2025 Volume 12 Pages 133-138
A 24-year-old woman, who was diagnosed with cardiac sarcoidosis as an adolescent, was brought to the emergency room with right hemiparesis and impaired consciousness 21 days after giving birth to her second child by cesarean section. Brain magnetic resonance imaging revealed high diffusion-weighted signal changes in the left insular cortex and temporal lobe. Magnetic resonance angiography revealed occlusion of the left internal carotid artery. She was treated with alteplase administration and mechanical thrombectomy, resulting in the improvement of neurological symptoms. Subsequent examination revealed a ventricular aneurysm caused by cardiac sarcoidosis, leading to the diagnosis of cardioembolic stroke. It was also assumed that the patient's postpartum period caused increased coagulability, which contributed to the ischemic stroke. It is important to recognize that abnormal cardiac function and morphology due to cardiac sarcoidosis and increased coagulability during the postpartum period may contribute to ischemic stroke.
Sarcoidosis is an idiopathic systemic granulomatous disease. Clinically manifested cardiac sarcoidosis (CS) is a rare condition that occurs in approximately 2%-5% of sarcoidosis patients.1,2) However, findings from autopsy cases and increased detection rates due to advances in cardiac imaging indicate that the frequency of latent CS is higher.2-6) Reports on ischemic stroke associated with CS are extremely limited, and treatment has not been established.
During pregnancy and the postpartum period, physiological changes such as increased blood coagulation and venous stasis can lead to acute ischemic strokes as a complication.7) Pregnancy increases the risk of thrombosis in general, but especially during the delivery period and up to 6 weeks postpartum.8)
Here, we describe a rare case in which mechanical thrombectomy (MT) was performed for internal carotid artery occlusion (ICAO) associated with CS that occurred during the postpartum period.
The patient was a 24-year-old woman diagnosed with CS during adolescence at another hospital's cardiology department. She also underwent a cesarean section for the birth of her second child and was 21 days postpartum. She was brought to the emergency room with a sudden onset of right hemiparesis and impaired consciousness. On admission, her National Institutes of Health Stroke Scale (NIHSS) score was 28, and magnetic resonance imaging (MRI) showed slight high-signal changes in diffusion-weighted images of the left insular cortex and part of the temporal lobe (Fig. 1A). Magnetic resonance angiography showed a loss of signal in the left internal carotid artery (ICA) from its origin (Fig. 1B), leading to a diagnosis of acute cerebral infarction due to left ICAO. Coagulation function tests showed no obvious abnormalities, and the findings were as follows: prothrombin time 1.04, activated partial thromboplastin time 29.4 sec, fibrinogen 181 mg/dL, D-dimer 0.58 μg/mL. Alteplase was administered and MT was performed. Distal occlusion of the left ICA was confirmed by angiography. A balloon catheter was guided to the origin of the left ICA cervical portion, and the balloon was inflated. Manual aspiration was performed several times using a balloon catheter, and a large thrombus was collected, resulting in successful complete reperfusion and a Thrombolysis in Cerebral Infarction score of 3 (Fig. 2A-C). The thrombus collected during the thrombectomy was macroscopically identified as a red thrombus. No complications were observed, postoperative MRI revealed only a small infarct on the inner side of the left temporal lobe (Fig. 1C). Twelve hours after the MT, the manual muscle test scores of the right upper and lower limbs improved from 2 to 4, and 24 hours later, the patient was able to walk without assistance. Although mild aphasia symptoms persisted on the day after treatment, no obvious abnormalities were found in the neurocognitive function tests conducted two days after treatment. The NIHSS score was 0, with no apparent neurological deficits.
MRI at onset of internal carotid artery occlusion.
Diffusion-weighted MRI (A) showed acute infarction of the left frontotemporal lobe. Magnetic resonance angiography (B) showed occlusion of the left internal carotid artery. Diffusion-weighted MRI on the day after thrombectomy (C) revealed a high-signal region only on the inner side of the left temporal lobe.
MRI: magnetic resonance imaging
Cerebral angiography during mechanical thrombectomy.
The lateral view prior to thrombectomy did not show the left internal carotid artery bifurcation and beyond (A, arrow). After thrombectomy, frontal and lateral views showed complete recanalization with a Thrombolysis in Cerebral Infarction score of 3 (B, C).
Pathological evaluation of the thrombus indicated that it was a fresh thrombus consisting of fibrin, red blood cells, white blood cells, and platelets, suggesting it was a red thrombus. Transesophageal echocardiography (TEE) showed a significant decrease in the ejection fraction (EF, 20.9%) and suspected cardiac apical aneurysms in both the right and left ventricles; however, no obvious thrombus was identified. No patent foramen ovale was observed. The microbubble test results were negative. Cardiac computed tomography (CT) angiography revealed the presence of ventricular aneurysms on both sides but did not show any obvious thrombus (Fig. 3). Ultrasound evaluation of the lower-extremity veins did not reveal any deep vein thrombosis. Holter electrocardiography revealed no evidence of atrial fibrillation.
