Coexistence of Ebstein Anomaly and Cerebral Cavernous Malformation: A Case Report

ABSTRACT

In most patients who have Ebstein anomaly (EA), neurological symptoms are either associated with thromboembolic episodes or due to arrhythmic complications. Cerebral cavernous malformation (CCM) is a vascular anomaly made up of sinusoidally dilated blood vessels, often presenting with seizure activity or intracranial bleeding. There has never been any documented report regarding coexisting EA and CCM. Herein, we have reported a 32‐year‐old female with an established history of Ebstein anomaly diagnosed in 2013 who had a history of generalized tonic‐clonic fits since 2020. Neuroimaging studies showed the presence of a right frontal lobe mass with typical “popcorn‐like” appearance and hemosiderin ring on MRI, indicative of cerebral cavernous malformation. The patient declined surgery and was managed conservatively with levetiracetam. With the occurrence of further fits in 2025, neuroimaging showed similar findings but without the presence of intratumoral bleeding. Subsequently, she underwent a left frontoparietal craniotomy for GTE of the lesion with cavernoma on histopathology. The neurological status of the patient was stable during her discharge on the fourth postoperative day. This case documents a previously unreported coexistence of Ebstein anomaly and cerebral cavernous malformation in a single patient. Given the rarity of both conditions, coexistence is coincidental. This indicates the need for genetic and molecular studies to determine whether a real biological association exists.

Key Clinical Message

Neurological manifestations in patients with Ebstein anomaly cannot always be linked to either thromboembolism or arrhythmia. Structural vascular disorders like cerebral cavernous malformation may occur concomitantly and need to be considered in cases where patients suffer from seizures or focal neurological problems.

Abbreviations

ADC

apparent diffusion coefficient

CCM

cerebral cavernous malformation

CT

computed tomography

DWI

diffusion‐weighted imaging

EA

Ebstein anomaly

MRI

magnetic resonance imaging

MV

mitral valve

RWMA

regional wall motion abnormality

T1WI

T1‐weighted image

T2WI

T2‐weighted image

TV

tricuspid valve

1. Introduction

EA is an uncommon congenital cardiac disorder making up less than 1% of cases of congenital heart defects. The feature of EA is displacement and dysplasia of the three leaflets of the tricuspid valve. This causes right ventricular atrialization with tricuspid insufficiency, cyanosis, and arrhythmias [1]. The presentation of EA is variable. There have been reports of extracardiac involvement in this condition, which include neuromuscular or vascular disease [1, 2, 3, 4].

CCMs are a type of low flow vascular malformation consisting of enlarged capillary‐like sinusoidal channels that lack intervening normal brain tissue. This condition is typically associated with seizures, headaches, focal neurologic deficits, or hemorrhage [5]. The lesions are usually seen on MRI with a distinctive “popcorn” appearance due to hemosiderin deposition from recurrent bleeding episodes [5, 6].

The neurologic manifestations in the setting of EA are commonly linked to paradoxical emboli, cerebrovascular accidents, migraines, or ischemic events due to arrhythmias [3, 7, 8]. Nevertheless, cases of cerebral cavernous malformation complicating Ebstein anomaly have not been reported in the medical literature. This is an unusual case of a repeated seizure attack secondary to CCM in a patient with long‐standing EA. Given the low prevalence of both conditions, coexistence in this patient represents a rare occurrence. We have explored the embryologic, endothelial, and hemodynamic mechanisms that have been proposed to connect vascular malformations of the heart and brain. But, these are hypothetical in the absence of molecular confirmation.

1.1. Case History and Examination

The patient is a 32‐year‐old female admitted in our institution with symptoms of recurring fits since the year 2020. From the year 2013 onwards, she was found to be suffering from Ebstein anomaly of the tricuspid valve (TV) with conservative management. However, from 2020 onwards, the patient developed symptoms of generalized tonic‐clonic convulsions for which she consulted her doctor. This is followed by further tests such as CT scan and brain MRI.

2. Methods

2.1. Investigation and Differential Diagnosis

Brain CT scan revealed a large, heterogeneous, and highly attenuated lesion located in the right frontal region without mass effect. Cerebral vessels CT angiogram revealed calcified lesions and no other vascular abnormalities. 3D reconstructed arteriogram was also normal in relation to any possible vascular abnormalities (Figure 1). Further imaging was carried out via MRI on the same day that showed the presence of a lesion with heterogeneous signal intensity in relation to brain parenchyma in T1WI. The lesion became predominantly hyperintense with popcorn‐like appearances in T2WI and FLAIR sequences with an incomplete hypointense rim. After the use of gadolinium, a minimal lesion enhancement could be seen. There were also partially restricted areas in the DWI/ADC maps with areas of blooming in GRE sequence. Cerebral vessels MR angiogram showed a cluster of vessels that are supplied by the right middle cerebral artery (MCA) (Figure 2).

FIGURE 1.

