Cerebral Venous Malformations Research Articles

The story of N-butyl cyanoacrylate saphenous vein ablation

In 2009, our group was approached by an experienced radiologist who proposed to close refluxing saphenous veins with glue; an idea based on his experience with N-butyl cyanoacrylate (TRUFILL) embolization of cerebral arterial venous malformations. We henceforth began with a swine model, 1 Almeida J.I. Min R.J. Rabe R. McLean D.J. Madsen M. Cyanoacrylate adhesive for the closure of truncal veins: 60-day swine model results. Vasc Endovascular Surg. 2011; 45: 631-635 Crossref PubMed Scopus (74) Google Scholar and then moved to first-in-human studies 2 Almeida J.I. Javier J.J. Mackay E. Bautista C. Proebstle T. One-year follow-up of first human use of cyanoacrylate adhesive for treatment of saphenous vein incompetence. J Vasc Surg Venous Lymphatic Disord. 2013; 1: 174-180 Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar for nonthermal ablation of the saphenous vein with their proprietary N-butyl cyanoacrylate glue. Of interest, during the regulatory development pathway, this product was approved as a device, not a drug. It's efficacy has proved excellent, and during the past decade cyanoacrylate closure (CAC) has been adopted widely worldwide. However, reports of hypersensitivity-related adverse events, and granulomas, have begun to surface. It is timely that Dr Athavale and his team have recently published an excellent systematic review on CAC. Based on the available literature, the adverse events related to cyanoacrylate glue can be divided into the following: phlebitis, hypersensitivity (type I and type IV), foreign body granuloma, endovenous glue induced thrombosis and infection. These adverse events may require prolonged steroid use or vein excision. Cyanoacrylate glue reactions: A systematic review, cases, and proposed mechanismsJournal of Vascular Surgery: Venous and Lymphatic DisordersVol. 11Issue 4PreviewCyanoacrylate glue closure was first used in humans 10 years ago to treat venous reflux of the axial veins. Studies have since shown its clinical efficacy in vein closure. However, great need exists to elucidate further the types of specific adverse reactions that cyanoacrylate glue can cause for better patient selection and to minimize these events. In the present study, we systematically reviewed the literature to identify the types of reported reactions. In addition, we explored the pathophysiology contributing to these reactions and proposed the mechanistic pathway with inclusion of actual cases. Full-Text PDF

Acceleration of Brain Susceptibility-Weighted Imaging with Compressed Sensitivity Encoding: A Prospective Multicenter Study.

While three-dimensional susceptibility-weighted imaging has been widely suggested for intracranial vessel imaging, hemorrhage detection, and other neuro-diseases, its relatively long scan time has necessitated the clinical verification of recent progresses of fast imaging techniques. Our aim was to evaluate the effectiveness of brain SWI accelerated by compressed sensitivity encoding to identify the optimal acceleration factors for clinical practice. Ninety-nine subjects, prospectively enrolled from 5 centers, underwent 8 brain SWI sequences: 5 different folds of compressed sensitivity encoding acceleration (CS2, CS4, CS6, CS8, and CS10), 2 different folds of sensitivity encoding acceleration (SF2 and SF4), and 1 without acceleration. Images were assessed quantitatively on both the SNR of the red nucleus and its contrast ratio to the CSF and, subjectively, with scoring on overall image quality; visibility of the substantia nigra-red nucleus, basilar artery, and internal cerebral vein; and diagnostic confidence of the cerebral microbleeds and other intracranial diseases. Compressed sensitivity encoding showed a promising ability to reduce the acquisition time (from 202 to 41 seconds) of SWI while increasing the acceleration factor from 2 to 10, though at the cost of decreasing the SNR, contrast ratio, and the scores of visual assessments. The visibility of the substantia nigra-red nucleus and internal cerebral vein became unacceptable in CS6 to CS10. The basilar artery was well-distinguished, and diseases including cerebral microbleeds, cavernous angiomas, intracranial gliomas, venous malformations, and subacute hemorrhage were well-diagnosed in all compressed sensitivity encoding sequences. Compressed sensitivity encoding factor 4 is recommended in routine practice. Compressed sensitivity encoding factor 10 is potentially a fast surrogate for distinguishing the basilar artery and detecting susceptibility-related abnormalities (eg, cerebral microbleeds, cavernous angiomas, gliomas, and venous malformation) at the sacrifice of visualization of the substantia nigra-red nucleus and internal cerebral vein.

