Study points to IVIG as treatment for "Depression"

[duncan]

Luckily for Lyme patients in North or South America, anciendaze, depression as a by-product of NB is a non-issue since NB really doesn't happen all that much in either continent apparently according to the IDSA and CDC...and when it does, it's easily eradicated, so depression likely won't have a chance to present.

 

[Sidereal]

Brain magnetic resonance imaging (MRI) showed scattered white matter foci of increased signal. Single photon emission computed tomography (SPECT) showed moderate to severe frontal hypoperfusion.

However, given the abnormal nonspecific brain MRI and SPECT imaging findings, there was also concern about a low-grade encephalitic process, such as seronegative autoimmune encephalitis, that might be treatable.

To be honest, the only thing remarkable about this case is that he received a million dollar diagnostic workup and treatment. Other patients with treatment-resistant depression are just left to rot when standard treatments like antidepressants and ECT fail.

MRI and SPECT are not routinely performed on patients diagnosed with depression (brain biopsies most certainly not) but when they are, results tend to be what they were here: MRI tends to show white matter hyperintensities (damage to white matter is much more evident on DTI than normal T2 weighted MRI) and frontal lobe hypometabolism. I don't know why this was interpreted as possibility of "low-grade encephalitis process" unless you're willing to concede that all cases of depression are.

Accordingly, a brain biopsy was obtained and was used to exclude an encephalitic process. Histological examination showed mild nonspecific inflammation without lymphocytic infiltration, with mild perivascular macrophage histiocytic infiltration and mild to moderate subcortical astrogliosis. Ultrastructural analysis revealed lipofuscin granule accumulation exclusively within the neurovascular unit, indicative of oxidative stress leading to blood-brain barrier dysfunction. While the medical literature had previously documented increased central nervous system oxidative stress in MDD, this was the first demonstrated evidence of oxidative injury of the neurovascular endothelium.

This isn't the first study to show neurovascular damage in depression. A previous study which carried out autopsies (granted these were on patients with late-life depression) found that all the white matter hyperintensities in depression were vascular in origin whereas in controls there was a mix of vascular and non-vascular causes. There have been others studies.

Because of the confirmed presence of inflammation, intravenous immunoglobulin (IVIG) pulse therapy was started and continued twice weekly for nine months. Three months after initiation of IVIG, intravenous minocycline was started because of its anti-inflammatory and antidepressant effects demonstrated in animal models of depression.

It is unfortunate that they administered IVIG and minocycline concurrently so we don't know which contributed more to the patient's clinical improvement but my money is on minocycline due to its microglial inhibiting properties and the fact that they introduced minocycline after three months of IVIG which presumably led to no improvement. I wish we had access to the full text. There is no indication that this patient had an immune deficiency and certainly no evidence of Lyme disease. All that's happening is that we live in strange times where you have 100 thousand papers on Pubmed showing depression is an inflammatory process but patients, with rare exceptions, are still treated with various drugs aimed at manipulating neurotransmitter levels because no better treatments exist currently.

 

[PearlGirl26]

I would not put too much weight on IVIG solving decades of health problems. There is no reason to think that IVIG would have any long term effect on an autoimmune state - and in general that has been the experience in the past.

Unless someone was born with an immune deficiency that had gone undiagnosed until then. How many of us are battling recurring infections and low IG subclass levels, yet are not given the proper diagnosis of CVID or PI that have been causing low level symptoms in us for years (that mimics depression and/or other mental illness) until a major life event causes us to go chronic? That's what I'm wondering.

I saw three well-regarded CFS doctors who missed these diagnosis. It wasn't until I saw a regular immunologist that put two and two together and got the approval for SCIG. My point is, maybe we rely a little too much on CFS doctors who stop looking for alt diagnoses because it's not in their wheelhouse. One doc dismissed IVIG because it was taking blood from the gen pop, which is bullocks. The amount of screening done on this stuff is insane. He just wanted to sell me synthetic GG, which he profits off of.

 

[duncan]

Sidereal, what prompts you to say "certainly no evidence of Lyme disease"? All I noticed was a passing reference to the patient having at one time being told he had NB. The authors seem dismissive of that, but I saw no indications of any 2T testing or C6 for this patient coming back negative. Did I miss something?

ETA: Ah, perhaps the "unremarkable" serologies and CSF exams. If so, I would want them to expand on "unremarkable".

 

[A.B.]

All that's happening is that we live in strange times where you have 100 thousand papers on Pubmed showing depression is an inflammatory process but patients, with rare exceptions, are still treated with various drugs aimed at manipulating neurotransmitter levels because no better treatments exist currently.

