JMV—Journal de Médecine Vasculaire (2020) 45, 62—66 Available online at ScienceDirect www.sciencedirect.com ORIGINAL ARTICLE Basilar artery fenestration and ischemic stroke: An unclear causal relationship夽 H. El Otmani ∗, V. Fotso , B. El Moutawakil , M.A. Rafai Department of neurology-neurophysiology, IBN Rochd university health center, Casablanca, Morocco Received 3 August 2019; accepted 31 December 2019 Available online 12 March 2020 KEYWORDS Basilar artery fenestration; Basilar artery duplication; Ischemic stroke Summary Basilar artery fenestration is the second most commonly observed fenestration of the cerebral arteries. In addition to our case, we reviewed the clinical, imaging findings, treatment, and prognosis of 9 other reported cases. Patients’ mean age was 45.1 years. Half of them had cardiovascular risk factors. Mean time to diagnosis was 9.4 days. The main symptoms were right hemiparesis and dysarthria. Basilar artery fenestration was found in all patients, as well as ours, in addition to a thrombus, found in 2 cases. One patient was treated by IV thrombolysis and thrombectomy. In other cases, antiplatelet drugs or anticoagulants were used. A favorable outcome was observed in most cases with one reported death. © 2020 Elsevier Masson SAS. All rights reserved. Introduction Basilar artery (BA) fenestration, defined as a segmental duplication, is a developmental abnormality due to aberrant fusion of the primitive longitudinal neural arteries in the fifth week of fetal life [1,2]. Cerebral artery fenestration was reported with the frequency of approximately 23% Abbreviations: BA, Basilar Artery; MRI, Magnetic Resonance Imaging; MRA, Magnetic Resonance Angiography; CTA, Computed Tomography Angiography; AHT, Arterial Hypertension; AICA, Anterior Inferior Cerebellar Artery. 夽 This work was presented as a poster at the Maghrebian congress of neurology, 2018, December 13—15, Marrakech, Morocco. ∗ Corresponding author. E-mail address: hichamotmani@hotmail.com (H. El Otmani). https://doi.org/10.1016/j.jdmv.2020.01.147 2542-4513/© 2020 Elsevier Masson SAS. All rights reserved. in the anterior circulation and 7% in the posterior circulation [3]. BA fenestration is the second most reported fenestration of the cerebral arteries [4]. This variant may predispose to aneurysm formation and subarachnoid hemorrhage, dissection or thromboembolic events [5,6]. Generally, basilar artery occlusion is due to atherosclerosis with a superimposed thrombosis [5]. Therefore, the causal relationship between this anatomic variant and cerebral events is unclear and controversial. Here we report a case of symptomatic BA fenestration revealed by a brainstem infarction and review other published reports in the literature. Observation A 33-year-old Ivorian male, with a smoking history, presented with sudden onset of vertigo, tingling of the Basilar artery fenestration and ischemic stroke 63 Figure 1 A. Diffusion-weighted MR imaging showing high signal intensity in the left pontine area: recent ischemic lesion. B. MRA: BA fenestration (red arrow). C. CTA: BA fenestration (orange arrow). D. Normal aspect: the primitive longitudinal neural arteries merge (dashed area) to form the basilar artery. Basilar artery fenestration: partial fusion of these arteries (blue arrow). D. PCOM: posterior communicating arteries PICA: posterior inferior cerebellar arteriesAICA: anterior inferior cerebellar arteries SCA: superior cerebellar arteries. left hemiface, diplopia and speech difficulties. His condition worsened 2 hours later by an acute onset of right-sided paresis. Neurological examination showed rightsided hemiparesis with left facial palsy and dysarthria (National Institutes of Health Stroke Scale (NIHSS): 8/42); mRs = 4. Diffusion-weighted magnetic resonance imaging (MRI) revealed a hypersignal in the left pontine area, compatible with an ischemic lesion (Fig. 1A). Magnetic resonance angiography (MRA), using time-of-flight technique, displayed a focal signal intensity loss within the basilar artery (Fig. 1B). This was confirmed by Computed tomography angiogram (CTA) which also showed no dissection (Fig. 1C). A complete etiological assessment; lipid panel, biological and, especially, cardiac workout (24-hour Holter electrocardiogram, transthoracic echocardiogram and supra-aortic trunks ultrasound) were all normal. Blood cell count didn’t show signs of anemia or sickle cell disease. According to these findings, diagnosis of an acute thromboembolic brainstem infarction due to BA fenestration was suspected. The patient was treated with an antiplatelet drug (aspirin 100 mg daily) as well as motor rehabilitation, for six months, with a notably favorable outcome at 3 months (mRs = 1 vs. 4). Material and methods We performed a literature review of MEDLINE, Science Direct and Google Scholar databases for articles published in English or French from December 1987 to December 2018 using the search terms ‘‘basilar artery fenestration,’’ and ‘‘basilar artery duplication.’’ We also examined all manuscripts that had been referred in these articles. We finally included symptomatic cases of BA fenestration in the form of infarction. We excluded cases without infarction and articles not written in English or French. We added our case to 9 other published reports of symptomatic BA fenestration (Table 1). Results Symptomatic cases The symptomatic cases are: • characteristics of the study population (10 cases): patients’ mean age was 45.1 years (range, 5 to 76 years); 64 Table 1 Cases of ischemic stroke secondary to basilar artery fenestration. Case reports Age/Gender Background/ Mean time to diagnosis Symptoms Our case 33/M Tobacco/3 days Right hemiparesis, dysarthria Mei nel et al. [7] 76/M Scherer et al. [4] 69/M Gold et al. [1] 12/M AHT, OSA, Dyslipidemia/90 min AHT, Diabetes, Dyslipidemia/3 days /1 day S. He et al. [3] 28/M Woo et al. [2] 55/F Kloska et al. [10] 05/M Palazzo et al. [8] Vessels Therapy Outcome MRI/MRA/CTA Left pontine ischemia BA fenestration Good Right hemiparesis, hemiataxia, dysarthria Right hemiparesis, dysarthria, dysphagia MRI/MRA/ Angiography Left pontine ischemia MRI/MRA/ Virtual endoscopy Left pontine ischemia BA fenestration/ Thrombus BA fenestration Trombocytes agrégation inhibitors IV thrombolysis/ thrombectomy Right hemiparesis, dysmetria MRI/MRA/ Angiography Bilateral cerebellar ischemia /1 month Numbness of limbs CTA AHT, Diabetes/1 day /3 weeks Right hemiparesis + facial palsy, dysarthria Headache, dizziness, severe somnolence 59/M AHT/3 weeks Berry et al. [5] 43/M /2 weeks Dysarthria, left dysmetria, right superior quadrantanopia Eyesight, headache, status epilpticus Uchiyama et al. [9] 71/M AHT/1 day Imaging technique Parenchyma MRI/MRA/ virtual Endoscopy Apolipoprotein MRI/MRA (a) and heterozygotic factor XII deficiency Normal MRI/MRA/CTA Left pontine ischemia CT/MRI/Auto psy Increased T2-weighted image in the pons Multiples lacunae + atrophy Hyperuricemia CT/ Angiography Left paramedian pons and the left PCA ischemia Left PCA + cerebellar infarction BA fenestration BA fenestration + moya moya BA fenestration Heparin/ trombocytes agrégation inhibitors Aspirin Heparin BA fenestration or thrombus Trombocytes agrégation inhibitors BA fenestration Good Heparin/clopidogrel Good Proximal BA fenestration BA fenestration/ Thrombus NIHSS = 0 Good Death H. El Otmani et al. Unsteady gait, dysarthria, diplopia Etiological assesment Basilar artery fenestration and ischemic stroke included 9 men (90%). Half of them had cardiovascular risk factors (5 patients): hypertension was found in 5 patients (50%) [2,4,7—9], diabetes in 2 patients (20%) [2,4], dyslipidemia in 2 patients (20%) [4,7], obstructive sleep apnea and overweight in 1 patient (10%) [7]. Our patient’s smoking habit was stopped 7 years earlier. The mean time to diagnosis was 9.4 days; the main symptoms were right hemiparesis and dysarthria [1,2,4,7]; • imaging results: ischemic stroke was found in the basilar artery territory, except one patient with multiple lacunae and atrophy. There was no hemorrhagic transformation. The BA fenestration was found in all patients as well as ours with an associated thrombus, suspected in one case [8] and confirmed in 2 cases [5,7]. There was no aneurysm nor dissection; • etiological assessment: found, essentially, apolipoprotein(a) and heterozygotic factor XII deficiency [10]. Concerning the other cases, no abnormality was noted in the etiological assessment, especially the cardiac workout; • treatment: one patient was treated by IV thrombolysis and thrombectomy. In the other cases, antiplatelet agents or heparin were used in addition to physiotherapy; • outcome: almost all cases have seen their symptoms improved except for one notified death. Discussion Patients’ mean age was 45.1 years; this age of occurrence is younger than that seen in all 5657 sequential cerebral CTA of patients analyzed by Gao et al. (mean age, 54.3 years) [6]. Fenestration in the cerebrovascular system (particularly the vertebral arteries) was first detected, on autopsy, in 1866. Since then, many cases have been documented [6]. The incidence of BA fenestration varies from 0.3% in angiographic examinations to 5.26% in the autopsy series [2,7]. There are two types of cerebral arteries fenestrations: true duplications, which have a relatively large arterial window, and arterial slits, which are considered to be intraluminal defects [2,4]. Fenestration is referred to the localized duplication of a vessel [2] (Fig. 1D). Diagnosis CTA can be helpful, in addition to MRA, for diagnosis. But both have pitfalls in the diagnosis