Eur J Pediatr (1999) 158: 650±652

Ó Springer-Verlag 1999

INFECTIOUS DISEASES

B. L. Loeys á R. N. Van Coster á L. R. Defreyne á J. G. Leroy

Fungal intracranial aneurysm in a child
with familial chronic mucocutaneous candidiasis

Received: 8 October 1998 / Accepted in revised form: 11 February 1999

Abstract We report on a patient who presented at 5 years of age with a hemiparesis due
to a middle cerebral artery infarction. An embolism had originated from a mycotic
aneurysm located in the internal carotid artery. For several months prior to admission he
had been su€ering from therapeutically resistant candidiasis of the mouth and nails.
Family history revealed chronic mycotic infections of the skin, hair, nails and mouth in
the father and paternal grandmother suggestive of chronic mucocutaneous candidiasis
with autosomal dominant mode of inheritance. Clipping of the aneurysm, after 3 months
of anti-mycotic treatment, followed by sustained treatment with itraconazole and ¯uconazole, led to a favourable outcome.
Conclusion Chronic mucocutaneous candidiasis can be associated with an intracranial
aneurysm and complicated by cerebral infarction.
Key words Fungal aneurysm á Familial mucocutaneous candidiasis

Introduction

Case report

The term `mycotic aneurysm' was introduced by Osler
[15] to describe aneurysms caused by any infectious
agent. Most of these aneurysms were complications of
bacterial endocarditis. This misnomer has prevailed in
the literature for many years. The term `mycotic aneurysm' should be reserved for infected aneurysms
caused by a fungal infection, and the designation
`bacterial aneurysm' for aneurysms due to bacterial
infection. The presented patient had a true fungal aneurysm as a complication of candidiasis, a condition
from which several family members su€ered. He is the
®rst reported instance of possibly familial chronic mucocutaneous candidiasis and associated intracranial
fungal aneurysm.

Our patient, the second child of consanguineous parents, was born
without complications following an uneventful pregnancy. Initial
mental and motor development was normal. For several months
prior to the hospital admission, he had been su€ering from therapy-resistant candidiasis of the mouth and nails. Family history
revealed a chronic mycotic infection of skin, hair, nails and mouth
in the father and the paternal grandmother. At 5 years of age, the
boy was found in bed in a state of stupor. On admission to hospital
a right hemiparesis was observed. His eyes were deviated to the left.
Deep tendon re¯exes were hyperactive and Babinski sign was
present on the right. General physical examination revealed
no abnormalities. The CSF was hemorraghic (2.4 ´ 105 RBC and
2.9 ´ 103 WBC/lL, 59% polymorphonuclear cells). Hypocalcaemia (6.4 mg/dl) and hyperphosphataemia (6.9 mg/dl) suggested hypoparathyroidism, subsequently documented by the low
serum parathormone concentration (6.6 pg/ml, normal >10). No
coagulopathy was detected. Kidney, adrenal and liver function tests
were normal, as was routine urinanalysis. A transthoracal echocardiogram was normal. The cerebral CT scan showed a large

R. N. Van Coster (&) á B. L. Loeys á J. G. Leroy
Department of Paediatrics,
Ghent University School of Medicine,
185, De Pintelaan, B-9000 Ghent, Belgium
Tel.: +32-9-240 35 85, Fax: +32-9-240 38 75

L. R. Defreyne
Department of Interventional Radiology,
Ghent University School of Medicine,
Ghent, Belgium

651
Fig. 1 Left internal carotid
artery angiogram (50 days after
admission) showing anterior
(left) and pro®le (right) view of
the aneurysm in the C2-segment
of the A. carotis interna

