Who is currently doing some of the best research in neurology?

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Is there anyone whose papers you always want to read? I know the "best" in the subject lineis very subjective, but that's the intent. Are you a real fan of the research work coming out of the lab of one neurologist or another? Is their perhaps a neuroscientist or neuropathologist whose work you continue to find compelling and exciting?

Thanks so much! Hopefully many can benefit from some collective ideas.

Eelco F.M.Wijdicks for Clinical neurology and Karl Deisseroth for Neuroscience!!

The discovery of anti-NMDA receptor encephalitis by Dalmau is probably the biggest discovery in neurology in the last decade. People were drooling to go to his talk at the AAN this year.

Dalmau's lab does good work. However, the prevalence of anti-NMDA receptor antibody encephalitis is very low (probably, but it certainly isn't high). To call it the biggest discovery in neurology in the last decade discredits incrementally smaller discoveries in stroke, PD, AD, and MS that have a comparatively large impact on medical resource utilization and lives impacted. Things like the drug development of dabigatran in AF and oral disease-modifying therapy in MS are not very "sexy", but change disease management in a huge population.

I would say that's debatable. Previously these patients w/ anti-NMDA recepter Ab encephalitis would either die or at least be quite disabled. Now you can diagnose and completely cure most of them with immunosuppressants or teratomectomy. Most of these are young women in the prime of their lives. It's true that the numbers are probably small, but the ability to diagnose and treat these patients is tremendous. I'm not trying to discredit other advances, but I just don't see them as being huge breakthroughs. Looking back several years from now, the advances you mention probably will be bigger, but this is my view at present:

Dabigatran - no antidote, $$, GI side effects. I've prescribed it to only one patient who was allergic to coumadin. I really don't see it coming into wide spread use until it goes off patent.

Oral MS therapy - $$$$$, early clinical trials look good, but no one has much clinical experience with them. Arguments have been made that the injectable DMT's are not worth it if you look at it in terms of cost / quality adjusted life years. These oral agents are even more expensive.

That's exactly my point; they aren't big breakthroughs.

Tiny advancement x millions of people > big advancement x dozens of people

Believe me, I've managed probably 5-10 people with anti-NMDA receptor antibody encephalitis over the past 5 years or so, and it is great to help them. "Cure" is a strong word, however. Most are still not back to completely normal. But yes, it is fabulous to prevent a young woman from dying of an otherwise very treatable disease. But a 5% improvement on ICH outcomes and the resultant decrease in long term care expenditure would quite literally allow us to provide free childhood immunizations to the entire country.

I really don't want to argue with you -- I respect your opinion on Dalmau and his lab's discoveries. I'm just explaining my logic (or perhaps lack thereof).

I like Hal Blumenfeld's work at yale. He studies impaired consciousness in epilepsy, and I think that's one of the most fascinating approaches to topics like consciousness.

Anti-NMDA receptor antibody encephalitis is the biggest discovery in neurology in the last decade? I agree with Typhoon for the reasons he stated above, the impact is just too small. Grotta is doing great work with hypothermia protocols in stroke.

Yes - good points on small improvements having a huge impact when you look at it in terms of dollars and cents. It's hard to see this in the day to day of seeing and treating patients.

Guys I want your input. I hav access to data from my stroke center. This center is small and bing an IM residency program without neurology nobody is interested in touching the data. I am not crazy about neurology but I would love to gt some decent publication. Any ideas as to what i shd look at or which research questions would be interesting?

Originally Posted by ROBINHO

Guys I want your input. I hav access to data from my stroke center. This center is small and bing an IM residency program without neurology nobody is interested in touching the data. I am not crazy about neurology but I would love to gt some decent publication. Any ideas as to what i shd look at or which research questions would be interesting?

Write up an IRB protocol and send me the data (all of it) and I'll take care of it. Thanks.

You can be a middle author.

Seriously, though, I'm not giving you research questions. I feed my family through my stroke research.

Originally Posted by ROBINHO

Guys I want your input. I hav access to data from my stroke center. This center is small and bing an IM residency program without neurology nobody is interested in touching the data. I am not crazy about neurology but I would love to gt some decent publication. Any ideas as to what i shd look at or which research questions would be interesting?

Not interested in neurology but you want to do research? I think you need to do some more reading of articles to see what questions you might be able to answer with your data set. Or find a mentor to help. No one on here will spoon feed you. You are an adult now.

Lol u guys in neurology are brutal. I have substantial research experience in Cardiology. Sncerely, I am not interested in Neurology but the reason why I am looking at the data is because nobody cares for it around here because the neurology department is weak and allm the other residents find neurology boring.

