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High-frequency rTMS for the Treatment of Chronic Fatigue Syndrome: A Case Series

hixxy

Senior Member
Messages
1,229
Location
Australia
Intern Med. 2016;55(23):3515-3519. Epub 2016 Dec 1.

High-frequency rTMS for the Treatment of Chronic Fatigue Syndrome: A Case Series

Kakuda W, Momosaki R, Yamada N, Abo M.

Abstract
Structural and functional abnormalities of the prefrontal cortex seem to correlate with fatigue in patients with chronic fatigue syndrome (CFS). We consecutively applied facilitatory high-frequency repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC) of seven CFS patients over three days. Five patients completed the 3-day protocol without any adverse events. For the other two patients, we had to reduce the stimulation intensity in response to mild adverse reactions. In most of the patients, treatment resulted in an improvement of fatigue symptoms. High-frequency rTMS applied over the DLPFC can therefore be a potentially useful therapy for CFS patients.

PMID: 27904120
DOI: 10.2169/internalmedicine.55.7354

https://www.ncbi.nlm.nih.gov/pubmed/27904120
 

IreneF

Senior Member
Messages
1,552
Location
San Francisco
Intern Med. 2016;55(23):3515-3519. Epub 2016 Dec 1.

High-frequency rTMS for the Treatment of Chronic Fatigue Syndrome: A Case Series

Kakuda W, Momosaki R, Yamada N, Abo M.

Abstract
Structural and functional abnormalities of the prefrontal cortex seem to correlate with fatigue in patients with chronic fatigue syndrome (CFS). We consecutively applied facilitatory high-frequency repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC) of seven CFS patients over three days. Five patients completed the 3-day protocol without any adverse events. For the other two patients, we had to reduce the stimulation intensity in response to mild adverse reactions. In most of the patients, treatment resulted in an improvement of fatigue symptoms. High-frequency rTMS applied over the DLPFC can therefore be a potentially useful therapy for CFS patients.

PMID: 27904120
DOI: 10.2169/internalmedicine.55.7354

https://www.ncbi.nlm.nih.gov/pubmed/27904120
Seven patients, three days, two dropouts, and "most" (three of the five?) showed improvement, presumably self-reported. Can we say, "waste of time"?
 

CFS_for_19_years

Hoarder of biscuits
Messages
2,396
Location
USA
Full text available here (bolding mine):
https://www.jstage.jst.go.jp/article/internalmedicine/55/23/55_55.7354/_pdf
Among the seven patients, 5 completed the scheduled six
rTMS sessions over three days. These 5 patients showed no
adverse events during hospitalization. The other two studied
patients (Patients 6 and 7) showed certain pathological reactions
that could be considered adverse events of rTMS application.

One patient experienced nausea, vomiting and
headache after two sessions of rTMS. The other patient developed
acute hypotension due to vasovagal reflex during
the first session of rTMS. However, the symptoms were
transient in both patients and disappeared within several
hours without any medical intervention.
Therefore, after more than 24 hours, one 25-minute session of 10-Hz high
frequency rTMS with a stimulation intensity of 80% was
administered to both patients. After the session with less intensity,
none of the two patients showed any adverse symptoms.
None of the seven patients experienced any pathological
symptoms during the two-week period after discharge.[......]

The present study has certain limitations. First, this is a
case-series pilot study with only a small number of patients
that lacked a control group. Comparative studies, such as
randomized controlled design studies that include a large
number of patients, are needed to confirm the efficacy of
rTMS in CFS patients.


Second, although all patients met the
inclusion criteria for rTMS application, they were a hetero-
geneous group based on the wide variability of age, duration
of illness and severity of the fatigue symptoms. The identifi-
cation of the clinical factors that correlate with the efficacy
of rTMS can help in the selection of patients who will best
benefit from the treatment.

Third, although it is difficult to
stimulate deep brain lesions using the currently available
technology, the stimulation of other brain areas with functional
or structural abnormalities in CFS, such as the cingulate
cortex and brainstem, may produce a better clinical improvement.
Furthermore, for one left-handed patient, we applied
high-frequency rTMS to the right hemisphere unlike
the other six patients. The appropriateness of this therapeutic
strategy of rTMS depending on whether patients were right-
handed or left-handed should be also confirmed.
 
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Messages
2,158
I don't think it can be dismissed out of hand, since some patients improved. It was a pilot study to see whether anyone responded and to test whether it was worth setting up a proper clinical trial. Much too early to tell whether it has any long term or clinically significant benefits.

@roller, I don't think it's anything like ECT.
 

IreneF

Senior Member
Messages
1,552
Location
San Francisco
They could have followed the subjects for longer.

