Familial cerebral cavernous angiomas

Three families with two or more members affected by cavernous angiomas of the brain are described and the other 17 reported in the literature are reviewed. The familial occurrence of cerebral cavernous angiomas has been considered a rare event; nevertheless, the experience of the authors (positive familiarity in three patients where two or more relatives have been explored radiologically) suggests that cavernous angiomas of the brain might be, at least in most cases, a familial disease. Therefore, when a patient with cerebral cavernous angioma is observed, a careful familial history and the exploration of the familial members by computerized tomography or better still by magnetic resonance must be performed. The high frequency of multiple lesions in familial cases, the surgical indications and the role of the ultrasonic prenatal diagnosis are also discussed.     

Familial cerebral,hepatic, and retinal cavernous angiomas: a new syndrome

New, non-invasive neuroradiological techniques [computed tomography (CT) and magnetic resonance (MR)] have led to reassessment of the incidence of cavernous angioma of the brain (CCA), which is sometimes multiple and associated with cavernomas in other organs. CCA is known to be familial, with dominant autosomal transmission. This paper concerns a family with multiple CCA, sometimes in association with liver angiomas, in ten members belonging to four different generations. These malformations can vary in clinical expression: no neurological symptoms have been detected in subjects from the first or second generations, but they were found in adult age in subjects from the third generation; two fourth-generation patients came under our observation at 2.5 years of age. Symptoms include partial epileptic fits, which sometimes become generalized later and which are generally controlled adequately by therapy. Patients also present paresthesia and occasional motor deficiencies corresponding to CCA bleeding episodes; these symptoms have always abated with medical treatment alone. None of the patients are mentally retarded or restricted in their daily lives. Neuroradiological investigations (CT, MR, angiography) reveal typical multiple brain lesions in all patients. Given the first-generation patient's clinical history of symptomatic hepatomegaly and the postmortem finding of multiple liver and brain cavernomas, liver ultrasonography was performed on all members of the family. Liver angioma was detected in two subjects from the second and third generations. Retinal angioma was detected in one patient with quadrantanopsia. (a) This association of brain, liver and retinal angiomas had not been reported in the past; (b) the significant radiological findings contrast sharply with the relatively benign clinical picture; and (c) expression of the disease varies in consecutive generations, with an increasingly early onset. The authors emphasize the need for neuroradiological studies using CT and MR, liver ultrasonography, ophthalmologic evaluation, and genetic evaluation for CCA patients and their relations.     

Familial cerebral cavernous malformation

Cavernous malformations (CMs) occur in approximately 0.5% of the general population and represent 5-10% of the central nervous system vascular malformations. The majority of CMs appear sporadically but genetically determined familial forms account for 10% to 15% of all cases. The aim of this study was to discuss the clinical, pathological and genetic aspects of familial cerebral cavernous malformations (CCMs). We report on five members of a family who underwent surgery due to CCMs. However, only two members were treated in our Department. The age of onset of symptoms in these cases (4 men and 1 women) ranged from 3 to 28 years. Three members of the family were asymptomatic but it turned out that they were obligatory gene carriers and in one of them the cavernous malformation was confirmed by neuroimaging study. The clinical symptoms of CCMs included seizure (three patients) and focal neurological deficit (two patients). Multiple CCMs were identified in two symptomatic patients (two lesions) and in one asymptomatic patient (three lesions). The lesions were located superficially (4), in the basal ganglia (1), in the brainstem (2) and in the cerebellar vermis (1). In two patients, the subsequent imaging studies showed a single de novo CCM formation. Only one patient with mutation of CCM2 gene was treated surgically. In patients with cavernous malformations the detailed clinical and family history of neurological events ought to be collected. This is particular important in patients with multiple changes or with de novo CCMs formation, identified in subsequent imaging studies. A well-documented family history can help to establish the final diagnosis and makes it possible to offer all members of the family proper neurological and genetic care.     

The surgical management of cerebral cavernous angiomas

Abstract

Caver~ou: angioma (CA) is a h.amartomatous hemorrhagic lesion which has received a great deal of atention In recent years due to Improvement of neuroimaging with magnetic resonance and heightened clInIcal awareness. Long consIdered to be rare, its actual prevalence is now recognized to be of 0.9%. Cavernous angiomas may be multiple, particularly in patients with familial form. It may be associated with a variety of clinical syndromes attributed to focal microhemorrhages or less frequently to gross bleeding. CA are usually dIagnosed between the age of 20 and 50 with a highest clinical. incidence in the fourth decade. A female predominance is observed in regard to bleeding. The male patients are more at risk for seizures. The recent series ofMR ima~ing confirm that CA even when multiple can be asymptomatic in a significant number of cases. Surgery IS the treatment of choice in order to eliminate the risk of hemorrhage and improve the control of seizures. Minimally invasive approaches are now adopted with reduced postopertive .morbldlty. We report our expenence in surgical management of cerebral CA and suggest a clasSIfication of the lesIons accordIng to surgical accessibility and residual morbidity. [Neural Res 1998 20: 597–606]     

Familial cavernous angiomas of the brain in an Hispanic family

We found cavernous angiomas (CA) in 10 of 22 members of a large Hispanic family. The proband had seizures, and a CA was found at surgery. He and two sisters with seizures had normal angiograms, but CT or MRI showed lesions compatible with CA. Similar abnormalities were found in two cousins with seizures and 5 of 17 asymptomatic relatives studied. MRI proved to be more sensitive than CT for identifying CA. Hispanic families appear to have a predisposition for dominantly inherited CA of the brain.     

