White matter map and why it matters

This article describes a new, life- and reality-based map of the white matter in the human brain:

First Micro-Structure Atlas of Human Brain Completed

It addresses two crippling gaps in our understanding of the brain:

1. Hitherto, brain models have been derived from microscopic analysis of a handful (so to speak) of cadaver brains.  Since significant physical and chemical changes begin to happen immediately upon death, this puts a hard limit on  how accurate these models can be — and gives us no real clue about the true extent of the inaccuracy, because there were no living models to compare them with.

2. Until now, the science has focused on grey matter. We don’t even really know what white matter does, except convey the messages the grey matter processes. (It’s a bit like not knowing anything about your internet uplink — not ISP contact info, speed, bandwidth, nor hardware — even though your work and connections depend on your internet access. You can still get something done, but if anything goes wrong, where do you start?) One day in the near future, we’re going to be really embarrassed about ignoring white matter for so long.

This map was made as follows:
- using MRI that yields unprecedented resolution, able to provide solid estimates of such details as the width of different neuron fibers (!),
- done on living brains,
- in the skulls of 100 different people — a much more meaningful sample.

This is a great day in neurology. All of us with CNS disorders have a brighter future, with information from this map making its way into the science.

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Pain Manifesto

This came out of cold chronic CRPS type 1, a debilitating condition of intractable chronic pain, nervous system disruption, and multi-system dysregulation — destroying the body’s ability to manage heat/cold, blood sugar, immune defense, circulation, sensation, bone density, movement, vision, digestion, heart function, and ultimately survival.

“Standard” treatments don’t work well for me; moreover, they involve invasive procedures too brutal to tolerate and medications I’m either outright allergic to, or that impair me so profoundly I can no longer function. At all.

So I took myself off my meds, thought things over, and came to the following conclusions.

MY CHRONIC PAIN MANIFESTO

Yes, it hurts.
It’s going to anyway.

So should I hoard my days
And fast from life?
Comfort myself with poisons,
Blister-packed and FDA approved?

Some think it would be best all ’round.
I’d cure them if I could (heh!)
But I’m too tired for
Yet another pointless struggle.

The sunlight pours through trees like prosecco
And reminds me what it means to live:

Voices warm with love, the
Mouth-smack of good food,
The hug of hills and the
Rough snuggles of the sea.

Hoard my days? I’ll spend each one
Like it’s stuffed with jewels
Pouring through my hands like a miser’s dream.

Feast on this:
The cost of life is much the same.
The difference lies in how you spend it.

How is this relevant to medical science? For one thing, it shows just how badly off base it is in vivo. Like any manifesto, it makes an explicit declaration: fundamental attitudes must change.

Policy determines what will be profitable, and profit opportunities determine what science gets funded. There is no profit in fully-functioning people, but there’s plenty in people who are too sick to function but not sick enough to die … for awhile.

Policy could allow my insurance to cover the things that do work (massage, reiki, homeopathy, yoga), especially given the detailed and vivid documentation I’ve provided of just how well they work. Nobody will fund science studies on these in any volume, because it is so much more profitable to drug people into silence.

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Scared of the wrong things: depressive chemistry and danger

Funny how the whole delicate neurological/neurochemical structure is so interwoven:

“…The researchers suggest that the strange defensive behavior exhibited by the enzyme-deficient mice may actually reflect a limited range of adaptive responses and lack of emotional flexibility — the mice may only have one gear for fear.”

We’ve all known people who make exaggerated choices around danger that make no sense to ourselves. (Having heard my mother and my sometime partner on the subject of my riding motorcycles, I’m pretty sure of that.) However, only at my most desperately depressed have I engaged in unsafe sex, which is the second stupidest risk I can think of (the first having nothing to do with motorcycles.) 
The role of MAO-A and depressive neurotransmitters, combined with the dopamine-deficient sense of hopelessness and diminished executive function, make that make sense: 
Monoamine oxidase A is the main enzyme in the brain that breaks down serotonin, norepinephrine and dopamine…”
Which makes me think that it’s possible, in humans in vivo, to be deficient in both MAO-A and in dopamine, serotonin, etc. It would explain a lot about certain mental states, even though it seems chemically tautological at first glance to be both Big 3-deficient and MAO-A deficient. As I’ve learned, though, deficiency and dysregulation do have additive effects, they don’t cancel each other out. 
I’d like to see more studies which monitor serum and brain levels of these key chemicals together, preferably in humans. Science tends to take the simplest possible approach, which is rarely the most realistic and not necessarily the most telling. It does get funded and it does make it simpler to design the studies. 

