Journal of Neurology, Neurosurgery, and Psychiatry 1991;54:590-594 Cavernomas of the central nervous system: clinical and neuroimaging manifestations in 47 patients I Requena, M Arias, L L6pez-Ibor, I Pereiro, A Barba, A Alonso, E Mont6n Hospital Provincial, Santiago de Compostela, Spain Neurology Service I Requena M Arias A Barba A Alonso Neuroimaging Service L L6pez-Ibor I Pereiro E Mont6n Correspondence to: Dr Requena, Aptdo Correos 474, Santiago de Compostela, Spain Received 26 February 1990 and in revised form 7 September 1990. Accepted 31 October 1990 Abstract Forty seven cases of central nervous sys- tem cavernous angioma (21 males and 26 females) are described. The main clin- ical signs were epilepsy and brainstem syndromes. Digital subtraction intra- arterial angiography, when used, failed to reveal cavernoma. CT detected many of the lesions, but the most successful supplementary diagnostic procedure was MRI which produces highly characteris- tic images of cavernous angioma. The diagnosis of cavernous angioma was con- firmed in the 18 cases in which the tumour was removed surgically. The four categories of vascular malformations of the CNS are, in descending order of incidence, arteriovenous malformation, caver- nous angioma, venous angioma and telangiec- tasis.' Since cavernous angiomas (cavernomas) are slow-flow vascular lesions, their angiogra- phic appearance is avascular, and they are accordingly classed together with venous angioma, telangiectasis and thrombosed arteriovenous angioma as "cryptic" or "angiographically occult" CNS vascular mal- formations.27 Cavernomas consist of sinusoid vascular spaces with a single layer of endoth- elial cells separated from each other by con- nective tissue without intervening neural components. They have no connective cap- sule, but are usually well delimited by peri- pheral gliosis. Intrinsic thrombosis and haemorrhage frequently occur, as does cal- cification, which is probably secondary to the former events. Cholesterol and haemosiderin deposits may also be found."' The incidence of cavernomas is not known precisely, different studies have reported them as accounting for 2-17% of CNS vascular malformations."2"5 In 1976 Voigt and Yasar- gil'6 reviewed 164 published cases, 100 of them based on necropsies. There are multiple and familial cavernomas."'20 Cavernomas are often asymptomatic, and when symptoms are present they depend on the location and the size of the lesion. Cavernomas are usually located in the supratentorial compartment, preferably in the white matter, but have also been reported in intraventricular, pineal and dural locations and in the cavernous sinus, in Meckel's cave and the ponto-cerebellar angle.2""2 Clinical manifestations, the most important of which are epilepsy and focal neurological deficits,'5 are due to compression, but cavernomas never give rise to ischaemic symptoms such as occur with high-flow vas- cular malformations.8 Except in the rare case of hypervascular cavernomas,26 cavernomas do not show up on angiograms, or at most give rise to nonspecific angiographic abnormal- ities." CT and MRI, however, have both proved to be valuable diagnostic aids, the latter especially27 28 (the number of caver- nomas diagnosed may be expected to increase rapidly in the near future). CT shows caver- nomas as hyperdense or heterogeneous lesions (more rarely as hypodense ones), and a vari- able degree of enhancement after intravenous contrast injection is quite common, as is cal- cification.2"'0 Triple-dose injection with delayed detection has b'een used to improve sensitivity."l 32 In this article we describe and discuss the clinical, angiographic, CT and MRI signs of 47 patients with CNS cavernomas. Patients and methods We studied retrospectively 47 patients in a three year period (December 1986-November 1989) with various neurological manifesta- tions, referred to our centre from all areas of our country. In all cases clinical histories were recorded and neurological examination per- formed by a neurologist. Digital subtraction intra-arterial angiography was carried out in 24 cases (double contrast dose injection and repeated radiology was not used). Cranial CT was performed in 45 patients before and after intravenous contrast injection; in no cases was a triple dose with delayed detection used. MRI was performed in all 47 patients using a Philips 0.5 T Gyroscan; 6-8 mm sagittal, axial and coronal sections were taken using spin-echo sequences with Ti (TR 500 ms, TE 50 ms) and T2 (TR 1500-2200 ms, TE1 50 ms, TE2 100 ms) weighted and without paramagnetic contrast; the number, location, size (maximum diameter) and signal charac- teristics of lesions was recorded in each case. Neuroimaging studies were carried out and evaluated by a neuroradiologist. Results Of the 47 patients studied, 26 (55 3%) were females and 21 (44-7%) males. Age at diag- nosis was 39 years (range 5-79 years) in the whole patients group, 44 5 years in the female group (range 15-69 years) and 32-2 years in the male group (range 5-79 years). Clinical signs are listed in table 1 together with the number and percentage of cases in which each was observed. None of the 24 angiograms showed the presence of a cavernoma. The abnormalities that did show up in angiograms were avas- 590 on June 1, 2020 by guest. Protected by copyright. http://jnnp.bmj.com/ J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.7.590 on 1 July 1991. Downloaded from
