Management of Low-Flow Vascular Malformations: Clinical Presentation, Classification, Patient Selection, Imaging and Treatment

Abstract BACKGROUND AND IMPORTANCE Cavernous malformations (CMs) are angiographically occult low-flow vascular malformations that infrequently involve the optic pathway and the hypothalamus (OPH). CLINICAL PRESENTATION A 23-yr-old male presented with bitemporal hemianopia due to chaismal apoplexy. Imaging revealed a CM involving the OPH. The CM was resected by an extended endonasal approach. The patient had improvement in his visual field defects, and postoperative magnetic resonance imaging (MRI) revealed a gross total resection of the CM. CONCLUSION This case demonstrates the surgical technique of endoscopic endonasal resection of a CM involving the optic pathway.

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Spontaneously Resolved Macrocystic Lymphatic Malformations: Predictive Variables and Outcomes

Plastic Surgery ◽

10.1177/2292550317693815 ◽

2017 ◽

Vol 25 (1) ◽

pp. 27-31 ◽

Cited By ~ 1

Author(s):

Michael J. Phang ◽

Douglas J. Courtemanche ◽

Marija Bucevska ◽

Claudia Malic ◽

Jugpal S. Arneja

Keyword(s):

Respiratory Tract ◽

Median Time ◽

Vascular Malformations ◽

Neck Region ◽

Retrospective Chart Review ◽

Spontaneous Resolution ◽

Low Flow ◽

Upper Respiratory Tract ◽

Lymphatic Malformations ◽

Upper Respiratory

Introduction: Lymphatic malformations are benign, low-flow vascular malformations that typically present at or near birth. Due to morbidity associated with operative treatment, nonoperative treatment with injection of sclerosant has become the mainstay of therapy. Over the past 15 years, several patients at our centre with macrocystic (>2 cm cyst size) lymphatic malformations have seen their lesions resolve spontaneously while awaiting treatment. In this study, we review features of these patients that may contribute to spontaneous resolution. Method: A retrospective chart review was conducted from our Vascular Anomalies Clinic database (1999-2014) of all macrocystic lymphatic malformations; characteristics of patients with spontaneous resolution were reviewed. Results: Of 61 patients with macrocystic lymphatic malformations, 7 cases (11.5%; 4 females, 3 males) resolved spontaneously. Median age at malformation appearance was 2 years (range: 0-6.5 years), with median age at resolution of 4 years (range: 10 months-7 years). Median time from appearance to resolution was 24 months (range: 3-43 months), with a median follow-up time of 4 years (range: 1-15 years). All but 1 case was associated with local or upper respiratory tract infection antecedent to resolution. Six of the 7 lesions were located in the neck. Conclusion: Among the cases reviewed, there was a common theme of upper respiratory tract or local infection antecedent to spontaneous lesion resolution. Compared to the literature, our proportion of malformations presenting after birth and the proportion of malformations presenting in the neck region were higher than those of other series. Although side effects associated with treatment are generally mild and/or rare, risks related to sclerotherapy and the accompanying requirement for general anesthesia in pediatric populations nevertheless exist. As the median time from lesion appearance to resolution was 24 months, it may be reasonable to observe these malformations for up to 24 months before proceeding with treatment if the lesion does not impair function and disfigurement is not considerable, particularly if the lesion presents after birth and/or is located in the neck region.

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Bleomycin for orbital and peri-orbital veno-lymphatic malformations – A systematic review

Interventional Neuroradiology ◽

10.1177/1591019920972514 ◽

2020 ◽

pp. 159101992097251

Author(s):

Khunsa Faiz ◽

Stephanos Finitsis ◽

Janice Linton ◽

Jai Jai Shiva Shankar

Keyword(s):

Systematic Review ◽

Pulmonary Fibrosis ◽

Vascular Malformations ◽

Symptomatic Improvement ◽

Low Flow ◽

Cochrane Database ◽

Objective Reduction ◽

Retrospective Cohort Studies ◽

Subjective Reduction

Background Orbital and peri-orbital venolymphatic malformations (VLM) are low flow vascular malformations. Intralesional bleomycin is now commonly being used to treat such malformations. Objective The purpose of this systematic review is to synthesize evidence on the safety and efficacy of bleomycin/pingyangmycin sclerotherapy for the treatment of orbital and peri-orbital VLM. Methods We searched Medline, Embase, Scopus and Cochrane database for studies reporting outcomes of bleomycin/pingyangmycin sclerotherapy for orbital and peri-orbital VLM between 1974 to April 5th, 2019. Nine retrospective cohort studies enrolling 132 patients were included. Two reviewers independently screened and extracted data and assessed the risk of bias. Predefined outcome measures were subjective and objective reduction of the lesion and associated complications. Results Subjective reduction of the lesions was seen in 96.2% of the studies. Objective reduction of the lesion and symptomatic improvement were reported in 91.6 and 95% of the studies respectively. Non responders were 9.0%. Minor adverse events were reported in 18.1% of the studies. Major complications like pulmonary toxicity or pulmonary fibrosis was not encountered in any of the included studies. Quality of evidence was generally low. Conclusion Bleomycin/pingyangmycin sclerotherapy is very effective and relatively safe for the treatment of orbital and periorbital VLM and is not associated with any major side effects including pulmonary fibrosis. Limitations: The systematic review is limited mainly due to low quality of the included studies with retrospective design.