Antidepressants do have some anti-inflammatory capabilities. Immune cells have serotonin receptors. There are some reasons to believe that this is actually how they work: http://www.cytokines-and-depression.com/chapter1.html

 

[anciendaze]

I want to add that acquired immune deficiencies which stop far short of AIDS are neither impossible nor unknown. They may be caused by pathogens acting to protect themselves (though this does not involve intent, merely random experimentation.) It may also result from host defenses against viral infection, which often involve microRNA interference with viral replication. These can temporarily "knock-down" host genes as well. Even when a gene is expressed it may not be completely expressed because RNA interference has caused a large deletion.

I doubt that patients with the 37 kilodalton variant of RNAse-L all had this gene (allele) at birth, without suffering really serious problems from viral diseases in childhood.

The complicated genetics of immune defenses are constantly generating new combinations of sequences in response to changing environmental threats. These can be completely new and previously unknown in nature, which means that evolutionary selection has not had much chance to act on them. In this situation it should be no surprise if some of these resemble viral sequences. The fact that some 8% of human genomes already consist of viral sequences, and that pathogens often use molecular mimicry to evade defenses, makes this almost certain to occur.

The extent to which studies of genetics fail to find these changes, and the high probability that they must occur, though not always the same defects, means that our knowledge of how immune defenses behave in pathological situations is largely based on guesswork.

 

[Sidereal]

Sidereal, what prompts you to say "certainly no evidence of Lyme disease"? All I noticed was a passing reference to the patient having at one time being told he had NB. The authors seem dismissive of that, but I saw no indications of any 2T testing or C6 for this patient coming back negative. Did I miss something?

ETA: Ah, perhaps the "unremarkable" serologies and CSF exams. If so, I would want them to expand on "unremarkable".

It's hard to tell without having seen the full paper but from what is in the press release there is no indication of Lyme, just years of unsuccessful treatments by LLMDs with antibiotics and herbal supplements. Such alternative doctors tend to diagnose anyone who presents with the symptom complex of fatigue, pain and neuropsychological dysfunction with Lyme disease.

 

[Sidereal]

Antidepressants do have some anti-inflammatory capabilities. Immune cells have serotonin receptors. There are some reasons to believe that this is actually how they work: http://www.cytokines-and-depression.com/chapter1.html

Sure, they're immune modulators, just not very good ones.

 

[A.B.]

Sure, they're immune modulators, just not very good ones.

Which is presumably why they don't work very well. I don't think it's a coincidence that depression is so similar / identical to cytokine induced sickness behaviour.

 

[Sidereal]

Which is presumably why they don't work very well. I don't think it's a coincidence that depression is so similar identical to cytokine induced sickness behaviour.

Exactly.

 

[anciendaze]

Antidepressants do have some anti-inflammatory capabilities. Immune cells have serotonin receptors. There are some reasons to believe that this is actually how they work: http://www.cytokines-and-depression.com/chapter1.html

Don't forget that such common antidepressants as fluoxetine have strong effects on enteroviruses. This seems to extend to most SSRIs.

I would also point out that minocycline will actually lower viral titers, even though it is labeled as an antibiotic.

The extent to which clinical outcomes are based on sheer ignorance of causes ought to be a wake-up call.

 

[duncan]

Sidereal, we don't know he was treated by LLMDs, although agreed the therapies noted are not standard IDSA-issued.

All we do know is the patient was told he had complications from Lyme. He may have been 2T positive to earn that diagnosis years prior, and after treatment, sunk below that threshold, yet still presented with neurological symptoms because the Bb had not been fully eliminated.

If he did not meet 2T requirements, the result may have been the write-up we have just read, despite him grappling with a wicked case of unresolved Lyme.

But, as you pointed out, we are not given enough information to draw any meaningful inference one way or another.

 

[Sidereal]

Sidereal, we don't know he was treated by LLMDs, although agreed the therapies noted are not standard IDSA-issued.

All we do know is the patient was told he had complications from Lyme. He may have been 2T positive to earn that diagnosis years prior, and after treatment, sunk below that threshold, yet still presented with neurological symptoms because the Bb had not been fully eliminated.

If he did not meet 2T requirements, the result may have been the write-up we have just read, despite him grappling with a wicked case of unresolved Lyme.

But, as you pointed out, we are not given enough information to draw any meaningful inference one way or another.

Well, the press release says:

The results of these tests were unremarkable until the patient was 38, when he was told that he was suffering neurological complications of Lyme disease. Before being referred to NYU Langone, he was treated elsewhere with antibiotics, acupuncture, over-the-counter supplements, transcranial magnetic stimulation, and hyperbaric oxygen.

Sounds to me like he came in contact with the Lyme industry.

