What is being described is what I expected to see due to "borrowed" gp120 envelope glycoproteins. Thanks Ralph.
The Molecular and Pharmacological Mechanisms of HIV-Related Neuropathic Pain (2013)
...The most common complaint of HIV-DSP is pain on the soles; the pain is typically bilateral, of gradual onset, and described as ‘aching’, ‘painful numbness’, or ‘burning’[34]. Patients often have hyperalgesia and allodynia in a stocking and/or glove distribution. The feet are tender to touch, wearing shoes is painful, and the gait becomes ‘antalgic’. In a typical length-dependent fashion, the dysesthesias ascend proximally up the lower extremities over months, and may begin to involve the fingertips at around the same time as they reach the mid-leg level [33, 35]. It is usually most severe on the soles of the feet, and is typically worse at night.
Pathologically, the most common histological feature of both DSP and ATN is characterized by loss of DRG sensory neurons, Wallerian degeneration of the long axons in distal regions, DRG infiltration by HIV-infected macrophages, and a 'dying back' sensory neuropathy [36-40]. Early on, small, unmyelinated sensory fibers are lost, with eventual destruction of the large myelinated fibers as the disease progresses in the patients with HIV. In the periphery and the DRG, there is infiltration of macrophages and other inflammatory cytokines [41]. Clinically, these two forms (HIV-DSP and ATN) of HIV sensory neuropathies are difficult to distinguish.
Thanks for this. I haven't delved deeper into the literature aside from the information to write this post, although I did see that HIV has been associated with small fiber neuropathy. I'd have to look more into the literature if I were to make a more sound judgement.
So from what I can gather, and I should have made more clear, is that it appears treatment options seem to alleviate the symptoms likely until nerve development regrows these small fibers. Otherwise, the two treatments (IVIG and the plasma exchange) suggest that blocking or removing of the autoantibodies may help in recovery since you're essentially removing the thing that is targeting the nerves. I think this fact points to a rather strong indication that some of the neuropathy (at least with the small fiber forms) are due to an autoimmune response to the body's nerves, so likely halting the overactive immune response and allowing the nerves to regrow seems to be the approach, but because people differ in their ability to develop new nerves the time until symptom alleviation will differ greatly between people.
Hopefully that helps. In short, it's management until nerves regrow while possibly removing the autoantibodies to accelerate the process.
This makes me wonder about post chemo neuropathy... why don't the nerves heal over time if they were just damaged? Does the chemo create auto-antibodies? I had somehow been thinking it was due to demyelination but there is no myelin on those short fibers so it's just regrowth that's needed? My brother suffers from this 4 yrs post platinum chemo and it has now moved from his feet to his hands which shouldn't be happening if it was a once and done injury?( I have it off and on now in one broken wrist - guess I needed to learn empathy- and patience lol) Brother was coerced by dr and wife into 1 pfizer shot so perhaps that is why it is attacking more nerves. AMD brought up the CDR issue - could cells be stuck in one stage of that so that even with a halt on antibodies, improvement could be stymied? Wish there were one key to all this... I wonder if low dose naltrexone would work on multiple levels?
I'm not informed on nerves so I can't provide any insights. I should have been more careful and noting that the case report above shows regrowth within the calf of this patient and so not within the hands and feet.
The world of neuroregeneration (if that's a word-Substack doesn't seem to think so) seems to be a mix of controversy and pseudoscience. It's been argued for decades that neurons, similar to cells of the heart, have very low replication capacity, and so they don't regrow once damaged.
In the past few years there's been a debate to the degree that this is true. There's an argument over neuroplasticity and neural reformation, but I don't know if much of this research has come to fruition.
One experience that many people have that sort of refutes this regrowth is burning hands. Consider how often you may have touched a hot stove or cookery and burned your fingers. You may have noticed over time you don't really notice those sensations to the same degree, and it's likely because your hands have experienced some form of neuropathy. It's not as if they regrow and you somehow gain that sensation back.
So a lot of this is really difficult to discern. Either the spike is causing damage, or the autoantibodies are. Then there's an argument over how long each persist for. I think the fact that the two cases above show treatments where they either removed the autoantibodies (plasma exchange) or flood the body to shut the autoantibodies off (IVIG) showed improvement.
So I did a quick glance because I was a bit suspicious, and the cause for chemo-related neuropathy appears to be due to actual neurotoxic effects of some drugs, which are also their anticancer effects. So in this case it's likely not an autoimmune response. Neuropathy is known to occur due to drugs and toxins so there's likely other factors to consider aside from autoimmunity.