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Transcriptome-wide Profiling of Cerebral Cavernous Malformations Patients Reveal Important Long noncoding RNA molecular signatures

Scientific Reports ◽

10.1038/s41598-019-54845-0 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Santhilal Subhash ◽

Norman Kalmbach ◽

Florian Wegner ◽

Susanne Petri ◽

Torsten Glomb ◽

...

Keyword(s):

Noncoding Rna ◽

Vascular Malformations ◽

Cerebrovascular Disorders ◽

Gene Set Enrichment Analysis ◽

Differentially Expressed ◽

Low Flow ◽

Pcr Analysis ◽

Cerebral Cavernous Malformations ◽

Cavernous Malformations ◽

Non Coding Rnas

AbstractCerebral cavernous malformations (CCMs) are low-flow vascular malformations in the brain associated with recurrent hemorrhage and seizures. The current treatment of CCMs relies solely on surgical intervention. Henceforth, alternative non-invasive therapies are urgently needed to help prevent subsequent hemorrhagic episodes. Long non-coding RNAs (lncRNAs) belong to the class of non-coding RNAs and are known to regulate gene transcription and involved in chromatin remodeling via various mechanism. Despite accumulating evidence demonstrating the role of lncRNAs in cerebrovascular disorders, their identification in CCMs pathology remains unknown. The objective of the current study was to identify lncRNAs associated with CCMs pathogenesis using patient cohorts having 10 CCM patients and 4 controls from brain. Executing next generation sequencing, we performed whole transcriptome sequencing (RNA-seq) analysis and identified 1,967 lncRNAs and 4,928 protein coding genes (PCGs) to be differentially expressed in CCMs patients. Among these, we selected top 6 differentially expressed lncRNAs each having significant correlative expression with more than 100 differentially expressed PCGs. The differential expression status of the top lncRNAs, SMIM25 and LBX2-AS1 in CCMs was further confirmed by qRT-PCR analysis. Additionally, gene set enrichment analysis of correlated PCGs revealed critical pathways related to vascular signaling and important biological processes relevant to CCMs pathophysiology. Here, by transcriptome-wide approach we demonstrate that lncRNAs are prevalent in CCMs disease and are likely to play critical roles in regulating important signaling pathways involved in the disease progression. We believe, that detailed future investigations on this set of identified lncRNAs can provide useful insights into the biology and, ultimately, contribute in preventing this debilitating disease.

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Clinical and angioarchitectural characteristics of spinal vascular malformations of the cervical spine

Journal of Neurosurgery Spine ◽

10.3171/2019.11.spine19798 ◽

2020 ◽

Vol 32 (5) ◽

pp. 755-762 ◽

Cited By ~ 1

Author(s):

Waleed Brinjikji ◽

Elisa Colombo ◽

Giuseppe Lanzino

Keyword(s):

