e-ISSN 1941-5923 © Am J Case Rep, 2023; 24: e938548 DOI: 10.12659/AJCR.938548 Received: Accepted: 2022.10.03 2023.01.19 A 37-Year-Old Man with Familial Hereditary Available online: Published: 2023.01.27 2023.02.26 Hemorrhagic Telangiectasia and Pulmonary Arteriovenous Malformations Presenting with Seizures and a Diagnosis of Brain Abscesses Authors’ Contribution: ABCDEFG 1,2 Nerea Hernández-de Sosa 1 Department of Internal Medicine, Hospital Santa Creu i Sant Pau, Barcelona, Study Design A AB 1 Ruben Cardona Corrales Spain Data Collection B 2 Universitat Autònoma de Barcelona, UAB, Barcelona, Spain Statistical Analysis C ACDEF 1,2 Jordi Casademont Data Interpretation D Manuscript Preparation E Literature Search F Funds Collection G Corresponding Author: Nerea Hernández-de Sosa, e-mail: nhernandezd@santpau.cat Financial support: None declared Conflict of interest: None declared Patient: Male, 37-year-old Final Diagnosis: Brain abscesses • hereditary haemorrhagic telangiectasia • pulmonary arteriovenous malformations Symptoms: Tonic-clonic seizures Clinical Procedure: Embolization Specialty: General and Internal Medicine Objective: Rare disease Background: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant genetic disease associated with arteriovenous malformations involving diverse organs. Neurological complications from brain abscesses (BA) secondary to pulmonary arteriovenous malformations (PAVMs) is a serious and recognized, albeit infrequent, medical problem. We report the case of a 37-year-old man with familial HHT and PAVMs who presented with seizures as a manifestation of BA. Case Report: A 37-year-old man was admitted for first tonic-clonic seizures. He had a history of recurrent epistaxis and re- current gastrointestinal bleeds treated with fulguration and oral iron therapy. A diagnosis of HHT was made because the patient met 3 of 4 Curaçao criteria. Physical examination revealed hypoxemia without dyspnea. A chest X-ray detected nodular pulmonary lesions in both lower lobes. Cranial computed tomography (CT) re- vealed 3 space-occupying lesions. Antiepileptics and dexamethasone were started. Cranial magnetic resonance and positron emission tomography suggested that lesions were BA. Thoracoabdominal CT with contrast re- vealed several bilateral PAVMs. Blood cultures were repeatedly negative. With the presumptive diagnosis of septic-embolic BA, empirical antibiotic therapy was started for 8 weeks. Neurological symptoms resolved and malformations >2 cm were selectively embolized. A genetic study revealed exon5 mutations in the ENG gene. Conclusions: This report highlights the association between PAVMs in a patient with HHT and development of BA. Clinicians should be aware of this association so that diagnosis and treatment can be provided as fast as possible to en- sure the best outcome for the patient. Embolization was performed as preventive treatment, and a genetic study was conducted as it is potentially useful for primary prevention in the patient’s offspring. Keywords: Arteriovenous Malformations • Embolization, Therapeutic • Telangiectasia, Hereditary Hemorrhagic • Brain Abscess • Seizures • ENG Protein, Human Full-text PDF: https://www.amjcaserep.com/abstract/index/idArt/938548 1179   —   2   21 Publisher’s note: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher This work is licensed under Creative Common Attribution- Indexed in: [PMC] [PubMed] [Emerging Sources Citation Index (ESCI)] NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) e938548-1 [Web of Science by Clarivate] Hernández-de Sosa N. et al: Familial hereditary hemorrhagic telangiectasia… © Am J Case Rep, 2023; 24: e938548 Background echocardiography with physiological saline revealed delayed right-to-left passage of bubbles and no signs of endocarditis. Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is an autosomal genetic dis- These results suggested a diagnosis of septic-embolic brain ease associated with multiple arteriovenous malformations [1]. lesions due to PAVMs and HHT. Empirical antibiotic therapy There is a recognized association between pulmonary arterio- was started with ceftriaxone and metronidazole for 8 weeks, in venous malformations (PAVMs) and the development of brain the absence of evidence of infection in the collected cultures. abscesses (BA) [2]. PAVMs are associated with HHT [3,4] and Neurological symptoms resolved and, in the control cerebral neurological complications from BA are a serious medical prob- CT, the lesions had disappeared. After malformations >2 cm lem and can potentially recur if untreated. We report the case were selectively embolized (right upper lobe apical segment of a 37-year-old man with familial HHT and PAVMs who pre- and left lower lobe AVMs) (Figure 2), the chronic hypoxemia sented with seizures and diagnosis of BA. (PaO2 87 mmHg) also normalized. Three months after discharge, CT confirmed the absence of Case Report any brain radiological sequelae. A genetic study revealed exon5 mutations in the ENG gene that would explain the findings A 37-year-old non-smoking man was admitted in a post-critical for this patient. state for tonic-clonic seizures preceded by peri-oral paraesthe- sia. He had a history of thalassaemia minor, recurrent epistax- is, and microcytic anaemia secondary to recurrent gastrointes- Discussion tinal bleeds due to angiectasias, treated with fulguration and oral iron therapy. Originally from Argentina, his mother also HHT, also known as Rendu-Osler-Weber disease, is an inherit- had a history of thalassaemia minor, as well as clinically di- ed (autosomal dominant) vascular dysplasia with prevalence agnosed HHT with epistaxis and cutaneous and gastrointesti- of 1 in 5000-8000 [6,7]. It is characterized by recurrent epi- nal telangiectasias. A diagnosis of HHT was made because the staxis, muco-cutaneous telangiectasia, gastrointestinal bleed- patient met 3 of 4 Curaçao criteria [5]. The patient explained ing, and multiple arteriovenous circulatory malformations in that it was his first seizure episode. He reported no toxic syn- the lung, brain, and liver [3,4]. Today, diagnosis of HHT is es- drome, fever, dyspnea, or other clinical problems. On physical tablished on the basis of the Curaçao criteria [5]. examination, the patient had finger and toe clubbing, did not have cyanosis, and did have central right facial palsy. An arte- PAVMs are abnormal communications between the pulmonary rial blood gas test indicated partial pressure of oxygen (PaO2) arteries and pulmonary veins, mostly congenital and associated 63.8 mmHg (oxygen saturation [SatO2] 93.4%). with HHT in approximately 70% of cases [8]. PAVM frequency in HHT is reported to be 5-15% [3,4] and provide a right-to-left A chest X-ray performed in the Emergency Department detect- shunt between the pulmonary arterial and venous circulation. ed nodular pulmonary lesions in both lower lobes. Cranial com- PAVMs may remain asymptomatic or manifest with hypoxaemia, puted tomography (CT) revealed 3 space-occupying lesions, 2 hemoptysis, hemothorax, and/or neurologic symptoms. BA and in the frontal lobes and 1 in the right parietal lobe. Treatment ischemic strokes are serious PAVM complications [1,2], with in- was started with levetiracetam and dexamethasone and the cidence reported to be 5-6% in large series [8]. A careful review patient was admitted to Internal Medicine. of a cohort in London with PAVMs, found that 79.5% of patients were diagnosed by chance or in the context of screening pro- Differential diagnosis of the lesions included malignancies and grams of PAVMs in families with HHT, and only 21.5% of individ- infectious causes. Blood, urine, and cerebrospinal cultures and uals were diagnosed because of respiratory manifestations [9]. serology tests for HIV, syphilis, cysticercoids, and mycobacte- Our patient never had dyspnea even though he regularly partic- ria were all negative. ipated in sports. His first symptoms appeared in the third de- cade of life, similar to what has been reported in diverse series Cranial magnetic resonance (CMR) and positron emission tomog- [9,10]. He had recurrent epistaxis and gastrointestinal lesions raphy (PET) (Figure 1) suggested BA at a different area in both but had not yet been diagnosed with HHT. Shovlin et al report- frontal lobes and in the right parietal lobe. A PET extension study ed that only 39.3% of HHT cases are diagnosed prior to a first ruled out extracranial acute inflammation. Thoracoabdominal neurological event. The abscesses tend to occur in the third to CT with contrast revealed several bilateral pulmonary arterio- fifth decade of life and are associated with high mortality [11]. venous malformations (PAVMs) in the right upper lobe api- The current