Since you mentioned platinum I'm assuming it's along the lines of cisplatin or those forms of drugs.
A quick glance showed these two review articles which may be of interest:
"Chemotherapy-Induced Peripheral Neuropathy: A Current Review":
Thanks for clarifying on the calf part... but seems like regrowth should be possible elsewhere then.
Yes, in spite of the dr claiming that he'd never had a patient develop long term neuropathy, we found research that the platinum can stay around for at least 19 yrs. There's no doubt cancer chemos ruin the immune system as well .... which now that I think of it... the failure of cancer treatments over the past 50 yrs should have been enough to reign in the FDA et al years ago. We have learned a lot about the body's functioning but treatments always come down to money.
You have to put a space in there... neuro regeneration ;)
The Body Electric and Dr Doidge's books are quite interesting regarding neurons and plasticity.
Hypothetically, it should, although regrowth in the extremities appears to take the longest since the nerves appear to regrow closer to the center of the body and spread outward, so calf nerve regeneration would appear before feet regeneration...supposedly.
A book I read a while back which I believe may be of interest is The Emperor of All Maladies by Dr. Siddhartha Mukherjee. I read it after finishing my undergrad, and fortunately having the little bit of med chem background I was able to understand some of the book. It's pretty interesting to see how how much damage a lot of these cancer treatments did. I believe cisplatin was mentioned several times in the book, but it's been a few years since I've read it so I can't recall the degree it was mentioned.
I'll have to look into those books. I've read a few on neuroplasticity, and the general sentiment in regards to these books is that they may be far too...optimistic, I should say, or relying on something that hasn't been fully substantiated yet, although with how medicine is one always has to grapple with the idea that status quo tends to trump differing viewpoints.
"You have to put a space in there"- and thus is the strangeness of the English language, where neurodegeneration is one word and neuro-regeneration must be hyphenated!
hyphen??! good grief... so much for relying on AI software as mine took it with only a space... oh well... right now it seems that language rule is anything goes... I mean, if a male is really a female.....
What is being described is what I expected to see due to "borrowed" gp120 envelope glycoproteins. Thanks Ralph.
The Molecular and Pharmacological Mechanisms of HIV-Related Neuropathic Pain (2013)
...The most common complaint of HIV-DSP is pain on the soles; the pain is typically bilateral, of gradual onset, and described as ‘aching’, ‘painful numbness’, or ‘burning’[34]. Patients often have hyperalgesia and allodynia in a stocking and/or glove distribution. The feet are tender to touch, wearing shoes is painful, and the gait becomes ‘antalgic’. In a typical length-dependent fashion, the dysesthesias ascend proximally up the lower extremities over months, and may begin to involve the fingertips at around the same time as they reach the mid-leg level [33, 35]. It is usually most severe on the soles of the feet, and is typically worse at night.
Pathologically, the most common histological feature of both DSP and ATN is characterized by loss of DRG sensory neurons, Wallerian degeneration of the long axons in distal regions, DRG infiltration by HIV-infected macrophages, and a 'dying back' sensory neuropathy [36-40]. Early on, small, unmyelinated sensory fibers are lost, with eventual destruction of the large myelinated fibers as the disease progresses in the patients with HIV. In the periphery and the DRG, there is infiltration of macrophages and other inflammatory cytokines [41]. Clinically, these two forms (HIV-DSP and ATN) of HIV sensory neuropathies are difficult to distinguish.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763758/
Thanks for this. I haven't delved deeper into the literature aside from the information to write this post, although I did see that HIV has been associated with small fiber neuropathy. I'd have to look more into the literature if I were to make a more sound judgement.
Perchance, did any of these studies offer treatment ideas?
So from what I can gather, and I should have made more clear, is that it appears treatment options seem to alleviate the symptoms likely until nerve development regrows these small fibers. Otherwise, the two treatments (IVIG and the plasma exchange) suggest that blocking or removing of the autoantibodies may help in recovery since you're essentially removing the thing that is targeting the nerves. I think this fact points to a rather strong indication that some of the neuropathy (at least with the small fiber forms) are due to an autoimmune response to the body's nerves, so likely halting the overactive immune response and allowing the nerves to regrow seems to be the approach, but because people differ in their ability to develop new nerves the time until symptom alleviation will differ greatly between people.
Hopefully that helps. In short, it's management until nerves regrow while possibly removing the autoantibodies to accelerate the process.
