Search Results (59)

Background and Objective: Cerebral cavernous malformation (CCM) is a vascular disorder causing seizures, neurological deficits, and hemorrhagic stroke. It can be sporadic or inherited via CCM1, CCM2, or CCM3 gene mutations. Inflammation is broadly recognized as a promoter of cerebral vascular malformations. This study explores inflammatory mechanisms and differences behind CCM-related hemorrhage and epilepsy. Material and Methods: The study group comprised 28 patients, ten patients with CCM-related epilepsy, and 18 patients who clinically presented with a cerebral hemorrhage at diagnosis. All patients underwent microsurgical resection of the CCMs. Formaldehyde-fixed, paraffin-embedded tissue samples were immunohistochemically stained using a monoclonal antibody against Cyclooxygenase 2 (COX-2) (Dako, Santa Clara, CA; Clone: CX-294) and NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) (ABCAM, Cambridge, MA, USA; ab214185). MRI and clinical data were correlated with immunohistochemical findings, and the analysis was conducted utilizing the Trainable Weka Segmentation algorithm. Results: Median CCM volume was 1.68 cm³ (IQR: 0.85–3.07 cm³). There were significantly more NLRP3-positive cells (32.56% to 91.98%; mean: 65.82%, median: 68.34%; SD: ±17.70%), compared to COX-2-positive cells (1.82% to 79.69%; mean: 45.87%, median: 49.06%; SD: ±22.56%). No correlation was shown between the volume of CCMs and a hemorrhage event (p = 0.13, 95% CI: 0.99–1.02). Symptomatic brain hemorrhage showed a significantly increased inflammatory enzyme upregulation from both COX-2 (p < 0.001) and NLRP3 (p = 0.009) versus patients with symptomatic CCM-related epilepsy at first diagnosis. Conclusions: Inflammatory processes in CCMs seem to be driven by broad and multiple pathways because both COX-2 and NLRP3-driven inflammatory pathways are consistently activated. As a novelty, this study showed that patients with symptomatic hemorrhage showed upregulated inflammatory enzyme activity compared to patients with CCM-related epilepsy. No direct links between NLRP3, COX-2 expression, and radiological, pathological, or preexisting patient conditions were found. Full article

Objective: This study aims to analyze the diagnostic patterns of cavernoma-related epilepsy, the management of antiseizure medications, and clinical outcomes following microsurgical treatment in patients with late-diagnosed epilepsy secondary to cavernous malformations in the Central Asian region. Methods: A retrospective cross-sectional study was conducted on 60 patients who underwent microsurgical resection for brain cavernous malformations over a 12-year period (2010–2022) at the National Centre for Neurosurgery, Astana, Kazakhstan. All participants were 18 years or older and presented with seizures. Follow-up evaluations were conducted by neurologists, and seizure outcomes were assessed using the 2017 classification criteria of the International League Against Epilepsy. Results: The mean follow-up period was 83.77 ± 39.81 months. In total, 51.67% of participants demonstrated positive ILAE outcomes, 33.33% had moderate ILAE outcomes, and the remaining 15.00% experienced negative ILAE outcomes. Approximately 47% of patients received antiseizure medication before surgery, primarily as monotherapy with carbamazepine (33%), and administered at a low dose (40%). Early microsurgical resection showed a positive post-surgery seizure outcome. Approximately 67% of patients who experienced seizures within one year prior to surgery showed positive ILAE outcomes, whereas those with a seizure history extending beyond five years were roughly 32% seizure-free (p = 0.01). Conclusions. Cavernoma-related epilepsy in Central Asia remains a significant clinical challenge, particularly with respect to diagnostic accuracy and antiseizure medication management. In our cohort, only approximately half of patients achieved favorable seizure control following microsurgical resection. Notably, early surgical intervention within one year of seizure onset was associated with improved outcomes, whereas delayed surgery, restricted availability of intraoperative technologies, and suboptimal antiseizure medication practices were linked to less favorable outcomes. Strengthening diagnostic pathways, antiseizure medication management, and expanding access to advanced surgical technologies are critical steps to improving treatment outcomes in a studied patient population. Full article

