Brain Pathology Case of the Month - May 2012


DIAGNOSIS AND DISCUSSION DIAGNOSIS

Disseminated Nocardiosis

DISCUSSION

Nocardia species are ubiquitous, aerobic Actinomycetes that dwell predominantly in soil and water. Infection in humans usually occurs as opportunistic disease following respiratory inhalation of Nocardia asteroides [1,4]. Primary pulmonary infection may manifest as subclinical, transient, or progressive chronic disease. Introduction through the skin occurs less frequently after trauma or intravenous drug abuse and may spread via lymphocutaneous routes.

Hematogenous dispersal of Nocardia species occasionally develops after primary inoculation and involvement by two or more organs qualifies as dissemination of disease. The occurrence of disseminated nocardiosis has increased during recent years, concurrent with survival rates of immunodepressed populations (particularly transplant recipients, AIDS and cancer patients, and those with chronic diseases necessitating long-term corticosteroid/cytotoxic therapies). Disease may also afflict immunocompetent persons [8]. Although hematogenous spread of infection to the central nervous system (CNS) is still rare, preferential migration to this site has been well-documented [4]. Less common sites of dissemination include the skin, bone, and joints [4]. Endogenous retinitis and endophthalmitis also occurs secondary to hematogenous dispersal, while ocular surface lesions (e.g. keratitis) generally result from penetrating injury or airborne spread [3,6]. Primary lesions may resolve spontaneously, however, making diagnosis of disseminated nocardiosis challenging [1,2,4,5].

Symptomatology in CNS disease is variable and may include meningeal symptoms, focal neurological deficit(s), seizures, and/or altered mental status with or without febrile episodes. CNS nocardiosis may also occasionally be asymptomatic. On brain MRI, lesions often manifest as a singular localized mass with loculation, ring-enhancement, and perilesional edema. Alternatively, imaging studies may highlight dispersed homogeneous micronodules. Therefore, the clinico-radiological features often raise a broad differential including high-grade primary astrocytoma, stroke, lymphoma, vasculitis, mycotic infection, miliary Tuberculosis, or metastatic disease [5]. Septic emboli were also considered early in the course of this patient with artificial heart valve and long-term anticoagulation for management of chronic atrial fibrillation. However, Nocardia brasiliensis was ultimately cultured from the patient's lower extremity wound and appropriate therapy was instituted.

A high degree of clinical suspicion is necessary for timely diagnosis and treatment of CNS nocardiosis as steroid therapy may exacerbate infection. In cases without known primary lesions, stereotactic aspiration with culture and antimicrobial sensitivity studies are desirable, if possible, to document disease. Tissue biopsy may also help rule out malignancy or co-infection by other microorganisms. Histopathologic changes on biopsy are variable but most frequently include focal meningitis, disseminated granulomata, or large pyogenic abscesses with or without fibroinflammatory encapsulation. GMS stain highlights beaded, branched, filamentous organisms. Typically, Gram stain yields positive rods while results of Acid-Fast and Fite stains are variable. For proper culture, the microbiology laboratory should be informed of suspected nocardiosis as prolonged incubation is required for in vitro growth.

Appropriate definitive therapy for CNS nocardiosis depends on individual factors such as extent of disease and patient immune status. Medical management includes prolonged antibiotic regimen (often exceeding one year), as recurrent and/or resistant infection may develop in inadequately-treated patients. Sulfonamides are the preferred oral agent due to their suitable CSF penetration [7]. Surgical excision is performed for large, multiloculated, or thick-walled abscesses. Early detection and management of CNS nocardiosis can yield favorable outcomes in immunocompetent patients. Nevertheless, prognosis of CNS nocardiosis remains guarded in immunodepressed individuals due to insidious onset, impaired host responses and usual delay in diagnosis.

REFERENCES

  1. Beaman BL, Beaman L (1994) Nocardia species: Host-parasite relationships Clin Microbiol Rev. 7:213-64.
  2. Chakrabarti P, Nandi SS, Todi SK (2008) Nocardia brain abscess in a diabetic patient. Indian J Pathol Microbiol. 51:151-3.
  3. Knouse MC, Lorber B (1990) Early diagnosis of Nocardia asteroides endophthalmitis by retinal biopsy: Case report and review. Rev Infect Dis. 12:393-8.
  4. Lerner PI (1996) Nocardiosis. Clin Infect Dis. 22:891-903.
  5. Menkü A, Kurtsoy A, Tucer B, Yildiz O, Akdemir H (2004) Nocardia brain abscess mimicking brain tumour in immunocompetent patients: Report of two cases and review of the literature. Acta Neurochir. 146:411-4.
  6. Sridhar MS, Gopinathan U, Garg P, Sharma S, Rao GN (2001) Ocular Nocardia infections with special emphasis on the cornea. Surv Ophthalmol. 45:361-78.
  7. Wallace RJ Jr, Steele LC, Sumter G, Smith JM (1988) Antimicrobial susceptibility patterns of Nocardia asteroides. Antimicrob Agents Chemother. 32:1776-9.
  8. Yaakup NA, Rahmat K, Ramli N, Sia SF (2009) Cerebral nocardiosis in an immunocompetent patient: A diagnostic dilemma. European Journal of Radiology Extra. 71:e47-e51.

Contributed by Arnob K. Mukherjee, MD, Orestes E. Solis, MD, Noriko Salamon, MD, Rupal I. Mehta, MD


International Society of Neuropathology