hypodense area in the left parieto-occipital region compatible with
infarction of the A. cerebri media area. A contrast enhanced CT
scan as well as an angiographic study (Fig. 1) revealed an aneurysm
in the C2-segment of the A. carotis interna with location cranial to
the origin of the A. communicans posterior. This ®nding was
con®rmed by MRI. The CSF culture was positive but blood cultures negative for Candida albicans. The patient was treated with
oral ¯ucytosine and nystatine, combined with amfotericine B intravenously. After a few days the boy became more alert and recovered from the hemiparesis. Because fever persisted and CSF
cultures remained positive for Candida albicans, intravenous ¯uconazole was added to the treatment. Eventually, after 3 weeks,
cultures were sterile. Abnormal T-cell function against Candida
albicans was demonstrated using a lymphocyte transformation test
which showed a ¯at dose response curve. The general lymphocyte
transformation test was normal. Precipitines were high, indicating a
normal B-cell function. Finally, a Multitest showed no response to
Candida albicans. De®nitive treatment of the aneurysm consisted of
neurosurgical clipping of the aneurysm 3 months later. Sustained
anti-mycotic treatment with itraconazole and ¯uconazole has led to
a favourable outcome.

Discussion

This patient su€ered from chronic oral candidiasis with
onset before the age of 5 years. In addition he had therapy-resistant candidiasis of the nails. Finding these two
components prompted the diagnosis of chronic mucocutaneous candidiasis. The family history was positive in
the father and paternal grandmother. The latter history is
compatible with an autosomal dominant mode of inheritance. There have been other reports of dominantly inherited forms of chronic mucocutaneous candidiasis [10].
Because of this hypoparathyroidism at the time of
admission, the diagnosis of candidiasis-endocrinopathy
syndrome was entertained. Because over the following
years hypoparathyroidism did not recur nor did other
endocrinological dysfunctions appear, the candidiasisendocrinopathy syndrome was thought unlikely although not completely ruled out diagnosis. No family
members, in particular those with mucocutaneous mycosis, had any sign of an endocrinological disorder.
Thus, familial candidiasis endocrinopathy could not be

upheld in these persons either. Moreover it is worth a
reminder that this rare monogenic disorder is known to
be autosomal recessively inherited. Nevertheless, patients should be checked yearly for endocrine failure and
for auto-antibodies against endocrine tissues because
endocrine failure can develop later in adulthood. Establishing baseline values for cellular immunity using a
Multitest could be helpful in the future.
Because the CSF cultures were positive for Candida,
the cerebral infarction in the A. cerebri media region
diagnosed on cranial CT and MRI scan was caused by
mycotic embole originating in the A. carotis interna
aneurysm. Ultrasonographic study had ruled out a
possible cardiac origin.
Fungal or ``true mycotic'' aneurysms are very rare.
Mielke et al. [12], in reviewing the literature, found only
15 patients reported, 7 of whom where under the age of
20 years. Fungal aneurysms are usually located in major
intracranial vessels, whereas bacterial aneurysms preferentially reside at peripheral branches of the middle
cerebral artery [7]. The former tend to be relatively large
and usually multiple, the latter rather small (1±2 mm in
diameter) [1]. Few surviving patients with intracranial
aneurysms due to Candida have been reported [11].
Karsner [8] grouped infectious aneurysms into three
types based on pathogenesis. Most frequent are aneurysms of embolic origin due to bacterial endocarditis. Of
patients with endocarditis 2%±10% develop aneurysms
[2] with neurological symptoms as the clinical onset.
Another type of aneurysm is of extracardiac origin and
occurs in patients with meningitis, otitis media, or
osteomyelitis of the skull, cavernous sinus thrombophlebitis, or in patients with skin abscesses or sinus
infections. Finally, an aneurysm is considered `primary'
or `cryptogenic' when no in¯ammatory focus can be
detected. Among the several mechanisms they have
proposed for the development of infectious aneurysms,
Molinari et al. [13] suggested that the latter arise at the
site of an infected embolus. In our patient, the chronic
mucocutaneous candidiasis must have been accompa-

