Firsttrimester Diagnosis and Therapy @ 11 - 13 +6 Weeks of Gestation - Part 2 : Guideline of the DEGUM, ÖGUM, SGUMGG, DGGG, ÖGG, Gynecologie Suisse, DGPM, DGPGM, BVF, ACHSE (AWMF S2e LL 085-002 1.1.2024) (https://register.awmf.org/de/leitlinien/detail/085-002).

This extensive AWMF 085-002 S2e-guideline "First Trimester Diagnosis and Therapy @ 11 - 13 +6 Weeks of Gestation" has systematically analyzed high-quality studies and publications and the existing evidence (evidence tables) and produced recommendations (level of recommendation, level of evidence, strength of consensus). This guideline deals with the following topics in the context of the 11 - 13 +6 weeks scan: the legal basis, screening for anatomical malformations, screening for chromosomal defects, quality assessment and audit, screening for preeclampsia and FGR, screening for preterm birth, screening for abnormally invasive placenta (AIP) and placenta accreta spectrum (PAS), screening for velamentous cord insertion and vasa praevia, screening for diabetes mellitus and LGA. Screening for complications of pregnancy can best be carried out @ 11 - 13 +6 weeks of gestation. The issues of how to identify malformations, chromosomal abnormalities and certain disorders of placentation (high blood pressure and proteinuria, intrauterine growth retardation) have been solved. The problem of how to identify placenta percreta and vasa previa has been partially solved. What is still unsolved is how to identify disorders of glucose metabolism and preterm birth. In the first trimester, solutions to some of these problems are available: parents can be given extensive counselling and the risk that a pregnancy complication will manifest at a later stage can be delayed and reduced. This means that screening is critically important as it helps in decision-making about the best way to manage pregnancy complications (prevention and intervals between follow-up examinations). If no treatment is available and if a termination of pregnancy is considered, the intervention can be carried out with far lower complications compared to the second trimester of pregnancy. In most cases, further examinations are not required and the parents can be reassured. A repeat examination at around week 20 of gestation to complete the screening for malformations is recommended. Note: The guideline will be published simultaneously in the official journals of both professional societies (i.e. Ultraschall in der Medizin/European Journal of Ultrasound for the DEGUM and Geburtshilfe und Frauenheilkunde for the DGGG).

Neurological and cardiopulmonary manifestations of pulmonary arteriovenous malformations.

Pulmonary arteriovenous malformations (PAVMs) are direct pulmonary artery-to-vein connections without pulmonary capillaries that result in intrapulmonary right-to-left blood shunts. Although most patients with PAVMs may be entirely asymptomatic, PAVMs can induce a series of complications involving the neurological, cardiovascular, and respiratory systems that can lead to catastrophic and often fatal clinical sequelae. In this study we review the available literature and summarize the reported PAVM-related complications among patients with PAVMs. The reviewed studies included observational studies, case studies, prospective studies, and cohort studies, and we provide an overview of PAVM-related neurological and cardiopulmonary manifestations, including stroke, cerebral abscess, transient ischemic attack, cerebral hemorrhage, migraine, seizure, dizziness, cardiac failure, arrhythmia, myocardial infarction, cough, hypoxemia, dyspnea, respiratory failure, hemoptysis, and hemothorax. Identifying and treating PAVMs before the presentation of major complication is important because this can prevent the occurrence of complications and can result in better outcomes. PAVM patients should thus be better evaluated and managed by a multidisciplinary team because they may be in a treatable phase prior to their condition becoming life-threatening.

Cost-utility of sirolimus in the treatment of vascular malformations.

Sirolimus is being increasingly employed to manage specific vascular anomalies. We performed an exploratory cost-utility analysis to evaluate sirolimus as a treatment for vascular malformations from the Australian healthcare system perspective. Over a one-year time horizon, sirolimus treatment was associated with an increased expenditure of AU$2832.80 and a gain of 0.08 quality-adjusted life years (QALYs) when compared to supportive care, resulting in an incremental cost-effectiveness ratio of AU$35,410/QALY. By most metrics, sirolimus would be considered a cost-effective treatment for vascular malformations.

Clinical, myopathological, and genetic features of two Chinese families with Andersen-Tawil syndrome.

