Facial Angioedema and Stroke

Abstract

Background: Angioedema (AE) in stroke has been reported exclusively after thrombolysis with recombinant tissue-type plasminogen activator (rtPA). Previous studies proposed the insular cortex to play a specific role in the development of AE after stroke. We evaluated the incidence of AE in acute stroke and tried to identify the predominantly involved brain structures. Methods: We performed a retrospective search of our stroke database for patients with an AE. MRI data were analyzed by adapting the images to a standard size and superimposing the infarctions. The areas of overlap were assumed to represent the areas of interest. Results: 865 of 4,789 (18.1%) consecutive patients with acute stroke received IV rtPA, 20 of them (2.3%) developed AE. One patient developed AE without prior thrombolysis. The odds ratio for AE after rtPA was 93 (95% CI: 12-693). Of the 21 AE patients, 15 (71.4%) had ACE-inhibitor treatment (ACEi) and 7 (33.3%) had diabetes. In all but one patient, AE was clearly lateralized; then the AE was contralateral to the side of the ischemia in 18 of 20 patients (90.0%). An insular/peri-insular involvement was detected in 17/21 (81.0%). About 80.0% of the patients had a suspected MCA branch occlusion. Conclusions: In contrast to AE in other conditions, AE in stroke seems to feature a unique cerebral pathology because it is mostly lateralized (contralateral to an infarction), is associated with a distinct brain area, may even occur without rtPA, and is far more frequent than after thrombolysis for other indications. rtPA is the major risk factor. Similar to prior studies, we identified ACEi to be another risk factor, and a diabetic autonomic instability might further increase the risk. Central pathways involving the insular and peri-insular cortex seem to play a major role in the pathophysiology of AE in stroke.

Orolingual angioedema after thrombolysis is not associated with insular cortex ischemia on pre-thrombolysis CT

“…Higher frequency of insular involvement in OA patients was found by Hill et al [2], however, a nonblinded assessment of imaging was performed by the treating physician, which could have introduced a potential imaging assessment bias. The high frequency of insular cortex ischemia in OA patients (80%) found by Werner et al, was evaluated by MRI in 15 patients with OA, however, patients without OA were not analyzed [5]. Although we are not able to definitely exclude a possible contribution of insular ischemia for development of alteplase-related OA, our study does not support the suggestion that insular ischemia plays a key role in its pathophysiology.…”

“…Other case control-studies found a higher frequency of OA in women [3,5] and, in our study, female sex was an independent risk factor for OA, which is in accordance to a large cohort study of medication-related angioedema incidence [9]. The reason for this sex difference is not clear, but may include the influence of sex hormones on the regulation of inflammation and an increased T h 2 immune response in women [10], which is further supported by the female predominance of chronic urticaria, a condition with a pathophysiology closely linked to acquired angioedema [11].…”

“…In addition to contribute to several high order complex cerebral functions, insular cortex is known to mediate autonomic responses and it is involved in cardiac and vascular autonomic tone regulation and visceromotor control. The imbalance of sympathetic and parasympathetic control induced by insular ischemic lesions was proposed by several authors to contribute to the pathophysiology of OA [2][3][4][5]. Our aim was to study risk factors for OA occurrence in ischemic stroke patients treated with alteplase, in particular association with insular ischemia.…”

“…It consists of painless swelling of lips, tongue, face and occasionally oropharynx, occurring shortly after intravenous alteplase administration, which usually resolves during the first 24 h. Most case-control studies recognize use of angiotensin-converting enzyme inhibitors (ACE-I) as the main risk factor for occurrence of this potentially serious adverse event [1][2][3][4], and other authors found a higher frequency of insular ischemia in patients who developed angioedema [2,5]. In addition to contribute to several high order complex cerebral functions, insular cortex is known to mediate autonomic responses and it is involved in cardiac and vascular autonomic tone regulation and visceromotor control.…”

Orolingual Angioedema During or After Thrombolysis for Cerebral Ischemia

“…After reading of these 53 articles, 18 were selected for the combined analysis. 11,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] Seventeen articles were published in English 11,[13][14][15][16][17][19][20][21][22][23][24][25][26][27][28][29] and 1 in German. 18 The flow chart of the selection of articles is presented in Figure. None of these 18 articles 11,13-29 reported information on the prestroke mRS, alcohol consumption, weight, NIHSS at 2 and 24 hours and at 7 days, presence of infarct on imaging at 22 to 36 hours, s-ICH, infection, malignant infarct, and outcome at 3 months.…”