Meningioangiomatosis - Oxford Academic

Brain (1999),122,709–726

MeningioangiomatosisA comprehensive analysis of clinical and laboratory features

Samuel Wiebe,1 David G. Munoz,1,2 Sharyn Smith2 and Donald H. Lee1,3

Departments of1Clinical Neurological Sciences, Correspondence to: Dr Samuel Wiebe, Department of2Neuropathology and3Diagnostic Radiology, University of Clinical Neurological Sciences, London Health SciencesWestern Ontario, London, Ontario, Canada Centre, University Campus, 339 Windermere Road,

London, Ontario, Canada N6A 5A5E-mail: [email protected]

SummaryMeningioangiomatosis (MA) is a rare, benign, focal lesionof the leptomeninges and underlying cerebral cortexcharacterized by leptomeningeal and meningovascularproliferation. It may occur sporadically or in associationwith neurofibromatosis type 2. Previous reports haveemphasized histological and imaging features. Data onthe management of these patients are sparse, andelectrophysiological features of MA lesions have not beenpublished. We assessed the clinical, electrophysiological,histopathological and imaging features as well as thesurgical outcome in MA, and compared MA with andwithout neurofibromatosis. Seven patients with MA atour centre were investigated and their outcome wasassessed. A review of the literature is included. MAexhibits a wide range of clinical, imaging, histopatho-logical and electrophysiological features, making thediagnosis difficult. Sporadic MA cases are not associatedwith neurofibromatosis and the two disorders aregenetically distinct. Medically refractory, localization-related epilepsy is the commonest presentation in sporadiccases, but atypical presentations also occur. Unlikesporadic cases, MA with neurofibromatosis is often foundincidentally, does not produce seizures, occurs less

Keywords: meningioangiomatosis; electrophysiology; histopathology; imaging; seizure outcome

Abbreviations: ECoG 5 electrocorticography; GFAP5 glial fibrillary acidic protein; MA 5 meningioangiomatosis;NF 5 neurofibromatosis

IntroductionMeningioangiomatosis (MA), a focal lesion of the lepto-meninges and underlying cerebral cortex, was originallydescribed in association with von Recklinghausen’s disease(Bassoe and Nuzum, 1915) and has since been known to alsooccur sporadically. Histopathologically, it is characterized bycortical meningovascular proliferation and leptomeningealcalcification (Halperet al., 1986). MA presents clinically aspartial seizures that are difficult to control or as an incidental

© Oxford University Press 1999

frequently (ratio of 1 : 4), and is multifocal. MRI findingsin MA correspond to the histological picture. However,the appearance on imaging is non-specific and may suggestcystic atrophy, angioma and tumours. Severalabnormalities have been found in close proximity to MAlesions, i.e. meningioma, oligodendroglioma, arterio-venous malformation, encephalocoel and orbital erosion.In spite of histopathological diversity, MA lesions areeither predominantly cellular or vascular. Immuno-histochemical results are inconsistent among cases, addlittle to the diagnosis, and do not support a meningealorigin. Electrocorticographic recordings from the surfaceand within MA lesions revealed a spectrum ofelectrophysiological expressions. Intrinsic epileptogenicityof MA lesions was documented in some cases.Epileptogenicity was confined to the perilesional cortexin some patients and it was complex (extralesional,multifocal, generalized) in others. Only 43% of ourpatients became seizure-free postoperatively comparedwith 68% previously reported, and >70% of our patientsand those in the literature continued to requireantiepileptic drugs. This is in keeping with the diverseelectrophysiology of MA and suggests a less optimisticpostoperative outcome than previously recognized.

finding in individuals who are asymptomatic, experiencevague neurological complaints (headache, nausea) or haveneurofibromatosis (NF) (Halperet al., 1986; Pauluset al.,1989; Partingtonet al., 1991; Prayson, 1995). The electro-physiological characteristics of seizure-producing MA lesionshave not been well described. Furthermore, although epilepsysurgery is briefly described as producing good results in MA(Kasantikul and Brown, 1981; Halperet al., 1986; Sakaki

Dow

nloaded from https://academ

ic.oup.com/brain/article/122/4/709/295869 by guest on 26 July 2022

710 S. Wiebeet al.

et al., 1987; Kuznieckyet al., 1988; Liuet al., 1989; Ogilvyet al., 1989; Partingtonet al., 1991; Tienet al., 1992; Gomez-Anson et al., 1995; Prayson, 1995), outcome assessment isnot described, and attention has not been given to thediagnostic and therapeutic problems faced by clinicianstreating this condition. Using our experience and a systematicreview of the literature, we delineate the spectrum of clinical,electrophysiological, imaging and pathological features ofMA. In addition, we compare the features of MA with andwithout phakomatoses and assess the surgical outcome insymptomatic cases.

MethodPatientsWe reviewed neuropathological records from 1980 to 1997for cases of MA at the London Health Sciences Centre inLondon, Ontario, Canada. Clinical features and results ofimaging and electrophysiological investigations wereobtained. Data on the surgical outcome were obtained throughclinicians’ interviews or by telephone using standard formsthat enquired about seizures, antiepileptic drugs andneurological deficits. All clinical data were independentlyobtained by two of the authors to ensure reproducibility.Disagreements were resolved at conference. All imaging andEEG studies were reviewed blind.

Subdural electrocorticographic (ECoG) recordingsemployed strip electrodes consisting of linearly arrayedplatinum contacts at 10-mm intervals, led to a seven-pinconnector by stainless-steel wires through Silastic-coatedTeflon tubing. Intraoperative ECoG used carbon-coated ballelectrodes in monopolar fashion. Cortical exposures weredetermined by clinical, imaging and ictal/interictal EEGfindings.

The following immunohistochemical stains wereperformed on each case to determine the origin of proliferatingor lesional cells: cytokeratin (low molecular weight, cam5.2) to assess epithelial differentiation; vimentin, a non-specific marker of mesenchymal cells; epithelial membraneantigen, a marker of arachnoid cap cells, positive in mostmeningiomas; S-100 protein, found in cells with neuroecto-dermal or Schwannian differentiation; glial fibrillary acidicprotein (GFAP), an intermediate filament in cells of astroglialdifferentiation; smooth muscle actin, a marker of smoothmuscle in blood vessel walls; neuronal specific enolase, anon-specific marker of neuronal cells; and factor VIII, anendothelial cell marker.

Literature reviewWe used free-text and MeSH terms to search the followingdatabases: Medline® 1966 to April, 1997; CANCERLIT®

1983–96; Current Contents® 1996–97. In addition, wesearched neurological and neuropathological textbooks andtheir references for additional cases. Cases were included if

histopathological descriptions contained at least one of thetwo classical features of MA, i.e. leptomeningeal proliferationand meningovascular proliferation, and if the authorsclassified them as MA. The following information wassought: demographic features, association with phakomatosesin patients and their family, clinical features, location of MA,imaging and EEG data, surgical treatment and outcome,and histopathological findings. Literature searches and dataabstraction were performed independently by two of theauthors to ensure accuracy and reproducibility. Disagreementswere resolved at conference.

AnalysisDescriptive statistics were used to analyse the distribution ofvariables of interest. Ninety-five percent confidence intervalsfor means and binomial proportions were obtained.Continuous variables were compared with independent-groupt tests. For discrete variables,χ2, Fisher’s exact or binomialtests of proportions versus standard were used. Associationwas expressed as the odds ratio where indicated.

