A calvarial osteolytic lesion of probable vascular origin in a Maya juvenile from the Classic Period ( 250-900 CE).

OBJECTIVE: This case study evaluates a focal osteolytic lesion in the right sulcus sinus transversi of an isolated os occipitale. MATERIALS: The os occipitale is from a juvenile from the Cueva de Sangre at the Classic Period (250-900 CE) site of Dos Pilas, Guatemala METHODS: The lesion was examined macroscopically, microscopically, and radiographically. RESULTS: The oval lesion has a well-circumscribed margin, endocranial origin, and involves cortical destruction of the inner and outer tables. Subperiosteal bone reaction around the lesion is present on the ectocranial surface. Skeletal evidence of increased vascularity, diploë expansion, and perimortem fracture near the lesion are not observed. CONCLUSIONS: The lesion appears to reflect a response to the presence of an expansile process that has caused pressure erosion. The anatomical location of the lesion and the endocranial origin suggest a probable vascular anomaly, such as a vascular malformation. SIGNIFICANCE: This case study represents one of the few bioarchaeological evaluations of probable vascular anomaly in a juvenile. As such, it expands our knowledge about vascular anomalies in the past and provides a comparative and core reference for guiding future paleopathological investigations on cranial osteolytic lesions. LIMITATIONS: The skeletal assemblage is commingled and fragmentary preventing the assessment of the distribution of lesions across the skeleton. SUGGESTIONS FOR FUTURE RESEARCH: Further scrutiny of bioarchaeological collections is needed to better understand the distribution of vascular anomalies in the past.

Endovascular Treatment and Peri-interventional Management of Ruptured Cerebrovascular Lesions During Pregnancy : Case Series and Case-based Systematic Review.

PURPOSE: Hemorrhagic stroke, particularly occurring from ruptured cerebrovascular malformations, is responsible for 5-12% of all maternal deaths during pregnancy and the puerperium. Whether endovascular treatment is feasible and safe for both the mother and the fetus, is still a matter of debate. The main objective of this case series and systematic review was to share our multi-institutional experience and to assess the feasibility and safety of endovascular treatment during pregnancy, as well as the corresponding maternal and fetal outcomes based on currently available evidence. METHODS: We report a case series of 12 pregnant women presenting with hemorrhagic stroke from ruptured cerebrovascular arteriovenous malformations or aneurysms who underwent endovascular treatment prior to delivery. A systematic literature review of pregnant patients with endovascular treated cerebrovascular malformations, published between 1995 and 2022, was performed. Clinical patient information, detailed treatment strategies, maternal and fetal outcomes as well as information on the delivery were collected and assessed. RESULTS: In most patients the course was uneventful and an excellent outcome without significant neurological deficits (mRS ≤ 1) was achieved. Furthermore, the maternal outcome was not worse compared to the general population who underwent endovascular treatment of ruptured vascular brain lesions. Also, in most cases a healthy fetus was born. CONCLUSION: Endovascular treatment of ruptured cerebrovascular malformations during pregnancy is safe and feasible regarding both aspects, the maternal and fetal outcomes. Still, a stronger knowledge base is needed to correctly approach future cases of intracranial hemorrhage in the pregnant population.

Neonatal Aneurysm Rupture in a Child with a De Novo Variant to ANKRD17.

Ankyrin repeat domain 17 (ANKRD17) is postulated to play a role in the integrity of blood vessels and has been reported to be associated with developmental delays, epilepsy, and growth restriction. Whereas ANKRD17-deficient mice have been demonstrated to experience catastrophic hemorrhages, vascular malformations have not been reported in human patients with pathogenic variants to ANKRD17. We report a term male neonate with a heterozygous de novo variant to ANKRD17 (ANKRD17; c6988 C > G, P.[P2330a]) who experienced subarachnoid hemorrhage from a ruptured aneurysm involving the left middle cerebral artery. He experienced acute symptomatic seizures and required clipping of his aneurysm at 35 days of life, later progressing to developing multifocal drug-resistant epilepsy. To our knowledge, this case represents the first report of a cerebrovascular malformation from a patient with ANKRD17. Further work is needed to investigate whether pathogenic variants to ANKRD17 can lead to cerebral aneurysms or other cerebrovascular malformations in children.