Purpose: To explore the clinical, muscle pathological, and pathogenic gene mutation characteristics of Andersen-Tawil Syndrome (ATS) and enhance the understanding of ATS among clinical practitioners. Methods: Retrospective analysis of clinical data and muscle pathology of two ATS families, along with genetic testing for probands and some family members. Results: In Family 1, spanning four generations, four individuals were affected, while Family 2 had two affected individuals across four generations. All six patients in both families experienced onset in childhood, presenting with periodic paralysis, arrhythmias, and craniofacial skeletal abnormalities. In Family 1, the proband's periodic paralysis was more triggered by low temperature and exercise, occurring several times a year, lasting 4-7 days. All three adult patients in Family 1 had a history of hypokalemia, and the frequency and severity of attacks were reduced after regular oral potassium supplement therapy. Two adult females in Family 1 experienced limb weakness triggered by stress, exertion, and premenstrual period, with milder symptoms than the proband. In Family 2, the proband's periodic paralysis typically occurred the day after excessive exertion, with a frequency of approximately 2-3 months. Two years prior, the proband developed arrhythmias without palpitations or chest tightness. The proband's brother experienced intermittent limb weakness during adolescence, remained untreated, and had sudden death at age 40. Physical examination revealed characteristic features in Family 1 and both probands: small mandible, wide eye spacing, and fifth-digit clinodactyly. Four adult patients were shorter in stature, while the growth status of a pediatric patient was indeterminate. Supplementary tests showed a history of hypokalemia during muscle weakness episodes in Family 1, while Family 2 patients had normal potassium levels during episodes. The long exercise tests were positive in both probands. Muscle MRI showed no significant abnormalities, but muscle pathology revealed rimmed vacuoles and tubular aggregates. Genetic testing identified KCNJ2 gene mutations in two probands and some of their family members, with c.407C > T (p.S136F) heterozygous mutation in Family 1 and c.652C > T (p.R218W) heterozygous mutation in Family 2. Conclusion: Among the clinical symptoms of the patients with Andersen-Tawil Syndrome in this study, not everyone exhibits the full triad of signs: periodic paralysis is the most common initial symptom, craniofacial and digit skeletal abnormalities are characteristic signs, and ventricular arrhythmias pose the most serious potential risk. Given that these typical symptoms were observed in 5 out of 6 patients, clinicians should pay special attention to these typical symptoms, and patients with these symptoms should be followed up over time. Muscle biopsy May reveal pathological changes such as tubular aggregates, but genetic testing for KCNJ gene mutations remains a crucial diagnostic criterion for this syndrome.

Prevalence, characteristics and risk factors of birth defects in central China livebirths, 2015-2022.

Objective: This study analyzed the prevalence, epidemiological characteristics and risk factors of birth defects among livebirths in central China, aiming to provide evidences for the prevention of birth defects and government Decision-makings. Methods: Birth data from China's Hubei Province between 2015 and 2022 were collected, including basic information of the livebirths, the mothers and the fathers, as well as information about delivery and each prenatal examination. The livebirths prevalence of birth defects was calculated and the trends were mapped. The basic characteristics of birth defects were evaluated by the difference analysis between case and health groups. Univariate and multivariate Poisson regression was performed to examine the independent risk factors for birth defects. Results: Among 43,568 livebirths, 166 livebirths were born with birth defects, resulted in a total prevalence rate of 3.81 per 1,000 livebirths, showing a remarkable uptrend from 0.41per 1,000 livebirths in 2015 to 9.23 per 1,000 livebirths in 2022. The peak of the prevalence was in January and February. Congenital malformation of the musculoskeletal system was the main type of birth defect in central China livebirths, followed by cleft lip and cleft palate. Overall, newborns with birth defect had significantly earlier delivery gestational age, poorer health and higher proportion of infants with low birth weight than healthy births. The gender of livebirths, excess weight at delivery (≥80 kg) of mothers, more than 2 times of gravidity or parity of mothers, and advanced paternal age (≥40 years) were independent risk factors for birth defects (or specific birth defects). Conclusion: The livebirths prevalence of birth defects shows increasing trend in central China, which deserves the attention of the government and would-be parents. Elevated paternal age, excess maternal weight, gravidity and parity should be considered when planning their families.

foxe1 mutant zebrafish show indications of a hypothyroid phenotype and increased sensitivity to ethanol for craniofacial malformations.