Cavernoma in the medulla oblongata – Case presentation and review of the literature

Cerebral cavernous venous malformations (also called cavernous hemangiomas or cavernomas) are the third most common cerebral vascular malformations having an incidence of 0.4-0.8% in the general population and being diagnosed more frequently incidentally during an imaging procedure. Usually solitary, but cavernomas can also be present as multiple lesions with autosomal dominant inheritance pattern. We present a rare case and the MRI imaging of a type I Zabramski cavernoma that bled, localized in the medulla oblongata of a 41-year-old man, admitted with paresthesia of the right upper limb, very mild right hemiparesis and impaired fine motor movements of the right hand and intractable persistent hiccups.

The spectrum of venous anomalies associated with atretic parietal cephaloceles: A literature review.

Background: Parietal atretic cephalocele (PAC) is a small, subscalp lesion with underlying extracranial meningeal, neural, and glial tissues. In this paper, we analyze the related literature on the continuum of PAC-associated venous anomalies and report an exemplary case.Methods: The PubMed Medline database was searched using the following search algorithm: (Atretic encephalocele) OR (Rudimentary meningocele,) OR (Atypical meningocele) OR (Meningocele manqué) OR (Meningeal heterotopia). Only papers detailing the venous anomalies associated with PACs have been included.Results: A total of 30 papers in our search documented PAC-associated venous abnormalities. The overall number of cases reported was 68 (including our exemplary case). The most frequently identified associated venous anomaly was the presence of a “fenestrated superior sagittal sinus” recorded in 48.5% of cases (n = 33), followed closely by “persistent falcine sinus” in 47% (n = 32) and vertical embryonic positioning of the straight sinus (SS) in 44% (n = 30). The complete absence of a SS was reported in 39.7% (n = 27) and various anomalies of the Galenic system were reported in 26.8% of cases (n = 12).Conclusion: Although benign in nature, PACs are often a marker for the presence of complex and variable cerebral venous malformations, requiring extensive preoperative imaging workup for both the superficial and deep venous systems to obtain an accurate understanding of the anatomy of the venous system and guide surgical planning.

Aberrant regulation of retinoic acid signaling genes in cerebral arterio venous malformation nidus and neighboring astrocytes

BackgroundCerebral arterio venous malformations (AVM) are a major causal factor for intracranial hemorrhage, which result in permanent disability or death. The molecular mechanisms of AVM are complex, and their pathogenesis remains an enigma. Current research on cerebral AVM is focused on characterizing the molecular features of AVM nidus to elucidate the aberrant signaling pathways. The initial stimuli that lead to the development of AVM nidus structures between a dilated artery and a vein are however not known.MethodsIn order to understand the molecular basis of development of cerebral AVM, we used in-depth RNA sequencing with the total RNA isolated from cerebral AVM nidus. Immunoblot and qRT-PCR assays were used to study the differential gene expression in AVM nidus, and immunofluorescence staining was used to study the expression pattern of aberrant proteins in AVM nidus and control tissues. Immunohistochemistry was used to study the expression pattern of aberrant proteins in AVM nidus and control tissues.ResultsThe transcriptome study has identified 38 differentially expressed genes in cerebral AVM nidus, of which 35 genes were upregulated and 3 genes were downregulated. A final modular analysis identified an upregulation of ALDH1A2, a key rate-limiting enzyme of retinoic acid signaling pathway. Further analysis revealed that CYR61, a regulator of angiogenesis, and the target gene for retinoic acid signaling is upregulated in AVM nidus. We observed that astrocytes associated with AVM nidus are abnormal with increased expression of GFAP and Vimentin. Triple immunofluorescence staining of the AVM nidus revealed that CYR61 was also overexpressed in the abnormal astrocytes associated with AVM tissue.ConclusionUsing high-throughput RNA sequencing analysis and immunostaining, we report deregulated expression of retinoic acid signaling genes in AVM nidus and its associated astrocytes and speculate that this might trigger the abnormal angiogenesis and the development of cerebral AVM in humans.