What I wanted to know is what kind of research questions are considered sexyyy these days and what kind of things I shd look out for to be able to tell if its decent data. Anyway on second thoughts I dont think I would have spoon fed anybody in a forum with my cardio ideas so your reactions are natural

Originally Posted by ROBINHO

Lol u guys in neurology are brutal. I have substantial research experience in Cardiology. Sncerely, I am not interested in Neurology but the reason why I am looking at the data is because nobody cares for it around here because the neurology department is weak and allm the other residents find neurology boring.

What I wanted to know is what kind of research questions are considered sexyyy these days and what kind of things I shd look out for to be able to tell if its decent data. Anyway on second thoughts I dont think I would have spoon fed anybody in a forum with my cardio ideas so your reactions are natural

Pick up your local Stroke or NCC journal and read around. Use some pubmed. Ask questions others are not.

Originally Posted by ROBINHO

Lol u guys in neurology are brutal. I have substantial research experience in Cardiology. Sncerely, I am not interested in Neurology but the reason why I am looking at the data is because nobody cares for it around here because the neurology department is weak and allm the other residents find neurology boring.

What I wanted to know is what kind of research questions are considered sexyyy these days and what kind of things I shd look out for to be able to tell if its decent data. Anyway on second thoughts I dont think I would have spoon fed anybody in a forum with my cardio ideas so your reactions are natural

Well, a less-than-enthusiastic post begets a less-than-enthusiastic response among people who actually care about Neurology and you consider that "brutal"?

There are many potential avenues in stroke research, but it depends on what kind of data you have and the number and type of patients. What I would ask myself is: is there something unique about my patient population that could contribute something unique to our knowledge?

My advice would be that if you are really interested, why not pick up a copy of the journal Stroke or other relevant journal and see what types of articles/topics they are publishing these days?

Originally Posted by alamo4

Is there anyone whose papers you always want to read? I know the "best" in the subject lineis very subjective, but that's the intent. Are you a real fan of the research work coming out of the lab of one neurologist or another? Is their perhaps a neuroscientist or neuropathologist whose work you continue to find compelling and exciting?

Thanks so much! Hopefully many can benefit from some collective ideas.

Pretty much gone are the days (did they actually exist?) when there is a single monolithic lab doing work in a field. Many of the big advances these days are done by collaborative groups, particularly for clinical trials and other clinical research, but also in basic science. The pace of science is so rapid, the technology advancing so quickly, and the bar for publication in the best journals raising so fast, that it is almost impossible for a single monolithic lab to get published. Collaborative science is where it is at, with different groups pooling their strengths, i.e. molecular biology, cellular neurophysiology, tissue analysis, behavioral studies to produce high-quality work.

If you are solely interested in reading about "sexy" neuroscience topics or "being a fan" of neuroscience, just pick up a copy of Nature, Science, Cell, Nature Neuroscience, Neuron, etc. However, if your goal is to get into Neuroscience and do high-quality laboratory work, there are usually several good labs in any given area, a group of the "top" experts in a sub-field. Some do flashy science, which may sell journal subscriptions and help some careers, but much more important is the quality of scientist you become. That is much more dependent on how good a mentor that person actually is.

just a correction of my last statement(in my last post).
What I meant to say that on second thought....I think I wont have given anybody free ideas on cardiology research in a forum...so I understand your reaction.

Anyway today I was given access to the data and gleamed over the data set. Only 700 patients( doesnt look big to me...but again I dont know what to xpect from a small community stroke center).

Anyway pointing me to the journals to read was helpful

Originally Posted by ROBINHO

just a correction of my last statement(in my last post).
What I meant to say that on second thought....I think I wont have given anybody free ideas on cardiology research in a forum...so I understand your reaction.

Anyway today I was given access to the data and gleamed over the data set. Only 700 patients( doesnt look big to me...but again I dont know what to xpect from a small community stroke center).

Anyway pointing me to the journals to read was helpful

700 stroke cases could be quite useful as a replication or extension dataset for numerous things. Do you have outcome data? That would make your dataset even more useful to groups looking to validate outcome scores or the like. Neuroimaging data? Stroke volumes on DWI, CTAs for cutoffs, perfusion imaging would all be very useful. Drug exposures, like statins, warfarin, antithrombotics could all be valuable.

