Spontaneous cerebellar intracerebral haemorrhage: treatment and long-term outcome

This Ph.D. thesis, ‘Spontaneous cerebellar intracerebral haemorrhage: treatment and long-term outcome’, described clinical research on associations between haematoma evacuation and outcome in patients with spontaneous cerebellar ICH. It also includes studies which assessed the long-term outcome after a first cerebellar ICH, including ICH recurrence, ischaemic stroke, myocardial infarction and major vascular surgery. In the extensive systematic review as presented in Chapter 1, we demonstrated that the available evidence was highly heterogeneous. Therefore, we were unable to make any valid comparisons between treatment strategies and refrained from analysing the optimum timing of surgery (as no such data was available). The cohort studies which were available were retrospective, described a small number of patients (most often <100 patients per study) and had high risk of bias and confounding by indication. We concluded that based on the available literature and the methodological limitations of this evidence, there was insufficient data to make any recommendations about when and for whom haematoma evacuation in cerebellar ICH patients would be beneficial. In addition, we have provided novel evidence that there may be a subgroup of patients for which conservative treatment, rather than neurosurgical interventions, is indicated (Chapter 2). This observation does not align with the current AHA recommendations, which state that all patients with a cerebellar hematoma diameter larger than 3cm should be treated with immediate hematoma evacuation. In two large Dutch university medical centers, we found that a large proportion of patients with a cerebellar ICH diameter >3cm were treated conservatively. As approximately two third of the patients with a cerebellar haematoma diameter >3cm treated conservatively was alive at three months, and half of them have a good functional outcome, this seemed a reasonable alternative to immediate haematoma evacuation. We also emphasized that clinical condition, in addition to the diameter of the ICH, predicted outcome in cerebellar ICH. Furthermore, this Ph.D. thesis demonstrated the first-ever evidence on the positive and statistically significant associations between the CTA spot sign with speed of hematoma expansion and mortality in patients with spontaneous cerebellar ICH (Chapter 3). Lastly, we have established an international, multicenter collaboration for patients with cerebellar ICH, consisting of 8 university medical centers across Europe, the United Kingdom and United States of America (Chapter 4). This international collaboration has assembled the largest sample-size to date of patients with spontaneous cerebellar ICH. In this study, the case fatality of patients with a first cerebellar ICH who were alive at discharge from the hospital was 20% at 1-year post-stroke. This cohort study stressed the need for evidence-based secondary prevention measures after both cerebellar ICH and supratentorial ICH. It could also assist physicians and policy makers in formulating such clinical guidelines. In conclusion, this Ph.D. thesis has created the largest sample size of patients with spontaneous cerebellar ICH. The studies described in this thesis have identified an important lack in the literature of high-quality evidence on whom, how and when to treat patients with cerebellar ICH (Chapter 1). By performing multiple high-quality investigations (Chapters 2-4), we have laid the groundwork for a future randomized controlled trial on the treatment of patient with spontaneous cerebellar ICH. An in-depth protocol for such a clinical trial has been proposed in the general discussion of this Ph.D. thesis (Chapter 5). Ultimately, randomized evidence is pressingly warranted to formulate evidence-based international treatment guidelines for cerebellar ICH