I look forward to having more sophisticated thinkers (and funders) get into this branch of psychoneurology, since all these lively lovely tiny bits of info won’t come together in a meaningful way until we can look at them in concert with a higher degree of exactitude and completeness. I suppose I’ll have to be patient. And careful. 
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Putting the "con" in mitochondria, the "funk" in dysfunction

Mitochondria (from the Greek, meaning “string grain” — yeah, it’s lame, but it sounds good in Greek) are independent little one-celled organisms that live inside your cells and make energy for them. If you ever studied the ATP cycle (also called the Krebbs cycle or the citric acid cycle, depending on where you went to school and how deeply they went into it), then you should know that this is where the ATP cycle takes place.

Without mitochondria, you have no way of converting food into energy.

When you were being conceived, half your cells’ genes came from your mother and half from your father. All of the other stuff that goes inside a cell came from your mother. This includes the mitochondria. (This is why mitochondrial DNA is used to track maternal inheritance: it always comes down the female line.) Your mother’s cell hosts conception, just as (normally) your mother’s body hosts gestation.

Mitochondria have a fairly smooth outer layer and a deeply-rumpled inner layer. Most of the action happens inside the rumpled layer. This is where the ribosomes, most of the fluids and loose protein, and the ATP-making particles hang out.

Cells, including mitochondria, need various proteins to do their work with. Large proteins get carefully handed from the outside world, through the outer layer of the mitochondrion (singular of “mitochondria” — sorry, it’s still Greek), then into the inner layer.

If the smooth outer layer is damaged, this makes this transfer process screw up, and the inner layer gets disrupted, ripping up the cell. Granules and nucleic acids all over the place. Bang goes that ATP production.

Those are some busted mitochondria.

This kind of damage happens in response to certain kinds of toxins (including certain medications for AIDS and all psychoactives — including antidepressants and pain medications, which seems especially mean!), occasionally from genetic disturbance, and occasionally as a consequence of illness — or nerve injury and its complications.

Mitochondrial dysfunction has been repeatedly and profoundly linked to neurogenerative diseases like Alzheimer’s and Parkinson’s; cell-metabolism problems like heart disease, insulin resistance and type II diabetes; and several diseases often mistaken for CRPS.

Not surprisingly, symptoms of mitochondrial dysfunction are the worst in tissues that use the most energy and have the largest number of mitochondria per cell: nerves, muscles, brain.

Recently, it has been strongly associated with CRPS. And the cherry on top: it plays a vital role in neuroplasticity, or the way your nerves and brain change — for better or worse.

Hell-o, “pain-brain.” We thought we knew ya!

Knowing why it’s so damnably exhausting to walk a mile, when it used to be fun — fun! — to run 3, is a bit of a relief. First question that leaps to my mind: How do I fix ‘em? How do I give them what they need to get better and protect themselves?  The answer seems simple: antioxidants are what’s needed to prevent and repair that damage (good explanation of that here) to the walls of the mitochondrial cell.  Mitochondria are both the biggest makers of reactive oxygen species and the biggest scavengers of them, so of course it makes sense that that’s exactly the kind of help they need when they can’t keep up.

Downing antioxidants by the bucketful is one way to get them in. Intriguing for three reasons:

  • Taking moderate amounts of the antioxidant Vitamin C after surgery hugely reduces your chances of getting CRPS. (Upper limb and lower limb surgeries were studied.)
  • There’s some indication that Vitamin K may help combat the progress of CRPS.
  • Taking antioxidants is pretty easy: delicious food, accessible pills, not bad.

Kind of depressing for one simple reason: it’s iffy whether, once you’ve got the disease process going, the antioxidants can get where they’re needed and save your poor beleaguered mitochondria. … Having said that, I notice that the writers of that article seem to be trying to sell something, and that makes me very suspicious of their conclusions.

Next, I’ll offer suggestions for patients, suggestions for clinicians, and then wind this up with a foray into the question of whether mitochondrial issues have a genetic component, like being X-linked — the way a cat’s fur color is! 

For people with CRPS — So what is a poor, confused CRPSer to do?

Two things that you hardly need reminding of:

  1. Trust your sense of your own body.
  2. Do what works for you.

Most antioxidants are not going to hurt you, without letting you know first (that is, make you nauseous or feel funny.) Take vitamin C in doses no larger than 500mg, since larger doses tend to trigger your gut to throw the C away. Go ahead and try stress-vitamins, co-enzyme Q-10, N-acetylcysteine, hair-skin-&-nails vitamins (these are really fat-soluble antioxidants) … try things, take what helps, and put aside the rest if they don’t do anything. Keep in mind that things change: what doesn’t work now might work later, and vice-versa.

Also, eat all the leafy greens you can get: seaweed snacks, Mom’s collard greens, kale krunchies, spinach salad, you name it. It’s amazing nerve food.

For antioxidant powerhouses, look for dark-red and dark-blue fruits: pomegranates, blueberries, red wine, chocolate (though some CRPS people have to avoid that for its nerve effects), mangosteen (my favorite fruit), cranberries, and so on.