Metabolic correlates of epileptic spikes in cerebral cavernous angiomas

BACKGROUND: Cerebral cavernous angiomas (CCA) are frequently associated with focal intractable epilepsy. Epileptogenicity is usually attributed to hemosiderin deposits. Combined recording of electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) is a new method to investigate epileptic discharges. METHODS: We used EEG-fMRI to identify BOLD responses to interictal spikes in patients with CCA. Responses were analyzed in the lesional and perilesional area, and at distance. RESULTS: Eight patients were scanned, all with temporal lobe epilepsy and spikes. One patient had bilateral spikes, analyzed separately, and three studies with less than two spikes were excluded. All six studies analyzed showed BOLD responses. No response was found in the lesion itself or immediate periphery, and the raw fMRI signal showed signal loss in lesional and perilesional areas in all patients. Responses were close to the perilesional area in 2/6 studies. All patients showed responses at a distance from the lesions. CONCLUSIONS: Despite susceptibility artifacts caused by iron deposits, we demonstrated EEG-fMRI responses involving the perilesional areas in 33% of studies. We also demonstrated diffuse rather than focal responses, in accordance with previous studies in lesional and non-lesional temporal lobe epilepsy, confirming the frequent distant effect of epileptic spikes.     

脑内海绵状血管瘤的MRI和CT诊断

目的分析脑内海绵状血管瘤的CT和MRI影像学特点。方法回顾性分析68例CT和MRI表现,并比较CT和MRI优缺点。结果海绵状血管瘤位于幕上55例,幕下脑干4例,小脑9例。68例病灶有出血54例,钙化17例。MRI检查。T1加权像病灶显示为短T1高信号,周边为轻度低信号影;T2加权像病灶中央呈高、低混杂信号影,周边为极低黑色信号环。增强有轻度强化或无强化。CT平扫为斑片状不规则形高密度区。增强后有轻度强化或无强化。结论应用MRI诊断脑内海绵状血管瘤,其敏感性高,特异性强。对脑内海绵状血管瘤的显示MRI明显优于CT。     

Intracerebral cavernous angiomas

We studied 31 patients with histologically verified intracerebral cavernous angiomas. Twenty-two patients were symptomatic; nine were asymptomatic. All 22 symptomatic patients had seizures, three had intracranial hemorrhage, and one had signs of a space-occupying lesion. Twenty-seven lesions were located in the neocortex, three in the brainstem, and one in the cerebellum; all exhibited characteristic gross and microscopic features of cavernous angiomas. CT identified the location and extent of the lesion in 16 of 27 cases. Six of seven lesions demonstrated contrast enhancement, and ten of 27 scans harbored densities consistent with intracerebral calcium. Angiography was performed in 17 cases and was completely normal in eight. MRI revealed mixed signal intensity centrally with a ring of decreased signal intensity peripherally on T2-weighted images and was diagnostic in five cases. Surgical treatment offers an excellent prognosis for seizure control in patients with such lesions.     

脑内海绵状血管瘤的临床特点与微侵袭手术治疗

目的 总结脑内海绵状血管瘤（CA）的临床特点及手术治疗经验.方法 回顾性分析21例脑内型CA的临床资料和手术方法.首发症状为癫（癎）者16例,偏瘫或偏身感觉障碍者4例,无症状1例.采用神经导航辅助显微手术,其中4例同时做了颞叶部分切除,10例切除了胶质疤痕和含铁血黄素沉积带,2例在皮层脑电图监测下切除病灶和癫（癎）灶,余5例以含铁血黄素沉积带为界面切除病灶.结果 病灶均全切.21例患者随访0.5～4年恢复良好或无变化.结论 脑内型CA应积极手术治疗.合理采用微侵袭神经外科技术并遵循个体化原则有利于提高手术疗效.     

