Table 1.
Current guidelines on acute treatment or prevention of stroke relevant to presumed lacunar ischaemic stroke.
| Name of guideline | Date pub | Key findings related to acute phase treatment of SVD related stroke | Key findings related to secondary prevention of SVD related stroke | Key findings when presence SVD influences other treatments |
|---|---|---|---|---|
| ESO Guidelines | ||||
| ESO Guideline on covert cerebral small vessel disease 1 |
2021 | Nil specific – focussed on patients with SVD and no diagnosis stroke/TIA/Cognitive imp/mood/mobility | Nil | Nil |
| European Stroke Organisation (ESO) – European Society for Minimally Invasive Neurological Therapy (ESMINT)Guidelines on Mechanical Thrombectomy in Acute Ischaemic Stroke 13 |
2019 | Nil | Nil | Nil |
| A European Stroke Organisation (ESO) guideline on antithrombotic treatment for secondary prevention of stroke and other thromboembolic events in patients with stroke or transient ischemic attack and non-valvular atrial fibrillation. 14 | 2019 | Nil | Recommendations are weak regarding treatment with oral anticoagulants in . . . specific patient subgroups including those with small vessel disease, because of a lack of strong evidence; Recommendations. In patients with non-valvular AF, previous ischemic stroke or TIA and SVD, we cannot make recommendations about whether non-vitamin K antagonist oral anticoagulants should be preferred over vitamin K antagonists for reducing recurrent stroke or thromboembolism: Quality of evidence – Low; Strength of recommendation: Weak |
No randomised controlled trials investigating the efficacy and safety of: antiplatelet therapy compared to no antithrombotic treatment; vitamin K antagonists versus antiplatelet therapy; or direct oral anticoagulants versus vitamin K antagonists, for prevention of recurrent stroke or other adverse outcomes in patients with non-valvular AF and SVD (WMH and CMBs). |
| European Stroke Organisation and European Academy of Neurology joint guidelines on post-stroke cognitive impairment 15 | 2021 | Nil on treatment, focussed on post stroke cognitive impairment | Nil on treatment | WMH on MRI may predict post stroke cognitive impairment |
| European Stroke Organisation (ESO) guideline on pharmacological interventions for long-term secondary prevention after ischaemic stroke or transient ischaemic attack 16 |
2022 | Nil | Nil | Nil |
| Consensus statements and recommendations from the ESO-Karolinska Stroke Update Conference, Stockholm 11–13 November 201817 |
11–13 November 2018 | Nil | Nil | Individual decision making on OAC after ICH should consider (Grade C): quality of BP control, age, ICH location, burden of small vessel disease (cerebral microbleeds (CMBs), leukoaraiosis, cortical super- ficial siderosis, CAA), additional antiplatelet therapy. OAC in patients with evidence of CMBs should not be withheld (Grade C). |
| EAN/ERS/ESO/ESRS statement on the impact of sleep disorders on risk and outcome of stroke 18 | 2020 | Nil | Nil | Nil |
| European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke 19 |
2021 | Although there are ongoing discussions about the use of IVT in patients with lacunar stroke, there is currently no strong evidence that it should be avoided |
Nil | IVT is recommended in the presence of a small-to-moderate burden of white matter lesions and suggested in the presence of a high burden of lesions When CMB burden is unknown or known to be low (e.g. <10), we suggest intravenous thrombolysis with alteplase. When CMB burden has been previously reported to be high (e.g. >10), we suggest no intravenous thrombolysis. All members suggest against screening with MRI to assess CMB burden before making a treatment decision regarding IVT |
| European Stroke Organisation (ESO) guidelines on management of transient ischaemic attack 20 |
2021 | Nil | Low risk TIA was defined by absence of high risk features (i.e. those in whom brain-tissue damage has not been detected on diffusion-weighted imaging, with no documented stenosis in the ipsilateral cerebral artery, no major cardiac source of embolism, no small vessel disease, and an ABCD2 score of less than 4) |
|
| Other European Guidelines | ||||
| Monogenic cerebral small-vessel diseases: diagnosis and therapy. Consensus recommendations of the European Academy of Neurology 12 |
2020 | Patients with CADASIL should not receive thrombolysis for acute small-vessel ischaemic stroke (which is almost always the case) |
Anticoagulants are not recommended for stroke prophylaxis in CADASIL due to the risk of intracerebral haemorrhage, but they are not contraindicated if there is another strong indication (e.g. atrial fibrillation, pulmonary embolus) |
Nil |
| AHA/ASA | ||||
| 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack - A Guideline From the American Heart Association/American Stroke Association 21 | 2021 | Nil | In patients with ischemic stroke related to small vessel disease, the usefulness of cilostazol for secondary stroke prevention is uncertain Targeted strategies for secondary prevention after small vessel stroke that also reduce the risk of vascular dementia are lacking Studies that showed benefit from PFO closure excluded lacunar strokes |
Nil |
| Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke 22 |
2019 | Nil | For prevention of recurrent stroke, the use of MRI is reasonable in some patients with AIS to provide additional information to guide selection of appropriate secondary stroke prevention treatments. [Two studies from the 1990s evaluating repeat neuroimaging recommended repeat CT over additional MRI for most clinical situations in AIS with the exceptions of documenting lacunar and infratentorial infarcts, but they did not present evidence of a benefit on outcome for these situations] |
