Association of inferior division MCA stroke location with populations with atrial fibrillation incidence

Abstract

Background and Aim: Considering the anatomical features of Middle Cerebral Artery (MCA) bifurcation, larger emboli are more likely to enter the inferior division over the superior division. Since emboli of cardiac origin are larger on average than emboli of arterial origin, we hypothesize that the infarcts in temporal and parietal lobes are more likely associated to atrial fibrillation than those in the frontal lobes, therefore occurring more often in populations with higher incidence of atrial fibrillation, such as male (compared to women) and white (compared to black) patients.

Methods: We included 197 patients with MCA “temporoparietal predominant” infarcts and 105 with “frontal predominant” infarcts. Variations between stroke location (frontal or temporoparietal), sex, and race were examined via Chi-square test.

Results: Male patients were more likely than female patients to be afflicted by temporoparietal strokes versus frontal strokes, while white patients had greater likelihood than black patients to be afflicted by temporoparietal strokes versus frontal strokes. Patients with confirmed diagnosis of atrial fibrillation display more temporoparietal strokes compared to frontal strokes.

Conclusion: Temporoparietal MCA ischemic strokes occur more frequently in male and white patients: populations with known increased incidence of atrial fibrillation. In addition, population-specific anatomical characteristics of the MCA bifurcation might favor the larger cardiac emboli to enter the inferior division and cause temporoparietal infarcts. This association can help guide search for the most likely etiology of infarcts.

1. Introduction

Previous studies have reported associations between MCA infarct location and etiology [1]. Wernicke's aphasia (due to left temporoparietal stroke) is often due to cardioembolic stroke [2], [3]. This association was explained by a gravitational model, based on 3D volume rendering CT angiography (CTA) in 103 patients, that showed inferior division lumen diameter was larger than superior division. The angle between the MCA trunk and superior division was less severe than the angle between the MCA trunk and inferior division [4], and the takeoff of the inferior division was downward relative to gravity while the takeoff of the superior division was upward. Thus, considering the anatomical features of MCA bifurcation, larger emboli favor entering the inferior division, with larger vessel diameter, more linear path, and greater gravitational predilection, over the superior division [4].

Based on these previous data, we hypothesize that the infarcts in temporal and parietal lobes are more likely associated with atrial fibrillation than those in the frontal lobes, therefore occurring more often in populations with higher incidence of atrial fibrillation, such as men (compared to women) and white (compared to black) patients [5], [6]. These populations may also exhibit anatomical characteristics that favor the larger cardiac emboli to enter the inferior division. Confirmation of this hypothesis would help prioritize search for cardioembolic source in patients with inferior division MCA ischemic stroke and provide the basis for educating patients with atrial fibrillation about non-motor signs of stroke.

2. Methods

This study is based on a dataset of MRIs and metadata of patients with the clinical diagnosis of ischemic stroke, admitted to the Johns Hopkins Hospital Comprehensive Stroke Center between 2009 and 2019 (Flowchart for data inclusion in Fig. 1). Details of this publicly available dataset [7] are in [8]. Of note, the dataset is reperesentative of the total population of acute ischemic stroke patients at Johns Hopkins, as the vast majority of stroke patients at this center have MRI of the brain as part of their acute stroke evaluation. We have complied with all relevant guidelines and ethical regulations of the Johns Hopkins Institutional Review Board and received approval for the present study (IRB00290649).

Figure 1.

Flowchart of data inclusion

We included 105 patients with “frontal predominant” MCA strokes (if at least 75% of the infarct lesion was in the frontal lobe), and 197 patients with “temporoparietal predominant” MCA strokes (if at least 75% of the infarct lesion was in the temporal or parietal lobes). The lesion core from which the infarct volume was calculated was defined in DWI, in conjunction with the Apparent Diffusion Coefficient (ADC). Two experienced evaluators defined the lesion core, a neuroradiologist provided revisions, and a final decision was reached by consensus. Additional details are present in our previous publication [9]. The frontal and temporoparietal portions of the MCA were defined using a digital atlas of brain arterial territory [10], [11]. Information on the time of symptom onset is not reliably available for many patients, which is a common issue in stroke cohorts. However, most of the scans were 6h post symptoms (for patients with time of onset recorded) and therefore the probability of significant changes in stroke volume based on the time of onset is small [12].

Differences between infarct location (frontal or temporoparietal), sex, and race were examined via Chi-square test. Race is defined here according to the Revisions to the Standards for the Classification of Federal Data on Race and Ethnicity [13]. By this classification, “white” is a person having origins in any of the original peoples of Europe, the Middle East, or North Africa and “black or African American” is a person having origins in any of the Black racial groups of Africa. Because our population includes a lower percentage of Hispanic/Latinx and Asian patients, this study is limited to white and black people. In a secondary, exploratory analysis, we reviewed the patient's records to find whether the clinical diagnosis of atrial fibrillation was confirmed (by electrocardiogram monitoring).