As previous posters so astutely point out, unless you have a huge research apparatus (and even then) enrolling thousands of patients, we all have to pool our data to reach the ever higher fruits of retrospective observational research. You can't just write a paper in a small cohort showing that statin exposure improves stroke outcomes anymore, because we've already done that. You also don't have institutional controls (it sounds like). If you're really interested in moving forward, I would reach out to the stroke group at the nearest big academic center, and let them know what you have and whether they'd like to collaborate. Once the IRB hurdles are cleared, your 700 subjects could easily make a substantial contribution to a meta-analysis or something, and you could get a nice co-authorship for your willingness to share. That said, I'm sure many other people did a lot of work to enroll and catalog those 700 patients, and they would need to approve and be recognized as well.

I rarely write a paper with fewer than 20 named co-authors anymore. It can be tough for some of the old-school PhD folks to understand, but amassing these datasets takes a village. Rarely does a Nature article get written off the sweat of a couple authors' brows anymore.

Originally Posted by ROBINHO

just a correction of my last statement(in my last post).
What I meant to say that on second thought....I think I wont have given anybody free ideas on cardiology research in a forum...so I understand your reaction.

Anyway today I was given access to the data and gleamed over the data set. Only 700 patients( doesnt look big to me...but again I dont know what to xpect from a small community stroke center).

Anyway pointing me to the journals to read was helpful

I know you won't be able to answer this with your current data but if you designed a study looking at the genetic component of ischemic strokes and which genotype might be at a greater risk for hemorrhagic conversion. Turn that into a bedside test and then you might know which patients you would need to be more aggressive with. Now that would be interesting.

Name one genetic test you can get back within a week.

Originally Posted by bblue

Name one genetic test you can get back within a week.

I think that was their point. The purpose of science and research is to improve on things, no?

Yes but you should have realistic goals for your research.

Originally Posted by bblue

Yes but you should have realistic goals for your research.

You're right, we should only do research on things that have immediate bedside applications. Nothing else is "realistic". I'll go draft my resignation letter now, and I'll forward your post to Francis Collins.

are there NCC folks doing basic science bench type research and what kind of topics are they looking into? Just trying to get a feel for what NCC physician scientists are doing these days.

Originally Posted by daptomycin

are there NCC folks doing basic science bench type research and what kind of topics are they looking into? Just trying to get a feel for what NCC physician scientists are doing these days.

Yes. Several people in our group are doing bench work, including animal models, tissue culture, genetic analysis (rare and common variant), biomarkers, statistical modeling, LCMS, NIRS, etc.

Topics can include things like delayed cerebral injury after SAH, ICH pathogenesis, modifiers of BBB degradation after ischemia and trauma, malignant cerebral edema after stroke, and stuff like that.

Originally Posted by daptomycin

are there NCC folks doing basic science bench type research and what kind of topics are they looking into? Just trying to get a feel for what NCC physician scientists are doing these days.

Sure there are quite a few.

Greg Zipfel @ WashU- role of ApoE4 and MMP-9 in cerebral vasospasm following SAH in mice.

Agnieszka Ardelt @UChicago- role of estradiol on neuroprotection/repair after ischemic stroke as well as angiogenesis in ischemic strokes.

There are others, but those are the two that came to mind.

Originally Posted by bblue

Yes but you should have realistic goals for your research.

Come again? Not sure what part of my hypothetical study couldn't be done? If anything, there are groups already looking at the genetic component of strokes. Labs like Rosand's @ MGH. Obviously not the exact same question I posed, but I wouldn't be surprised if someone was working on something similar to that.

Originally Posted by bblue

Yes but you should have realistic goals for your research.

I don't get the point of your statement to be honest. If it was straightforward and easy it would have been done already. Don't go along the route of Bill Gates and think 640k of RAM iis enough too!

Originally Posted by ROBINHO

Guys I want your input. I hav access to data from my stroke center. This center is small and bing an IM residency program without neurology nobody is interested in touching the data. I am not crazy about neurology but I would love to gt some decent publication. Any ideas as to what i shd look at or which research questions would be interesting?

The funnest part is coming up with the research question & design! Having the freedom to design your own project is awesome... take advantage.

"I want stroke to go away, I'll design a completely unrealistic model based on theories that aren't even fully proven and expand on them with years of trials. Yaay!"
I've done research, I've designed research, and I've had it be successful and not so successful. The project that got me submitted to the International Stroke Conference as a PGY2 expanded on a currently proven theory with bench research, and is now ready to be translated into clinical trials. I stand by my comment that you should be realistic in your research. Because stroke research is currently looking at acute treatments, I think it's ridiculous to try to design a genetic test at bedside, when implementation of this would be nearly impossible in the acute setting. Yes, theoretically it could be done, but we can also theoretically implant little radar guns inside people's carotid arteries and shoot out plaques like Space Invaders.