 

[PearlGirl26]

I think the whole point is to have other peoples blood - it wouldn't work using your own.
I have been offered IVIG and if i can get to the clinic for treatment then i am still going to consider it. A couple of studies have been done that suggest it can be helpful in M.E/CFS see Nigel Speights key note speech at Invest In Me last year discussed these (cant find a link to it anywhere unfortunately as its very good)

http://www.cortjohnson.org/treating...onic-fatigue-syndrome-mecfs-and-fibromyalgia/

SCIG (subcutaneous) is done at home by the patient. A nurse is with you the first few times to make sure you are properly administering it. The side effects are much less and have shown to offer better immunity overall as it is administered weekly or biweekly, thus offering continuous coverage. IVIG only lasts for 3 weeks and change, so that the patient is vulnerable those last couple of days, plus feels weak. Insurance will only cover IVIG every 30 days. SCIG is also easier to get covered under insurance.

 

[duncan]

Perhaps, Sidereal. That's one interpretation. Another might be that he was accurately diagnosed with Bb through an IDSA member, but when standard IDSA Guidelines for therapy failed him, he was forced to turn to alternatives, and they failed him as well.

These backstories can be telling.

If I could have whispered advice into this group who ended up profiling him in this study, I would have recommended looking just a little deeper for signs of Borrelia - did they do a C6? Did he have any IgG or IGm bands Bb specific? How was his AI and other CSF results? Where did they fall on the spectrum, e.g. might any have been equivocal? - and temporarily put aside the unforgiving rigidity of the guidelines before I proclaimed him Lyme-free. But that's just me.

 

[Jonathan Edwards]

Unless someone was born with an immune deficiency that had gone undiagnosed until then. How many of us are battling recurring infections and low IG subclass levels, yet are not given the proper diagnosis of CVID or PI that have been causing low level symptoms in us for years (that mimics depression and/or other mental illness) until a major life event causes us to go chronic? That's what I'm wondering.

I saw three well-regarded CFS doctors who missed these diagnosis. It wasn't until I saw a regular immunologist that put two and two together and got the approval for SCIG. My point is, maybe we rely a little too much on CFS doctors who stop looking for alt diagnoses because it's not in their wheelhouse. One doc dismissed IVIG because it was taking blood from the gen pop, which is bullocks. The amount of screening done on this stuff is insane. He just wanted to sell me synthetic GG, which he profits off of.

For immunodeficiency yes, but the use of IVIG in autoimmunity has nothing to dow with immunodeficiency or infection. I have to say that the account given in this case report is a bit confusing since Lyme does seem to come up as part of the story. To my way of thinking Lyme has nothing to do with autoimmunity.

 

[Misfit Toy]

They give people IVIG with Lyme all the time. It's all over the Lyme disease websites.

They wanted me on it because I kept getting infections. I realize this thread is not about low IgG or immunodeficiency, I just wanted to tell my story.

I was thinking about this last night and how people would take it for depression. I think the new way of giving is great and not as hard as the IVIG or even the sub q.

I know that Ema has had great results with it. But I have to say out of all the treatments I've ever tried I was never so sick as I was with this one. A lot of times they give you Benadryl and you have to drink so much water when you take it. It's crazy how much water you have to drink and I think it's just hard to do.

There is a point, if I get sick again or keep getting infections in the future that my immunologist will want me on it again and I can tell you I'm not going to jump on it. For those of us who are sensitive to medicines this isn't just straight up IgG from other people- they put other additives in it that people are allergic to. Hizentra is a perfect example. Many people cannot take it. I GG is a very sticky substance. It's thick. That stickiness that goes into our system can sometimes cause people to have reactions and aseptic meningitis.

I was diagnosed with CVID and local subclasses back in 2013 and I have been on the CVID board since that time. Many people on there every week are in the hospital due to aseptic meningitis from the IgG treatment. That's even with subQ. It can be time consuming but when it works, it works!

I think if one is so sick it's worth a try. Why not! Just don't go in really excited because a lot of people hate it and wish they didn't have to take it. It disrupts their life.

A lot of Lyme folks on the Lyme groups hate it. It makes them sick. The side effects. They talk of how sick they get from it and they either use it as an adjunct, or because their IGG is low or for neurological symptoms.

I think low IGG subQ given everyday is the way to go...less IGG, less side effects coming your way...

Daffodil, I was on a low dose. Eventually, on the gammaguard, I started having reactions within an hour on the Ivig. I would start choking.....and this medicine worked well for me for a few months and then bam...it turned on me. That can be common.

 

[Sam Carter]

It's hard to tell without having seen the full paper but from what is in the press release there is no indication of Lyme, just years of unsuccessful treatments by LLMDs with antibiotics and herbal supplements. Such alternative doctors tend to diagnose anyone who presents with the symptom complex of fatigue, pain and neuropsychological dysfunction with Lyme disease.

The full paper is available to download from ResearchGate at this url.

 

[Daffodil]

i think KDM used to give gammaguard but has switched to Gammanorm now, subQ. not sure what he gives IV for people who can come to his office in person. I heard gammaguard can cause side effects more often.

burrascano said that IVIG is important for late stage lyme, maybe you are supposed to take it at a later stage, after a certain time on antibiotics? who knows.