De novo formation of an aneurysm in a case of unusual intracranial fibromuscular dysplasia

Clinical Neurology and Neurosurgery 102 (2000) 259 – 264 www.elsevier.com/locate/clineuro

Case report

De novo formation of an aneurysm in a case of unusual intracranial fibromuscular dysplasia Makoto Nakamura a,*, Steffen K. Rosahl a, Peter Vorkapic a, Christine Fo¨rster c, Madjid Samii a,b a

Department of Neurosurgery, Nordstadt Hospital, Haltenhoffstrasse 41, 30167 Hanno6er, Germany b Department of Neurosurgery, Medical School, Hanno6er, Germany c Institute of Pathology, Nordstadt Hospital, Hanno6er, Germany Received 15 March 2000; received in revised form 29 September 2000; accepted 5 October 2000

Abstract Intracranial fibromuscular dysplasia (FMD) is a vascular disease of unknown origin occurring predominantly in young women. The internal carotid artery is most often involved, but other cerebral arteries may also be affected. We report the case of a young woman presenting with an unusual angiographic appearance of intracranial FMD of the internal carotid artery (ICA) that could not be categorized into any type of the Osborn–Anderson classification. During follow up the patient presented with an intracerebral and subarachnoid hemorrhage. Repeated angiography revealed multiple aneurysms in the pathologic segment of the vessel. The patient underwent surgical treatment with clipping of the aneurysms, wrapping of the pathologic segment of the ICA and biopsy of the superficial temporal artery. Histopathological sections revealed FMD of the intimal type. a1-antitrypsin blood levels were normal. Cases of intracranial FMD previously reported in the literature are reviewed and various aspects of this rare disease are discussed. © 2000 Elsevier Science B.V. All rights reserved. Keywords: Fibromuscular dysplasia; Aneurysm; Internal carotid artery

1. Introduction Fibromuscular dysplasia (FMD) is a multifocal vascular disease of unknown etiology. It is most commonly affecting the aortic branch arteries, especially the renal arteries. The incidence of FMD ranges from 0.5 to 1.5% in autopsy and angiographic series [1 – 4]. Cerebral FMD most frequently involves the ICA at the level of the second vertebra [5]. Intracranial FMD is rare and often located in the carotid canal and cavernous part of the ICA [6,7,5,8–18]. Cerebral FMD has been reported to be associated with intracranial aneurysms in up to 50% of the cases in larger series [19,2 – 4]. We report about an unusual case of intracranial FMD of the internal carotid artery with angiographic * Corresponding author. Tel.: +49-511-9701535; fax: + 49-5119701828.

documentation of a de novo formation of an aneurysm at the C2-segment of the vessel. To the best of our knowledge this is the first case to be reported in this setting.

2. Case report A 23-year-old woman presented with an episode of headache, blurred vision and diplopia 4 years ago. In the initial CT scan multiple aneurysms at the carotid siphon, the dilated medial cerebral artery and anterior and posterior communicating arteries on the right side were suspected. MRI, however, revealed an ectasis of the right internal carotid artery proximal to the circle of Willis continuing into the middle cerebral artery. At that time, intracerebral or subarachnoid hemorrhage could be ruled out.

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Fig. 1. Angiogram of the right internal carotid artery with AP (A, B) and lateral (C) projections. The C2-segment is dilated and elongated. No aneurysms were seen at that time but there is a slight narrowing of the M1 segment of the right middle cerebral artery.

For further diagnostic work-up, an angiography was performed. On admission, the patient was asymptomatic and the neurological examination was unremarkable. Interestingly, angiography did not reveal any aneurysm but an elongated and dilated right internal carotid artery with slight narrowing of the M1 segment of the right middle cerebral artery (MCA) (Fig. 1A–C). The patient was followed up in our outpatient clinic.

Three years later she inquired about risks of intracranial hemorrhage during pregnancy and delivery. As she had not experienced any recurrent symptoms, we saw no reason to dissuade her from pregnancy which subsequently took an uneventful course. However, a few months later she presented with sudden onset of headache. She reportedly took a considerable amount of aspirin but the headache persisted for several days before she consulted a general practitioner who initiated admission to our hospital. The past medical history of the patient did not reveal any illnesses except for an operation at the left ellbow, where a calcified artery was surgically treated. On admission the patient was lethargic, although arousable and generally oriented. The physical examination demonstrated a slight mydriasis with delayed light reflex on the right side. A central left facial palsy was noticed and a slight leftsided hemiparesis were prominent in the neurological exam. There were no sensory deficits. Tendon reflexes were more brisk on the right side of the upper extremities. Computed tomography revealed a large intracerebral and subarachnoid hemorrhage extending from the fronto-basal aspect into the frontal lobe on the right side. There was no intraventricular bleeding, but a slight enlargement of the ventricles was noted. The right carotid artery was partially calcified (Fig. 2A–C). Doppler-ultrasonography demonstrated high flow velocity in the right middle cerebral artery. Turbulent flow was seen in the right carotid artery at the level of the circle of Willis. The angiogram disclosed multiple aneurysms distributed along the C2-segment of the elongated right carotid artery with a formation of one de novo aneurysm (arrows, Fig. 3A–D). The right M1 segment now showed marked narrowing. Since FMD was suspected, the a1-antitrypsin blood level was determined, but found to be within normal limits (113 mg/dl, normal range: 90–200 mg/dl).

