Cavernous malformations are low-flow vascular malformations that are histologically characterized by the lack of mural elements of mature vascular structures and intervening parenchymal neural tissue. They are often clinically quiescent, and may grow, bleed, and regress, but can also manifest clinically as neurologic deficits or seizures in the setting of an acute hemorrhage. The low-flow nature of cavernous malformations renders them inherently occult on cerebral angiography. Magnetic resonance imaging has become the mainstay imaging modality in evaluating cavernous malformations, producing characteristic imaging features that usually provide a straightforward diagnosis. Features on magnetic resonance imaging include a reticulated pattern of mixed hyper- and hypointensity on T1- and T2-weighted imaging, with a characteristic hypointense rim best appreciated on T2-weighted imaging or gradient-echo sequences. Contrast enhancement is useful for revealing coexisting developmental venous anomalies that are frequently associated with sporadic cavernous malformations, and may further support the diagnosis. Susceptibility-weighted imaging is highly sensitive for cavernous malformations and accompanying developmental venous anomalies, and is superior to gradient-echo sequences in screening for multifocal, familial cavernous malformations.

Cavernous sinus hemangioma (CSH) is a rare extra-axial vascular neoplasm that accounts for 2% to 3% of all cavernous sinus tumors. Their location, propensity for profuse bleeding during surgery, and relationship to complex neurovascular structures are factors which present difficulty in excising these lesions. The authors describe their experience of 22 patients with CSH over 14 years at a tertiary care center. Patients were managed with microsurgical resection using a purely extradural transcavernous approach (13 patients) and with Gamma Knife radiosurgery (GKRS; Elekta AB, Stockholm, Sweden) (nine patients). Retrospective data analysis found headache and visual impairment were the most common presenting complaints, followed by facial hypesthesia and diplopia. All but one patient had complete tumor excision in the surgical series. Transient ophthalmoparesis (complete resolution in 6-8 weeks) was the most common surgical complication. In the GKRS group, marked tumor shrinkage (>50% tumor volume reduction) was achieved in two patients, slight shrinkage in five and no change in two patients, with symptom improvement in the majority of patients. To our knowledge, we describe one of the largest series of CSH managed at a single center. Although microsurgical resection using an extradural transcavernous approach is considered the treatment of choice in CSH and allows complete excision with minimal mortality and long-term morbidity, GKRS is an additional tool for treating residual symptomatic lesions or in patients with associated comorbidities making surgical resection unsuitable.

Cavernous hemangioma (CH) is a benign vascular malformation. Intracranial CH is generally localized as an intracranial-intraaxial and responsible for 5-13% of all intracranial vascular malformations. Intracranial-extraaxial CHs are rare rather than intracranial-intraaxial CHs. Clinical findings, imaging characteristics, and surgical approach of extraaxial CHs are rather different than intraaxial CHs. Diagnosing cavernous sinus CH preoperatively is very important, but its radiological differential diagnosis is quite difficult. In this study, we present magnetic resonance imaging findings of a 48-year-old male who was considered preoperatively to have meningioma but was diagnosed with cavernous sinus CH during surgery by pathological examination.

Molecular imaging comprises a range of techniques, spanning not only several imaging modalities but also many disease states and organ sites. While advances in new technology platforms have enabled a deeper understanding of the cellular and molecular basis of malignancy, reliable non-invasive imaging metrics remain an important tool for both diagnostics and patient management. Furthermore, the non- invasive nature of molecular imaging can overcome shortcomings associated with traditional biological approaches and provide valuable information relevant to patient care. Integration of information from multiple imaging techniques has the potential to provide a more comprehensive understanding of specific tumor characteristics, tumor status, and treatment response.

The development of novel angiogenesis-directed therapeutics is hampered by the lack of non-invasive imaging metrics capable of assessing treatment response. We report the development and validation of a novel molecular imaging paradigm to rapidly assess response to angiogenesis-directed therapeutics in preclinical animal models.

A monoclonal antibody-based optical imaging probe targeting vascular endothelial growth factor receptor-2 (VEGFR2) expression was synthesized and evaluated in vitro and in vivo via multispectral fluorescence imaging.

