Is It Neuropsychiatric Systemic Lupus Erythematosus (NPSLE)?

I don’t know. Maybe?

I have no idea what’s actually wrong with me (I can’t write that in the past tense yet, unfortunately).

This post is meant to explore my opinions on what I’ve potentially been dealing with since becoming extremely sick following vaccination with the Pfizer covid vaccine. It’s kind of a weird spot presenting this to people, where if you’re a layperson I’ll probably be touching on concepts of health and medicine with which you aren’t familiar. And if you’re a medical professional, well….I at least hope you read this with an open mind. I very much welcome your input or ideas. 

Anyway… I didn’t title this post the way I did because I absolutely believe I have (or have had) neuro-lupus, but because I certainly believe it’s a possibility and have had it at least suggested by a rheumatologist. I do very strongly believe I have an autoimmune condition. NPSLE is one possibility.

Neuropsychiatric lupus is a particular manifestation of systemic lupus erythematosus (SLE), characterized by nervous system disorders. You can read about the symptoms here if you want – they include headache, aseptic meningitis, cognitive dysfunction, delirium, autonomic dysfunction, and peripheral nerve issues.¹

The Evidence for NPSLE

Anti-Sm and ANA

The argument that I have NPSLE specifically boils down to a couple key points. One is my symptom presentation, which, particularly before significant dietary intervention, matched many of the symptoms characteristic of NPSLE. I’ll outline them all at the bottom, but if you’ve already read the main introductory post I made you’re largely familiar with many of them.

The second key point is the (inconstant, to be clear!) abnormal autoimmune results potentially suggestive of lupus or an associated condition. Arguably the most important of these are the Anti-Sm antibodies, as they are most specific to lupus. In fact, studies demonstrate that a finding of positive Anti-Sm is 98-99% specific for lupus.^2,3 Anti-Sm isn’t always positive in lupus patients, but it is only rarely positive for any other reason.^2–4 Once that marker is positive, I don’t really believe “not Lupus” can remain such a strong default assumption. At the very least a very valid reason for why it is not Lupus should be proposed, which is something I don’t feel like I’ve received. At the same time, I was also positive for two other markers commonly associated with lupus and other similar conditions, like mixed connective tissue disease.

The rheumatologist who ordered those labs was hesitant to make any diagnosis because at the time of the positive anti-Sm result, I paradoxically did not have a positive ANA result (any longer. It had been positive on a previous occasion). ANA – anti-nuclear antibodies – is the most “general” autoimmune marker, so to speak, and is often used as an initial screening tool to check for possible autoimmune disease. More often than not, ANA will be positive in a patient with an autoimmune condition.

Here's where we get to a bit of opinion and speculation – “more often than not” is, to me, the important part of that last sentence. In my experience, both speaking to doctors and reading public info such as the lupus foundation website, its widely believed that ANA must virtually always be positive if a patient is to have an autoimmune condition.⁵ But…This position really isn’t supported by the literature.

I suspect this misconception results from a population-wide conflation of “ANA is a general autoimmune screening tool” with “It can’t be an autoimmune disease if the patient doesn’t have positive ANA.” It feels like doctors get in the habit of always checking ANA first and either forget or have no idea that ANA is far from definitive. I also suspect this is a one of the reasons that it takes an average of SIX YEARS from first symptom for a patient to be accurately diagnosed with lupus.⁶ I have serious doubts that a lot of physicians are well-read on the literature, including…

A study that finds “ANA-negative SLE is more common than generally realized” ⁷

A study that finds “a considerable portion of Swedish patients with SLE lose ANA-positivity over time” ⁸

A lengthy follow-up study found that that only 17 percent (!!!!) of patients previously diagnosed with NPSLE continued to return a positive ANA test.⁹

There’s actually quite a bit of literature detailing the inconsistent, fluctuating, unreliable nature of ANA as a marker of lupus and similar conditions.^10–15

What does that mean for me? I don’t know! I think it means I may very well have been diagnosed with NPSLE had only my positive ANA occurred in concert with my other positive autoimmune results. I think it means I may very well have been diagnosed with NPSLE if my rheumatologist was aware that positive ANA frequently fluctuates and fades. I think it means that SOMEBODY should at least try to answer my questions about this research rather than shut them down.  