BACKGROUND: FOXE1 mutations in humans are associated with cleft palate and hypothyroidism. We previously developed a foxe1 mutant zebrafish demonstrating mineralization defects in larvae. In the present study, we investigate the thyroid status and skeletal phenotype of adult foxe1 mutants. RESULTS: Mutant fish have increased expression of tshß in the pituitary, and of hepatic dio1 and dio2. In plasma, we found higher Mg levels. Together these findings are indicative of hypothyroidism. We further observed mineralization defects in scales due to enhanced osteoclast activity as measured by increased expression levels of tracp, ctsk, and rankl. Gene-environment interactions in the etiology of FOXE1-related craniofacial abnormalities remain elusive, which prompts the need for models to investigate genotype-phenotype associations. We here investigated whether ethanol exposure increases the risk of developing craniofacial malformations in foxe1 mutant larvae that we compared to wild types. We found in ethanol-exposed mutants an increased incidence of developmental malformations and marked changes in gene expression patterns of cartilage markers (sox9a), apoptotic markers (casp3b), retinoic acid metabolism (cyp26c1), and tissue hypoxia markers (hifaa, hifab). CONCLUSION: Taken together, this study shows that the foxe1 mutant zebrafish recapitulates phenotypes associated with FOXE1 mutations in human patients and a clear foxe1-ethanol interaction.

Undiagnosed scrotal swelling in a 36-year-old man: A congenital arteriovenous malformation.

We have reported the case of a 36-year-old man with severe scrotal swelling that had remained undiagnosed after multiple diagnostic tests. The patient had presented with scrotal swelling, multiple weeping ulcers on the dorsal aspect of the scrotum, and worsening pain affecting his day-to-day functioning. Duplex ultrasound showed low- to no-flow hypervascularity and dependent edema suspicious for a vascular malformation. Treatment included sequential Gelfoam (Pfizer, New York, NY) embolization using ultrasound-guided direct cannulation and traditional angiography. The scrotal circumference decreased by 65%, with moderate relief of his pain. The details from the present case have highlighted the significance of vascular malformations, various diagnostic and therapeutic techniques used, and value of endovascular embolization.

Adjunctive venous sinus stenting in transvenous embolization of vein of Galen malformations.

BACKGROUND: Vein of Galen malformations are congenital arteriovenous malformations primarily treated by endovascular embolization via transarterial or transvenous approaches. transvenous embolization can be utilized to close the malformation but may be difficult in patients with venous stenosis or blockages, which drive venous hypertension and lead to significant neurologic consequences. Here, we illustrate the atypical placement of an intracranial venous sinus stent to improve outflow after transvenous embolization in pediatric patients with the vein of Galen malformation. METHODS: A retrospective review of clinical databases at two high-volume endovascular centers from January 2018 to March 2023 identified all vein of Galen malformation patients who received a venous sinus stent during transvenous embolization. Clinical data, imaging, angioarchitecture, operative details, postoperative management, and follow-up were reviewed. RESULTS: Three patients presented for transvenous embolization after multiple staged transarterial embolizations of their vein of Galen malformation. Transvenous access was complicated by lateral sinus stenosis, which was temporarily relieved by balloon angioplasty. After transvenous embolization by pressure cooker technique, the dural sinuses were stented using the existing venous guide catheter. Venous angiography demonstrated improved flow across the stenosed areas and post-embolization angiography demonstrated normalized venous drainage with widely patent stents. One patient experienced postoperative oculomotor nerve palsy unrelated to the stent placement. All patients demonstrated a complete cure of their vein of Galen malformations with patent venous sinus stents on follow-up. CONCLUSION: In patients with the vein of Galen malformation and venous hypertension receiving transvenous embolization, venous sinus stenting may be a safe and effective option to reduce aberrant cortical venous drainage and improve normal outflow. Further studies are warranted to investigate its benefit in high-flow vascular malformations.

A non-genetic model of vascular shunts informs on the cellular mechanisms of formation and resolution of arteriovenous malformations.

