Lacunar Infarct. Dr. Tapas Kumar Banerjee Medical Director & Chief Consultant Neurologist National Neurosciences Centre Calcutta

Lacunar Infarct Dr. Tapas Kumar Banerjee Medical Director & Chief Consultant Neurologist National Neurosciences Centre Calcutta

Aetiologies of Ischemic Stroke Atherothrombo-embolic Cardio-embolic

Aetiologies of Ischemic Stroke (contd) Lacunar infarction Miscellaneous Blood disorders Other non-atheromatous disease of vessel wall- SLE, PAN, Wegener s granulomatosis, etc Cryptogenic or Embolic stroke of unknown source (ESUS)

Lacunar infarct Are small, discrete, often irregular subcortical infarcts, ranging usually from 3mm to 1.5 cm in size (definitely 2cm). Caused by occlusion of a single penetrating branch of a large cerebral artery. These branches arise at acute angles from large arteries of the circle of Willis, stem of the middle cerebral artery, or the basilar artery. The gliotic infarct area removed by macrophages leaving tiny cavities or lacunes ; hence the name lacunar infarct.

Lacunar infarct (contd) Most commonly located in putamen (37%), pons (16%), thalamus (14%), caudate nucleus (10%), posterior limb of internal capsule (10%). Less common in anterior limb of internal capsule and cerebellum. Rarely exist in cerebral peduncles, pyramids, and subcortical white matter. NOT found in cerebral and cerebellar cortices. D/D: Dilated Virchow-Robin spaces- round or linear, < 3mm and located in lower basal ganglia region.

Symptoms and signs Classical Lacunar Syndromes - if located mostly at internal capsule or pons where clinically eloquent ascending and descending neural tracts are concentrated. Lacunar infarcts manifested with other types of neurological deficits. Cognitive decline- from strategically located single infarct in basal ganglia Clinically silent

Classic Lacunar Syndromes Fisher CM. Neurology 1982;32: 871-6. Pure motor stroke/hemiparesis (commonest; 33-45%) Ataxic hemiparesis (2 nd commonest) Pure sensory stroke Mixed sensorimotor stroke Dysarthria-clumsy hand syndrome Hemiplegia/ hemiparesis that typically affects the contralateral face, arm, or leg Contralateral weakness with hemi-ataxia Conralateral persistent numbness or paresthesia Contralateral hemiplegia/ hemiparesis with hemisensory impairment Dysarthria with clumsiness of hand, especially during writing; probably a variant of ataxic hemiparesis

Classic Lacunar Syndromes(contd) No visual field defect No visuo-spatial disturbance No aphasia No brain-stem dysfunction, such as vertigo, diplopia, deafness, tinnitus, nystagmus, stance and gait ataxia No drowsiness

Other clinical manifestations of lacunar infarcts Dysphagia, dysarthria, even mutism with mild facial weakness. No limb paresis Often bilateral with pseudo-bulbar palsy and emotional incontinence Non-pyramidal hemimotor syndrome- hemi-parkinsonism, hemichorea, clumsiness, slight increased resistance to passive movement Ipsilateral 3 rd cranial nerve palsy with contralateral hemiparesis (Weber s syndrome) Ipsilateral 6 th cranial nerve palsy/ internuclear opthalmoplegia/ conjugate-gaze palsy with contralateral hemiparesis

Lacunar infarct in thalamus or in caudate nucleus Abulia- decreased activity, lack of motivation, long delays in response to commands Cognitive decline- strategic infarct dementia Fluctuating alertness

Lesion sites in lacunar syndromes

Lesion sites in lacunar syndromes (contd)

Risk factors for lacunar infarction Age Gender Hypertension Diabetes mellitus Smoking Obesity (body mass index 30kg/ m 2 ) Dyslipidemia Cardiac valvular disease

Pathology & pathophysiology of lacunar infarction Two types of pathology: 1. Segmental arterial disorganisation or lipohyalinosis 2. Atheroma either at the mouth or along the length of penetrating arteries

Risk factors for lacunar infarction (contd) If pathology is lipohyalinosis: 1. Age 2. Hypertension 3. Diabetes mellitus If pathology is microatheroma: 1. Hypertension 2. Diabetes mellitus 3. Hypercholesterolemia 4. Smoking 5. Male gender 6. Obesity

Risk factors for lacunar infarcts Hypertension: prerequisite for the development of lacunar infarction, with OR of 2.64. The nature of cerebral small-vessel disease has been changed by more effective treatment of hypertension in the population during the last decade. Diabetes mellitus: another major risk factor in lacunar infarction with OR of 1.55. Obesity: BMI 30kg/ m 2 is also an independent risk factor associated with lacunar infarcts. Hypercholeterolemia: risk factor for microatheroma but not for lipohyalinosis

Risk factors for incident lacunes In Rotterdam Scan Study (RSS): the incident lacunes (3-20 mm) are associated with age, female sex, and baseline carotid atherosclerosis. In Leukoaraiosis And Disability Study (LADIS): the incident lacunes (3-10 mm) were associated with WMH load, systolic BP, and low highdensity lipoprotein (HDL) cholesterol levels. There were unexpected associations with high diastolic BP and high LDL cholesterol as factors protecting against incident lacunes. This disparity between the above studies is because individual with small lacunes and with at least some degree of WMH were only included in the 2 nd study.

