Research Article

Lacunar Infarcts: Clinical and Risk Factors in 864 Patients

Adrià Arboix1*, Maria Alsina1, Marta Caballero1, Olga Parra1, Joan Massons1, María-José Sánchez1 and Luís García-Eroles2
1Department of Neurology, University of Barcelona, Spain
2Department of United Organization Systems Information, Hospital Germans Trias, Badalona, Spain


*Corresponding author: Arboix A, Department of Neurology, Hospital Universitari del Sagrat Cor, c/Viladomat 288, 08029 Barcelona, Spain


Published: 25 Apr, 2017
Cite this article as: Arboix A, Alsina M, Caballero M, Parra O, Massons J, Sánchez M-J, et al. Lacunar Infarcts: Clinical and Risk Factors in 864 Patients. J Heart Stroke. 2017; 2(3): 1023.

Abstract

Background: To assess the clinical features and incidence rate of lacunar infarcts.
Methods: Hospital-based descriptive study of 864 patients with lacunar infarcts consecutively admitted for stroke during a period of 24 years, and compared to the rest of patients admitted for ischemic non-lacunar stroke (n=2,404).
Results: Lacunar infarcts represented 26.4% of all ischemic strokes. Factors independently associated with lacunar infarcts were arterial hypertension (OR=2.52; 95% CI (2.07-3.06) p<0.001), diabetes mellitus (OR= 1.55; 95% CI (1.26–1.90), p<0.001), female gender (OR= 0.68; 95% CI (0.57-0.82), p<0.001), valvular heart disease (OR=0.61; 95% CI (0.37-0.99), p=0.049), ischemic heart disease (OR=0.68; 95% CI (0.52-0.88), p=0.004), atrial fibrillation (OR=0.124; 95% CI (0.19–0.32), p<0.001), sudden onset (OR=0.74; 95% CI (0.61–0.89), p=0.030), headache (OR=0.26; 95% CI (0.14–0.50), p<0.001), early seizures (OR=0.11; 95% CI (0.02–0.45), p=0.003), nausea/vomiting (OR= 0.44; 95% CI (0.28–0.70), p=<0.001; altered consciousness (OR=0.12; 95% CI (0.08–0.19), p<0.001); sensory disturbances (OR=0.73; 95% CI (0.60-0.91; p=0.010), hemianopia (OR=0.04; 95% CI (0.02–0.08), p<0.001); speech disturbances (OR=0.48; 95% CI (0.39–0.58), p<0.001) and cranial nerve palsy (OR=0.55; 95% CI (0.35–0.85), p=0.005).
Conclusion: Lacunar infarcts represent 26.4% of cerebral infarcts and present their individual and differentiated clinical profile.
Keywords: Lacunar infarcts; Cerebral infarction; Risk factors; Etiology


Introduction

Lacunar infarctions together with leukoaraiosis, dilatation of perivascular spaces, cerebral microbleeds and cerebral atrophy, are the usual anatomical manifestations of small vessel diseases [1-3]. The onset of small vessel disease may be silent, but will subsequently cause lacunar focal neurological syndromes, cognitive impairment or subcortical type dementia, and mood disturbances [4].
Lacunar infarcts, possibly due to their lower incidence and better short-term recovery, have been less studied in stroke hospital registries in spite of their significant health impact. Thus, there are still many controversial aspects about their natural history when compared to the rest of cerebral infarctions, such as risk factors profile and clinical characteristics.
The present study serves a twofold purpose: on the one hand, analyze the frequency of presentation, cardiovascular risk factors and clinical features of lacunar infarcts; secondly, to perform a comparative analysis between lacunar infarcts and the rest of non-lacunar cerebral infarcts. Toward that end, we analyzed a sample of 864 consecutive patients with lacunar infarctions, and compared it with 2,404 consecutive patients with non-lacunar cerebral infarctions.