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Journal ofNeurology, Neurosurgery, and Psychiatry 1991;54:590-594
Cavernomas of the central nervous system: clinicaland neuroimaging manifestations in 47 patients
I Requena, M Arias, L L6pez-Ibor, I Pereiro, A Barba, A Alonso, E Mont6n
Hospital Provincial,Santiago deCompostela, SpainNeurology ServiceI RequenaM AriasA BarbaA AlonsoNeuroimaging ServiceL L6pez-IborI PereiroE Mont6nCorrespondence to:Dr Requena, Aptdo Correos474, Santiago deCompostela, SpainReceived 26 February 1990and in revised form 7September 1990.Accepted 31 October 1990
AbstractForty seven cases of central nervous sys-tem cavernous angioma (21 males and 26females) are described. The main clin-ical signs were epilepsy and brainstemsyndromes. Digital subtraction intra-arterial angiography, when used, failedto reveal cavernoma. CT detected manyof the lesions, but the most successfulsupplementary diagnostic procedure wasMRI which produces highly characteris-tic images of cavernous angioma. Thediagnosis of cavernous angioma was con-firmed in the 18 cases in which thetumour was removed surgically.
The four categories of vascular malformationsof the CNS are, in descending order ofincidence, arteriovenous malformation, caver-nous angioma, venous angioma and telangiec-tasis.' Since cavernous angiomas (cavernomas)are slow-flow vascular lesions, their angiogra-phic appearance is avascular, and they areaccordingly classed together with venousangioma, telangiectasis and thrombosedarteriovenous angioma as "cryptic" or"angiographically occult" CNS vascular mal-formations.27 Cavernomas consist of sinusoidvascular spaces with a single layer of endoth-elial cells separated from each other by con-nective tissue without intervening neuralcomponents. They have no connective cap-sule, but are usually well delimited by peri-pheral gliosis. Intrinsic thrombosis andhaemorrhage frequently occur, as does cal-cification, which is probably secondary to theformer events. Cholesterol and haemosiderindeposits may also be found."'The incidence of cavernomas is not known
precisely, different studies have reported themas accounting for 2-17% of CNS vascularmalformations."2"5 In 1976 Voigt and Yasar-gil'6 reviewed 164 published cases, 100 ofthem based on necropsies. There are multipleand familial cavernomas."'20 Cavernomas areoften asymptomatic, and when symptoms arepresent they depend on the location and thesize of the lesion. Cavernomas are usuallylocated in the supratentorial compartment,preferably in the white matter, but have alsobeen reported in intraventricular, pineal anddural locations and in the cavernous sinus, inMeckel's cave and the ponto-cerebellarangle.2""2 Clinical manifestations, the mostimportant of which are epilepsy and focalneurological deficits,'5 are due to compression,but cavernomas never give rise to ischaemicsymptoms such as occur with high-flow vas-cular malformations.8 Except in the rare case
of hypervascular cavernomas,26 cavernomas donot show up on angiograms, or at most giverise to nonspecific angiographic abnormal-ities." CT and MRI, however, have bothproved to be valuable diagnostic aids, thelatter especially27 28 (the number of caver-nomas diagnosed may be expected to increaserapidly in the near future). CT shows caver-nomas as hyperdense or heterogeneous lesions(more rarely as hypodense ones), and a vari-able degree of enhancement after intravenouscontrast injection is quite common, as is cal-cification.2"'0 Triple-dose injection withdelayed detection has b'een used to improvesensitivity."l 32
In this article we describe and discuss theclinical, angiographic, CT and MRI signs of47 patients with CNS cavernomas.
Patients and methodsWe studied retrospectively 47 patients in athree year period (December 1986-November1989) with various neurological manifesta-tions, referred to our centre from all areas ofour country. In all cases clinical histories wererecorded and neurological examination per-formed by a neurologist. Digital subtractionintra-arterial angiography was carried out in24 cases (double contrast dose injection andrepeated radiology was not used). Cranial CTwas performed in 45 patients before and afterintravenous contrast injection; in no cases wasa triple dose with delayed detection used.MRI was performed in all 47 patients using aPhilips 0.5 T Gyroscan; 6-8 mm sagittal,axial and coronal sections were taken usingspin-echo sequences with Ti (TR 500 ms, TE50 ms) and T2 (TR 1500-2200 ms, TE150 ms, TE2 100 ms) weighted and withoutparamagnetic contrast; the number, location,size (maximum diameter) and signal charac-teristics of lesions was recorded in each case.Neuroimaging studies were carried out andevaluated by a neuroradiologist.
