A conversation with Turgut Tatlisumak, MD, PhD, from the Department of Clinical Neuroscience and Neurology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
Interviewed by Shashank Shekhar (@ArtofStroke), MD, MS, Assistant Professor, Division of Vascular Neurology, University of Mississippi Medical Center.
They will be discussing the article “Nontraumatic intracerebral haemorrhage in young adults,” published in Nature Reviews Neurology.
Dr. Shekhar: First, I would like to thank Prof. Tatlisumak for agreeing to do this interview. This is an interesting review paper in which you have discussed in detail nontraumatic intracerebral hemorrhage (ICH) in young adults. Could you tell the readers why you decided to write about hemorrhage in young adults?
Prof. Tatlisumak: We have long been investigating stroke in young adults, but most of our attention went to ischemic strokes. I wished to extend our research to ICH in young adults and found only few original patient series. Sometime later, I noticed that there is not a single review on this topic, and there is an unmet need. Then we set up a small group of experts sharing the tasks. That is how we started.
Dr. Shekhar: In the section risk factors, you have briefly but comprehensively mentioned the genetic risk factors associated with ICH.
- Could you mention why it is important to study the genetic association of the disease?
- Could you also provide some details about the genetic consortiums, e.g., BEAST consortium, that you have discussed briefly?
Prof. Tatlisumak: A number of conditions that lead to ICH are genetical diseases, but their frequency among all ICH patients is not large. However, there is good evidence that genetics play a larger role than we currently can detect. Young patients are generally more likely having a genetic factor or factors that increase their risk for bleeding. It may be a Mendelian condition or, in a larger number of cases, likely several loci that each increases the risk only slightly. I think there are specific genetical ICH diseases we do not yet know. BEAST consortium is a large international network collecting phenotypic and genotypic data on cerebral venous thrombosis patients and aims at deciphering genetical backgrounds of this disease. Approximately half of CVT patients harbor one or more bleedings, therefore related to ICH genetics. We are close to achieving enough power with this study. The larger effort is under the umbrella of the International Stroke Genetics Consortium, where numerous centers including ours are collecting data on ICH patients. Again, my priority is looking into younger patients and comparing with adequate controls.
Dr. Shekhar: The paper talks about the classification system SMASH-U. Could you talk briefly about this classification? Do you think developing such a classification system is important?
Prof. Tatlisumak: We have several classifications for ischemic stroke, but there was literally none for ICH. That is why we decided to develop one. It turned out to be difficult because there are several uncertainties stemming from ground definitions, such as whether intracranial tumor bleeding is a stroke or not. When is hypertension a risk factor, and when is it the cause? SMASH-U is an etiological classification developed on an over 1000 consecutive ICH patient dataset. Each letter stands for one large group: S for structural, M for medication, A for amyloid angiopathy, S for systemic diseases, H for hypertension, and lastly U for undetermined. SMASH-U has not yet been studied in a young ICH patient population. In general, we can expect few amyloid angiopathy patients and lesser medication-related hemorrhages because of rare use of anticoagulation at this age group. However, structural causes were common, and hypertension was not uncommon. SMASH-U is also quick and easy to do, there is good interrater agreement, and lastly it has good prognostic value. However, it must be tested in young patients before utilizing it widely in the young. Absolutely important to have a reliable classification, it forces us to systematic thinking for finding out the risk factors and causes. ICH diagnosis alone is not sufficient.
Dr. Shekhar: As neurologists, we rely heavily on neuroimaging. In a situation in which advanced imaging modality is not available, what would you recommend to a neurologist or a clinician who is practicing in remote locations who has only access to CT scan?
Prof. Tatlisumak: CT is a strong imaging modality when combined with contrast agent. If MRI is not available, CT, contrast-enhanced CT, and CT angiography together can answer many questions. We suggest non-invasive angiography even in deep hemispheric bleedings. One should not be too quick to decide that a deep locating ICH is equal to hypertensive ICH. Even if imaging is otherwise inconclusive regarding a pathological finding other than presence of deep ICH, one must really look for high blood pressure measurements, EKG signs of left ventricle hypertrophy, and, if necessary, perform a 24 h home blood pressure measurement before labeling an ICH as hypertensive.
Dr. Shekhar: You have an excellent diagnostic algorithm protocol for ICH (Figure 1). Could you go through it?
Prof. Tatlisumak: The credits for the algorithm should go to Prof. Brett Cucchiara. Nevertheless, the idea is to have a stepwise diagnostic approach offering either next investigation or the final diagnosis for every single patient until all are done. One important point is not to over- or underuse invasive procedures (here, digital subtraction angiography). In general, I think we are too conservative with it. We do not have strong data on its risks in a young adult patient population. Our algorithm starts with a stat CT scan, as it is widely available in emergency rooms and most ICH patients arrive as acute patients. CT showing ICH ignites promptly CT angiography that is same scanner and same session. If diagnosis is not reached, MRI is the next step. We always need to remember that having high technology available cannot replace a good patient history and decent clinical examination.
Dr. Shekhar: What is your opinion on aggressive blood pressure management in young adults with ICH in the acute setting? What blood pressure goals would be helpful for secondary stroke prevention?
Prof. Tatlisumak: In the lack of evidence-based data in the young, but taking into account that younger patients would likely stand lower blood pressures better than older patients with more comorbidities, atherosclerotic stenosis, and else, I think the target acute blood pressures in large randomized trials may well be applied to most young adults with ICH. There may be specific subgroups in which we do not have a good sense, such as moyamoya vasculopathy patients, but the major mechanism of bleeding is not hypertensive damage there.
Dr. Shekhar: ICH is marred by poor clinical outcome compared to ischemic stroke. Why is that? Are there any clinical trials looking at decompressive craniotomy in ICH patients?
Prof. Tatlisumak: It is similar for all age groups and not only for young adults that ICH has a more severe clinical picture or poorer prognosis. The mechanisms are very different, including an additional volume within the cranium and the strong edema effect of blood (thrombin) products in the vicinity of the hematoma. There is one ongoing multicenter randomized controlled trial in Europe (SWITCH) that is 1:1 randomizing young and middle-aged patients with mid-size ICH within 3 days either to best conservative treatment or best conservative treatment and decompressive craniectomy. It is in progress.
Dr. Shekhar: What recommendations do you have for the new breed of the clinical or non-clinical researchers in improving the management of ICH patients?
Prof. Tatlisumak: We need to build large networks of researchers, set up a list of burning issues in the field, and work on the most important ones. We are still lacking the very first effective treatment if we do not count stroke unit care. I anticipate we are not far from coming up with an effective treatment in the foreseeable future.
Disclosure: Dr. Shekhar had previously worked with Prof. Tatlisumak on different projects, but he does not have any conflict of interest with the current article.