a b s t r a c t

Background and purpose: Accurate diagnosis of Acute aortic dissection is sometimes difficult because of ac- companying central nervous system (CNS) symptoms. The purpose of this study was to investigate the clinical characteristics of Type A AAD (TAAAD) with CNS symptoms.

Methods: We retrospectively reviewed the medical records of 8403 patients ambulanced to our emergency and critical care center between April 2009 and May 2014.

Results: We identified 59 TAAAD patients for the analysis (mean age, 67.3 +- 10.5 years; 37 (62.0%) male). Eleven patients (18.6%) presented CNS symptoms at the onset of TAAAD, and these patients complained less frequently of typical chest and back pain than those without CNS symptoms (p b 0.0001). Initial systolic and diastolic blood pressure were lower (p = 0.003, and p = 0.049, respectively) and involvement of the supra-aortic artery was more frequent in patients with CNS symptoms (p b 0.0001).

Conclusion: Because CNS symptom can mask chest and back pain caused by TAAAD, physicians should always consider the possibility of TAAAD in patients with CNS symptoms in emergency medicine settings.

(C) 2017

Methods

Acute aortic dissection (AAD) is one of the most life-threatening car- diovascular diseases, and an accurate emergency diagnosis and early treatment are necessary [1-3]. The typical presentation for AAD is sudden-onset chest and back pain, and in particular, migrating pain from the chest to the lower back raises the likelihood of aortic dissec- tion. The primary symptoms of AAD, other than chest and back pain, are focal Neurological deficits resulting from brain or spinal cord ische- mia, syncope, and pain in the lower limbs. Because focal brain ischemia and ischemic encephalopathy are often complicated by disturbance of consciousness, speech impediment, and seizure in AAD patients pre- senting with central nervous system (CNS) symptoms, the diagnosis of AAD with brain ischemia is sometimes difficult. After a report of fatal- ities from intravenous thrombolysis for Brain infarction caused by AAD, AAD was added as a contraindication for this therapy in the Japanese guidelines [4]. An accurate diagnosis for AAD with brain injuries is es- sential in emergency medicine settings. Therefore, we aimed to investi- gate the clinical characteristics of AAD with CNS onset symptoms.

* Corresponding author at: Emergency and Critical Care Center, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

E-mail address: [email protected] (Y. Shono).

This was a retrospective single-center study approved by the institu- tional review board at the Kyushu University Hospital.

Patient selection

Eight thousand four hundred and three patients ambulanced to the emergency department of the Kyushu University Hospital between April 2009 and May 2014 were retrospectively enrolled in this study. Patients with a diagnosis of type A AAD (TAAAD) confirmed by contrast-enhanced computed tomography (CT) were selected from this group, for a medical record review.

Clinical assessment

We collected baseline characteristics, such as demographic factors, risk factors for atherosclerosis, chest and back pain, CNS symptoms, ini- tial Blood pressure and heart rate in the emergency department, from patients’ medical records. Shock Index was calculated by dividing the heart rate by the systolic BP (SBP). CNS symptoms were defined according to a previous study [5], and symptoms suspected to be caused by ischemic/hypoxic encephalopathy, ischemic stroke, or spinal ische- mia were included as CNS symptoms. To evaluate disturbance of

http://dx.doi.org/10.1016/j.ajem.2017.06.011

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Y. Shono et al. / American Journal of Emergency Medicine 35 (2017) 1836–1838 1837

consciousness, we used the Emergency Coma Scale (ECS), which con- sists of 3 major categories, and has previously been reported to be suit- able for evaluating patients in neurological emergency settings [6]. The 3-category structure of the ECS is as follows: category 1: The patients open their eyes, speak, and/or behave spontaneously; category 2: The patients can open their eyes, speak, and/or behave with stimulation; category 3: The patients can neither open their eyes nor speak with painful stimulation. Risk factors for atherosclerosis included hyperten- sion (SBP >= 140 mm Hg, Diastolic BP (DBP) >= 90 mm Hg, or a history of taking Antihypertensive medication); diabetes mellitus (fasting blood glucose >= 6.99 mmol/L, positive 75 g oral glucose tolerance test re- sult, or a history of antidiabetic medication or insulin); dyslipidemia (low-density lipoprotein cholesterol >= 3.62 mmol/L, high-density lipo- protein cholesterol b 1.03 mmol/L, triglycerides >= 1.69 mmol/L, or a his- tory of taking cholesterol-lowering medication); a smoking habit (previous or current); coronary heart disease; and chronic kidney dis- ease (estimated glomerular filtration rate b 60 ml/min/1.73 m²). contrast-enhanced CT for diagnosis of TAAAD and involvement of the supra-aortic arteries was interpreted independently by two or more physicians including a radiologist. Hemoglobin, hematocrit, Red blood cell count, D-dimer, and fibrinogen degradation product levels were measured using blood samples obtained in the emergency department.