AIMS: Arteriovenous malformations (AVMs), a disorder characterized by direct shunts between arteries and veins, are associated with genetic mutations. However, the mechanisms leading to AV shunt formation and how shunts can be reverted are poorly understood. METHODS AND RESULTS: Here, we report that oxygen-induced retinopathy (OIR) protocol leads to the consistent and stereotypical formation of AV shunts in non-genetically altered mice. OIR-induced AV shunts show all the canonical markers of AVMs. Genetic and pharmacological interventions demonstrated that changes in the volume of venous endothelial cells (EC)-hypertrophic venous cells-are the initiating step promoting AV shunt formation, whilst EC proliferation or migration played minor roles. Inhibition of the mTOR pathway prevents pathological increases in EC volume and significantly reduces the formation of AV shunts. Importantly, we demonstrate that ALK1 signalling cell-autonomously regulates EC volume in pro-angiogenic conditions, establishing a link with hereditary haemorrhagic telangiectasia-related AVMs. Finally, we demonstrate that a combination of EC volume control and EC migration is associated with the regression of AV shunts. CONCLUSION: Our findings highlight that an increase in the EC volume is the key mechanism driving the initial stages of AV shunt formation, leading to asymmetric capillary diameters. Based on our results, we propose a coherent and unifying timeline leading to the fast conversion of a capillary vessel into an AV shunt. Our data advocate for further investigation into the mechanisms regulating EC volume in health and disease as a way to identify therapeutic approaches to prevent and revert AVMs.

Presentation and management of cerebral proliferative angiopathy: a systematic review and meta-analysis on treatment outcomes.

Cerebral Proliferative Angiopathy (CPA) is a rare brain vascular malformation, similar to Arteriovenous Malformations (AVM) but lacking of early venous drainage. Presentation and treatment outcomes were investigated, examining for morbidity, mortality and complications. A meta-analysis was conducted according to PRISMA guidelines. PubMed, Embase and Web Of Science were searched with keywords such as "cerebral proliferative angiopathy" and "management". We pooled and meta-analyzed outcomes on documented CPA cases. 11,079 studies were pooled as a result of manual citation searching, 50 studies were included, adding up to 115 CPA cases. The majority of patients were females (1.38:1), with a mean age of presentation of 26.9 (19.4) years. Headache (46%) and seizures (34%) were the most common presenting symptoms. 37% of patients presented with focal neurologic deficit. Patients managed conservatively from the surgical standpoint (i.e. nonoperative management) did not undergo homogenous treatment strategies, and major complications were at 47% (95% CI: 17%, 76%), with a 1% mortality (95% CI: 0%, 6%). Surgical and embolization interventions presented the highest proportion of major complications, 66% (95% CI: 33%, 99%) and 73% (95% CI: 42%, 100%), respectively. The embolization subgroup led in mortality, with 3% (95% CI: 0%, 10%). No death was documented in patients undergoing surgery. CPA has a similar presentation to brain arteriovenous malformations, but its treatment outcomes are potentially worse. This difference is not attributable to heterogeneity in assigning patient treatment strategies. This highlights the need for more accurate diagnostic methods.

Multiple endpoints analysis of the effects of diesel oil on a commercial species, Carcinus maenas.

Fuel spills in marine environments pose significant threats to aquatic ecosystems, evidencing the intricate relationship between fuel utilization and its impact on benthic species of commercial value for human consumption. This interconnectedness of human, animal and environmental welfare falls within the One Health framework. The aim of the present study was to evaluate the toxicological effects of diesel oil on the green crab Carcinus maenas, and make a parallelism between tested concentrations and petrogenic hydrocarbon levels in natural environments. Mortality, locomotion and feeding behavior, molting, somatic growth, morphological malformations, stress biomarkers, and nutritional variables were analyzed in three different bioassays. In Bioassay 1, prepuberal females were exposed to diesel oil water accommodated fraction (WAF) to determine the median lethal concentration (LC50) at different periods. In Bioassay 2, prepuberal females were exposed to 168 h LC50 and LC25 of diesel oil WAF for 7 days, and were subsequently exposed to clean water. In Bioassay 3, prepuberal females were exposed to 168 h LC12 and LC6 of diesel oil WAF for 30 days. Petrogenic hydrocarbon levels in the field were quantified at a port and a nature reserve, with concentrations of aromatic hydrocarbons being 1.92 µg/g in the former and below 0.01 µg/g in the latter. In Bioassay 1, the 168 h LC50 was estimated to be 1.04 % of diesel oil. The results obtained in Bioassays 2 (LC50 and LC25) and Bioassays 3 (LC12 and LC6) suggest that environmental exposure to petrogenic hydrocarbons produces high mortality or interferes with the molting process of crabs, leading to reduced growth and developmental abnormalities. Such malformations were observed in chelipeds, pereiopods, gills chambers and eye peduncles, and affected feeding and locomotion behaviors. Overall, this could impact on population size and health, and consequently alter the ecological role and commercial exploitation of economically important species like C. maenas.