The optical imaging agent demonstrated specificity for the target receptor in cultured endothelial cells and in vivo. The agent exhibited significant accumulation within 4T1 xenograft tumors. Mice bearing 4T1 xenografts and treated with sunitinib exhibited both tumor growth arrest and decreased accumulation of NIR800-alphaVEGFR2ab compared to untreated cohorts (p = 0.0021).

Molecular imaging of VEGFR2 expression is a promising non-invasive biomarker for assessing angiogenesis and evaluating the efficacy of angiogenesis-directed therapies.

This article reviews the pathology, clinical course and management of cavernous angiomas in the brain stem and spinal cord. Both lesions have been diagnosed with increasing frequency as a result of magnetic resonance image scanning. Brain stem lesions tend to present dramatically; their treatment remains microsurgical excision despite some studies that have looked at the use of radiosurgery. Spinal lesions are either extra-, or more commonly, intramedullary. Intramedullary cavernomas present with a wide spectrum of symptoms ranging from acute haematomyelia to presentations that mimic demylelinating conditions; extramedullary cavernous angiomas tend to produce radicular symptoms or subarachnoid haemorrhage. Both are treated by microsurgical excision.

Cavernous sinus hemangiomas (CSHs) are uncommon lesions and comprise fewer than 1% of all parasellar masses. Because of their location, propensity for profuse bleeding during surgery, and relationship to complex neurovascular structures, they are notoriously difficult to excise.

The authors describe their experience with seven cases of CSHs. Headache and visual impairment were the most common presenting complaints, followed by facial hypesthesia and diplopia. Computed tomographic scans revealed iso- to hyperdense expansile lesions in the region of the cavernous sinus and middle cranial fossa. Magnetic resonance imaging scans revealed hypo- to isointense lesions on T1-weighted images and markedly hyperintense lesions on T2-weighted images, with marked homogeneous enhancement after contrast administration.

All CSHs were treated by a purely extradural transcavernous approach. This involved reduction of sphenoid ridge, exposure of the superior orbital fissure, drilling of the anterior clinoid process, coagulation and division of the middle meningeal artery, and peeling of the meningeal layer of the lateral wall of the cavernous sinus from the inner membranous layer. The cranial nerves in the lateral wall of the cavernous sinus were exposed (Cranial Nerves III and IV, as well as V1, V2, and V3). The tumor was accessed through its maximum bulge through either the lateral or anterolateral triangle. The tumor was removed via rapid decompression, coagulation of the feeder from the meningohypophyseal trunk, and dissection along the cranial nerves. All but one patient had complete tumor excision. Transient ophthalmoparesis (complete resolution in 6-8 wk) was the most common surgical complication.

To our knowledge, we describe one of the largest series of pure extradural transcavernous approaches to CSHs. CSHs are uncommon but challenging cranial base lesions. The extradural transcavernous approach allows complete excision with minimal mortality or long-term morbidity.

The clinical, radiological, and surgical issues concerning cavernous hemangiomas located within the dural confines of the cavernous sinus were analyzed on the basis of experience with 13 cases. The feasibility of radical resection by an entirely extradural approach using a basal temporal surgical route to this relatively rare and formidable surgical problem was investigated. Thirteen patients, four males and nine females, with cavernous hemangioma involving the cavernous sinus were treated from 1992 to 2001. The patients were aged from 15 to 55 years. Headaches and deficits of the cranial nerves coursing through the cavernous sinus were the principal symptoms at presentation. Vision was affected in four patients. The radiological features in all patients were similar with a characteristic pattern of extension and encasement of internal carotid artery. The maximum size of the tumor was 28 to 73 mm (mean 44 mm). An entirely extradural route using the basal temporal approach was used successfully in seven cases. Total resection was achieved in 12 patients and partial resection was achieved in one patient. The follow up ranged from 8 months to 9 years (mean 45 months). The outcome of extraocular movements was poor in our series, possibly due to the massive sizes of the tumors encountered. There was no recurrence or growth of the residual tumor and all patients were leading active lives.