ResultsPatientsOur records yielded seven cases of MA; all were surgicalspecimens (Table 1). Median age at presentation was 17years (range 10–37 years). All patients had refractory seizuresfor 1–18 years (median 7 years). Two patients had exclusivelysimple partial seizures, one with visual (right mesial occipital-parietal lesion) and one with motor phenomena (left Rolandiclesion). All other patients had complex partial seizures, withsecondary generalization in two and a tendency to statusepilepticus in one. Case descriptions follow.

Case 1An 18-year-old woman presented with increasingly frequentand severe simple partial seizures since age 10 years,consisting of coloured diamonds in the left lower visual fieldfollowed by experiential phenomena. Neurological, generaland visual field examinations were normal. Scalp EEGsshowed minimum posterior head slowing with no epileptiformactivity. Head CT showed a 33 5 cm, partially calcified,gyriform mass in the right supracalcarine, anterior mesialoccipital region, resembling a partially calcified arteriovenousmalformation. Cerebral angiogram revealed an avascularmass. Brain CT (Fig. 1A) and MRI (Fig. 1B) showed acortical, calcified, gyriform mixed signal pattern. MA wassuspected. ECoG revealed perilesional cortical spikes. Apartial lesionectomy was performed. Histopathology revealedMA. The patient has a persistent, incomplete, lefthomonymous hemianopia but remains seizure-free withoutantiepileptic drugs 7 years later.

Dow



Meningioangiomatosis 711

Table 1 Present series: clinical features and surgical outcome

Case Age Duration Clinical Neurological Location Surgical Seizure AEDs(years) of illness presentation examination (size cm) treatment outcome/sex (years) (time)

1 18/F 10 Refractory seizures: Normal R occipital- Partial resection Seizure-free (7 years) NoSP, visual parietal mesial

(3 3 5 cm)2 10/F 2 Haemorrhagic stroke- Normal L Rolandic Partial resection Seizures continue Yes

angioma. Refractory (23 2 cm) (6 years)seizures: SP, Rolandic

3 31/M 15 Refractory seizures: Normal L temporal (i) Lesionectomy Seizure-free after third NoCP, GTC inferior lateral (ii) Corticectomy surgery (10 years)

(4 cm) (iii) AH resection4 17/M 1 Refractory seizures: Normal R temporal Total resection of Seizures continue Yes

SP, CP convexity temporal insular (7 years)(2 cm) lesion

5 37/F 18 Refractory seizures: Normal R temporal pole Total resection Improved seizures YesCP, GTC, (2.5 cm) Partial AH (5 years)status epilepticus resection

6 33/F 7 Refractory seizures: CP Normal L temporal Total resection, Sporadic seizures Yesmesial temporal (4 years)(3 3 3 cm) lobectomy

7 12/M 6 Refractory seizures: CP, SP Normal L mesial Total resection Seizure-free (1 year) Yesoccipital (1.5 cm)

All cases presented with refractory, localization-related epilepsy. No case was associated with phakomatosis. CP5 complex partial; SP5 simple partial;GTC 5 generalized tonic–clonic; L5 left; R 5 right; M 5 male; F5 female; AEDs5 antiepileptic drugs; AH5 amygdala–hippocampus

Fig. 1 Case 1. (A) Enhanced CT scan. Axial slice shows right mesial occipital gyriform enhancement/calcification without mass effect orlocal white matter density change. (B) Gradient echo MRI (TR/TE/Nex 600/20/2): predominantly cortical, low signal, right mesialoccipital gyral lesion with underlying slight signal increase. Meningioangiomatosis was predicted.

Dow



712 S. Wiebeet al.

Case 2An 8-year-old diabetic girl presented with a violent headache,vomiting, transient dysarthria and right facial weakness.Initial head CT showed an acute, left inferior Rolandicparenchymal haemorrhagic lesion. The cerebral angiogramwas normal. One month later, simple partial seizuresdeveloped consisting of right facial numbness withhemicorporeal spread, slurred speech, drooling, a peculiartaste, and postictal dysphasia. Neurological and ophthalmicexaminations were normal. A cutaneous haemangioma wasfound at the T6 dermatome. Her mother had von Hippel–Lindau disease. Subsequent MRI revealed a 2-cmhaemorrhagic lesion with blood of various ages and well-demarcated surrounding hemosiderin. There was mild oedemaand a small amount of posterior gadolinium enhancementthat was probably related to reactive changes in the wall of thehaematoma (Fig. 2). This was considered highly suggestive ofa cavernous angioma. There were no features on imaging tosuggest the diagnosis of MA. An extensive search for systemicand spinal angiomata was negative. Scalp EEG showed lefttemporal–central–parietal spikes and generalized spike wave.ECoG was normal under general anaesthesia. The locationof the lesion near the dominant Rolandic cortex allowed onlya semicomplete lesionectomy. At surgery, the lesion gavethe impression macroscopically of a subcortical cavernousangioma. Histopathology revealed exclusively cortical MAwhich had previously bled several times into the brainparenchyma. This explained the impression of a cavernousangioma on imaging. The patient was seizure-free for 1year. Thereafter seizures recurred and remain refractory toantiepileptic drugs 6 years later.

Case 3A 21-year-old male presented with progressively intractablecomplex partial seizures with secondary generalization sinceage 16 years. Seizures consisted of experiential phenomena,loss of awareness, staring, drooling, automatisms and postictaldysphasia. Neurological examination was normal. Head CTscan demonstrated a left inferior lateral temporal enhancingmass interpreted as a glioma. Scalp EEG showed left temporaland left hemisphere spikes and delta-band activity. Clinicallytypical seizures originated in the left temporal area. ECoGrevealed widely synchronous left temporal and perisylviansharp waves and delta-band activity. Partial lesionectomyand temporal lobectomy were performed sparing theamygdala and hippocampus because of failed ipsilateralcarotid amytal memory testing. Post-resection ECoG showedprominent spikes overlying the residual lesion. As seizurescontinued unabated, a discrete, malignant-appearing lesionwas completely removed in a second operation. Electrodesdirectly on and within this lesion revealed very activeepileptogenesis (Fig. 3). Because of the striking hyper-cellularity, gliosis, vascular proliferation and leptomeningealinvasion and because the histopathological features of MA

were not widely recognized at the time (1978), the erroneousdiagnosis of glioblastoma multiforme was made by thepathologist. Ten years after the second surgery intractableseizures continued. Scalp EEGs showed left anterior temporalspikes and seizures. A left amygdalohippocampectomy wasperformed following a successful left carotid amytal test.ECoG showed very active hippocampal spike activityabolished by the resection. Hippocampal sclerosis was foundon histopathology. The patient remains seizure-free 10 yearslater on a single antiepileptic drug. Re-examination of thehistological slides revealed the characteristic features of MA,i.e. a plaque restricted to the cortex and meninges but sparingthe white matter, consisting of a dense proliferation of cellsand blood vessels, in the absence of pleomorphism andmitotic activity (Fig. 8H).

Case 4A 17-year-old male presented with a 1-year history ofprogressively frequent simple and complex partial seizuresconsisting of auditory illusions, visual blurring and formedvisual hallucinations (people, animals), loss of awareness,staring, pallor and diaphoresis followed by headaches.General and neurological examinations were normal. HeadCT scan showed a subtle right superior temporal, hyperdense,gyriform, mildly enhancing lesion consistent with a low-grade glioma. Brain MRI showed a heterogeneous lesionsurrounded by low signal on T2 sequences, suggesting MA(Fig. 4A and B). Scalp EEGs showed right mid-anteriortemporal spikes and subclinical seizures. ECoG revealedfrequent spikes directly over and around the lesion and inthe hippocampal depth electrodes independently (Fig. 4C).The indurated lesion, anterior temporal lobe, amygdalaand hippocampus were resected. Histopathology showedMA only. Seven years after surgery medically refractoryseizures persist with modest improvement in frequency andseverity.

