Cerebral cavernous malformations

Cavernomas are well circumscribed lesions formed by sinusoidal vascular channels. They tend to slowly expand in size and carry a 0.7% to 1. % annual risk of hemorrhage. Only 10% to 30% of intracranial cavernomas are located in the posterior fossa. When located in the brainstem they can cause recurrent hemorrhages and devastating neurological deficits. The authors report a series of cavernomas located in the brainstem and present a review on their epidemiology, pathogenesis, natural history, and methods of diagnosis and treatment. Although the surgical treatment of brainstem cavernomas can be associated with a significant risk, surgical resection is recommended of the lesions that have hemorrhaged or grown producing progressive deficits. The authors' experience on the surgical treatment of cavernous hemangiomas of the brainstem, indicating important aspects of intra-operative surgical techniques, is presented, including a clinical and anatomical correlation of different surgical approaches to brainstem cavernomas. [Neurol Res 2002; 24: 61-72]

Keywords: Brainstem; cavernomas; cavernous malformations; radiosurgery; surgical resection

INTRODUCTION

The term angiographically occult or cryptic vascular malformation represents a heterogeneous group of vascular malformations that are not visualized by cerebral1 angiography2-6. Russel and Rubinstein have classified the vascular malformations of the central nervous system into four categories that include arteriovenous malformations, telangiectasias, venous angioma, and cavernous malformations or cavernomas7. Cavernomas represent approximately 5%-13% of all vascular malformations.1,8 When these lesions are located in the brainstem, they carry significant risk of producing severe incapacitating neurological deficits. Traditionally, most neurosurgeons have avoided the surgical treatment of brainstem cavernomas because of the relatively high pre-operative morbidity rate, and these lesions used to be treated conservatively However, in the last few years several neurosurgeons have achieved encouraging surgical results after the surgical resection of brainstem cavernomas, and have recommended the resection of symptomatic lesion10-13 The present study presents the authors' experience on the surgical treatment of cavernous hemangiomas of the brainstem, providing a detailed revision of the clinical, radiological, biological, and surgical aspects, pointing up important aspects of intra-operative surgical techniques.

METHODS

A medline search in the English, French, and Spanish literature performed for the years 1966 to December 2000, and review of bibliographic citations for additional cases prior to 1966 was implemented. A consecutive series of patients who underwent a surgical approach for hemorrhage producing progressive neurological deficits was evaluated. The analysis included clinical and radiological features, as well as the choice of surgical approach and outcome (Table 1). Finally, a correlation of the surgical approaches with anatomical dissections was performed.

RESULTS

At Wayne State University, over a period of four years the authors have surgically resected eight brainstem cavernomas that presented with hemorrhage and progressive neurological deficits. Table 1 shows the demographic characteristics, presentation, surgical approach, and results. All patients were young, and presented with altered mental status and progressive focal neurological deficits. The most common location was the pons. The surgical approach depended on the location of the lesion. A subtemporal approach was employed to approach the lateral lesion of the mesencephalum, a posterior transpetrosal approach or a presigmoid retrolaberintic approach was used to approach lesions located at the pons, a far lateral approach was used to approach a lesion in the lateral medulla, while a suboccipital craniectomy was used to approach a lesion located in the posterior medulla (Table 1). Post-operatively, most patients presented transient cranial nerve deficits.

DISCUSSION

Epidemiology of cavernous malformations

Traditionally, cavernomas were thought to be extremely rare lesions, but relatively recent studies have demonstrated that cavernomas are more common than was previously believed. In a retrospective study of 6,686 autopsies, Berry et al.14 reported a prevalence of cavernous malformations of 0.02%. In a similar prospective study of 4,069 autopsies, McCormic and Boulter15 found a higher prevalence of cavernomas of 0.4%. In a revision of 24,535 autopsies Often et al.16 reported a prevalence of 0.53%.

The introduction of magnetic resonance imaging (MRI) has facilitated the diagnosis of cavernomas. In a retrospective analysis of 14,035 patients, Robinson et al. 17 found 76 lesions with the characteristic aspect of cavernomas, and reported an incidence of 0.47%. In a similar study of 8,131 MRI scans, Del Curling et al.18 calculated a prevalence of 0.39%. This information correlates well with the statistics previously reported in autopsy studies.

Some familiar, genetic, sexual, and racial factors may play a role in the natural behavior of cavernomas. The existence of a syndrome of familial cavernomatosis with an autosome-dominant inheritance pattern has been suspected since the beginning of the century19-21 Numerous genetic and imaging studies have confirmed that this familial syndrome possesses a higher prevalence of multiple cavernomas than the general population1,5,21-23. Recently, a genetic defect in the chromosome 7 has been linked with the syndrome of familial cavernomatosis24. Intra-cerebral cavernomas present with a similar frequency in both sexes, but extracerebral cavernomas seemed to be more frequent in oriental female patients25. Familiar occurrence and multiplicity are more common in descendants of Hispanic26--28 than in Caucasians and Asians.

Localization

Cavernomas can occur anywhere in the central nervous system, cranial nerves and peripheral nerves 29-33. Although most intracranial cavernomas (64%-84%) are supratentorial11, infratentorial cavernomas are more often life threatening34,35. Approximately 10%-30% of intracranial cavernomas are located in the posterior fossa. When these vascular lesions are located in the brainstem they frequently present with recurrent hemorrhages (in up to 79%) causing severe cumulative neurological deficit17,36,37. The pons is the most commonly affected site, followed by the cerebellum, the midbrain and the medulla, in decreasing order of frequency17,21,37,38.