CT scan of the brain demonstrated a large heterogeneous high attenuation lesion in the right frontal lobe with no mass effect (A–C). CT angiogram of cerebral vessels demonstrated discrete areas of calcification (marked by orange arrowhead) with no vascular anomalies (D, E). 3D reconstruction arteriogram was unremarkable for any vascular pathology (F).

FIGURE 2.

Brain MRI, axial T1WI demonstrated a mixed signal intensity lesion in relative to the brain parenchyma (A). The lesion become predominantly hyperintense with classic ‘popcorn’ or mulberry appearance in T2WI and FLAIR sequence (B, E). There is an incomplete hypointense rim (marked by orange arrowhead) surrounding the lesion (B). After administration of the gadolinium, there was minimal enhancement (C, D). There was partial restricted diffusion in DWI/ADC map (F, G) with areas of blooming in GRE sequence (H). MRA of cerebral vessels, right‐to‐left rotational view (I, J) and vertex to base rotational view (K) demonstrated a cluster of vessels, feeded by branches of right MCA (marked by yellow arrow).

Nevertheless, even after counseling the patient regarding the nature of disease, mode of treatment and outcome, they declined to go for any form of surgery. The patient was placed on medication with tab levetiracetam before experiencing seizures in December 2025. She was admitted in May 2026 to our department for further evaluation and management. An MRI of the brain along with MRA was carried out in order to establish whether there is any new intralesional hemorrhage or altered morphology of the lesion. Nevertheless, the lesion showed no changes from its previous characteristics. The 2D echocardiography established that the septal leaflet of TV was small and fused to the intraventricular septum as well as deeply seated to RV. The anterior leaflet appeared long and sail‐like. There was a distance of 21 mm between the septal leaflet of TV and MV. There is also enlargement of RA as a result of atrialization of the upper portion of RV with Grade II TR and absence of RWMA (Figure 3).

FIGURE 3.

2D echocardiogram demonstrated that the septal leaflet of TV is small and is attached to the IV septum and deep down to RV. Anterior leaflet is long and sail‐like. Distance between septal leaflet of TV and MV is 21 mm. RA is large due to atrialization of the upper part of the right ventricle. There is Grade II TR with no RWMA (A–F).

2.2. Management

Following written consent from the patient, surgical treatment involved left‐sided fronto‐parietal craniotomy and gross total removal of the lesion. Post‐dural opening, the lesion was found to be coffee yellow, well‐defined and located slightly above the Sylvian fissure. Gross examination showed the lesion to have a mulberry appearance with numerous sinusoidal spaces, having intralesional hemorrhage of varied ages (Figure 4). Microscopic examination of the excised specimen showed fibrous tissue and blood clots. The fibrous tissue included many large vascular channels, hemorrhage, features of organization, and hemosiderin‐containing histiocytes. Based on this observation, the lesion was confirmed to be cavernoma.

FIGURE 4.

Intraoperative photograph showing cavernoma post durotomy (A), during sharp arachnoid dissection (B), appearance of removed lesion as a single mass (C), and presence of old hemorrhages on the cut surface (D).

3. Results

3.1. Follow Up and Outcome

The postoperative period for the patient was without any complications and she was discharged on the fourth postoperative day with good neurological function. At 3 months follow‐up, she was neurologically intact with no history of post procedure seizure.

4. Discussion

The occurrence of both EA and CCM together is extremely rare, and to our knowledge, any pathogenic relationship between them has yet to be defined in the scientific literature. CCMs are reported to affect up to 0.5% of the general population [9]. Due to low prevalence, the coexistence of EA and CCM observed in this patient could plausibly represent a chance occurrence rather than a biologically meaningful association. We present the following embryologic, vascular, and genetic considerations not as evidence of a causal link, but as hypotheses that may guide future investigation.

Ebstein anomaly (EA) is a relatively uncommon form of congenital heart disease characterized by abnormal placement of the tricuspid valve leaflets along with atrialization of the right ventricle [1, 2, 3, 4, 5, 7, 8]. While this condition tends to occur sporadically, genetic mechanisms have increasingly been implicated in EA, specifically involving genes that play roles in the development of the heart and vasculature. Genes such as MYH7, NKX2‐5, GATA4, and GMDS have been identified in some patients with EA, suggesting that this condition could actually be a component of a more generalized syndrome rather than a purely cardiovascular disorder [10].

Advances in next‐generation sequencing (NGS), including whole‐exome and whole‐genome sequencing, and copy number variation (CNV) analysis have high prospects in congenital heart disease. Deleterious variants are identifiable in an estimated 8%–27% of patients depending on ascertainment and sequencing modality [11, 12]. These tools were not applied to our patient. These will have significant application for future work aimed at clarifying whether isolated or syndromic genetic variants underlie both cardiac and cerebrovascular findings.