Epidermal nevus syndrome with the mutation of PTCH1 gene and cerebral infarction: a case report and review of the literature.

BACKGROUND: Epidermal nevus syndrome is a group of congenital neuroectodermal and/or mesodermal disorders characterized by the epidermal nevi in common association with cerebral, eye, skeletal, cardiovascular, and renal abnormalities. Epidermal nevus syndrome is a rare syndrome, and epidermal nevus syndrome with the mutation of PTCH1 gene and cerebral infarction is even rarer and has not been reported to the best of our knowledge. CASE PRESENTATION: We report the case of a 10-month-old Chinese female patient who presented to our pediatric neurologic department, University of Wenzhou medical teaching Hospital, Hangzhou. She has mobility disorders on the right limbs and recurrent seizures. She had congenital disorder accompanied by brownish-black and verrucose plaques on the right side of the face as well as extensive brownish-black plaques and brown nevi on the right side of the trunk and the right arm. Epidermal nevus syndrome was diagnosed on the basis of her symptoms. Somatic sebaceous nevi and hypoplastic defects of skin, cerebra, eyes, skeleton, and cardiovascular and renal system were observed. However, in addition to the typical clinical characteristics, the patient also has a mutation (c.109G > T) in PTCH1 gene and cerebral infarction. We present a novel case report and literature review. CONCLUSION: To our knowledge, epidermal nevus syndrome with a mutation of PTCH1 gene and cerebral infarction has not been reported previously. This case report may contribute to characterizing the phenotype of epidermal nevus syndrome, help clinicians be aware of the association of this condition with PTCH1 gene and cerebral infarction, raise clinical suspicion, and improve early therapy.

Cerebral Cavernous Malformation Pathogenesis: Investigating Lesion Formation and Progression with Animal Models.

Cerebral cavernous malformation (CCM) is a cerebromicrovascular disease that affects up to 0.5% of the population. Vessel dilation, decreased endothelial cell-cell contact, and loss of junctional complexes lead to loss of brain endothelial barrier integrity and hemorrhagic lesion formation. Leakage of hemorrhagic lesions results in patient symptoms and complications, including seizures, epilepsy, focal headaches, and hemorrhagic stroke. CCMs are classified as sporadic (sCCM) or familial (fCCM), associated with loss-of-function mutations in KRIT1/CCM1, CCM2, and PDCD10/CCM3. Identifying the CCM proteins has thrust the field forward by (1) revealing cellular processes and signaling pathways underlying fCCM pathogenesis, and (2) facilitating the development of animal models to study CCM protein function. CCM animal models range from various murine models to zebrafish models, with each model providing unique insights into CCM lesion development and progression. Additionally, these animal models serve as preclinical models to study therapeutic options for CCM treatment. This review briefly summarizes CCM disease pathology and the molecular functions of the CCM proteins, followed by an in-depth discussion of animal models used to study CCM pathogenesis and developing therapeutics.

Somatic mosaicism in the MAPK pathway in sporadic brain arteriovenous malformation and association with phenotype.

OBJECTIVE: Sporadic brain arteriovenous malformation (BAVM) is a tangled vascular lesion characterized by direct artery-to-vein connections that can cause life-threatening intracerebral hemorrhage (ICH). Recently, somatic mutations in KRAS have been reported in sporadic BAVM, and mutations in other mitogen-activated protein kinase (MAPK) signaling pathway genes have been identified in other vascular malformations. The objectives of this study were to systematically evaluate somatic mutations in MAPK pathway genes in patients with sporadic BAVM lesions and to evaluate the association of somatic mutations with phenotypes of sporadic BAVM severity. METHODS: The authors performed whole-exome sequencing on paired lesion and blood DNA samples from 14 patients with sporadic BAVM, and 295 genes in the MAPK signaling pathway were evaluated to identify genes with somatic mutations in multiple patients with BAVM. Digital droplet polymerase chain reaction was used to validate KRAS G12V and G12D mutations and to assay an additional 56 BAVM samples. RESULTS: The authors identified a total of 24 candidate BAVM-associated somatic variants in 11 MAPK pathway genes. The previously identified KRAS G12V and G12D mutations were the only recurrent mutations. Overall, somatic KRAS G12V was present in 14.5% of BAVM lesions and G12D was present in 31.9%. The authors did not detect a significant association between the presence or allelic burden of KRAS mutation and three BAVM phenotypes: lesion size (maximum diameter), age at diagnosis, and age at ICH. CONCLUSIONS: The authors confirmed the high prevalence of somatic KRAS mutations in sporadic BAVM lesions and identified several candidate somatic variants in other MAPK pathway genes. These somatic variants may contribute to understanding of the etiology of sporadic BAVM and the clinical characteristics of patients with this condition.

