Aspergillosis presenting as spinal cord compression

Case report

JOEL L. SERES, M.D., HIROHISA ONO, M.D., AND ERNEST J. BENNER, M.D. Division of Neurosurgery, University o/ Oregon Medical School, Portland, Oregon

A case of pulmonary aspergillosis resembling bronchogenic carcinoma with extension to the thoracic vertebrae is presented. Therapy is discussed and the need for awareness of this potentially fatal infection stressed.

KEY WORDS aspergillosis fungus infection spinal cord vertebra

C LINICAL infections caused by sapro- phytic fungi are occurring with an in- creasing frequency in patients with al-

tered host defense. 3,~,6,8,~-~5,~,2~,2~,3~ An organism frequently encountered in these sit- uations is Aspergillus [umigatus? ~ This fun- gus usually produces a localized pulmonary infectionY ~ However, as host resistance is altered, local invasion 8 and disseminated in- fection occur? Involvement of the central nervous system occurs as granulomatous le- sions in the brain and meninges are dissemi- nated, 1,6,z9 or less commonly as a localized invasion of the spinal cordY 4 Our report de- scribes a patient with pulmonary aspergillo- sis which mimicked a carcinoma of the lung with erosion of thoracic vertebrae and spinal cord compression.

Case Report

This 62-year-old white woman noted a dull aching pain in the right forearm and wrist in August, 1966, gradually progressing to involve the right shoulder and chest. In February, 1967, she lost 12 lbs. and pro- duced large amounts of bloody sputum. A roentgenogram revealed an infiltrating mass

in the right upper lobe. She had enjoyed good health until the present illness. There had been no birds in her home, but there was contact with horses and cattle from 1963 to 1965.

Examination. When seen on March 10, 1967, the patient appeared chronically ill and had a right-sided Homer's syndrome. There was a fullness in the right supraclavi- cular fossa which was firm, nontender, and fixed to the surrounding tissue. There were decreased breath sounds and tales heard over the upper right chest. The neurological examination was unremarkable, except for decreased pain and light touch over the right T-1 dermatome. The preliminary diagnosis was that of a right superior sulcus tumor syndrome. The hemoglobin was 8 gm%, and the erythrocyte sedimentation rate (Win- trobe) was 83 mm at 45 rain. The white blood cell count was 7161/mm 3, with a nor- mal differential. The serum globulin was 3.8 gin% and albumin 2.6 gm%. Numerous tests of liver function, thyroid function, cal: cium metabolism, and renal function were normal, as was a metastic bone survey. An iron deficiency anemia was confirmed by

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Joel Seres, Hirohisa Ono and Ernest Benner

bone marrow and iron studies. The right lung infiltrate persisted (Fig. 1 ).

The second strength PPD (purified pro- tein derivative) test was positive, and the se- rum alkaline phosphatase value increased from 7.6 to 36.7 King Armstrong units, dur- ing her hospitalization. Despite this, neither tuberculosis nor tumor could be detected by bronchoscopy, multiple cytologic studies or sputum, scalene lymph node biopsy, or liver biopsy.

Operation. A right thoracotomy was done on April 18, 1967, and a small biopsy taken from the 6 X 8 cm mass in the right upper lobe. Fungi were found in the sections and subsequently grew in culture as Aspergillus ]umigatus (Fig. 2). An apical mass was re- moved with an intact upper right lobe on May 8, 1967; the specimen contained A. lu- migatus. The remainder of the lung was nor- mal, and no lymph nodes were palpated in the hilum or the upper mediastinum.

Postoperative Course. The patient did well until 5 days after the thoracic surgery when weakness of the right leg, bilaterial ex- tensor plantar reflexes, and hypesthesia of the T-2 dermatome appeared. Cerebrospinal fluid and manometrics were normal; the pro- tein content was 80 mg%. Leg weakness fluctuated, and then on May 16, 1967, be- came severe, with a sensory loss below T-6. A myelogram demonstrated a complete block at the T-2 level with displacement of the spinal cord to the left and an irregular roughening of the pedicles on the right at T- 2.

