FIBROMUSCULAR DYSPLASIA AND MULTIPLE DISSECTING ANEURYSMS/Wfe et al.
arterial and aortic beds, do not appear related to accumulation of apoproteins or their respective lipoproteins.
Acknowledgment
The author is indebted to the members of the Pathology Service, the
Methodist Hospital for assistance in procuring arterial specimens, to Dr.
Richard L. Jackson for providing purified apoproteins and their respective
antibodies, and to Carol L. Heideman for providing excellent technical
assistance.

References
1. Kannel WB, Dawber TR, Friedman GD: Risk factors in coronary heart
disease: An evaluation of several serum lipids as predictors of coronary
heart disease. The Framingham study. Ann Intern Med 61: 888-899,
1964
2. Kannel WB, Gordon T, Dawber TR: Role of lipids in the development of
brain infarction: The Framingham study. Stroke 5: 679-685, 1974
3. Goldstein JL, Hazzard WR, Schrodt HG, et al: Hyperlipidemia in coronary heart disease. 1. Lipid levels in 500 survivors of myocardial infarction. J Clin Invest 52: 1533-1577, 1973
4. Mathew NT, Davis D, Meyer JS, et al: Hyperlipoproteinemia as a risk
factor in occlusive cerebral vascular disease (stroke). JAMA 232:
262-266, 1975

393

5. Adams CWM: Lipids, lipoproteins and atherosclerotic lesions. Proc Soc
Med 64: 902-905, 1971
6. Hoff HF, Jackson RL, Mao JT, et al: Localization of low density
lipoproteins in arterial lesions from normolipemics employing a purified
fluorescent-labeled antibody. Biochim Biophys Acta 351: 407-415, 1974
7. Hoff HF, Lie JT, Titus JL, et al: Localization of apo-low density
lipoproteins (apo LDL) in atherosclerotic lesions of human normo- and
hyperlipemics. Arch Path 99: 253-258, 1975
8. Hoff HF, Heideman CL, Gaubatz JW- Apo low density lipoprotein
localization. Intracranial and extracranial atherosclerotic lesions from
human normolipoproteinemics and hyperlipoproteinemics. Arch Neurol
33: 600-605, 1975
9. Hoff HF, Heideman CL, Jackson RL, et al: The localization patterns of
plasma apolipoproteins in human atherosclerotic lesions. Circulation
Research 37: 72-79, 1975
10. Hoff HF, Heideman CL, Noon GP, et al: Localization of apolipoproteins
in human carotid artery plaques. Stroke 6: 531-534, 1975
11. Morrisett JD, Jackson RL, Gotto AM: Lipoproteins: Structure and function. Annu Rev Biochem 44: 183-207, 1975
12. Walton KW, Williamson N: Histological and immunofluoresccnt studies
on the human atheromatous plaque. J Atheroscler Res 8: 599-624, 1968
13. Walton KW: Identification of lipoproteins involved in human atherosclerosis. In Schettler G, Weizel A (eds): Atherosclerosis III. Proceedings
of the Third International Symposium on Atherosclerosis. West Berlin,
1973. New York, Springer-Verlag, p 93, 1974

Fibromuscular Dysplasia and Multiple Dissecting
Aneurysms of Intracranial Arteries
A Further Cause of Moyamoya Syndrome
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P. PlLZ, M.D.,* AND H. J. HARTJES, M.D.f

SUMMARY A 16-year-old boy, who had sudden left-sided hemiplegia, died two weeks following onset of symptoms. A right carotid
angiogram showed stenosis at the termination of the internal carotid
artery. The middle cerebral artery had a beaded appearance and
some of its branches were occluded. A basal "moyamoya" syndrome

and transdural anastomoses were present. At autopsy, multiple intracranial dissecting aneurysms were found. Arteries of the body displayed fibromuscular dysplasia (FMD). The relevance of dysplastic
changes of intracranial arteries and the relationship to moyamoya
syndrome are discussed.