652

nied by systemic C. albicans infection, which led to the
development of the mycotic aneurysm, the mycotic
embolism and ultimately the cerebral infarction.
Treatment of chronic mucocutaneous candidiasis is
dicult. In recent reports itraconazole has been recommended as the most e€ective antifungal agent [5]. The
diagnostic and therapeutic strategy for infective aneurysms is controversial [3, 4]. Cerebral CT scan alone is
insucient for establishing a diagnosis. It is impossible
to predict whether an aneurysm will become smaller and
eventually disappear following appropriate therapy, or
whether it will expand and rupture [3, 4, 6, 14]. Some
aneurysms will rupture without angiographic enlargement. Brust et al. [4] recommended four-vessel angiography without delay whenever a mycotic aneurysm is
suspected. A single accessible distal mycotic aneurysm in
clinically stable patients should be treated surgically as
soon as possible. Recommendations for patients with
multiple or proximal infective aneurysms must be individualized. Salgado et al. [16] advised that angiography
be repeated after completion of the antibiotic or antimycotic treatment in patients with initially negative
angiographic results. Aspoas and De Villiers [2] concluded that elective surgery should be performed after 6
weeks of treatment if, on repeat angiography, the
aneurysm is still present. Surgery becomes urgent if an
increase in the size of the aneurysm is noticed. Clipping
of the aneurysm is the favoured procedure. Recently,
Khayata et al. [9] reported their experience with a
promising alternative endovascular technique in patients
with distal or deeply located aneurysms where surgical
treatment was neither indicated nor possible.
Cerebral infarction caused by an embolus originating
from a mycotic aneurysm is assumed to be the most
likely cause of the acute hemiparesis observed in the
patient presented who su€ered from mucocutaneous
candidiasis also present in close family members. Following clipping of the aneurysm preceded by 3 months

of antimycotic therapy, the evolution was favourable
under long-term anti-mycotic treatment.
References
1. Ahuja GK, Jain N, Vijayaraghavan M, Roy S (1978) Cerebral
mycotic aneurysm of fungal origin. J Neurosurg 49:107±110
2. Aspoas A, De Villiers JC (1993) Bacterial intracranial aneurysms. Br J Neurosurg 7:367±376
3. Bingham WF (1977) Treatment of mycotic intracranial aneurysms. J Neurosurg 46:428±437
4. Brust JCM, Dickinson PCT, Hughes JEO, Holtzman Robert
NN (1990) The diagnosis and treatment of cerebral mycotic
aneurysms. Ann Neurol 27:238±246
5. DePadova-Elder SM, Ditre CM, Kantor GR, Koblenzer PJ
(1994) Candidiasis endocrinopathy syndrome. Arch Dermatol
130:19±22
6. Frazee JG, Cahan LD, Winter J (1980) Bacterial intracranial
aneurysms. J Neurosurg 53:633±641
7. Horten BC, Abbott GF, Porro RS (1976) Fungal aneurysms of
intracranial vessels. Arch Neurol 33:577±579
8. Karsner HT (1947) Acute in¯ammation of arteries. Charles
C. Thomas, Spring®eld
9. Khayata MH, Aymard A, Casasco A, Herbreteau D, Woimant
F, Merland JJ (1993) Selective endovascular techniques in the
treatment of cerebral mycotic aneurysms. J Neurosurg 78:661±
665
10. Kirkpatrick CH (1994) Chronic mucocutaneous candidiasis.
J Am Acad Dermat 31:S14±S17
11. Lipton SA, Hickey WF, Morris JH, Loscalzo J (1984) Candidal
infection in the central nervous system. Am J Med 76:101±108
12. Mielke B, Weir B, Oldring D, Westarp C von (1981) Fungal
aneurysm: case report and review of the literature. Neurosurgery 9:578±582
13. Molinari GF, Smith L Goldstein MN, Satran R (1973)
Pathogenesis of cerebral mycotic aneurysms. Neurology
23:325±332
14. Morawetz RB, Karp RB (1984) Evolution and resolution of
intracranial bacterial (mycotic) aneurysms. Neurosurgery
15:43±49
15. Osler W (1885) Malignant endocarditis. Lancet 1:415±418
16. Salgado AV, Furlan AJ, Keys TF (1987) Mycotic aneurysms,
subarachnoid hemorrhage, and indications for cerebral angiography in infective endocarditis. Stroke 18:1057±1060