Vascular malformations in pediatric patients: 10-year experience of a vascular anomalies clinic.

BACKGROUND: Vascular malformations (VaMs) are caused by errors in vascular morphogenesis. Diagnosis and treatment can be complex. Few specialized centers care for these patients, and limited literature exists regarding their characteristics and clinical course. The vascular anomalies clinic (VAC) at the Instituto Nacional de Pediatría (National Institute for Pediatrics) is a multidisciplinary team and has been a reference center for patients with VaMs since 2012. We sought to describe the characteristics of patients cared for at the VAC, types of VaMs, treatments used, and clinical course. METHODS: This was a descriptive, observational, retrospective, and cross-sectional study conducted from 2012 to 2022. RESULTS: We included 435 patients with VaMs; the median age of presentation was 1 month. The most frequent signs and symptoms were increased volume (97.2%), superficial color change (65.5%), and pain (43.3%). The most common VaMs were lymphatic (36.7%) and venolymphatic (18.3%). Sclerotherapy was the most frequent treatment (73.4%), followed by medical treatment with sirolimus (18.5%); response to both was excellent/good in > 85% of cases. CONCLUSION: In this retrospective study of children with VaMs, we found that low-flow malformations were the most common, and sclerotherapy and sirolimus were the most frequently used treatments. The therapeutic response was excellent/good in most cases.

INTRODUCCIÓN: Las malformaciones vasculares (MaV) son secundarias a errores en la morfogénesis vascular. El diagnóstico y tratamiento puede ser complejo. Existen pocos centros especializados en su atención y escasa literatura respecto a características y evolución clínica. La Clínica de Anomalías Vasculares (CAV) del Instituto Nacional de Pediatría es un equipo multidisciplinario y centro de referencia para estos pacientes desde 2012. Buscamos describir las características de los pacientes atendidos en la CAV, tipo de MaV, tratamiento y evolución clínica. MÉTODOS: Estudio descriptivo, observacional, retrospectivo y transversal del periodo 2012 al 2022. RESULTADOS: Se incluyeron 435 pacientes con MaV, con edad mediana de presentación de 1 mes de vida. Los síntomas y signos más reportados fueron aumento de volumen (97.2%), cambio en coloración de la piel (65.5%) y dolor (43.3%). Las MaV más comunes fueron linfáticas (36.7%), siguiéndoles las venolinfáticas (18.3%). La escleroterapia fue el tratamiento más frecuente (73.4%) y el tratamiento médico más utilizado fue sirolimus (18.5%), ambos con excelente/buena respuesta en > 85% de los pacientes. CONCLUSIONES: En este estudio retrospectivo de niños con MaV encontramos que las más frecuentes son de bajo flujo y el tratamiento más usado escleroterapia y sirolimus. La respuesta terapéutica de la mayoría fue excelente/buena.

A rare cause of epileptic encephalopathy: case report of a novel patient with PEHO-like phenotype and CCDC88A gene pathogenic variants.

BACKGROUND: The Coiled-Coil Domain-Containing Protein 88 A (CCDC88A) gene encodes the actin-binding protein Girdin, which plays important roles in maintaining the actin cytoskeleton and in cell migration and was recently associated with a specific form of epileptic encephalopathy. Biallelic protein-truncating variants of CCDC88A have been considered responsible for progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO)-like syndrome. To date, only three consanguineous families with loss-of-function homozygous variants in the CCDC88A gene have been reported. The described patients share many clinical features, such as microcephaly, neonatal hypotonia, seizures, profound developmental delay, face and limb edema, and dysmorphic features, with a similar appearance of the eyes, nose, mouth, and fingers. CASE PRESENTATION: We report on a child from a nonconsanguineous family who presented with profound global developmental delay, severe epilepsy, and brain malformations, including subcortical band heterotopia. The patient harbored two heterozygous pathogenic variants in the trans configuration in the CCDC88A gene, which affected the coiled-coil and C-terminal domains. CONCLUSIONS: We detail the clinical and cerebral imaging data of our patient in the context of previously reported patients with disease-causing variants in the CCDC88A gene, emphasizing the common phenotypes, including cortical malformations, that warrant screening for sequence variants in this gene.

