Personalised stroke evaluation and management: tailoring individualised patient care for hereditary haemorrhagic telangiectasia.

SummaryHereditary haemorrhagic telangiectasia (HHT) has an estimated prevalence of 1 in 5000-8000 individuals globally with pulmonary arteriovenous malformations (PAVMs) affecting approximately 15%-50% of HHT patients. Ischaemic stroke is a known complication of PAVMs that affects ≤30% of patients with PAVMs. Studies have shown that patients with PAVMs have ischaemic stroke a decade earlier than routine stroke. The predominant mechanism of ischaemic stroke in HHT patients is paradoxical embolism due to PAVMs, but most HHT-related PAVMs are asymptomatic. Additionally, HHT is often underdiagnosed in patients and poses a challenge to physicians due to its rarity. We present a case of a patient with ischaemic stroke who was subsequently diagnosed with HHT and found to have a PAVM on further evaluation. This case highlights the importance of using an individualised patient-centred stroke evaluation and screening for PAVMs in patients who had a stroke with possible or suspected HHT and definite HHT.

Macrocheilia as an Atypical Clinical Presentation of Capillary Malformation-Arteriovenous Malformation Type 2.

This case report describes a 53-year-old man with multiple erythematous macules and papules diffusely distributed on the frontal area, cheeks, eyelids, nose, and supralabial skin.

Renal arteriovenous malformation causing hematuria: Case report and review of the literature.

RATIONALE: Renal arteriovenous malformations are rare vascular morphological anomalies that can be classified as congenital, idiopathic and acquired, of which congenital renal arteriovenous malformations are the most common. This disease is a rare cause of hematuria. In this case report, we report the diagnosis and treatment of a patient with renal arteriovenous malformation. We also review the symptoms, diagnosis and treatment of renal arteriovenous malformations in the published literature. PATIENT CONCERNS: A 35-year-old female patient presented to a local hospital with right-sided lumbar abdominal pain with hematuria for 2 days. Physical examination showed percussion pain in the right renal area. Laboratory tests such as routine blood and blood biochemistry did not show any significant abnormalities when the patient entered the hospital. Considering the patient's medical history, a urological computed tomography scan showed blood accumulation in the right renal pelvis, upper middle ureter and bladder. Subsequently, routine blood tests showed that the patient's red blood cells and hemoglobin continued to decrease. An emergency renal arteriogram was performed, which showed a tortuous right upper renal pole branch artery and multiple thickened veins communicating with it. DIAGNOSIS: This patient was diagnosed with cirsoid renal arteriovenous malformation. INTERVENTIONS: Renal artery embolization was performed immediately after the renal arteriogram was performed on the patient. OUTCOMES: On review of the angiogram, the tortuous right upper renal pole branch artery was found to be obstructed, and the thickened vein disappeared, and the renal vein was normally visualized in due course. On the third postoperative day, the patient was free of hematuria. Physical examination showed no percussion pain in the renal area. The patient healed and was discharged. A 1-year follow-up was performed and the patient gave feedback that she no longer had symptoms such as back pain and hematuria in her daily life. LESSONS: This case illustrates that early use of vascular interventions is an important method for the diagnosis and treatment of cirsoid renal arteriovenous malformations.

Longitudinal Assessment of Curaçao Criteria in Children with Hereditary Hemorrhagic Telangiectasia.

OBJECTIVE: To assess the utility of the Curaçao criteria by age over time in children with hereditary hemorrhagic telangiectasia (HHT). STUDY DESIGN: This was a single-center, retrospective analysis of patients attending the HHT clinic at the Hospital for Sick Children (Toronto, Canada) between 2000 and 2019. The evaluation of the Curaçao criteria was completed during initial and follow-up visits. Screening for pulmonary and brain arteriovenous malformations was completed at 5 yearly intervals. RESULTS: A total of 116 patients with genetic confirmation of HHT were included in the analysis. At initial screening at a median (IQR) age of 8.4 (2.8, 12.9) years, 41% met criteria for a definite clinical diagnosis (≥3 criteria). In children <6 years at presentation, only 23% fulfilled at least 3 criteria initially. In longitudinal follow-up, 63% reached a definite clinical diagnosis, with a median (IQR) follow-up duration of 5.2 (3.2, 7.9) years (P = .005). Specifically, more patients met the epistaxis and telangiectasia criteria at last visit compared with initial (79% vs 60%; P = .006; 47% vs 30%; P = .02) but not for the arteriovenous malformation criterion (59% vs 57%; P = .65). CONCLUSIONS: In the pediatric population, most patients do not meet definite clinical criteria of HHT at initial presentation. Although the number of diagnostic criteria met increased over time, mainly due to new onset of epistaxis and telangiectasia, accuracy remained low during follow-up visits. Relying solely on clinical criteria may lead to underdiagnosis of HHT in children.