MANY REPORTS have been published in recent years on
fibromuscular dysplasia (FMD) and moyamoya syndrome
and they have been reviewed in the Journal de Neuroradiologie, volume 1, numbers 1 and 2, 1974. We present a
case which shows features of both these conditions and, in
addition, dissecting aneurysms of the intracranial arteries.

arm and hemianesthesia of the left side. The left plantar response was extensor and the right was flexor. He had slight
miosis and ptosis on the right side, no visual disturbances,
and normal fundi. No bruit was heard in the neck. The blood
pressure was 110/70 mm Hg, the blood cell count was normal, and the ESR was 6 mm in the first hour. The cerebrospinal fluid was clear and the pressure was 250 mm H2O.
The cell count was 1 cell per cubic millimeter, and Pandy's
test was negative. The EEG showed a marked delta focus in
the right frontoparietal region. X-rays of the skull were normal. On March 19, 1974, the right common carotid artery
was punctured during general anesthesia. The cervical part
of the internal carotid artery showed regular corrugation
(stationary waves). Stenosis was present in the supraclinoidal portion of this artery. The terminal part of the internal carotid artery and its main intracranial branches
showed multiple, repeated stenoses (beaded appearance) and
some branches were occluded. The frontopolar artery was
extremely thin.
The lenticulostriate arteries and the anterior choroidal
artery were very prominent. A flush was present in the
striate and the contour of the head of the caudate was out-

Case Report

RM, a 16-year-old boy, had had repeated attacks of middle ear infection and frontal sinusitis in recent years. The
family history was unremarkable. On March 10, 1974, after
throwing a snowball he suddenly had a severe headache and
lost consciousness. After admission to the hospital he
regained consciousness but was unable to move the left side
of his body and he still had a headache. On physical examination he was alert and correctly orientated but a little
euphoric. He laid on his left side and had no neck stiffness.
He had a left hemiparesis affecting more severely the left
'Neurological Department and t Radiological Department, Landesnervenklinik Salzburg, Ignaz-Harrer-Str. 79, Salzburg, Austria.

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VOL. 7, No. 4, JULY-AUGUST 1976

lined very well. There was early filling of the internal cerebral veins (figs. 1A and B).
Transdural anastomoses were present in two regions. The
parietal branch of the superficial temporal artery seemed to
communicate with the peripheral part of the callosomarginal artery, which filled in a retrograde fashion.
Another anastomosis was present between the middle
meningeal and fronto-opercular arteries (fig. 1C).
The isotope brain scan did not show any significant uptake. Immunoelectrophoresis and direct Coombs test were
normal. The Wassermann reaction of the blood serum was
negative. The patient was treated with rheomacrodex and
dexamethasone but his condition did not change. He died
suddenly two weeks after the onset of hemiparesis.
The postmortem examination was performed 30 hours
following death. The organs in the trunk were normal. When
the internal carotid arteries in the neck were opened, there
was slight undulation of the intimal surface. The renal
arteries were not stenosed. The brain weighed 1,470 gm. The
right cerebral hemisphere was soft in consistency and was
much larger than the left. The right cerebral convolutions
were flattened. The arteries at the base of the brain were
thinner than normal. The right anterior, middle and

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FIGURE 1 A. Right carotid angiogram: The cervical part of the internal carotid shows regular corrugation (stationary waves). The
termination of the internal carotid and the proximal part of the middle and anterior cerebral artery have a beaded appearance.
Branches of the middle cerebral artery are occluded. A moyamoyalike flush of the basal ganglia is present. The lenticulostriate arteries
are prominent.

i
FIGURE 1B. Right carotid angiogram: Stenosis of the supraclinoidal part of the internal carotid (C2) and occlusion of a main
branch of the middle cerebral artery. A basal moyamoya syndrome
and early filling of the internal cerebral veins are present.

FIGURE 1C. Right carotid angiogram: Transdural anastomoses
are present. The middle cerebral artery shows multiple stenoses.
The lenticulostriate arteries are very prominent.

FIBROMUSCULAR DYSPLASIA AND MULTIPLE DISSECTING ANEURYSMS//»;/z et al.

