Stem Cells for Stroke: Expensive, Unproven and Unavailable.

I'm not a big fan stem cell treatment to help stroke recovery. 

Not yet anyway.

Part of the problem (bluntly) is the surgery.  A hole is drilled through the skull— and that's the least invasive part of the procedure. 

Through that hole, a long needle is directed (multiple times) to the area around the stroke (infarct) in the brain. 

Remember: the stroke kills part of the brain. After the stroke, that dead area "cavitates"— literally forms an empty cave in the brain. Nature hates a vacuum and the cavitation is a vacuum. So it doesn't remain empty— it fills with cerebral spinal fluid (the fluid that flows in, through, and around the brain). That fluid-filled area is dead, and no amount of stem cells, or any other sort of treatment is going to bring those dead brain cells (neurons) back. 

Stem cells treatment aims to overcome the loss by injecting stem cells in the survivor's brain, just outside of the area that was killed. 

Those cells will then turn into brain cells (neurons). That's the idea, and it does hold tremendous promise. And they will get it right, one day. But that day ain't yet. 

A study that is often cited as a seminal stem cell/ stroke study is entitled Clinical Outcomes of Transplanted Modified Bone Marrow–Derived Mesenchymal Stem Cells in Stroke. This study, done at Stanford and one other site, enrolled a total of 18 patients. 

The study has 3 problems: 

1. No control group. 

2. A Lot of people screened, few qualified. 

3. The data (for the primary movement test they used, at least) appears underwhelming.

No control group. 

Everyone got the treatment. Not great. Because with no control, everyone doing the data collection knew that everyone got the treatment. Uncontrolled studies like this put tremendous pressure on the folks who are measuring progress. If the scores go down, the whole study looks bad, which can affect future funding. So there's a tendency to want to "cheat" the score up, either consciously or unconsciously.

A Lot of people screened. Few qualified. 

379 stroke survivors were considered (screened). And out of those 379, only got 18 the qualified. Why was the qualification ratio so low? It's hard to say. According to the data supplement available with the study, they had a lot of "exclusion criteria"— things that might keep people from the study. But, it is a pretty basic list of exclusions for a stroke study. So why were so many people turned down? Maybe they weren't. Maybe potential participants refused be be enrolled. Why would they refuse? Let me explain...

In research you have to do what's called "informed consent." You have to tell the participant (or the less modern term "subject") every aspect of every aspect of the study that pertains to that participant. This is a federal and international law. Why is it so important to inform participants? Let's put it this way... the Nazis did not inform Jewish (and other) prisoners of the experiments the prisoners would be involved in. And, really, nobody wants be a Nazi. 

But it wasn't just the Nazis. Consider the U.S. Public Health Service Syphilis Study at Tuskegee, a horror show that withheld life saving treatment from African American men so  "scientists" could track the "natural progression" of syphilis.  That didn't end until 1972!

The upshot were a whole bunch of very strict rules when it came to human participants. We now have to tell any potential participant EVERYTHING that may affect them in the study. This process— the process of explaining everything, again, is called informed consent.

OK, back to stem cell research and why I think they had a lot of people run out of Stanford as fast as they could.

During informed consent, the participants were probably shown the needles that would go into their brain. They'd probably also were informed that there would be some brain damage as the needle tore through brain tissue on the way to the target. 

The data appears underwhelming.

This study had one primary way of measuring movement: A test called the Fugl-Meyer. I did this test for 12 years straight, every day, often multiple times a day. I think I've done it more than anyone in the Galaxy.

Bottom line, there wasn't much of a change. Just over 11 points. That's 11 points out of a possible 88. This is a relatively modest increase. It is true, modest increases may make a huge difference. But 11 or 12 points can be potentially garnered by being able to straighten the elbow a little more.

But the authors ride it for all its worth. This is unfortunate because scientists have a hard enough time explaining their science to the world without the added burden of  exaggeration.