Cerebral cavernous malformation (CCM) is a cluster of abnormal blood vessels in the brain that leads to severe neurological deficits, seizures, and fatal hemorrhagic stroke. Currently, there is no available drug treatment for CCM. Most CCMs are conservatively managed by observing change in appearance (MRI), recent hemorrhage, or any clinical symptoms. Neurosurgery is the only current treatment option, but it is only effective in a few cases. Since most CCM lesions are surgically inaccessible, when left untreated they lead to severe neurological deficits, seizures, and fatal hemorrhagic stroke. Hence, new non-invasive, safe, and effective treatment strategies are urgently needed. Recent research has identified gut microbiome dysbiosis and its innate immune response as the critical stimulus in experimental CCM pathogenesis, demonstrating the importance of the gut–brain axis in CCM. Importantly, CCM patients also manifest gut microbiome dysbiosis and gut barrier health can impact CCM disease course. This review highlights the emerging involvement of the gut microbiome in CCM pathogenesis and its potential as a therapeutic target. While preclinical data suggest mechanistic links, the lack of clinical intervention studies limits current applicability and underscores the need for translational research. Full article

Introduction: Hypertrophic olivary degeneration (HOD) is a rare form of trans-synaptic degeneration involving the Guillain–Mollaret triangle, characterized by enlargement of the inferior olivary nucleus—unlike the atrophy typical of most neurodegenerative processes. It is usually associated with stroke, surgical injury, or demyelination, but rarely follows hemorrhage from a cavernous malformation (CM). This report presents a case of HOD secondary to a mesencephalic CM hemorrhage, with emphasis on imaging findings and diagnostic considerations. Case Description: A 55-year-old woman presented with acute-onset, right-sided facial, torso, and limb hypoesthesia, along with gait instability. Neurological examination revealed sensory impairment in the right maxillary (V2) and mandibular (V3) trigeminal territories, as well as diminished pain and temperature sensation throughout the right hemibody. MRI revealed a hemorrhage in the posterior mesencephalon near the left red nucleus, leading to the diagnosis of a CM with an associated venous angioma. She was managed conservatively and improved clinically. Six months later, MRI showed hypertrophy and T2/FLAIR hyperintensity of the left inferior olive, consistent with developing HOD. At 1.5 years follow-up, olivary enlargement had progressed—now consistent with stage 2 HOD—and a bilateral palatal tremor was observed, more pronounced on the right side. DTI revealed asymmetric volume loss in the left brainstem fiber pathways at the level of the medulla oblongata, confirming trans-synaptic degeneration. Conclusions: This case highlights HOD as a rare but important complication of mesencephalic CM hemorrhage. Recognition of its characteristic imaging features—olivary hypertrophy with persistent T2/FLAIR hyperintensity—is essential for accurate diagnosis. DTI supports the trans-synaptic mechanism, helping distinguish HOD from other pathologies and preventing unnecessary investigations. Full article

Background: Venous malformation, formerly designated as cavernous hemangioma, is a rare vascular lesion characterized by significant endothelial cells proliferation, predominantly affecting young females. Diagnosis is challenging due to its low incidence and variety of clinical, radiological, and histological presentations. Objectives: The aim was to review the current scientific understanding of maxillary venous malformation based on the available literature and present an additional rare case of venous malformation of the upper maxilla. Methods: A systematic review was conducted across PubMed, Google Scholar, and Embase databases for studies published between January 1990 and April 2025. Inclusion criteria encompassed meta-analyses, systematic reviews, randomized controlled trials, non-randomized controlled trials, cohort studies, and case reports describing cavernous hemangiomas and venous malformation of the maxilla. All clinical and radiological characteristics were considered. Results: Out of 10,021 studies identified through our database search, 22 met the inclusion criteria, describing 28 (29 with our case) clinical cases of maxillary venous malformation. Conclusions: Maxillary venous malformation presents complex and varied clinical and radiological aspects, which are crucial for preoperative assessment and management. Appropriate measures may be necessary to prevent bleeding complications during lesion removal. To the best of our knowledge, this is the first comprehensive review on venous malformation of the maxilla. In addition, we report an unusual case identified incidentally during implant planning and successfully removed through isolated bone augmentation. Full article

Background/Objectives: Vascular anomalies represent a complex group of conditions including vascular malformations and haemangiomas. Haemangiomas are benign tumours that have an endothelial origin. In contrast, vascular malformations are characterized by the abnormal dilation of vessels without proliferation. Depending on the extension of the disease, there is a higher risk of life-threatening haemorrhages that may occur during simple dental procedures. The aim of this case report is to present the interdisciplinary treatment for patients with venous malformation and to discuss the possible dental management of these patients. Methods: A 66-year-old male patient with an extensive venous malformation of the head and neck was referred for a tooth extraction. The venous malformation involved lips, buccal mucosa, tongue, and floor of the oral cavity. Its proximity to the tooth requiring extraction was associated with a high risk of severe bleeding. Results: Prior to the treatment, CBCT and CT scans were performed to confirm the extensions of the lesion and visualise its margins. Considering the possible risks related with venous malformation, the procedure consisted of tooth removal in a hospital setting with control over severe bleeding complications. Conclusions: The presence of an extensive vascular malformation in the head and neck region is burdened with a higher risk of haemorrhages during simple dental procedures. The radiological and clinical planning enables the choice of an accurate treatment strategy to avoid possible difficulties. In cases where such complications cannot be avoided, it is important to perform the treatment in a hospital setting with the cooperation of maxillofacial surgeons. Full article