Fgf8 contributes to the pathogenesis of Nager syndrome.

Nager syndrome (NS, OMIM 154400) is a rare disease characterized by craniofacial and limb malformations due to variants in the gene encoding splicing factor 3B subunit 4 (SF3B4). Although various noncanonical functions of SF3B4 unrelated to splicing have been previously described, limited studies elucidate molecular mechanisms underlying NS pathogenesis. Here we showed that sf3b4-deficient fish displayed craniofacial and segmentation defects associated with suppression of fgf8 levels, which perturbed FGF signaling and neural crest cell (NCC) expression. Our finding also pointed out that oxidative stress-induced apoptosis was prominently detected in sf3b4-deficient fish and may further exaggerate the bone remodeling process. Notably, injection of exogenous FGF8 significantly rescued the demonstrated defects in sf3b4-deficient fish, which further supported the participation of Fgf8 in NS pathogenesis. Overall, our study provides valuable insights into the molecular mechanism underlying developmental abnormalities observed in NS and suggests future therapeutic strategies to protect against the pathogenesis of NS and possibilities for preventing severe outcomes.

Supplementation of high doses of vitamin D during the gestational period do not cause reproductive, teratogenic and genotoxic damage in mice.

Vitamin D deficiency during pregnancy may have adverse effects on embryo-fetal and postnatal development. Indeed, vitamin D supplementation has been indicated for pregnant women. However, there are no studies that indicate the safe dose of this supplementation during the gestational period. Therefore, the present study assessed the effects of high doses of vitamin D and vitamin D combined with calcium on reproductive performance, embryo-fetal development, and DNA integrity in Swiss mice. A total of 140 pregnant female mice treated with vitamin D and vitamin D combined with calcium were analyzed in two experiments. In one experiment, mice received intramuscular supplementation at doses of 600,000, 6,000,000, or 60,000,000 IU of vitamin D. These same doses were also associated with the dose of 8.56 mg/kg of calcium. In the other experiment, mice received a single oral dose of 6,000, 60,000, or 600,000 IU of vitamin D. These same doses were also associated with the dose of 8.56 mg/kg of calcium. The treatments were always carried out in the 10th gestational day. The results show that neither intramuscularly nor orally administered vitamin D and vitamin D combined with calcium affected reproductive performance, embryo-fetal development, or DNA integrity at the different doses tested. These pioneering results confirm the safety of using this type of high doses of supplementation, including during pregnancy.

Stereotactic radiosurgery alone for brain arteriovenous malformations: a single-institute experience.

OBJECTIVE: Brain arteriovenous malformations (BAVMs) represent an ongoing clinical challenge because of their complex nature. The long-term outcomes of BAVMs patients treated with stereotactic radiosurgery (SRS) alone are unclear. METHODS: We conducted a retrospective analysis of 201 patients treated for BAVMs from January 2010 to December 2019. The identified predictors of obliteration or hemorrhage in the multivariate analysis were estimated by odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: A total of 201 patients treated with gamma knife radiosurgery (GKRS) alone as the primary treatment for BAVMs were included. The mean age at GKRS treatment was 31.4 ± 1.1 years, and 61.2% of the patients were male. Multivariate logistic regression revealed that a higher radiosurgery-based AVM score (OR 1.847, 95% CI = 1.292-2.641; p = 0.001) was significantly associated with worse obliteration, and a higher margin dose significantly favored obliteration (OR 0.352, 95% CI = 0.189-0.658; p = 0.001). Multivariate analysis revealed that an increased lesion volume of 1 cm3 (OR 1.279, 95% CI = 1.023-1.600; p = 0.031) and a high margin dose (OR 0.363, 95% CI = 0.134-0.983; p = 0.046) were significant prognostic factors for post-SRS hemorrhage. CONCLUSIONS: In conclusion, our study investigated the available clinical and radiological prognostic factors for BAVMs and revealed that a higher margin dose significantly improved both the obliteration rate and nonhemorrhagic outcomes. Currently, the most appropriate candidates, Spetzler-Martin grade, and optimal radiation dose are still being defined by prospective trials.