“We did not expect to see significant recovery. We were quite startled by the remarkable recovery some of the patients showed.” I could get more points than that using intensive repetitive practice-- and without the pesky brain needles. And please! Stay away from the term significant! Significant means one thing in the world of scientific statistics, but to laymen reading your interview it means "a lot".

“She was what we call one of our miracle patients." [sic] There were only had 18 "patients." How many miracles were there? 

"Patients who were in wheelchairs are walking now.” Possible. Not likely. 

We all want something that works. But stem cell therapy isn't there yet. What is weird is that this study does have important findings that move the science forward. Establishing safety across multiple parameters (as this study did) is important. 

Please note that stem cell therapy for stroke recovery is not available in the US or Europe, except in clinical trials. However, I know a survivor who had a series of stem cell treatments for his stroke. This was over the years  2013- 2015 in Thailand and China. You can find info about this option here:

https://beikebiotech.com http://thebrightdirection.com/stem-cell-treatment/stereotactic-brain-surgery/ http://www.wumedicalcenter.com

This survivor reports that he thinks the treatment cost ~16k USD.

Don't let PERFECT be the enemy of BETTER

There's a perspective most clinicians have that is false, and that can hurt your recovery. Bluntly, their perspective is: There is a right and a wrong way to move. And stroke survivors move wrong. 

Further, they'll say, if you move the wrong way, its bad for your body, and brain. 

"You'll hurt your brain."

They'll contend that since you're moving wrong, the brain will "ingrain" that movement. The brain will learn that bad movement, become satisfied with that movement, and that will become your movement strategy forevermore.

"You'll hurt your body."

They'll say that, because you're moving wrong, and the human body is designed to move right, you'll cause orthopedic (bone/ muscle/ ligament/ etc.) damage.

Both of the above are only true if you completely discount two fundamental aspects of human motor behavior:

a. For 250 thousand years humans have learned to move the same way: Move, self correct, move again better, self correct, move again better... but if you are discouraged from moving, where is the opportunity to self correct?

b. The injury to the brain makes the whole move, self correct process slower than clinicians can deal with for 2 reasons: 1. Therapy has limited amount time with the survivor. This is a bigger problem in the USA than many other countries, but everywhere its a problem. 2. Many therapists have a lot of experience with brain injured patients, to be sure. But the frustration, fatigue, depression, changes in the brain, emotional issues, etc., etc. is something therapists can attempt empathize with. But they don't really understand unless they've lived it. There are therapists who have lived in both worlds. I've met quite a few of them. They know. Here's one. 

The upshot of a and b is that the clinician— through word and deed— assumes that the survivor will never learn to move "right." And so, "you'll hurt your brain" and, "you'll hurt your body."

So the question clinicians are trying to answer is "How can I best coach them to move right?" Instead the question should be is, "How can I get them to move better?" Better is always achievable. (Clinicians, look at it this way: Chip away at their present AROMs. If the have 20° of elbow extension, go for 30°.)

In some ways, stroke survivors have the same dilemma as high level athletes. Both athletes and survivors are trying to push through a ceiling in their ability to move. And just like a an athlete, the survivor's progress will be slow and very (very) incremental. 

And that's OK, because its not about "right". 

Its about better.

Early Walking After Stroke is Good, No it Isn't

There has been a debate for many years about early rehab. Should stroke rehab in the first 1-7 days be intensive? Intensive is a buzzword that means "hard"; more repetitions, more weight, longer distances, etc. Some people suggest you should do a lot very early after a stroke, some suggest (I'm in this camp) that you should wait until the subacute phase.

Within this "early-more-better" argument is a sub-category: Walking. The survivor should walk within 24 hours of their stroke, they say.

I've written about this before. Note that the following link has clickable links so you can have a look at the actual article yourself. Here.

Here's the bottom line: Early is not better. Introduce intensity during the subacute phase, not the acute phase. 

Bottom line: If you have the survivor get intensive during the... 