Cavernomas can present in a solitary form or as multiple lesions. In the syndrome of familial cavernomatosis lesion multiplicity has been reported in 50%73% of the cases, compared with multiple lesions present in less than 33% of sporadic cases19,21,22,38-41.

Cavernous malformations have also been found in association with other types of vascular lesions, including capillary telangiectasias, venous malformations, and true arteriovenous malformations42-47. The coexistence of cavernomas with another type of vascular lesion has been reported in approximately 8%-36% of cases. The most common mixed lesion is the combination of a cavernoma with a venous malformation. In these mixed lesions the cavernoma component is responsible for producing the neurological symptoms or hemorrhage37,44.

Pathologic features

Cavernomas are circumscribed, lobulated and well defined lesions, of reddish to purple color, with a similar aspect to a cluster of mulberries. They lack the features of afferent arterial feeders or draining arteriolized veins, typical of arteriovenous malformations.

Microscopically, cavernomas are formed by a series of sinusoidal channels lined by a single layer of endothelium, separated by a collagenous stoma devoid of elastin, smooth muscle, or any other mature vascular elements. Characteristically there is lack of intervening nervous tissue parenchyma between the vascular channels4,7,15,17.

The surrounding cerebral tissue typically demonstrates evidence of previous microhemorrhages with hemosiderin discoloration, gliosis, and hemosiderinfilled macrophages. Areas of hyalinization, thrombosis, cysts, calcification, and cholesteral crystals are frequent.

Clinical presentation

Although most cavernomas are clinically silent and asymptomatic, they can hemorrhage or produce neurological symptoms. They present more commonly in young people between the second and fourth decade of life. Contrary to supratentorial cavernomas that often present with seizures or headaches (due to intra- or perilesional hemorrhage)48,49, while posterior fossa cavernomas frequently present with hemorrhage and progressive neurological deficits50. Brainstem cavernomas can produce focal signs such as cranial nerve deficits or can produce unspecific symptoms including vertigo, gait disturbances, nausea and vomiting13,17,51,52. Patients with cerebellar hemorrhages frequently present with headaches, nausea, vomiting, ataxia, vertigo and nystagmus. Patients with hemorrhages in the brainstem typically present with diplopia, hemiparesis or hemisensorial loss, and alterations of the level of conscienc53-55.

The first hemorrhage is relatively self-limited and most patients recover clinically. However, patients who present with recurrent hemorrhages suffer a progressive nuerological deterioration11. Many patients with hemorrhages in the brainstem present with periods of exacerbation and remission, simulating the clinical presentation of demyelinating diseases11. In patients with cavernomas the inital hemorrhage increases the risk of subsequent hemorrhages1,36,38,56-59.

Diagnostic imaging

The inability to angiographically detect cavernous malformations, telangiectasias, and small, thrombosed arteriovenous malformations, led to the grouping of these lesions under the term angiographically occult vascular malformations. Cerebral angiography is normal in the great majority of the patients with cavernomas1-3,6,58,60,61. Occasionally, cerebral angiography may demonstrate an avascular mass or minimal vascular abnormalities such as a small early or late drainage vein, a capillary blush, or evidence of neovascularity5,6,38,60. When a cavernous malformation is associated with a venous malformation, the venous angioma is angiographically identifiable by its characteristic caput medusae pattern of abnormal venous drainage, whereas the cavernoma component of the lesion is angiographically occult.

Computed tomography may show a nodular circumscribed lesion, of uniform or heterogeneous density, that reflects the juxtaposition of calcifications, hemorrhages and cystic components that comprise these lesions62. Although the computed tomography is very sensitive for the detection of supratentorial cavernomas, it is not very spec ific63. Computed tomography allows one to visualize areas of calcification or hemorrhages, but does not delineate an underlying lesion or differentiate the lesion type. In the evaluation of the brainstem lesions, artifacts caused by the skull base obscures the observation field.

MRI scan is currently the method of choice for the detection of cavernomas, since it allows the identification, analysis, and follow-up of incidental lesions, providing an indication of the biological behavior of the lesion, such as expansion, hemorrhage and thrombos64-67. The typical imaging appearance of cavernomas consists of a well-defined lobulated lesion with a central area of mixed intensity, surrounded by a ring of low intensity. The central area represents the combination of the vascular channels with areas of subacute hemorrhage on different states of thrombus organization and calcifications66. Recurrent perilesionar microhemorrhages explain the typical circumferential deposition of hemosiderin that characterizes these lesions. The differential diagnosis of cavernomas includes thrombosed arteriovenous malformations, mixed vascular lesions, infectious, inflammatory and neoplastic processes67,68.

Natural history of cavernomas

Recent reports demonstrated that cavernomas are dynamic lesions. Several clinical series that included serial MRI scans have demonstrated that these lesions change in size and signal characteristics, as well as the emergence of new cavernomas over time 69. A sequence of changes includes internal (intralesional) microhemorrhages, thrombosis of vascular channels, calcification, cystic formation, and involution of caverns. The spontaneous thrombosis of capillary channels produces blood stasis, resulting in expansion of the lesion and light increase of pressure inside the caverns which may result in hemorrhage inside the cavernoma (intralesional hemorrhage). This intralesional hemorrhage and expansion of the cavernoma can produce a perilesional hemorrhage into the surrounding brain.

Some investigators have documented that cavernomas respond to hormonal changes and manifest an aggressive behavior during pregnancy. In a series of patients with cavernomas that presented with hemorrhage, 84% of patients were females, and a third of them were in their first trimester of pregnancy 36,70,71. Another study of 2,000 MRIs corroborated that 75% of patients with cavernomas presenting with neurological deficits were females, two thirds of whom were pregnant72.