Fig. 2. Axial computed tomography showing a large intracerebral hemorrhage in the right frontal lobe and subarachnoid blood around the right internal carotid artery with interhemispheric extension (A, B, C). The right carotid artery is partially calcified.

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the right MCA. Yellowish, xanthochromic discoloration was noted on the right optic nerve and the right frontobasal cortex. After mobilising the fusiform loops of the ICA, which were inbedded in the right optic nerve and optic tract, the first aneurysm was seen. This aneurysm was oriented cranially to the frontal lobe located just prior to the origin of the very hypoplastic A1 segment of the right anterior cerebral artery. This aneurysm was clipped with a straight Zeppelin-clip. The second aneurysm, which lies just adjacent to the first one, is clipped with a curved Sugita-Clip. Finally, the whole dilated segment of the right internal carotid artery was wrapped with Gortex and a small slit-like incision was left to allow passage for the anterior choroidal artery. The Gortex wrap was fixed with an additional clip. A short segment of the superficial temporal artery was also excised for further histological examination. It showed marked dysplasia and thickening of the intima suggesting FMD of intimal type (Fig. 5). Postoperatively, the left-sided hemiparesis continued to improve. Three months after surgery an angiogram was performed, showing an elongated right carotid artery but no new formation of aneurysms (Fig. 4A–D). All neurological deficits had resolved by that time.

3. Discussion

Fig. 3. Angiogram of the right internal carotid artery with AP (A, B) and lateral (C, D) projections showing formation of a new aneurysm along the dilated and elongated C2-segment (arrows). More medial on AP view (A, B) a second aneurysm is suspected, but due to the different projection compared with Fig. 1 (A, B) a de novo formation cannot be proven.

Via a right-sided, frontolateral craniotomy, the right sylvian fissure was opened from lateral to medial and a fusiform dilation of the right internal carotid artery (ICA) was seen, which was extending to the origin of

Manifestation of FMD in cerebral vessels has been described previously, most frequently involving the ICA at the level of the second vertebra [5]. Intracranial FMD is often located in the carotid canal and the cavernous part of the ICA but other cerebral arteries may also be involved [5,14,17]. Histological criteria of FMD were originally introduced by Harrison and McCormick in the renal arteries and later modified by Stanley et al. [20]. The histologic patterns appear to be the same in all affected vessels. The most common medial type consists of areas of concentric rings of fibrous proliferation or smooth-muscle hyperplasia causing thickening at the tunica media and disruption of the smooth muscle layer. This histologic pattern results in the angiographic ‘string of beads’ appearance, which is seen in 60–80% of the cases [14]. Dysplasia of intimal or adventitial layers are characteristic of other rare forms of FMD. The disruption of vessel layers may lead to areas of marked mural thinning and aneurysmal dilatation. The reported incidence of intracranial aneurysms in association with FMD varies from 20 to 50%. The etiology of FMD is still unknown. A multifactorial origin with predisposing hereditary factors accompanied by exogenous stimuli are discussed [2,3].

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Cerebral FMD is most often diagnosed by angiography in patients being evaluated for neurological symptoms. Subarachnoid or intracerebral hemorrhage occurs

Fig. 4. Angiogram of the right internal carotid artery with AP (A, B) and lateral (C, D) projections showing status post successful clipping of two aneurysms and wrapping of the C2-segment. There are no new aneurysms. Although a slit-like incision was made in the gortex-wrap to allow passage of the right anterior choroidal artery, this artery does not appear on this postoperative study.