 

Diet and Autoimmunity

My health began changing for the better with strict carbohydrate (ie. plant) restriction, with many or most seemingly benign plants apparently capable of triggering symptom flares and relapses.

Here’s the part that most people and medical professionals are apt to consider controversial – eating plants is horrible for autoimmune disease, and frankly I think most plants are an overall negative influence on health in general. Mainstream advice is obviously not going to agree with this statement, but I don’t consider that advice to be particularly evidence-based.^16,17 The primary reason plant consumption is detrimental in the instance of autoimmune disease is the presence of immune-triggering defense chemicals such as lectins.

Quick non-scientific overview of plant defense chemicals – Every organism on earth evolved to still be alive and keep reproducing and every organism has strategies and adaptations to help with the “staying alive” part. Animals have active defense mechanisms – horns, wings, speed, camouflage, etc. Plants can’t really move or fight back, so their defense mechanisms are largely passive. These are the chemical compounds – lectins, gluten, oxalates, etc. - designed to make themselves more difficult to digest and make you sick if you eat them. If you walk out into a field and try to eat a stalk of wheat, you will feel sick. You will be disinclined to eat it a second time, and the rest of the wheat will keep living. That’s how the process is supposed to work. Modern humans have obviously messed with the process pretty significantly, but a machine pre-digesting some of the wheat for you doesn’t make it healthy.

The major general exception to this paradigm is fruit. Do you know why fruit is bright and colorful and sweet? That’s because it “wants” you to eat it, so you can poop out the seeds (pre-fertilized!) somewhere new. That’s also why unripe fruit is green and bitter and more difficult to eat – it doesn’t want to be eaten yet! The ripening process includes a breakdown of the defense chemicals that might otherwise harm you if you eat the fruit too early. Green things do not want to be eaten!! That’s literally the reason green and brown things are green and brown – blending in is a survival mechanism. Turning blue or red is a survival mechanism too, one that makes fruit significantly less harmful than other plants for people with or without autoimmune disease.

Part of the argument for the health benefits of vegetables is actually that these compounds make you “stronger” by stimulating that immune response. Kinda like exercise might. That’s all a discussion for another time, but for now I’m going to link to a couple dozen papers below for anybody that wants to read about how these plant compounds adversely affect the immune system and how those with autoimmune disease frequently improve with the removal of various plants from their diet, or by fasting.^18–49

I’ll highlight one study in particular – to my knowledge the only study that placed participants on a strict lectin elimination diet and tracked markers of autoimmune disease.⁵⁰ 102 participants with various serologically confirmed autoimmune disease (lupus and others) were followed for nine months, at the end of which more than ninety percent of subjects were negative for all autoimmune markers. Eighty percent of patients had improved enough to cease all medication.

The reason I highlight that finding is because not only does it reflect how I’ve been eating, but very crucially it reflects how I was already eating for months before I was tested for any autoimmune markers. For the first several months of this ordeal, I was down a neurology rabbit hole or sorts, and so I have no autoimmune testing from anything really even resembling the worst of it. In fact Anti-sm, that lupus-specific marker, is known to correlate with flares and disease severity, and became negative as I felt amazing at the end of a week of continuous fasting.^51–53

At this point it should be clear that I’m of the opinion that the “insufficiency” of my autoimmune markers very plausibly reflects both an improvement in health and a decrease in markers that should absolutely be expected in a person consuming a diet of primarily meat and no grains, vegetables, etc. I’m also of the opinion that the massive moderating effect of diet on my symptoms is strong evidence that my issues are likely autoimmune in nature. With all that in mind – the stark effect of diet on my symptom presentation, the various adverse autoimmune markers, the dramatic neurological nature of my condition, and other factors we haven’t touched on here – I have a hard time believing my (primary) condition can be anything other than neuro-autoimmune in nature.

This post is focused on NPSLE specifically not because I’m literally making the argument that it has to be neruo-lupus or even that its highly probable I have neruo-lupus. It is because my symptoms, bloodwork, and rheumatologist’s comments all suggest the possibility, and because I think that possibility far better reflects the severity of the situation than does the common physician desire to pretend I’m just tired and dismiss everything as “long covid.” 

 

Other Possibilities

A quick overview of some other explanations I find varying degrees of plausible. Note that these aren’t mutually exclusive – an autoimmune condition doesn’t necessarily preclude some kind of nerve damage, for example.