395

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posterior cerebral arteries had the appearance of a string of
beads, and seemed to be occluded by a thrombus. The wall
of the supraclinoidal part of the internal carotid arteries was
thickened and had a cartilaginous consistency, more marked
on the right side which was thought to be occluded. No berry
aneurysm of the intracranial arteries was found. The right
uncus herniated through the tentorium cerebelli. The brain
was cut coronally. There were swelling and softening of the
right cerebral hemisphere: the frontal, temporal and parietal regions were affected. The midline structures were displaced 2 cm to the left. The head of the caudate nucleus,
parts of the internal capsule, the medial part of the lentiform body, and the lateral part of the thalamus showed an
older infarct and shrinkage, and the vessels in these regions
were prominent.
The tissue was fixed in neutral 10% formalin saline and
embedded in paraffin. The brain, myocardium, liver, spleen
and kidneys were examined and particular attention was
given to the following arteries: aorta, renal, femoral,
carotid, middle meningeal, basilar, vertebral and anterior,
middle and posterior cerebral. Sections were stained by
hematoxylin-eosin, cresyl violet, Cluver Barrera, Weigert's
elastic, Azan and Berlin Blue.
Some proliferation of vasa vasorum in the aorta was
noted. Longitudinal sections of the right internal carotid
artery in the neck showed corrugation of the wall (figs.
2A-D). In these regions either fibroelastic intimal cushions
or attenuation of the medial coat were present. There were
multiple interruptions and calcification in the internal elastic
lamina. There was marked loss in elasticfibersof the media.
Increase of metachromatic ground substance and fibro-

blasts were found between smooth muscle cells. The ground
substance contained many vacuoles. Some muscle cells
showed large, dark, distorted nuclei. Similar changes occurred in the renal and femoral arteries. In addition, the
right carotid siphon showed a stenosis which was due to
muscular hyperplasia of the medial coat (fig. 3 A). In the left
carotid siphon large intimal cushions were found (fig. 3B). A
dissecting aneurysm was present in the terminal part of the
right internal carotid artery (fig. 4). Serial sections of this
part of the artery showed multiple folds of internal elastic
lamina which were separated from the medial coat; endothelial cells lined both aspects of the elastic lamina, but no
rupture was found in the intima in the numerous sections examined from this region.
Recent dissections were present in branches of the right
anterior, middle and posterior cerebral arteries, and the
original lumen was compressed (fig. 5A). In addition, main
branches of the right anterior and middle cerebral arteries
presented older dissections which showed organization and
endothelialization of the false lumen (fig. 5B). Dissection
was discontinuous and resulted in repeated attenuations of
the lumen in longitudinal sections (fig. 6). Proliferation of
mesenchymal cells and abundant metachromatic ground
substance occurred adjacent to the external surface of the internal elastic lamina. Cellular bridges permeated the blood
in the dissecting aneurysm and sometimes these cells formed
sinusoidal channels (fig. 6). A rupture was found in the internal elastica of a main branch of the middle cerebral artery
and endothelial cells had proliferated and covered the edges
of the ruptured elastica (fig. 7A). Two lumina were present
in some of the small perforating basal arteries (fig. 7B). A

FIGURE 2A.
X90.

Normal internal carotid artery. Weigert's elastic,

FIGURE 2C. Longitudinal section of the internal carotid artery
shows corrugation of the internal surface. Weigert's elastic, X54.

FIGURE 2B. The media of the internal carotid artery of this
patient shows loss of elastic fibers. Weigert's elastic, X54.

FIGURE 2D. Internal carotid artery shows calcification of fragments of the internal elastic lamina. Hematoxylin and eosin, X390.

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VOL. 7, No. 4, JULY-AUGUST 1976

dissecting aneurysm was present in an intracerebral artery in
the right lentiform nucleus. The following dysplastic changes
were noted throughout all intracranial arteries (figs. 3B, 7A,
and 7C): large fibroelastic intimal cushions sometimes containing smooth muscle cells, thickening and splitting of the
internal elastic lamina, irregular arrangement of muscle
fibers, attenuation and defects of the medial coat, fibroplasia between the internal elastic lamina and the media, and
fibrous thickening of the adventitia. Both middle meningeal
arteries showedfibroelasticthickening of the intima. Extensive infarction had occurred in the corpus striatum, globus
pallidus, lateral thalamus and white matter on the right side.
The infarcted regions showed proliferation of the
capillaries and were infiltrated by fat granule cells. Foci of
disseminated infarcts of similar appearance occurred in the
hypothalamus and the cortex of the frontal, temporal and
parietal regions of the right hemisphere. Extensive recent inFIGURE 3A. /?(#/» carotid siphon (C2) shows stenosis of the
lumen due to hyperplasia of the media. Weigert's elastic, X33.

