SYNDROME DUE TO ASPERGILLOSIS
Yvens B. Fernandes1,
Marcos V.C. Maldaun4,
Jayme A. Maciel Jr.5
ABSTRACT ¾ We report
the case of a 73-year-old female who presented facial numbness and
pain in the first division of the trigeminal nerve, ptosis, diplopia
and visual loss on the right side for the previous four months. The
neurological, radiological and histological examination demonstrated a
rare case of invasive fungal aspergillosis of the central nervous
system, causing orbital apex syndrome, later transformed in temporal
brain abscess. She died ten months later due to respiratory and renal
failure in spite of specific antimycotic therapy.
aspergillosis, orbital apex syndrome, mycoses, brain abscess.
Síndrome do ápice
da órbita causada por aspergilose: relato de caso
RESUMO ¾ Relatamos o
caso de mulher de 73 anos de idade que apresentou nos últimos 4 meses
amortecimento facial, dor no território do primeiro ramo do nervo
trigêmeo, ptose palpebral, diplopia e perda da acuidade visual, à
direita. A investigação neurológica, radiológica e histológica
demonstrou se tratar de uma lesão no ápice da órbita de origem fúngica,
aspergilose com transformação tardia em abscesso cerebral. A paciente
faleceu 10 meses após o tratamento inicial embora tenha sido tratada
com medicação antifúngica específica.
aspergilose, síndrome do ápex da órbita, micose, abscesso cerebral.
Orbital apex syndrome
is a paralysis of all three nerves supplying the external ocular muscles
and a sensory deficit in the distribution of the first division of the
trigeminal nerve, combined with an optic nerve lesion1.
Aspergillus is a fungus
found in soil and organic debris. It commonly presents as a localized
disease of the lungs or paranasal sinuses and mainly affects
immunocompromised individuals, usually as a fatal opportunistic
infection in acquired immunodeficiency syndrome (AIDS)2,3.
Patients with diabetes, leukemia and lymphoma are at higher risk. It can
also affect normal or mildly immunocompromised patients, usually as an
invasive chronic form4. Opportunistic infections frequently
involve the anterior and posterior segments of the eye, orbit and
sinuses, with possible secondary intracranial extension. Orbital
aspergillosis is a rare condition that may clinically mimic non-specific
orbital inflammatory disease.
We report on a case of
Aspergillus fumigatus infection, which caused an orbital apex
syndrome and later a temporal brain abscess in a non-immunocompromised
A 73-year-old Caucasian
woman presented with a one-year history of headaches. She also
complained of facial numbness and pain in the first trigeminal division
territory in the last four months, ptosis, diplopia and visual blurring
on the right side. Neurological examination disclosed complete
right-sided ophthalmoplegia with mydriasis, first trigeminal division
hypoalgesia, diminished corneal reflex and severe visual loss. Magnetic
resonance imaging (MRI) showed an enhanced lesion on the right sphenoid
sinus extending to the orbital apex. Human immunodeficiency virus (HIV)
tests to point out AIDS were negative. Blood tests revealed she was immunocompetent.
In view of the
examination results an orbital apex syndrome was considered. The
presumptive diagnosis was a skull base tumor. A right pterional
craniotomy was performed with opening of the orbital apex. An
infiltrative process involving the orbital fat, vessels and nerves was
found. Neurolysis of the first and second branches of the trigeminal
nerve up to Meckel's cave was carried out. The postoperative course was
uneventful, the patient was relieved of her trigeminal pain.
Histological examination showed cellular contents compatible with
"chronic active inflammatory process". Based on this diagnosis oral
prednisone (40 mg/day) was prescribed and she was discharged five days
after the surgical procedure.
Four months later the
patient presented episodes of low fever, loss of appetite and lately
mental confusion. A new MRI revealed a large lesion pointing out to a
right temporal abscess.
