Neurological manifestations of hereditary hemorrhagic telangiectasia (rendu-osler-weber disease): Report of 2 cases and review of the literature

Two cases of hereditary hemorrhagic telangiectasia (HHT) with neurological involvement are presented. One patient had multiple vascular malformations including telangiectasias of the brain, medulla, and spinal cord and a berry aneurysm of the internal carotid artery; she also had a large cerebellar abscess, presumably reflecting the presence of a pulmonary arteriovenous fistula. The second patient had an idiopathic subarachnoid hemorrhage. In more than 200 reported patients with HHT involving the nervous system, 61% had lesions secondary to a pulmonary arteriovenous fistula (cerebral hypoxemia, paradoxical and septic emboli, and brain abscess). The findings emphasize the need for early surgical correction of such fistulas. In 36% of the patients with neurological involvement and HHT, vascular malformations of the brain and spinal cord were documented, and in 3%, portal-systemic encephalopathy was noted. Multiple lesions were frequent. HHT should be considered a generalized vascular dysplasia (universal or systemic angiomatosis), and not simply a benign mucocutaneous disease.     

Paradoxical Brain Embolism Caused by Isolated Pulmonary Arteriovenous Fistula Successfully Treated with Recombinant Tissue Plasminogen Activator

Pulmonary arteriovenous fistula (PAVF), a vessel malformation connecting the pulmonary circulation to the systemic circulation while bypassing the pulmonary capillaries, can cause paradoxical cerebral infarction. It is often associated with hereditary hemorrhagic telangiectasia (HHT), a genetic disease characterized by multiple dermal, mucosal, and visceral telangiectasia causing recurrent bleeding. Paradoxical cerebral embolism caused by PAVF without HHT is rare. Here, we report a patient with isolated PAVF who experienced an ischemic stroke caused by a paradoxical embolism from deep venous thrombosis; the patient was successfully treated with recombinant tissue plasminogen activator. She presented with a decrease in arterial oxygen saturation to 91%, and lung disease was suspected. A PAVF was subsequently found in the right S6 region using contrast computed tomography. Interventional radiologists successfully occluded the shunt using 6 microcoils. PAVF should be considered when determining the pathogenesis of cerebral ischemia in patients with hypoxia, which can be the only symptom of PAVF.     

Spinal cord arteriovenous malformations in two patients with hereditary hemorrhagic telangiectasia

We report two cases, in first cousins, of spinal arteriovenous malformations (AVMs) of the perimedullary fistula type and hereditary hemorrhagic telangiectasia (HHT). Spinal AVMs are a rare clinical presentation of HHT, but can be the first manifestation in a child with this disorder. The importance of considering a coexisting disorder of vascular dysplasia, such as HHT, when a child presents with a spinal AVM is discussed. Received: 13 August 1998     

Brain abscess as the first clinical manifestation of multiple pulmonary arteriovenous malformations in a patient with hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease)

In this report we described a case of a cerebral abscess that developed in presence of asymptomatic pulmonary arteriovenous malformations (PAVMs) in a 53-year-old woman with hereditary hemorrhagic telangiectasia (HHT). The brain abscess was aspirated with good clinical result and the arteriovenous fistulae qualified for transcatheter embolotherapy. Each patient suspected to suffer from HHT should be diagnosed for the presence of visceral vascular malformations. Most of them are found in the lungs, liver and brain. Early diagnosis and treatment of PAVM prevent the occurrence of severe neurological complications such as brain stroke or brain abscess. Cases of a cerebral abscess in adults of unexplained etiology should raise the suspicion of an asymptomatic PAVM.     