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FIGURE 3B. Left carotid siphon (C2) shows a fibroelastic intimal
cushion. Hematoxylin and eosin, X33.

FIGURE 5A. A recent dissecting aneurysm is present in the right
posterior cerebral artery. The original lumen is compressed.
Hematoxylin and eosin, X66.

FIGURE 4. The supraclinoidal part of the right internal carotid
(Cl) artery contains multiple folds of internal elastic lamina; endothelial cells line both sides of the folds of the elastic lamina. An intimal cushion is present on the dissected internal elastic lamina. The
media is attenuated (right upper corner) and the adventitia is
thickened. Hematoxylin and eosin, X54.

FIGURE 5B. Early organization of a dissecting aneurysm in the
pericallosal artery, of which the original lumen is stenosed. Proliferation of mesenchymal cells is seen outside the internal elastic
lamina. Cluver-Barrera, X60.

FIBROMUSCULAR DYSPLASIA AND MULTIPLE DISSECTING ANEURYSMS/P/Vz et al.

397

FIGURE 6. The right middle cerebral artery presents a dissecting
aneurysm which periodically varies in its extension. Sinusoidal
channels are present in the dissected area. Weigert's elastic, X42.

farcts and severe edema also occurred in the right hemisphere. An increase in the number of vascular channels was
particularly marked in the basal ganglia on the right side.
Many of the vessels showed cuffing by lymphocytes.
Significant changes were not found in the myocardium,
lungs, spleen and kidney. The liver showed some fatty infiltration.

FIGURE 7B. A small perforating basal artery has two lumina.
Hematoxylin and eosin. X90.

Discussion

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The main morphological findings were dissecting
aneurysms limited to the intracranial arteries and arterial
dysplasia1 which was generalized. The main arteries of the
right cerebral hemisphere were occluded by recent dissecting
aneurysms and the resulting massive infarction accounted
for the sudden death of the patient. Most occlusions were
not present at arteriography one week earlier. Other dissecting aneurysms at different stages of organization were present in branches of the middle and anterior cerebral arteries.
It is assumed that some blood flow was present in the false
lumen of the dissected arteries since the blood was not
clotted; in addition, there was no breakdown of hemoglobin, and some arteries had two patent lumina. Dissection
was not distributed equally over the arterial wall. The internal elastic lamina was still fixed to the medial coat in many

FIGURE 7A. The right middle cerebral artery exhibits a large intimal cushion which shows splitting of the intima (to the left). The
internal elastic lamina is ruptured (arrow). Weigert's elastic. X27.

FIGURE 7C. Fibroplasia between the internal elastica and the
media is seen in a small artery of the island ofReil. Cresyl violet,
X90.

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places, which is shown in figure 6. The dissection resulted in
multiple stenoses of the lumen and showed the beaded radiological and macroscopic appearance.
Dissecting aneurysms of the intracranial arteries are rare
but are well documented in the literature as a cause of
sudden hemiplegia in young subjects,2 with arteriography
demonstrating occlusion or stenosis of the intracranial
arteries in these cases. As in the present case, dissection occurs always between the internal elastic lamina and the
media. Discontinuous dissection and early organization so
far have not been reported.
The changes in large extracranial arteries are compatible
with fibromuscular dysplasia3 and are most pronounced
throughout the internal carotid artery. Dysplastic changes
also were found in the intracranial arteries of the carotid and
vertebrobasilar systems. But what do the dysplastic changes
mean? Hassler* described them as physiological changes in
newborn and healthy young individuals, but other authors5-6
regard them as pathological and related to arteriosclerosis.
The following arguments favor the view that the changes in
intracranial arteries are part of a generalized arterial disorder.

