Infection

Spinal Aspergillus VertebralOsteomyelitis With ExtraduralAbscess: Case Report and Reviewof LiteratureSandeep Vaishya, M.S., M.Ch., and Manish Singh Sharma, M.S., M.Ch.Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India

Vaishya S, Sharma MS. Spinal Aspergillus vertebral osteomyelitiswith extradural abscess: case report and review of literature.Surg Neurol 2004;61:551–5.

BACKGROUNDSpinal extradural abscesses caused by Aspergillus speciesare rare and occur mostly in immunocompromised pa-tients or in patients with Aspergillomas elsewhere in thebody. In this report, the authors draw attention to arapidly developing syndrome of extradural compressivemyelopathy in an immunocompetent patient. Only fourother cases have been reported previously.CASE DESCRIPTIONA 35-year-old female presented with rapidly progressivepainful paraparesis progressing to paraplegia in 15 daysdespite adequate empiric antitubercular therapy. Mag-netic resonance imaging (MRI) revealed D11 vertebralbody destruction and an extradural mass compressingthe cord from D10 to D12. The patient underwent a D11corpectomy and spinal stabilization with an iliac bonestrut graft, ‘Z’ Plate and screw fixation. The biopsyshowed fungal hyphae with dichotomous branching diag-nostic of Aspergillosis. Despite treatment with Amphoter-icin B and oral Itraconazole the patient developed rapidlyprogressive multiorgan failure and expired after 2months.CONCLUSIONSThe authors report the fifth and extremely rare case ofAspergillus vertebral osteomyelitis with an extradural ab-scess in an immunocompetent patient. Therapy is con-troversial and predicated on the use of highly toxic drugswith inconsistent efficacies. Mortality remains grievouslyhigh. © 2004 Elsevier Inc. All rights reserved.

KEY WORDSAbscess, Aspergillus, extradural, osteomyelitis.

Spinal extradural abscesses caused by Aspergil-lus species are rare [1,2,5,8,11–14,16,18,19,21].

Most of the previous reports have dealt with immu-

nocompromised patients with malignancies under-going chemotherapy, Acquired ImmunodeficiencySyndrome (AIDS) patients, those on steroid therapyfor other pre-existing disease processes such asbronchial asthma, hepatic encephalopathy orchronic granulomatous disease, and patients withAspergillomas elsewhere in the body [1,5,8,11,12–14,16,19,21]. In this report, we draw attention to arapidly developing syndrome of extradural com-pressive myelopathy in an immunocompetent pa-tient. Only four other cases have been reportedpreviously [2,6,7,18].

Case ReportA 35-year-old female was admitted in April 2001 withcomplaints of back pain radiating to the right flankfor the last 2 months, followed by a progressiveascending, flaccid, asymmetrical paraparesis begin-ning in the right foot a month later that rapidlyprogressed to paraplegia with urinary and fecal in-continence within a span of 2 weeks. There was nohistory of trauma, fever, cough, hemoptysis, drugintake, sexually transmitted disease, steroid ther-apy, malnutrition, or any other history that mayhave contributed to an immunocompromised state.She had previously undergone a hysterectomy 1year earlier for abnormal uterine bleeding. Neitherthe operative details nor the biopsy were available.The patient had been started on empiric anti-tubercular therapy by another neurosurgeon basedon the magnetic resonance imaging (MRI) findingsof the dorsolumbar spine but deteriorated furtherdespite the same.

Examination revealed a well-nourished lady ofaverage build in obvious pain. Cranial nerves andupper limbs were normal. No inter-costal or sub-costal retractions were seen, chest expansion was 4

Address reprint requests to: Dr. Sandeep Vaishya, Assistant Professor,Department of Neurosurgery, All India Institute Of Medical Sciences, An-sari Nagar, New Delhi, India 110029.

Received February 19, 2003; accepted June 17, 2003.