Risk of hemorrhage

The risk of hemorrhage from cavernous malformations is not known with precision. Numerous autopsy studies, evaluation of surgical specimens, and imaging methods of diagnosis have documented the occurrence of subclinical intralesional hemorrhages inside the malformation. Almost all cases present evidence of previous microhemorrhages. Overt cerebral hemorrhages are less frequent, but have a more important clinical significance. The occurrence of overt hemorrhage does not appear to be related to the size or location of the cavernoma73. Clinical studies have estimated an overall incidence of cerebral hemorrhage of 8%-37% of patients with cavernomas. The risk of hemorrhage appears to be age related; there is evidence to suggest that the risk of hemorrhage is higher in pediatric patients and young adu In general, considering all ages, the annual risk of hemorrhage for cavernomas has been estimated17,26,74 to be 0.7%-1.1 %. Most hemorrhages occur in the tissue surrounding the cavernoma, but patients can present with subarachnoid or intraventricular hemorrhage.

In patients with mixed lesions harboring a combination of cavernomas with venous angiomas, the hemorrhage is invariably caused by the cavernoma and not by the venous malformation44.

Cavernomas that have produced hemorrahe posses an increased risk of producing further hemorrhages. The incidence of recurrent hemorrhages has been reported1,38,75-79 to vary between 30% and 80%. In a series of patients treated conservatively after a first hemorrhage, in a third of the patients a second hemorrhage was observed within one year. In another study79 of cavernomas treated conservatively, 75% of the patients presented with a second hemorrhage within 26 months. Based on the existing evidence from the literature these authors recommend the surgical resection of the cavernomas that have caused hemorrhage.

Treatment of the cavernomas of brainstem

Asymptomatic patients with single or multiple incidental lesions present a minimal annual risk of producing a first hemorrhage11. The literature does not support the aggressive surgical treatment of these purely incidental lesions. In these incidental cases, a clinical follow-up with serial MRIs seems reasonable. On the other hand, patients that present with hemorrhage in the brainstem or progressive neurological deficits due to growing lesions, should undergo a surgical resection of the lesion

In patients with multiple cavernomas clinical and imaging follow-ups with serial MRIs are recommended, with the surgical resection of the lesions that grow, produce neurological symptoms, or hemorrhages.

Radiosurgery and cavernous malformations

Radiosurgery has been established as an effective alternative option for the treatment of small arteriovenous malformations in eloquent areas or deep regions of the brain 4,82. However, cavernomas exhibit a poor clinical response to the standard doses used for radiosurgery and present a high incidence of complications83. In a series of 16 patients (including three patients with mixed lesions cavernomas-venous angioma), no radiological improvement was seen in 80% of the patients, 37.4% developed radiation-induced lesions, one patient experienced a recurrent hemorrhage, and 12.5% of the patients had persistent neurological defic its84. Coffey and Lunsford85 reported a series of 36 patients with cavernomas of the brain stem treated with a Gamma knife (with a follow-up of at least two years in 24 patients). Only three patients improved, 27 continued stable, three patients deteriorated temporarily, two patients had permanent deterioration, and one patient died. Two patients presented recurrent hemorrhage within 18 months of the treatment.

As an alternative method of treatment, some groups have suggested the use of heavy particles (protons or helium ions) for the treatment of the cavernomas. In a series of 57 patients with occult vascular malformations treated with radiosurgery using helium ions86, 32% of the patients experienced symptomatic hemorrhage after radiosurgery, with a calculated annual risk of hemorrhage of 9.4%86. In a series of 10 patients who underwent surgical resection after treatment with radiosurgery, all the patients presented incomplete thrombosis as determined intra-operatively and histologically87.

The treatment of cavernomas by radiosurgery has been related to a significant percentage of complications. Chang et al.86 reported that 7% of their patients developed symptomatic radiation-induced cerebral edema, and 2% experienced radiation necrosis. AminHanhani et al.88 reported an incidence of 16% of permanent neurological deficits and a 3% mortality rate, which could be attributed to radiographically-confirmed radiation-induced complications. Kondziolka89 documented a 26% complication rate in patients with cavernous malformations after treatment with Gamma knife radiosurgery.

In conclusion, the value of radiosurgery for the treatment of patients with cavernous malformations has not been well documented. A prospective, multicenter, randomized trial with long-term rigorous clinical and MRI monitoring will be necessary to define the potential benefit of radiosurgery in these patients.

Brief surgical vascular anatomy of the brainstem

We have previously described the subarachnoid cisterns and corresponding vascular and neural structures90,91. The vertebral arteries enter the posterior cranial fossa through the lateral aspect of the foramen magnum, penetrate the dura lateral to the cervicomedullary junction, and join the opposite vertebral artery to form the basilar artery at the level of or above the anterior surface of the pontomedullary junction. Intracranial branches from the vertebral arteries include the posterior meningeal artery, direct perforating bulbar arteries to the medulla, the anterior spinal artery, the posterior inferior cerebellar artery (PICA), small basal meningeal arteries, and occasionally, the posterior spinal artery92,93. The site of origin of the PICA varies in location from below the foramen magnum to the vertebrobasilar junction. The basilar artery courses vertically along the anterior aspect of the brainstem, bifurcating within the interpenduncular fossa to form the two posterior cerebral arteries 94. This area contains numerous perforating vessels95. The basilar artery is typically curved with a concavity towards either the right or the left side. The artery frequently presents elongation and does not always lie in close proximity to the brainstem surface. During its course, the basilar artery gives rise to numerous perforating median and paramedian pontine arteries, internal auditory arteries, the anterior inferior cerebellar artery, and the superior cerebellar arteries94-99.

