Small Vessel Stroke Domenico Inzitari Careggi University Hospital Florence (Italy)
Topics Lacunar stroke The small vessel conundrum Small and large Conclusions
Fisher s lacunar syndromes Pure motor hemiparesis Pure sensory stroke Sensorymotor stroke Ataxic hemiparesis Dysarthria-clumsy hand syndrome Other lacunar syndromes
Lacunar stroke: incidence & main features 15%-20% of all ischemic strokes Incidence rate: 30-50/100.000/year More common among Asians, Blacks, Hispanics Incidence increasing with age Small deep infarct of 1,5 (2,0-1,0) maximum diameter Basal ganglia, internal capsule, pons and centrum semiovale sites Lenticulostriate or paramedian BA branches territory
Lacunar Infarct: pathogenesis Penetrating artery vessel wall fibro-lipo-jalinosis Superimposed thrombosis (Fisher s hypothesis) Microatheroma at the ostium of penetrating artery Hemodynamic effect Microembolism (Futrell s hypothesis)
Natural history of lacunar stroke Low mortality: 2-5% in one month after the acute event High progression rate: 20-30% in the first 48/72 hrs Group A: Progression Group B: No Progression Steinke and Ley, 2002
Definitions Small vessel or small stroke: what does come first? Scenarios (and likely definitions) are changing
Outcome by stroke type in the NASCET Trial Risk and Severity of Stroke According to Cause Inzitari D et al. N Engl J Med 2000
Risk of ipsilateral stroke at 3 years by presenting stroke category and treatment group for patients with 50 to 99% internal carotid artery stenosis Inzitari, D. et al. Neurology 2000;54:660
STRIVE MRI findings for lesions related to small vessel disease Lancet Neurol 2013; 12: 822 38
Neuroimaging standards for research into small vessel disease Lancet Neurol 2013; 12: 822 38
Infarction caused by lipohyalinosis: an island of ischemic tissue located in distal region within the parenchyma Infarction caused by microatheroma: usually located in the proximal region near to the parent artery Nah HW et al. Stroke 2010; Phan TG et al. Cerebrovasc Dis 2013
SSS is generally considered to have a better prognosis than other stroke subtypes (Sacco S et al. Neurology 2006). However, about 20-30% of patients experience worsening of neurological deficit in the first hours or even days after the stroke onset (Nakamura K et al. Neurology 1999). Deterioration especially involves motor function; small vessel disease strokes are the major cause of progressive motor deficits (Steinke W et al. Stroke 2002). Progression may be associated with poor functional outcome (Cuadrado-Godia E et al. Atherosclerosis 2011).
Biochemical mechanisms: - Excitotoxicity (Serena J et al. Stroke 2001) - Inflammation (Castellanos M et al. Stroke 2002) Blood brain barrier dysfunction and development of peri-infarct oedema (Wardlaw JM et al. Stroke 2003) Hemodynamic insufficiency of perforators (Yamada M et al. AJNR 2004) Branch Atheromathous Disease (Kim S et al. Int J Stroke 2012): local thrombosis superimposed to the ostial atheroma or thrombus propagation with progressive enlargement of the ischemic area
Association between increasing number of vascular risk factors and risk of progression Nannoni S, in preparation
THE SMALL VESSEL CONUNDRUM
The small vessel conundrom and its contribution to stroke outcome
Arsava et al. Neurology 2009
Small vessel or small stroke? (the small vessel stroke mimics)
Anterior choroidal artery infarcts
Anterior choroidal artery infarcts: large vs small 1350 acute ischemic stroke series 112 (8%) AchA cases, 70 small (<20 mm) Cardio-embolic source: 31% large, 9% small >70% arterial stenosis: 31% large, 10% small Progression: 38% large, 17% small Poor outcome: 43% in large, 16% in small Ois A, et al, J Neurol Scie 2009)
Nelles M, AJNR, 2008
Thalamic small infarcts
Figure 1. Artist s rendition of origin of arteries to thalamus arising from the vertebrobasilar system. Schmahmann J D Stroke. 2003;34:2264-2278 Copyright American Heart Association, Inc. All rights reserved.
