Aortic Dissection as a Possible Underlying Cause of Acute Ischemic Stroke

Ischemic stroke is caused by various pathological conditions. The etiology can be categorized into 3 major mechanisms: cardioembolism, large-artery atherosclerosis and small-vessel occlusion, and others (uncommon or undetermined etiology). Aortic dissection is not a major, but possible cause of ischemic stroke. If patients do not present with typical symptoms of aortic dissection, physicians may not take such a hidden disorder into consideration as a possible underlying cause of ischemic stroke. Although aortic dissection is an uncommon cause of ischemic stroke, neurologic manifestations are not rare in patients with aortic dissection. Neurologic deficits involving the brain, spinal cord, or peripheral nerves have been reported to occur in 13–42% of patients with aortic dissection.^1–6 Among them, ischemic stroke is the most frequent complication, which affects 6–32% of patients with aortic dissection.^1,5,7

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Aortic dissection can cause abrupt occlusion or narrowing of proximal lesions of the extracranial carotid or vertebral arteries branching from the aorta. The prevalence of involvement of supra-aortic branches in aortic dissection was reported as 29% by postmortem investigation¹ or 43% by imaging or intraoperative visualization.⁵ In particular, carotid circulation (81%) and right-sided arteries (69%) are often affected.⁵ There are 2 possible mechanisms for ischemic stroke secondary to aortic dissection. First, dissection obstructs blood flow through the true lumen of branching arteries, thus reducing cerebral perfusion and eventually causing brain tissue damage. Second, in the case of reentry into the true lumen, thrombus is transferred to the distal portion of the arteries and causes thromboembolism. Gaul et al reported that in stroke patients with aortic dissection, supra-aortic arteries were involved in 62.5%, whereas others suffered from ischemic stroke without extension of the dissection toward the supra-aortic vessels, indicating that stroke is caused by an embolic mechanism.⁵

Most patients with aortic dissection present with sudden onset of chest pain and this typical or distinctive pain is indicative of aortic dissection. However, dissection without pain may occur. The frequency of painless aortic dissection is 6–15%.^1–5,7 In the case of aortic dissection complicated by ischemic stroke, the presentation of pain may be less frequent. A previous study showed that only two-thirds of patients had chest pain, although most patients without initial neurologic symptoms experienced pain.⁵ Chest pain at onset may be missed in patients with impaired consciousness or aphasia, because of difficulty in inquiring about onset symptoms. Moreover, syncope occurs in 6–19% of patients with aortic dissection,^2–5,7 and this may also contribute to unawareness of aortic dissection.

If ischemic stroke develops secondary to aortic dissection, thrombolytic therapy is deleterious. Table shows previous case reports of ischemic stroke treated by thrombolytic therapy,^5,8–15 despite aortic dissection. Thrombolysis potentially causes critical adverse effects, such as cardiac tamponade or hemothorax. In Japan, a nationwide post-marketing survey was performed after approval of alteplase as a treatment for acute ischemic stroke. From October 2005 to September 2006, data sheets obtained from 2,069 ischemic stroke patients who were treated with intravenous alteplase disclosed that 10 patients died of exacerbation of thoracic aortic dissection or rupture of thoracic aortic aneurysm. Currently, intravenous thrombolytic therapy with alteplase is contraindicated for patients with aortic dissection.

Table. Reports of Cases of Acute Ischemic Stroke Secondary to Aortic Dissection Treated With Thrombolytic Therapy

Age, years	Sex	SBP/DBP, mmHg	NIHSS	Affected site	Chest symptoms	Chest X-ray	Carotid ultrasonography	Outcome	Reference
54	M	106/55	–	L	No pain	No MW	–	Death	8
44	M	–	18	R	Left flank and back pain after rt-PA therapy	–	CCA dissection	Independent walking at 1 m	9
56	F	108/56	16	R	Midsternal pain	No MW	CCA occlusion	mRS 4 at 3 m	10
76	F	–	–	R	No pain	–	–	Death	5
69	F	140/90	8	R	Chest discomfort Chest pain*	MW	–	NIHSS 0 at 3 m	11
72	F	160/110	16	R	No pain	No MW	–	Death	12
81	F	174/122	22	R	No pain	MW	CCA dissection	mRS 3 at 3 m	13
55	M	82/41	6	R, L	Retrosternal discomfort*	MW	CCA dissection	No symptom at 18 m	14
70	M	137/92	9	R	Dorsal discomfort after rt-PA therapy	No MW	CCA dissection	NIHSS 2 at 12 m	15