treatment of choice is transcatheter embolization cal segment, right lower lobe, and left lower lobe (diameters with coils or detachable balloons [9,12-15]. Embolization can 25 mm, 30 mm, and 26 mm, respectively). Transoesophageal be used to treat PAVMs if the condition is recognized, but no This work is licensed under Creative Common Attribution- Indexed in: [PMC] [PubMed] [Emerging Sources Citation Index (ESCI)] NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) e938548-2 [Web of Science by Clarivate] Hernández-de Sosa N. et al: Familial hereditary hemorrhagic telangiectasia… © Am J Case Rep, 2023; 24: e938548 A B Figure 1. Cranial images showing space-occupying lesions suggestive of brain abscesses. (A) Cranial magnetic resonance imaging of the brain showing increased signal in T2-weighted of the right parietal lobe (white arrow) and left frontal lobe (black arrow). (B) Positron emission tomography imaging showed increased signal at the same locations: in right parietal lobe (white arrow) and left frontal lobe (black arrow). direct evidence for reduction of BA or stroke incidence has been cultures are negative when a diagnosis of BA is made [2,18] reported [9]. As ischemic stroke and brain abscesses are attrib- and that HHT patients often have >1 bacterial isolate com- uted to paradoxical embolic events through PAVM right-to-left pared to non-HHT patients [19]. shunts, this offers the opportunity to explore potentially rele- vant mechanisms related to other more common conditions, This report documents a rare case of possible embolic BA in such as patent foramen ovale [16]. Therefore, it is advisable to the presence of PAVMs in a patient with HHT. BA secondary to perform appropriate examinations to rule out these options. PAVMs is a serious medical problem and can recur if untreat- ed. Early detection and prevention of secondary neurological Diverse microbiological cultures were negative in our case, episodes could help increase life expectancy and quality of life similar to the 2 HHT patients with PAVMs and BA described in patients with HHT. We selectively embolized the largest mal- by Larsen et al [17]. The literature shows that about 30% of all formations to reduce the possible recurrence of neurological This work is licensed under Creative Common Attribution- Indexed in: [PMC] [PubMed] [Emerging Sources Citation Index (ESCI)] NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) e938548-3 [Web of Science by Clarivate] Hernández-de Sosa N. et al: Familial hereditary hemorrhagic telangiectasia… © Am J Case Rep, 2023; 24: e938548 A B Figure 2. (A, B) Pulmonary images demonstrations the presence of multiple arteriovenous malformations. Chest X-ray showing some pre-embolectomy fluoroscopy images larger than 2 centimeters. Two were localized at the right upper lobe apical segment and 1 at the left lower lobe (white arrows). Post-embolectomy fluoroscopy image at left lower lobe (black arrow). events and to improve the patient’s chronic hypoxia. This rec- Conclusions ommended prevention and treatment is described in the liter- ature [1,9]. A genetic study revealed exon5 mutations in the This report highlights the neurological complications from BA ENG gene in HHT type 1 [1]. The ENG gene codes for endog- secondary to PAVMs, a condition very commonly associated lin on chromosome 9 [20], which is essential for maintaining with HHT, which is a serious medical problem. Clinicians should vascular integrity [21]. This genetic study allowed us to make be aware of this association so that diagnosis and treatment a preventive diagnosis to his offspring and thus facilitate a can be initiated as fast as possible to ensure the best out- personalized follow-up the Pediatric Unit. come for the patient. Embolization as preventive treatment to This work is licensed under Creative Common Attribution- Indexed in: [PMC] [PubMed] [Emerging Sources Citation Index (ESCI)] NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) e938548-4 [Web of Science by Clarivate] Hernández-de Sosa N. et al: Familial hereditary hemorrhagic telangiectasia… © Am J Case Rep, 2023; 24: e938548 avoid future complications should be considered for BA due to Declaration of Figures’ Authenticity PAVMs. Genetic studies may be useful, allowing primary pre- vention for the patient’s offspring. 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