This makes me wonder about post chemo neuropathy... why don't the nerves heal over time if they were just damaged? Does the chemo create auto-antibodies? I had somehow been thinking it was due to demyelination but there is no myelin on those short fibers so it's just regrowth that's needed? My brother suffers from this 4 yrs post platinum chemo and it has now moved from his feet to his hands which shouldn't be happening if it was a once and done injury?( I have it off and on now in one broken wrist - guess I needed to learn empathy- and patience lol) Brother was coerced by dr and wife into 1 pfizer shot so perhaps that is why it is attacking more nerves. AMD brought up the CDR issue - could cells be stuck in one stage of that so that even with a halt on antibodies, improvement could be stymied? Wish there were one key to all this... I wonder if low dose naltrexone would work on multiple levels?
I'm not informed on nerves so I can't provide any insights. I should have been more careful and noting that the case report above shows regrowth within the calf of this patient and so not within the hands and feet.
The world of neuroregeneration (if that's a word-Substack doesn't seem to think so) seems to be a mix of controversy and pseudoscience. It's been argued for decades that neurons, similar to cells of the heart, have very low replication capacity, and so they don't regrow once damaged.
In the past few years there's been a debate to the degree that this is true. There's an argument over neuroplasticity and neural reformation, but I don't know if much of this research has come to fruition.
One experience that many people have that sort of refutes this regrowth is burning hands. Consider how often you may have touched a hot stove or cookery and burned your fingers. You may have noticed over time you don't really notice those sensations to the same degree, and it's likely because your hands have experienced some form of neuropathy. It's not as if they regrow and you somehow gain that sensation back.
So a lot of this is really difficult to discern. Either the spike is causing damage, or the autoantibodies are. Then there's an argument over how long each persist for. I think the fact that the two cases above show treatments where they either removed the autoantibodies (plasma exchange) or flood the body to shut the autoantibodies off (IVIG) showed improvement.
So I did a quick glance because I was a bit suspicious, and the cause for chemo-related neuropathy appears to be due to actual neurotoxic effects of some drugs, which are also their anticancer effects. So in this case it's likely not an autoimmune response. Neuropathy is known to occur due to drugs and toxins so there's likely other factors to consider aside from autoimmunity.
Since you mentioned platinum I'm assuming it's along the lines of cisplatin or those forms of drugs.
A quick glance showed these two review articles which may be of interest:
"Chemotherapy-Induced Peripheral Neuropathy: A Current Review":
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656281/
"Mechanisms of Chemotherapy-Induced Peripheral Neuropathy":
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471666/
Thanks for clarifying on the calf part... but seems like regrowth should be possible elsewhere then.
Yes, in spite of the dr claiming that he'd never had a patient develop long term neuropathy, we found research that the platinum can stay around for at least 19 yrs. There's no doubt cancer chemos ruin the immune system as well .... which now that I think of it... the failure of cancer treatments over the past 50 yrs should have been enough to reign in the FDA et al years ago. We have learned a lot about the body's functioning but treatments always come down to money.
You have to put a space in there... neuro regeneration ;)
The Body Electric and Dr Doidge's books are quite interesting regarding neurons and plasticity.
Hypothetically, it should, although regrowth in the extremities appears to take the longest since the nerves appear to regrow closer to the center of the body and spread outward, so calf nerve regeneration would appear before feet regeneration...supposedly.
A book I read a while back which I believe may be of interest is The Emperor of All Maladies by Dr. Siddhartha Mukherjee. I read it after finishing my undergrad, and fortunately having the little bit of med chem background I was able to understand some of the book. It's pretty interesting to see how how much damage a lot of these cancer treatments did. I believe cisplatin was mentioned several times in the book, but it's been a few years since I've read it so I can't recall the degree it was mentioned.
https://www.goodreads.com/book/show/7170627-the-emperor-of-all-maladies
I'll have to look into those books. I've read a few on neuroplasticity, and the general sentiment in regards to these books is that they may be far too...optimistic, I should say, or relying on something that hasn't been fully substantiated yet, although with how medicine is one always has to grapple with the idea that status quo tends to trump differing viewpoints.
"You have to put a space in there"- and thus is the strangeness of the English language, where neurodegeneration is one word and neuro-regeneration must be hyphenated!
https://www.youtube.com/watch?v=Q8mD2hsxrhQ
hyphen??! good grief... so much for relying on AI software as mine took it with only a space... oh well... right now it seems that language rule is anything goes... I mean, if a male is really a female.....