• acute phase (1st 7 days), you can make the infarct (stroke) worse
• hyperacute phase (1st 6 hours), you can kill them.

There was a long, large study that was done on walking very early after stroke. Note their bottom line for walking early: Fewer patients in the very early mobilisation group had a favourable outcome than those in the usual care group.

Want to know whats going on early after stroke in the survivors brain? Have a look at this.

Don't waste your $$: There's No School like Old School Stroke Recovery

There are a lot of virtual reality/ gaming stroke recovery systems out there. And a ton of folks that try to convince you that, because its a gaming glove, or VR, or even a robot... its just better. Because, haven't you heard? New is better.

Except its not. Motor learning-- the kind of learning stroke survivors have to do to recover-- has been going on in humans forever. So the stuff that always worked to move better, still works. 

Don't take my word for it. In this article the authors looked at the difference in motor learning after stroke in 2 groups:

1. Virtual Realty training with the Nintendo Wii system

2.  Playing cards, bingo, Jenga, or a game with a ball

After collecting the data on the two groups, this was their conclusion:

The type of task used in motor rehabilitation post-stroke might be less relevant, as long as it is intensive enough and task-specific. 

Other studies (see below) say the same thing: Normal activities work as well as machines, as long as its as long as it is intensive enough and task-specific."

32. Lo AC, Guarino PD, Richards LG, et al. Robot-assisted therapy for long-term upper-limb impairment after stroke. N Engl J Med. 2010;362:1772–83.[PMC free article] [PubMed]

33. Duncan PW, Sullivan KJ, Behrman AL, et al. Body-weight-supported treadmill rehabilitation after stroke. N Engl J Med. 2011;364:2026–36.[PMC free article] [PubMed]

Wanna move better after stroke? Watch the Super Bowl.

    

There's this thing called "action observation" and you can use to promote your own recovery. 

     In simple terms, action observation (AO) is what humans use to communicate with each other. We had it (evolutionarily) even before we had the ability to speak. Let's say, you and I are in the same tribe and we're hunting big game, and we can't yell for fear of spooking our next meal. We can communicate a lot through facial expression and body movement. Humans used AO in hunter-gatherer tribes to be able to communicate intention, movement, pain, sadness, excitement, etc. This survival tool allowed us to express our human experiences quickly and accurately. 

   

     In some ways AO can be expressed in one word:

Empathy. You feel what I feel, I feel what you feel. Most of this is processed in the much-discussed mirror neurons; specialized nerve cells in the brain that  allow us to feel what others are feeling. 

      If I observe you burning your hand, my mirror neurons activate, and I'll wince. If I observe you throwing a tight spiral, my neurons will feel that movement.

How can you use AO in your recovery?

      Let's say you're a survivor trying to make you walking beter, faster, and with less fear of falling. Observe other people walking. Feel them walking. There is quite a few researchers yelling from the tallest buildings: This helps people recover! 

       Listen to them!

Here are some links to action observation in stroke:

• Action-Observation In Stroke Rehabilitation (an overview)
• Effect of action observation therapy on daily activities and motor recovery in stroke patients
• Action observation for upper limb rehabilitation after stroke

Some Good News: New Guidelines will help Ischaemic (block) survivors.

This month the American Stroke Association issued new guidelines that will help people who have had a stroke. Unfortunately, for most of the readers of this blog, "that ship has sailed" because these recommendations cover the first 24 hours post stroke. Still the guidelines are good news; they  will lesson the severity of stroke going forward.

And they come with a cool graphic!

Original article in the Journal of stroke here.

Simplified version here.

So. You want to get into Clinical Research. Here are some suggestions

I do a lot of talks to clinicians. Every couple of talks I get "How did you get into clinical research? And, how do I get into it?"

Kessler, West Orange, NJ, where I worked early in my career. 