A national analysis of 9655 pediatric cerebrovascular malformations: effect of hospital volume on outcomes.

OBJECTIVE: Comprehensive multicenter data on the surgical treatment of pediatric cerebrovascular malformations (CVMs) in the US are lacking. The goal of this study was to identify national trends in patient demographics and assess the effect of hospital case volume on outcomes. METHODS: Admissions for CVMs (1997-2012) were identified from the nationwide Kids' Inpatient Database. Admissions with and without craniotomy were reviewed separately. Patients were categorized by whether they were treated at low-, medium-, or high-volume centers (< 10, 10-40, > 40 cases/year, respectively). A generalized linear model was used to evaluate the association of hospital pediatric CVM case volume and clinical variables assessing outcomes. RESULTS: Among the 9655 patients, 1828 underwent craniotomy and 7827 did not. Patient age and race differed in the two groups, as did the rate of private medical payers. High-volume hospitals had fewer nonroutine discharges (11.2% [high] vs 16.4% [medium] vs 22.3% [low], p = 0.0001). For admissions requiring craniotomy, total charges ($106,282 [high] vs $126,215 [medium] vs $134,978 [low], p < 0.001) and complication rates (0.09% [high] vs 0.11% [medium] vs 0.16% [low], p = 0.001) were lower in high-volume centers. CONCLUSIONS: This study revealed that further investigation may be needed regarding barriers to surgical treatment of pediatric CVMs. The authors found that surgical treatment of pediatric CVM at high-volume centers is associated with significantly fewer complications, better dispositions, and lower costs, but for noncraniotomy patients, low-volume centers had lower rates of complications and death and lower costs. These findings may support the consideration of appropriate referral of CVM patients requiring surgery or with intracranial hemorrhage toward high-volume, specialized centers.

Vein of Galen Malformations: The Texas Children's Hospital Experience in the Modern Endovascular Era.

BACKGROUND: Vein of Galen malformations (VOGM) comprise nearly a third of pediatric cerebrovascular anomalies, with potentially devastating neurological and systemic complications. Advances in endovascular therapies have dramatically improved outcomes compared to historical surgical treatments, and neurosurgeons are an essential component of the multidisciplinary critical care team. OBJECTIVE: To retrospectively review pediatric patients with VOGM treated at Texas Children's Hospital (TCH), a quaternary referral center, over 15 yr, and present lessons learned in treating children with modern endovascular techniques. METHODS: Charts from TCH were retrospectively reviewed for the past 15 yr. Patients with diagnosis including "Vein of Galen," "Vein of Galen malformation," "Vein of Galen aneurysmal malformation," or any abbreviations (ie, VOG, VOGM, VOGAM) were reviewed. Presentation, imaging, treatment specifics, and clinical outcomes were reported. RESULTS: There were 18 patients with VOGM managed at TCH from 2002 to 2018 with a total of 29 embolizations. Seventeen were performed with a single embolisate (NBCA or Onyx), and 12 with a combination. A dual lumen balloon catheter was used as an adjunct in 3 embolizations. Complications occurred in 5 embolizations (24%), including hemorrhage, embolisate migration, and femoral vessel occlusion. Surviving patients were followed for a mean of 38 mo, with 12 having normal or near-normal neurological development. CONCLUSION: VOGM can present with a myriad of neurological and systemic symptoms, potentially in extremis. Neurosurgical involvement in these cases is critical, as urgent treatment can be lifesaving. Patients may require multiple treatment sessions using a variety of endovascular tools and techniques.

Increased Prevalence of Cerebrovascular Disease in Hospitalized Patients with Marfan Syndrome.