© 2004 Elsevier Inc. All rights reserved. 0090-3019/04/$–see front matter360 Park Avenue South, New York, NY 10010–1710 doi:10.1016/j.surneu.2003.06.005

cm, and there was no hollowing, wasting or phan-tom hernia. Beevor’s sign was positive. Her lowerlimbs had normal bulk, were flaccid in tone andparaplegic. No tendon jerks were elicited, and herplantar response was absent bilaterally. The anus

was patulous and the patient had an indwellingFoley catheter. All sensations were absent belowthe L1 dermatome, bilaterally. No spinal deformitywas present, but there was mild tenderness overthe D10 vertebral spinous process. The respiratory

1 (A) Dorsolumbar MRI (sagittal T2weighted image) showing destruction of

the D 11 vertebral body, with extradural com-pression and cord changes. (B) Axial T2weighted image depicting vertebral body, rightpedicular, and transverse process destruction.

552 Surg Neurol Vaishya and Sharma2004;61:551–5

and cardio-vascular systems were normal on aus-cultation and percussion, and the abdominal exam-ination similarly revealed no abnormality. Her he-matologic profile revealed a hemoglobin of 10.8 g%,and a total leukocyte count of 6.400/mm3 (neutro-phils 64%, lymphocytes 30%, monocytes 2%, andeosinophils 4%). Blood urea, creatinine and theurine examination were normal. She tested nega-tively for the human immunodeficiency virus.

The chest and lumbosacral spine X-rays werenormal. The MRI (Figure 1A, B) detected involve-ment of the D11 vertebral body, the right–sidedpedicle and transverse process with a heteroge-neous hypo to hyper intense signal in both T1 andT2 weighted images. An extradural soft tissue masscompressing the thecal sac from D10-D12 was seen,which was isointense on both T1 and T2 weightedimages. Cord hyperintensity was also present fromD8 to the conus, which was unlikely to be a result ofthe compression itself.

The patient was operated using a right postero-lateral thoracotomy approach. A D11 corpectomywas performed, a strut iliac crest bone graft wasplaced in the inter space, the spine stabilized witha “Z” plate and screw fixation (MEDTRONIC®), andan intercostal tube drain placed. During surgery,the vertebral body appeared to be normal for mostof the anterior part, except for the most posterioraspect, which was partly destroyed. There were afew drops of pus along with vascular granulationtissue, which was compressing the cord marginally.

The preoperative impression had been tubercu-

losis and arteritis, suspected to have been thecause of the dense paraplegia, as the extent of duralcompression was unlikely to produce the clinicaleffects present. The histopathological examination(Figure 2) showed fungal hyphae with dichotomousbranching diagnostic of Aspergillus. Surroundingsoft tissues revealed an inflammatory infiltrate con-sisting of plasma cells, lymphocytes, neutrophils,and nonviable bone.

She withstood the operative procedure well, andher chest tube was removed after six days. Antitu-berculous therapy was terminated, and the patientwas started on injection Amphotericin B, which wasthen gradually increased in dosage. The patient’sliver function tests were, however, affected with herserum proteins measuring 2.6g % (Albumin: Globu-lin � 1.5:1.1). Her enzymes were also elevated (As-partate Transaminase/Alanine Transaminase/Alka-line Phosphatase � 159/519/122 IU/liter). Thepatient’s serum tested positively for Aspergillosisas evident by the high Ig G levels against the As-pergillus antigen.

Amphotericin B was stopped and then restartedonce her liver functions normalized. She also re-ceived tablet Itraconazole 200-mg b.i.d. After a6-week course, there was no improvement in herclinical condition even after the cumulative admin-istration of 2 g of Amphotericin B. Two months aftersurgery she developed rapid onset multiorgan fail-ure with deranged renal and hepatic function sec-ondary to drug toxicity and expired.

2 Photomicrograph (H&E stains�250) revealing septate As-

pergillus hyphae with dichotomousacute angled branching.