We examined newly developed three-dimensional angiography to understand the anatomy for surgery and for intravascular surgery in order to decide when treatment should be stopped. The subjects were 23 patients chosen randomly (angiography, 22). The diagnoses in these patients included aneurysm (5), arteriovenous malformation (6), meningioma, glioma, vascular tumours of the brain and the neck (5), and vascular diseases (6) including carotid artery stenosis, Moya-Moya disease, middle cerebral artery occlusion, and megadolico-ectasia (6). The new technique was used for intravascular surgery in six cases, which allowed the neck of the aneurysm and the bifurcation to be revealed. This method is useful for determining whether another coil should be inserted. In patients with basilar top aneurysm using this technique during coil embolization the intra-aneurysmal blood flow disappeared because complete embolization was performed. This technique was more useful during coil embolization, especially to decide the timing of withdrawal in intravascular surgery compared with conventional DSA.

Of 168 patients operated on consecutively for a supratentorial cavernous malformation, 77 had seizures as the initial symptom. The effectiveness of surgery in controlling seizures and the risk of surgery were evaluated by retrospective review of the patients' charts. The follow-up period was 1 to 9 years (mean 39 months) and the review period totalled 284 lesion-years. Only two patients showed postoperative deterioration in neurological status (morbidity risk: 2.6%), no patient died (mortality: 0%). Sixty-eight (88.3%) patients were seizure-free after operation and five (6.5%) showed a marked reduction in the frequency of their seizures. This corresponds to an overall positive effect of surgery of 94.8% of the patients. There was no substantial evidence that excision of the haemosiderin-stained tissue around the cavernoma along with the lesion itself provided better results than resection of only the cavernoma. Better results with regard to seizure control, however, were associated with shorter duration of symptoms before surgery.

Intracranial cavernous malformations are vascular anomalies consisting of endothelium-lined caverns filled with blood at various stages of thrombosis and organization and separated by a collagenous stroma devoid of mature vessel wall elements. They occur in an estimated 0.45 to 0.9% of the population, with male and female patients equally affected and all ages represented. They commonly manifest as seizures, gross intracranial hemorrhage, and focal neurological deficits. Lesions are frequently multiple in the same patient, and 10 to 30% are associated with familial clustering. Several reports have documented a dynamic clinical-radiological lesion behavior with de novo lesion genesis, intralesional and perilesional hemorrhage, and corresponding fluctuations in lesion size. Hemorrhagic risk and neurological disability seem to be related to multiple factors, including lesion location, age, gender, state of reproductive cycle, and previous hemorrhage. Lesions may behave aggressively with repetitive hemorrhages and cumulative disability or may remain quiescent for many years. Management strategies include expectant follow-up in patients with asymptomatic or inaccessible lesions, excision of symptomatic and accessible lesions, and radiosurgery of progressively symptomatic lesions in inoperable locations. Relevant disease-specific outcome parameters are proposed to guide clinical decisions and future research. Prospective, stratified, hypothesis-driven studies using rigorous epidemiological methods must be undertaken to delineate patient and lesion factors influencing clinical aggressiveness. Biological studies are essential to uncover strategies to predict and modify lesion behavior.

Ten cases of symptomatic cavernous malformations affecting the spine and spinal cord were retrospectively reviewed. The cases display a spectrum of pathological findings involving the vertebral body, vertebral body with epidural extension, epidural space without bony involvement, intradural extramedullary space, and intramedullary lesions. Lesions at all locations are identical histologically, electron microscopically, and immunohistochemically. This perspective, in which cavernous malformations are envisioned as a single entity arising at numerous locations, runs contrary to the view found in the neurosurgical literature. In most discussions of cavernous malformations, vertebral body lesions are depicted as separate entities from intradural lesions. Cavernous malformations, also called cavernous hemangiomas, are developmental vascular hamartomas that, by definition, do not grow by mitotic activity. Yet, the expansion of these lesions is well documented both in the literature and among our cases. The therapeutic modalities used in our series included observation, embolization, radiation, and surgical resection alone or in combination. All modalities are effective but must be tailored to the specific needs and condition of the patient. The embryology, methods of treatment, and proposed mechanisms of growth, plus similarities and differences between cavernous malformations at each location, are reviewed. Analogies between spinal and intracranial lesions are presented. On the basis of this series and a review of the literature, we conclude that cavernous malformations represent a single entity regardless of location. Segregation based on location, as is prevalent throughout the neurosurgical literature, hinders an overall understanding of these lesions. Cavernous malformations are more appropriately viewed as a single pathological entity arising in a multitude of locations. The difficulties encountered when managing cavernous malformations at various locations are unique to the location and not the lesion.