*Symptoms were retrospectively confirmed after thrombolytic therapy. CCA, common carotid artery; L/R, left/right; mRS, modified Rankin scale; MW, mediastinal widening; NIHSS, National Institute of Health Stroke Scale; rt-PA, recombinant tissue plasminogen activator; SBP/DBP, systolic/diastolic blood pressure.

To diagnose underlying aortic dissection in patients with ischemic stroke at an early stage, chest or back pain at onset needs to be confirmed with the possibility of this disease in mind. A cautious physical examination is also required regarding pulse or blood pressure differentials and a murmur of aortic regurgitation. A chest X-ray should be routinely performed to evaluate mediastinal or aortic widening. Further, carotid ultrasonography is indispensable for identifying arterial dissection because the non-invasive test can be performed at the bedside without wasting time. Previous case reports (Table) implicate the importance of these procedures before starting thrombolytic therapy.

The diagnosis of aortic dissection is confirmed by computed tomography (CT), magnetic resonance imaging, transthoracic and transesophageal echocardiography, or aortography. Sensitivity of these diagnostic tests is 65–100% and specificity is 85–100%.¹⁶ Although each diagnostic test has advantages and limitations,¹⁶ tests are performed considering their availability, as well as urgency and acceptability of ischemic stroke patients. Definitely ruling in and out acute aortic syndrome is important. Unenhanced CT can rule in acute aortic syndrome but does not have good properties regarding ruling out acute aortic syndrome.¹⁷ Therefore, contrast-enhanced CT may be required to definitely rule out aortic dissection. However, use of contrast medium is often avoided to reduce the time to administer recombinant tissue plasminogen activator in patients with ischemic stroke.

In this issue of the Journal, Yoshimuta et al¹⁸ suggest the usefulness of d-Dimer in the early diagnosis of aortic arch dissection causing ischemic stroke. They retrospectively investigated the d-Dimer values within 24 h of onset in 1,236 consecutive patients with ischemic stroke, among whom 9 patients suffered concomitant Stanford type A aortic arch dissection. They concluded that a cut-off value of 6.9 μg/ml of d-Dimer discriminated aortic dissection with a sensitivity of 100%, specificity of 94.8%, positive predictive value of 14.7%, and negative predictive value of 100% in patients with acute ischemic stroke. Because the prevalence of underlying aortic dissection is low overall in ischemic stroke patients, the positive predictive value is low. Therefore, d-Dimer above the cut-off value does not necessarily indicate the presence of aortic dissection, although a high d-Dimer value may indicate a possibility. In contrast, when d-Dimer is below the cut-off value, involvement of aortic dissection may be less likely, although a definite rule out is still required. Recently, a new clinical policy for thoracic aortic dissection was published by the American College of Emergency Physicians.¹⁹ According to this policy, the use of d-Dimer to rule out aortic dissection was assigned a Level C recommendation. The prognosis of patients with ischemic stroke secondary to aortic dissection is often catastrophic. Further study is required to validate the usefulness of d-Dimer in the early diagnosis of underlying aortic dissection in patients with acute ischemic stroke.