Material and Methods

We present a clinical study performed at the Department of Neurology of the Hospital Universitari del Sagrat Cor in Barcelona for 24 years (1986-2009, both inclusive) and based on the analysis of the hospital-based prospective stroke registry. This registry has been previously published and validated [5]. Stroke subtypes, cardiovascular risk factors, and clinical and etiological features were classified according to the recommendations of the Committee of Experts on Cerebral Vascular Diseases of the Catalan Society of Neurology [6] and have been used by our group in other studies [5,7].
According to the methodology and classification of previous studies [8,9] and to the nomenclature of the study group of cerebral vascular diseases of the Spanish Society of Neurology and the Official Guides of Vascular Cerebral Diseases of the Societat Catalana de Neurologia [5], lacunar infarcts were defined as ischemic strokes characterized by a classical lacunar syndrome (pure motor hemiparesis, pure sensory stroke, sensorimotor stroke, ataxic hemiparesis or dysarthria-clumsy hand), or as an atypical lacunar syndrome lasting longer than 24 hours and caused by a cerebral infarct with maximum lesion diameter of 20 mm, visualized or not by neuroimaging and located in the vascular territory of the perforating cerebral arterioles, in the absence of cortical cerebral ischemia, arterial stenosis (> 50%) of the supraaortic trunks, or in the presence of an embolic etiology of cardiac origin.
We retrospectively analyzed data of the 4,597 patients included in the stroke registry whom were admitted for ischemic stroke, and selected the subgroup of patients with cerebral infarction. For the purposes of this study, we compared the subgroup of patients with lacunar infarct to those with non-lacunar infarcts.
The study population consisted of 3,268 patients, 864 of which were lacunar strokes and 2,404 non-lacunar strokes, with the following distribution: 956 cardioembolic, 944 atherothrombotic, 374 cerebral infarcts of essential cause and 128 cerebral infarcts of unusual etiology.
Demographic characteristics, vascular risk factors and clinical features of patients with lacunar infarct were compared with those with non-lacunar infarct. Univariate analysis for association of individual variables with lacunar infarcts was analyzed with the Student’s t test for continuous variables and the chi-square (χ 2) test (with Yate’s correction when necessary) for categorical data. Statistical significance was set at p<0.05. The degree of association was estimated by the odds ratio (OR) and the 95% confidence interval (CI). Significant variables related to lacunar infarcts were subjected to multivariate analysis with a logistic regression procedure and forward stepwise selection. The study was approved by the Clinical Research Ethics Committee of our hospital.


Table 1

Another alt text

Table 1
Results of univariate analysis in patients with cerebral infarction due to lacunar infarct compared with patients with non-lacunar infarct.

SD: Standard Deviation; COPD: Chronic Obstructive Pulmonary Disease.


Table 2

Another alt text

Table 2
Variables independently related to lacunar infarction.

CI: Confidence Interval; OR: Odds Ratio. β = -0.109; SE (β) = 0.117; goodness-of-fit χ2 = 5,401; gl = 8; P =0.714


Results

Of the initial 3,268 patients with cerebral infarctions, 864 (26.4%) were lacunar infarcts. Mean age (SD) was 74.4 (10.4) years. Overall, 16.2% was older than 85 years and 5.9% younger than 55 years. Men made up 56.5% of patients (n=488) and women 43.5% (n=376). The main cardiovascular risk factors recorded –in order of decreasing frequency- were: hypertension 71.5%, diabetes mellitus 30%, dyslipidemia 24%, previous cerebral ischemia 15.4%, ischemic heart disease 13.1%, and heavy smoking 13%.
Major neurological symptoms were motor disorders in 75.2% of cases, speech disturbances in 43.2%, sensory disturbances in 30.9%, headache in 9%, ataxia in 7.4%, and cranial nerves alteration in 3.7%. The most frequent topographies were internal capsule (32.4%), thalamus (15%), pons (11%), basal ganglia (9.3%), centrum semiovale (5.8%) and mesencephalus (0.7%). Lacunar syndromes included pure motor hemiparesis in 48% of patients, pure sensory syndrome in 17.3%, pure sensorimotor in 11.3%, ataxic hemiparesis in 3.3%, dysarthria clumsy hand in 8%, and atypical lacunar syndrome in 12%.
In-hospital mortality was 0.6% (n=5). The causes of death were sepsis in 1 patient, respiratory infection in 1 patient, sudden death in 1 patient and unknown causes in 2 patients. There was no neurological deficit at discharge in 21.1% of patients. The average length of hospital stay (SD) was 11.6 (7.8) days, with 29.3% of patients staying longer than 12 days.
When the groups of lacunar and non-lacunar infarctions were compared (Table 1), male sex, hypertension, diabetes, obesity, smoking and dyslipidemia were more frequent in the lacunar group. There were less frequent: female sex, ischemic heart disease, valvular heart disease, atrial fibrillation, sudden onset, headache, early seizures, decreased consciousness, nausea or vomiting, sensory disturbances, hemianopia, speech disturbances, cranial nerve palsy, and neurological, respiratory, urinary, cardiac, vascular and infectious complications at admittance, and in-hospital mortality.
In the multivariate analysis (Table 2), significant independent variables related to lacunar infarcts were hypertension (OR=2.52; 95% CI (2.07-3,06); p<0.001), diabetes mellitus (OR= 1.55; 95% CI (1.26–1.90; p<0.001), female sex (OR= 0.68; 95% CI (0.57-0.82); p<0.001), valvular heart disease (OR=0.61; 95% CI (0.37-0.99; p=0.049), ischemic heart disease (OR=0.68; 95% CI (0.52-0.88); p=0.004), atrial fibrillation (OR=0.124; 95% CI (0.19–0.32); p<0.001), sudden onset (OR=0.74; 95% CI (0.61–0.89); p=0.030), headache (OR=0.26; 95% CI (0.14–0.50); p<0.001), early seizures (OR=0.11; 95% CI (0.02–0.45); p=0.003), nausea and vomiting (OR= 0.44; 95% CI (0.28–0.70); p<0.001; decreased consciousness (OR=0.12; 95% CI (0.08–0.19); p<0.001); sensory disturbances (OR=0.73; 95% CI (0.60-0.91); p=0.010), hemianopia (OR=0.04; 95% CI (0.02–0.08); p<0.001); speech disturbances (OR=0.48; 95% CI (0.39–0.58; p<0.001) and cranial nerve palsy (OR=0.55; 95% CI (0.35–0.85); p=0.005). Results from the area under the ROC curve are shown in Figure 1.