We report 14 cases of intracranial cavernous angioma, analyzing the clinical features, with special reference to the risk of bleeding, radiological images and treatment in these and in 153 published cases, 167 in all. Cerebral hemorrhage occurred in 44%: typical (intraparenchymal or subarachnoid) in 24.6%, and masked by epilepsy, headache or neurological deficits in 19.2%. In patients with the typical hemorrhagic pattern posthemorrhagic mortality was 12.2%. Of the patients who had a hemorrhage 42.5% were left with more or less disabling neurological deficits, and 16.4% had a rebleed. In discussing treatment we consider four groups of intracranial cavernous angioma: A) symptomatic in a zone of low surgical risk; B) asymptomatic with low surgical risk; C) symptomatic with high surgical risk; D) asymptomatic with high surgical risk. The treatment is surgical, except in the high risk asymptomatic variety, best followed initially with sequential CT scan and MRI and then considered for surgery if the lesion becomes symptomatic, increases in size or presents neuroradiological signs of bleeding.

A surgical series of 19 patients under the age of 18 years with pathologically verified cavernous angioma is presented. Most lesions were located in the cerebral hemispheres, but four were in the pons or midbrain, two in the diencephalon, and one in the spinal cord. Fourteen patients presented with an acute or progressing neurological deficit, three with seizures, one infant with irritability, and one with headache alone. Five patients had family histories of vascular malformations of the central nervous system, and five had multiple lesions. Surgery for small or deep lesions was aided considerably by intraoperative ultrasonographic or stereotactic localization techniques. Pathological examination of the resected malformations revealed a complex histology containing not only typical closely approximated cavernous vessels, but also areas of marked proliferation of granulation tissue and partially re-endothelialized hemorrhage, suggesting a mechanism for the apparent growth of certain cavernous angiomas. The postoperative results were good, with only one patient suffering a permanent worsening of neurological status after surgery. Incomplete resection was initially carried out in five patients, two of whom rebled within 1 year after operation. Long-term follow-up findings in these patients have emphasized the unusual history of certain of these malformations.

Cavernomas are vascular malformations composed of a compact mass of sinusoidal-type vessels that are immediately contiguous with one another and have no intervening parenchyma. Cavernous malformations were previously held to be a rare pathology occurring predominantly in adults. New neuroradiological techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) demonstrate, on the contrary, that these lesions are also more frequent during childhood than was previously thought. In our institution we observed 17 cases of cavernous malformations in patients aged between 18 months and 16 years, 16 of whom were diagnosed after 1982. In 4 of these cases there was a documented familial history; in 2 multiple malformations were present. The most common site was the subcortical frontal region, but in 1 case the malformation was located in the pineal region. The most frequent (in 12 cases) initial symptom was hemorrhage, with the characteristics of an intracerebral hematoma. In 4 cases the initial symptom consisted of epileptic fits and 2 of these patients subsequently suffered hemorrhage. In one case the symptoms observed were those of an expansile process. All our patients underwent cerebral angiography and only in 1 case did this show a vascular abnormality. CT, performed in 16 patients, gave positive results in all cases. MRI, performed in 12 patients, gave highly significant images in all cases. Radical surgical removal of the malformation was performed in 15 of the 17 patients, and the results can be considered excellent in the majority of cases. Cavernous malformations are, therefore, more frequent lesions than had previously been thought, especially in pediatric patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Radiological findings of surgically verified cavernous hemangiomas of the cavernous sinus are presented with special reference to the appearance in magnetic resonance imaging. Differences in radiological features of the cavernous sinus cavernous hemangiomas and intracerebral cavernous hemangiomas are discussed.

