By Dr Rajiv Advani

Chairs: Susanne Wegener and Annette Fromm

Hemodynamic Stroke: When the Tide Challenges the Moon

Risk Factors for Hemodynamic Stroke – Catharina JM Klijn

Prof. Klijn started the session presenting causes of hemodynamic stroke. Hypoperfusion due to systemic (blood loss) or structural (stenoses) causes occur in conjunction with embolism and local vasculopathy. These factors work together in the pathophysiological mechanism also contributing to an impaired washout of emboli. A multitude of risk factors such as carotid artery occlusion with or without cerebral microinfarcts, vertebrobasilar occlusion, precipitating factors (rising from supine position, transition from cold to warm environment, postprandial hypotension, exercise) are described. Patients can present with loss of consciousness, retinal claudication, sign of cognitive impairment, limb shaking. Limb shaking is described as a more course activity than myoclonus, that can often be mistaken for epileptic activity, but is rather a sign of hypoperfusion in the anterior circulation. Factors that can stratify a patient as high risk for a new event are continuing symptoms after a documented ICA occlusion, more leptomeningeal collaterals and hemodynamic characteristics, amongst others.

PET Imaging of the effects of Hemodynamic Carotid artery disease on brain perfusion and cell function – Jean Claude Baron

Prof. Baron presented a historical perspective on hemodynamic stroke. PET scans have been used since the late 1970s to demonstrate increased oxygen extraction fraction (OEF) in areas with reduced cerebral blood flow (CBF) and case reports were published from the early 1980s onwards. This led to the coining of the phrase ‘misery perfusion’. The use of EC-IC bypass surgery to improve vascularisation of areas effected by misery perfusion soon followed. Definitions of autoregulation and the relationship between cerebral perfusion pressure and cerebrovascular resistance were established during this era. It was also established that increased cerebral blood volume (CBV) was a marker of compromised hemodynamic reserve. The use of vasodilatory drugs such as acetazolamide were used to evaluate the cerebral vasodilatory capacity and terms such as Robin Hood Syndrome were coined. These works led to the establishment of mean transit time (MTT) – the time taken for blood to transit through the cerebral circulation. SPECT with HMPAO has been used to assess hemodynamic reserve but has largely been replaced by TCCD (breath holding test), CT and MR Perfusion. Compromised hemodynamic circulation, specifically misery perfusion, is associated with up to a six-fold increased risk of ipsilateral stroke.  The multitude of factors involved in the pathophysiology of cerebral perfusion have contributed to the negative trials conducted so far (CMOSS, COSS, EC-IC bypass trial).

Hemodynamic Imaging for treatment selection: New perspectives for EC/IC flow augmentation bypass surgery – Christian Henrik Bas van Nifrtik

Dr. van Nifrtik started by recapping the findings of the COSS study which showed no significant difference between best medical management and EC-IC bypass for patients with impaired cerebral circulation. This study however posed further questions relating to the thresholds of CBV and CBF and the sensitivity of OEF measurements in these patients. In Zurich they have implemented the use of 15O2 H2O PET imaging with acetazolamide, subtracting these values from the PET CBF prior to acetazolamide administration to assess cerebrovascular reactivity (CVR). This quantitative analysis, the BOLD CVR analysis, is more applicable in the general population (reproducible data) and can also determine CVR voxel by voxel in larger and smaller areas of the brain. A mean scan time of just under 5 minutes means than it is safer than the use of acetazolamide challenge in terms of adveres TIA/hypoxic events during examination. This technique can be used to better quantify CBV and misery perfusion while also being comparable to the assessment of leptomeningeal collaterals whilst also being very territory specific (ACA, MCA, PCA). In their study BOLD CVR values were used to evaluate the risk of recurrent stroke. BOLD CVR values of 0.1 can be potentially used to establish clinical cut-offs to select patients that can benefit from EC-IC bypass surgery.

Blood Pressure management for intracranial atherosclerotic stenosis – Colin P Derdeyn

Dr. Derdeyn presented the evidence for BP reduction and stroke risk reduction in stable and unstable ICAD patients. Using a subset of patients from the COSS study a finding that sBT > 130 mmHg was associated with a greater risk of ipsilateral stroke was seen. The VERTIAS study contradicted COSS where patients with low flow and low sBT were at higher stroke risk at sBT under 140mmHg. The SOpHIA study further backed up this finding where lower pressure ratios (PR) were at higher risk of ipsilateral stroke. SAMMPRIS didn’t not find an increased risk of border zone strokes in lower sBT. Therefore, there is a recommendation of sBT < 140 mmHg in stable ICAD. Why might lower BP be associated with an increased stroke risk? The right shift of the autoregulatory curve in impaired cerebral circulation means that pushing the sBT to under 140mmHg pushes patients into higher stroke risk by further worsening CBF. These patients are often hemodynamically symptomatic and have more unstable ICAD, also demonstratable by cerebral microinfarcts. These patients require an individualised approach where BP needs to be maintained at a level where symptoms gradually reduce/resolve. Hemodynamic impairment in the Vertebrobasilar system – Joanna Schaafsma

Dr. Schaafsma talked about the vertebrobasilar system which accounts for almost 30% of all strokes whilst also having a higher risk of recurrence compared to the anterior circulation. The posterior circulation is less well studied due to bony artifacts, the need for high resolution imaging, a greater variability in the collateral circulation and many small collaterals vessels cannot be imaged. Using infarct patterns to determine hemodynamic strokes is very challenging due the somewhat unclear border zones in the posterior circulation. There are also lower velocities in the posterior circulation vessels, and this leads to inaccurate imaging on MRI TOF. In the VERITAS study, 14% of patients had a recurrent stroke where 40% had a hemodynamic stroke and established low distal flow, but the majority were also in some way embolic/atherosclerotic. The latter confirms the interplay of factors as previously mentioned by Prof. Klijn. DSA, CT and MR perfusion, 4D MRI can be used to assess the posterior circulation but all modalities have their limitations and most likely a combined approach is required. Stroke in the posterior circulation, specially regarding endovascular treatment, is most definitely individualised medicine where patient selection poses significant challenges.