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(1) The intracranial dissecting aneurysms showed rupture of
the intima adjacent to an intimal cushion where the
media was defective.7
(2) Also, in cases of intracranial dissecting aneurysms the
arteries of the body show foci of medial necrosis and of
fragmentation of the elastica.8
(3) In patients with berry aneurysms of the intracranial
arteries the fibroelastic intimal cushions and defects of
the media are larger and more frequent than normal.9
(4) Intracranial berry aneurysms occur frequently in
patients with fibromuscular dysplasia of the renal and
carotid arteries.10'11
We assume that berry aneurysms and dissecting
aneurysms of intracranial arteries are different manifestations of the same underlying disorder. However, clear-cut
criteria are lacking which would separate relevant dysplastic changes of intracranial arteries from incidental or
even physiological findings. The relation of medial
degeneration12 and fibromuscular dysplasia also has not
been elucidated.
There are three reports on intracranialfibromusculardysplasia and they are based on the beaded appearance of the
arteries in the angiograms in analogy to the observations in
the renal and internal carotid arteries;13"16 they were not confirmed by autopsy. In another case there was histological
"evidence" in intracranial arteries, but the authors
emphasized that the changes were "infraradiological" and
the angiogram appeared to be normal.11 In our case the
beaded appearance of the right middle cerebral artery was
due to the peculiar form of a dissecting aneurysm. In addi-

VOL. 7, No. 4, JULY-AUGUST 1976

tion to the dissecting aneurysm, fibroplasia between the internal elastic lamina and the media was the only finding
which was sufficient to account for stenosis of an intracranial artery (fig. 7C), but this finding was more likely due
to organization of a dissecting aneurysm rather than to primary fibroplasia. The beaded angiographical appearance of
the right internal carotid artery in the neck displayed stationary waves.16 At autopsy this artery showed definite
pathological changes (fig. 2). These findings favor the
suggestion of Bergquist et al.17 that stationary waves may be
the precursor of fibromuscular dysplasia. The radiological
and morphological findings in the right hemisphere are compatible with the changes found in the moyamoya syndrome
except that in this case the changes were unilateral. A radiological appearance very similar to that seen in the moyamoya syndrome may occur in occlusion of the middle cerebral artery in children, due to hypertrophy of the striate
branches.18 This might be the more likely explanation of the
present case.
Acknowledgment
We thank Professor J. Thurner for granting permission to publish the data
presented in this paper.

References
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3. Harrison EG Jr, McCormack LJ: Pathologic classification of renal
arterial disease in renovascular hypertension. Mayo Clin Proc 46:
161-167, 1971
4. Hassler O: Physiological intima cushions in large cerebral arteries of
young individuals. Acta Path Microbiol Scand 55: 19-27, 1962
5. Ratinov G: Extradural, intracranial portion of carotid artery. Arch
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6. Stehbens WE, Silver MD: Arterial lesions induced by methyl cellulose.
Am J Path 48: 483-501, 1966
7. Wollmann L: Cerebral dissecting aneurysms. Brain 82: 276-291, 1959
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9. Hassler O: Morphological studies on the large cerebral arteries: With
reference to the aetiology of subarachnoid haemorrhage. Acta Psychiat
Neurol Scand 154 (Suppl) 1961
10. Wylie EJ, Binkley FM, Palubinskas AJ: Extrarenal fibromuscular hyperplasia. Am J Surg 112: 149-155, 1966
11. Manelfe C, Clarisse C, Fredy D, et al: Fibromuscular dysplasia of the
cervico-cephalic arteries. J Neuroradiol 1: 150-229, 1974
12. Watson AJ: Dissecting aneurysms of arteries other than the aorta. J Path
Bact 72: 439-449, 1956
13. Huber P, Fuchs WA: Gibt es eine fibromusculare Hyperplasie zerebraler
Arterien? Fortschr Roentgenstr 107: 119-126, 1967
14. Elias WS: Intracranial fibromuscular hyperplasia. JAMA 218: 254-256,
1971
15. Josul A, Kier EL, Ostrow D: Fibromuscular dysplasia involving the intracranial vessels. J Neurosurg 37: 749-752, 1972
16. Theander G: Arteriographic demonstration of stationary arterial waves.
Acta Radiol (Stockholm) 53: 417-425, 1960
17. Bergquist E, Erikson U, Ulfendahl HR: Stationary wave or segmental
vasoconstriction. Acta Radiol (Diagn) 11: 497-505, 1971
18. Simon J, Giudicelli G, Signargout J: Differential diagnosis of the "Moyamoya" syndrome. J Neuroradiol 1: 102-112, 1974