She was immediately submitted to surgical drainage. Microscopic
examination of the exudate displayed numerous hyphae of Aspergillus
fumigatus. Amphotericin B (1.0 mg/kg/day) was given by intravenous
infusion, during three weeks. After three weeks a control CT scan still
showed residual abscess and a new drainage of the abscess was done. The
patient was discharged after two months of maximum recommended doses of
antimycotic therapy (1.2 mg/kg/day).
One month later she
developed again signs of systemic infection and the CT scan showed a
persistent large right temporal abscess. A new surgical procedure was
carried out with total removal of the abscess capsule and removal of the
bone flap. The patient was kept under amphotericin B given intravenously
but died two months later due to respiratory and renal failure.
Unfortunately a review
of a second section of the histogical specimen of the first surgery
showed a few hyphae morphologically compatible with Aspergillus
In spite of the high gravity of human aspergillosis and its
dissemination, in this case, the misdiagnosed histological examination
during the first admission undoubtedly contributed to the fatal outcome
of our patient.
The orbital apex
syndrome might have other causes like optic nerve glioma, infraclinoid
aneurysm of the internal carotid artery, trauma, orbital tumors and
Paget's disease. Only rarely is aspergillosis the causative pathology1,5.
Aspergilli are moulds
with a ubiquitous distribution in indoor and outdoors environments. In
humans, almost all the invasive Aspergillus infections are caused by
Aspergillus fumigatus. It was first described by Fresenius in 1863,
who isolated it from an airway infection in poultry6. In
invasive human infections A. flavus, A. glaucus, A.
niger, A. restrictus, A. terreus and A.
versicolor have been found as causative agents, although they are
rare and of minor medical importance. Aspergillus fumigatus is
the most frequent species isolated in human infections, followed by
A. flavus4,7. Invasive aspergillosis is an opportunistic
infection and occurs very often in the granulocytopenic patient.
Predisposing causes include alcoholism, low-dose prednisone therapy and
insulin-dependent diabetes mellitus. The route of infection is
frequently by inhalation of Aspergillus spores and conidia or
airborne metabolites of Aspergillus, causing at first allergic
aspergillosis. Acute bronchopulmonary aspergillosis is increasingly
being observed. Peribronchial eosinophilic infiltrations may occur and
the disease can lead to exogenic allergic alveolitis, the so-called
"farmer's lung". Acute allergic conjunctivitis and rhinitis have been
reported. Most allergic diseases caused by Aspergillus species
are attributable to A. fumigatus6.
The main routes of
central nervous system (CNS) contamination are hematogenous
dissemination from a distant primary source, mainly lung, and contiguous
spread from an adjacent focus such as orbit or paranasal sinuses3,8,9.
Involvement of the CNS is present in 10-15% of patients with
disseminated disease4. It may manifest as single solid
granuloma, multiple abscesses, necrotic lesions or meningitis10.
Recently Coleman et al.10 made a detailed review of the
literature and showed that invasive CNS aspergillosis is a dramatic
disease, mainly in the immunosuppressed host, with mortality rate over
90% in most series. The definitive diagnosis of invasive aspergillosis
is often confirmed post-mortem, especially in the immunocompromised host3.
Invasive infections can
be detected by imaging procedures such as X-ray, CT scan, MRI and
sonography, but laboratory confirmation is of great importance.
Respiratory secretions, bronchoalveolar lavage fluid as well as other
clinical specimens from infected sites should be examined both under the
microscope and in cultures. Some problems can arise with immunological
procedures in the diagnosis of aspergillosis. Patients with allergic
aspergillosis often show high specific IgG antibody titers against
Aspergillus polysaccharide and/or glycoprotein antigens combined
with high serum IgE titers and also often specific anti-Aspergillus
IgA titers3. On average, about 90% of the patients with
aspergillomata show specific IgG antibody titers against Aspergillus
antigens, often combined with specific IgA titers. Altogether, the
interpretation of serological results in Aspergillus-associated
diseases is problematic and must be combined with clinical diagnostic
procedures, and microscopic and microbiological techniques3,6.