Clinical features, hemorrhage risk and epilepsy outcomes of familial cerebral cavernous malformation: A 20-year observational pragmatic single-center study.

INTRODUCTION: Familial Cerebral Cavernous Malformations (fCCMs) are rare, hereditary conditions characterized by multiple central nervous system lesions. Despite their rarity, CCMs can cause significant clinical challenges when symptomatic, manifesting as seizure and symptomatic hemorrhage (CASH). Guidelines suggest neurosurgical intervention for symptomatic or previously symptomatic lesions, while conservative management is recommended for new-onset epilepsy. However, the natural history and optimal management remain unclear, necessitating further research. OBJECTIVE: This study aims to provide a comprehensive analysis of the clinical features, hemorrhage risk, and epilepsy outcomes in fCCM patients over an extended follow-up period, offering a more precise estimate of CASH and epilepsy rates in this population. METHODS: This retrospective longitudinal cohort study included fCCM patients enrolled from 2001 to May 2024. Data collected included demographic information, new neurological symptoms, symptomatic hemorrhages, seizures, and modified Rankin Scale (mRS) scores. Incidence rates of first symptomatic events and Kaplan-Meier survival curves were calculated, with logistic and Cox-proportional hazard regression models used to evaluate outcomes. RESULTS: A total of 47 patients were included in this study, with a mean age at diagnosis of 37.51 years. At diagnosis, 68 % were symptomatic, with 30 % having CASH and 36 % experiencing seizures without CASH. During a median follow-up of 126.0 months (interquartile range, 110.5 months), 17 % had a new CASH event, 20 % had seizures without CASH, and 60 % remained asymptomatic. The bleeding rate was 1.02 % per patient-year, with new focal neurological symptoms at 2.045 per 1000 patient-years and new CASH at 10.225 per 1000 patient-years. Most patients maintained minimal or no disability (mRS 0 or 1). Presenting with epilepsy at baseline significantly increased the odds of future seizures (OR 18.13, p = 0.001). CONCLUSION: This study highlights the complex presentation and progression of fCCMs, emphasizing the necessity for long-term monitoring. Baseline epilepsy is a significant predictor of future seizures, underscoring the need for individualized management strategies. Future research with larger cohorts and standardized criteria is essential to refine the understanding and management of fCCMs.

Efficacy and safety of hyaluronic-polidocanol foam in sclerotherapy for head and neck venous malformations.

Background: Foam sclerotherapy is currently the first-line treatment for venous malformations (VMs). Hyaluronic acid-polidocanol (HA-POL) foam has been used in the treatment of head and neck VMs recently; however, its clinical efficacy and safety have yet to be further evaluated, and the impact of age and other related factors on its safety is still unclear. Objective: To assess the efficacy and safety of HA-POL foam in the treatment of head and neck VMs. Methods and materials: We performed a single-center retrospective review of all patients with VMs involving the head and neck region undergoing HA-POL foam sclerotherapy from February 2015 to February 2022 in the Oral and Maxillofacial Surgery Department of Qilu Hospital Shandong University. Patients' medical records were collected and all patients enrolled were followed up for 1-6 months (group 1), part of them were followed up for 3-9 years (group 2). Results: A total of 223 patients with head and neck VMs were enrolled in the study, with 36 patients who were followed for 3-9 years. Total response rate in group 1 was 96.41% (n = 215), of which 30.94% (n = 69) of the patients met the criteria of "resolution," and 65.47% (n = 146) of the patients had "significant improvement." In group 2, the total response rate was 72.22% (n = 26), of which the rates of the patients met the criteria of "resolution" and patients had "significant improvement" were all 36.11% (n = 13)0.144 (64.57%) patients experienced complications like localized swelling, pain and fever, and no serious complications occurred. The risk of developing complications after treatment was independent of age, and was weakly associated with the dose of HA-POL foam. Conclusion: The HA-POL foam sclerotherapy is safe and effective in the treatment of head and neck VMs.