Cardiac computed tomography angiography, coronary section, showed the presence of ventricular aneurysms on left ventricle (arrow) but no obvious thrombus.
The detailed history of the patient's CS diagnosis was as follows. At the time of initial diagnosis, a detailed examination was performed because of palpitations and echocardiography revealed cardiac dysfunction and a right ventricular apical thrombus. Anticoagulation therapy with heparin and warfarin was administered, and the disappearance of the thrombus was confirmed. Although the myocardial biopsy did not show strong evidence of sarcoidosis, such as the formation of granulomas with epithelioid cells, further investigations indicated CS. Late gadolinium enhancement MRI was positive, and resting-state fluorodeoxyglucose (FDG) positron emission tomography revealed abnormal accumulation of FDG in areas including the apex to the anterior wall, posterior septum to the posterior wall, and inferior wall (Fig. 4). These results led to the diagnosis of CS, and prednisone therapy was continued. At the time of the stroke, the patient was taking 5 mg/day of prednisone.
Resting state FDG positron emission tomography.
Abnormal FDG accumulation is seen in the apex to anterior wall, posterior septum to posterior wall, and inferior wall (arrows).
FDG: fluorodeoxyglucose
Based on these findings, we determined that the patient had an embolic stroke due to a thrombus arising from ventricular aneurysms associated with CS. Heparin therapy was initiated and subsequently replaced with warfarin to prevent recurrence. The prothrombin time-international normalized ratio was adjusted to 2.0-3.0, and the patient was discharged home on the 13th day of admission. Anticoagulant therapy with warfarin has been continued, and there has been no recurrence of cerebral infarction for 10 months.
Informed consent was obtained from the patient for the publication of the patient's information and images and was recorded.
There are very few reports on ischemic stroke associated with CS (Table 1).9-13) In CS, cardiomyopathy leads to impaired cardiac function, resulting in hypokinesis and the formation of ventricular aneurysms. Subramanian et al.12) reported that the frequency of ischemic stroke in patients with CS was 7.2%; left ventricular dysfunction was present in all patients who developed ischemic stroke, and a left ventricular apical clot was found in half of the patients who developed ischemic stroke. Additionally, in patients diagnosed with CS-related stroke who presented with reduced EF, left ventricular angiography revealed turbulent flow in the ventricular aneurysm, suggesting blood stasis.13) Another report showed the presence of a large left ventricular thrombus in a CS patient with a decreased EF.14) Stasis of blood flow due to decreased ventricular function is considered to be a risk of inducing thrombus formation.15) As one of the potential causes of ischemic stroke in CS patients, left ventricular thrombus resulting from hypokinesis and ventricular aneurysm formation due to impaired cardiac function may be a contributing factor. In our case, a thrombus was not detected on TEE or cardiac CT. However, hypokinesis and a left ventricular aneurysm were apparent, suggesting a similar mechanism leading to thrombus formation. Furthermore, inflammation caused by sarcoid cardiomyopathy may also influence thrombus formation in the left ventricle.16) Atrial fibrillation occurs in approximately 18% of patients with CS,17) which is also considered one of the causes of ischemic stroke. The proportion of ischemic stroke cases associated with CS complicated by atrial fibrillation is low; however, it is remarkable that a decrease in left ventricular function was observed in all cases.9-13) Atrial fibrillation was not detected in our case.
Clinical characteristics of ischemic stroke associated with cardiac sarcoidosis cases
| Case no. (Reference) | Age | Sex | Vessel of occlusion/Area of infarction | Cardiac function evaluation | EF (%) | rt-PA | MT | Antithrombotic therapy |
|---|---|---|---|---|---|---|---|---|
| EF, ejection fraction; rt-PA, recombinant tissue plasminogen activator; MT, mechanical thrombectomy; M, male; F, female PCA, posterior cerebral artery; LV, left ventricle; ND, no data; MCA, middle cerebral artery; ACA, anterior cerebral artery OAC, oral anticoagurant; VKA, vitamin K antagonist; ICA, internal carotid artery |
||||||||
| 1 (9) | 54 | M | PCA | hypokinesis of left inferior ventricular wall | 35 | no | no | aspirin |
| 2 (10) | 42 | M | cerebellum | dyskinesis at the apical lesion, LV thrombus | ND | no | no | warfarin |
| 3 (11) | 28 | M | MCA (M2) | restrictive cardiomyopathy | ND | yes | no | no |
| 4 (12) | 49 | M | ACA | mild LV dysfunction, LV apical clot | 45 | no | no | aspirin |
| 5 (12) | 62 | M | parietal MCA | severe LV dysfunction, atrial fibrillation | 31 | no | no | aspirin, OAC (VKA) |
| 6 (12) | 40 | M | corona radiata | severe LV dysfunction | 29 | yes | no | no |
| 7 (12) | 43 | M | MCA | severe LV dysfunction, LV clot | 26 | no | no | aspirin |
| 8 (12) | 42 | M | ICA | severe LV dysfunction, atrial flutter/fibrillation | 33 | no | yes | OAC (VKA) |
| 9 (12) | 45 | M | frontparietal cortex | mild LV dysfunction | 45 | no | no | aspirin |
| 10 (12) | 33 | M | cerebellar | severe LV dysfunction, LV apical clot | 32 | no | no | aspirin |