Cervical Spine ◽

Lower Extremity ◽

Clinical Presentation ◽

Vascular Malformations ◽

Case Series ◽

Acute Onset ◽

Lower Extremity Weakness ◽

Arteriovenous Fistulas ◽

Spinal Vascular Malformations ◽

Interventional Neuroradiologist

OBJECTIVEVascular malformations of the cervical spine are exceedingly rare. To date there have been no large case series describing the clinical presentation and angioarchitectural characteristics of cervical spine vascular malformations. The authors report their institutional case series on cervical spine vascular malformations diagnosed and treated at their institution.METHODSThe authors retrospectively reviewed all patients with spinal vascular malformations from their institution from January 2001 to December 2018. Patients with vascular malformations of the cervical spine were included. Lesions were characterized by their angioarchitectural characteristics by an interventional neuroradiologist and endovascular neurosurgeon. Data were collected on clinical presentation, imaging findings, treatment outcomes, and long-term follow-up. Descriptive statistics are reported.RESULTSOf a total of 213 patients with spinal vascular malformations, 27 (12.7%) had vascular malformations in the cervical spine. The mean patient age was 46.1 ± 21.9 years and 16 (59.3%) were male. The most common presentations were lower-extremity weakness (13 patients, 48.1%), tetraparesis (8 patients, 29.6%), and lower-extremity sensory dysfunction (7 patients, 25.9%). Nine patients (33.3%) presented with hemorrhage. Fifteen patients (55.6%) had modified Rankin Scale scores of 0–2 at the time of diagnosis. Regarding angioarchitectural characteristics, 8 patients (29.6%) had intramedullary arteriovenous malformations (AVMs), 5 (18.5%) had epidural arteriovenous fistulas (AVFs), 4 (14.8%) had paraspinal fistulas, 4 (14.8%) had mixed epidural/intradural fistulas, 3 (11.1%) had perimedullary AVMs, 2 (7.4%) had dural fistulas, and 1 patient (3.7%) had a perimedullary AVF.CONCLUSIONSThis retrospective study of 27 patients with cervical spine vascular malformations is the largest series to date on these lesions. The authors found substantial angioarchitectural heterogeneity with the most common types being intramedullary AVMs followed by epidural AVFs, paraspinal fistulas, and mixed intradural/extradural fistulas. Angioarchitecture dictated the clinical presentation as intradural shunts were more likely to present with hemorrhage and acute onset myelopathy, while dural and extradural shunts presented as either incidental lesions or gradually progressive congestive myelopathy.

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Pilot study in patients with congenital low-flow vascular malformation treated with low dose sirolimus

10.21203/rs.3.rs-132412/v1 ◽

2020 ◽

Author(s):

Veroniek Harbers ◽

Gerard Rongen ◽

van der Carine Vleuten ◽

Bas Verhoeven ◽

de Peter Laat ◽

...

Keyword(s):

Pilot Study ◽

Adverse Events ◽

Vascular Malformation ◽

Low Dose ◽

Liver Toxicity ◽

Vascular Malformations ◽

Low Flow ◽

Bone Marrow Toxicity ◽

Serious Adverse Events ◽

Grade Iii

Abstract Background Patients with congenital low-flow vascular malformations (capillary (CM), lymphatic (LM), venous (VM) or combined) may have an impaired quality of life (QoL), due to their symptoms, which include pain, swelling, bleeding, thrombosis, and functional impairment. Unfortunately, current treatment methods are challenging and not always successful. Previous studies have shown that the mTOR-inhibitor sirolimus is an effective treatment for these patients. Target levels of 10–15 ng/ml were well tolerated; however, grade three adverse events were observed (ranged 20–40%). Methods A pilot study was performed using a Challenge–Dechallenge–Rechallenge (CDR) design to determine the pharmacodynamics of low target levels of sirolimus (target levels 4–10 ng/ml) in respect of efficacy and adverse events in patients with disabling low-flow vascular malformations without treatment alternatives. The patients received sirolimus over a three-to-six-month period (Challenge), followed by the withdrawal of sirolimus (Dechallenge). If the complaints returned, sirolimus was reintroduced during a twelve month period (Rechallenge). Efficacy was determined on pain (end point of the pilot study) and other symptoms related to the vascular malformation; and adverse events were determined in all phases of the study. Results An improvement in symptoms was seen in 92% (n = 11/12) of patients during the Challenge phase. In the Rechallenge phase, a positive response rate of 78% was found (n = 7/9). These response rates are comparable to those found in the literature despite low target levels of sirolimus. However, less serious adverse events were observed with low dose sirolimus, especially bone marrow toxicity and grade III liver toxicity. Conclusions This pilot using low dose sirolimus showed high efficacy in patients with therapy resistant and disabling low-flow malformation, with a lower incidence of serious adverse events (especially bone marrow toxicity and grade III liver toxicity). This is extremely relevant to patients with low-flow vascular malformation, as current clinical protocols tend to advise lifelong treatment. Trial registration The pilot study was part of a phase III study. Trial registration: EudraCT number: 2016-002157-38 and ClinicalTrials.gov Identifier: NCT03987152, registered 06/14/2019 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03987152?term=sirolimus&cond=Vascular+Malformations&cntry=NL&draw=2&rank=1

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Angiomatosis in the neck and mediastinum: an example of low-flow vascular malformations

European Radiology ◽

10.1007/s00330-002-1555-3 ◽

2003 ◽

Vol 13 (5) ◽

pp. 981-985 ◽

Cited By ~ 1

Author(s):

Sifrid Hendrickx ◽

Robert Hermans ◽

Guy Wilms ◽

Raf Sciot

Keyword(s):

Vascular Malformations ◽

Low Flow

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Abstract 1122‐000135: Application of the Berenstein‐DeLeacy Grading Scale to Assess Treatment Outcome in Orbital Lymphatic Malformations

Stroke: Vascular and Interventional Neurology ◽

10.1161/svin.01.suppl_1.000135 ◽

2021 ◽

Vol 1 (S1) ◽

Author(s):

Reade De Leacy ◽

Maximilian J Bazil ◽

Neha Siddiqui ◽

Stavros Matsoukas ◽

Tomoyoshi Shigematsu ◽

...