Was there any explanation of why the researchers thought it might be effective? AFAIK rTMS is used for depression and neuropathic pain.
 

CFS_for_19_years

Hoarder of biscuits
Messages
2,396
Location
USA
They could have followed the subjects for longer.

Was there any explanation of why the researchers thought it might be effective? AFAIK rTMS is used for depression and neuropathic pain.

From the article (bolding mine):
https://www.jstage.jst.go.jp/article/internalmedicine/55/23/55_55.7354/_pdf
.....recent studies identified certain functional and
structural abnormalities in the brain of CFS patients,
including lesions in the dorsolateral prefrontal cortex
(DLPFC
)
, which seems to be an important part of the neural
network involved in the sensation of such fatigue symptoms.
Repetitive transcranial magnetic stimulation (rTMS) is a
new neuromodulatory therapy
used in patients with neuro-
logical and psychiatric disorders,
such as stroke and depression
. [........]

To our knowledge, rTMS
has not yet been used either therapeutically or for research
purposes in CFS patients. Theoretically, the application of
rTMS to the DLPFC should improve neural malfunction and
thus improve such fatigue symptoms.
The purpose of this
pilot case-series study was to evaluate the safety and feasi-
bility of high-frequency rTMS applied over the DLPFC in
the treatment of CFS. [........]

Among these areas showing local abnormalities in CFS
patients, the DLPFC has been especially considered to be an
important part of the neural network involved in regulating
the sense of fatigue
. For example, a malfunction of the
DLPFC is considered to cause a functional interruption of
the striatal-thalamic-frontal cortical loop, resulting in an enhanced fatigability.
[........]
We considered that high-frequency rTMS can stimulate
the DLPFC and increase the neural activity in that area,
leading to the alleviation of fatigue symptoms.

[........]
While our pilot study did not investigate the underlying
mechanisms for the obtained improvement, we speculate
that the effect was mediated through the neural activation of
the DLPFC in the dominant hemisphere
. [........]

........the duration of each rTMS session and
the total number of rTMS sessions were determined arbitrarily.
It is desired to investigate the optimal treatment duration
for CFS patients
. Such an investigation could help to elucidate
the correlation between the length of treatment and the
long-term clinical benefits.
 

perrier

Senior Member
Messages
1,254
About three weeks ago the programme Ideas, on the CBC in Canada had a piece on this form of magnetic stimulation. They reported good success with depression, helping people who had been on anti depressants for ages without relief.

My understanding is there are no negative side effects. If anyone knows otherwise, please inform.

CFS was not mentioned in the programme. But it's worth a try.

I'm not sure where and if this is available in Canada, where we live.
 
Messages
3,263
This study is obviously very weak. But the idea of treating CFS with rTMS is also pretty lame. It is like trying to mop up the floor while the bath is still overflowing! The CFS disease process that causes the brain fog is still there.

I suppose if you really can't stop the bath overflowing, you might still try to mop the floor. And given there's no treatment that modifies the CFS disease process, people might consider trying rTMS. But you'd wanna see strong evidence of effectiveness. And when you add in the effort involved in getting the treatment (I presume visits to the lab), and the transitory nature of the improvements, most people would probably conclude its not worth it.
 

RogerBlack

Senior Member
Messages
902
I was somewhat interested, as construction of a rTMS seems easy (I have unusual skills).
However.
This was a tiny study, with no control group.
Most critically - that hospitalised people.

Another reasonable hypothesis might be that having to do nothing for 5 days brought patients to their baseline state from one where some of them were suffering a degree of PEM.
Or the first couple of days were stressful, though not enough to induce PEM, inducing extra fatigue, followed again by return to baseline.
 
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Messages
96
rTMS has a low placebo effect in some mental disorders like depression (due to it being often a last-resort, even then it's about 10%) but in other patient cohorts it can exceed 30% improvement - which essentially dictates that in this small case series rTMS may operate worse than placebo in chronic fatigue syndrome at one week and is indistinguishable from baseline at two.

In the United States one treatment protocol as used in the study would cost at minimum $3500. If anything Irene was delicate in her criticism. I'd take this study at the value of someone making a post here that TMS helped them a bit - which sometimes I do!
 

Sidereal

Senior Member
Messages
4,856
DLPFC is the neuroanatomical target of rTMS treatment in depression. I would imagine that the pathetic effect they've obtained in this study might be attributable to a mild mood bump these patients may have experienced.
 