PS I'm cutting funding to all of the above projects

Originally Posted by bblue

"I want stroke to go away, I'll design a completely unrealistic model based on theories that aren't even fully proven and expand on them with years of trials. Yaay!"
I've done research, I've designed research, and I've had it be successful and not so successful. The project that got me submitted to the International Stroke Conference as a PGY2 expanded on a currently proven theory with bench research, and is now ready to be translated into clinical trials. I stand by my comment that you should be realistic in your research. Because stroke research is currently looking at acute treatments, I think it's ridiculous to try to design a genetic test at bedside, when implementation of this would be nearly impossible in the acute setting. Yes, theoretically it could be done, but we can also theoretically implant little radar guns inside people's carotid arteries and shoot out plaques like Space Invaders.

PS I'm cutting funding to all of the above projects

Why is performing research that could eventually lead to a bedside test unrealistic? Genotypic markers are used in oncology to direct treatment all the time. Speed is not a particularly difficult hurdle to overcome, if clinical decision-making could be substantially improved.

1. We are developing ways to increase the availability and utility of genetic testing data at the bedside, and by "we" I mean me and people like me. This is something I actually know quite a bit about, and while we aren't there yet, we aren't going to get any closer by sitting around.

2. Searching for genetic variants associated with ischemic and hemorrhagic stroke endophenotypes is not only useful from a genetic standpoint, but also can help to identify new pathways that inform us about the underlying biology of these diseases. These searches can take the form of hypothesis-informed or completely agnostic strategies such as GWAS or exome/whole genome sequencing.

3. If you are up on the recent RFAs from NINDS, which it is my job to be, you may find that "acute stroke treatment" is not the only big push that Drs. Landis and Koroshetz are interested in fostering. Recovery and outcome is a big deal, with enormous associated healtcare costs, and genetic association testing has great potential in advancing the search for both novel therapeutic agents as well as valuable prognostic information for physicians and families.

I would humbly suggest that perhaps a more open-minded approach to cerebrovascular research might be valuable. Just because a project's goals aren't in line with your own does not mean that a) the project is not tractable or useful, or b) that it won't merit a higher priority score than yours. But congrats on going to ISC.

Originally Posted by typhoonegator

Why is performing research that could eventually lead to a bedside test unrealistic? Genotypic markers are used in oncology to direct treatment all the time. Speed is not a particularly difficult hurdle to overcome, if clinical decision-making could be substantially improved.

1. We are developing ways to increase the availability and utility of genetic testing data at the bedside, and by "we" I mean me and people like me. This is something I actually know quite a bit about, and while we aren't there yet, we aren't going to get any closer by sitting around.

2. Searching for genetic variants associated with ischemic and hemorrhagic stroke endophenotypes is not only useful from a genetic standpoint, but also can help to identify new pathways that inform us about the underlying biology of these diseases. These searches can take the form of hypothesis-informed or completely agnostic strategies such as GWAS or exome/whole genome sequencing.

3. If you are up on the recent RFAs from NINDS, which it is my job to be, you may find that "acute stroke treatment" is not the only big push that Drs. Landis and Koroshetz are interested in fostering. Recovery and outcome is a big deal, with enormous associated healtcare costs, and genetic association testing has great potential in advancing the search for both novel therapeutic agents as well as valuable prognostic information for physicians and families.

I would humbly suggest that perhaps a more open-minded approach to cerebrovascular research might be valuable. Just because a project's goals aren't in line with your own does not mean that a) the project is not tractable or useful, or b) that it won't merit a higher priority score than yours. But congrats on going to ISC.

Ditto.

In addition, some single nucleotide polymorphisms can alter levels of expression of certain substances which can have an outcome on prognosis/recovery. Therefore a genetic test could help (where the blood levels are not reliable indicators) to alter choice of type or dose of pharmacological therapy to improve outcome.

There is no harm in looking far in the future, but it could be closer than one thinks!

Originally Posted by typhoonegator

Why is performing research that could eventually lead to a bedside test unrealistic? Genotypic markers are used in oncology to direct treatment all the time. Speed is not a particularly difficult hurdle to overcome, if clinical decision-making could be substantially improved.

1. We are developing ways to increase the availability and utility of genetic testing data at the bedside, and by "we" I mean me and people like me. This is something I actually know quite a bit about, and while we aren't there yet, we aren't going to get any closer by sitting around.

2. Searching for genetic variants associated with ischemic and hemorrhagic stroke endophenotypes is not only useful from a genetic standpoint, but also can help to identify new pathways that inform us about the underlying biology of these diseases. These searches can take the form of hypothesis-informed or completely agnostic strategies such as GWAS or exome/whole genome sequencing.