NBCA栓塞治疗脑动静脉畸形并发症分析

目的探讨NBCA栓塞治疗脑动静脉畸形(AVM)的并发症的发生率及高危因素.方法回顾性研究469例施行NBCA栓塞治疗的脑AVM的临床和影像学资料,总结并发症的情况以及分析他们的血管构筑学特征.结果469例脑AVM共行1108次栓塞,每例栓塞1～8次,平均2.3次;共发生并发症11例(出血性并发症4例,缺血性并发症7例),其中死亡2例,植物生存l例,轻度永久性神经功能缺损1例,短暂性神经功能缺损7例.结论本组脑AVM行NBCA栓塞治疗有较低的手术相关并发症.但对于栓塞高危病人,应采取特殊的栓塞策略.     

脊髓血管畸形合并胸腔血管畸形

脊髓血管畸形的临床发病率较低,仅为颅内血管畸形或脊髓新生物的1/10左右.本病可能与其它组织的血管异常同时存在,如皮肤血管痣(Cobb综合征),皮肤、粘膜病变,和Klipple-Trenaunay-Weber综合征等.本文报告的与胸腔血管畸形同时存在的脊髓血管畸形,我们尚未见诸报道.本文还结合文献就脊髓血管畸形导致脊髓功能损害的病理生理作了阐述.     

Novalis Stereotactic Radiosurgery for Spinal Dural Arteriovenous Fistula

The spinal dural arteriovenous fistula (SDAVF) is rare, presenting with progressive, insidious symptoms, and inducing spinal cord ischemia and myelopathy, resulting in severe neurological deficits. If physicians have accurate and enough information about vascular anatomy and hemodynamics, they achieve the good results though the surgery or endovascular embolization. However, when selective spinal angiography is unsuccessful due to neurological deficits, surgery and endovascular embolization might be failed because of inadequate information. We describe a patient with a history of vasospasm during spinal angiography, who was successfully treated by spinal stereotactic radiosurgery using Novalis system.     

Malformation vasculaire cérébrale découverte dans le bilan pré-thrombolyse d’un infarctus cérébral. Impact sur la décision thérapeutique

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

脊髓血管畸形(附70例分析)

目的探讨脊髓血管畸形的临床特征、诊断及治疗方法.方法回顾性分析70例经MRI、DSA和(或)手术病理证实的脊髓血管畸形病例,其中髓内血管畸形38例,髓周动静脉瘘21例,硬脊膜动静脉瘘11例.结果单纯性栓塞治疗24例,先栓塞后手术5例,单纯手术治疗39例,保守治疗2例.随访56例,痊愈12例,好转29例,无变化11例,恶化4例.结论MRI与DSA结合是诊断脊髓血管畸形的最好手段.针对不同病变特点和影像特征,选择恰当的治疗方法是成功的关键.     

Therapy insight: stroke risk and its management in patients with sickle cell disease

Children with sickle cell disease, a chronic hemolytic anemia, present with a wide variety of neurological syndromes, including ischemic and hemorrhagic stroke, transient ischemic attacks, 'soft neurological signs', seizures, headache, coma, visual loss, altered mental status, cognitive difficulties, and covert or 'silent' infarction. Those with ischemic stroke usually have stenosis or occlusion of the distal internal carotid and proximal middle cerebral arteries. Indefinite transfusion prevents recurrence in most patients who have had a stroke, and can prevent first stroke in those with high transcranial Doppler velocities. High white cell count, low hemoglobin and oxyhemoglobin desaturation predict neurological complications. Other risk factors for overt ischemic stroke include hypertension, previous transient ischemic attack, covert infarction and chest crisis. For hemorrhagic stroke, aneurysms are common in adults but not children, who often present with hypertension after transfusion or corticosteroids. Seizures are particularly common in patients with cerebrovascular disease and covert infarction; the latter is also associated with hyposplenism and infrequent pain. Factors associated with cognitive difficulties include thrombocytosis, infarction, large-vessel disease, and perfusion abnormality on neuroimaging. As well as investigating the role of genes and the possibility that hydroxyurea or blood pressure control reduce neurological complications, we should explore the modifiable effects of poor nutrition, chronic infection, hemolysis and oxyhemoglobin desaturation on stroke risk.     