FIO. 1. Chest film demonstrating right apical mass. Note deviation of trachea.

F1o. 2. Photomicrograph demonstrating fungi in pulmonary tissue producing an acute inflammatory process. H & E, x 150.

Second Operation. A decompressive lam- inectomy of C-7 to T-3 was performed and a large epidural mass extending to the pedicles of T-2 found. The mass was stripped with difficulty from the dura and small pockets of purulent material were noted; the dura was not opened.

Second Postoperative Course. Within the first 36 hours after surgery the neurological deficit progressed to a state of complete paraplegia. A sharp sensory level was pres- ent at T-2 and has persisted to date. Therapy with intravenous amphotericin B was insti- tuted. The patient received increasing doses for 4 days, then 60 mg daily for 15 days. She tolerated this treatment satisfactorily with no evidence of renal dysfunction, as determined by blood urea nitrogen and serum creatinine values. She was discharged on June 6, 1967. Neurological function has remained stable. There has been no evidence of recurrence of the infectious process.

Comment

Aspergillus infection of the central ner-

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Asperg iUos i s p r e s e n t i n g as sp ina l cord c o m p r e s s i o n

vous system occurs as single or multiple granulomata or abscesses, chronic granulo- matous meningitis, or meningoencephalitis, 11 or local compression of the spinal cord; however these lesions are usually in associa- tion with disseminated infection. ',9,1~ In- volvement of the central nervous system may be hematogenous with multiple perivascular infections, arteritis, or thromboses2 2 It may occur by direct extension from eye, 2~ ear, or sinus 2~ infections2 7 On rare occasions it causes spinal cord compression as an epi- dural abscess or through involvement of the thoracic vertebrae, r,24,26

Our patient's illness closely mimicked the symptomatology of a bronchogenic carci- noma. The presence of the Homer's syn- drome, nerve root involvement producing radicular pain, and destruction of the upper thoracic vertebrae with spinal cord compres- sion all suggested a fairly typical superior sulcus mass with metastases. The central nervous system involvement without evi- dence of systemic spread to other organs was unusual. It is also noteworthy that the diag- nosis was made by the frozen section.

It is important that this disease be consid- ered whenever there is a generalized lower- ing of the host resistance as in lymphoma or leukemia, a focal point of entry, or the use of broad spectrum antibiotics or corticoste- roids favoring the growth and spread of fungi. Specific precipitins against antigenic extracts of cultures and protein fractions suitable for highly specific skin testing ~ are available for the diagnosis of chronic asper- gillosis infection2 ,19

Little is known about specific therapy for this infrequent infection. Amphotericin B has been found effective in some cases, 29 but the overall results have been poor, even with massive intracaval doses. 2.,24 Recently, hy- perbaric oxygen has been found helpful in treating pigeons, however its uses have not been described in man. 28 Certainly, aware- ness of this infection in susceptible individu- als provides for earlier diagnosis and start of specific treatment. 18,19

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mia as factors predisposing to fatal mycoses: mucormycosis, aspergillosis cryptococcosis. Amer J Clin Path 37:358-373, 1962

3. Burston J, Blackwood W: A case of Aspergillus infection of the brain. J Path Bact 86:225-229, 1963

4. Buttrick DD, Roberts L: Generalized cytome- galic inclusion disease. Amer J Dis Child 110: 319-328, 1965

5. Cawley EP: Aspergillosis and the aspergilli. Arch Intern IVied 80:423-434, 1947

6. Epstein S, Miale TD, Moossy J, et al: Experi- mental intracranial aspergillosis. J Neuropath Exp Neurol 27:473-482, 1968

7. Finegold SM, Will D, Murray JF: Aspergillo- sis: a review and report of 12 cases. Amer J Med 27:463-482, 1959

8. Grekin RH, Cawley EP, Zheutlin B: General- ized aspergillosis: report of a case. Arch Path 49:387-392, 1950

9. Heffernan AG, Asper SP Jr: Insidious fungal disease: a clinicopathological study of secon- dary aspergillosis. Bull Hopkins Hosp 118:10- 26, 1966