·       Other autoimmune problems - Anti-ACE2 or similar: ACE2 is an enzyme primarily located in the blood vessels that happens to be the main method by which covid-19 binds and enters your body. There’s some research showing that long covid patients with neurological complications have near universally present anti-ACE2 antibodies. Problem is there are no labs in the US that test for these antibodies, so I have no idea if I have or had them myself. Many other long covid and post-vaccine injury patients have reported antibodies to ACE2 and other related proteins, though, so there exists the possibility that this is actually the root problem. I don’t exactly know how to connect this possibility to the neurological presentation, but there is some ACE2 expression in the nervous system so it seems plausible. In this case it would be presumed that the other abnormal autoimmune results I’ve returned are largely cross-reactive/incidental rather than a primary issue.^54–64

·       Craniocervical Instability (CCI): This would be some kind of nerve damage/compression/irritation/etc. that results from connective tissue damage to the neck. Essentially connective tissue damage leads to a weak/unstable neck, in turn leading to compression or irritation of the spinal cord and cranial nerves, in turn leading to all the neurological symptoms. The biggest reasons to consider this possibility are: 1) The autoimmune markers are suggestive of potential connective tissue problems, 2) Neck pain is my most persistent symptom, 3) Neck pain/weakness/instability is one of the most frequently reported symptoms in those with vaccine injuries, 4) Posture and position has a noticeable effect on symptom presentation, 5) CCI is increasingly thought to be common in chronic fatigue syndrome. Which is obviously different than what I’m dealing with but certainly can be thought of as similar – a lot of people think “long covid” is really just CFS, for whatever that’s worth. I again don’t believe this can make sense as the sole explanation for my condition but I think it (or something similar) is a reasonably likely secondary issue.

·       Lasting neurological damage: I don’t actually know what this would look like, but I think it must be considered a distinct possibility that I could have some yet undetected nervous system damage. The fact that my symptoms have been so highly amendable to diet and lifestyle intervention leads me to want to disregard this as a primary issue, but as higher levels of cognition become the most persistent impediment to normalcy it certainly has to be considered a distinct possibility. 

·       Depression: I’m kidding. It’s not fucking depression. But four different medical professionals have floated the idea so here we are.

Symptoms

 

Below is a fairly complete list of symptoms I’ve experienced. At this point really only the neck pain persists on a day-to-day basis, with some headache/nausea if it’s bad enough. The vast majority of these symptoms are in the past though, or only subject to significant cognitive strain. 

It all seems kind of benign when I write it out like this, as if words like “headache” and “dizziness” and “nausea” could ever capture the sensation of a brain being ripped apart from within. When it takes an hour to get from the couch to the bed, as it sometimes did, there’s really nothing that can convey how miserable that hour really is – how electric and painful it is, how completely detached from reality it feels, how absolutely heavy everything feels when you try to move, how badly it makes you wish for death. And then, ironically, when I’ve finally dragged my body to bed, how fucking certain I am that death is what awaits me as I drift to sleep.

If you’re a medical professional reading this (even a year or two after it was posted), I really do welcome your opinion. If you’ve made it all the way through both this and the first intro post you have now given this more thought, and have a more complete picture, than most of the ~15 doctors I’ve seen in the last year and a half. Main clinical abnormalities – intermittently positive ANA, Anti-Sm, Anti-Ro, Anti-U1 RNP, PR3, elevated IL6. Also found a compound heterozygous MTHFR gene mutation that may or may not have any bearing on my health at all, and have been assessed to have some kind of potential/probable/mild generalized hypermobility or hEDS. Fire away with thoughts or questions.

 

·       Headache/migraine – This is the easiest place to start. Occipital pain has been consistent throughout, with more “standard” temporal headaches occurring frequently. I use the word “migraine” here to refer to severe headache accompanied by nausea. Frequently, especially when symptoms have been generally worse, the pain has been far more electric and diffuse in nature. Powerful shooting pain that would quickly dart around was not uncommon.

·       Brain tremors? – Not technically but I don’t know what else to call it. Have you ever been stressed or didn’t sleep well and ended up with an eyelid that wouldn’t stop twitching? Imagine that feeling, but deep in the center of your brain. It’s like an electrical flickering, but instead of just feeling twitchy it also hurts and seems to short-circuit thoughts and emotions every couple of seconds. This tended to present only during the worst stretches.