ResultsOf the 47 patients studied, 26 (55 3%) werefemales and 21 (44-7%) males. Age at diag-nosis was 39 years (range 5-79 years) in thewhole patients group, 44 5 years in the femalegroup (range 15-69 years) and 32-2 years inthe male group (range 5-79 years). Clinicalsigns are listed in table 1 together with thenumber and percentage of cases in which eachwas observed.None of the 24 angiograms showed the
presence of a cavernoma. The abnormalitiesthat did show up in angiograms were avas-
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cular masses associated with vascular dis-placement (in four patients), early venousdrainage (two patients) and an abnormal sur-face venous system arrangement (in onepatient).CT allowed detection of lesions in 40 of the
45 patients with whom it was used. Theimages were hyperdense or heterogeneous in35 cases and hypodense in 5. Nine lesionswere calcified. One patient exhibited tri-ventricular hydrocephalus with suspected in-trinsic aqueductal stenosis, and another aparasagittal meningioma. Intravenous con-trast injection achieved variable enhancementof lesions that were visible under CT withoutcontrast.MRI showed 56 cavernomas in the 47
patients studied, six of the patients proved tohave multiple lesions. The T2-weightedimages of the cavernomas showed well-definedlesions with a low peripheral signal due tohaemosiderin and a heterogeneous central sig-nal due to haemosiderin, calcium and blood invarious states (flow, thrombosis, haemorr-hage), while recently growing cavernomas(because of intralesional haemorrhage orthrombosis) occasionally produced imageswith a high-signal outer ring due to gliosisand/or oedema. The Ti-weighted images
Table 2 MRI signal characteristics of cavernomacomponents
showed the haemosiderin peripheral low sig-nal with a heterogeneous central signal, whilstperipheral oedema and gliosis were undetec-ted (isosignal) (fig 1 and table 2). Of the 56cavernomas, 33 (59%) were supratentorial, 22(39%) infratentorial and one (2%) spinal(table 3). Their maximum diameters in theMRI images ranged from 1 to 4 cm.The six patients with multiple cavernomas
(fig 2) comprised three females with threelesions each, two females with two lesionseach and one male with two lesions. A womanwith multiple cavernomas showed aqueductalstenosis due to a lesion in the anterior
Table 3 Locations of 56 CNS cavernomas in 47patients
Figure 1 A) SagittalMR image (T2, TE1) ofa medullar cavernoma:peripheral low signal ring(haemosiderin) andcentral heterogeneoussignal. B) Axial MRI(T2, TE2) of a pontinecavernoma with twohaemorrhagic noduleswithin the lesion (arrow)and one outside(arrowhead). Note theparenchymal high signalbecause of oedema (*).
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Figure 2 Coronal MRI( T2, TE1) of a patientwith multiple cavernomas:left cerebellar lesion withhomogeneous high signalbecause of recenthaemorrhage and a secondright temporal one (a thirdright parietal lesion notincluded in this image).
Figure 3 A) Axial CTimage showingtriventricularhydrocephalus withoutevidence ofparenquimatous lesion.B) Coronal MRI (T2,TEl) of the same womanreveals a superior vermiancavernoma causingaqueductal stenosis and aright cerebellarcavernoma.
r.
Figure 4 Incidentalfindinig of a small left occipitalcavernoma in axial MR image (T2, TE2) of a patientwith Parkinson's disease.
cerebellar vermis and triventricular hydro-cephalus (fig 3). A case of cavernoma of thecorpus callosum also showed parasagittalmeningioma. Two patients had associatedcavernous-venous malformations, and themale with two cavernomas showed abnormalsurface venous drainage due to partial agen-esis of the superior longitudinal sinus. In fivepatients cavernoma was an incidental finding(fig 4).