References

• 1.    Meszaros  I,  Morocz  J,  Szlavi  J,  Schmidt  J,  Tornoci  L,  Nagy  L, et al. Epidemiology and clinicopathology of aortic dissection. Chest 2000; 117: 1271–1278.
• 2.    von Kodolitsch  Y,  Schwartz  AG,  Nienaber  CA. Clinical prediction of acute aortic dissection. Arch Intern Med 2000; 160: 2977–2982.
• 3.    Mehta  RH,  O’Gara  PT,  Bossone  E,  Nienaber  CA,  Myrmel  T,  Cooper  JV, et al. Acute type A aortic dissection in the elderly: Clinical characteristics, management, and outcomes in the current era. J Am Coll Cardiol 2002; 40: 685–692.
• 4.    Trimarchi  S,  Nienaber  CA,  Rampoldi  V,  Myrmel  T,  Suzuki  T,  Mehta  RH, et al. Contemporary results of surgery in acute type A aortic dissection: The International Registry of Acute Aortic Dissection experience. J Thorac Cardiovasc Surg 2005; 129: 112–122.
• 5.    Gaul  C,  Dietrich  W,  Friedrich  I,  Sirch  J,  Erbguth  FJ. Neurological symptoms in type A aortic dissections. Stroke 2007; 38: 292–297.
• 6.    Gaul  C,  Dietrich  W,  Erbguth  FJ. Neurological symptoms in aortic dissection: A challenge for neurologists. Cerebrovasc Dis 2008; 26: 1–8.
• 7.    Hagan  PG,  Nienaber  CA,  Isselbacher  EM,  Bruckman  D,  Karavite  DJ,  Russman  PL, et al. The international registry of acute aortic dissection (IRAD): New insights into an old disease. JAMA 2000; 283: 897–903.
• 8.    Fessler  AJ,  Alberts  MJ. Stroke treatment with tissue plasminogen activator in the setting of aortic dissection. Neurology 2000; 54: 1010.
• 9.    Chua  CH,  Lien  LM,  Lin  CH,  Hung  CR. Emergency surgical intervention in a patient with delayed diagnosis of aortic dissection presenting with acute ischemic stroke and undergoing thrombolytic therapy. J Thorac Cardiovasc Surg 2005; 130: 1222–1224.
• 10.    Uchino  K,  Estrera  A,  Calleja  S,  Alexandrov  AV,  Garami  Z. Aortic dissection presenting as an acute ischemic stroke for thrombolysis. J Neuroimag 2005; 15: 281–283.
• 11.    Hong  KS,  Park  SY,  Whang  SI,  Seo  SY,  Lee  DH,  Kim  HJ, et al. Intravenous recombinant tissue plasminogen activator thrombolysis in a patient with acute ischemic stroke secondary to aortic dissection. J Clin Neurol 2009; 5: 49–52.
• 12.    Takeuchi  S,  Takasato  Y,  Masaoka  H,  Otani  N. Administration of recombinant tissue plasminogen activator to a case of cerebral infarction in the setting of painless aortic dissection. Neurol India 2009; 57: 808–809.
• 13.    Noel  M,  Short  J,  Farooq  MU. Thrombolytic therapy in a patient with acute ischemic stroke caused by aortic dissection. Clin Neurol Neurosurg 2010; 112: 695–696.
• 14.    Ramalingam  VS,  Sinnakirouchenan  R,  Sudhakar  S,  Brasch  AV. Acute ischemic stroke in aortic dissection: Case report and review of literature. Indian J Med Sci 2010; 64: 385–389.
• 15.    Mendes  A,  Mendonca  T,  Sousa  A,  Moreira  G,  Carvalho  M. Stroke secondary to aortic dissection treated with a thrombolytic: A successful case. Neurol Sci 2012; 33: 107–110.
• 16.    Pretre  R,  Von Segesser  LK. Aortic dissection. Lancet 1997; 349: 1461–1464.
• 17.    Kurabayashi  M,  Okishige  K,  Ueshima  D,  Yoshimura  K,  Shimura  T,  Suzuki  H, et al. Diagnostic utility of unenhanced computed tomography for acute aortic syndrome. Circ J 2014; 78: 1928–1934.
• 18.    Yoshimuta  T,  Yokoyama  H,  Okajima  T,  Tanaka  H,  Toyoda  K,  Nagatsuka  K, et al. Impact of elevated D-dimer on diagnosis of acute aortic dissection with isolated neurological symptoms in ischemic stroke. Circ J 2015; 79: 1841–1845.
• 19.    Diercks  DB,  Promes  SB,  Schuur  JD,  Shah  K,  Valente  JH,  Cantrill  SV; American College of Emergency Physicians Clinical Policies Subcommittee (Writing Committee) on Thoracic Aortic Dissection. Clinical policy: Critical issues in the evaluation and management of adult patients with suspected acute nontraumatic thoracic aortic dissection. Ann Emerg Med 2015; 65: 32–42.