A case of pericapillary arteriovenous malformation

BackgroundPericapillary arteriovenous malformation (pAVM) frequently causes intracerebral hemorrhage (ICH). However, definitive diagnosis of pAVM is difficult, as it manifests angiographically as cerebral venous malformations. Case descriptionA 57-year-old woman presented with sudden headache. Computed tomography revealed left parietal subcortical hemorrhage. Angiography demonstrated abnormal veins at the hematoma. Under suspicion of pAVM, resection was performed 3 months after the onset of symptoms. Color Doppler identified one vein with both red and blue colored flows running into the subcortex. This vein was followed, and a cluster of abnormal vessels was identified and resected. Histological investigation demonstrated that one of the arterioles connected directly to a dilated thin-walled venule, leading to a diagnosis of pAVM. ConclusionsICH is rarely caused by venous malformation, but is frequently triggered by pAVM. Therefore, pAVM should be suspected when angiography shows abnormal vessels resembling venous malformation in patients with ICH. pAVM is only definitively diagnosed by histology. Angiographically identified abnormal vessels are draining veins, and a core pAVM is not seen radiologically. Surgery comprises the following steps: 1) following the abnormal vein along the sulcus; 2) aspiration of a small amount of cortex tissue to enable the vein to be followed; 3) identification of a cluster of abnormal arterioles in the subcortex; 4) en bloc removal of these abnormal vessels. Identification of the draining vein is the key point; color Doppler is useful for this, as a mixture of red and blue colors are displayed due to the presence of back and forth blood streams.

Heterogeneous Continuum of Cerebral and Cervicofacial Venous Malformations.

In this issue, Brinjiki et al[1][1] demonstrate a remarkable association between cervicofacial venous malformations (VMs) and cerebral developmental venous anomalies (DVAs), as well as between cervicofacial VMs and dural venous sinus anomalies in a retrospective study involving healthy age- and sex-

Facial Venous Malformations Are Associated with Cerebral Developmental Venous Anomalies.

A number of studies have demonstrated the existence of segmental vascular disorders affecting soft tissues of the head and neck along with the intracranial vasculature. The purpose of this study was to determine whether there is an association between cerebral developmental venous anomalies and venous malformations of the face, head, and neck. A consecutive series of patients with head and neck venous malformations who underwent MR imaging of the brain with postcontrast T1- or T2*-weighted imaging were included. Developmental venous anomaly prevalence in this patient population was compared with an age- and sex-matched control group without venous malformations at a ratio of 1:2. All images were interpreted by 2 neuroradiologists. Data were collected on venous malformation location, developmental venous anomaly location, developmental venous anomaly drainage pattern, and metameric location of venous malformations and developmental venous anomalies. Categoric variables were compared using χ2 tests. Forty-two patients with venous malformations were included. The mean age was 38.1 ± 11.1 years, and 78.6% of patients were female. The prevalence of developmental venous anomalies in this patient population was 28.6%. The control population of 84 patients had a mean age of 40.0 ± 5.9 years, and 78.6% of patients were female. The prevalence of developmental venous anomalies in this patient population was 9.5% (P = .01). In 83.3% of cases, developmental venous anomalies were ipsilateral to the venous malformation, and in 75% of cases, they involved the same metamere. Our case-control study demonstrated a significant association between brain developmental venous anomalies and superficial venous malformations. These findings suggest that there may be a similar pathophysiologic origin for these 2 entities.

Cerebral Venous Malformations in a Chinese Population: Clinical Manifestations, Radiological Characteristics, and Long-Term Prognosis

We elucidated the clinical and radiological characteristics and analyzed the risk factors for hemorrhage and poor outcomes of cerebral venous malformations (CVMs) in a northern Chinese population. We included 60 consecutive patients with CVM patients in Beijing Tiantan Hospital from January 2011 to February 2018. The clinical manifestations, radiological characteristics, management, and outcomes were elucidated and analyzed. The patients were followed up for 5-64 months (median, 26). Poor outcomes included repeat bleeding, secondary infarction, severe disability (modified Rankin scale score ≥3), and death. Infratentorial CVMs were more prone to intracranial hemorrhage (75% vs. 28.6%; P < 0.001), dizziness (37.5% vs. 10.7%; P= 0.017), and focal neurological deficits (65.6% vs. 25%; P= 0.002) than were supratentorial CVMs. Supratentorial CVMs were more prone to seizure (32.1% vs. 0%; P= 0.001) than were infratentorial CVMs. Multivariate logistic regression revealed that the major risk factors for intracranial hemorrhage in CVMs were infratentorial lesions (P= 0.003) and complicated cavernous angiomas (P= 0.016). Compared with conservative treatment, resection of hematoma or cavernous angiomas with CVM preservation did not increase the risk of poor outcomes (P= 0.646). However, CVM resection significantly increased that risk (odds ratio, 44.0; P= 0.003). Our results have shown that conservative treatment of CVMs results in a relatively good prognosis. For those complicated by hemorrhage or cavernous angiomas requiring surgical interventions, the integrity of the CVM should be preserved, irrespective of the treatment. In exceptional cases, before CVM resection, the CVM drainage should be comprehensively evaluated.