·       Persistent cervical spine pain – My neck has hurt pretty much 24/7 for the last year and a half. Its far from my worst symptom, but definitely one of the most consistent. The pain is highly localized to the central spinal column and is made moderately/progressively worse by unfavorable posture but significantly worse by acute mental strain. The other component is how susceptible my neck is to “falling asleep” with any significant deviation from neutral, like your arm would if you slept on it wrong. And that’s basically what it feels like in my neck and head. Sitting much is the most problematic trigger.

·       Nausea – seemingly secondary to the headaches

·       Dizziness

·       Shakiness/tremors in the extremities

·       Numbness and tingling in the extremities

·       Weakness/neuromuscular failure

·       Constant sympathetic activation – This is the “fight of flight” response, the stimulating half of your autonomic nervous system. Physical manifestations have included persistently elevated body temperature, blood pressure, racing heart rate, etc.

·       Trigeminal neuralgia – acute bouts of sharp, stabbing facial pain presumably related to damage or dysfunction of the nerve innervating that area

·       Chest pain and palpitations – This might be the closest thing to a non-neurological symptom. But given the persistent presentation of the previous pair of symptoms, I think these are probably are just resultant from vagus never irritation/dysfunction

·       Deficits of balance and coordination – When overall presentation was worse, I would struggle consistently with balance and coordination. However, this effect was only ever extreme upon waking. Particularly before dietary intervention, I would struggle mightily with standing and walking in the minutes after waking. This would leave me frequently collapsing while attempting to get out of bed, and navigating stairs either down on my butt or up on all fours to avoid tumbling down.

·       Deficits of cognition – Independent of the brain twitching. There’s probably a better way to label that, because its certainly more severe than the “brain fog” I suffered immediately after the acute covid infection. It’s more of a complete failure of executive function. This would occur acutely and regularly when overall presentation was bad, and leave me generally incapacitated for a bout of time. I don’t know how to explain what it feels like to not be able to put together complete thoughts or sentences, but that’s basically what was happening. This was usually or always accompanied by extreme cervical warmth.

·       Acutely sharp cerebral pain – This would usually occur while walking or moving around, and was characterized by extreme, localized pain somewhere in my head. It tended to only last for a handful of moments, was always accompanied by pronounced lightheadedness, and would routinely bring me to my knees.

·       Intrusive thoughts – I don’t know what to call them. This was probably my least favorite symptom, that I’ve thankfully been more or less free from in the last 6-8 months. I would routinely experience vivid, unwanted…visions? Thoughts? Of events that usually involved my death or the death of somebody close to me. The worst episodes were the ones in which I was somehow responsible for harm to my wife or parents. The sight of almost anything that could be dangerous or used as a weapon would trigger these thoughts. I struggled in the kitchen, because I couldn’t see the sink without also seeing my hand ripped off by the garbage disposal. I couldn’t see the knife block without seeing myself stabbing somebody. I could be driving down the road thinking about something else entirely when any random car passing would trigger the vision of that car running over my dad on his bike. I really don’t know how to describe these events other than to say that they seemed so distinctly different than normal “imagination.” They seemed much more viscerally real, and something I had simply no control over.

·       Psychosis? – Again, I don’t know what to actually call it. The main presentation here was a complete inability to separate sleep from death. For months I literally lost the capacity to understand on a cognitive or emotional level what was happening when I went to sleep. Which I’m sure sounds very weird, and I’m sure I’m not going to be able to describe it well. When I would get closer to falling asleep, it seemed my connection to reality would fade away. Every single night, and every single nap, I simply KNEW that I was dying. I always felt a weird mix of panic and desperate desire to come to terms with what was happening before I slipped away. This would also happen regularly upon waking, wherein I would also be sure I was about to die as I woke up. I would often find myself looking around for who or what was going to kill me, or I would be plagued by a sensation that I would drop dead as soon I tried to stand up. This obviously made sleep more difficult that it needed to be, and I still can’t really go to sleep without listening to a podcast so as to avoid the uncomfortable sensation of being “alone” in the situation I largely came to associate with death.

 

 

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