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DiscussionAspergillus species are ubiquitous opportunisticfungi that develop hyphae in the pathogenic phase.The incidence of invasive Aspergillus infection hasbeen estimated at 12/1,000,000/year. Presentationin the central nervous system is either because oftheir space occupying capacity resulting in granu-lomas, abscesses, and hydrocephalus, or as a veryrare form of compressive myelopathy which is thebasis of this report. Aspergillus is also known toproduce arteritis with infarction, hemorrhage, ne-crosis, and mycotic aneurysms [3]. The speciesinvolved include A. fumigatus, A. flavus, A. niger, andmore recently A. nidulans var. echinulatus [12]. CNSinvolvement is via contiguity, hematogeneousspread or inoculation against almost always a back-drop of underlying neoplastic disease, iatrogenicimmunosuppression, or AIDS. Host defense againstAspergillus is primarily a function of neutrophilswith help from local macrophages and monocytes[9,10,20]. Yet, involvement has been noted in immu-nocompetent patients such as ours [2,6,7,18]. As-pergillus species occur as commensals in as manyas 10% of random sputum samples with no hostresponse [6]. The three possible origins of a spinalepidural abscess are: 1) contiguous spread from anadjacent involved organ most commonly the lung,2) hematogenous spread from a distant focus, and3) iatrogenic inoculation [2,13,19,21]. In our casethe mode of spread remains obscure as the chestskiagrams were normal, all blood and sputum cul-tures for the fungus were negative, and the patienthad never been subjected to a lumbar puncture.Most spinal lesions are granulomatous and arisefrom contiguity, whereas hematogenous dissemina-tion results in abscess formation. Cord compres-sion in spinal Aspergillosis may be a result of acombination of vertebral osteomyelitis, granuloma,and/or abscess formation in either the epidural ordisc spaces. Spinal epidural abscesses affect youngpatients with presentations varying from rapidlyprogressive paraparesis (such as in our case) togradually progressive myelopathy without sensoryloss or dysautonomia [12].

Diagnosis depends on a high index of suspicionwith biopsy being the only foolproof test. Hemato-logic examination, erythrocyte sedimentation rate(ESR) and radiology are at best nonspecific. How-ever, high Ig G levels against A. fumigatus antigens inblood may be useful in both diagnosis and follow upfor efficacy of therapy [14].

Therapy is multi-modal with one arm being de-compressive surgery (with or without spinal stabi-lization), which usually provides the histopathol-

ogy in cases where the diagnosis is in doubt. Themainstay, however, is aggressive drug therapy us-ing amphotericin B, itraconazole, 5-flucytosine, andinterferon alpha [13,15,17]. This is probably be-cause of the fact that the nature of the disease iswidespread, and surgery is unlikely to clear in-volved tissue of the disease pathology. In fact, Brid-well et al are of the opinion that surgical interven-tion ought to be limited to cases of failure ofmedical management [4]. Furthermore, the role ofsimultaneous spinal stabilization is unclear as cer-tain reports favor the use of simple decompressionof purulent, necrotic, and exuberant granulation tis-sue because more extensive procedures, especiallyin the immunocompromised, would produce morecomplications [12].

Morbidity and mortality are in the range of 95%[12]. Yet there may be an age-related difference insurgical outcome with younger children faring bet-ter than adults irrespective of their immune status[1,12].

ConclusionAspergillus osteomyelitis and extradural abscessformation is a rare cause of spinal compressivemyelopathy. Definitive diagnosis without biopsy isimprobable. The current standard of care is predi-cated on the use of toxic drugs like amphotericin B(which has inconsistent results) combined withsurgical debridement with or without stabilization.Mortality rates remain grievously high.

REFERENCES1. Auletta JJ, Chandy JC. Spinal epidural abscesses in

children: a 15 year experience and review of the lit-erature. Clin Infect Dis 2001;32:9–16.

2. Beaudoin MG, Klein L. Epidural abscess followingmultiple spinal anesthetics. Anaesth Intensive Care1984;12:163–4.

3. Bhattacharya MK, Bhattacharya A, Siridhar K. FungalInfections. In: Ramamurthy B, Tandon PN, eds. Text-book of Neurosurgery, 2nd ed., Vol. 1. New Delhi:Churchill Livingstone, 1996:553–66.

4. Bridwell KH, Campbell JW, Barenkamp SJ. Surgicaltreatment of hematogenous vertebral Aspergillus os-teomyelitis. Spine 1990;15:281–5.