The anterior medial pontomesencephalic vein and the median anterior medullary veins course vertically, in a parallel fashion in close proximity to the basilar artery. The lateral medial pontomesencephalic vein, and the lateral anterior medullary veins course vertically on the anterolateral surface of the brainstem100. The vein of the pontomedullary sulcus runs transversely at the junction of the pons and medulla while the vein of the pontomescencephalic sulcus runs transversely at the junction of the pons and mesencephalum. In addiiton, small transverse pontine and transverse medullary veins course horizontally across the pons and medullar respectively. During surgery of the brainstem, it is important to identify and preserve bulbar, pontine, and mesencephalic perforating branches.

Surgical considerations for the surgical approach of brainstem cavernomas

Direct surgery to the brainstem is considered one of the most difficult operations because of the high density of important neural structures such as nuclei and neural tracts. Hence high morbidity and mortality have been reported even with biopsy in this area. However, several clinical series have reported good clinical results following the resection of brainstem cavernomas located in the pial or ventricular surface 35,74,101. Lesion accessibility is an important determinant of the surgical risk11. Zimmerman et al.59 reported a series of 24 patients, 16 of whom were operated upon, and recommended nonsurgical treatment for neurologically stable patients with deep cavernomas of the brainstem that do not contact the pial surface. When such lesions produced recurrent hemorrhages or progressive neurological deficits they recommended a surgical resection.

In a series of patients with cavernomas of the brainstem presenting with neurological symptoms and treated conservatively, Simrad et al.102 reported progression of symptoms or fatalities in 70% of the cases. The literature13,35,79,103 reports an overall general risk of mortality between 0% and 20% for cavernomas of the brainstem, with transitory neurological worsening in 20%-40% of patients, and permanent deficits in less than 20%. Some authors9,104-106 have recommended the use of electrophysiological monitoring and mapping of brainstem motor nuclei during the resection of brainstem cavernomas. However, there is some controversy and variability regarding which modality should be used, and when.

The election of the surgical approach depends on the localization of the lesion. We recommend a pterional trans-sylvian or a subtemporal approach for lesions located in the interpeduncular cistern, anterolateral surface of the midbrain or pontomesencephalic junction. However, more inferior lesions located in the anterolateral surface of the pons are difficult to reach with these approaches. The use of skull base approaches such as a posterior transpetrosal approach, presigmoidretrolaberintic, transigmoid, or a combination of these approaches assists in reaching the anterolateral surface of the pons. The authors prefer to place the patient in a supine position, with a roll under the shoulder, and the head rotated toward the opposed side to the lesion. Different degrees of aggressiveness are suited according to the size and characteristics of each particular patient.

The authors recommend an infratentorial supracerebellar approach for lesions located in the pineal region, dorsal surface of the midbrain, superior medullary velum, and superior cerebellar peduncles. Although this approach can be performed in a prone, semi-sitting, or three-quarter prone position, we prefer the latter.

A standard suboccipital craniotomy allows the resection of lesions located in the cerebellar vermis or hemispheres, floor of the fourth ventricle, and dorsal surface of the medulla and pons. We prefer to perform this approach in a prone position, and open the foramen magnum. Gentle retraction of the cerebellar tonsils allows exposure of the vermis and we prefer to dissect the plane between the vermis and cerebellar hemisphere rather than splitting the vermis.

A far lateral approach allows the approach of lesions of the anterolateral surface of the medulla. A variable degree of aggressiveness can be used, ranging from a simple exposure or skeletonization of the sigmoid sinus and jugular bulb, to a partial resection of the occipital condile and mobilization of the vertebral artery. These more complex measures are seldom necessary, and a more limited approach allows the total resection in most cases.

The authors have noted that during the exposure, most cavernomas are visible on the pial surface or produce a region of discoloration in the surface of the brainstem, caused by hemosiderin residuals resulting from previous hemorrhages. In cases with superficial lesions visible from the surface, the cavernomas can be resected directly. However, in patients with deep lesions that are not visible in the surface of the brainstem, the use of a frameless image-guided approach facilitates the localization of smaller deep-seated lesions minimizing the neurological damage. As an alternative to the use of image-guided technology, a careful pre-operative analysis of the MRI allows the identification of a surgical corridor based on neuroanatomical structures, such as the root entry zone of a cranial nerve. We have observed that most cavernomas are surrounded by a cavity containing degradation products from prior hemorrhage. Once the lesion has been located, a circumferential dissection from the plane of gliosis that surrounds the cavernoma is performed under the microscope using high magnification, with a fine bipolar forceps under low voltage107, in order to limit heat propagation to surrounding vital structures. The result is a devascularization of the cavernoma. Very small lesions can be resected in a single piece whereas larger lesions should be removed in a piecemeal fashion rather than attempting to deliver the intact malformation through a small opening. Finally, the remaining portions of the capsule are dissected from the surface of the brainstem and nerves. All perforating arterial vessels must be meticulously dissected and preserved. It is important to perform a complete resection of the lesion since recurrences are frequent following a partial resection, with regrowing of the cavernoma and the risk of recurrent hemorrhages and neurological deficits10,12,59.

When the combination of a cavernoma with a venous malformation is found, a complete resection of the cavernoma leaving the venous malformation intact should be attempted, since interruption of a venous malformation can threaten venous drainage from normal parenchyma and result in a venous infarction.