Figure 1

Another alt text

Figure 1
Area under the ROC curve=0.820; sensitivity 81.6%, specificity 65.9%, positive predictive value =46.2%, negative predictive value =90.9%, correct classification: 70.06%.

Discussion

In our study, lacunar infarcts accounted for 26.4% of cerebral infarctions, and these findings are similar to those reported by other studies ranging from 28.6% [10] to 19.2% [11]. The most common vascular risk factors independently associated with lacunar infarcts were hypertension in 71.5% of cases and diabetes in 30%. These findings are similar to those obtained by Pv “et al.” [10], in which hypertension and white matter hyperintensities were variables independently related to lacunar infarction compared with cerebral ischemia of large vessels. By contrast, in the study of Ntaios “et al.” [11] performed in a sample of diabetic patients, it was noteworthy that small and large vessel diseases showed a similar incidence, despite prognosis was worse in patients with non-lacunar infarcts.
It is remarkable the reduced incidence of ischemic heart disease, valvular heart disease and atrial fibrillation in lacunar infarcts, which could be explained by being the main vascular risk factors of cardioembolic infarcts [12], which constitute, in turn, the subtype of cerebral infarction with a worse functional prognosis.
The lower frequency of sudden onset of neurological deficit, the presence of headache, early seizures, decreased level of consciousness, nausea and vomiting, sensory symptoms, visual and speech disturbances, and cranial nerves alterations could also be explained by the fact that these clinical variables are mainly related to atherothrombotic, cardioembolic or unusual cause strokes [13]. Neurological semiology characteristic of lacunar infarcts, instead, occurs in the form of classical lacunar syndromes and, less frequently, atypical lacunar syndromes [14,15] as observed in the present clinical series, thus fulfilling the lacunar hypothesis initially described by Miller Fisher, which states that lacunar syndromes are mainly due to cerebral infarctions of the lacunar type [2].
Our study also revealed the significant good short-term prognosis of lacunar infarcts, as neurological, respiratory, urinary, cardiac, vascular and infectious complications were uncommon during in hospital stay, and mortality rate was only 0.6%, with a total recovery of neurological deficit at discharge in 21% of patients. These findings are consistent with the results of other studies [10,11,16,17]. However, it should be noted that this good short-term prognosis is totally misleading since it has been shown that lacunar infarcts present a higher risk of cerebral vascular relapse, of silent progression of small vessel disease, mainly related to an increase in white matter hyperintensities, of cerebral atrophy, and are the most common cause of subcortical vascular dementia [18-20].
It is therefore necessary an adequate control of cerebrovascular risk factors, hypertension and diabetes mellitus in this case, together with a correct antiplatelet therapy [3] as an optimal secondary prevention of relapse of cerebral ischemia and progression of small cerebral vessel disease.
In summary, approximately one in four patients admitted for cerebral infarction suffers a lacunar infarct, which shows a differentiated clinical profile compared to the rest of cerebral infarctions.


Acknowledgement

This report is partly based on the “Final Bachelor’s Degree Project (academic year 2015-16) of Maria Alsina Valle, graduate of the University of Barcelona Medicine School.