5. Byrd WF, Weiner MM, McGee MA. Aspergillus spinalepidural abscess. JAMA 1982;248:3138–9.

6. Chee YC, Poh SC. Aspergillus epidural abscess in apatient with obstructive airway disease. PostgradMed J 1983;59:43–5.

7. Dietz R, Huber G, Thetter O. Aspergillosis of the lungwith osteoclasis and paraplegia. Neuroradiology1982;23:219–21.

8. Dubbeld P, van Oostenbrugge RJ, Twinjstra A,Schouten HC. Spinal epidural abscess due to Aspergil-

554 Surg Neurol Vaishya and Sharma2004;61:551–5

lus infection of the vertebrae: report of three cases.Neth J Med 1996;48:18–23.

9. Fromtling RA, Shadomy HJ. An overview ofmacrophage-fungal interaction. Mycopathologia 1986;93:77–93.

10. Gerson SL, Talbot GH, Harwitz S. Prolonged granulo-cytopenia: the major risk factor for invasive pulmo-nary Aspergillosis in patients with acute leukemia.Ann Intern Med 1984;100:345–51.

11. Go BM, Ziring DJ, Kountz DS. Spinal epidural abscessdue to Aspergillus sp. in a patient with Acquired Im-munodeficiency Syndrome. South Med J 1993;86(8):957–60.

12. Gupta PK, Mahapatra AK, Gaind R, Bhandari S, MusaMM, Lad SD. Aspergillus spinal epidural abscess. Pe-diatr Neurosurg 2001;35:18–23.

13. Hendrix WC, Arruda LK, Platts-Mills TA, Haworth CS,Jabour R, Ward GW Jr. Aspergillus epidural abscessand cord compression in a patient with aspergillomaand empyema. Survival and response to high dosesystemic amphotericin therapy. Am Rev Respir Dis1992;145:1483–6.

14. Ingwer I, McLeish KR, Tight RR, White AC. Aspergillusfumigatus epidural abscess in a renal transplant re-cipient. Arch Intern Med 1978;138:153–4.

15. Kim M, Shin JH, Suh SP, et al. Aspergillus nidulansinfection in a patient with chronic granulomatousdisease. J Korean Med Sci 1997;12:244–8.

16. Polatty RC, Cooper KR, Kerkering TM. Spinal cordcompression due to an aspergilloma. South Med J1984;77:645–8.

17. Scamoni C, Dario A, Pozzi M, Dorizzi A. Drainage ofAspergillus ‘primitive’ brain abscess with long-termsurvival. Case report. J Neurosurg Sci 1990;34:155–8.

18. Seres JL, Ono H, Benner EJ. Aspergillosis presentingas spinal cord compression. J Neurosurg 1972;36:221–4.

19. Wagner DK, Varkey B, Sheth NK, Da Mert GJ. Epidural

abscess, vertebral destruction and paraplegia causedby extending infection from an aspergilloma. Am JMed 1985;78:518–22.

20. Waldorf AR. Host-parasite relationship in opportunis-tic mycoses. Crit Rev Microbiol 1986;13:133–172.

21. Witzig RS, Greer DL, Hyslop NE Jr. Aspergillus flavusmycetoma and epidural abscess successfully treatedwith itraconazole. J Med Vet Mycol 1996;34:133–7.

COMMENTARYFungal spinal infections are quite uncommon andordinarily occur in immunocompromised persons,but also in those patients receiving parenteral hy-peralimentation, or those with intravenous drugabuse. By far the most usual cause of these fungalagents are Candida species, followed by Aspergillusand others. A delay in diagnosis and treatment iscommon because of the diffuculty in making a diag-nosis and additionally since fungal isolation andidentification is often time consuming. As the au-thors note, amphotericin B and itraconazole havesuccessfully been used to treat aspergillosis in thepast, but were not effective in the patient describedin this case report. More recently, caspofungin andvoriconazole have been employed to treat systemicaspergillosis and are new compounds that couldfavorably affect the dismal outcome of fungal spinalinfections.

Lawrence A. Cone, M.D., F.A.C.P.Eisenhower Medical CenterRancho Mirage, California

Politics is the gentle art of getting votes from the poor andcampaign funds from the rich, by promising to protect each

from the other.

—Oscar Ameringer

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