10. Hughes WT: Generalized aspergillosis: a case involving the central nervous system. Amer J Dis Child 112:262-265, 1966

11. Jackson IJ, Earle K, Kari J: Solitary Aspergil- lus granuloma of the brain: report of 2 cases. J Neurosurg 12"53-61, 1955

12. Keye JD Jr, Magee WE: Fungal diseases in a general hospital: a study of 88 patients. Amer J Clin Path 26:1235-1253, 1956

13. Khoo TK, Sugai K, Leong TK: Disseminated aspergiUosis: case report and review of the world literature. Amer J Clin Path 45:697- 703, 1966

14. Levene N, Rivarola CH, Blue ME: Surgical considerations in pulmonary tuberculosis com- plicated by bronchopulmonary aspergillosis. Amer Rev Resp Dis 91:262-267, 1965

15. Levy ES, Cohen DB: Systemic moniliasis and aspergiUosis complicating corticotropin ther- apy. Arch Intern Med 95:118-122, 1955

16. Luke JL, Bolande RP, Gross S: Generalized aspergillosis and Aspergillus endocarditis in in- fancy. Pediatrics 31:115-122, 1963

17. Lyer S, Dodge PR: Two cases of Aspergillus infection of the central nervous system. J Neurol Neurosurg Psychlat 15:112, 1965

18. Mukoyama M, Gimple K, Poser CM: Asper- gillosis of the central nervous system. Neurol- ogy (Minneap) 19:967-974, 1969

19. Mearns M, Longbottom J, Batten J: Precipi- tating antibodies to Aspergillus Jumigatus in cystic fibrosis. Lancet 1:538-539, 1967

20. Montreuil F: Fungus infection of antrum. J Laryngol 69:559-566, 1955

21. Mostafa MSE: Aspergillus niger infection of eye. Amer J Ophthal 62:1204--1205, 1966

22. Newman WH, Cordell AR: Aspergillus endo- carditis after open-heart surgery: report of a case and review of literature. J Thorac Cardio- vasc Surg 48:652-660, 1964

23. Peet MM: .4spergillus Jumigatus infection of the cerebellum. Trans Amer Neurol Ass 71: 165, 1946 (abstract)

24. Redmond A, Carr6 IJ, Biggart JD, et ah Asper- gillosis (,4spergillus nidulans) involving bone. J

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Path Bact 89:391-396, 1965 25. Schwarz J, Baum GL, Straub M: Cavity histo-

plasmosis complicated by fungus ball. Amer J Med 31:692-700, 1961

26. Shaw FW, Warthen HJ: Aspergillosis of bone. Southern Med J 29:1070-1071, 1936

27. Spens N, Tattersall WH: Fungal infection of central nervous system supervening during routine chemotherapy for pulmonary tubercu- losis. Brit Med J 2:862, 1965

28. Strelling MK, Rhaney K, Simmons DAR, et al: Fatal acute pulmonary aspergillosis in two children of one family. Arch Dis Child 41:34- 43, 1966

29. Tobler VW, Minder W: Generalisierte chron- ische aspergillose beim kind und ihre bezie- hung zur antibiotischen therapie. Heir Paedlat Acta 9:209-230, 1954

30. Torack RM: Fungus infections associated with

antibiotic and steroid therapy. Amer J Med 22: 872-882, 1957

31. Tveten L: Cerebral mycosis: a clinico-patho- logical report of four cases: Acta Neurol Stand 41:19-33, 1965

32. Tveten L, LCken AC, Hauge T: Aspergillus cerebri: report of a case. Aeta Chit Scand 130: 149-156, 1965

33. Wahl EF, Erickson MJ: Primary pulmonary aspergillosis. J Med Ass Georgia 17:341-349, 1928

34. Zimmerman LE: Fatal fungus infections com- plicating other diseases. Amer J Clin Path 25: 46-65, 1955

Received for publication October 27, 1970. Address reprint requests to: Joel L. Seres, M.D.,

Division of Neurosurgery, University of Oregon Medical School, 3181 S.W. Sam Jackson Park Road, Portland, Oregon 97201.

224 I. Neurosurg. / Volume 36 / February, 1972