3. Results

The summary of demographics and lesion profiles is in Table 1. There was no difference in patients' age between frontal and temporoparietal strokes. Temporoparietal infarcts were significantly larger than frontal. The group with frontal infarcts was composed predominantly by women and black patients. The statistical comparison (Fig. 2) revealed that male patients were more likely than female patients to have temporoparietal strokes versus frontal strokes (p-value=0.005), both in black (p-value=0.04) and white (p-value=0.03) groups. White patients were marginally more likely than black patients to have temporoparietal strokes versus frontal strokes (p-value=0.049). From the 85 patients with confirmed diagnosis of atrial fibrillation, the majority (55; 65%) had temporoparietal strokes, compared to frontal strokes (30; 35%).

Table 1.

Demographic and lesion characteristics. Continuous variables are shown as mean (standard deviation).

	Total (N=302)	Frontal (N=105)	Temporoparietal (N=197)
Age in years	63.3 (14.8)	64.4 (14.5)	62.7 (14.9)
Sex (female / male)	146 (48.3%) / 156 (51.7%)	64 (61.0%) / 41 (39.0%)	82 (41.6%) / 115 (58.4%)
Race (black / white)	155 (51.3%) /147 (48.7%)	62 (59.0%) / 43 (41.0%)	93 (47.2%) / 104 (52.8%)
lesion volume in ml	23.3 (39.6)	11.9 (16.6)	29.3 (46.4)

Figure 2.

Incidence of MCA strokes in frontal and temporoparietal areas, according to patient sex and race. P shows the p-values of the Chi-square test between groups. Male were more likely than female to have temporoparietal strokes versus frontal strokes (p-value=0.005), both in black (p-value=0.04) and white (p-value=0.03) groups. White patients were marginally more likely than black patients to have temporoparietal strokes versus frontal strokes (p-value=0.049).

4. Discussion

In this set of black and white patients with acute ischemic MCA strokes, we found temporoparietal strokes occurring more frequently than frontal strokes in populations with higher incidence of atrial fibrillation (male and white people [5], [6]). This confirmed a previous association observed in left hemisphere stroke patients [4], which has important clinical implications. For example, posterior (temporoparietal) infarcts should raise the suspicion for a cardioembolic source of stroke, and might indicate need for longer monitoring for atrial fibrillation or transesophageal echocardiogram in patients with appropriate risk factors.

Secondly, it is important to note that the symptoms of temporoparietal infarcts are often less obvious (especially to the patient) than symptoms of frontal infarcts. While Wernicke's aphasia may be very noticeable to listeners, the patient himself/herself might not be aware of the deficits in comprehension and meaningful speech. Moreover, left temporoparietal strokes may result in alexia, agraphia, acalculia, or right-left confusion. Even more of a concern is that right temporoparietal strokes may result in deficits that are difficult to detect without careful assessment, such as impaired empathy [14], impaired recognition of emotions in tone of voice or facial expressions, and altered discourse and appreciation of humor and metaphor [15], [16], [17], [18], [19]. Even hemispatial neglect is often not detected in patients with right hemisphere stroke [20]. These patients often have anosognosia for even obvious deficits [21]. Thus, patients with atrial fibrillation should be educated that they are at risk for strokes without motor symptoms.

In addition to the higher incidence of atrial fibrillation in certain groups, population-specific anatomical characteristics observed in the MCA bifurcation can provide a plausible account for the infarct location. That is, the larger vessel diameter, more linear path, and greater gravitational predilection in the inferior versus superior division MCA may explain why large cardiac emboli are more likely to cause temporoparietal than frontal strokes. A limitation of the present study is that we did not obtain independent evidence for the gravitational mechanism underlying this association proposed by Liebeskind and colleagues [4], which can be done in the future by arteriography and quantitative analysis of vessels' anatomy, including caliber and tortuosity.

Credit authorship contribution statement

AVF and AH conceived and designed the experiments; AVF, GK, EV performed the experiments; AVF, GK, MDS, AH, and JS analyzed and interpreted the data; AVF and AH contributed analysis tools and data; AVF, GK, EV, MDS wrote the paper.

Sources of funding

This research was supported in part by the National Institutes of Health, National Institute of Deaf and Communication Disorders, NIDCD, through R01 DC05375, R01 DC015466, P50 DC014664 (AEH, EV, MDS, AVF) and the National Institute of Biomedical Imaging and Bioengineering, NIBIB, NIBIB, through P41 EB031771 (AVF).

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Data availability

The data that supports this study is available in Zenodo https://doi.org/10.5281/zenodo.5722425 [22]. The dataset utilized is available at [7].