A large pituitary fossa cavernous haemangioma in a 48-year-old male is presented. The rarity of this lesion is stressed. The relevant literature is reviewed.

Twelve patients with slow flow brain stem vascular malformations had magnetic resonance scans performed on a 1.5 Tesla scanner using T1 (TR = 400-800 ms, TE = 25 ms) and T2 (TR = 2000 ms, TE = 20, 25, 80 ms) weighted scans. Eight patients (70%) had solitary brainstem vascular malformations while 4 (30%) had multiple lesions both supra and infratentorially. Five patients had venous angiomas demonstrated by angiography and MR. There were 26 lesions seen on MR of which only 14 were identified by CT. These lesions demonstrated a specific MR image pattern indicative of subacute or chronic parenchymal hematoma. It was characterized by an iso to hyperintense central signal surrounded by a well defined thin band of low signal intensity. The central zone could appear to be single or multilocular. In multilocular lesions the hemorrhages within different cells could be of different ages. One patient did not have findings of a chronic hematoma but exhibited only low signal secondary to calcification and a venous angioma. None of these lesions had surrounding edema. Despite the variable etiologies of slow flow vascular malformations of the brainstem, their MRI manifestations seem to indicate a final common pathway of chronic hematoma. These lesions are quite distinct from MS or tumor, the usual clinical considerations in the differential diagnosis.

Our experiences with cerebrovascular malformations in Japanese patients have been reviewed, presenting 29 cases of venous malformation, 30 cases of cavernous angiomas and one case of capillary telangiectasis. We also present the data from the 763 cases of AVM obtained in the cooperative studies which were supported by the Ministry of Health and Welfare of Japan, and discussed the epidemiological and clinicopathological aspects in relation to those reported in the literature. The cooperative studies on these subjects were primarily done in conjunction with the investigation of Moya-Moya disease which is by far frequently found in Japan. Regarding the vascular malformations of the C.N.S., there seem to be no noticeable differences in the epidemiological aspects as seen in Japan and in other countries. It should be stressed also from our experiences that all kinds of vascular malformation, either intracranial or intraspinal, bleed probably more often than we expect. Neurosurgeons should pay more careful attention to these vascular malformations with appropriate concepts of the disease.

The authors review 30 documented cases of intracranial and orbital cavernous angiomas treated at their institution between 1965 and 1984. The diagnosis was based on computerized tomography (CT) or surgery; three patients were treated in the pre-CT era (1965 to 1976) and 27 since the advent of CT. The number of cases diagnosed preoperatively markedly increased after the introduction of CT, and 22 cases were verified histopathologically at surgery. Six cases were in children (aged 2 months to 17 years) and 24 in adults (aged 19 to 73 years). There was no significant sex difference (male:female ratio was 14:16). Nineteen lesions were intraparenchymal, five were intraventricular, three were in the middle fossa, two were intraorbital, and one originated from the tentorium. Symptoms varied according to the site of the lesion; hemorrhage occurred in 11 cases. Calcifications were seen on CT scans in all cases, but on plain skull films in only two. Angiography revealed hypovascular masses in all cases excluding those with lesions in the middle fossa; in two cases, tumor stain could be detected only with prolonged-injection angiography. Radionuclide brain scanning showed a dense hot area in eight of 19 patients. Recent experience has shown that magnetic resonance imaging clarified anatomic relationships that were obscure on CT. The overall outcome was favorable except for one patient who died in the postoperative period. The clinical results in this series are summarized and some diagnostic and therapeutic problems are discussed.

A case is reported of an infant with a giant cerebellar vermis hemangioma which was totally removed. The excised specimen contained both cavernous angioma-like and telangiectasia-like portions with intervening cerebellar tissue. The tumor was considered to be a mixture of cavernous hemangioma and telangiectasia.

We present a case of a 15-month-old infant with intracranial cavernous angioma in the right frontal lobe in which the cerebral angiogram revealed transmedullary collecting veins characteristic of venous angioma around the lesion. This vascular malformation was histologically confirmed to be a cavernous angioma.