A case of spinal dural arteriovenous malformation associated with the broad lesion within spinal cord--diagnostic value of MRI with Gd-DTPA enhancement

A 70-year-old man, with slowly progressive gait disturbance, numbness in his lower limbs and dysuria, was admitted to our hospital in July, 1988. Neurological examination revealed flaccid paraparesis, hyperesthesia below the level of Th-10 combined with the disturbance of pain and temperature sensations below the level of Th-11, and neurogenic bladder. Midsagittal Tl-weighed image of MRI did not reveal any abnormal finding except for a mild enlargement of the conus medullaris. With Gadolinium (Gd)-DTPA injection, however, the spinal cord was diffusely enhanced below the level of the 9th thoracic spine. This enhancement effect was particularly remarkable at the periphery of the spinal image showing several high intensity spots in the posterior aspect of the spinal cord, which was thought to be incompatible with the spinal cord neoplasm. The angiographic examination of the selective Th-7 intercostal artery on the left showed vascular malformation lying adjacent to the 7th intervertebral foramen with markedly dilated tortuous spinal veins going upwards and downwards, which was compatible with spinal dural arteriovenous malformation (AVM). After the artificial embolization, draining veins as well the nidus of AVM had completely disappeared on angiogram. There was an improvement on his neurological findings and Gd-DTPA enhancement had been diminished on MRI. It was suggested that Gd-DTPA enhancement on MRI was due to the dilated and remarkably congestive spinal veins, and that both the elevated venous pressure and reduction of intramedullary arteriovenous pressure gradient were the cause of the development of clinical symptoms.     

Hemorragia subaracnoidea masiva durante la embolización de una malformación arterovenosa espinal de tipo iv. Complicación del tratamiento endovascular

Spinal arteriovenous malformations are rare diseases with a low prevalence and a complex diagnosis that usually requires the several neuroscience disciplines collaboration. Multidisciplinary approach requires fluid communication, favorable work environment and a correct social relationship, thus avoiding the conflict of interest appearance.We reported a 31 years old female referred to our department with progressive asymmetric spastic paraparesia for 10 months of evolution and occasional bladder dysfunction. With the diagnosis of a type IV arteriovenous malformation, a scheduled embolization was performed resulting in a massive subarachnoid hemorrhage due to the ASA laceration requiring an emergency bifrontal craniectomy. We discuss the neurosurgeońs role in complications during endovascular spinal vascular pathology treatment.     

Spinal arteriovenous shunts presenting before 2 years of age: analysis of 13 cases

Background and purpose A minority of patients with spinal arteriovenous malformations (SAVM) are symptomatic as neonates or infants. We analyzed the clinical and anatomic factors associated with this early presentation, and reviewed our experience in treating patients with these lesions.Methods A retrospective review of clinical records and imaging studies was performed for patients with SAVM who presented at less than 2 years of age and who were examined by the diagnostic and interventional neuroradiology service at our institution. Clinical, imaging and treatment data had been entered prospectively into a department database.Results Thirteen patients were identified that had SAVMs that were either diagnosed or that became symptomatic before 2 years of age (nine boys, four girls). These represented 13% of the SAVM seen during the same period of time. The mean age at presentation was 6.9±6.4 months. Of the 13 patients, 11 had neurologic symptoms attributable to the spinal lesion. The presentation was nonhemorrhagic in ten patients and associated with hemorrhage in three. Ten lesions were fistulas [spinal cord arteriovenous fistulas (SCAVFs)] (77%); two were of the nidus type of malformation. There were syndromic associations in eight patients: hereditary hemorrhagic telangectasia (HHT) in six patients, all but one of these lesions were intradural high-flow perimedullary SCAVFs (46% of overall SAVM and 56% of SCAVF), and spinal arteriovenous metameric syndrome in two patients. One patient had Hirschprung’s anomaly. Eight patients underwent endovascular treatment alone, one had surgery and embolization, and four were not treated. In all patients undergoing embolization, n-butyl cyanoacrylate liquid adhesive was used. Of those patients who underwent endovascular treatment, the lesion was completely obliterated in 7 and a 90% reduction in nidal size was achieved in the remaining 2. There was one treatment complication (infection) which resolved with medical therapy. No procedure-related permanent morbidity or mortality was seen. Follow-up data were available (mean 31.4 months) in ten patients (nine treated). All treated patients were either stable or improved, with none showing further deterioration following treatment.Conclusion Factors associated with early presentation in neonates and infants with spinal arteriovenous shunts include the presence of high-flow, solitary fistulas and HHT. Specifically, the presence of SCAVF in a child less than 2 years of age is highly suggestive of HHT. Despite the aggressive nature of these lesions, many are amenable to endovascular treatment, and this is associated with a favorable posttreatment course in most cases.     