Patient grouping and statistical analysis

All data are expressed as the mean +- standard deviation. The pa- tients were dichotomized according to the presence of CNS symptoms (CNS group and non-CNS group), and clinical characteristics were com- pared using an unpaired t-test, Mann-Whitney U test, or ?² test where appropriate. All statistical analyses were performed using JMP software version 11.0.0 for Windows(R) (SAS Institute Inc. Cary, NC). A p-value b

0.05 was considered statistically significant.

Results

TAAAD was diagnosed in 59 patients (0.7%) with a mean age of 67.3

+- 10.5 years, including 22 females (38.0%). Eleven cases (18.6%) of TAAAD showed CNS symptoms at their initial presentation, and distur- bance of consciousness was evident in all 11 of those patients. Among them, five patients were classified as category 3, three patients were classified as category 2, and the remaining three patients were classified as category 1 on the ECS. Left hemiparesis was the second most frequent symptom, present in four patients. One patient each had the following symptoms: dysarthria, unilateral spatial neglect, eye deviation, and in- voluntary movement. No patients presented symptoms of spinal cord ischemia. Two of all 59 patients were diagnosed with TAAAD by the contrast-enhanced CT that was performed after admission with a differ- ent diagnosis. Initial diagnoses of the two patients were ischemic stroke and gastro-esophageal reflux disease, respectively.

There was no significant difference in age, sex, and frequency of risk

factors for atherosclerosis between the two groups (Table 1). The presence of chest and back pain was significantly less frequent in the

Table 1

Patients’ baseline characteristics.

CNS group than in the non-CNS group (p b 0.0001), and initial SBP and DBP were significantly lower in the CNS group (p = 0.003 and p = 0.049, respectively). Initial heart rate did not differ between the two groups, but the shock index was higher in the CNS group. There was no significant difference in erythrocyte profile and coagula- tion markers, but the supra-aortic vessels were affected more frequently in the CNS group than in the non-CNS group (p b 0.0001) (Table 2). Thir- teen patients were examined by carotid duplex ultrasonography in the emergency department, with positive predictive value and negative predictive value of 100% for lesions in the aortic branches detected by contrast-enhanced CT. The in-hospital mortality rate was not signifi- cantly different between the CNS (27.3% (3/11 patients)) and non-CNS groups (22.9% (11/48 patients)).

One patient was treated with intravenous thrombolysis, as follows: A 66-year-old man presented a decreased level of consciousness, dysar- thria, and left hemiparesis, without complaints of chest or back pain. Magnetic resonance imaging (MRI) was performed emergently, and re- vealed occlusion of the right Internal carotid artery. Although intrave- nous recombinant tissue-type plasminogen activator (rtPA) infusion was begun 100 min after the onset of symptoms, it did not improve his neurological symptoms. Immediate follow-up MRI identified the dissection of the right Common carotid artery. The subsequent contrast-enhanced CT confirmed TAAAD extending from the Ascending aorta to the bilateral common iliac arteries. The patient then underwent urgent total aortic arch replacement. He was transferred to a rehabilita- tion hospital for his remaining left hemiparesis on the 47th day after onset.

Discussion

Our results showed that 18.6% of TAAAD patients presented CNS symptoms as primary symptoms and that the TAAAD patients with CNS symptoms complained less frequently of typical chest and back pain than those without CNS symptoms. We also found that initial blood pressure was lower and the supra-aortic artery was affected more frequently in TAAAD patients with CNS symptoms. Several previ- ous studies have focused on neurological symptoms in TAAAD patients, reporting an incidence of CNS symptoms of 16.6%-32% [3,5,7], compara- ble with our findings.

Regarding the frequency of chest and back pain, Gaul et al. retrospec-

tively examined 102 patients with TAAAD [7] and reported that two- thirds of patients with neurological symptoms presented chest or back pain, a significantly lower proportion than what was observed in pa- tients without CNS symptoms. Bossone et al. analyzed data from 2202 TAAAD patients and showed that TAAAD patients with stroke presented chest and back pain less frequently than those without stroke (69.7% vs. 82.3%, 32.4% vs. 43.4%, respectively) [8]. These results are similar to our findings, but the difference between the two groups in our study was more remarkable (36.4% vs. 89.6%). Whereas the study of Gaul et al. in- cluded all neurological symptoms such as peripheral nerve deficits in the symptomatic group and Bossone et al. included only stroke, we in- cluded stroke and ischemic encephalopathy. Thus, chest and/or back pain may have been masked or overlooked due to CNS symptoms in our case group.

To our knowledge, there have been no previous studies evaluating

SD: standard deviation.