in up to 57% of reported cases [1–3,14,4]. According to the angiographic appearance FMD has been categorized into three separate types by Osborn and Anderson [14]. The most common angiographic type is characterized by so-called ‘string of beads’, showing patterns of multiple concentric luminal narrowing alternating with normal or dilated areas. It was found in more than 80% of reported cases in the literature [3,14,4]. The histologic type usually associated with this angiographic appearance is fibroplasia of the media. The second type with focal tubular stenosis is less common and has been observed in  7% of reported cases [14]. It may be associated with any histologic type of FMD. Type 3, classified as atypical FMD, is rare and affects only one wall of the involved segment with an outpouching of the vessel wall. To confirm the diagnosis of FMD, surgical inspection and histopathologic examination are considered to be essential, but intracranial FMD has been histologically confirmed in only a few cases [19]. Since the disease may involve vessels of wide distribution a histologic specimen — as taken from the superficial temporal artery in our case-may reveal dysplastic abnormalities which are diagnostic for FMD [15,16,21]. In the present case the first angiography revealed an extensive diffuse dilatation of the intracranial internal carotid artery with multiple looping of the vessel. A slight narrowing of the M1 segment of the right MCA was noted but no aneurysms were seen at that time. Four years later the second angiography showed the development of at least one new aneurysm in the C2-segment of the ICA (arrows, Fig. 3A–C). A second aneurysm was suspected but due to the different projections in the AP view compared to the first angiographic study a de novo formation of that aneurysm could not be stated. Although the unusual angiographic appearance could not be classified into any known type of FMD, the development of multiple aneurysms was highly suspicious of intracranial FMD. Another case with extensive intracranial involvement of fusiform dilatations and multiple aneurysms along the internal carotid artery was reported only recently [22]. Unfortunately, no histopathologic examination was performed so that the underlying structural changes in the vessel wall remained unclear. In our case, biopsy of the superficial temporal artery revealed a marked disruption and patchy thickening of the intima. The texture of the tunica media appeared unaffected — both findings characteristic for FMD of the intimal type (Fig. 5). Other pathologic conditions with similar angiographic appearance like atherosclerosis, arteritis and posttraumatic aneurysms were excluded based on clinical history, physical examination, laboratory analysis and neuroradiologic studies. Recently, a1-antitrypsin deficiency has been implicated in the development of fibromuscular dysplasia [23]. a1-an-

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Fig. 5. Transverse section of the right superficial temporal artery. It shows marked dysplasia and thickening of the intima suggestive of intimal FMD (van Gieson stain, ×200).

titrypsin is a small glycoprotein synthesized in the liver and secreted into the bloodstream. Because of its antiproteolytic properties, it plays an important role in maintaining the structural integrity of connective tissues. It is hypothetized that a deficiency of a1-antitrypsin could result in significant degradation of connective tissue, including the arterial wall [24]. In a recent retrospective study analysing the frequency of occurence of FMD in patients with and without a1-antitrypsin deficiency, arterial FMD was found in 33.3% of patients with a1-antitrypsin deficiency in comparison with 0.3% of patient without this condition [23]. We examined the a1-antitrypsin blood level in our patient but the result was within normal limits. This finding does not exclude the presence of FMD because the etiology for this condition is still unknown and a multifactorial origine is suggested. Previous reports about cases of intracranial FMD with failure to show aneurysms in the initial angiogram exist but subsequent angiograms showed multiple aneurysm formation in many different cerebral vessels [6,19]. In our case, the aneurysms were restricted to a short segment of the ICA. The case is also original because a biopsy of the superficial temporal artery confirmed the histopathologic diagnosis of intimal FMD. Various forms of treatment have been recommended for intracranial FMD in the past, ranging from medical therapy to endovascular or surgical treatment. Transluminal dilatation procedures have recently emerged as the treatment of choice for obstructional FMD and may be performed effectively depending on the type, size, extension, and location of the pathology [25–27]. In our case a localized area of slight stenosis of the M1 segment of the right MCA could be seen next to the very unusual appearance of the ICA on the first angiography but at that time the patient did not have any neurological deficits, which could have been explained by this angiographic finding. No such treatment had to be initiated. There were no clinical signs to herald its

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complications and since patients with known FMD rarely experience further neurological deficit within 5 years after diagnosis [1], serial angiographic follow-up was felt to be too invasive. However, subarachnoid or intracerebral hemmorrhage has been estimated to occur in 13–57% of patients with cerebral FMD [1–4,14]. In our case at least one new aneurysm developed in only 4 years and aneurysms have only been detected after one of them had ruptured. Therefore, even if in many cases intracranial FMD is an incidental finding that does not require aggressive treatment and may well represent a benign condition, a yearly follow-up with non-invasive methods such as MR- or CT-based angiography may provide invaluable information about the progress of the disorder in each individual.