Case 5A 36-year-old woman presented with progressively severecomplex partial and frequent secondarily generalized seizuresstarting at age 19 years, consisting of deja vu, loss ofawareness, vacant staring, drooling, right hand dystonicposturing and bimanual automatisms without postictal deficit.General and neurological examinations were normal. HeadCT, previously reported as normal, was not available forreview. Brain MRI demonstrated a 2.5 cm (axial plane) righttemporal pole cystic lesion (Fig. 5A) with increased corticalsignal on proton density images (Fig. 5B), interpreted ascystic encephalomalacia or tumour (Fig. 5A–C). There wereno MRI changes suggestive of mesial temporal sclerosis.Scalp EEG revealed right temporal-frontal spikes and delta-band activity. Seizures had an ambiguous onset in the righthemisphere. Subdural EEG recordings showed independentright mesial temporal, inferior anterior temporal and

Dow




Fig. 2 Case 2. (A) T2-weighted MRI (TR/TE/Nex 2800/80/1): heterogeneous low signal and slightly higher signal lesion in left frontalopercular region with surrounding high signal cavernoma was suspected. (B) T1-weighted MRI (TR/TE/Nex 350/16/2) of pre-contrastimage showing high signal intensity mass and (C) after contrast image showing faint enhancement at the rear of the lesion (arrowhead).

Dow



714 S. Wiebeet al.

Fig. 3 Case 3. ECoG shows independent and synchronousepileptiform discharges on the surface (surface) and within(depth) the MA lesion but not in the adjacent neocortex.

orbitofrontal spikes. Seizures started in the right temporalpole and hippocampus. A right anterior temporal lobectomyincluding 1.5 cm of the anterior hippocampus was performed.Histopathology showed MA and mesial temporal sclerosis.She continues to have generalized motor and partial seizures5 years after surgery, with moderate improvement infrequency and severity.

Case 6A 33-year-old woman had refractory simple and complexpartial seizures starting at age 26 years, consisting of acephalic sensation, intrusive thoughts, inability to understandor speak, loss of awareness, right hand automatisms andpostictal dysphasia. General and neurological examinationswere normal except for otosclerosis. Head CT was normal.Brain MRI demonstrated a left amygdalohippocampal masswhose signal was hyperintense on T2-weighted images (Fig.6A) and homogeneously isointense with white matter on T1-weighted images (Fig. 6B), consistent with a low-gradetumour. EEG revealed left anterior temporal spikes, delta-band activity and seizures. ECoG revealed prominent spikeactivity in electrodes within and directly over the lesion (Fig.6C). Left anterior temporal lobectomy and amygdalohippo-campectomy were performed. Histopathology revealed MAentirely replacing the amygdala and hippocampus. The patienthas sporadic seizures 3 years after surgery on single antiepi-leptic drug therapy.

Case 7A developmentally normal 12-year-old boy experiencedtypical febrile convulsions at age 2 years. At age 6 years,refractory complex partial seizures developed consisting ofa blank stare and bimanual and oroalimentary automatismswithout postictal deficit. General and neurological examina-

tions were normal. Head CT disclosed a non-enhancingleft anterior mesial occipital-cingulate lesion. On MRI, thecortical cystic lesion was hypointense on T1-weighted imagesand hyperintense on T2-weighted images with surroundingincreased T2 signal (Fig. 7A and B). A tentative diagnosisof dysembryoplastic neuroepithelial tumour was given. ScalpEEGs showed generalized spike wave and independentlyoccurring frontal and occipital epileptiform discharges(Fig. 7C). Seizures had an ambiguous onset without occipitalpredominance. Subdural electrode recordings showed spikesprincipally in the left mesial temporal and convexity regions,but also in the left mesial frontal and posterior cingulatearea. Seizures originated in the perilesional cortex with latepropagation to the ipsilateral posterior temporal convexity,hippocampus and mesial frontal region. The lesion andadjacent cortex were resected. Histopathology showed MA.He remains seizure-free 1 year after surgery on twoantiepileptic drugs.

HistopathologyAll our patients’ MA lesions were confined to the cortex,with variable involvement of the overlying leptomeninges.Although all lesions shared unifying features, i.e. corticalvascular proliferation and perivascular cell proliferation, eachwas unique. Cases were easily classified into those withpredominantly cellular (patients 3–7) and those withpredominantly vascular (patients 1 and 2) lesions.

Predominantly cellular cases demonstrated moderate tohigh cellularity (Fig. 8A and B). Varying architecture wasnoted, consisting of focal areas of storiform, rhythmicpalisading and fascicular patterns (Fig. 8C). All cellular caseshad lesional cells that in areas appeared to emerge from theperivascular location and infiltrate the cortex. This occurredcentrally within the lesions, where cellularity was most dense.Peripherally, the perivascular relationship of the cells becameevident (Fig. 8D). The blood vessels in these cases had asimilar appearance, i.e. they were thin-walled, slit-like andincreased in number. Predominantly vascular cases containedthick-walled, hyalinized and calcified blood vessels withminimal perivascular cell proliferation. (Fig. 8E and F). Inone case (patient 2) the MA lesion showed evidence ofhaemorrhage. Neither case demonstrated cortical invasion byproliferating cells.

Despite cellularity, the proliferating cells in all cases hadbland cytological features, without significant atypia, mitosesor necrosis. Two of the cellular (patients 1 and 2) and bothvascular cases contained a meningeal component. Of these,three showed calcification in areas of meningeal proliferationand within the cortex (patients 2, 5 and 6). Extensivepericellular reticulin deposition occurred in two of the fivecellular cases (patients 2 and 4) (Fig. 8G). In all other cases,reticulin was confined to blood vessels.

Bielschowsky staining and tau immunostaining demon-strated neurofibrillary tangles in the cortex adjacent to thelesion only in patient 4. One case (patient 3) demonstrated

Dow




Fig. 4 Case 4. (A) T2-weighted MRI (TR/TE/Nex 2800/80/1). Low signal, right superior temporal, non-mass-producing lesion extendinginto the inferior insular cortex. Higher signal areas occur in the insula, adjacent external/extreme capsule and adjacent superior temporalgyrus white matter. (B) T2-weighted axial MRI (TR/TE/Nex 2800/80/1). The lower signal and local mass in the superior temporal gyrus/insular cortex was prospectively called meningioangiomatosis. (C) ECoG demonstrating independent epileptiform discharges (spikes andspike-waves) on the MA lesion (surface) and in hippocampal depth electrodes (HC depth). Lesional spikes are of higher amplitude andduration than hippocampal spikes.

cortical dysplastic neurons adjacent to the MA focus(Fig. 8H). All cases showed gliosis within and adjacent tothe lesion.

Correspondence between imaging and pathologicalfindings was good, For example, in patient 5 a cyst identifiedon MRI corresponded with a white matter cyst underlyingthe cortical MA lesion.