Surgical treatment of spinal vascular malformations performed using intraoperative indocyanine green videoangiography

This study aims to evaluate the benefits of intraoperative indocyanine green (ICG) videoangiography and associated surgical outcomes of patients with spinal vascular malformations. ICG videoangiography was used during 24 surgical interventions to treat spinal vascular malformations at the Beijing Tiantan Hospital from August 2009 to May 2011. The vascular malformations were removed or the fistulae were occluded with the assistance of ICG videoangiography. The completeness of fistula clipping or nidus extirpation and each patient’s neurological status were evaluated. Among these 24 patients, there were seven with spinal dural arteriovenous fistulae, five glomus arteriovenous malformations, one juvenile arteriovenous malformation, nine perimedullary arteriovenous fistulae, and two perimedullary arteriovenous fistulae in combination with perimedullary arteriovenous malformations. Intraoperative ICG videoangiography confirmed the definite clipping of the fistulous points and complete removal of intramedullary arteriovenous malformations in all but one patient. All patients had satisfactory preservation of spinal cord blood supply and venous return. No adverse effects or complications related to ICG videoangiography occurred. Three patients were lost to follow up; 21 patients were followed clinically with a mean follow up of 7.5 months. The neurological deficits completely resolved in six patients, improved significantly in 10, remained stable in two, and were aggravated in three patients. Our experience shows that intraoperative ICG videoangiography offers useful information on the pathological and physiological vascular anatomy encountered during surgery for spinal vascular malformations.     

Ischemic spinal cord infarction in children without vertebral fracture

Spinal cord infarction in children is a rare condition that is becoming more widely recognized. There are few reports in the pediatric literature characterizing etiology, diagnosis, treatment, and prognosis. The risk factors for pediatric ischemic spinal cord infarction include obstruction of blood flow associated with cardiovascular compromise or malformation, iatrogenic or traumatic vascular injury, cerebellar herniation, thrombotic or embolic disease, infection, and vasculitis. In many children, the cause of spinal cord ischemia in the absence of vertebral fracture is unknown. Imaging diagnosis of spinal cord ischemia is often difficult, due to the small transverse area of the cord, cerebrospinal fluid artifact, and inadequate resolution of magnetic resonance imaging. Physical therapy is the most important treatment option. The prognosis is dependent on the level of spinal cord damage, early identification and reversal of ischemia, and follow-up with intensive physical therapy and medical support. In addition to summarizing the literature regarding spinal cord infarction in children without vertebral fracture, this review article adds two cases to the literature that highlight the difficulties and controversies in the management of this condition.     

Cerebral cavernous malformation: novel mutation in a Chinese family and evidence for heterogeneity

Familial cerebral cavernous malformation (CCM) is an autosomal dominant disorder producing vascular anomalies throughout the central nervous system associated with seizures and hemorrhagic stroke. Linkage analysis has shown evidence for at least three genetic loci underlying this disorder with a founder mutation in the Mexican/Hispanic community. We report the first family of Chinese ethnic origin with CCM having a novel mutation in the CCM1 gene. The mutation in exon 19 causes a premature stop codon (Q698X) predicted to produce a truncated Krev1 interaction-trapped 1 (KRIT1) protein. Members of the family with this mutation have a wide range in age of onset with seizures, ataxia, spinal cord vascular malformation, headaches and skin lesions. An additional unrelated sporadic subject with brain lesions compatible with CCM as well as vascular skin findings suggesting the blue rubber bleb nevus (BRBN) syndrome has no mutation detected in the CCM1 gene. These findings expand the phenotype of and demonstrate further evidence for the heterogeneity in the CCM syndrome.     