脑内海绵状血管瘤的CT及MRI诊断

目的探讨CT及MRI对脑内海绵状血管瘤(cavernous angiomas,CA)的表现和诊断价值。方法收集资料完整经手术病理证实的36例脑内CA患者的CT及MRI资料,重点分析其影像表现特征。结果 CA可位于脑内任何部位,单发病灶多见,周围无或轻度水肿,无占位效应,CT平扫为稍高密度影,钙化占68.7%,增强扫描大都无强化;MRI表现为桑椹状混杂高信号,周围有云絮状低信号环,增强后病灶大都无强化。结论脑内海绵状血管瘤的MRI表现有特异性,MRI对脑实质内CA的检出率优于CT,特别是MRI的T2WI像有助于明确诊断。     

Management of cerebral cavernous angiomas in children presenting with seizures

Until recently intracranial cavernous angiomas were thought to be rare vascular malformations that usually presented in adulthood as an intracerebral hemorrhage, an expanding mass lesion, or with the new onset of seizures. Prior to the advent of computed tomography (CT), and more recently magnetic resonance imaging (MRI), their diagnosis in childhood was extremely rare. However, the CT and MRI features of cavernous angioma are quite distinctive and allow early diagnosis and treatment. Advances in surgical techniques permit successful removal of these potentially devastating lesions and amelioration of the associated seizure disorder. Seven children with cerebral cavernous angiomas have been treated at the Children's Hospital Medical Center since 1980. Six children presented with seizures and one with an intracerebral hemorrhage. All had characteristic findings on CT and/or MRI and underwent surgical excision of symptomatic lesions. Intraoperative sonography, electrocorticography, and cortical mapping were used when indicated and were found to be helpful in the surgical management of these patients. Our experience suggests that symptomatic cerebral cavernous angiomas in children are not as rare as previously thought and that surgical treatment using modern neurosurgical techniques is both safe and appropriate and can be helpful in the management of associated seizures.     

Genetics of cavernous angiomas

Cerebral cavernous malformations (CCM) are vascular malformations that can occur as a sporadic or a familial autosomal dominant disorder. Clinical and cerebral MRI data on large series of patients with a genetic form of the disease are now available. In addition, three CCM genes have been identified: CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10. These recent developments in clinical and molecular genetics have given us useful information about clinical care and genetic counselling and have broadened our understanding of the mechanisms of this disorder.     

Intracerebral radiation-induced cavernous angiomas

We present four cases of cerebral cavernous angioma that developed after radiatherapy for brain tumor in three cases and for cavernous angioma in one case. The time interval between irradiation and the detection of the cavernous angioma varied from three to nine years and the doses from 24 to 60 Grays. Brain hemorrhage appeared in two cases. Explanation for the formation of cavernous malformations is unclear but is probably related to proliferation and dilatation of the vascular endothelium with formation of capillary telangiectasis with evolution to cavernous angiomas. The pediatric brain appears particularly vulnerable to radiation injury. The risk of hemorrhage appears higher than with spontaneous cavernous malformations.     

幕上脑内海绵状血管瘤与癫痫(46例报告)

目的探讨幕上脑内海绵状血管瘤所致癫痫的临床特点及治疗方法。方法1998—2003年在北京天坛医院顺序入院的72例幕上脑内海绵状血管瘤患者中，46例伴有癫痫发作。详细记录和分析癫痫发作的临床类型和特点，同时给予手术和药物治疗。并对治疗效果进行随访。结果46例患者行显微手术治疗，其中40例术前均给予抗癫痫药物治疗。药物治疗后27例发作次数减少，13例病情无改善。手术治疗后，癫痫均得到良好控制。结论幕上脑内海绵状血管瘤伴发癫痫单纯通过药物控制效果不佳，而显微外科手术效果良好。     

Stereotactic-guided surgery for cavernous angiomas

Intracerebral cavernous angiomas may cause hemorrhage, epileptic seizures and neurological deficits. The diagnosis of these lesions became easier with the advent of the magnetic resonance image (MRI). Radical resection is the treatment of choice. Due to frequent subcortical or deep location, image-guided techniques, such as stereotactic-guided surgery, offer many advantages as smaller skin incision and craniotomy, less brain manipulation with consequently lower morbidity. We present a series of nine cavernous angiomas treated by stereotactic-guided radical surgical resection. The diagnosis was done by MRI and confirmed by pathologic studies in all cases. Mean age of patients was 30 years old (range 20-54 years). Postoperative morbidity occurred in two cases: one patient had a convulsion on the third postoperative day and the other presented dysphasia and hemiparesis on the second postoperative day, both with total recovery. Total resection of the lesion was possible in all cases with no neurological deficit.     

颅内海绵状血管瘤的显微手术治疗

海绵状血管瘤 (cavernous angiomas, CA),约占隐匿性血管畸形的20%[1].由于其"隐匿性"的特点,使得临床诊断、治疗较为困难.本文报道了1999年6月至2004年6月间,同济医院经手术及病理证实、资料完整的颅内CA患者21例,介绍其临床特点及处理方法.     

脊髓海绵状血管瘤的外科治疗

脊髓海绵状血管瘤是一种少见的脊髓髓内血管畸形,常致严重的脊髓损害.本文总结四年来作者治疗此病12例的经验.病人多为青壮年,肢体瘫痪和二便失禁为其主要症状.病变为一团浆果样薄壁血管窦,出血后血块上皮化使病变体积增大,多发生于脊髓胸段,病程可为急性发病型、双峰型和慢性进行型.反复小量出血和脊髓微循环失调是脊髓受损的主要机理.MRI为确诊的唯一手段.手术完全切除病变是最主要的治疗方法.