The Shunt of It.

Pulmonary arteriovenous malformations (PAVMs) are rare and most often identified in patients with hereditary hemorrhagic telangiectasia (HHT). We describe a patient with severe hypoxemia and orthodeoxia with imaging findings consistent with PAVMs. Resected lung pathologic findings confirmed the presence of numerous microscopic vascular abnormalities within the right lower lobe that was consistent with diffuse pulmonary arteriovenous shunts. Family history was negative for HHT but was positive for pulmonary arterial hypertension (PAH) in two second-degree relatives. A vascular malformation gene panel was negative for genes that commonly are associated with HHT but identified a pathogenic variant in the gene encoding bone morphogenetic protein receptor-2 (BMPR2 p.Cys123∗). Pathogenic variants in BMPR2 are a well-known cause of hereditary PAH; there have been several reports to date of patients with PAVMs and PAH. However, this is the first patient to be reported with a pathogenic variant in BMPR2 to have PAVMs in isolation.

Colorectal Arteriovenous Malformations causing Prolonged Bleeding were Managed Successfully by Laparoscopic Low Anterior Resection with Sphincter Preservation: A Case Report.

Gastrointestinal arteriovenous malformations (AVMs) are a rare disease. Sigmoid-anorectal AVM has only been reported in a few cases. The condition is usually detected when patients have gastrointestinal bleeding complications. The diagnosis and treatment of colorectal AVMs are still challenging. This paper presents a case of an Asian 32-year-old female patient admitted to hospital because of lower gastrointestinal bleeding lasting 17 years. The patient was diagnosed with sigmoid-rectal arteriovenous malformation and failed with other medical treatments. The damaged gastrointestinal tract was removed by a laparoscopic low anterior resection. The results were positive after a three-month follow-up; the bleeding was resolved, and the anal sphincter function was intact. Laparoscopic low anterior resection is a safe, less invasive, and effective approach for managing patients with digestive tract bleeding due to extensive colorectal AVM and preservation of the anal sphincter.

High-depth next-generation sequencing panel testing in the evaluation of arteriovenous malformations.

Arteriovenous malformations (AVMs) are vascular lesions in which an overgrowth of blood vessels of varying sizes develops with one or more direct connections between the arterial and venous circulation. We performed a retrospective review of a cohort of 54 patients with AVMs referred to our clinical genomic laboratory for high-depth next-generation sequencing (NGS) panel of Disorders of Somatic Mosaicism (DoSM). Thirty-seven of 54 patients were female (68.5%). Among the 54 cases, 37 (68.5%) cases had pathogenic and/or likely pathogenic (P/LP) variants identified, two cases (3.7%) had variants of uncertain clinical significance, and the remaining 15 cases (27.8%) had negative results. MAP2K1 variants were found in 12 cases, followed by eight cases with KRAS variants and seven with TEK variants, and the remainder being identified in several other genes on the panel. Among the 37 positive cases, 32 cases had somatic alterations only; the remaining five cases had at least one germline P/LP variant, including four cases with PTEN and one with RASA1. Of note, two cases had the unexpected co-existence of two P/LP variants. In summary, this study illustrated the molecular diagnostic yield (68.5%) of this cohort of patients with a clinical indication of AVMs by our high-depth DoSM NGS panel.

Arteriovenous malformation of the small intestine presenting with a transfusion-dependent anaemia in pregnancy.