References [1] Corrin LS, Sandok BA, Houser OW. Cerebral ischemic events in patients with carotid artery fibromuscular dysplasia. Arch Neurol 1981;38:616 – 8. [2] Mettinger KL. Fibromuscular dysplasia and the brain: II. Current concept of the disease. Stroke 1982;13:53 – 8. [3] Mettinger KL, Ericson K. Fibromuscular dysplasia and the brain: observations on angiographic, clinical and genetic characteristics. Stroke 1982;13:46 – 52. [4] So EL, Toole JF, Dalal P, Moody DM. Cephalic fibromuscular dysplasia in 32 patients: clinical findings and radiologic features. Arch Neurol 1981;38:619 – 22. [5] Frens DB, Petajan JH, Anderson R, Deblanc HJ, Jr. Fibromuscular dysplasia of the posterior cerebral artery: report of a case and review of the literature. Stroke 1974;5:161 – 6. [6] Abdul Rahman AM, Abu-Salih HS, Brun A, Kin H, Ljunggren B, Mizukami M, Moquist-Olsson I, Sahlin Ch, Svendgaard NA, Thulin CA. Fibromuscular dysplasia of the cervicocephalic arteries. Surg Neurol 1978;9:217 – 22. [7] Elias WS. Intracranial fibromuscular hyperplasia. J Am Med Assoc 1971;48:254. [8] Hartman JD, Young I, Bank AA, Rosenblatt SA. Fibromuscular hyperplasia of internal carotid arteries. Stroke in a young adult complicated by oral contraceptives. Arch Neurol 1971;25:295 – 301. [9] Hill LD, Antonius JI. Arterial dysplasia. An important surgical lesion. Arch Surg 1965;90:585 – 95. [10] Hirsch CS, Roessmann V. Arterial dysplasia with ruptured basilar artery aneurysm: report of a case. Hum Pathol 1975;6:749– 58. [11] Houser OW, Baker HL, Jr. Fibromuscular dysplasia and other uncommon diseases of the cervical carotid artery: angiographic aspects. Am J Roentgenol 1968;104:201 – 12. [12] Huber P, Fuchs WA. Gibt es eine fibromuskula¨re hyperplasie zerebraler arterien? Fortschr Roentgenstr 1967;107:119–26. [13] Josue A, Kier EL, Ostrow O. Fibromuscular dysplasia involving intracranial vessels. J Neurosurg 1972;37:749 – 51. [14] Osborn AG, Anderson RE. Angiographic spectrum of cervical and intracranial fibromuscular dysplasia. Stroke 1977;8:617–26. [15] Pollock M, Jackson BM. Fibromuscular dysplasia of the carotid arteries. Neurology 1971;21:1226 – 30. [16] Rinaldi I, Harris WO, Jr, Kopp JE, Legier J. Intracranial fibromuscular dysplasia: report of two cases, one with autopsy verification. Stroke 1976;7:511 – 6.

264

M. Nakamura et al. / Clinical Neurology and Neurosurgery 102 (2000) 259–264

[17] Saygi S, Bolay H, Tekkok IH, Cila A, Zileli T. Fibromuscular dysplasia of the basilar artery: a case with brain stem stroke. Angiology 1991;41:658–61. [18] Wylie EJ, Binkley FM, Palubinskas AJ. Extrarenal fibromuscular hyperplasia. Am J Surg 1966;112:149. [19] Kalyanaraman UP, Elwood PW. Fibromuscular dysplasia of intracranial arteries causing multiple intracranial aneurysms. Hum Pathol 1980;11:481–4. [20] Stanley JC, Gewertz BL, Bove EL, Sottiurai V, Fry WJ. Arterial fibrodysplasia: histopathologic character and current etiologic concepts. Arch Surg 1975;110:561–6. [21] Anderson PE. Fibromuscular hyperplasia of the carotid arteries. Acta Radiol 1970;10:90–6. [22] Belen D, Bolay H, Firat M, Akpinar G, Bertan V. Unusual appearance of intracranial fibromuscular dysplasia. Angiology 1996;47:627 – 32.

.

[23] Schievink WI, Bjo¨rsson J, Parisi JE, Prakash UBS. Arterial fibromuscular dysplasia associated with severe a1-antitrypsin deficiency. Mayo Clin Proc 1994;69:1040 – 3. [24] Schievink WI, Puumala MR, Meyer FB, Raffel C, Katzmann JA, Parisi JE. Giant intracranial aneurysm and fibromuscular dysplasia in an adolescent with a1-antitrypsin deficiency. J Neurosurg 1996;85:503 – 6. [25] Hasso AN, Bird CR, Zinke DE, Thompson JR. Fibromuscular dysplasia of the internal carotid artery: percutaneous transluminal angioplasty. Am J Roentgenol 1981;136:955 – 60. [26] Starr DS, Lawrie GM, Morris GC. Fibromuscular disease of carotid arteries: long-term results of graduated internal dilatation. Stroke 1981;12:196 – 9. [27] Wilms GE, Smits J, Baert AL, De Wolf L. Percutaneous transluminal angioplasty in fibromuscular dysplasia of the internal carotid artery: 1 year clinical and morphological follow-up. Cardiovasc Intervent Radiol 1985;8:20 – 3.