Keyword(s):

Granulation Tissue ◽

Vascular Malformations ◽

Low Flow ◽

Complete Regression ◽

Lymphatic Malformations ◽

Interval Change ◽

Radiologic Findings ◽

Scale Scores ◽

Complete Obliteration ◽

Initial Imaging

Introduction : Lymphatic malformations (LMs) are low‐flow vascular malformations that arise as a result of erroneous vascular development during embryogenesis. Prior to the advent of the Berenstein‐De Leacy (BDL) scale, no reproducible grading system had been designed to compare sclerotherapy outcomes on the basis of radiologic findings. The soft‐tissue detail, absence of ionizing radiation, safety profile, and ubiquity of MR imaging made it an ideal technique on which the imaging‐based criteria was developed. The BDL scale ranges from 1–7 denoting complete obliteration to significant progression respectively. A “B” modifier is assigned for identification of granulation tissue in the treatment bed. We examine and validate the BDL scale on a cohort of 16 orbital LMs from our practice. Methods : Orbital LMs treated with sclerotherapy at our practice between 2000 and 2021 were assessed by an attending physician prior to initial and after final treatment to assign scale scores. The assigned scores represent changes in the orbit as defined by pre‐ and post‐septal spaces, above and below eyelids, and intra/extraconal spaces going to the coronal apex without the cavernous sinus. Results : The median age at initial imaging was 24 months (range: 1–445 months) and 108 months (range 12–528) at final imaging. The median imaging interval was 61 month. Males and females were represented in our cohort equally. Six cases presented with right orbital LMs (37.5%) and 10 presented on the left (62.5%). Six cases presented with macrocystic malformations (37.5%), five cases with microcystic (31.25%), and five cases with mixed (31.25%). 11 patients were treated with bleomycin and 5 patients were treated with bleomycin and doxycycline. BDL scale scores ranged from 2–7 with one case assigned the “B” modifier. Two cases were labelled as BDL7, or gross interval progression of the LM. Four cases were labelled as BDL6, or regression of the LM in one region with progression into a previously uninvolved/untreated area. Three cases were labelled as BDL5 with minimal or no gross interval change. One case was labelled as BDL4 and assigned the “B” modifier for partial regression with >50% estimated volume of residual malformation and granulation tissue in the treatment bed. Three cases were labelled as BDL3, or partial repression with <50% estimated volume of residual malformation. One case was labelled as BDL2 with near‐complete regression with trace residual of the lesion. No cases were labelled as BDL1, or complete regression of the lesion. Conclusions : The BDL scale was applied to a series of 16 orbital LMs to demonstrate its versatility in describing the treatment progression of this historically difficult‐to‐classify malformation. We hope visualization of BDL scores for orbital LMs will assist other interventionalists with incorporating this scale as a metric for treatment progression and outcomes.

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Un’opprimente tumefazione laterocervicale... da far mancare il respiro

Medico e Bambino pagine elettr ◽

10.53126/mebxxiv015 ◽

2021 ◽

Vol 40 (1) ◽

pp. 15-18

Author(s):

Chiara Mellino ◽

Pietro Gasperini ◽

Maria Luisa Conte ◽

Valeria Dell’Omo ◽

Francesca Libertucci ◽

...

Keyword(s):

Early Childhood ◽

Lymphatic System ◽

Clinical Presentation ◽

Hormone Level ◽

Male Infant ◽

Low Flow ◽

Lymphatic Malformations ◽

Live Births ◽

Adjacent Structures ◽

Life Threatening

Lymphatic malformations are low-flow vascular anomalies of the lymphatic system that occur in one out of 2-4,000 live births. They may be classified as macrocystic (diameter > 1 cm), microcystic (diameter < 1 cm) or mixed. Lymphatic malformations that are not prenatally diagnosed are typically diagnosed at birth or in early childhood. The clinical presentation can be quite variable, ranging from a focal area with minimal swelling to large involvement with compromise of adjacent structures. Up to 75% of lymphatic malformations are found in the cervicofacial region and their presence in the aerodigestive tract can lead to life-threatening airway obstruction. Lesions can grow slowly or rapidly and suddenly due to infection, trauma, bleeding or hormone level changes. The paper describes the case of a 9-month-old male infant with cervical macrocystic lymphangioma appeared during a febrile airway infection and misdiagnosed with bacterial lymphadenitis.

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