On immunostaining, the proliferating cell populationexpressed vimentin uniformly. Results for other markersvaried, i.e. three cases (patients 3, 5 and 6) showed focalGFAP positivity, two were focally positive for neuronalspecific enolase (patients 3 and 5) and one was positive forS-100 (patient 3). All were negative for cytokeratin, factorVIII and actin. Our results illustrate the variability of

Dow



716 S. Wiebeet al.

Fig. 5 Case 5. (A) T1-weighted coronal MRI (TR/TE/Nex 500/20/2) showing a low-signal lesion, signalling similar to CSF. (B andC)Proton density (TR/TE/Nex 2800/30/1) (B) and T2-weighted MRI (TR/TE/Nex 2800/80/1) (C) showing signal isointense to CSF in thelesion. Cystic encephalomalacia or a cystic neoplasm was predicted.

Dow




Fig. 6 Case 6. (A) Proton density MRI (TR/TE/Nex 2800/30/1). Mass lesion in left uncus extending across the tentorial margin, withuniform high signal in the uncus and adjacent amygdala. A low-grade tumour was suspected. (B) T1-weighted MRI (TR/TE/Nex450/15/2) shows mass lesion isointense with temporal white matter, extending into the left side of the suprasellar cistern and distortingthe uncus. (C) ECoG showing spikes and polyspikes arising from the surface of (surface) and within (depth) the MA lesion, andoccurring independently of temporal neocortical discharges.

Dow



718 S. Wiebeet al.

Fig. 7 Case 7. (A) Proton density MRI (TR/TE/Nex 2500/32/1). A high-signal lesion is seen in the left temporal isthmus, posterior andinferior to the callosal splenium with fluid type signal centrally, high signal peripherally and mild mass effect. (B) T1-weighted sagittalMRI (TR/TE/Nex 516/13/1). The retrosplenial cystic lesion with local mass effect suggested a low-grade tumour. (C) Scalp EEGdemonstrating abundant epileptiform discharges with a broad and complex distribution, prominently involving the frontal region in thispatient with posteriorly located MA.

immunostaining and suggest that proliferating MA cells donot correspond to a known, normally occurring cell type.Notably, epithelial membrane antigen, a known meningo-thelial cell marker, was focally positive in only two cases(patients 5 and 6).

Literature reviewFifty-six cases with histopathological confirmation of MAwere found in the literature. Only 13 (23%) occurred in

association with NF (Table 2). Forty-three cases without NFhave been described in 18 series prior to our report, startingwith the initial description by Kasantikul and Brown (1981)(Table 3). The following sections refer to our series and theliterature cases combined.

Demographic featuresThe mean age at the time of diagnosis was 28 and 21 yearsfor MA with and without NF, respectively. Because MA with

Dow




Fig. 8 (A) Case 6. Low-power view of MA demonstrating full-thickness cortical involvement. There is complete effacement of corticalarchitecture. The heterogeneous pattern of cellularity and vascularity gives an uneven appearance. Haematoxylin and eosin,318.(B) Case 6. Higher power demonstrates subpial and perivascular cell proliferation. Haematoxylin and eosin,390. (C) Case 5. Highlycellular lesion with a central area showing ‘rhythmic palisading’ and storiform architecture. Haematoxylin and eosin,372. (D) Case 5.Periphery of MA lesion in a predominantly cellular case. The perivascular cellular position becomes evident. Haematoxylin and eosin,372. (E) Case 1. Predominantly vascular case with thick-walled vessels in the meninges and cortex. Haematoxylin and eosin,345.(F) Case 1. Higher power showing calcified cortical blood vessel with minimal perivascular cellular proliferation. Haematoxylin andeosin,3144. (G) Case 4. Reticulin stain showing extensive network of reticulin fibres (reticulin deposition) in a predominantly cellularcase.3144. (H) Case 3. Numerous dysplastic neurons (one indicated by an arrow) are present in the cortex immediately adjacent to theMA lesion. These neurons show multinucleation, irregular nuclear contours, prominent nucleoli and inconspicuous cytoplasm.Haematoxylin and eosin,3180.

Dow



720 S. Wiebeet al.

Table 2 Meningioangiomatosis with neurofibromatosis

Series Age Family history Presentation Location Imaging EEG LMC Pathology NFT(years) of phakomatosis MVP

Bassoe and Nuzum (1915) 15/M NS Incidental at Right frontal ND ND1 1 NSautopsy

Foerster and Gagel (1932) 21/M NS Incidental at Multifocal: frontal, temporal, ND ND2 1 NSautopsy parietal, white matter

Worster-Drought (1937) 25/M NS Incidental at Right frontal ND ND 1 1 NSautopsy

Beck (1938) 23/F NS Incidental at Third ventricle ND ND 1 1 NSautopsy

Beck (1939) 35/M NS Incidental at Parietal ND ND 1 1 NSautopsy

Hozay (1953) 39/M NS Incidental at Multifocal: occipital, temporal, ND ND NS 1 NSautopsy frontal, parietal

Rubinstein (1963) 16/F NS Incidental at Multifocal: frontal, parietal ND ND NS 1 NSautopsy

32/M NS Incidental at Cingulate gyrus ND ND NS 1 NSautopsy

23/F NS Incidental at Pulvinar, cerebral peduncle ND ND NS1 NSautopsy

Feigin (1971) NS NS Incidental at Cerebral cortex ND ND NS 1 NSautopsy

Johnson and Nielsen (1976)* 23/M NS Incidental at Cerebral cortex NS NS2 1 1autopsy

Halperet al. (1986) 38/F Neurofibromatosis Incidental at Multifocal: parietal, temporal, ND ND2 1 1autopsy bifrontal

Husonet al. (1988) 43/M NS Headaches, Right frontal Right NS NS NS NSdrowsiness frontalMisdiagnosed tumouras astrocyma on CTinitially

Only 13 cases of MA have been reported in association with NF. All but one were found incidentally at autopsy. MA lesions are often multifocal.NS 5 not stated; ND5 not done; LMC5 leptomeningeal calcification; MVP5 meningovascular proliferation; NFT5 neurofibrillary tangles;1 5 present; –5 absent.*Not classified as meningioangiomatosis by original authors.

NF was diagnosed incidentally at the time of autopsy in mostcases, the age difference reflects only the average survivalof patients with NF in earlier series. MA without NF presentsat an early age; 12, 25 and 60% of patients were,5, ,10and ,20 years old, respectively, and only 10% wereù40years old. The youngest patient in this group was 9 months old(Blumenthalet al., 1993). MA occurred twice as frequently inmales as in females in both groups (P 5 0.05). The durationof seizures prior to diagnosis of MA wasø1 year in 30%of patients, from 2 to 9 years in 46% andù10 years in 24%.A family history of phakomatosis (NF, type unknown) wasfound in one patient with NF, and in one of our patientswithout NF whose mother had von Hippel–Lindau disease(Tables 1–3).

Location of MAThe chance of having multifocal MA lesions was almost 10times higher (odds ratio5 9.78) in the presence of NF thanin its absence. Five cases (38%) in the NF group had multipleMA foci compared with only one (2%) of those without NF(P 5 0.017). MA involved the cortex in 90% of all patients.However, extracortical lesions occurred three times morefrequently (odds ratio5 2.6) with NF (23% compared with

6% for cases without NF). Unusual MA locations includedthe third ventricle (Beck, 1938) and the pulvinar-cerebralpeduncle (Rubinstein, 1963) in those with NF, and the corpuscallosum (Jun and Burdick, 1984), trigeminal ganglion (Garenet al., 1989), and the medulla intra-axially (Kolliaset al.,1994) in those without NF. Seventy percent of all lesionsoccurred in the frontal temporal region, and the single mostfrequent location was the temporal lobe (40%). In theposterior head, the distribution was similar between theoccipital and parietal lobes (four cases each). The mesialaspect of the occipital, frontal and temporal lobes wasinvolved in three, four and two patients, respectively.Although the numbers were small, there was a statisticallysignificant association between occipital lobe and mesialsurface involvement (odds ratio5 7.7). In 46 patients withunilateral lesions, the right hemisphere was affected twiceas frequently as the left [32 and 14 cases, respectively(P 5 0.005)].