Computed tomography and angiographical findings of cavernous haemangiomas of the brain are reported on the basis of six cases of the authors, and a review of the literature. Computed tomography showed well demarcated, round densities with tiny calcifications, and mild contrast enhancement (0-25 HU), with no mass effect and with open sulci round the lesion. The angiographical findings were normal except in one patient with an early draining vein and in another with a late draining vein; consequently an injection of at least 10 to 15 ml of contrast medium, and a prolonged angiographical series are recommended. According to the literature, capillary blush may also be seen in angiography. If both CT and angiography are used the diagnosis is definitive, and a neoplasm can be excluded. In five of our patients the diagnosis was verified surgically and histologically, while the sixth patient was not operated on because the frontoparietal lesion was near the motor region. In most cases, surgical removal is easy and successful.

A cavernous hemangioma in the pineal region of a 22-year-old man is reported. Because the patient had diabetes insipidus and a contrast-medium-enhanced mass in his pineal region on computed tomography, a germinoma was suspected. A ventricular shunt was made and the tumor was irradiated, but without a response. After irradiation the tumor was entirely removed, and postoperatively the diabetes insipidus improved.

A case of intraventricular cavernous hemangioma in a neonate is reported. In over 200 previously reported cases of intracranial cavernous hemangioma, 11 histologically verified cases have been collected and analyzed. The present case is the second occurring in a neonate.

In a kindred of 122 individuals we found 5 individuals with cerebral vascular malformation, 3 representing typical cavernous angiomas. The condition was inherited as an autosomal dominant trait with variable expressivity. Forty-three relatives were examined prospectively by cranial computed tomography (CCT) and lesions were found in 15; 7 were followed prospectively with CCT scans for 5 years. Angiography in 5 of these cases failed to demonstrate the lesion. In 3 patients with previously normal CCT scans a change in blood volume or membrane permeability allowed visualization of the lesion on contrast scans. In 2 individuals, both parents of affected children, a normal CCT scan was found. This emphasizes the limitations of CCT in detecting this disorder. Biochemical and red blood cell immunological genetic linkage studies were done in 36 persons. No linkage was found with any of the markers. The natural history of this disorder, characterized by marked clinical and radiographic variation in site of lesion, and the timing and severity of intracranial hemorrhage, make it a useful model for investigating contributing factors and consequences of intracranial hemorrhage in general. For at-risk and affected patients early and sequential CCTs are necessary. Familial cavernous angioma should be included in the differential diagnosis of all young persons presenting with cerebrovascular impairment, seizures, intracranial calcifications or hemorrhage.

Cerebral angiomas consisting of two distinct types of malformations are rare. A case of combined arteriovenous and cavernous angioma is reported. For what is believed to be the first time, the cavernous portion of the angioma was clearly demonstrated by angiography and appeared similar to cavernous malformations occurring outside the central nervous system. This case emphasizes the continuous overlapping spectrum of cerebral vasculature anomalies.

The radiological manifestations of 16 pituitary adenomas, six meningiomas and 14 craniopharyngiomas were reviewed. The differential diagnosis of these tumors is possible with a few exceptions when skull radiography, CT, angiography and metrizamide cisternography are carefully evaluated. Prolonged injection angiography (PIA) is particularly important for demonstrating the contours of pituitary adenomas and meningiomas. Metrizamide cisternography is indicated when the tumor contours are obscure using PIA, or when the differential diagnosis is uncertain.

The radiological manifestations of primary intracranial sarcomas may be non-specific and they vary widely according to their histological variations. Reticulum cell sarcomas, however, can be included in the differential diagnosis with a high degree of reliability when one observes a hypovascular mass with arterial encasement and deep medullary veins. Tumor vessels and tumor stains supplied by dilated feeding arteries suggest the possibility of a sarcoma of the brain or of the meninges in infants. Nine reticulum cell sarcomas, four undifferentiated sarcomas, and one fibrosarcoma are presented here with their radiological manifestations, especially on angiography.