Here are some suggestions: 

• Educate yourself. There are all kinds of opportunities for folks with bachelors or associates degrees. Heck, there's probably jobs in clinical research that you don't need any degree. But if you do want to go the advanced degree route (I didn't): Typically, a PhD is more important in research, while the DPT is important in teaching. There is a doctorate of OT, but again, the PhD is helpful in research. 
• Cast a wide net. Find folks doing research in your geographic area and volunteer or ask for a job. Where can you find such a list? Go here and find the list under "Find Stroke-Recovery Research in Your Area." Look for email address/ contact info and make contact.
• Be willing to take a pay cut. I took a 1/3 pay cut to get into research. It was a temporary pay cut, but I didn't know that at the time. You'll tend to get paid on the back end. In a variety of ways.
• Hitch your wagon to dynamic (and smart) folks. Once you're in, that's not the end. Find the folks who are actually getting funding and align yourself with them. Also, look for people who are publishing a lot. One of the guys I aligned myself with early was publishing about 5 to 1 compared to others in our research facility. Of course, you can start on your own grant-getting journey, but even then you need a mentor to begin with. Also, don’t judge expertise on degree, base it on conversations. There are a lot of PhDs in research who are not dynamic, get little funding, have little vision, etc. Find the good people.
• Don’t listen to the road more traveled crowd. My friends in my class in college suggested I not go into research. "How long will it last?" they asked skeptically. 20 years, so far.   
• Learn stuff that no one else is willing to learn. Once you learn that machine or program or outcome measure, they'll need you because for every grant that is funded that involves that thing because, well, you are qualified and often the only option. Boom, job security.

Half out of it: What you can do about unilateral neglect

Unilateral neglect is a phenomenon where the survivor does not/ cannot attend to the "bad" (affected) side. Here is a visual explanation...

If a survivor with unilateral neglect is asked to bisect a line at the midpoint they'll do this: 

If a survivor with unilateral neglect is asked to cross out every instance of a given item they'll do this:

If a survivor with unilateral neglect is asked to fill in the numbers on a clock face they'll do this:

Here I'll discuss two options for, hopefully, decreasing unilateral neglect. And decreasing it is important: If the arm is not payed attention to, the survivor will not use it. And you know the brain... its very use it or lose it. 

The 2 options: Limb activation, and taping. These are not the only options. For more options go here and search for the word unilateral.

Limb activation. 
Typically, clinical studies of this treatment have used a "Limb Activation Device." 

These machines cue the survivor to pay attention by buzzing, making a sound, or lighting up. So, there's the problem: You need a machine. You could buy a watch that vibrates and set it for every minute or so. When it vibrates the survivor knows to do a movement with that arm. This is different from most treatments for unilateral neglect. Usually, the survivor is told to attend to the affected side (turn their head, and find their affected side). But that is the head finding the arm. With vibration, the arm reminds the head.

Or you could just touch the survivor's affected side at a set interval, and the survivor then moves that limb.

There is quite a bit of research that limb activation works.

Taping

This is one I got from a therapist at one of my seminars. Although its much less evidenced based, its much simpler, and worth a try.

The survivors neck is taped with Kinesio Tape (also known as KT Tape or TheraTape). 

You know the stuff, athletes wear colorful tape on their body and its supposed to reduce pain, or increase performance. Many of these claims are questionable.

In a survivor with unilateral neglect the tape would be used to provide a pull towards the affected side. The tape is stretchy, so if the survivor turns towards the "good" side, they would be reminded by the feeling of stretch to turn towards the "bad" side. This would be the approximate line of tape (and line of pull).

Clever, huh? 
Therapists are clever.

Boring stats

795,000 Americans have a stroke per year and unilateral neglect occurs in approximately 30% of individuals who experience a CVA. Left unilateral neglect is more prevalent, affecting 40-50% of left hemis.