CONCLUSION

Brainstem cavernomas can cause recurrent hemorrhages and significant neurological deficits. Although the surgical treatment of brainstem cavernomas presents a high risk of serious complications, the authors recommend the surgical resection of the lesions that have hemorrhaged or grown producing progressive deficits when the overall medical condition of the patient allows it. An appropriate surgical approach should be based on the localization of the lesion. Prospective multicenter trials are necessary to determine the precise role of radiosurgery in the treatment of brainstem cavernomas.

REFERENCES

1 Giombini S, Morello G. Cavernous angiomas of the brain. Account of fourteen personal cases and review of the literature. Acta Neurochir (Wien) 1978; 40: 61-82

2 Tomlinson FH, Houser OW, Scheithauer BW, Sundt TM Jr, Okazaki H. Angiographically occult vascular malformations: A correlative study of features on magnetic resonance imaging and histological examination. Neurosurgery 1994; 34: 792-799

3 Voigt K, Yasargil MG. Cerebral cavernous haemangiomas or cavernomas. Incidence, pathology, localization, diagnosis, clinical features and treatment. Review of the literature and report of an unusual case. Neurochirurgia (Stung) 1976; 19: 59-68

4 Wilkins RH. Natural history of intracranial vascular malformations: A review. Neurosurgery 1985; 16: 421-430

5 Rigamonti D, Drayer BP, Johnson PC, Hoening-Rigamonti K, Knight JT, Spetzler R. Cerebral cavernous malformations. N Engl J Med 1988; 319: 343-347

6 Rapacki TF, Brantley Mj, Furlow TW Jr, Geyer CA, Toro VE, George ED. Heterogeneity of cerebral cavernous hemangiomas diagnosed by MR imaging. J Comut Assist Tomogr 1990; 14: 18-25

7 Russel D, Rubinstein L. Tumors and hematomas of the blood vessels. In: Russel D, Rubinstein L, eds. The Pathology of Tumors of the Nervous System, London: Edward Arnold, 1977: pp. 126-145

8 Lonjon M, Roche JL, George B, Mourier KL, Paquis P, Lot G, Grellier P. Intracranial cavernoma. 30 cases. Presse Med 1993; 22:990-994

9 Chang SD, Lopez JR, Steimberg GK. The usefulness of electrophysiological monitoring during resection of central nervous system vascular malformations. J Stroke Cerebrovasc Dis 1999; 8: 412-422

10 Steinberg GK, Chang SD, Gewirtz RJ, Lopez JR. Microsurgical resection of brainstem, thalamic, and basal ganglia angiographically occult vascular malformations. Neurosurgery 2000; 46: 260-271

11 Maraire JN, Awad IA. Intracranial cavernous malformations: Lesion behavior and management strategies. Neurosurgery 1995; 37: 591-605

12 Bertalanffy H, Gilsbach JM, Eggert HR, Seeger W. Microsurgery of deep-seated cavernous angiomas: Report of 26 cases. Acta Neurochir (Wien) 1991; 108: 91-99

13 Symon L, Jackowski A, Bills D. Surgical treatment of pontomedullary cavernomas. Br Neurosurg 1991; 5: 339-347

14 Berry R, Alpers B, White J. The site, structure, and frequency of intracranial aneurysms, angiomas, and arteriovenous abnormalities. In: Milikan C, ed. Research Publications: Association for Research in Nervous and Mental Disease, Baltimore: Williams & Wilkins, 1966: pp. 4-72

15 McCormick WF, Boulter TR. Vascular malformations ('angiomas') of the dura mater. J Neurosurg 1966; 25: 309-311

16 Otten P, Pizzolato GP, Rilliet B, Berney J. 131 cases of cavernous angioma (cavernomas) of the CNS, discovered by retrospective analysis of 24,535 autopsies. Neurochirurgie 1989; 35: 128-131

17 Robinson JR, Awad IA, Little JR. The natural history of the cavernous angiomas. J Neurosurg 1991; 75: 709-714

18 Del Curling 0, Kelly DL, Elster AD, Craven TE. An analysis of the natural history of cavernous angiomas. J Neurosurg 1991; 75: 702-708

19 Bicknell JM. Familial cavernous angioma of the brain stem dominantly inherited in Hispanics. Neurosurgery 1989; 24: 102-105

20 Bicknell JM, Carlow TJ, Kornfeld CT. Familial cavernous angiomas. Arch Neurol 1978; 35: 746-749

21 Hsu F, Rigamonti D, Huhn SL. Epidemiology of cavernous malformations. In: Awad IA, Barrow DL, eds. Epidemiology of Cavernous Malformations, Park Ridge, IL: AANS, 1993: 13-23

22 Dobyns WB, Michels VV, Groover RV, Mokri R. Familial cavernous malformations of the central nervous system and retina. Ann Neurol 1987; 21: 578-583

23 Gil-Nagel A, Wilcox KJ, Stewart JM, Anderson VE, Leppik El, Rich SS. Familial cerebral cavernous angioma: Clinical analysis of a family and phenotypic classification. Epilepsy Res 1995; 21: 27-36

24 Gunel M, Awad IA, Anson j, Lifton RP. Mapping of a gene causing familiar cavernous malformation to 7q".2q.- . Proc Natl Acad Sci USA 2000; 96: 6620-6624

25 McCormick PC, Michelson Wi. Management of intracranial cavernous and venous malformations. In: Barrow DL, ed. Intracranial Vascular Malformations, Park Ridge, IL: AANS, 1990: pp. 197-217