of intracranial vascular disease [8]. Therefore, virtual endoscopy may be useful in some cases in combination with conventional techniques [4]. CTA was performed in our patient confirming a diagnosis of BA fenestration already suspected in MRA. The proximal end of the basilar artery, at vertebral arteries convergence, seems the most prone to fenestration [1,2]. BA fenestration is classified into 4 types according to its location and the AICA’s origin (anterior inferior cerebellar artery) [6]. Other associated malformations Fenestrations of cerebral arteries can be multiple [4]. The formation of saccular aneurysm is the most common 65 complication [1]. Gao et al. reported 34 cases of aneurysms in 132 cases of BA fenestration from a total of 5657 CTAs [6]. In addition, it can be associated with cerebral arteriovenous malformation, persistent trigeminal artery [4], Moya Moya disease and azygos anterior cerebral artery [3,6]. There was no associated vascular abnormality in our case as shown by CTA. Pathophysiology An association of cerebral artery fenestration with a subarachnoid hemorrhage is more frequently reported than an ischemic event. In general, when BA fenestration is symptomatic; it results in a subarachnoid hemorrhage due to a saccular aneurysm rupture [9]. Because BA fenestration is uncommon and is usually an incidental product on autopsy or angiography [3,9]; little is known about it’s functional consequences [1]. In addition, its clinical significance remains controversial. However, there is a defect in the media of the arterial wall with turbulent blood flow and hemodynamic disturbances at the fenestration site that could explain the formation of thrombi and consequently the occurrence of ischemic stroke [2,5,6,10]. Gold et al. hypothesized this to be the cause of stroke in their patient [1]. We assume that it was the case in our patient. Aneurysm formation can be explained by the same mechanism [2,3]. To date, only a few case reports presume a causal association between brainstem infarction and basilar artery fenestration [10]; these cases are reported here (Table 1). If an AICA arises from the thrombosed fenestrated segment of the BA, both pontine and cerebellar infarctions may develop [1,8]. A misinterpretation of BA fenestration as an arterial dissection or thrombosis, especially in patients with stroke, can result in wrong diagnostic, and thus therapeutic, approaches. Its management is more or less aggressive depending on the case [4]. Conclusion Our literature review and case report showed that 75% of patients with ischemic stroke due to BA fenestration have a pontine paramedian involvement. Therefore, such location in a patient without vascular risk factors (in particular atherosclerosis) should suggest this diagnosis. Our patient presented with a suspected symptomatic BA fenestration as there was a corollary between the brainstem infarction location and that of the vascular abnormality with a negative etiological assessment otherwise. Disclosure of interest The authors declare that they have no competing interest. References [1] Gold JJ, Crawford JR. An unusual cause of pediatric stroke secondary to congenital basilar artery fenestration. Case Rep Crit Care 2013;2013:627972. [2] Woo SR, Seo MW, Kim YH, Kwak HS, Han YM, Chung GH, et al. Extreme Duplication-type, Non separated Fenestration of the 66 Basilar Artery in a Patient with Pontine Infarction: Confirmation with Virtual Arterial Endoscopy. J Clin Neurol 2006;2:74—7. [3] He S, Wu YY, Zhao T, Chen S, Zhang J. Vertebro-basilar artery fenestration with moya-moya disease. Neurol Sci 2016;37:301—3. [4] Scherer A, Siebler M, Aulich A. Virtual arterial endoscopy as a diagnostic aid in a patient with basilar artery fenestration and thromboembolic pontine infarct. AJNR Am J Neuroradiol 2002;23:1237—9. [5] Berry 3rd AD, Kepes JJ, Wetzel MD. Segmental duplication of the basilar artery with thrombosis. Stroke 1988;19:256—60. [6] Gao L-Y, Guo X, Zhou JJ, Zhang Q, Fu J, Chen WJ, et al. Basilar artery fenestration detected with CT angiography. Eur Radiol 2013;23:2861—7. H. El Otmani et al. [7] Meinel TR, Pult F, GrallaJ, Arnold M, Bassetti C, Jung S. Successful endovascular recanalization of a partially occluded basilar artery fenestration. Interv Neuroradiol 2019;25:44—6. [8] Palazzo P, Ruff M, Lyerly MJ, Alexandrov AV. Basilar artery thrombus vs. fenestration: a differential diagnostic challenge in acute ischemic stroke. J Neuroimaging 2014;24:607—9. [9] Uchiyama S, Yoshinaga T, Shima T. A case of basilar artery fenestration with recurrent attacks of vertebrobasilar insufficiency. No To Shinkei 1987;39:1163—9. [10] Kloska SP, Schlegel PM, Sträter R, Niederstadt TU. Causality of pediatric brainstem infarction and basilar artery fenestration? Pediatr Neurol 2006;35:436—8.