In contrast, CCMs are hamartomas that consist of enlarged sinusoidal capillaries without mature structure of the vascular wall. Familial cases of CCMs have mutations in KRIT1/CCM1, CCM2, and PDCD10/CCM3, which play an important role in endothelial biology, angiogenesis, and vascular leakage [9, 11, 12]. Targeted NGS panels and structural variant analysis have identified previously undetected CCM‐associated structural rearrangements in patients without classic single‐nucleotide mutations. This indicates the importance of genomic evaluation in unexplained or atypical cases [13]. Even though mutations in those genes have not been related to EA, both diseases involve abnormal interaction between the mesenchyme and endothelium during early fetal development [9, 10]. The common pathogenetic mechanism suggests that other variants within vascular biology pathways might be predisposing factors for both heart and brain vascular defects. Endothelial regulatory pathways involving microRNAs have also been implicated in vascular remodeling and angiogenesis in other disease contexts. For example, miR‐10b‐5p has been shown to promote pro‐angiogenic signaling in oncology [14]. This evidence originates from an unrelated disease process and cannot be directly extrapolated to EA or CCM. Endothelial microRNA regulation may modulate vascular malformation biology and could represent a candidate area for future mechanistic study.

Yet another possible association may relate to altered venous hemodynamics. The formation of CCMs and their hemorrhagic conversion is thought to be linked with abnormal venous drainage and dynamics. Some cases of newly formed CCMs close to developmental venous anomaly sites have been documented, implying that chronically increased venous pressures or abnormal flow dynamics may play a role in CCM pathogenesis [15]. Right atrial pressure elevation, tricuspid insufficiency, cyanosis, and right‐to‐left shunt across congenital atrial septal defects or patent foramen ovale are common characteristics seen in EA patients [1, 2, 3, 4, 15]. These chronic hemodynamic changes may affect the brain's venous circulation or alter endothelial cell stress. However, this hypothesis has not been tested in any population and should be regarded as speculative rather than an established mechanism.

Neurological signs are now becoming more common in cases of EA due to paradoxical embolus, arrhythmia‐induced ischemia, migraines, or stroke. Reports in the literature have shown transient ischemic attacks or cerebral infarction caused by paradoxical emboli in EA [16]. In addition, there is evidence of ocular abnormalities and migraine syndromes associated with EA, implying that extra cardiac vascular dysfunction could occur [17]. Nonetheless, CCM has never been associated with the clinical profile of EA before.

The presence of both rare conditions in one patient raises the theoretical possibility of an unrecognized syndromic process, though no such mechanism has been demonstrated. Similar discussions have been raised in some published articles describing coexisting vascular or developmental anomalies without a clear genetic etiology [18]. In familial cases of CCM, a two‐hit model has been proposed in which genetic susceptibility is followed by somatic endothelial mutation. Chronic hypoxia, endothelial shear stress, or inflammatory processes related to congenital heart disease could act as environmental triggers in genetically predisposed individuals. These are entirely speculative and unsupported by direct evidence.

Both EA and CCM are rare, and their random coexistence in a single patient is far rarer. The evidence in this report does indicate a biological, genetic, developmental, or epidemiological association. At the current time, there is no scientific data to advocate for neurovascular screening in all patients with EA or cardiac screening in all patients with CCM. From a diagnostic view, imaging is central to the identification and longitudinal monitoring of CCM. Artificial intelligence (AI)‐assisted approaches such as automated lesion segmentation, radiomic characterization, and hemorrhage‐risk prediction are being incorporated into neuroradiology workflows. They may improve the detection of incidental or evolving vascular lesions [19]. Nonetheless, this case illustrates one of many potential extracardiac manifestations that may be seen in patients with congenital heart disease and serves as a reminder for physicians to consider a broad range of diagnoses when neurological symptoms occur in a patient with EA.

The absence of genetic testing, family history analysis, molecular characterization, and systematic review of previously reported cases are important limitations of this study. With genomics and pathway‐based analyses, incorporating next‐generation sequencing and structural variant discovery, future work may help clarify whether such coexistence is coincidental or biologically meaningful.

4.1. Learning Points

• The occurrence of both EA and CCM could be an unrecognized association.

• There are other neurologic symptoms associated with congenital heart disease that do not arise from thromboembolism and can be due to structural cerebrovascular problems.

• Common pathogenetic processes involving endothelium or development can be behind the concurrent presence of congenital heart and brain blood vessel defects.

• More cases need to be studied to establish whether this phenomenon is causally related or coincidental.

5. Conclusion

This case highlights the rare coexistence of Ebstein anomaly and cerebral cavernous malformation and warrants further research for molecular investigations which may help to determine a true pathological association.

Author Contributions

Nazmin Ahmed: conceptualization, methodology, data curation, investigation, formal analysis, writing – original draft, writing – review and editing. Mohaiminul Islam: software, data curation, investigation, formal analysis. Md. Raad Kazi: software, data curation, investigation, formal analysis. Jubair Ahmed Sikder: software, data curation, investigation, formal analysis. Tajrian Sultana: investigation, writing – review and editing, methodology. Mohammad Nazrul Hossain: conceptualization, supervision, validation, visualization, project administration.

Funding

The authors have nothing to report.

Consent

Written informed consent from the patient was obtained for publication according to journal guidelines.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.