Session Report: Covert cerebrovascular disease

Prof. Joanna Wardlaw and Dr. Markus Kneihsl chaired this session regarding an often overlooked topic in cerebrovascular disease. Overall, the session has been rich of delivered contents with a lot of interaction and questions from the floor.

Silja Raty, Finland

“Patients with Covert brain infarcts-which diagnostic workup is needed?”

The first talk tackled the diagnostic workup in patients with covert brain infarcts (CBI), a frequent occurrence in clinical practice. A wide investigation in a basically asymptomatic patient may be time and resource consuming, on the other hand, there is a non-trascurable risk of subsequent stroke in such population. Currently, two guidelines (American Heart Association and European Stroke Association) have been published and provide hints on how to manage the diagnostic workup. First of all, is important to know whether infarction was really symptomatic (few or underrated symptoms from the patient), so the clinical history is fundamental to move the next steps. Besides, implementation of primary prevention strategies is mandatory, particularly hypertension, glucose and lipid control. This is particularly relevant since most CBI are caused by small vessel disease. Moreover, CBI have been associated with intracranial artery stenosis, so it may be worth to investigate the vascular status with extra and intracranial vessel study. Radiologist and clinicians should also strive to identify the phenotype of CBI (embolic vs non embolic), since this may predict the subsequent risk of hemispheric stroke. This is why the vascular surgery guideline suggest to consider endarterectomy in patients with carotid stenosis and CBI ipsilateral to the stenosis. Finally, CBI are associated also with AF, thus cardiac investigations such as heart rate monitoring and echocardiography are recommended. Regarding PFO, there are data that show no clear association with CBI. Ongoing studies may provide valuable insights on this topic, so far, further investigations should performed on individual basis.

Aristeidis Katsanos, Canada

“Does the pattern of covert brain infarcts indicate etiology and influence prognosis?”

Suabanalysis of randomized controlled studies or observational studies may provide meaningful data to answer to this question. Data from the Northern Manhattan Study (NOMAS) show that 18% of people enrolled had at least one CBI. Intracranial artery stenosis may be causative, so it should be promptly investigated. We also know that phenotype of CBI may provide valuable hints on their etiology: AF caused CBI are different from those caused by atherosclerosis, as showed by dedicated studies (Swiss-AF, COMPASS MIND). Furthermore, small vessel disease features such as lacunar infarcts seem ot have a different distribution between AF and atherosclerosis: while AF is associated either with absence of lacunar infarcts or presence of multiple lacunes; atherosclerosis is usually associated with presence of a single lacunar infarct. In the COMPASS study, incident CBIs were mostly cortical, and around a third located in the cerebellum. PACIFIC-Stroke also performed a suba-analysis regarding incident CBI and found no clear relationship between the location of CBI when etiology of stroke was considered. However, cortical CBI were more prevalent in AF, while chronic cavitated lesions more prevalent in atherosclerosis and small vessel disease. Finally, in patients with ischemic stroke, the burden of pre-existing CBI is associated with increased stroke severity, mainly in the basal ganglia. In conclusion, some phenotypical imaging characteristics of CBI may guide etiological investigations.

Maria Hernandez Perez, Spain

“Silent” periinterventional brain infarcts: do they matter?

Silent periinterventional infarcts may be a complication of every surgical intervention, this is relevant given the high number of patients who undergo surgery every year. Actually, there is an overall risk of increase of around 33%. MRI with diffusion sequences is the reference standard for diagnosis, since it can detect recent infarct and provide a temporal link with surgery. Such infarcts are usually very small (around 0.2 ml of volume) and do have clinical consequences such as cognitive impairment and postoperative delirium. From observational data there is evidence that higher small vessel disease burden associated with higher risk of having a periinterventional brain infarct. Moving to carotid surgery, it is well established that in carotid surgery or stenting there is a three-fold increased risk increased risk of perioperative infarct. In patients with aneurysm coiling CBIs are frequent (67%), and the risk of severe stroke, disability, and cognitive impairment is related to the number of perioperative infarcts, therefore careful selection of patients eligible for treatment is needed. There is a lack of evidence regarding the long-term impact of periinterventional brain infarcts. In conclusion, it is likely that procedural, operator and patient factor may contribute to periinterventional infarcts, which are frequent and virtually present in every type of surgery. More studies are needed to understand mechanisms and consequences of this type of brain infarct.

Markus Kneihsl, Austria

Atrial fibrillation and covert brain infarcts

CBI is the most frequent incidental finding in clinical practice for a stroke physician. CBI in people with stroke/TIA and CBI in people without TIA/stroke should be likely managed in a different way. Subanalysis of ELAN trial provided valuable information regarding the first group. For example, people with covert brain infarcts may benefit from early anticoagulation since it seems the risk of recurrence is increased with the late anticoagulation. Additionally, the phenotype of CBI has also an impact, since non-lacunar CBIs seem to have a higher risk of stroke recurrence and may benefit of early anticoagulation, while such risk does not seem higher CBIs of non-embolic origin. Cerebellar lesions: some insights come from studies of microbleeds that showed a different pattern distribution (cortical vs deep) in patients with microbleeds, suggesting a different type of origin: deep cerebellar infarcts may recognize a small vessel disease origin, while cortical cerebellar infarct may be associated with AF, and the latter may benefit from anticoagulation. Further analysis may improve our understanding of the link between AF and covert brain infarcts.

Thomas Meinel-Switzerland

Setting up a dedicated referral pathway and clinic for covert cerebrovascular disease

The last talk was about a dedicated outpatient clinic for management of CBI. The risk of stroke at one year in patients with CBI is 2.4%, and from observational studies we know that around 8% of all MRIs show a CBI as incidental finding. Not all patients should be referred to a dedicated CBI clinic, for example patients with dementia or terminal cancer, or those with previous stroke/TIA should not. The phenotype of the potential ischemic lesion needs to be accurately differentiated from other origins of lesion, and suspect lesions should be graded according to the probability to be ischemic. For example, cavitatory lesions have high potential to be ischemic, whereas unspecific lesions or dilated perivascular spaces are not. In parallel, Dr. Meinel suggested that neuroradiologist should closely collaborate with stroke physicians to ensure harmonization of protocols and pathways of care. Some examples from the outpatient clinic from Dr. Meinel’s Hospital are: understanding the clinical implications of CBI with talks and seminars, urgent referral pathways for acute ischemic lesions, a list in PACS to refer suspect CBI accidentally found in patients, and the use of smartphrases in the reports to contact the CBI outpatients clinic in case of suspect lesions. Also, double check if patient has a previous brain imaging stored to narrow down the timepoint at which CBI had occurred. In case of a referral, the use of a simple structured and reproducible

questionnaire may help, and asking about previous surgical procedures, particularly cardioaortic, is mandatory. In cases of a real CBI, given that there have been no symptoms and, patient preferences are a very important point to consider: someone may just want to ignore o prefer a referral to GP rather than start an extensive diagnostic work-up and possibly start a therapy. Neurological exam should look for covert deficits and gait abnormalities, diagnostic work-up should encompass labs, cardiac and neck/head vessels exams, blood pressure monitoring and possibly targeted therapy. Mood and cognitive problems are often neglected in such patients, so they should not be overlooked. ESO guidelines on diagnosis and management covert small vessel disease are available, but they do not cover cortical CBI. For the future, a network of dedicated CBI clinics is the key to generate better evidence for this condition.