, problems falling asleep, very fatigued and heavy all the time (this was the stage that gave me a lot of new symptoms)

I feel like it's a progressing type for me @purrsian. I might get a little little bit better, but overall it got worse over the timespan of 3 years. This might be caused bc I can never rest very long after a "new stage" hits me (because of school).

I agree with @Mary it might be that you may need to pace/rest more to see if you can slow progression? I was eventually signed off work in 2014 and spent 5 months resting and pacing to establish my new base line. I was actually amazed at the time at how low this was at the beginning but I managed to crawl back up slowly with pacing to something that is more manageable and I seem to have reduced the cognitive and joint pain symptoms and my PEM episodes are milder and less frequent. I really regret how I continued working for the last 6 months when things got really bad. Is there a way you can take more breaks?

 

[sleepingbeautyxxx]

Right now I only do my school work and then I try to sleep as much as possible and use the weekends to restore my energy. This would be enough if I wouldn't get colds all the time. Right now there is absolutely no way for me to get more rest since there are only one and a half years left until graduation. I could drop out, but I really don't want to especially bc I like my classmates and one of my good friends (she has severe cfs) comes into my class after the summer break, and this would give me a lot of emotional support. I could take a break too, but I really hope I don't have to.
I mean, I could like miss school a month, but this won't change a lot, since I didn't improve a lot in my summer holidays. And I couldn't really rest, since I would still need to do all the school work so I don't get behind...

I'm kinda stuck right now, I'll see how things go. @arewenearlythereyet

 

[arewenearlythereyet]

Right now I only do my school work and then I try to sleep as much as possible and use the weekends to restore my energy. This would be enough if I wouldn't get colds all the time. Right now there is absolutely no way for me to get more rest since there are only one and a half years left until graduation. I could drop out, but I really don't want to especially bc I like my classmates and one of my good friends (she has severe cfs) comes into my class after the summer break, and this would give me a lot of emotional support. I could take a break too, but I really hope I don't have to.
I mean, I could like miss school a month, but this won't change a lot, since I didn't improve a lot in my summer holidays. And I couldn't really rest, since I would still need to do all the school work so I don't get behind...

I'm kinda stuck right now, I'll see how things go. @arewenearlythereyet

Good luck with your studies @sleepingbeautyxxx i know these can be intense and a lot of the time the workload is out of your control. I hope you can try some pacing to get yourself through the tough bits. important thing is look after yourself.

 

[sleepingbeautyxxx]

Thank you very much @arewenearlythereyet
I try to!

 

[Hip]

This poll of forum members found that 34% were gradual onset, and the rest 66% were sudden onset.

So that tally well with the study mentioned in this earlier post, which found that 31% were gradual onset, and 69% were sudden onset.

 

[Hip]

@Jonathan Edwards, if we consider the fact that sudden onset ME/CFS can appear very quickly, within a timescale of a few hours to a few days, and typically after a flu-like illness, what does this rapid appearance of ME/CFS tell us about the pathophysiological mechanisms driving this disease?

If we are looking out for immune-based mechanisms that may be causing ME/CFS, such as autoimmunity, then presumably these mechanisms must be able to trigger and switch on fully within 24 hours, in order that ME/CFS can appear so fast.

So that might help narrow down the possibilities in terms of mechanisms: we'd need to find a disease mechanism that can trigger and switch on fully very rapidly in this way.

 

[arewenearlythereyet]

This poll of forum members found that 34% were gradual onset, and the rest 66% were sudden onset.

So that tally well with the study mentioned in this earlier post, which found that 31% were gradual onset, and 69% were sudden onset.

The PR poll appears to have bias introduced from the phrasing of the questions not being balanced. I think I'll stick with the 50% figure and I think it would be good to try and have an explanation for these people as well. Autoimmune or just plain simple immune dysregulation. I think if I'm right MS isn't classed as an autoimmune disease but has as much variation to onset as CFS/ME does.

 

[Jonathan Edwards]

@Jonathan Edwards, if we consider the fact that sudden onset ME/CFS can appear very quickly, within a timescale of a few hours to a few days, and typically after a flu-like illness, what does this rapid appearance of ME/CFS tell us about the pathophysiological mechanisms driving this disease?

If we are looking out for immune-based mechanisms that may be causing ME/CFS, such as autoimmunity, then presumably these mechanisms must be able to trigger and switch on fully within 24 hours, in order that ME/CFS can appear so fast.

So that might help narrow down the possibilities in terms of mechanisms: we'd need to find a disease mechanism that can trigger and switch on fully very rapidly in this way.

I don't think it helps. Several inflammatory mechanisms triggered by autoantibodies have positive feedback loops involving innate immune pathways that play out over a period of hours. So in lupus a rash can appear very suddenly, in RA a joint flare can occur overnight. But the autoimmune process may have been there for ten years without symptoms.

 

[Hip]

But the autoimmune process may have been there for ten years without symptoms.

That certainly is an interesting concept: a latent asymptomatic autoimmunity that was present for years, but which suddenly flares up and manifests symptom as a result of an infection, or some other immunostimulatory event, like for example vaccination.

 

[Hip]

I think I'll stick with the 50% figure

Myself I have some doubts whether the staged onset, described as a "two-phase illness onset, which began with a sharp deterioration and subsequent improvement in phase one, that was then followed by another deterioration of symptoms in phase two," is really a separate type of onset.

ME/CFS sometimes has ups and downs, and to me this two-phase staged onset sounds like it could be a sudden onset, after which there was some improvement for a while, followed by a return to the initial illness baseline. So if we consider a staged onset to be just a type of sudden onset, then the study you mentioned above in effect found that:

25% of CFS patients are gradual onset
75% of CFS patients are sudden onset

These are figures comparable to the other study.

I think if I'm right MS isn't classed as an autoimmune disease but has as much variation to onset as CFS/ME does.

MS is thought to autoimmune.