Endothelial cells respond to forces generated by laminar blood flow with changes in vasodilation, anticoagulant, fibrinolytic, or anti-inflammatory functions which preserve vessel patency. These responses to flow shear stress are primarily mediated by the modulation of the following transcription factors: Krüppel-like factors 2 and 4 (KLF2 and KLF4). Notably, disturbed flow patterns, which are found in vascular areas predisposed to atherosclerosis, significantly reduce the endothelial expression of KLF2 and KLF4, resulting in changes in the transcriptome that exacerbate inflammation and thrombosis. The endothelial CCM (Cerebral Cavernous Malformation) complex, comprising KRIT1 (Krev1 interaction trapped gene 1), CCM2 (Malcavernin), and CCM3 (Programmed cell death protein 10), suppresses the expression of KLF2 and KLF4. Loss of function of the CCM complex has recently been suggested to protect from coronary atherosclerosis in humans. We thus hypothesized that the silencing of KRIT1, the central scaffold of the CCM complex, can normalize the atherogenic effects of disturbed flow on the human endothelial transcriptome. Bulk RNA sequencing (RNA-seq) was conducted on human umbilical vein endothelial cells (HUVECs) after the expression of KRIT1 was silenced using specific small interfering RNA (siRNA). The endothelial cells were exposed to three different conditions for 24 h, as follows: pulsatile shear stress (laminar flow), oscillatory shear stress (disturbed flow), and static conditions (no flow). We found that silencing the KRIT1 expression in HUVECs restored the expression of the transcription factors KLF2 and KLF4 under oscillatory shear stress. This treatment resulted in a transcriptomic profile similar to that of endothelial cells under pulsatile shear stress. These findings suggest that inhibition of the CCM complex in endothelium plays a vasoprotective role by reactivating a protective gene program to help endothelial cells resist disturbed blood flow. Targeting CCM genes can activate well-known vasoprotective gene programs that enhance endothelial resilience to inflammation, hypoxia, and angiogenesis under disturbed flow conditions, providing a novel pathway for preventing atherothrombosis. Full article

Background/Objectives: Cerebral cavernous malformations (CCMs) are neurological disorders that increase the risk of hemorrhagic stroke. The Mexican Hispanic population has a higher prevalence of both CCMs and metabolic syndrome (MetS), defined by the presence of three or more of the following: central obesity, elevated triglycerides, low HDL, dyslipidemia, hypertension, or elevated fasting glucose. MetS is also associated with an increased risk of hemorrhagic stroke. However, the connection between MetS and hemorrhagic stroke in Hispanic CCM patients remains uncertain. Additionally, it is unclear if Hispanic CCM patients have different cardiometabolic profiles compared to controls. Methods: We analyzed a retrospective cohort of Mexican Hispanic adult CCM patients, including age- and gender-matched controls from the NHANES database. Fisher’s exact test or an unpaired Student’s t-test was used to compare risk factors between the CCM cohort and controls. Additionally, we conducted relative risk regression analysis to assess the adjusted association of MetS with hemorrhagic stroke. Results: The CCM cohort showed higher rates of epilepsy (24.6% vs. 1.6%, p < 0.001) and hemorrhagic stroke (36.6% vs. 3.6%, p < 0.001), but a lower prevalence of MetS (14% vs. 54.8%, p < 0.001) compared to age- and gender-matched Mexican Hispanic controls. The adjusted analysis revealed that among CCM patients in the older age group (age ≥ 50 years), MetS was associated with hemorrhagic stroke (RR = 2.38, 95%CI: 1.40–4.02, p = 0.001). Conclusions: This study reveals distinct features of CCMs in the Mexican Hispanic population, indicating a higher risk of hemorrhagic stroke and epilepsy compared to other ethnic groups. To mitigate the risk of hemorrhagic stroke, controlling blood pressure and managing comorbidities like metabolic syndrome (MetS) and epilepsy are essential, particularly in CCM patients aged 50 years and above. Full article