DiscussionA striking feature of these findings is the agedifference between the male and female groups.Eleven of the 21 males (52 4%) were diagnosedas cavernoma cases before the age of 30 years,compared with only three of 26 females(11-5%). It seems possible that as yet unknownhormonal factors may play some role in thebiology of cavernomas.The incidence of cavernoma has been repor-
ted to be greater among males than females,33greater among females than males,34 and thesame for both sexes.'6 In this study there weremore female than male patients (26 against 21)and more females had multiple lesions thanmales (19 2% versus 4 8%).As in other studies8 16 18 the incidence of
familial cavernomas in this series was low, thetwo patients who were sisters, making up just4-3% of the group, but we did not sys-tematically investigate the families of thepatients. Family screening increases the num-ber of diagnoses of familial cavernoma;35Rigamonti et al22 found that 54% of theirpatients were familial cases, and that multiplecavernoma was much commoner in this group.The location of the cavernomas (table 3)
correlated well with clinical manifestations.Eighteen of the 33 patients with supratentoriallesions had epilepsy, while 14 of 22 infra-tentorial lesions had ictal, progressive or fluc-tuating brainstem syndromes. Tentative clini-
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Cavernomas of the central nervous system: clinical and neuroimaging manifestations in 47 patients
cal diagnoses in some infratentorial casesincluded multiple system atrophy, multiplesclerosis and Miller-Fisher syndrome. Therewas a high incidence of asymtomatic lesions,21L4% (12 lesions) if the clinically unobtrusivelesions of the multiple cavernoma cases areincluded. The commonest site of supraten-torial cavernomas was temporal lobe (13lesions), and that of infratentorial cavernomasthe pons (10 lesions).
In all the 24 cases in which it was performed,angiography failed to reveal cavernoma. Theobserved angiographic alterations (vasculardisplacement, early drainage) are not specificfor cavernomas, since they may also beobserved in cases of telangiectasis, venousangioma, thrombosed arteriovenous malfor-mations, ischaemic lesions, glioma and inflam-matory states.3" In no case did we observeperipheral capillary blush, but then this showsup better after a second injection series4' thatwas not performed in this study. Nor did wedetect any case of so-called hypervascular duralcavernoma of the middle cranial fossa.2324264'The abnormal surface drainage vein of the manwith two cavernomas is attributed to the partiallack of the superior sagittal sinus.CT detected 40 cavernomas in the 45
patients with whom it was performed. Theradiological characteristics of these lesionswere similar to those described pre-vioUsly:2829304243 35 (87-5%) had high orheterogeneous density, were poorly delinatedand were only slightly enhanced by intravenouscontrast injection, while five (12-5%) werehypodense. Nine (22-5%) exhibited calcifica-tion. No totally calcified cavernoma, or"cerebral stone" 44 45 was observed. Triple-dosecontrast injection was not used because MRIwas available; reports3' that it improves caver-noma detection by CT have not been confirmedby other authors.32
In the 45 patients on whom both CT andMRI were employed, MRI detected 54 caver-nomas, including 14 that CT had failed todetect (most of them small lesions located deepin the temporal fossa or in the infratentorialcompartment). No cavernoma detected by CTwent undetected by MRI. CT is more specificfor detecting calcium, which in MRI imagesmay be confused with blood flow, haemosiderinor other alterations, but calcified areas were notinvisible in MRI images as has been reported.6Since the shape and location of the lesions andthe signal characteristics listed in table 2 madethe MRI ofthe cavernomas much more distinc-tive than their CT images, we consider MRI tobe both more sensitive and more specific thanCT for cavernoma diagnosis. MRI is alsouseful for monitoring the evolution, since sig-nals vary according to the stage after ahaemorrhage and with the variations in oedemaaround the lesion. Mass effect, diffuse highsignals and other possible features of caver-nomas or their images may hinder differentialdiagnosis of entities such as metastases andhaematomas; in such cases diagnosis shouldbe based on clinical and neuroimagingfeatures.2728 4The spinal (D4) cavernoma, which like the
other 17 surgically removed tumours was con-firmed histopathologically, was not detected bycomputer-assisted myelography.
In two radiated brainstem cavernomas, MRIshowed transient high peripheral T2 signalsdue to oedema, which disappeared in twoweeks, so that the pre- and post-radiatedimages were similar. Some authors847 considersurgical treatment to be mandatory in cases-including brainstem cases8-which exhibitrecent haemorrhage or mass effect, since theirremoval is facilitated by the circumscribingperipheral gliosis.We conclude that cavernomas with clinical
consequences seem to occur at an earlier age inmales than in females. Multiple lesions aremore common among females. The main clin-ical manifestations are epilepsy and brainstemsyndromes, though many lesions are asymp-tomatic. Angiography fails to detect this kind ofCNS vascular malformation, and a significantnumber go undetected by CT. The mostsensitive and specific technique for detection,characterisation and monitoring ofCNS caver-nomas is MRI.
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