Figure 2. Thalamic vascular supply. Schmahmann J D Stroke. 2003;34:2264-2278 Copyright American Heart Association, Inc. All rights reserved.
Figure 5. Diffusion-weighted MRI of acute thalamic infarction in 2 patients. Schmahmann J D Stroke. 2003;34:2264-2278 Copyright American Heart Association, Inc. All rights reserved.
Figure 7. T2-weighted MRI of bilateral paramedian thalamic infarction in a patient with a top of the basilar embolus involving midbrain and hypothalamus. Schmahmann J D Stroke. 2003;34:2264-2278 Copyright American Heart Association, Inc. All rights reserved.
Figure 8. Diffusion-weighted MRI of acute infarction in the left inferolateral artery territory causing the clinical triad of ataxia, mild hemiparesis, and hemisensory loss on the contralateral side. Schmahmann J D Stroke. 2003;34:2264-2278 Copyright American Heart Association, Inc. All rights reserved.
Ann Transl Med, 2014
Small vessel stroke: treatment
Metanalysis: RRs (lacunar vs nonlacunar stroke ) for prevalence of hypertension Jackson and Sudlow, Stroke 2005
Metanalysis: RRs (lacunar vs nonlacunar stroke) for prevalence of diabetes Jackson and Sudlow, Stroke 2005
OACS WARSS (Warfarin-Aspirin Recurrent Stroke Study) - Warfarin (INR 1.2 2.8) vs Aspirin (325 mg) - follow-up 2 years - 2206 pts with non cardioembolic stroke (lacunar 55%) - End point: stroke recurrence and death - Results: no difference in the primary end point (17.8 vs. 16/100 patients/year) - Greater incidence of hemorrhage in the group on Warfarin (2.2 vs. 1.5/100 patients/year) Mohr J et al, N Engl J Med 2001
Thrombolysis Anticoagulants Antiplatelets Mg sulphate Statins Acute treatment
Heparin and heparinoids IST - 20.000 pts - 24 % LACI (OCSP) - heparin vs aspirin - end point: death or dependency at 6 months - no difference between treatments TOAST - 1281 pts - 306 lacunar - danaparoid vs placebo - no benefit
Clinical studies in patients with lacunar stroke treated with intravenous thrombolysis compared with other stroke subtypes Cerebrovasc Dis 2014;37:5 13
Pantoni L et al, Cerebrovasc Dis, 2013
Outcome by number of lacunes after thrombolysis Canadian Alteplase for Stroke Effectiveness Study cohort, CASES Palumbo V et al, Neurology 2007
Nesi M, et al, J Stroke Cerebrovasc Dis, 2013
Magnesium for Treatment of Acute Lacunar Stroke Syndromes. Further analysis of the IMAGES Trial Efficacy dataset: interaction between Mg treatment and LACS Aslanyan S. et al, Stroke 2007
Prevenzione Secondaria Antiaggreganti Anticoagulanti Statine
Antiplatelet Drugs in the Secondary Prevention After Stroke Differential Efficacy in Large vs Small Vessel Disease? A subgroup analysis from ESPS II Crude annual risk of vascular events in patients with Small Vessel vs Large Vessel Disease according to 4 different treatment Ariesen MJ et al, Stroke 2006
Cilostazol Stroke Prevention Study RCT Multicentric, double blind 1095 patients (75% lacunar) Cilostazol 3x100 mg RRR 41.7% (CI 9.2-62.5) Recurren ce Event rate/year RRR CI P-value LACUNAR 43.4 3.0-67.0 0.0373 Cilostazol 2.97 Placebo 5.25 ATHEROT HROMBO TIC Cilostazol 6.37 Placebo 10.58 39.8-55.4-76.7 0.2620 Gotoh at al, J Stroke Cerebrovasc Dis 2000
1.52 HR for Intracranial hemorrhage in the Aspirin plus clopidogrel
Small vessel stroke: conclusions The worst defined stroke type Difficult distinction from large vessel/ce Hetherogeneous mechanisms Often combined with widespread SVD Best treatment: still a mistery Novel imaging technologies could help