Hemorrhagic neurovascular diseases, with high mortality and poor outcomes, urge novel biomarker discovery and therapeutic targets. Micro-ribonucleic acids (miRNAs) are potent post-transcriptional regulators of gene expression. They have been studied in association with disease states and implicated in mechanistic gene interactions in various pathologies. Their presence and stability in circulating fluids also suggest a role as biomarkers. This review summarizes the current state of knowledge about miRNAs in the context of cerebral cavernous malformations (CCMs), a disease involving cerebrovascular dysmorphism and hemorrhage, with known genetic underpinnings. We also review common and distinct miRNAs of CCM compared to other diseases with brain vascular dysmorphism and hemorrhage. A systematic search, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline, queried all peer-reviewed articles published in English as of January 2025 and reported miRNAs associated with four hemorrhagic neurovascular diseases: CCM, arteriovenous malformations, moyamoya disease, and intracerebral hemorrhage. The PubMed systematic search retrieved 154 articles that met the inclusion criteria, reporting a total of 267 unique miRNAs identified in the literature on these four hemorrhagic neurovascular diseases. Of these 267 miRNAs, 164 were identified in preclinical studies, while 159 were identified in human subjects. Seventeen miRNAs were common to CCM and other hemorrhagic diseases. Common and unique disease-associated miRNAs in this systematic review motivate novel mechanistic hypotheses and have potential applications in diagnostic, predictive, prognostic, and therapeutic contexts of use. Much of current research can be considered hypothesis-generating, reflecting association rather than causation. Future areas of mechanistic investigation are proposed alongside approaches to analytic and clinical validations of contexts of use for biomarkers. Full article

Background: Cerebral cavernous malformations (CCMs) are vascular lesions linked to mutations in the CCM1, CCM2, and CCM3 genes, resulting in angiogenesis dysregulation. This case study highlights the clinical course of a child with severe CCMs and explores the genetic basis of the condition. Methods: We used comprehensive clinical assessment and magnetic resonance imaging (MRI) to monitor the patient’s neurological status and CCM progression and genetic analysis by whole-exome sequencing to identify mutations in CCM-related genes. Results: The patient presented with developmental delays, multiple CCMs, and recurrent hemorrhagic events, requiring five surgical interventions. Genetic analysis revealed a novel frameshift mutation in the PDCD10 gene. Despite surgical efforts, the patient developed significant disability by age 13. Conclusions: This case illustrates the aggressive clinical course associated with CCMs, particularly in patients with CCM3 mutations. It underscores the importance of genetic screening and monitoring in understanding hereditary CCM progression and guiding treatment strategies. Full article

Orbital cavernous venous malformations (CVMs) are the most common primary lesions in the orbit, characterized by slow growth and benign nature. CVMs that become symptomatic require intervention. Surgical management is guided by the expertise of the operating surgeon. Common surgical techniques include anterior orbitotomy (transconjunctival and transcutaneous), lateral and transcranial orbitotomy, and endoscopic transnasal approaches. Liquid agent embolization aids in easier lesion resection with reduced blood loss and potential prevention of recurrence. Our case reports detail the advantages and disadvantages of this approach, showcasing collaboration between neuroradiologists and orbital surgeons. Full article

Background: Cerebral cavernous malformations (CCMs), particularly when located in the cerebellum, pose unique clinical challenges due to the risk of hemorrhage and proximity to critical neurovascular structures. Surgical resection is often necessary to prevent further neurological deterioration. This case report describes the management of a symptomatic cerebellar cavernoma, emphasizing the use of microsurgical techniques and long-term follow-up. The objective of this study is to illustrate the surgical approach and outcomes of a patient with a hemorrhagic cerebellar cavernoma. Methods: A 63-year-old female presented with vertigo, and neuroimaging revealed a hemorrhagic cavernous malformation located in the right cerebellar hemisphere. Follow-up was conducted at two months and one year postoperatively, with serial imaging to assess lesion recurrence and neurological recovery. Results: Complete resection of the cavernoma was achieved without postoperative neurological deficits. Imaging at two months and one year post-surgery showed no signs of recurrence or new lesion formation. The patient remained asymptomatic, with no cranial nerve deficits or other long-term complications. Conclusions: This case demonstrates the effectiveness of microsurgical resection in treating symptomatic cerebellar cavernomas. The use of advanced intraoperative tools, such as neuronavigation and IONM, contributed to the successful outcome and prevention of postoperative complications. Long-term follow-up remains crucial to monitor for recurrence or the development of de novo lesions. Full article

