Small Vessel Stroke. Domenico Inzitari Careggi University Hospital Florence (Italy)

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1 Small Vessel Stroke Domenico Inzitari Careggi University Hospital Florence (Italy)

2 Topics Lacunar stroke The small vessel conundrum Small and large Conclusions

3 Fisher s lacunar syndromes Pure motor hemiparesis Pure sensory stroke Sensorymotor stroke Ataxic hemiparesis Dysarthria-clumsy hand syndrome Other lacunar syndromes

4 Lacunar stroke: incidence & main features 15%-20% of all ischemic strokes Incidence rate: 30-50/ /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

5 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)

6 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

8 Definitions Small vessel or small stroke: what does come first? Scenarios (and likely definitions) are changing

9 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

10 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

11 STRIVE MRI findings for lesions related to small vessel disease Lancet Neurol 2013; 12:

12 Neuroimaging standards for research into small vessel disease Lancet Neurol 2013; 12:

13 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

14 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).

15 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

16 Association between increasing number of vascular risk factors and risk of progression Nannoni S, in preparation

17 THE SMALL VESSEL CONUNDRUM

18 The small vessel conundrom and its contribution to stroke outcome

19 Arsava et al. Neurology 2009

23 Small vessel or small stroke? (the small vessel stroke mimics)

24 Anterior choroidal artery infarcts

26 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)

27 Nelles M, AJNR, 2008

28 Thalamic small infarcts

29 Figure 1. Artist s rendition of origin of arteries to thalamus arising from the vertebrobasilar system. Schmahmann J D Stroke. 2003;34: Copyright American Heart Association, Inc. All rights reserved.

Figure 2. Thalamic vascular supply. Schmahmann J D Stroke.

Figure 5. Diffusion-weighted MRI of acute thalamic infarction in 2 patients.

33 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: Copyright American Heart Association, Inc. All rights reserved.

34 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: Copyright American Heart Association, Inc. All rights reserved.

37 Ann Transl Med, 2014

38 Small vessel stroke: treatment

40 Metanalysis: RRs (lacunar vs nonlacunar stroke ) for prevalence of hypertension Jackson and Sudlow, Stroke 2005

41 Metanalysis: RRs (lacunar vs nonlacunar stroke) for prevalence of diabetes Jackson and Sudlow, Stroke 2005

42 OACS WARSS (Warfarin-Aspirin Recurrent Stroke Study) - Warfarin (INR ) vs Aspirin (325 mg) - follow-up 2 years 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

43 Thrombolysis Anticoagulants Antiplatelets Mg sulphate Statins Acute treatment

44 Heparin and heparinoids IST pts - 24 % LACI (OCSP) - heparin vs aspirin - end point: death or dependency at 6 months - no difference between treatments TOAST pts lacunar - danaparoid vs placebo - no benefit

45 Clinical studies in patients with lacunar stroke treated with intravenous thrombolysis compared with other stroke subtypes Cerebrovasc Dis 2014;37:5 13

46 Pantoni L et al, Cerebrovasc Dis, 2013

47 Outcome by number of lacunes after thrombolysis Canadian Alteplase for Stroke Effectiveness Study cohort, CASES Palumbo V et al, Neurology 2007

48 Nesi M, et al, J Stroke Cerebrovasc Dis, 2013

49 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

50 Prevenzione Secondaria Antiaggreganti Anticoagulanti Statine

51 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

52 Cilostazol Stroke Prevention Study RCT Multicentric, double blind 1095 patients (75% lacunar) Cilostazol 3x100 mg RRR 41.7% (CI ) Recurren ce Event rate/year RRR CI P-value LACUNAR Cilostazol 2.97 Placebo 5.25 ATHEROT HROMBO TIC Cilostazol 6.37 Placebo Gotoh at al, J Stroke Cerebrovasc Dis 2000

54 1.52 HR for Intracranial hemorrhage in the Aspirin plus clopidogrel

56 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

Stroke School for Internists Part 1

Stroke School for Internists Part 1 November 4, 2017 Dr. Albert Jin Dr. Gurpreet Jaswal Disclosures I receive a stipend for my role as Medical Director of the Stroke Network of SEO I have no commercial