Clinical presentationAll but one of the cases with NF were found incidentally atautopsy (Table 2). One patient presented with headaches,drowsiness and a right frontal mass on CT. After partial

Dow




Table 3 Meningioangiomatosis without neurofibromatosis: clinical and demographic features

Series Age (years) Duration Clinical Location/sex of illness presentation

Willson et al. (1977)* 62/M NS Seizures, mental retardation Right frontalRhodes and Davis (1978)* 27/F 3 years Headaches Right frontalKasantikul and Brown (1981) 15/M 14 years Refractory seizures: Jacksonian Right frontal

23/M 10 years Refractory seizures: CP Right temporalAuer et al. (1982)* 15/M 2 months Headache, meningismus Right frontalJun and Burdick (1984)* 55/M NS Headache, vomiting, dizziness Corpus callosumSakakiet al. (1987) 30/F 25 years Refractory seizures: GTC, SP sensory Right opercularKunishio et al. (1987) 39/M – Incidental after head trauma Right parietalHalperet al. (1986) 26/M 9 years Seizures: GTC, SP, febrile convulsions Left temporal

70/M – Incidental at autopsy. Renal cell carcinoma Left occipital10/F NS Seizures: unknown type Right opercular30/M 3 years Refractory seizures: CP Right frontal17/F 8 years Refractory seizures: SP sensorimotor, Right opercular

(febrile convulsions, bilateral painfulseizures)

Kuznieckyet al. (1988) 24/M 8 years Refractory seizures: CP, GTC Right temporalMatias-Guiuet al. (1988) 42/M 1 years Infrequent seizures: SP motor left arm Right parietal

Left arm weaknessOgilvy et al. (1989) 9/M 6 years Frequent seizures: CP, rare GTC Right opercularLiu et al. (1989) 22/F 3 years Refractory seizures: CPS, GTC Left frontalPauluset al. (1989) 5/M 4 years Seizures: absence, myoclonic-astatic. Left Multifocal, patchy,

hemiparesis. (Found incidentally at autopsy) bifrontal temporalGarenet al. (1989)* 44/M 6 years Atypical facial pain Right trigeminal ganglionWhiting et al. (1990) 18/F 5 years Refractory seizures: CPS. Associated with Left temporal

temporal encephalocoelLouw et al. (1990)* 33/M 2 years R supraorbital pain, visual obscurations Right frontalWilson et al. (1991) 17/M ? years Controlled seizures. Personality changes FrontalPartingtonet al. (1991) 19/M 6 years Intractable seizures: CPS Right frontal

17/F 6 months Single seizure: GTC Right frontalAizpuru et al. (1991) 2.5/M NS Seizures: NS Right parietal

5/M NS Seizures: NS Right temporal21/M NS Seizures: NS Right temporal9/F NS Seizures: NS Left temporal

Goateset al. (1991) 13/F 2 years Refractory seizures: Jacksonian right arm; Left parietalGTC

Oka et al. (1991) 14 months/F Months Seizures: NS Left temporalTien et al. (1992) 20 months/F 2 months Atypical febrile convulsion: left-sided with Right occipital

postictal weakness7/M 6 years Refractory seizures: CPS Left frontal

Blumenthalet al. (1993) 9 months/M Days Single seizure: left-sided tonic–clonic Right frontalFujimoto et al. (1993) 7/F NS NS NSKim et al. (1993) 18/M 15 years Refractory seizures: NS Right temporalHaradaet al. (1994) NS NS ?Seizures NSKollias et al. (1994) 3.5/F 2 weeks Vomiting, left facial weakness Medulla intra-axialPrayson (1995) 14/F 3 years Refractory seizures: CP Right temporal

11/M 2 years Refractory seizures: CP?; learning disability Right opercular32/F 30 years Refractory seizures: CP, GTC Left frontal

Gomez-Ansonet al. (1995) 4/M 3 months Seizures: CP, personality change Bifrontal mesial12/M 8 months Refractory seizures: CP Right temporal

Lopezet al. (1996) 15/M Months Single seizure: CP Left temporal

Clinical and demographic features of 43 cases of MA not related to NF reported in the literature. CP5 complex partial; GTC5 generalized tonic–clonic;NS 5 not stated; SP5 simple partial; L5 left; R 5 right; M 5 male; F5 female. *Not classified as meningioangiomatosis by original authors.

resection and radiotherapy the patient developed seizures butsurvived for many years. This prompted review of thespecimen and reclassification from astrocytoma to MA(Husonet al., 1988).

In MA without NF, seizures were the only or predominantproblem in 42 patients (85%) (Tables 1 and 3). Seizures werethe exclusive clinical problem in all patients with temporaland opercular lesions. Information on seizure type wasavailable for 29 of 39 patients (74%). Eighteen of the 29patients (62%) had only partial seizures without secondarygeneralization. Localization of seizure onset by clinical

features corresponded with MA location. There was noassociation between location and tendency to generalizedseizures. Seizures were refractory to antiepileptic drugs in33 of 39 (85%) patients. In the remaining six patients, earlyimaging and surgery were done because of focal neurologicaldeficits in four patients (Matias-Guiuet al., 1988; Wilsonet al., 1991; Tienet al., 1992; Blumenthalet al., 1993) andfollowing single seizures in two patients (Partingtonet al.,1991; Lopezet al., 1996). Febrile convulsions occurred infour patients, two with mesial occipital (Tienet al., 1992)(patient 7) and two with opercular and temporal MA,

Dow



722 S. Wiebeet al.

respectively (Worster-Droughtet al., 1937; Halperet al.,1986). Atypical febrile convulsions occurred in one patient(Tien et al., 1992).

Eight patients (16%) did not have seizures. They presentedwith headache (three cases with frontal or anterior callosalMA), facial pain (two patients with trigeminal and orbitalMA) or lower cranial nerve palsies (one case withintramedullary MA), or were asymptomatic (two patientswith incidental parietal MA). Atypical clinical featuresincluded fatal subarachnoid haemorrhage from right frontal-mesial MA (Auer et al., 1982), and facial pain andpapilloedema from right frontal-temporal MA eroding theorbital roof (Louwet al., 1990).

ElectrophysiologyInterictal scalp EEG data, available for 24 of 39 patientswith seizures, showed congruence in location of epileptiformdischarges and MA in 18 (75%) patients. Extralesionalmultifocal spikes or generalized spike-wave were seen in sixpatients (25%), three with frontal, two with temporal andone with occipital lobe lesions. Ictal scalp EEG was reportedin five patients, all with MA and seizures confined to thetemporal lobe.

Our patients’ surface and depth ECoG disclosed a widearray of findings. In three patients with temporal lobe MA(patients 3, 4 and 6), spikes and sharp waves were recordedfrom the surface and within MA lesions (Figs 3, 4C and 6C).MA and hippocampal spikes occurred independently anddiffered in morphology. In patient 6, what appeared to behippocampal spikes and seizures proved to originate fromMA which entirely displaced the normal mesial temporalstructures. In other patients (patients 1, 2 and 7), MA waselectrographically quiescent and the surrounding cortex gaverise to spikes and seizures. In patient 2, parenchymalhaemorrhage and destruction could explain the lack oflesional epileptogenicity. Three of our patients had multifocalextralesional spikes; two had generalized spike-wave withoutsecondary bilateral synchrony, one with occipital and onewith opercular MA. Mesial temporal ECoGs, obtained in fiveof our patients, recorded spikes in each instance.