Background/Objectives: Endovascular embolization is an effective treatment option for cerebral arteriovenous malformation (AVM) and dural arteriovenous fistulas (DAVFs). The objective of this study was to assess the safety and efficacy of Menox^TM in patients with cranial dural arteriovenous fistulas. Methods: From January 2021 to January 2023, 19 patients with intracranial DAVFs underwent embolization procedures. All patients were treated by embolization with Menox^TM or/and in combination with other embolization products such as Onyx (Covidien, Irvine, California), PHIL (MicroVention, Tustin, California), and Squid (Balt Extrusion, Montmorency, France). Treatment approaches were selected depending on the anatomical location of the fistula. Patients were monitored and followed-up for 12 months. Results: The patients’ mean age was 56.26 ± 16.49 years. Of these 19 patients, 58% (n = 11) were treated with the Menox^TM liquid embolizing agent (LEA) alone or in combination with different LEAs, while n = 7 were treated with other LEAs and 1 patient was treated solely with coils. Complete occlusion of DAVFs with Menox^TM and other agents was evident in 68.4% (n = 13/19) of patients. Complete occlusion (100%) was observed in the sinus rectus, transverse sinus, and diploic veins of the orbital roof, while complete occlusion was observed in 50% of falcotentorial patients and 60% of superior sagittal sinus patients. The lowest rate of complete fistula obliteration was observed in the dural carotid cavernous fistula (CCF) group (25%). An intra-procedural adverse event occurred in one patient. No other post-procedural adverse events were noted. Furthermore, in patients treated with Menox^TM, total occlusion was achieved in 72.7% (n = 8) of patients, whereas the non-Menox^TM group had 62.5% (n = 5) of patients with 100% occlusion and 37.5% (n = 3) of patients with subtotal occlusion. Conclusions: Outcomes using Menox^TM alone and in combination with other agents were effective, and it is safe for the treatment of dural arteriovenous fistulas. Full article

Cerebral cavernous malformations (CCMs) are abnormal expansions of brain capillaries that increase the risk of hemorrhagic strokes, with CCM1 mutations responsible for about 50% of familial cases. The disorder can cause irreversible brain damage by compromising the blood–brain barrier (BBB), leading to fatal brain hemorrhages. Studies show that progesterone and its derivatives significantly impact BBB integrity. The three CCM proteins (CCM1, CCM2, and CCM3) form the CCM signaling complex (CSC), linking classic and non-classic progesterone signaling within the CmPn network, which is crucial for maintaining BBB integrity. This study aimed to explore the relationship between CCM1 and key pathways of the CmPn signaling network using three mouse embryonic fibroblast lines (MEFs) with distinct CCM1 expressions. Omics and systems biology analysis investigated CCM1-mediated signaling within the CmPn network. Our findings reveal that CCM1 is essential for regulating cellular processes within progesterone-mediated CmPn/CmP signaling, playing a crucial role in maintaining microvessel integrity. This regulation occurs partly through gene transcription control. The critical role of CCM1 in these processes suggests it could be a promising therapeutic target for CCMs. Full article

Background: Patients with supratentorial cavernous malformations (SCMs) commonly present with seizures. First-line treatments for cavernoma-related epilepsy (CRE) include conservative management (antiepileptic drugs (AEDs)) and surgery. We compared seizure outcomes of CRE patients after early (≤6 months) vs. delayed (>6 months) surgery. Methods: We compared outcomes of CRE patients with SCMs surgically treated at our large-volume cerebrovascular center (1 January 2010–31 July 2020). Patients with 1 sporadic SCM and ≥1-year follow-up were included. Primary outcomes were International League Against Epilepsy (ILAE) class 1 seizure freedom and AED independence. Results: Of 63 CRE patients (26 women, 37 men; mean ± SD age, 36.1 ± 14.6 years), 48 (76%) vs. 15 (24%) underwent early (mean ± SD, 2.1 ± 1.7 months) vs. delayed (mean ± SD, 6.2 ± 7.1 years) surgery. Most (32 (67%)) with early surgery presented after 1 seizure; all with delayed surgery had ≥2 seizures. Seven (47%) with delayed surgery had drug-resistant epilepsy. At follow-up (mean ± SD, 5.4 ± 3.3 years), CRE patients with early surgery were more likely to have ILAE class 1 seizure freedom and AED independence than those with delayed surgery (92% (44/48) vs. 53% (8/15), p = 0.002; and 65% (31/48) vs. 33% (5/15), p = 0.03, respectively). Conclusions: Early CRE surgery demonstrated better seizure outcomes than delayed surgery. Multicenter prospective studies are needed to validate these findings. Full article