| 11 (12) | 66 | F | MCA | severe LV dysfunction, LV apical clot | 28 | no | no | aspirin |
| 12 (13) | 70 | F | MCA (M1) | anterolateral wall dyskinesia, LV aneurysm | 40 | yes | yes | warfarin |
| 13 (current) | 24 | F | ICA | severe LV dysfunction, apical aneurysm | 21 | yes | yes | warfarin |
In our case, the thrombus collected during thrombectomy appeared macroscopically red and histologically confirmed the characteristics of a fresh red thrombus. The observed characteristics of the thrombus collected during MT in our case were similar to those of thrombi obtained through MT in cases of CS-related ischemic stroke, which was relevant to ventricular aneurysm formation and ventricle thrombus that had been surgically removed in the past.13,14) Red thrombi (fibrin-rich thrombi) are likely to occur in environments where blood flow is diminished, as seen in conditions such as atrial fibrillation or deep vein thrombosis.18-20) Blood coagulation is considered more important in the formation of red thrombus than platelet adhesion and aggregation; therefore, anticoagulant medications are often preferred.21) When atrial fibrillation is associated with CS, anticoagulant therapy is indicated to prevent embolism.22) However, there are no specific guidelines for the treatment of CS-associated ischemic stroke due to other causes, such as ventricular aneurysm or reduced EF, and the choice between antiplatelet agents and anticoagulants for secondary preventive therapy varies depending on the reported cases.9-13) In our case, considering the indications of impaired cardiac function, ventricular aneurysm, and the pathological examination of the thrombus, we chose anticoagulation therapy for the prevention of recurrent strokes. Considering that cardiac dysfunction and ventricular aneurysms are present in CS-related ischemic stroke9-13) and that the histopathological findings of the reported thrombus were fresh red thrombi,13,14) anticoagulants might be appropriate; however, further accumulation of cases is necessary. Corticosteroids are expected to suppress cardiomyopathy and improve cardiac function.12) There is no established consensus on whether antiplatelet or anticoagulant agents should be continued for ischemic stroke prevention after improvement in cardiac function. Additionally, for cases of CS without a history of ischemic stroke, but with cardiac dysfunction or ventricular aneurysm, there is currently no evidence regarding whether primary preventive therapy for ischemic stroke is needed.
Thromboembolic complications can increase during pregnancy and the postpartum period due to physiological changes in circulation and increased coagulability, and the incidence of ischemic stroke during pregnancy and the postpartum period is approximately 4.2 to 21 per 100,000 deliveries.7,23) According to a report by Kamel et al.,8) the risk of cerebral infarction is particularly high during the 6 weeks after childbirth. In our case, the cerebral infarction occurred 21 days after childbirth, and the postpartum period may have been a risk factor. No abnormalities were observed in the blood coagulation test at the time of cerebral infarction onset. This is thought to be due to blood coagulation functions, which increase during pregnancy and the postpartum period and generally return to almost normal 3 weeks after the postpartum period.24) The identifiable etiologies of ischemic stroke associated with pregnancy and puerperium are diverse and include eclampsia, preeclampsia, cardiac emboli, paradoxical emboli, coagulopathy, and arterial dissection.7,25) In our case, the etiology of the ischemic stroke was cardiac embolism related to CS. Recent reports have shown the safety and effectiveness of thrombectomy during pregnancy and the postpartum period,26,27) and in our case, we achieved a favorable outcome with endovascular thrombectomy for severe ICAO. Dicpinigaitis et al.26) reported that the unadjusted univariate analysis showed a lower incidence of intracranial hemorrhage after MT in women during pregnancy/postpartum compared with that in non-pregnant women (11% versus 24%, p = 0.069), and multivariate logistic regression analysis also showed that pregnant/postpartum status was independently associated with a lower likelihood of developing intracranial hemorrhage (adjusted odds ratio 0.26 [95% confidence interval 0.09-0.70]; p = 0.008).
In conclusion, this is a rare case in which a young woman in the postpartum period underwent MT, and a cardiogenic stroke of CS origin was diagnosed upon postoperative examination. CS is associated with decreased cardiac function and ventricular aneurysm formation that can lead to thrombus formation in the left ventricle. In the postpartum period, physiological changes in circulation and increased coagulability increase thrombotic complications. It is important to be aware that, although rare, these factors may contribute to ischemic stroke. A combination of factors led to an atypical, fatal stroke in a young woman; however, endovascular treatment resulted in a favorable prognosis.
The authors also thank Editage (www.editage.jp) for English language editing.
Author Haruhiko Kishima is one of the Editorial Board members of the Journal. This author was not involved in the peer-review or decision-making process for this paper.
All authors have no conflict of interest.