BACKGROUND AND PURPOSE: Small studies have suggested that Marfan syndrome is associated with a number of cerebrovascular complications. We sought to determine whether a clinical diagnosis of Marfan syndrome is associated with a higher prevalence of cerebrovascular diseases than the general population by performing a case-control study of hospitalized patients in the Nationwide Inpatient Sample (NIS). METHODS: Using the 2000-2012 NIS, we performed a case-control study matching cases of Marfan syndrome to controls without such a diagnosis. The prevalence of various cerebrovascular diseases between the 2 groups were compared, and multivariate logistic regression was used to adjust for suspected comorbidities. RESULTS: Between 2000 and 2012, there were a total of 13,883 discharges carrying a diagnosis of Marfan syndrome. On univariate analysis, patients with Marfan syndrome were more likely to have a primary or secondary diagnosis of hemorrhagic stroke (0.5% versus 0.3%, odds ratio [OR] = 1.56, 95% confidence interval [CI] = 1.06-2.29, P = 0.02) as well as intracranial hemorrhage (subarachnoid hemorrhage [SAH] and hemorrhagic stroke) (0.3% versus 0.2%, OR = 1.72, 95% CI = 1.05-2.82, P = 0.03). Patients hospitalized with Marfan syndrome were significantly more likely to have carotid dissection (0.3% versus 0.0%, OR = 11.69, 95% CI = 3.60-38.08, P <. 0001) and cerebral aneurysms (0.2% versus 0.1%, OR = 3.67, 95% CI = 1.76-7.68, P = 0.0002). On multivariate analysis adjusted for age, race, and comorbidities, patients with Marfan syndrome had significantly higher odds of ischemic stroke (OR = 1.20, 95% CI = 1.02-1.43, P = 0.03), hemorrhagic stroke (OR = 1.75, 95% CI = 1.18-2.63, P = 0.005), carotid artery dissection (OR = 11.94, 95% CI = 4.23-50.03, P < 0.0001), and cerebral aneurysm (OR = 3.95, 95% CI = 1.95-8.90, P <0.0001). CONCLUSIONS: There is a modestly increased prevalence of ischemic stroke, hemorrhagic stroke, and cerebral aneurysms in hospitalized patients with Marfan syndrome when compared with controls.

[Diagnosis and treatment of extracranial internal carotid artery lesion combined with cerebrovascular malformation]. / Diagnostika i lechenie porazhenii ékstrakranial'nogo otdela vnutrennei sonnoi arterii v sochetanii s sosudistoi mal'formatsiei golovnogo mozga.

AIM: To analyze own experience of diagnosis and treatment of patients with extracranial internal carotid artery lesion and cerebrovascular malformations. MATERIAL AND METHODS: There were 16 patients with combined lesion of extracranial and intracranial internal carotid artery for the period January 2013 - December 2014. Occlusive-stenotic lesion and tortuosity of ICA were observed in 11 and 5 cases respectively. RESULTS: Incidence of combined ICA lesion was 5.2% (16 out of 308 observations of extracranial internal carotid artery lesion). Surgical treatment was performed in 7 patients including two-stage intervention in 4 cases and simultaneous surgery in 3 cases. Mean time between neurosurgical and vascular stages was 6 months. Complications and mortality were absent. CONCLUSION: Two-stage surgical approach with intracerebral vascular malformation correction followed by extracranial ICA reconstruction may be safe and effective in patients with combined lesion of ICA. Further trials are necessary for certain conclusions.

Increased Prevalence of Cerebrovascular Disease in Hospitalized Patients with Ehlers-Danlos Syndrome.