References

  1. Moran C, Phan TG, Srikanth VK. Cerebral small vessel disease: a review of clinical, radiological, and histopathological phenotypes. Int J Stroke. 2012;7:36-46.
  2. Fisher CM. Lacunar infarcts - A review. Cerebrovasc Dis. 1991;1:311-13.
  3. The SPS3 Investigators, Benavente OR, Hart RG, McClure LA, Szychowski JM, Coffey CS, Pearce LA. Effects of clopidogrel added to aspirin in patients with recent lacunar stroke. N Engl J Med. 2012;367:817-25.
  4. Grau-Olivares M, Arboix A. Mild cognitive impairment in stroke patients with ischemic cerebral small-vessel disease: a forerunner of vascular dementia? Expert Rev Neurother. 2009;9:1201-17.
  5. Arboix A, Massons J, Oliveres M, García L, Titus F. Análisis de 1.000 pacientes consecutivos con enfermedad cerebrovascular aguda. Registro de patología vascular cerebral de la Alianza-Hospital Central de Barcelona. Med Clin (Barc). 1993;101:281-85.
  6. Catalan Society of Neurology. Official Guidelines for diagnosis and treatment. In: Cerebrovascular Diseases. 2nd ed. Barcelona: Societat Catalana de Neurologia; 2011;159-240.
  7. Arboix A, Vall-Llosera A, García-Eroles L, Massons J, Oliveres M, Targa C. Clinical features and functional outcome of intracerebral hemorrhage in patients aged 85 and older. J Am Geriatr Soc. 2002;50:449-54.
  8. Arboix A, García-Plata C, García-Eroles L, Massons J, Comes E, Oliveres M, et al. Clinical study of 99 patients with pure sensory stroke. J Neurol. 2005;252(2):156-62.
  9. Arboix A1, Bell Y, García-Eroles L, Massons J, Comes E, Balcells M, et al. Clinical study of 35 patients with dysarthria-clumsy hand syndrome. J Neurol Neurosurg Psychiatry. 2004;75(2):231-4.
  10. Lv P, Jin H, Liu Y, Peng Q, Liu R, Sun W, et al. Comparison of risk factor between lacunar stroke and large artery atherosclerosis stroke: a cross-sectional study in China. PLoS One. 2016;11:e0149605.
  11. Ntaios G, Milonis H, Vemmos K, Makaritsis K, Ferrari J, Strbian D, et al. Small-vessel occlusion versus large-artery atherosclerotic strokes in diabetics: patient characteristics, outcomes, and predictors of stroke mechanism. Eur Stroke J. 2016;1:108-13.
  12. Arboix A, Alio J. Acute cardioembolic cerebral infarction: answers to clinical questions. Curr Cardiol Rev. 2012;8(1):54-67.
  13. Arboix A, Bechich S, Oliveres M, García-Eroles L, Massons J, Targa C. Ischemic stroke of unusual cause: clinical features, etiology and outcome. Eur J Neurol. 2001;8(2):133-9.
  14. Jickling GC, Stamova B, Ander BP, Zhan X, Tian Y, Liu D, et al. Profiles of lacunar and nonlacunar stroke. Ann Neurol. 2011;70(3):477-85.
  15. Arboix A, López-Grau M, Casasnovas C, García-Eroles L, Massons J, Balcells M. Clinical study of 39 patients with atypical lacunar syndrome. J Neurol Neurosurg Psychiatry. 2006;77:381-4.
  16. Micheli S, Agnelli G, Palmerini F, Caso V, Venti M, Alberti A, et al. Need for extensive diagnostic work-up for patients with lacunar stroke. J Neurol. 2008;255(5):637-42.
  17. Jackson C, Sudlow C. Are lacunar strokes really different? A systematic review of differences in risk factor profiles between lacunar and nonlacunar infarcts. Stroke. 2005;36(4):891-901.
  18. Jackson CA, Hutchison A, Dennis MS, Wardlaw JM, Lindgren A, Norrving B, et al. Differing risk factor profiles of ischemic stroke subtypes: evidence for a distinct lacunar arteriopathy? Stroke. 2010;41:624-9.
  19. Putaala J, Yesilot N, Waje-Andreassen U, Pitkaniemi J, Vassilopoulou S, Nardi K, et al. Demographic and geographic vascular risk factor differences in European young adults with ischemic stroke: the 15 cities young stroke study. Stroke. 2012;43:2624-30.
  20. Grau-Olivares M, Arboix A, Bartrés-Faz D, Junqué C. Neuropsychological abnormalities associated with lacunar infarction. J Neurol Sci. 2007;257:160-5.