Administration of IV alteplase in eligible patients without first obtaining MRI to exclude cerebral microbleeds (CMBs) is recommended In otherwise eligible patients who have previously had a small number (1–10) of CMBs demonstrated on MRI, administration of IV alteplase is reasonable. In otherwise eligible patients who have previously had a high burden of CMBs (>10) demonstrated on MRI, treatment with IV alteplase may be associated with an increased risk of sICH, and the benefits of treatment are uncertain. Treatment may be reasonable if there is the potential for substantial benefit. |
| AHA/ASA Scientific Statement – Prevention of Stroke in Patients With Silent Cerebrovascular Disease 23 |
2017 | Nil | Nil | It is reasonable to provide anticoagulation therapy to patients with microbleeds when there is an indication (e.g. AF). It is reasonable to provide antiplatelet therapy to patients with microbleeds when there is an indication. It is reasonable to administer intravenous alteplase to patients with acute ischemic stroke and evidence of microbleeds if it is otherwise indicated. It is reasonable to perform endovascular thrombectomy in patients with acute ischemic stroke and evidence of microbleeds. |
| Canadian Stroke Best Practice Recommendations | ||||
| Canadian Stroke Best Practice Recommendations – secondary prevention 24 | 2020 | Nil | Recommends aggressive blood pressure in patients with lacunar stroke (systolic target of consistently lower than 130 mmHg) | Lacunar stroke contraindicates PFO closure |
| Canadian Stroke Best Practice Recommendations – acute management 25 | 2022 | Nil | Nil | Nil |
| UK-based guidelines | ||||
| Royal College of Physicians – National clinical guideline for stroke 26 |
2016 | Nil | Mentioning the SPS3 trial that suggests targeting a systolic BP of below 130 mmHg in patients with recent lacunar stroke | Reminding that pre-existing cSVD should be assessed when evaluating the association between statin use and cerebral haemorrhage |
| NICE guideline – Stroke and transient ischaemic attack in over 16s: diagnosis and initial management; https://www.nice.org.uk/guidance/NG128 | 2019 | Nil | Nil | Nil |
| Australia/New Zealand | ||||
| Australian and New Zealand Clinical Guidelines for Stroke Management – Acute stroke management 27 | 2021 | Mentions a substudy of WAKE-UP which was able to show a very similar benefit of alteplase in the lacunar subgroup compared to non-lacunar patients, providing reassurance that lacunar stroke patients do indeed benefit from thrombolysis. | Secondary prevention with antihypertensives in patients with recent lacunar stroke is safe and effective. | CMBs at brain MRI do not contraindicate i.v. thrombolysis |
| Australian and New Zealand Clinical Guidelines for Stroke Management – Secondary prevention 27 | 2021 | Nil | Antiplatelet treatment (without specific drug preference) is effective for secondary lacunar stroke prevention | Patients with lacunar stroke should not undergo PFO closure |
| Asian countries | ||||
| Chinese Stroke Association guidelines for clinical management of cerebrovascular disorders: executive summary and 2019 update of clinical management of ischaemic cerebrovascular diseases
28
Also see Chinese guideline for diagnosis and treatment of cerebral small vessel disease 2020. 29 |
2020 | At present, it is recommended to manage blood pressure, and use of aspirin, clopidogrel or cilostazol (class I, level of evidence B). The blood pressure of patients should be closely monitored (class IIa, level of evidence B). Control of systolic and diastolic pressure is the key factor to control the incidence and progression of cerebral small vessel disease (class IIa, level of evidence B). It is necessary to monitor the 24 hours ambulatory blood pressure in patients with cerebral small vessel disease. When conditions permit, it is best to detect changes in blood pressure during head upright tilt test (class I, level of evidence B). |
Nil | Routine use of MRI to identify intracranial microhaemorrhage, which can affect decisions to IV thrombolysis, is not recommended (class III, level of evidence B). Prethrombolytic MRI examination showed that IV thrombolysis was reasonable in patients with a number of (1–10) cerebral microbleeds (class IIa, level of evidence B). Prethrombolytic MRI examination showed that IV thrombolysis was associated with an increased risk of symptomatic intracerebral haemorrhage in patients with a number of (>10) cerebral microbleeds, and the clinical benefit is not clear. If there may be significant potential benefits, IV thrombolysis may be reasonable (class IIa, level of evidence B). |
| Japanese Stroke Guidelines 30 | 2021 | Nil | In patients who experience ischemic stroke or TIA, without bilateral severe carotid artery stenosis and occlusion of major intracranial artery, who present with lacunar infarction, or undergoing antithrombotic therapy, as lower target value of blood pressure is favourable if possible, a target value of <130/80 mmHg for antihypertensive therapy is reasonable (Grade B, LOE Moderate) | Nil |
SVD: small vessel disease; WMH: white matter hyperintensities on MRI; CMB: cerebral microbleeds; CAA: cerebral amyloid angiopathy; BP: blood pressure; OAC: oral anticoagulation; PFO: patent foramen ovale; AIS: acute ischaemic stroke; IVT: intravenous thrombolysis.