3. If you are up on the recent RFAs from NINDS, which it is my job to be, you may find that "acute stroke treatment" is not the only big push that Drs. Landis and Koroshetz are interested in fostering. Recovery and outcome is a big deal, with enormous associated healtcare costs, and genetic association testing has great potential in advancing the search for both novel therapeutic agents as well as valuable prognostic information for physicians and families.

I would humbly suggest that perhaps a more open-minded approach to cerebrovascular research might be valuable. Just because a project's goals aren't in line with your own does not mean that a) the project is not tractable or useful, or b) that it won't merit a higher priority score than yours. But congrats on going to ISC.

As always, typhoonegator, well stated and straight to the point. I agree with everything you wrote.

Originally Posted by bblue

"I want stroke to go away, I'll design a completely unrealistic model based on theories that aren't even fully proven and expand on them with years of trials. Yaay!"
I've done research, I've designed research, and I've had it be successful and not so successful. The project that got me submitted to the International Stroke Conference as a PGY2 expanded on a currently proven theory with bench research, and is now ready to be translated into clinical trials. I stand by my comment that you should be realistic in your research. Because stroke research is currently looking at acute treatments, I think it's ridiculous to try to design a genetic test at bedside, when implementation of this would be nearly impossible in the acute setting. Yes, theoretically it could be done, but we can also theoretically implant little radar guns inside people's carotid arteries and shoot out plaques like Space Invaders.

PS I'm cutting funding to all of the above projects

If you don't think the research is worthwhile, then I guess you won't have to worry about it receiving funding or being published. Oh wait, there are already groups working on this subject. As with most things in life, more humility goes a long way. Whether you don't agree with the research or don't think it is worthwhile, you should at least appreciate the purpose of asking these questions. I for one am excited for what genetics will be contributing to these questions and am all for them exploring what they might be able to contribute to our diagnostic, treatment or prevention of theses diseases. If you don't think this topic is worthwhile, why not send a letter or email to Dr. Francis S. Collins?

I think a certain degree of hubris is needed to call this research junk or rubbish at this point unless of course one knew everything there was to know about genetics and neuro.

Originally Posted by bblue

"I want stroke to go away, I'll design a completely unrealistic model based on theories that aren't even fully proven and expand on them with years of trials. Yaay!"

I don't see anyone talking about designing a completely unrealistic model of strokes to make them go away? Not sure what you are referring to. One thing I have learned, if you want to be a 3rd or 4th author on some abstract you follow the status quo. If you want to make some ground breaking conclusions and do real research, you have to think outside the box and do something that others aren't doing yet. You don't get famous for following after others and repeating their same experiments.

Originally Posted by bblue

I stand by my comment that you should be realistic in your research. Because stroke research is currently looking at acute treatments, I think it's ridiculous to try to design a genetic test at bedside, when implementation of this would be nearly impossible in the acute setting.

So every person doing stroke research needs to look at acute treatments? I sure hope you aren't saying prevention isn't important.

Why do you think a genetic test at bedside is so ridiculous? I think it is a great idea. Point of care genetic testing is the future whether or not some want to believe so. There was a recently published article this year in lancet regarding point of care genetic testing http://www.ncbi.nlm.nih.gov/pubmed/22464343 They were able to predict complications post cardiac stenting. Don't see why something similar couldn't be done in strokes.

Oh yes, the Lancet study. The exact research study I was thinking of and the same machine (Spartan RX PCR machine). Can get results in <10min. Bblue, I appreciate your interests but unfortunately your opinion wont change my stance.

Whoa whoa sorry lol! I'm honestly just playing devil's advocate. Everyone who knows me on here knows I'm usually very supportive. But I do stand by my statement that bedside genetic markers for use in acute stroke would be very difficult, and as of yet, noone still has mentioned a genetic test you can get back from Athena or wherever in less than a week, nevermind within a 3 or 4.5 hour time window. I do understand the importance of genetic biomarkers though, UCSD has been doing great work on it for awhile as are the other places mentioned above.

BTW, how come noone countered that there actually are stroke projects that essentially try to shoot plaques like Space Invaders!? I was hoping that would get more of a response. It's the whole idea behind 2MHz US in clot lysis, which is extremely effective (but dangerous).

Originally Posted by bblue

But I do stand by my statement that bedside genetic markers for use in acute stroke would be very difficult, and as of yet, noone still has mentioned a genetic test you can get back from Athena or wherever in less than a week, nevermind within a 3 or 4.5 hour time window.

Who says you need to use Athena when you have the ability to test @ point of care. No need to have a send out when you can do it basically at bed side in 5-10 minutes. Not sure why you are hung up on the limitations of having a lab send out?

I've just never been at an institution with bedside genetic tests...