Gastrointestinal bleeding that originates in the small intestine is often difficult to diagnose. Bleeding from a small intestinal arteriovenous malformation (AVM) is rare, with congenital AVMs more commonly located in the rectum or sigmoid. There is a relative paucity of cases reported in the literature. In the gastrointestinal tract, it can cause acute and chronic bleeding, which can be fatal. Although the incidence of small bowel AVMs is quite low, such lesions can be identified as the bleeding source in patients with obscure gastrointestinal bleeding (OGIB) harbouring severe, transfusion-dependent anaemia. It can be exceedingly difficult to localise and diagnose gastrointestinal tract bleeding, particularly in cases of occult small bowel AVMs. CT angiography and capsule endoscopy can help to establish the diagnosis. Laparoscopy is an appropriate and beneficial treatment modality for small bowel resection. The authors present the case of a primigravida woman in her late 20s diagnosed with a symptomatic transfusion-dependent anaemia during her pregnancy. She developed OGIB and despite no history of chronic liver disease became encephalopathic. Due to her physical deterioration and uncertain diagnosis, her caesarean section was performed at 36+6 weeks to expedite investigations and treatment. She was diagnosed with a jejunal AVM and underwent coiled embolisation of her superior mesenteric artery. She became haemodynamically unstable and underwent a laparotomy and small bowel resection. A full non-invasive liver screen was negative, however, her MRI liver described multiple focal nodular hyperplasia (FNH) lesions raising the possibility of FNH syndrome in the context of a previous AVM malformation. A prompt stepwise, multimodality diagnostic approach is required to prevent patient morbidity and mortality.

Fontan completion of a 10-year-old Kawashima patient with extensive arteriovenous malformations: consideration for a lobectomy.

A significant contributing factor to the progression of late cyanosis in individuals undergoing Kawashima operation is pulmonary arteriovenous malformations. Following the Fontan procedure, arteriovenous malformations may regress. However, in cases with extensive malformations causing severe cyanosis, lobectomy can also be a possible treatment approach. Thereby, we present our two-step treatment strategy in a late Fontan completion complicated by arteriovenous malformations in a Kawashima patient.

Genetic Profile of Arteriovenous Anomalies of the Head and Neck: Implications in Progression and Therapeutic Approaches.

BACKGROUND: Arteriovenous Malformations (AVMs) are complex vascular anomalies that are usually sporadic and can have a variable clinical course. Treatment of AVMs can lead to severe sequeale and require thorough decision-making. There is a lack of standardized treatment protocols showing a growing need for pharmacological targeted therapies, specially in the most severe cases where surgery may not be feasible. Current knowledge in molecular pathways and genetic diagnosis have shed light in the pathophysiology of AVMs, opening possibilities for personalized treatment strategies. METHODS: We performed a retrospective review of patients with head and neck AVMs treated in our department between 2003 and 2021 and performed a complete physical examination and imaging with ultrasound and angio-CT or MRI. Patients underwent genetic testing on AVMs' tissue samples and/or peripheral blood samples. Patients were grouped according to the genetic variant and a correlation between phenotype and genotype was studied. RESULTS: 22 patients with head and neck AVMs were included. We found eight patients with varians in MAP2K1, four patients with pathogenic variants in KRAS, six patients with pathogenic variants in RASA1, one patient with a pathogenic variant in BRAF, one patient with a pathogenic variant in NF1, another patient with a pathogenic variant in CELSR1 and one patient with pathogenic variants in PIK3CA and GNA14. Patients with MAP2K1 variants were the biggest group, with a moderate clinical course. Patients with KRAS mutations showed the most aggressive clinical course and a high rate of recurrence and osteolysis. Patients with RASA1 variants showed a characteristic phenotype with an ipsilateral capillary malformation in the neck. CONCLUSION: We found a correlation between genotype and phenotype in this group of patients. The genetic diagnosis of AVMs is recommended in order to stablish a personalized treatment strategy. Targeted therapies are currently being investigated with promising results and may be recommended in addition to conventional surgical or embolization procedures, specially in the most complex cases. LEVEL OF EVIDENCE: Level IV.

A 39-Year-Old Man With an Arteriovenous Malformation With New Dyspnea and Lower Limb Edema.

CASE PRESENTATION: A 39-year-old man with a history of arteriovenous malformation in the upper right limb that was complicated with vascular-type ulcers and repeated soft tissue infection and who had needed a supracondylar amputation of the limb when he was 27 years old presented a new soft tissue infection that manifested with fever, chills, increase in the diameter of the stump with local skin erythema, and painful necrotic ulcers. The patient reported mild dyspnea for 3 months (World Health Organization functional class II/IV) that had worsened during the last week (World Health Organization functional class III/IV) with chest tightness and bilateral lower limb edema.