BACKGROUND AND PURPOSE: Small studies have suggested that Ehlers-Danlos syndrome (EDS) is associated with a number of cerebrovascular complications. We sought to determine whether a clinical diagnosis of EDS is associated with a higher prevalence of cerebrovascular diseases than the general population by performing a case-control study of hospitalized patients in the Nationwide Inpatient Sample (NIS). METHODS: Using the 2000-2012 NIS, we performed a case-control study matching cases of EDS to controls without such a diagnosis. The prevalence of various cerebrovascular diseases between the 2 groups was compared, and multivariate logistic regression was used to adjust for suspected comorbidities. RESULTS: Between 2000 and 2012, there were a total of 9067 discharges carrying a diagnosis of EDS. On univariate analysis, patients with EDS were more likely to be hospitalized for carotid dissection (.2% versus .01%, odds ratio [OR] = 18.0, confidence interval [CI] = 2.41-135.12, P < .0001), vertebral dissection (.1% versus 0%, P = .008), cervical artery aneurysm (.1% versus .01%, OR = 9.01, CI = 1.14-71.11, P < .0001), cerebral aneurysm (.4% versus .09%, OR = 4.89, CI = 2.28-10.47, P < .0001), and cerebrovascular malformation (.1% versus .02%, OR = 5, CI = 1.10-22.85, P = .021), compared to the controls. On multivariate analysis adjusted for age, race, and comorbidities, EDS patients had significantly higher odds of carotid dissection (OR = 15.02, CI = 3.08-270.87, P < .0001), vertebral dissection (OR = 2406539.5, P = .0037), cervical artery aneurysm (OR = 11.75, CI = 2.11-220.71, P = .0026), cerebral aneurysm (OR = 5.59, CI = 2.69-13.18, P < .0001), and cerebrovascular malformation (OR = 4.67, CI = 1.20-30.87, P = .0243). CONCLUSIONS: Carotid and vertebral dissections, cervical and cerebral aneurysms, as well as other cerebrovascular malformations are more common in hospitalized patients with EDS compared to controls.

Glioma coexisting with angiographically occult cerebrovascular malformation: A case report.

Angiographically occult cerebrovascular malformation (AOVM) is a type of complex cerebrovascular malformation that is not visible on digital subtraction angiography (DSA). Vascular malformation coexisting with glioma is clinically rare, and glioma coexisting with AOVM is even more rare. To the best of our knowledge, the present study is the first to report glioma coexisting with AOVM in the literature. The present study reports a rare case of glioma coexisting with AOVM in a 30-year-old male patient. Computed tomography (CT) scan revealed calcification, hemorrhage and edema in the right frontal lobe. CT angiography revealed a vascular malformation in the right frontal lobe, which was not observed on DSA. Finally, glioma coexisting with AOVM was confirmed by 2.0T magnetic resonance imaging and postoperative pathological examination. The present patient had a positive outcome and no neurological dysfunctions during the 6-month follow-up subsequent to surgery.

Derivation of Self-inhibitory Helical Peptides to Target Rho-kinase Dimerization in Cerebrovascular Malformation: Structural Bioinformatics Analysis and Peptide Binding Assay.

Rho-kinase dimerization is essential for its kinase activity and biological function; disruption of the dimerization has recently been established as a new and promising therapeutics strategy for cerebrovascular malformation (CM). Based on Rho-kinase dimer crystal structure we herein combined in silico analysis and in vitro assay to rationally derive self-inhibitory peptides from the dimerization interface. Three peptides namely Hlp1, Hlp2 and Hlp3 were successfully designed that have potential capability to rebind at the dimerization domain of Rho-kinase. Molecular dynamics (MD) simulations revealed that these peptides are helically structured when bound to Rho-kinase, but exhibit partially intrinsic disorder in unbound state. Binding free energy (BFE) analysis suggested that the peptides have a satisfactory energetic profile to interact with Rho-kinase. The computational findings were then substantiated by fluorescence anisotropy assays, conforming that the helical peptides can bind tightly to Rho-kinase with affinity KD at micromolar level. These designed peptides are considered as lead molecular entities that can be further modified and optimized to obtain more potent peptidomimetics as self-competitors to disrupt Rho-kinase dimerization in CM.

[Cerebrovascular malformation revealed during the prethrombolysis workup in acute ischemic stroke. Impact on therapeutic decision making]. / Malformation vasculaire cérébrale découverte dans le bilan pré-thrombolyse d'un infarctus cérébral. Impact sur la décision thérapeutique.

Intravenous recombinant tissue plasminogen activator for acute ischemic stroke is contraindicated in patients harboring an asymptomatic intracranial vascular malformation, whether it is incidentally discovered at the time of the initial cerebral imaging or previously known. Because thrombolysis is associated with a risk of serious intracerebral hemorrhage, it is theoretically possible that this treatment increases the risk of bleeding or rupture of these malformations. However, this risk seems very low in clinical practice. We report two cases, one with a probable brainstem cavernous malformation treated with alteplase for a supratentorial ischemic stroke who developed just after treatment a fatal brainstem hemorrhage, and another one with asymptomatic dural arteriovenous fistula, treated by endovascular thrombectomy solely. This approach was safe and effective, and the patient had an endovascular embolization of the fistula one month later as it became symptomatic. Based on the literature, we discuss the bleeding risk of asymptomatic intracranial vascular malformations in acute ischemic stroke patients treated with alteplase, depending on the type of malformation (intracranial aneurysm, arteriovenous and cavernous malformation or fistula), and the alternative therapeutic options.