Allergic diseases are
generally treated symptomatically and the causative allergen must be
eliminated as far as possible. Systemic aspergillosis is a life
threatening opportunistic infection that requires specific antimycotic
therapy. In some cases, antimycotic therapy is able to stop the
infection but has no curative effect until the patient's underlying
state of immunosuppression has improved. Despite its high nephrotoxicity,
amphotericin B is the first-line drug for systemic therapy. In the case
of aspergillomata treatment includes aggressive surgical debridement and
antifungal therapy with amphotericin B, itraconazole, voriconazole or
intracavitary drug administration2,5,11-14. Despite these
efforts mortality remains very high3,6.
We reported a rare case
of invasive fungal aspergillosis of the CNS, in a 73-year-old
immunocompetent female, causing orbital apex syndrome and later a
temporal brain abscess; she died ten months later due to respiratory and
renal failure in spite of antifungical treatment.
1. Bray WH, Giangiacomo
J, Ide CH. Orbital apex syndrome. Surv Ophthalmol 1987;32:136-140.
2. Weinstein JM,
Sattler FA, Towfighi J, Sassani J, Page RB. Optic neuropathy and
paratrigeminal syndrome due to Aspergillus fumigatus. Ach Neurol
3. Denning DW. Invasive
aspergillosis. Clin Infect Dis 1998;26:781-805.
4. Swift AC, Denning DW.
Skull base osteitis following fungal sinusitis. J Laryngol Otol
5. Massry GG, Hornblass
A, Harrison W. Itraconazole in the treatment of orbital aspergillosis.
6. Latgé JP.
Aspergillus fumigatus and aspergillosis. Clin Microbiol Rev
7. Murai H, Kira J,
Kobayashi T, Goto I, Inoue H, Hasuo K. Hypertrophic cranial
pachymeningitis due to Aspergillus flavus. Clin Neurol Neurosurg
8. Wiles CM, Kocen RS,
Symon L, Scaravilli F. Aspergillus granunola of the trigeminal ganglion.
J Neurol Neurosurg Psychiatry;1981,44:451-455.
9. Camarata PJ, Dunn
DL, Farney AC, Parker RG, Seljeskog EL. Continual intracavitary
administration of amphotericin B as an adjunct in the treatment of
aspergillus brain abscess: case report and review of the literature.
10. Coleman JC, Hogg GG,
Rosenfeld JV, Waters KD. Invasive central nervous system aspergillosis:
cure with liposomal amphotericin B, itraconazole, and radical surgery:
case report and review of the literature. Neurosurgery 1995;36:858-863.
11. Scamoni C, Dario A,
Pozzi M, Dorizzi A. Drainage of aspergillus "primitive" brain abscess
with long-term survival. J Neurosurg Sci 1990;32:155-158.
12. Cahill KV, Hogan
CD, Koletar SL, Gersman M. Intraorbital injection of amphotericin B for
palliative treatment of Aspergillus orbital abscess. Ophthal Plast
Reconstr Surg 1994;10:276-277.
13. Borges-Neto V,
Medeiros S, Ziomkowski S, Machado A. Successful treatment of
mucormycosis and Aspergillus sp, rhinosinusitis in an
immunocompromised patient. BJID 1998;2:209-211.
14. Schwartz S,
Milatovic D, Thiel E. Successful treatment of cerebral aspergillosis
with a novel triazole (voriconazole) in a patient with acute leukaemia.
B J Haematol 1997;97:663-665.
Neurocirurgia (DNC) e Disciplina de Neurologia Clínica (DNE) do
Departamento Neurologia e Departamento de Anatomia Patológica (DAP) da
Faculdade de Ciências Médicas da Universidade Estadual de Campinas (UNICAMP),
Campinas SP, Brasil : Médico
Contratado, DNC; Professor
Doutor, DNC; Professor
Doutor, DAP; Médico
Residente, DNC; Professor
Received 1 December
2000, received in final form 23 May 2001. Accepted 28 May 2001.
Dr. Yvens Barbosa
Fernandes - Rua Maestro João de Túlio 140 / 82 - 13024-160 Campinas SP -