Chapter 26 - Developmental venous anomalies

Developmental venous anomalies (DVAs) are relatively common lesions, present in up to 3% of the population. The defining characteristic of these lesions is the confluence of radially oriented veins into a single dilated venous channel. DVAs are also known as cerebral venous angiomas, cerebral venous malformations, and cerebral venous medullary malformations. They are the most common type of cerebral vascular malformation found on autopsy studies, and they are often encountered as incidental findings on neuroimaging studies. DVAs are congenital lesions thought to arise from aberrations that occur during venous development, but continue to provide the normal venous drainage to the cerebral territory in which they reside. Although the natural history of DVAs is benign, they may be associated with cavernous malformations or other vascular abnormalities, which can lead to hemorrhage in the vicinity of the DVA. Surgical or endovascular obliteration of DVAs carries a significant risk of venous infarction; thus, conservative management is the treatment of choice for patients with these lesions.

New Trends in Management of Epilepsy in Patients with Cerebral Venous Malformations: Our Experience

New Trends in Management of Epilepsy in Patients with Cerebral Venous Malformations: Our Experience

Cerebral venous malformation with meningioma: A case report.

A 43-year-old female patient was admitted to The First Hospital of Jilin University (Changchun, China) on 1st October 2011 with a 10-day history of discontinuous, whole-brain headache and a 1-year history of impaired vision and memory deterioration, accompanied by right facial numbness. Clinical signs and radiological features observed using magnetic resonance imaging (MRI) led to the diagnosis of an intracranial meningioma accompanied by a cerebral venous malformation (CVM). The patient underwent neurosurgical resection of the meningioma, but required no further treatment for the CVM. At a 1-year follow-up examination, the patient continued to complain of discontinuous headache. Digital subtraction angiography (DSA) was used to reconfirm the CVM diagnosis; however, no treatment was administered due to the high risks of treatment and only mild symptoms experienced by the patient. The present case demonstrates the efficacy of DSA for detecting the presence and specific nature of CVM, and compares the value of MRI and DSA in the diagnosis of CVM. The majority of CVM patients exhibit no clinical symptoms, and the disease prognosis is typically favorable.

Cerebral Venous Malformation as a Cause of Neonatal Intra-Ventricular Haemorrhage and Unexplained Infant Subdural Haemorrhage

An Intra-ventricular Haemorrhage (IVH) is a bleeding into the brain’s ventricular system. Most intra-ventricular haemorrhages occur in the first 72 hours after birth. They originate in a layer of tissue (Germinal Matrix), under the lining of the ventricles (Ependymal), while it is in the process of manufacturing neurons and glia. This has normally regressed by term but may still be active in premature infants. Pathological investigations have found accumulations of peri-venous plasma and blood suggesting that excessive cerebral venous pressure has disrupted vessels, initiating the intra-ventricular bleeding observed. This has led to unsuccessful searches for evidence of A-V shunts within the developing cerebrum, or loss of auto regulation in arterioles, producing excessive cerebral venous hypertension. An alternative mechanism , reported here, is of venous rather than arterial origin; that high venous pressure results from inadequate venous drainage. Forcing increasing cerebral flow through inadequate venous vasculature requires increasing cerebral venous pressure. This is particularly significant at birth when the brain is suddenly stimulated to widespread activity which requires increased blood flow. This would explain why this disorder occurs shortly after birth. However, if rising cerebral pressure is insufficient to cause damage at birth, the infant may survive with a chronically high cerebral venous pressure. Then, minor stresses such as short falls, vomiting in pyloric stenosis, violent coughing, etc., may provide sufficient extra pressure to initiate haemorrhaging. In the embryo the pattern of arteries is pre-programmed, but veins climb gas gradients and their normal patterns are quite variable. Neonatal intra-ventricular haemorrhage is typically highly asymmetrical, and a typical inappropriate venous pattern is described. Recognition of inadequate venous patterns may not benefit the infant itself, but may protect any siblings from loss of home and parents.