Application of 3.0T susceptibility-weighted magnetic resonance imaging in diagnosing cerebrovascular malformations / 中华神经医学杂志

Objective To evaluate the value of 3.0T susceptibility-weighted magnetic resonance imaging (SWI) in the diagnosis of cerebrovascular malformations. Methods Forty-six patients with cerebrovascular malformations, admitted to our hospital fiom May 2008 to December 2010, were examined with a 3.0T MR scanner. All patients were examined with MRI conventional sequences T1WI,T2WI, 3DTOF, and their results were compared with SWI sequence so as to evaluate the value of SWI in the diagnosis of cerebrovascular malformations.Results Twenty-five patients had arteriovenous malformation (AVM), 10 with cavernous hemangioma, 8 with venous malformations, and 3 with telangiectasis in the 46 patients with cerebrovascular malformations. SWI could delineate all the cerebrovascular malformation lesions, especially small lesions, but could not display all supplying artery in AVM. 3DTOF was a better technique in delineating large AVM lesions. Conclusion SWI is much more sensitive in showing small cerebrovascular malformations; and combined with other MR sequences,clear diagnosis of cerebral vascular malformations can be made by SWI.

Comparative Study of PC-MRA,CTA and 3D-DSA in the Diagnosis of Cerebrovascular Disease / 实用放射学杂志

Objective To evaluate the accuracy and clinical efficacy of low field phase-contrast magnetic resonance angiography(PC-MRA),CTA and 3D-DSA in the diagnosis of cerebrovascular disease.Methods 70 patients with clinically suspected cerebrovascular diseases were examined with PC-MRA,CTA and 3D-DSA.The sensitivity in detecting the cerebrovascular disease with these three methods were compared.Results Fifty-one patients were detected with cerebrovascular diseases in seventy patients by three imaging methods,including 36 aneurysms in 33 cases and 18 arteriovenous amlformations.33,34 and 35 aneurysms,17,16 and 18 arteriovenous malformations were detected by PC-MRA , CTA and 3D-DSA respectively , the sensitivity were 91.67% and 94.44%,94.44% and 88.89%,97.22% and 100% respectively.There were no significant difference in the sensitivity of detecting aneurysm and arteriovenous malformation between these three imaging methods(P＞0.05).Conclusion PC-MRA,CTA and 3D-DSA are no of difference in diagnosis of cerebrovascular malformation.

Radiosurgical Treatment of Cerebrovascular Malformations / 대한뇌혈관학회지

The application of stereotactic radiosurgery for cerebrovascular malformations began in the early 1970s. Despite pooly documented response of vascular malformations to externally fractionated radiotherapy, single fraction, high dose, small-field, focused irradiation of small vascular malformations were found to be effective and non-invasive method to obliterate vascular malformations. During last thirty years, overall role of stereotactic radiosurgery has been established in the management of carefully selected vascular malformations. By 1998 world-wide, more than 20,000 patients had undergone Gamma Knife radiosurgery for arteriovenous malformations. In comparison to other forms of nonsurgical management or surgical excision, stereotactic radiosurgery has number of advantages. In properly selected, small volume AVMs, the total obliteration rate at two years appears to be acceptably high(more than 80%), and is associated with low morbidity(less than 2-3%). In contrast to open surgical removal, radiosurgery is associated with none of the risk of microsurgical resection such as blood loss, infection, acute neurological deficits and operative mortality. And yet, major problem of radiosurgery is that it is still exposed to any potential risk of bleeding during latent period before complete obliteration of arteriovenous malformations. Continuous study and researches are recommended for radiobiological clearance. To solve this problem and to enhance the effectiveness of treatment, new energy source should be developed to reduce latent period until complete obliteration would be secured, while reducing the chance of risk by irradiation. Presently, radiosurgery is applied to other vascular malformations such as cavernous angioma or venous angioma, yet, the result is still subject to controversy. Thus, more rigorous research, clinical experience, and enhanced treatment plan should be sought.