Treatment of Challenging Extracranial Arteriovenous Malformations: A Single-Center Experience and Literature Review.

ABSTRACT: Extracranial arteriovenous malformation (AVM) is a high-flow congenital vascular malformation, where direct communication between the arteries and veins impedes perfusion of capillary beds and causes disfigurement of the affected tissue. Surgery and endovascular therapy are currently the main treatment for extracranial AVMs. Nevertheless, management of complex cases is sometimes challenging because of severe complications such as refractory ulceration, life-threatening bleeding, and even cardiac insufficiency. Here, we reviewed the development and potential treatment for extracranial AVMs and shared our single-center experiences of diagnosis and treatment of this challenging disease.

Vascular Malformations of the Head and Neck in Children.

BACKGROUND/AIM: Vascular malformations are congenital abnormalities that result from disturbances in the embryologic development of the vascular system. A retrospective study at a single institution was performed to determine the localization and treatment patterns for vascular malformations in children. PATIENTS AND METHODS: A total of 198 pediatric patients were identified. Age at diagnosis and presentation, sex, localization, diagnostics, and therapy were described. RESULTS: The most common diagnosis was lymphatic malformation (LM, 58.6%), followed by venous (VM, 31.8%) and arteriovenous malformation (AVM, 4.5%). The mean age at diagnosis was 2.2 years, while the mean age at presentation at our hospital was 7.2 years. The sex ratio showed a female predominance (1.44:1), which was most evident in children with AVM. The neck, cheek/parotid gland and oral cavity were the most predominant locations. Half of the patients required at least one intervention at our hospital. Especially, CM and LM were managed by watch-and wait, whereas lymphovenous malformation (LVM) and AVM were most often treated. Treatment differed between the various malformation types, the most common used treatment was conventional surgery followed by laser therapy. In case of treatment, the average number of procedures in our hospital was 1.58 for VM, 1.53 for LM, 1.33 for AVM, and 1.0 for LVM. CONCLUSION: In children with vascular malformations interventional treatment is often necessary, in many cases more than one treatment step is needed. Correct identification of the malformation type is important for optimal treatment and appropriate care of patients with vascular malformations.

BILATERAL CHOROIDAL VASCULAR MALFORMATIONS IN HEREDITARY HEMORRHAGIC TELANGIECTASIA.

PURPOSE: To describe a case of bilateral choroidal vascular malformations in a patient with hereditary hemorrhagic telangiectasia. METHODS: Case report. RESULTS: A 78-year-old man with hereditary hemorrhagic telangiectasia was incidentally noted to have focal, large deep choroidal vessels on optical coherence tomography with corresponding elevation of the overlying retina. Indocyanine green angiography revealed dilated, intensely fluorescent vessels in arterial phase emptying into massively dilated choroidal veins consistent with choroidal arteriovenous malformation. CONCLUSION: This case presents multimodal imaging findings of choroidal arteriovenous malformations in hereditary hemorrhagic telangiectasia. Choroidal vascular malformations may represent an underrecognized clinical feature of this syndrome.

Major Limb Amputation in Parkes-Weber Syndrome With Refractory Ulceration: A Case Report and Literature Review.

Parkes-Weber syndrome (PWS) is a rare congenital vascular syndrome consisting of capillary, venous, lymphatic, and arteriovenous malformation. There are many complications of PWS, such as ulceration, bleeding, infection, and cardiac failure. Among them, skin ulceration is one of the thorniest problems in PWS, requiring multidisciplinary approaches for the management. In this article, we presented the case of an elderly patient with refractory ulceration who received numerous treatments with no effect and finally underwent a major amputation to improve the quality of life. Moreover, we reviewed 23 previously reported cases to improve our understanding of the management for PWS patients with ulceration.

Iatrogenic arteriovenous fistula in an infant mimicking an arteriovenous malformation.

We report the case of a 12-month-old infant who presented with progressive lower limb enlargement associated with erythema mimicking an arteriovenous malformation. Computed tomography confirmed an arteriovenous fistula (AVF) between the deep femoral artery and the common femoral vein. This case describes the unique clinical and imaging findings of iatrogenic AVF and contrasts them with other congenital vascular entities.