Auto-immune antibodies and their relevance for stroke patients – a new paper in Stroke

KMfor CVD+mortatily after stroke, stratified to serostatus for the anti-NMDA-R auto-antibody. taken from (doi: 10.1161/STROKEAHA.119.026100)

We recently published one of our projects embedded within the PROSCIS study. This follow-up study that includes 600+ men and women with acute stroke forms the basis of many active projects in the team (1 published, many coming up).

For this paper, PhD candidate PS measured auto-antibodies to the NMDAR receptor. Previous studies suggest that having these antibodies might be a marker, or even induce a kind of neuroprotective effect. That is not what we found: we showed that seropositive patients, especially those with the highest titers have a 3-3.5 fold increase in the risk of having a worse outcome, as well as almost 2-fold increased risk of CVD and death following the initial stroke.

Interesting findings, but some elements in our design do not allow us to draw very strong conclusions. One of them is the uncertainty of the seropositivity status of the patient over time. Are the antibodies actually induced over time? Are they transient? PS has come up with a solid plan to answer some of these questions, which includes measuring the antibodies at multiple time points just after stroke. Now, in PROSCIS we only have one blood sample, so we need to use biosamples from other studies that were designed with multiple blood draws. The team of AM was equally interested in the topic, so we teamed up. I am looking forward to follow-up on the questions that our own research brings up!

The effort was led by PS and most praise should go to her. The paper is published in Stroke, can be found online via pubmed, or via my Mendeley profile (doi: 10.1161/STROKEAHA.119.026100)

Starting a research group: some thoughts for a new paper

isth-logo

It has been 18 months since I started in Berlin to start at the CSB to take over the lead of the clinical epidemiology research group. Recently, the ISTH early career taskforce  have contacted me whether I would be willing to write something about my experiences over the last 18 months as a rookie group leader. The idea is that these experiences, combined with a couple of other papers on similar useful topics for early career researchers, will be published in JTH.

I was a bit reluctant at first, as I believe that how people handle new situations that one encounters as a new group leader is quite dependent on personality and the individual circumstances. But then again, the new situations that i encountered might be more generalizable to other people. So I decided to go ahead and focus more on the description of the new situations I found myself in while trying to keep the personal experiences limited and only for illustrations only.

While writing, I have discerned that there are basically 4 new things about my new situations that I would have loved to realise a bit earlier.

  1. A new research group is never without context; get to know the academic landscape of your research group as this is where you find people for new collaboration etc
  2. You either start a new research group from scratch, or your inherit a research group; be aware that both have very different consequences and require different approaches.
  3. Try to find training and mentoring to help you cope with your new roles that group leaders have; it is not only the role of group leader that you need to get adjusted to. HR manager, accountant, mentor, researcher, project initiator, project manager, consultant are just a couple of roles that I also need to fulfill on a regular basis.
  4. New projects; it is tempting to put all your power, attention time and money behind a project. but sometimes new projects fail. Perhaps start a couple of small side projects as a contingency?

As said, the stuff I describe in the paper might be very specific for my situation and as such not likely to be applicable for everyone. Nonetheless, I hope that reading the paper might help other young researchers to help them prepare for the transition from post-doc to group leader. I will report back when the paper is finished and available online.

 

A year in Berlin

teamfoto-ag-siegerink

So, it is just over a year since I started here in Berlin. In this year I had the opportunity to start some great projects. Some of these projects have already resulted in some handsome -upcoming- publications.

For those who wonder, the picture gives a somewhat inflated impression of the size of the team, as we decided to include all people who currently work with us. This includes two of our five students and 2 virchow scholars that are visiting from Amsterdam and Hamburg. I included them all in the picture, as I enjoy my work here in Berlin because of all team members. Now, let’s do some science!

Spectrum of cerebral spinal fluid findings in patients with posterior reversible encephalopathy syndrome

source: http://www.springer.com

This is one of the first projects that I was involved with from start to finish since my start in Berlin to be published, so I’m quite content with it. A cool landmark after a year in Berlin.

Together with TL and LN I supervised a student from the Netherlands (JH). This publication is the result of all the work JH did, together with the great medical knowledge from the rest of the team. About the research: Posterior reversible encephalopathy syndrome, or PRES, is a syndrome that can have stroke like symptoms, but in fact has got nothing to do with it. The syndrome was recognised as a separate entity only a couple of years ago, and this group of patients that we collected from the Charite is one of the largest collections in the world.

It is a syndrome characterised by edema (being either vasogenic or cytotoxic), suggesting there is something wrong with the fluid balance in the brain. A good way to learn more about the fluids in the brain is to take a look at the different things you can measure in the cerebrospinal fluid. The aim of this paper was therefore to see to what extend the edema, but also other patients characteristics, was associated with CSF parameters.

Our main conclusion is indeed the total amount of protein in the CSF is elevated in most PRES patients, and that severe edema grade was associated with more CSF. Remind yourself that this is basically a case series (with some follow up) but CSF is therefore measured during diagnosis and only in a selection of the patients. Selection bias is therefore likely to be affecting our results as well as the possibility of reverse causation. Next to that, research into “syndromes” is always complicated as they are a man-made concept. This problem we also encountered in the RATIO analyses about the antiphospholipid syndrome (Urbanus, Lancet Neurol 2009): a real syndrome diagnosis could not be given, as that requires two blood draws with 3 months time in between which is not possible in this case-control study. But still, there is a whole lot of stuff to learn about the syndromes in our clinical research projects.

I think this is also true for the PRES study: I think that our results show that it is justified to do a prospective and rigorous and standardised analyses of these patients with the dangerous syndrome. More knowledge on the causes and consequences is needed!

The paper can be cited as:

Neeb L, Hoekstra J, Endres M, Siegerink B, Siebert E, Liman TG. Spectrum of cerebral spinal fluid findings in patients with posterior reversible encephalopathy syndrome. J Neurol; 2015; (e-pub) and can be found on pubmed or on my mendeley profile

Moving to Berlin!

After about 8 years learning and working in Leiden at the LUMC, it is time for something new. I’ve got a new job as the head of the ‘Clinical Epidemiology and Health Services Research in Stroke’ unit at the Center for Stroke research in Berlin (CSB, http://www.schlaganfallcentrum.de). This a very exciting opportunity for me: working with new colleagues on new projects, learning more about stroke research and strengthen the epidemiological studies that are executed at the CSB. I am looking forward to work with these brilliant and creative minds especially the guys from the CEHRIS team.

With moving to Berlin I will have to leave Leiden, which do regret. Not only because of the great research, but also because of the students and co-workers. Fortunately, I think that this new chapter in my academic life will provide ample opportunity to start new collaborations between Berlin and Leiden.