Stay smart. Stay loose. Keep going.

For medical people — clinical takeaways:

Most treatment standards, particularly for CRPS, are based on science that’s over a decade old. They shouldn’t be changed blithely but they can certainly be improved. There is plenty of room for that.

The following points are intended as additions to the standards you follow for CRPS, as they are good guidelines for mitochondrial and neurologic support in a system compromised by CRPS.

  •  After any limb surgery, give Vitamin C 500 mg, QD or BID, for a couple weeks beforehand and 30-50 days after — or to metabolic tolerance, if that’s too much. Use a food-associated form for best uptake. This one intervention will reduce the risk of developing CRPS by 80%, according to the best current data.
  •  We assume your patients are taking an adequate multivitamin and are eating plenty of greens, dark fruits, and wholesome proteins. So make sure they are.  Direct them to food bank, food stamps or other food assistance as needed. Give recipes. (No kidding.)  2 benefits: better antioxidant uptake if taken with antioxidant-rich food, and increasing the patient’s own sense of agency/participation improves pain and affect.  (If you don’t believe in multivitamins, then get out of the supermarket/pharmacy and get some real ones.)
  •  Stress the antioxidant vitamins.  In acute CRPS, give water-soluble antioxidant vitamins in 1-3x the doses you’d give a healthy person.  Give fat-soluble antioxidants (A, D, E) up to 2x normal, testing levels as indicated.  Consider vitamin K inj.
  •  In cold/chronic CRPS, give water-soluble antioxidant vitamins in 3-5x the doses you’d give a healthy person (start at 2x and work up).  Give fat-soluble antioxidants (A, D, E) up to 2-4x normal, testing levels as indicated; consider weekly mega-dose D (as used in AIDS.)  Give vitamin K inj.  Check serum or urine levels as indicated, especially as we develop absorption disorders.
  •  Give “uber-antioxidants” like ubiquinone (co-Q 10), N-acetylcysteine, or glutathione. There are indications that these can provide substantial benefit — though again, not normally curative of chronic CRPS. They are impressive, especially for mitochondrial-dysfunction issues.

These ranges are empirical; if you can find the funding to do the science to develop more reliable ranges for this population, so much the better.

Adequate tissue oxygenation and perfusion can return substantial function and significantly reduce pharmacologic burden. Patients can demonstrate this, even where the data have not been published and peer reviewed. Therefore, use antioxidants rigorously and intelligently.

Image credit: http://www.vrp.com/antioxidants/-r-lipoic-acid-unique-mitochondrial-antioxidant-fights-premature-aging.  (Article’s not bad.)

Why all that anti-oxidation when the medical literature is not definitive?  2 reasons, which you ought to know for yourselves:

  1. Between the cortisol and systemic oxidative stresses, it can’t hurt and it will help something. You’ll see a distinct improvement in affect, activity, motivation and well-being when the dose is optimized, even if it can’t be expected to be curative.  Making your patient’s life more bearable is an essential part of your job.
  2. Let’s say this together, everyone: statistics mean nothing in the case of the individual.  Accepted, standardized medicine is what you start with, but, when your case is taking you out to the margins, you go to the margins, because that’s where your success is most likely to await.  

Keep in mind that doctors are not the only scientists interested in the human body.  Be prepared to look into other disciplines for leads when your own offers no good options.

Try Nursing, PT, Nutrition, Therapeutic Massage — you’ll realize that nobody knows more about soft tissue’s functional physiology in vivo than therapeutic massage science, and if nothing else, the exercise in intellectual flexibility might do you good.

The accepted style is very different, but the info they have is tremendous.

Forward-looking thoughts:

  • Consider infusing vitamin K into CRPS-damaged tissues. I would love to see studies on that.
  • Figure out how to deliver antioxidants in a targeted way. (Now! Please!) This would be a good way to save a lot of lives and end tons of misery.

… And for all curious people …

Let’s go back to mitochondria in reproduction. Kind of in an X-rated way, figuratively speaking.

We know that women have two X chromosomes. The Y chromosome is a stubby little object with hardly any data to use, unless you’re into color-blindness or hemophilia; this means women have quantities of extra data, which can have even more devastating effects (as in, Down syndrome.) So how to handle the extra genes?

Pick one. Simple as that.

Shortly after conception, when the cells are just dividing like mad and haven’t decided what to be yet, every single cell turns off one of its two X chromosomes; each of that cell’s daughter cells inactivates the same X chromosome. As the cells continue to multiply, then fill out, fold, bend around, and specialize, to become a whole, separate being, it means that X-linked traits appear in a mottled pattern throughout the body, as the two sets of daughter cells continue reproducing and passing on their particular X-activations.  Isn’t that curious?