Messages
3,263
rTMS has a low placebo effect in some mental disorders like depression (due to it being often a last-resort, even then it's about 10%) but in other patient cohorts it can exceed 30% improvement - which essentially dictates that in this small case series rTMS may operate worse than placebo in chronic fatigue syndrome at one week and is indistinguishable from baseline at two.
In rTMS, you are supposed to use a design that includes three conditions: a) stimulation to your target region; b) stimulation to at least one other region not believed to be therapeutic; and c) sham stimulation (patient undergoes procedure, and hears all the same sounds, etc. but the magnet is held at the wrong angle).

So if you did it properly, you'd control for all this.

Some people say sham feels different to real TMS (so its not a complete control for TMS), so sham on its own is probably not enough.
 

RogerBlack

Senior Member
Messages
902
Some people say sham feels different to real TMS (so its not a complete control for TMS), so sham on its own is probably not enough.

Sham doesn't have to be holding the machine up to the head and not pressing the button.
For example, some sham surgeries have been done - for knee arthroscopy to attempt to patch up decaying knees. (and found that it has no effect on physical function a year on).
The sham surgery was just opening the skin, and sewing it back up.
If the patient doesn't know what the intervention should feel like, that is at least partially controlling.
 
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Messages
78
I am very lucky in that I have recently had a series of rTMS treatment for my ME. My consultant had been working with a local specialist hospital who use the equipment for treating depression. A few patients with ME were able to access the treatment as a non official trial.
The area treated was the DLPFC the same as with the depression cases. Initially we were given the standard 4 week course of about 45mins every day. The actual treatment is like having a 5 hour training session - it really tires your brain out. So for the first week I slept in the afternoons after treatment and went to bed very early and slept a lot longer at night. I also found the treatment very painful - most people just feel a slight tapping sensation but the other ME patient and I both had really high levels of pain.
After four weeks I hadn't noticed any difference in my ME symptoms but having to go to the hospital each day was taking it's toll. The first week I did have a relative drive me but then I was driving myself o the combination of travelling, being out in public, having treatment every day was cumulatively draining. I didn't realise at the time but the fact that I was still able to function meant that it was having an effect. There were some changes in that the brain fog lifted and I was able to be more animated when emailing people (which I always used to be but this had disappeared), I had more motivation so could actually get up and pick up the clothes I had left lying on the floor whereas before I didn't have the energy or inclination to do so. However I came down with a cold which developed into a chest infection and I ended up having to stop the treatment for two weeks as my breathing and coughing was so bad I wasn't able to sit still for the treatment.
I ended up having another 4 weeks so 8 weeks in all. At the end of this period I wasn't able to feel any major difference in my energy levels and it took me at least 6 weeks to recover my health and get back to previous normal level. This was when I noticed the difference and I found that i did have more energy for daily activities but not so that I was back to a normal person state. It was like having another level of power in a computer game so you can do more but the levels still drop back when you have used them up. One major difference was the recovery time. So if I did something strenuous one day I would previously have had to allow at least 2-3 days of "bed" time where I knew I didn't have to go out and do anything. After the treatment this reduced and it was only a day sometimes. I would normally also be extremely nauseous and this was very much reduced.
Speaking to the other ME patient they also experienced similar effects. However after a few months I did feel I was slipping back to previous levels. The treatment is not permanent but I can go back for top ups so it will be trial and error to see how often I will need to have these and whether they will be effective. Depression patients have the same issue - some might need to go back every 6 weeks for just a few days of treatment whereas others might be every 6 months. Top up treatments are much more condensed and would normally be 5 days.
So the treatment does have an effect but without more patients to compare it is difficult to say how much. I would say that this research report is very flawed in that there weren't enough sessions given (all treatments for other illnesses have many more sessions in the first instance), and the fact that the patients were not having to do anything else at the same time will have meant that they felt more rested anyway. But with the energy it takes just to have the treatment I would say the results would only be meaningful if reported after a month or two.
I did see that there was a study being carried out by Monash in Australia a couple of years ago and have tried to find out more about this but have not seen anything. There is also another paper that had been published but it is in Russian so I have no idea what their findings were but if anyone wants to look at it I will find the details.
Having a science background I also did some research around this and it seems that it may be more effective if carried out on different areas of the brain or using deeper pulses. As the research into this (rtms in general) is still ongoing I think it will be a while before we get to see this for ME. It is being used for stroke patients and people with mobility issues so hopefully those areas will show up which areas of the brain are best for targeting. It really needs a centre that can do fMRI at the same time to see how the brain is reacting so if one of those institutions does some research for ME then there may be a better way of getting results.
Hope that has been helpful but if you have any questions let me know - brain has reached capacity now!
 