CNS group

n = 11

Age (years) mean +- SD	66.7 +- 8.4	67.5 +- 11.0	0.826
Female, n (%)	2 (18.2)	20 (42.5)	0.178
Risk factors for atherosclerosis Hypertension, n (%)	7 (63.6)	31 (79.5)	0.424
Diabetes mellitus, n (%)	0 (0.0)	1 (2.6)	1.000
Dyslipidemia, n (%)	2 (18.2)	10 (25.6)	1.000
Smoking, n (%)	3 (27.3)	16 (41.0)	0.498
Coronary heart disease, n (%)	0 (0.0)	9 (23.1)	0.177
Chronic kidney disease, n (%)	6 (54.6.)	10 (25.6)	0.140

Non-CNS group

n = 48

p-Value

the association between blood pressure and neurological symptoms in TAAAD patients. One cohort study of TAAAD and stroke demonstrated no significant difference in SBP and DBP between TAAAD patients with and without stroke [8]. In our study, 6 of 11 patients with CNS symptoms presented solely disturbance of consciousness, which likely resulted from ischemic encephalopathy. Whole-brain hypo-perfusion caused by systemic hypotension is one of the pathophysiological mech- anisms of ischemic encephalopathy, which may explain the noticeably low blood pressure in our case group.

The more frequent involvement of the supra-aortic artery in the CNS group in our study is consistent with past studies [7,8]. This finding is

1838 Y. Shono et al. / American Journal of Emergency Medicine 35 (2017) 1836–1838

Table 2

Clinical examination, laboratory data, and radiological findings in TAAAD patients with and without CNS symptoms.

	CNS group	Non-CNS group	p-Value
	n = 11	n = 48
Chest and back pain, n (%)	4 (36.4)	43 (89.6)	b0.0001
Systolic blood pressure (mm Hg), mean +- SD	114.9 +- 28.9	151.0 +- 35.2	0.003
Diastolic blood pressure (mm Hg), mean +- SD	66.5 +- 17.3	83.6 +- 23.6	0.049
Heart rate (beat per minute), mean +- SD	73.4 +- 4.89	74.3 +- 2.60	0.869
Shock index, mean +- SD	0.706 +- 0.316	0.509 +- 0.118	0.0023
Hemoglobin (g/dL), mean +- SD	13.3 +- 1.59	12.9 +- 2.39	0.615
Red blood cell (x104/uL), mean +- SD	415 +- 53.0	425 +- 69.6	0.679
D-dimer (ug/ml), mean +- SD	27.4 +- 2.12	15.9 +- 18.8	0.137
FDP (ug/ml), mean +- SD	140.0 +- 205.3	66.3 +- 123.0	0.143
Involvement of supra-aortic artery, n (%)	11 (100.0)	13 (27.7)	b0.0001
Innominate artery, n (%)	11 (100.0)	10 (21.3)	b0.0001
Common carotid artery, n (%)	7 (63.6)	6 (12.8)	0.0012
Left subclavian artery, n (%)	4 (36.4)	7 (14.9)	0.193

SD, standard deviation.

valid because blockage of one or more brain-supplying aortic branches can lead to whole-brain hypo-perfusion or focal brain ischemia. Contrast-enhanced CT is a widely used technique recognized as one of the most reliable modalities for diagnosing TAAAD and lesions of the aortic branch [9]. However, it is difficult to routinely perform contrast- enhanced CT when a patient is restless or delirious, or when time is lim- ited due to a suspicion of acute cerebral infarction approved for rtPA therapy. Several reports have stated that Carotid ultrasonography is use- ful to avoid rtPA therapy in patients with ischemic stroke caused by TAAAD [10-13]. Because carotid ultrasonography is a simple, quick, and noninvasive technique, it may be a valuable tool for identifying TAAAD in ischemic stroke patients in emergency settings.

Limitations

As this study was retrospective and involved a single center, the number of cases was relatively small. Institutional bias may also be pres- ent, and not all results of this study can be generalized. Second, because of the emergency care nature of the disorder, analysis of this study was based mainly on information obtained from practice in the emergency department; therefore, we may have underestimated the risk factors for atherosclerosis.

Conclusion

CNS symptoms were found in 18.6% of TAAAD patients at symptom onset. Because chest and back pain are masked, TAAAD patients with initial CNS symptoms may not be recognized as TAAAD patients in emergency settings.

Competing interests and funding

None.

Contributions

Study concept and design: Shono.

Acquisition, analysis or interpretation of data: Shono.

Collection of data: Shono, Akahoshi, Mezuki, Momii, Kaku, Maki, Tokuda.

Drafting of the manuscript: Shono, Akahoshi, Mezuki.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Shono, Mezuki.

Study supervision: Ago, Kitazono, Maehara.

Final approval of the manuscript: Maehara.

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