Defined as a failure to report, respond, or orient to sensory stimuli presented to the side contralateral to the stroke lesion. Unilateral neglect (UN) is found in about 23% of stroke patients. • More common in patients with Right sided lesions (42%) than Left sided lesions (8%) and is more persistent with Right sided strokes. • Recovery of UN common; most recovery occurs in 1st 6 months and later recovery is less common. • UN associated with negative prognosis for functional outcome, poorer mobility, longer LOS in rehab, and slower rates of improvement; tend to be more functionally disabled at discharge.

This looks cool...

This blog gets a lot of attention from folks trying to sell stuff. Machines, products, services. I'm pretty selective about advocating anything where the balance between the manufacturer, book author, video producer, etc.— and the best interest of stroke survivors— does not exist. I got an email from the stroke survivor producing this video. It looks cool, and is deserving of support. 

Have a click, have a look!

Do Bleed Strokes Have a Penumbra? Nope.

 

I explain the penumbra after stroke fully here (with pictures!) and explain how important it is after stroke. 

But a question kept coming up in my clinical talks: Do hemorrhagic strokes have a penumbra?

Just some quick background:

After a block (ischemic) stroke, there is an area that the stroke kills (infarct) ("Stroked" in the image below). 

Then there's another LARGE area that, hopefully, comes back on line: The penumbra.

But what about a bleed stroke:? There is no penumbra in bleed (hemorrhagic) stroke.

There was a long debate about this, but as more experimentation was done, and as brain scanning has gotten better: Bleed stroke: No penumbra.

If you'd like a more science-y take:

The first thing to make clear is that hemorrhagic stroke is different to ischaemic stroke. In ischaemic stroke, all the fuss... is about perfusing and salvaging the penumbra of ischaemic brain tissue, surrounding the dead central tissue. This penumbra doesn’t exist around hemorrhagic tissue.

Or even nerdier!:

The most important finding of these studies is that different from ischemic strokes from proximal or distal middle cerebral artery occlusion a penumbra following the territory of arterial branches does usually not exist after intracerebral hemorrhage.

A Problem with the F.A.S.T test? Yes and no.

The FAST test (Face, Arm, Speech, Time) is used to tell if somebody is having a stroke. 

The problem is, it doesn't pick ~15% of strokes. Worldwide, that is ~2 million stroke not captured. 

The article referenced above, written in 2014, essentially adopted recommendations published in Stronger After Stroke in 2009. Here it is in a nutshell...

One thing they added, I kinda disagree with. "Leg" which involved a walking test. Which, you know, getting someone having a stroke to get up and walk may not be prudent?

Overall, it helps if everyone knows the symptoms of stroke.

In 90% of all people having a stroke, medical attention was sought by a bystander! Yay bystanders! Maybe we should call them bydoers!

Just over a third of all stroke survivors will have a another stroke within 10 years of their first stroke – a one in three chance.

Every stroke survivor knows that if they're having a stroke time is brain. The quicker you can get to the emergency room, the more options the doctors have. More options = more brain saved.

But how do you know if you're having another stroke? What if the symptoms are different than the last stroke? What if last time you had numbness and weakness in your left arm, and this time you have a blinding headache? Will you know? Will caregivers know?

The common wisdom is to use the FAST test. 

But there's a problem with the fast test. 3/4 of all "block" (ischemic) strokes have sudden weakness or numbness on one side of the body. But that same symptom drops to less than half in "bleed" (hemorrhagic) strokes. On the other hand, headache happens in 40% of bleed strokes, but less than 20% of block strokes. 

Don't get me wrong, the FAST test has been useful and effective. For instance in the UK, after the FAST TV campaign was rolled out, the time to hospital was reduced. The time from the stroke (the first symptom) to the hospital dropped by 66 minutes. That's amazing. 

Adolf "Woody" Hitler: If I had a stroke in 1937
it woulda been a good thing schlieben!

Had a stroke? Have daughters? You're in luck!

If you've had a stroke, and have daughters, you are more likely to go home than to an institution. (article here)

In fact, the more daughters you have, the more likely you are to go home!

As Sarah Silverman says: Sorry, its a boy!