Investigations MRI scan of brain in: T2-wt, FLAIR, T1-wt, DWI and ADC sequences

Figure Different shapes of lacunae-sized infarcts(a, B) On diffusion-weighted MRI, small single lacunar infarcts are observed in the left thalamus and left corona radiata. Dong Woo Ryu et al. Neurology 2012;78:1416-1419 Copyright 2012 by AAN Enterprises, Inc.

Investigations (contd) MR-angiography/ CT-angiography of intra-cranial and extra-cranial arteries

Treatment & prevention THROMBOLYSIS: IV t-pa was found to be as effective a treatment in acute lacunar stroke as in non-lacunar strokes. Current consensus guidelines do not distinguish between ischemic stroke subtypes in terms of t-pa efficacy. CONTROL OF HYPERTENSION: Reduction of systolic BP< 130 to prevent lacunar stroke. BP management may have be more cautiously made in patients with advanced age, a long history of hypertension, extensive WMH, or cognitive dysfunction. ROLE OF STATINS: Statins may increase the risk of bleeding, but this may be outweighed by reduction of ischemic stroke risk. So current guideline for statin use applicable in lacunar stroke as in other types.

Treatment & prevention (contd) ANTIPLATELETS: Currently aspirin, aspirin plus dipyridamole and clopidogrel are the acceptable options. Among patients with recent lacunar stroke, the addition of clopidogrel to aspirin does not significantly reduce the risk of recurrent stroke; on the contrary significantly increase the risk of bleeding and death. CONTROL OF DIABETES MELLITUS AVOIDANCE OF SMOKING WEIGHT REDUCTION

Outcome of lacunar infarct In lacunar infarcts, the rate of recovery is normally rapid, quite naturally because the primary lesion is small. Mortality was lowest in patients with lacunar stroke, intermediate in athero-thrombotic stroke and highest in cardio-embolic stroke. Small-artery occlusion subgroups were 3 times more likely to be alive at 2 years than those with cardio-embolism.

Outcome of lacunar infarct (contd) Risk of recurrent stroke: 1. The average rate of recurrent stroke at 1 year in all studies was 7 7% (range 2 12%) whereas the cumulative rate at 4 5 years was 22 4% (range 15 28%). 2. In most studies the risk of recurrent stroke after the first year was about 4 6% per year. 3. The annual rate of stroke recurrence decreased from about 5% during the first 5 years, to less than 1% between 5 and 10 years after the first stroke.

Outcome of lacunar infarct (contd) Prognosis for patients with lacunar infarct is more favorable in terms of survival and disability than for those with other stroke subtypes during the first few years, which is probably explained simply by the small lesion size. But there is progressive accumulation of silent multiple lacunar infarcts over the years. At 10 years after onset, a third or less of patients are still alive and free of recurrent stroke, but a large proportion of survivors are disabled, and have either some amount of cognitive impairment or are frankly demented (vascular dementia-parkinsonism)

Vascular Dementia Large-vessel vascular dementia Hemorrhagic vascular dementia Ischemic hypo-perfusive vascular dementia Subcortical ischemic vascular dementia (SIVD)

Subcortical ischemic vascular dementia (SIVD) Two core pathological features are: 1. Multiple lacunar infarcts (etat lacunaire) 2. Binswanger s disease

Multiple lacunar infarcts

Binswanger s disease Binswanger s disease is due to incomplete infarction or diffuse ischemia. Pathologically, there is demyelination as well as axonal and oligodendrocyte loss with sparing of the U- fibres. Cerebral MRI shows diffuse white matter hyperintensities with sparing of the U-fibres.

Figure 1 The Lancet Neurology 2002 1, 426-436DOI: (10.1016/S1474-4422(02)00190-4) Copyright 2002 Elsevier Ltd Terms and Conditions

Figure 2 The Lancet Neurology 2002 1, 426-436DOI: (10.1016/S1474-4422(02)00190-4) Copyright 2002 Elsevier Ltd Terms and Conditions

Pharmacotherapy for vascular dementia Risk factor modification (hypertension, diabetes mellitus, etc) is mandatory Cognition, stabilization of global functioning, behavior: donepezil, rivastigmine, galantamine, memantine Depression, anxiety: SSRI (tricylcic antidepressants discouraged owing to anticholinergic effects including orthostatic hypotension) Agitation, disruptive behavior: atypical antipsychotics Probably modest efficacy in vascular dementia: piracetam, aspirin, citicoline, pentoxiphyllin, etc

Conclusion Recent long-term prospective studies have changed our views of lacunar infarcts. Once thought benign and innocuous vascular lesions, lacunar infarct is now regarded as important markers of cerebral small-vessel disease with a high risk of unfavorable outcome with time. Asymptomatic progression of cerebral small-vessel disease is several times more common than new strokes, and is likely to be detrimental to brain function. Risk factor modification plays a central part in therapeutic intevention of lacunar infarcts.