ImagingPatients with and without NF had similar findings on thevarious imaging modalities and are reported as a singlegroup. Angiography was described in 24 patients. It wasnormal in 15 (63%) patients, showed an avascular mass inseven (29%) and suggested an arteriovenous malformationin two (8%) (Rhodes and Davis, 1978; Kasantikul andBrown, 1981).

The commonest finding on CT scan was a calcified,enhancing lesion with surrounding low density, occurring in21 (55%) of 38 patients.

MRI was reported in 25 cases. Low or mixed central signalon T1- and T2-weighted images and surrounding high signal

on T2-weighted sequences were found in 21 (84%) of 25patients. Gadolinium enhancement occurred in six of sevenreported patients. No MRI abnormality was produceddirectly by MA in four cases (16%), viz. one patient eachwith meningioma (Blumenthalet al., 1993), temporalencephalocoel (Whitinget al., 1990), low-grade tumour(oligodendroglioma) (Lopezet al., 1996) and normal MRI(Prayson, 1995). Although the white matter appeared to beinvolved by MA in eight (32%) cases, histopathology showedonly secondary changes, e.g. gliosis or haemorrhage into thewhite matter. MA resembled various diseases on MRI,including meningioma (Partingtonet al., 1991; Fujimotoet al., 1993; Prayson, 1995), acute haemorrhage (Aueret al.,1982; Goateset al., 1991) (2 cases), calcified arteriovenousmalformation (1 case) and encephalomalacia (6 cases).Review of our MRIs suggested MA in only two patients(patients 1 and 4), both with partly calcified, gyriformcortical lesions.

Associated abnormalitiesCranial abnormalities occurred in two reported cases, onewith a temporal lobe encephalocoel (Whitinget al., 1990)and one with orbital ‘erosion’ (Louwet al., 1990). MAwas associated with adjacent meningioma in four cases(Kasantikul and Brown, 1981; Louwet al., 1990; Wilsonet al., 1991; Blumenthalet al., 1993). A definitive vascularmalformation adjacent to the area of MA occurred in threereported cases (Kasantikul and Brown, 1981; Halperet al.,1986; Sakakiet al., 1987). MA was diagnosed incidentallyin proximity to an oligodendroglioma in one case (Lopezet al., 1996).

Seizure outcome following surgerySeizure-free rates in our series and in the literature were 43and 68%, respectively. Improvement in seizures occurred in30% of patients in our series and in the literature. Seizuresdid not improve in two (28%) of our patients, compared withonly one (5%) in the literature. Some of our unimprovedpatients had temporal (limbic and neocortical) and opercularseizures. One of our seizure free patients (patient 3) requiredthree operations. Seizures stopped only after resectingsclerosed amygdala and hippocampus. A similar proportionof patients in our series and in the literature continued torequire antiepileptic drugs (71 and 79%, respectively). Medianfollow-up was longer in our patients (6 years) than in theliterature (2 years). MA was partly removed in two of ourpatients. One is seizure-free (patient 1) while refractoryseizures persist in the other (patient 2). Information oncompleteness of lesion removal and seizure outcome wasavailable for 30 patients in the literature. Fifteen of 23 (65%)and four of seven (57%) patients who underwent completeor partial resections became seizure-free, respectively. Theseproportions were not significantly different (odds ratio51.4; 95% confidence interval, 0.25–7.9).

Dow




Age, MA location and size, duration of illness and interictalEEG findings did not correlate with seizure outcome.Therefore, our data suggest that seizure outcome after surgeryis variable and that resection of the lesion and of epileptogeniccortex may be required.

DiscussionMA is diagnosed with a frequency of approximately oneevery 1.5 years at our centre, where 40–50 patients undergoepilepsy surgery each year. With few exceptions, MA involvescortical grey matter only, although imaging studies, includingMRI, may give the impression of white matter involvement.The literature suggests higher occurrence in males and in theright hemisphere. The commonest presentation is progressivedifficulty in controlling partial seizures.

MA has histological features of meningiomas andangiomas. Solitary MA lesions measuring up to 5 cm areaccompanied by meningeal thickening and calcification,producing tan-yellow, gritty tissue. The histological spectrumcan be broadly classified into predominantly cellular andpredominantly vascular lesions. Although each lesion isunique, increased cortical vascularity and perivascular cellularproliferation are constant findings. The main histopathologicalfeatures are leptomeningeal meningothelial proliferation andmeningovascular proliferation. The literature includes a fewcases in which the second feature was absent. Except forbone formation, our seven cases demonstrate the full rangeof recognized histological morphologies, i.e. calcification,gliosis, perivascular connective tissue proliferation, dysplasticneurons, white matter cysts and large-vessel hyalinization.In many cases, proliferating perivascular cells infiltrate thecortex in association with marked cellularity and reactivegliosis. Unless the pathologist is familiar with the histologicalfeatures of MA, these features may lead to the erroneousdiagnosis of malignancy, as illustrated by our case 3 andother cases in the literature (Husonet al., 1988). Nuclearpseudoinclusions, typical of meningiomas, are not a majorfeature of MA. Neurofibrillary tangles, unassociated withamyloid plaques or granulovacuolar degeneration, may be areactive phenomenon rather than an intrinsic MA component.In the past, histopathological pleomorphism has createddiagnostic difficulties. Original diagnoses other than MAwere given for seven (14%) and two (15%) cases withoutand with NF, respectively. Pathological differential diagnosesinclude malignant meningioma and vascular lesions such asSturge-Weber syndrome and arteriovenous malformation.

Immunohistochemistry has limited diagnostic value, asstaining patterns vary among MA cases. Some immuno-staining was done in 24 published cases, although often notin a panel. Results of our immunostaining panel parallelthose in the literature, i.e. only vimentin, an intermediatefilament protein of fibroblasts and mesenchymal cells, isconsistently positive. Epithelial membrane antigen, a markerfor arachnoid cap cells, and cam 5.2, co-expressed in 10%of meningiomas, are often negative in MA. GFAP, S-100

Table 4 Immunohistochemistry of meningioangiomatosis

Immunohistochemistry No. cases No. cases Percentagepositive done positive

Vimentin 11 11 100EMA 2 8 25S-100 2* 11 18Leu-7 1 4 25GFAP 2* 10 20Lectin 3* 4 75Cam 5.2 1 2 50Actin 1* 2 50Desmin 0 3 0Factor 8 0 4 0Keratin 0 3 0MIB1 2** 2 100K1-67 0 1 0NSE 0 2 0α1-Antitrypsin 0 2 0Myosin 0 1 0Not stated or not done

With neurofibromatosis 13 – 100Without neurofibromatosis 24 – 56

Literature reports of immunostaining on 24 patients without NF.Variability of results is evident. No reports are available forpatients with NF. *Positive in blood vessels and glial cells but notin spindle cells; **weakly positive.

and neuronal specific enolase show inconsistent staining andfactor VIII was not expressed by the lesional cells (Table 4).These findings do not support a meningothelial origin for theperivascular cells. Instead, it is possible that a pluripotentcell line undergoes differentiation towards various cell types.