26 Zambramski JM, Wascher TM, Spetzler RF, Johnson B, Golfinos J, Drayer BP. The natural history of familiar cavernous malformations: Results of an ongoing study. ) Neurosurg 1994; 80: 422-432

27 Mason 1, Aase JM, Orison WW, Wics JD, Seigel RS, Bicknell JM. Familiar cavernous angiomas of the brain in an Hispanic family. Neurology 1988; 38: 324-326

28 Gunel M, Awad IA, Finberg K, Anson JA, Steinberg GK, Batjer HH, Kopitnik TA, Morrison L, Giannotta SL, Nelson-Williams C, Lifton RP. A founder mutation as a cause of cerebral cavernous malformation in Hispanic Americans. N Engl J Med 1996; 334: 946-951

29 Acciarri N, Padovani R, Giulioni M, Gaist G, Acciarri R. Intracranial and orbital cavernous angiomas: A review of 74 surgical cases. Br] Neurosurg 1993; 7: 529-539

30 Ryvlin P, Mauguiere F, Sindou M, Froment JC, Cinotti L. Interictal cerebral metabolism and epilepsy in cavernous angiomas. Brain 1995; 118: 677-687

31 Raveau P. Symptomatic trigeminal neuralgia caused by venous angioma of the posterior fossa. Ann Radiol (Paris) 1992; 35: 85-88

32 Basauri L. Cavernomas (cavernous angiomas). Report of two cases. Neurocirugia 1965; 23: 77-78

33 Di Rocco C, lannelli A, Tamburrini G. Cavernomas of the central nervous system in children. A report of 22 cases. Acta Neurochir (Wien) 1996; 138: 1267-1274

34 Fahlbusch R, Strauss C, Huk W. Pontine-mesencephalic cavernomas: Indications for surgery and operative results. Acta Neurochir Suppl (Wien) 1991; 53: 37-41

35 Fahlbusch R, Strauss C. Surgical significance of cavernous hemangioma of the brain stem. Zentralb Neurochir 1991; 52: 25-32

36 Abe H. Clinical presentation of vascular malformations in the brainstem: Comparison of angiographically positive and negative types. J Neurol Neurosurg Psychiatry 1989; 52: 167-175

37 Requena I, Arias M, Lopez-lbor L, Pereiro I, Barba A, Alonso A, Monton E. Cavernomas of the central nervous system: Clinical and neuroimaging manifestations in 47 patients. I Neurol Neurosurg Psychiatry 1991; 54: 590-594

38 Lobato RD, Perez C. Clinical, radiological, and pathological spectrum of angiographically occult intracranial vascular malformations. Analysis of 21 cases and review of the literature. I Neurosurg 1988; 68: 518-531

39 Gangemi M, Maiuri F, Donati P, Cinalli G, Di Caro M, Sigoma L. Familial cerebral cavernous angioma. Neurol Res 1990; 12: 131-136

40 Mori K, Handa H, Gi H, Mori K. Cavernomas in the middle fossa. Surg Neurol 1980; 14: 21-31

41 Duong H, del Carpio-O'Donovan R, Pike B, Ethier R. Multiple intracerebral cavernous angiomas. Can Assoc Radiol J 1991; 42: 329-334

42 Chaix Y, Grouteau E, Sevely A, Boetto S, Carriere JP. Association of venous angioma and cavernoma of the posterior fossa. Arch Pediatr 1996; 3: 685-688

42 Abdulrauf SI, Kaynar MY, Awad IA. A comparison of the clinical profile of cavernous malformations with and without associated venous malformations. Neurosurgery 1999; 44: 41-46

44 Awad IA, Robinson JR Jr, Mohanty M. Mixed vascular malformations of the brain: Clinical and pathogenetic considerations. Neurosurgery 1993; 33: 179-188

45 Fukui M, Matsushima T, Ikezaki K, Natori Y, Inamura T, Ohara S, Kawamura T. Surgery of angiomas in the brainstem with a stress on the presence of telangiectasia. Neurol Med Chir (Tokyo) 1998; 38 (Suppl.): 250-254

46 Hirsh LF. Combined cavernous-arteriovenous malformation. Surg Neurol 1981; 16: 135-139

47 Steno J, Bizik I, Lampert M. Concurrent cavernous and venous cerebral an iomas. Bratisl Lek Lists 1999; 100: 317-320

48 Casazza M, Broggi G, Franzini 'A, Avanzini G, Spreafico R, Bracchi M, Valentini MC. Supratentorial cavernous angiomas and epileptic seizures: Preoperative course and postoperative outcome. Neurosurgery 1996; 39: 26-32

49 Casey AT, Thomas DG, Harkness WF. Stereotactically-guided craniotomy for cavernous angiomas presenting with epilepsy. Acta Neurochir (Wien) 1995; 137: 34-37

50 Abe M, Ogawa A, Yoshida Y, Hidaka T, Suzuki M, Takahashi S. Surgical removal of cavernous angioma in the medulla oblongata. A case report. Neurosurg Rev 1997; 20: 128-131

51 Takahashi A, Kamiyama H, Abe H, Kuroda S, Imamura H, Saitoh H. Cavernous angioma of the cerebellum and cerebellar atrophy. Case report. Neurol Med Chir (Tokyo) 1992; 32: 762-764

52 Yoshimoto T, Suzuki J. Radical surgery on cavernous angioma of the brainstem. Surg Neurol 1986; 26: 72-78

53 Alvarez-Sabin J, Montalban J, Tintore M, Codina A. Pure sensory stroke due to midbrain haemorrhage. I Neurol Neurosurg Psychiatry 1991; 54: 843