Chapter 16 - Blue bleb rubber nevus syndrome

Vascular malformations are errors of development of vessels that occur during embryogenesis. They are rheologically divided into slow-flow (capillary, lymphatic, venous and combined) and fast-flow (arterial, arteriovenous, and combined) malformations. These congenital lesions grow proportionally with the patient and never spontaneously regress. Venous malformations (VM) are composed of ectatic venous-like channels. They are mainly sporadic but can be inherited as an autosomal pattern. Any tissue and organ can be affected. They can be isolated or part of syndromes. Blue rubber bleb naevus syndrome is characterized by multifocal rubbery cutaneous venous malformations, especially on palm and sole, that are associated with multiple gastrointestinal VM. Localized intravascular coagulopathy, with high D-dimer level and normal-to-low fibrinogen level, is commonly seen. As cerebral VM can also occur in this syndrome, brain MRI should be part of the screening of patients affected with BRBN. Management is often multidisciplinary and can include medical, interventional radiological and/or surgical treatment.

Cerebral Venous Malformation Associated with a Varix and Abnormal Signal in Surrounding Brain Parenchyma on Magnetic Resonance Imaging: A Case Report

Cerebral Venous Malformation Associated with a Varix and Abnormal Signal in Surrounding Brain Parenchyma on Magnetic Resonance Imaging: A Case Report

Corpus callosum hematoma secondary to cerebral venous malformation presenting as alien hand syndrome

A 26-year-old right-handed female presented with alien hand syndrome (AHS) secondary to corpus callosum (CC) hematoma. The patient had abnormal feelings in the left upper limb and exhibited intermanual conflict. Imaging studies demonstrated acute hemorrhage in the genu and body of the CC secondary to cerebral venous malformation. Callosal hemorrhage is usually caused by head trauma or a ruptured arteriovenous that extends beyond the CC. We report what may be the first case of AHS caused by callosal hemorrhage due to venous malformation.

A diagnosis not to miss: Pheochromocytoma during pregnancy

Sirs: Pheochromocytoma during pregnancy is a life-threatening situation for both mother and fetus. Its diagnosis is too often missed [1, 2], mainly due to three reasons. Firstly, pheochromocytoma is extremely rare with an estimated prevalence in full-term pregnancies of 1 in 54,000 [3]; secondly, it has the ability to mimic a huge number of acute, insidious clinical syndromes and the tumor has been correctly termed the “Great Masquerader” [1]; thirdly, pheochromocytoma can be asymptomatic until delivery. Classic attacks include acute hypertension, headache, sweating and tachycardia. However, patients can be completely free of manifestations between attacks. Thus, diagnosis of pheochromocytoma during pregnancy remains a great challenge, but is essential to prevent disastrous complications for both mother and fetus [2, 4]. Although a few recent reports exist in the obstetric and anesthetic literature on this condition, curiously, to our knowledge there are no reports in recent neurological literature. A 30-year previously healthy woman in the 26th week of her first pregnancy was referred from her gynecologist because of new-onset headache. Symptoms had started six weeks earlier with pain in the neck, lightheadedness, nausea and vomiting after prolonged sunbathing. While all symptoms vanished with bed rest, a stabbing neck pain persisted, which during the next two weeks evolved into a daily occipital squeezing headache of mild intensity, intermingled with periodic pulsating neck pain. Subsequently, she developed episodic frontal throbbing headaches of moderate to severe intensity, accompanied by nausea, vomiting and hyperventilation. Episodes occurred up to five times daily and lasted from a few minutes to one hour. On two occasions the patient had noted a scintillating scotoma in the left visual field. She had no history of migraine. Since proteinuria and edema were absent, preeclampsia had been ruled out by her gynecologist prior to referral. Neurological examination, including fundoscopy, was unremarkable. The patient had no fever and blood pressure was 130/85 mmHg in both arms. Routine laboratory testing revealed mild leucocytosis and trombocytosis, slightly increased C-reactive protein and liver enzymes, but normal thyroid function and blood glucose. While the initial symptoms were consistent with aseptic meningitis secondary to heat stroke and prolonged sunbathing, the subsequent complaints were neither fully compatible with migraine nor with any other primary headache syndrome. MRI of the head including MR angiography and a lumbar puncture were normal and thus, cerebral venous thrombosis, vascular malformations, vasculitis, hemorrhagic and ischemic cerebrovascular accidents, infectious or neoplastic processes, and sinusitis were ruled out. However, on day three after admission the patient was observed during a severe headache with marked tachycardia, sweating, pallor, tremor and anxiety. Blood pressure was 220/110 mmHg, pulse rate 115 beats/min. A working diagnosis of pheochromocytoma was made. Repeated 24 hour urinary catecholamine testing revealed increased levels of norepinephrine (3,200–20,000 nmol; reference interval 62–560 nmol), epinephrine (240–620 nmol; 9–101 nmol), metanephrines (32–115 μmol; 5–7 μmol), aldosterone (260–280 nmol; 11–56 nmol) and vanillylmandelic acid (85–280 μmol; < 34 μmol). MRI of the abdomen showed a 6x6 cm solid right adrenal mass (Fig. 1). The patient’s family history was unremarkable for neuroendocrine tumors. Genetic testing of the patient for mutations of RET, VHL, SDHB and SDHD genes was negative. Using a multidisciplinary approach involving endocrinologists, anesthetists, surgeons and neonatologists, it was decided to treat the patient with phenoxybenzamine (α-adrenoceptor antagonist) and await fetal maturity. Headaches vanished completely. In the 31st week of pregnancy the patient underwent an uncomplicated caesarean section combined with removal of the adrenal mass. Microscopic evaluation confirmed the diagnosis of pheochromocytoma. Pheochromocytoma is a catecholamine-producing tumor arising from the adrenal medulla in 85 % of cases and in the remaining patients from chromaffin cells in or about sympathetic ganglia in the abdomen, pelvis, and rarely in the chest or neck [1]. Tumors with a comparable biochemical and clinical profile include some chemodectomas derived from the carotid body and neuroblastomas; the LETTER TO THE EDITORS