Results of electron microscopy are sparse and inconsistentin the literature. Some cases suggest a meningothelialderivation, i.e. interdigitating cell membranes, cell junctionsand intermediate filaments, while others lack such features(Halper et al., 1986; Kunishioet al., 1987; Goateset al.,1991; Kim et al., 1993; Kolliaset al., 1994; Gomez-Ansonet al., 1995). Atypical neuronal inclusions resembling Pickbodies have been recently described in sporadic MA(Mokhtari et al., 1998).

The pathogenesis of MA remains unclear. Proposedhypotheses (Goateset al., 1991; Kolliaset al., 1994; Prayson,1995) suggest that: (i) MA is a hamartoma that undergoesdegenerative changes, and association with NF in some casessupports this theory; (ii) MA results from invasion of braintissue by a leptomeningeal meningioma, though not all caseshave a meningeal component and features of malignancy aretypically absent; (iii) a cortical vascular malformation inducesperivascular meningothelial proliferation of cells from vesselwalls or from pluripotent arachnoid cap cells in Virchow–Robin spaces. Leptomeninges and arachnoid cap cellsnormally surround blood vessels as they penetrate the cortex.Conceivably, chronic leptomeningeal stimulation by theunderlying cortical lesion could result in MA histo-pathological changes.

Presurgical diagnosis remains difficult because diagnostictools lack specificity. For example, MA does not have a

Dow



724 S. Wiebeet al.

typical CT or MRI appearance. Experienced neuroradiologistsat our centre suspected MA from the MRI only in two ofthe seven cases (cases 1 and 4), based on gyriform corticalpatterns with calcification or old haemorrhage. MRIerroneously suggested low-grade tumour, vascular malforma-tions and cystic encephalomalacia in the other five cases. CTand MRI enhancement occurs with sufficient frequency toblur the distinction between MA and other lesions.Furthermore, the electrophysiology of MA is complex.Interictally, it encompasses circumscribed backgroundslowing and epileptogenicity, multifocal extralesional spikesand sharp waves, and generalized spike-waves withoutdefinitive secondary bilateral synchrony. Ictal origin may becircumscribed to the region of MA or involve broader areas.

Our ECoG recordings showed intrinsic epileptogenicity ofsome MA lesions, a previously unrecognized phenomenon.In addition, MA exhibits a range of electrophysiologicalabnormalities. At one end of the spectrum, they resemblefocal, non-dysplastic lesions whose epileptogenicity isproduced by adjacent cortex. At the other end, theepileptogenicity of MA is similar to that of cortical dysplasiasin which the lesion itself produces spikes, in addition tomultifocal, independent epileptiform activity. The variableoccurrence of epilepsy in MA remains unexplained, as is thecase with other cortical lesions. Although we providedefinitive evidence of epileptogenicity of sporadic MA lesionsin some of our patients, other factors (e.g. genetic andbiochemical) must be at play in determining the expressionof epilepsy in MA. Genetic differences exist between sporadicMA and MA with NF-2 (Stemmer-Rachamimovet al.,1997). This suggests that genetic make up may play arole in determining the dissimilar clinical expression ofhistopathologically identical lesions.

The concept of prompt seizure control following partial orcomplete MA resection (Kasantikul and Brown, 1981; Halperet al., 1986; Sakakiet al., 1987; Kuznieckyet al., 1988; Liuet al., 1989; Ogilvyet al., 1989; Partingtonet al., 1991; Tienet al., 1992; Gomez-Ansonet al., 1995; Prayson, 1995)requires revision. Seizures persist in a significant proportionof patients despite removal of the lesion and apparentconfinement of epileptogenicity to one focus. In our series,43% of patients became seizure-free compared with 68% inthe literature. Systematic outcome assessment and longerfollow-up in our cases may account for this discrepancy.Furthermore, antiepileptic drug requirements continue in.70% of patients, several years after MA removal. Thiscorresponds with our findings of complex epileptogenicity,even with solitary MA lesions. No single factor emergedas determinant of seizure outcome following resection ofMA lesions.

Cranial abnormalities occurred in two reported patientswithout NF. In contrast to the osseous malformations seenin NF (sphenoid wing and posterior orbit agenesis and long-bone pseudoarthrosis), all abnormalities in MA overlay thelesions. Although MA and meningiomas may co-exist, theirrelationship remains unclear. Some suggest that meningiomas

may arise from MA (Wilsonet al., 1991) while others(Blumenthalet al., 1993; Gomez-Ansonet al., 1995) questionwhether cases of ‘sclerosing meningioma’ represent MA(Davidson and Hope, 1989). Other similarities between MAand meningiomas include an association with NF, multiplicityof lesions, and multifaceted histopathological expression.

Non-sporadic cases are associated with type 2 NF(Stemmer-Rachamimovet al., 1997). Sporadic MA is fourtimes more common than MA with NF. All symptomaticcases occur sporadically and do not exhibit NF-2 genemutations. Therefore, they probably do not represent formesfrustes of NF-2 (Stemmer-Rachamimovet al., 1997). Ouranalysis supports the preliminary notion that MA associatedwith NF differs from sporadic MA in that, in the former,lesions tend to be multiple and extracortical and are rarelyassociated with seizures.

ConclusionsThe wide spectrum of EEG and imaging expressions of MAoften impedes the clinical diagnosis. Although histopatho-logical diversity is common, MA can be classified intocases with predominantly cellular features and those withpredominantly vascular features. Little diagnostic gainaccrues from immunostaining because of its variability. Ourdata do not support a meningeal origin of MA, but suggestthat pluripotent cells may differentiate into various cell typesfound in MA. Sporadic MA commonly presents as refractorylocalization-related epilepsy, but other clinical presentationsare recognized. Although MA occurs infrequently, it isimportant to establish the correct diagnosis. For example, itshistologically benign and non-recurrent nature is prognostic-ally reassuring. On the other hand, extralesional epilepto-genesis and variable seizure outcome must be consideredwhen planning surgical treatment. Finally, the association ofsymptomatic MA with NF is extremely unusual and the twoare probably genetically distinct.

AcknowledgementsWe wish to thank Drs W. T. Blume, R. S. McLachlan,J. P. Girvin, A. Parrent and R. Sahjpaul for giving us accessto their patients, Dr W. T. Blume for comments on an earliermanuscript, Dr Alberto Dı´az for assistance with the literaturereview and Mrs Dorota Ociepa for preparing the electro-physiological data. We are especially grateful to the patientsfor their co-operation and timely reply to our enquiries. Partof this work was presented in abstract form at the CanadianCongress of Neurological Sciences in June, 1996.

ReferencesAizpuru RN, Quencer RM, Norenberg M, Altman N,Smirniotopoulos J. Meningioangiomatosis: a clinical, radiologic,and histopathologic correlation. Radiology 1991; 179: 819–21.

Dow




Auer RN, Budny J, Drake CG, Ball MJ. Frontal lobe perivascularschwannoma. Case report. J Neurosurg 1982; 56: 154–7.

Bassoe P, Nuzum F. Report of a case of central and peripheralneurofibromatosis. J Nerv Ment Dis 1915; 42: 785–96.

Beck E. Ein Beitrag zur Kenntnis der Neurofibromatose(Recklinghausensche Krankheit). Ztschr f d ges Neurol u Psychiat1938; 162: 426–42.

Beck E. Zwei Falle von Neurofibromatose mit Befallensein desZentralnervensystems. Ztchr f d Ges Neurol u Psychiat 1939;164: 748–89

Blumenthal D, Berho M, Bloomfield SS, Schochet SS Jr, KaufmanHH. Childhood meningioma associated with meningioangiomatotis.J Neurosurg 1993; 78: 287–9.