As an especially decorative instance, cats’ hair color is an X-linked trait:

Cool, huh? Love her accent, too.

But this fact brings me to a serious question about mitochondrial disease. If mitochondria are sex-linked, is there a relationship between the X chromosome and mitochondrial expression? It seems improbable that there wouldn’t be, because mitochondria reside inside the cell, and the cell’s action is determined by the genes within it. The mitochondria had to have developed a special relationship with the X’s in the 23rd chromosomal pair, after all those millenia.

It’s generally accepted that mitochondrial diseases are due to toxification or to complex, multigenetic issues. Ok, fine. But what about mitochondrial vulnerabilities that don’t become pathologic until they are damaged in some other way? To what degree is toxification an issue related to X-activation? In other words, is mitochnodrial vulnerability related to vulnerabilities in the active X chromosome?

Is there a patchy characteristic to the early stages of mitochondrial destruction? — You know, the early stages of rare disorders, the time when it’s impossible to get a diagnosis because the doctors are all so busy chasing their own tails around your irrational symptoms and their own ignorance.

Is that initial “mottled” activity one reason why these diseases are so damn weird?

Link list:

Wikipedia’s entry on mitochondria is pretty good:
http://en.wikipedia.org/wiki/Mitochondria

On mitochondria and AIDS meds:
http://www.ncbi.nlm.nih.gov/pubmed/20818734
On mitochondria and pyschoactives:
http://www.ncbi.nlm.nih.gov/pubmed/18626887

Alzheimer’s Foundation:
http://www.alzfdn.org

Michael J. Fox’s Parkinson’s foundation:
http://www.michaeljfox.org/

United Mitochondrial Disease Foundation, listing diseases which are often mistaken for CRPS:
http://www.umdf.org/

Mitochondria and neuroplasticity:
http://www.ncbi.nlm.nih.gov/pubmed/20957078

A good rundown (so to speak) of antioxidants’ function:
http://www.ionizedwateronline.com/Antioxidants.html

Vitamin C around surgery.
Upper limb:
http://www.ncbi.nlm.nih.gov/pubmed/17606778
http://www.ncbi.nlm.nih.gov/pubmed/20224742
Lower limb:
http://www.ncbi.nlm.nih.gov/pubmed/19840748

Vitamin K and CRPS progression:
http://www.ncbi.nlm.nih.gov/pubmed/20378261

Getting antioxidants where they’re most needed. Ignore the shystering towards the end:
http://www.ncbi.nlm.nih.gov/pubmed/21422516

ALA and regeneration of Vitamin E:
http://www.vrp.com/antioxidants/-r-lipoic-acid-unique-mitochondrial-antioxidant-fights-premature-aging

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Spinal cord changes in longstanding CRPS

This is brilliant:

Spinal cord histopathological alterations in a patient with longstanding complex regional pain syndrome

The authors did an autopsy on one person with longstanding CRPS and did comparative autopsies on 4 people who did not have CRPS. They checked samples from the neck, thorax, and low-back for microglia and astrocytes. These are the kinds of cells that not only are part of the nervous system’s immune response, but also increase the transmission of pain signals. That means, inflammation plus more pain! They found plenty in the CRPS patient’s spine.

They also found that the normal cells in the dorsal horn of the spine – the ones that carry sensations of light touch, vibration, and proprioception (the sense of the body in space) – are significantly fewer in the CRPS patient. This makes sense of the fact that allodynia (light touch) gets worse, vibration is so agonizing (making both riding public transit and holding a steering wheel pretty horrible), and we get clumsy over time because we can’t quite feel where our bodies are in space.

These strange cellular changes were found “most prominently at the level of the original injury, but extending throughout the entire length of the spinal cord.” That means that the allodynia, diminished balance, etc. physically spread from the original dorsal root, all the way up and down the spine, affecting the whole physical self.

So, with more cells for pain and immune attack, and fewer cells to transport normal messages of light touch, vibration, and proprioception, we have some stunningly clear evidence that the spreading allodynia, clumsiness, and intolerance to vibration is NOT IMAGINARY.

Given how many people get told that it’s all in their heads, they’re hurting because they’re thinking wrong or because they were abused as children, etc., this is an important thing to keep in mind. Let’s keep the cart behind the horse.

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A job well begun …

I have CRPS-1/RSD/causalgia, and when your condition has more than one name, it’s a bad sign. I was a nurse, I was a tech writer, and I remain fascinated by health and technology.

Some parts of my brain have blown gaskets, but examining the science relating to neurology/immunology/endocrinology — and mulling how it could work in real life — seems to go just fine. It’s appropriate to both my professions that I want to track, document, and share what I learn.

You’re invited to watch and engage in this interesting journey. It’s taking place at an unimaginably rich, burgeoning age of technological development and biological understanding.

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