Going High with Preexisting Neurological Conditions

This review presents the potential impact of high altitude exposure on preexisting neurological conditions in patients usually living at low altitude. The neurological conditions include permanent and transient ischemia of the brain, occlusive cerebral artery disease, cerebral venous thrombosis, intracranial hemorrhage and vascular malformations, multiple sclerosis, intracranial space-occupying lesions, dementia, extrapyramidal disorders, migraine and other headaches, and epileptic seizures. New developments in diagnostic work-up and treatment of preexisting neurological conditions are also mentioned where applicable. For each neurological disorder, the authors developed absolute and relative contraindications for a trip to high altitude. These recommendations are not based on the results of controlled randomized trials, but mainly on case reports, pathophysiological considerations, and extrapolations from the low altitude situation.

Response to Letter by Stahl and Felbor

Response: We would like to thank the authors Sonja Stahl and Ute Felbor for their very helpful comments on our article entitled “Cerebral Venous Malformations Have Distinct Genetic Origin from Cerebral Cavernous Malformations.” In this article, we presented a rare family in which 2 family members, the father and daughter, had documented cerebral cavernous malformations (CCM), and another daughter had documented cerebral venous malformations (CVM). We had hypothesized that both types of lesions may be attributed to the same genetic defect, and proceeded to sequence all 3 genes known to cause CCM: KRIT1, Malcavernin , and PDCD10 . As a result of our sequencing analysis, we determined that the father and daughter both possessed a frameshift mutation in exon 19 of the …

Cerebral Venous Malformations Have Distinct Genetic Origin From Cerebral Cavernous Malformations

Pathogenesis of cerebral venous malformation (CVM) is unknown. Because of coexistence of CVM and cerebral cavernous malformations (CCM), some studies have suggested that these 2 entities share a common origin and pathogenetic mechanism. We have identified and ascertained over 200 families with CCM. Among these, 1 unique family was found to have members affected by both disorders. We have performed mutational analysis in all 3 CCM genes, KRIT1, Malcavernin, and PDCD10, to identify the causative gene in the family. Mutational analysis revealed a frameshift mutation affecting exon 19 of the CCM1 gene (KRIT1) in members with CCM, whereas no such mutation was observed in the member with CVM. These findings support the hypothesis that CVM and CCM are 2 distinct entities with different pathogenetic mechanisms. This data further supports the hypothesis that CVM has a distinct biology and clinical behavior when compared to CCM. CVM is a benign developmental anomaly and should be managed separately from CCM.