54 Bentley CR, Bronstein AM, Faldon R. Fast eye movement initiation of ocular torsion in mesodiencephalic lesions. Ann Neurol 1998; 43: 729-737

55 Awad IA, Robinson JR Jr, Mohanty M. Comparison of the clinical presentation of symptomatic arteriovenous malformations (angiographically visualized) and occult vascular malformations. Neurosurgery 1993; 32: 876-878

56 Wakai S, Ueda Y, Inoh S, Nagai M. Angiographically occult angiomas: A report of thirteen cases with analysis of the cases documented in the literature. Neurosurgery 1985; 17: 549-556

57 Tagle P, Torrealba G. Transorbital projectile simulating a carotidcavernous fistula. Rev Chil Pediatr 1985; 56: 259-261

58 Weil SM, Tew JM Jr. Surgical management of brain stem vascular malformations. Acta Neurochir (Wien) 1990; 105: 14-23

59 Zimmerman RS, Spetzler RF, Lee KS, Zabramski JM, Hargraves RW. Cavernous malformations of the brain stem. J Neurosurg 1991; 75: 32-39

60 Arutiunov Al, Kornienko VN. Catheterization cerebral angiography in the diagnosis of vascular lesions of the brain. Vopr Neirokhir 1969; 33: 11-16

61 Hallam DK, Russel Ej. Imaging of angiographically occult cerebral vascular malformations. Neuroimaging Clin N Am 1998; 8: 323-347

62 Chin D, Harper C. Angiographically occult cerebral vascular malformations with abnormal computed tomography. Surg Neurol 1983; 20: 138-142

63 Ahmadi J, Miller CA, Segall HD, Park SH, Zee CS, Becker RL. CT patterns in histopathologically complex cavernous hemangiomas. Am j Neuroradiol 1985; 6: 389-393

64 Agnoli AL. Neuroradiologic study using modern imaging procedures (CT:NMR) in venous, cerebral vascular malformations. Neurochirurgia (Stuttg) 1986; 29: 225-229

65 Biondi A, Scialfa G. Morphological and blood flow MR findings in cerebral vascular malformations. J Neuroradiol 1988; 15: 253-265

66 Bien S, Friedburg H, Harders A. Schumacher M. Intracerebral cavernous angiomas in magnetic resonance imaging. Acta Radiol Suppl 1986; 369: 79-81

67 Bourgouin PM, Tampieri D. Multiple occult vascular malformations of the brain and spinal cord: MRI diagnosis. Neuroradiology 1992; 34: 110-111

68 Carcao M, Blaser SI, Grant RM, Weksberg R, Siegel-Bartelt J. MRI findings in macrocephaly-cutis marmorata telangiectatica congenita. Am J Med Genet 1998;i 76: 165-167

69 Aiba T, Tanaka R, Koike T, Kameyama S, Takeda N, Komata T. Natural history of intracranial cavernous malformations. J Neurosurg 1995; 83: 56-59

70 Yamasaki T, Handa H, Yamashita J, Paine JT, Tashiro Y, Uno A, et al. Intracranial and orbital cavernous angiomas: A review of 30 cases. J Neurosurg 1986; 64:197-208

71 Zauberman H, Feinsod M. Orbital hemangioma growth during pregnancy. Acta Ophthalmol (Copenh) 1970; 48: 422-432

72 Sage MR, Brophy BP, Sweeney C, Phillips S, Perrerr LV, Sandhu A, et al. Cavernous hemangioma (angiomas) of the brain: Clinically significant lesions. Austra/as Radiol 2000; 37: 147-155

73 Robinson JR, Awad IA. Clinical spectrum and natural course. In: Awad IA, Barrow DL, eds. Cavernous Malformations, Park Ridge, IL: AANS, 1993: pp. 25-36

74 Del Curling 0, Kelly DL, Elster AD, Craven TE. An analysis of the natural history of cavernous hemangiomas. J Neurosurg 1991; 75: 702-708

75 Chabert E, Morandi X, Carney MP, Riffaud L, Louail C, CarsinNicol B. Intramedullary cavernous malformations. J Neuroradiol 1999 26: 262-268

76 Farmer JP, Cosgrove GR, Villemure JG, Meagher M. Intracerebral cavernous angiomas. Neurology 1988; 38: 1699-1704

77 Hubert P, Choux M, Houtteville JP. Cerebral cavernomas in infants and children. Neurochirurgie 1989; 35: 104-105

78 Watanabe A, Hirano K, Ishii R. Dural caroticocavernous fistula with both ophthalmic arteries arising from middle meningeal arteries. Neuroradiology 1996; 38: 806-808

79 Sakai N, Yamada H, Tanigawara T, Asano Y, Andoh T, Tanabe Y, Takada M. Surgical treatment of cavernous angioma involving the brainstem and review of the literature. Acta Neurochir (alien) 1991; 113: 138-143

80 Porter RW, Detwiler PW, Spetzler RF, Lawton MT, Baskin JJ, Derksen PT, Zabramski JM. Cavernous malformations of the brain stem: Experience with 100 patients. J Neurosurg 1999; 90 50-58

81 Wascher TM, Spetzler RF. Microsurgical treatment of infratentorial cavernous malformations. In: Awad IA, Barrow DL, eds. Cavernous Malformations, Park Ridge, IL: AANS, 1993: pp. 117-132

82 Alexander E III, Loeffler JS. Radiosurgery for intracranial vascular malformations: Techniques, results, and complications. Clin Neurosurg 1992; 39: 273-291

83 Liscak R, Vladyka V, Simonova G, Vymazal J, Novotny J Jr. Gamma knife radiosurgery of the brain stem cavernomas. Minim