NexusOwl

Spanish advocate
Messages
49
Location
Spain
I've warned Cort Johnson about the use of this treatment in my country with AWFUL results. I can see why the dropout happened. I'll post here what I said in a comment to this article http://www.healthrising.org/blog/2016/12/17/fibromyalgia-clinical-trials-overview-2017/

Things like “transcraneal magnetic stimulation” have been used for years in Spain experimentally and in poor legal conditions.
And many (MANY) patients have reported worsening of the condition (FM and CFS/ME) and even developement of new diseases (MCS, EHS,…)
even some patients associations had to go into warning against it. And the most worrying thig is the $$ doctors make out of it (100€ for a session)
while they keep saying how harmless it is (they don’t even warn about how it is not fit for the people with metalic dental implants) and how you can’t leave treatment till you’ve done x number of sessions even if you are worse.
Here you can download the comunicate that many patient’s associations joined, warning about severe harms of the AZENTA treatment
http://gadaper.blogspot.com.es/2012/02/comunicado-afigranca-azenta.html
If you look for Azenta now, you’ll just find their blog where you have link to their webpage that no loger exists.
Unfortunatelly the same treatments have been used by other doctors with other names. Always in a kind of clandestine way. (the basement of private hospitals and clinics, by doctors who advertise themselves as FM and CFS/ME experts everywhere but don’t mention they offer those treatments, even if they ask almost every patient with FM of CFS/ME to go through it)

They’ve been claiming for years atonishing numbers in % of improvement of different symptoms, with no real research paper that I’ve been able to read even after asking for it several times.

They have also said to almost every person who told them they were getting worse something like “Well. you’re the first person till now that didn’t get any benefit/that got any worse”.

So, be careful with these expensive experiments on patients.
 
Messages
3,263
Thank you for posting, @Sbag. Interesting to hear first hand. Its not a great feeling, when you have initial hope in a treatment, you invest a lot in it, and are left wondering at the end if it was worth it. We've all been through that. :(

I notice too from your description that your physicians view CFS as a mental disorder "just like depression". Even if they don't say as much, its pretty clear from the type of stimulation you got.
 
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IreneF

Senior Member
Messages
1,552
Location
San Francisco
Thank you for posting, @Sbag. Interesting to hear first hand. Its not a great feeling, when you have initial hope in a treatment, you invest a lot in it, and are left wondering at the end if it was worth it. We've all been through that. :(

I notice too from your description that your physicians view CFS as a mental disorder "just like depression". Even if they don't say as much, its pretty clear from the type of stimulation you got.
That's what I was thinking--someone decided that CFS/ME was the same as/enough like depression that they could throw some antidepressant treatment at it and too bad if it didn't work.
 
Messages
78
I think the treatment was worthwhile but if having to pay for it then I probably wouldn't say it was worth thousands of pounds. It is supposed to carry on working after finishing so maybe i will see better results as time goes on.
Just to clarify the physicians don't classify as a mental illness. My consultant is part of the mental health team but he is a neuropsychiatrist. I think people probably were referred when it used to be lumped in with mental health. However my consultant looks at it as a biological disease with neural issues and he does look at treatments that incorporate endocrine, physical, hormonal etc so definitely treats it as a "body" issue. As a neural thing he also says that they see similar problems with traumatic brain injuries ie car crash head injury - it affects something in the head (cant remember this bit so would need to look it up) which then gives the brain fog, tiredness, word problems etc.
The reason i was treated at the psychiatric hospital is purely because they have the equipment which they use for depression. Because my consultant works with them on other psychiatric illnesses there was a crossover and the idea was that with the depression treatment they stimulate the motor function area and also found that the patients became more energetic and active as well as feeling less depressed. So they thought it would be a good idea to see if using on CFS would have the same effects and hence help ME/CFS patients. Any association with the mental health side is just facility related though.
As part of treatment I have also tried Thyroxine, HRT, Modafinil and am now looking at low dose naloxone.
I was very grateful to be given the opportunity for this treatment. Yes it was a big time investment - although treatment was less than an hour each day and an hour travelling it is then the down time needed to cope with it that means it basically takes up all your time. In my opinion it was worth it to for the potential benefit. It did have enough of an effect that i would do it again however some personal setbacks have meant that I have taken a few steps back recently so at the moment I am not seeing so much of the progress that I had. Hopefully this will change and it will be interesting to see what state I get back to.
I did a lot of research into this treatment for different conditions and the potential benefits seem amazing - think of it as opening up new pathways in the brain for ones which arent working as they should. To me it seemed like if you have a blocked artery and the blood then diverts into smaller vessels and capillaries around it to carry on the same job - rtms works in the same way to increase neuroplasticity in the brain area it is targetting. If you look at how it is used for other illnesses then it will give you a different view than the one you get when it is just associated with depression and ECT.
I hadn't managed to find negative reviews of it so am interested to look at the spanish info. I am very open to learning about this but also realise it can be viewed the wrong way at first glance.