Neuroimaging of hereditary hemorrhagic telangiectasia

Hereditary Hemorrhagic telangiectasia is an autosomal dominant vascular disorder with high penetrance and variable expressivity. Most cases are caused by mutations in the endoglin gene on chromosome 9 (HHT type 1) or the activin receptor-like kinase 1 gene on chromosome 12 (HHT type 2). HHT is characterized by mucocutaneous telangiectases and visceral arteriovenous malformations (AVMs). Neurological complications occur in 8 to 10% of the patients. Brain ischemia or abscess are often associated with pulmonary arteriovenous fistula. Cerebral or spinal arteriovenous malformations are frequent but have a lower risk of haemorrhage than sporadic AVMs and routine screening should not be practiced in adult patients. Routine screening should be discussed for children with a familial history of cerebral haemorrhage and/or HHT type 1.     

Arteriovenous malformation of the spinal cord in the neonate

A newborn baby boy with a high-flow arteriovenous malformation (AVM) of the dorsal spinal cord is reported. The baby was born paraplegic. The myelogram suggested an increased vasculature, showing irregular worm-like radiolucent lesions of the dorsal spinal cord. Spinal angiography showed a huge arteriovenous angioma of the dorsal spinal cord with an intra-spinal aneurysmal sac. The vascular supply was decreased after two embolizations. This was followed by complete surgical resection of the aneurysmal sac.     

Cerebral ischemia in Rendu-Osler-Weber disease

Neurologic manifestations occur in 8-12% of the patients with Rendu-Osler-Weber disease or hereditary hemorrhagic telangiectasia (HHT), principally infectious and hemorrhagic and, less frequently, ischemic ones. More than a half of these neurologic complications are associated with pulmonary arterio-venous malformations (PAVM). The diagnosis of HHT is based on the presence of telangiectases, hemorrhagic events and a family history with an autosomal dominant pattern. We report a case of a patient diagnosed as having HHT with transient ischemic attacks and a PAVM, which was occluded by the use of embolotherapy. Cerebral ischemia in HHT is related to the existence of a PAVM and results from three mechanisms: 1) secondary poliglobulia and hyperviscosity because of the hypoxemia due to a right-left shunt; 2) communication between the airway and the pulmonary circulation during cough access, which produces gas embolism and hemoptysis; 3) and, finally, paradoxical embolism trough the PAVM, the same mechanism proposed to the infectious neurologic manifestations of the disease. When the diagnosis of HHT is suspected, early search and treatment of PAVM, with embolotherapy or surgery, are necessary in order to avoid respiratory problems (hemoptysis, exertional dyspnea, cianosis, clubbing) and neurologic complications.     

Spinal cord infarction in meningitis: polygenic risk factors

We report a male with spinal cord infarction and tetraplegia after Streptococcus pneumoniae meningitis. He was subsequently found to have both a Chiari I malformation and factor V Leiden mutation. A literature search was conducted to identify previously reported cases of pediatric spinal cord infarction associated with acute bacterial meningitis, anatomic brain anomalies, and hypercoagulability disorders. This article is the first report of spinal cord infarction in a child with hypercoagulability disorder and structural brain anomaly in the setting of acute bacterial meningitis. The confluence of infection, inflammation, localized pressure, and predisposition to hypercoagulability produced unique conditions resulting in infarction of the cervical spine. This report emphasizes the polygenic nature of the expression of spinal cord infarction.