Davidson GS, Hope JK. Meningeal tumors of childhood. Cancer1989; 63: 1205–10.

Feigin I. The nerve sheath tumor, solitary and in vonRecklinghausen’s disease; a unitary mesenchymal concept. ActaNeuropathol (Berl) 1971; 17: 188–200.

Foerster O, Gagel O. Ein Fall von Recklinghausenscher Krankheitmit funf nebeneinander bestehenden verschiedenartigen Tumor-bildungen. Ztschr f d ges Neurol u Psychiat 1932; 138: 339–60.

Fujimoto K, Nikaidoh Y, Yuasa T, Nagata K, Ida Y, Fujioka M,et al. Meningioangiomatosis not associated with vonRecklinghausen’s disease—case report. Neurol Med Chir (Tokyo)1993; 33: 651–5.

Garen PD, Powers JM, King JS, Perot PL Jr. Intracranial fibro-osseous lesion. J Neurosurg 1989; 70: 475–7.

Goates JJ, Dickson DW, Horoupian DS. Meningioangiomatosis:an immunocytochemical study. Acta Neuropathol (Berl) 1991;82: 527–32.

Gomez-Anson B, Munoz A, Blasco A, Madero S, Esparza J,Cordobes F, et al. Meningioangiomatosis: advanced imaging andpathological study of two cases. Neuroradiology 1995; 37: 120–3.

Halper J, Scheithauer BW, Okazaki H, Laws ER Jr. Meningio-angiomatosis: a report of six cases with special reference to theoccurrence of neurofibrillary tangles. J Neuropathol Exp Neurol1986; 45: 426–46.

Harada K, Inagawa T, Nagasako R. A case ofmeningioangiomatosis without von Recklinghausen’s disease.Report of a case and review of 13 cases. [Review]. Childs NervSyst 1994; 10: 126–30.

Hozay J. Une angioneuromatose meningo-encephalique diffuse.Rev Neurol (Paris) 1953; 89: 222–36.

Huson SM, Harper PS, Compston DA. Von Recklinghausenneurofibromatosis. A clinical and population study in south-eastWales. Brain 1988; 111: 1355–81.

Johnson PC, Nielsen SL. Localized neurofibrillary degenerationin vascular malformations [Abstract]. J Neuropathol Exp Neurol1976; 35: 300.

Jun C, Burdick B. An unusual fibro-osseous lesion of the brain.J Neurosurg 1984; 60: 1308–11.

Kasantikul V, Brown WJ. Meningioangiomatosis in the absenceof von Recklinghausen’s disease. Surg Neurol 1981; 15: 71–75.

Kim YW, Choi WS, Lee J, Yang MH. Meningioangiomatosis—a case report. J Korean Med Sci 1993; 8: 308–11.

Kollias SS, Crone KR, Ball WS Jr, Prenger EC, Ballard ET.Meningioangiomatosis of the brain stem. Case report. J Neurosurg1994; 80: 732–5.

Kunishio K, Yamamoto Y, Sunami N, Satoh T, Asari S, YoshinoT, et al. Histopathologic investigation of a case of meningio-angiomatosis not associated with von Recklinghausen’s disease.Surg Neurol 1987; 27: 575–9.

Kuzniecky R, Melanson D, Robitaille Y, Olivier A. Magneticresonance imaging of meningio-angiomatosis. [Review]. Can JNeurol Sci 1988; 15: 161–4.

Liu SS, Johnson PC, Sonntag VK. Meningioangiomatosis: a casereport. Surg Neurol 1989; 31: 376–80.

Lopez JI, Ereno C, Oleaga L, Areitio E. Meningioangiomatosisand oligodendroglioma in a 15-year-old boy. [Review]. ArchPathol Lab Med 1996; 120: 587–90.

Louw D, Sutherland G, Halliday W, Kaufmann J. Meningiomasmimicking cerebral schwannoma. J Neurosurg 1990; 73: 715–9.

Matias-Guiu X, Molet J, Ferrer I, Prat J. Meningio-angiomatosis:a case report. Br J Neurosurg 1988; 2: 97–100.

Mokhtari K, Uchihara T, Clemenceau S, Baulac M, DuyckaertsC, Hauw JJ. Atypical neuronal inclusion bodies in meningio-angiomatosis. Acta Neuropathol (Berl) 1998; 96: 91–6.

Ogilvy CS, Chapman PH, Gray M, de la Monte SM. Meningio-angiomatosis in a patient without von Recklinghausen’s disease.J Neurosurg 1989; 70: 483–5.

Oka Y, Sakaki S, Yamashita M, Nakagawa K, Matsuoka K,Matsui H. A case of meningioangiomatosis in an infant. [Review].[Japanese]. No Shinkei Geka 1991; 19: 761–5.

Partington CR, Graves VB, Hegstrand LR. Meningioangiomatosis.[Review]. ANJR Am J Neuroradiol 1991; 12: 549–52.

Paulus W, Peiffer J, Roggendorf W, Schuppan D. Meningio-angiomatosis. [Review]. Pathol Res Pract 1989; 184: 446–54.

Prayson RA. Meningioangiomatosis. A clinicopathologic studyincluding MIB1 immunoreactivity. [Review]. Arch Pathol LabMed 1995; 119: 1061–4.

Rhodes RH, Davis RL. An unusual fibro-osseous component inintracranial lesions. Hum Pathol 1978; 9: 309–19.

Rubinstein LJ. Tumeurs et hamartomes dans la neurofibromatosecentrale. In: Michaux L, Feld M, editors. Les phakomatosescerebrales. Paris: S.P.E.I.; 1963. p. 426–51.

Sakaki S, Nakagawa K, Nakamura K, Takeda S. Meningio-angiomatosis not associated with von Recklinghausen’s disease.Neurosurgery 1987; 20: 797–801.

Stemmer-Rachamimov AO, Horgan MA, Taratuto AL, MunozDG, Smith TW, Frosch MP, et al. Meningioangiomatosis isassociated with neurofibromatosis 2 but not with somatic alterationsof the NF2 gene. [Review]. J Neuropathol Exp Neurol 1997;56: 485–9.

Dow



726 S. Wiebeet al.

Tien RD, Osumi A, Oakes JW, Madden JF, Burger PC.Meningioangiomatosis: CT and MR findings. J Comput AssistTomogr 1992; 16: 361–5.

Whiting DM, Awad IA, Miles J, Chou SS, Luders H. Intractablecomplex partial seizures associated with occult temporal lobeencephalocele and meningioangiomatosis: a case report. [Review].Surg Neurol 1990; 34: 318–22.

Willson N, Kaufman MA, Bodansky SM. An unusual intracerebralconnective tissue mass. J Neuropathol Exp Neurol 1977; 36:373–8.

Wilson D, Dempsey RJ, Clark DB. Meningioma developing fromunderlying meningioangiomatosis [Abstract]. J Neuropathol ExpNeurol 1991; 50: 371.

Worster-Drought C, Dickson WEC, McMenemey WH. Multiplemeningeal and perineural tumours with analogous changes in theglia and ependyma (neurofibroblastomatosis). Brain 1937; 60:85–117.

Received August 26, 1998. Revised November 3, 1998.Accepted November 23, 1998

Dow



Meningioangiomatosis - Oxford Academic

Documents

Transcript of Meningioangiomatosis - Oxford Academic