Invasive Neurosurg 2000; 43: 201-207

84 Stainer L, Lindquist L, Foster D, Backlund EO. Radiosurgery: Baseline and Trends, New York, 1991

85 Coffey Rj, Lunsford LD. Radiosurgery of cavernous malformations and other angiographically occult vascular malformations. In: Awad IA, Barrow DL, eds. Cavernous Malformations, Park Ridge, IL: AANS, 1993: pp. 187-200

86 Chang SD, Levi RP, Adler JR, Martin DP, Krakovitz PR, Steimberg GK. Stereotactic radiosurgery of angiographically occult vascular malformations: Fourteen years experience. Neurosurgery 1998; 43: 213-221

87 Gewirtz RJ, Steinberg GK, Crowley C. Pathological changes in surgically resected angiographically occult vascular malformations after radiation. Neurosurgery 1998; 42: 738-742

88 Amin-Hanjani S, Ojilvy CS, Canadia G, Lyons S, Chapman PH. Stereotactic radiosurgery for cavernous malformations: Kjellberg's experience with proton bean therapy in 98 cases at the Harvard cyclotron. Neurosurgery 1998; 42: 1229-1237

89 Kondziolka D, Lunsford LD, Flickinger JC, Kestle JR. Reduction of hemorrhage risk after stereotactic radiosurgery for cavernous malformations. J Neurosurg 1995; 83: 825-831

90 Vinas FC, Dujovny M, Fandino R, Chavez V. Microsurgical anatomy of the infratentorial trabecular membranes and subarachnoid cisterns. Neurol Res 1996; 18: 117-125

91 Vinas FC, Dujovny M, Fandino R, Chavez V. Microsurgical anatomy of the arachnoidal trabecular membranes and cisterns at the level of the tentorium. Neurol Res 1996; 18: 305-312

92 Abd el-Bary TH, Dujovny M, Ausman JI. Microsurgical anatomy of the atlantal part of the vertebral artery. Neurol Res 1995; 44: 392-400

93 Akar ZC, Dujovny M, Slavin KV, Gomez-Tortosa E, Ausman JI. Microsurgical anatomy of the intracranial part of the vertebral artery. Neurol Res 1994; 16: 171-180

94 Torche M, Mahmood A, Araujo R, Dujovny M, Dragovic L, Ausman JI. Microsurgical anatomy of the lower basilar artery. Neurol Res 1992; 14: 259-262

95 Pedroza A, Dujovny M, Ausman JI, Diaz FG, Cabezudo Artero J, Berman SK, Mirchandani HG, Umansky F. Microvascular

natomy of the interpeduncular fossa. J Neurosurg 1986; 64: 484-493

96 Mahmood A, Dujovny M, Torche M, Dragovic L, Ausman JI. Microvascular anatomy of foramen caecum medullae oblongatae. J Neurosurg 1991; 75: 299-304

97 Shrontz C, Dujovny M, Ausman JI, Diaz FG, Pearce JE, Berman SK, Hirsch E, Mirchandani HG. Surgical anatomy of the arteries of the posterior fossa. J Neurosurg 1986; 65: 540-544

98 Rothon A Jr. The cerebellar arteries. Neurosurgery 2000; 47: S29-S68

99 Fernandez PM, Dujovny M. Anatomical basis for the lateral approach to the fourth ventricle. Neurol Res 1999; 21: 444-456

100 Rothon AL Jr. The posterior fossa veins. Neurosurgery 2000; 47: S29-592

101 Scott RM, Barnes P, Kupsky W, Adelman LS. Cavernous angiomas of the central nervous system in children. J Neurosurg 1992; 76: 38-46

102 Simrad JM, Garcia BF, Ballinger WJ, Mickle JP, Quisling RG. Cavernous angioma: A review of 126 collected and 12 new clinical cases. Neurosurgery 1986; 18: 162-172

103 LeDoux MS, Aronin PA, Odrezin GT. Surgically treated cavernous angiomas of the brain stem: Report of two cases and review of the literature. Surg Neurol 1991; 35: 395-399

104 Cedzich C, Pechstein U, Zentner J, Van Roost D. Minimally invasive stereotactically-guided extirpation of brain stem cavernoma with the aid of electrophysiological methods. Minim Invas Neurosurg 1999; 42: 41-43

105 Eisner W, Schmid UD, Reulen HJ, Oeckler R, Olteanu-Nerbe V, Gall C, Kothbauer K. The mapping and continuous monitoring of the intrinsic motor nuclei during brain stem surgery. Neurosurgery 1995; 37: 255-265

106 Chang SD, Lopez JR, Steinberg GK. Intraoperative electrical stimulation for identification of cranial nerve nuclei. Muscle Nerve 1999; 22: 1538-1543

107 Dujovny M, Vas R, Osgood CP. Bipolar jeweler's forceps with automatic irrigation, for coagulation in microsurgery. Plast Reconstr Surg 1975; 56: 585-587

Federico C. Vinas*, Vicky Gordon^, Murali Guthikonda^ and Fernando G. Diaz^

*Department of Neurosurgery, Halifax Medical Center, Daytona Beach, FL ^Department of Neurological Surgery, Wayne State University, Detroit, Ml, USA

Correspondence and reprint requests to: Federico C. Vinas, MD, Department of Neurosurgery, Halifax Medical Center, 311 N. Clyde Morris Blvd., Suite 310, Daytona Beach, FL, USA.

[federicovinas@hotmail.com] Accepted for publication August 2001.

Copyright Forefront Publishing Group Jan 2002
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