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Diagnostic pitfalls in eosinophilic cryptococcal meningoencephalitis
Case report
Eosinophilic cryptococcal meningoencephalitis
Diagnostic pitfalls in eosinophilic cryptococcal meningoencephalitis Pascal Grosse, Joachim Schulz, Klaus Schmierer
A 64-year-old woman was admitted to our hospital in 2000 antibodies against Echinococcus granulosus. However, the lack with a persistent headache and progressive inattentiveness for of typical cystic lesions on cerebral MRI, the absence of 2 months. She also had abdominal pain; MRI before extracerebral disease, and the lack of Echinococcus granularis admission revealed abdominal lymphadenopathy. The patient antibodies in CSF made this diagnosis unlikely. Taking into had lived in South America before moving to Germany account the low glucose and high lactate concentrations in 6 months before admission. When we examined her, we CSF, tuberculosis or fungal infections—both compatible found that she was easily fatigued and with multiple gadolinium-enhancing had a reduced attention span. lesions and CSF eosinophilia—need MRI of the brain showed multiple to be considered. Among fungal gadolinium-enhancing lesions, up to infections, eosinophilic meningitis is 6 mm in diameter, which had infiltrated well-documented only in coccidoidothe adjacent meninges (figure). CSF mycosis, and has been reported in only analysis showed pleocytosis of 582x106 three patients with cryptococcosis.1–3 leucocytes/L (60% lymphocytes, 17% One child with cryptococcal meningoneutrophils, 6% monocytes, 12% encephalitis had blood, but not eosinophils, and 3% plasma cells). The CSF, eosinophilia.4 As with our patient, a pathogenetic link between CSF concentration of protein was high cryptococcosis and CSF eosinophilia (3·5 g/L) as was that of lactate has been established by the curing of (4·25 mmol/L). Glucose concentration both with antifungal treatment. In our was low (0·61 mmol/L). Leucocyte patient, eosinophilia regressed much count (11·1x109/L) was high (2·2x109/L lymphocytes, 4·6x109/L neutrophils, quicker in the blood than in the CSF. 3·4x109/L eosinophils, and 0·8x109/L Some immunocompromising dismonocytes). There were no bacterial, MRI showed four gadolinium-enhancing lesions orders associated with cryptococcosis, protozoal, or viral antibodies in the surrounded by perifocal oedema such as leukaemia and lymphoma, can serum and CSF. Cryptococcus cause blood eosinophilia and neoformans capsular antigen was found in serum and in CSF. eosinophilic meningitis by themselves.5 This is particularly In CSF, cryptococci were identified by use of india ink true for non-Hodgkin lymphoma, in which blood staining. The infection was identified as C neoformans var eosinophilia alone or with eosinophilic endomyocardial neoformans serotype A. No other mycoses were found; disease and tissue eosinophilia has been seen. Intriguingly, however, serum analysis for helminthic infection showed high non-Hodgkin’s lymphomatous meningitis has been reported titres of antibodies against Echinococcus granulosus on indirect as the only cause of eosinophilic meningitis. Despite the high haemagglutinin assay and ELISA in serial serum samples, but sensitivity and specificity of the Cryptococcus antigen test not in CSF. Brain biopsy confirmed cryptococcal (>90%), diagnostic brain biopsy might be needed in cases of menigoencephalitis. Bone-marrow biopsy revealed infiltration equivocal evidence. with monoclonal T-cells; this finding is consistent with the References diagnosis of an angioimmunoblastic T-cell lymphoma, which 1 Müller W, Schorre W, Suchenwirth RM, Konorza G. A case of fatal cryptococcus meningitis with intraventricular granuloma. Acta Neurochir 1978; 44: 223–35. was not treated subsequently. 2 Anderson P, Macklis J, Brown M, Ory D. Eosinophilic cerebrospinal fluid pleocytosis The patient’s headache and fatigue resolved within and cryptococcal meningitis. Ann Intern Med 1985; 103: 306–07. S, Reiter-Owona I, Hotz M, Mewes J, Biniek R. An unusual case of central 2 weeks of starting antifungal therapy (amphotericin 4 g/kg; 3 Schmidt nervous system cryptococcosis. Clin Neurol Neurosurg 1995; 97: 23–27. 5-flucytosin 200 mg/kg; fluconazole 400 mg/day) for 8 weeks. 4 Marwaha RK, Trehan A, Jayashree K, Vasishta RK. Hypereosinophilia in disseminated disease. Pediatr Infect Dis J 1995; 4: 102–03. Blood eosinophil and leucocyte counts returned to normal in 5 cryptococcal Weller PF, Liu LX. Eosinophilic menigitis. Semin Neurol 1993; 13: 61–168. the first week of treatment. CSF pleocytosis and eosinophilia regressed more slowly; after 3 weeks there was still CSF pleocytosis (417x106 leucocytes/L; 4% eosinophils). However, PG, JS, and KS are at the Department of Neurology, Charité, Campus Virchow-Klinikum, Humboldt-University Berlin, Germany after 7 weeks, no eosinophils were detected in the CSF, and the Correspondence: Dr Pascal Grosse, Sobell Department of Motor cerebral lesions on MRI were reduced in size. Neuroscience and Movement Disorders (Box 146), Institute of Eosinophilic meningoencephalitis commonly raises the Neurology, UCL, 8-11 Queens Square, London WC1N 3BG, UK. suspicion of helminthic infection, and our patient had serum Email [email protected]
512
THE LANCET Neurology Vol 2 August 2003
http://neurology.thelancet.com
For personal use. Only reproduce with permission from The Lancet.
Eosinophilic cryptococcal meningoencephalitis
Diagnostic pitfalls in eosinophilic cryptococcal meningoencephalitis Pascal Grosse, Joachim Schulz, Klaus Schmierer
A 64-year-old woman was admitted to our hospital in 2000 antibodies against Echinococcus granulosus. However, the lack with a persistent headache and progressive inattentiveness for of typical cystic lesions on cerebral MRI, the absence of 2 months. She also had abdominal pain; MRI before extracerebral disease, and the lack of Echinococcus granularis admission revealed abdominal lymphadenopathy. The patient antibodies in CSF made this diagnosis unlikely. Taking into had lived in South America before moving to Germany account the low glucose and high lactate concentrations in 6 months before admission. When we examined her, we CSF, tuberculosis or fungal infections—both compatible found that she was easily fatigued and with multiple gadolinium-enhancing had a reduced attention span. lesions and CSF eosinophilia—need MRI of the brain showed multiple to be considered. Among fungal gadolinium-enhancing lesions, up to infections, eosinophilic meningitis is 6 mm in diameter, which had infiltrated well-documented only in coccidoidothe adjacent meninges (figure). CSF mycosis, and has been reported in only analysis showed pleocytosis of 582x106 three patients with cryptococcosis.1–3 leucocytes/L (60% lymphocytes, 17% One child with cryptococcal meningoneutrophils, 6% monocytes, 12% encephalitis had blood, but not eosinophils, and 3% plasma cells). The CSF, eosinophilia.4 As with our patient, a pathogenetic link between CSF concentration of protein was high cryptococcosis and CSF eosinophilia (3·5 g/L) as was that of lactate has been established by the curing of (4·25 mmol/L). Glucose concentration both with antifungal treatment. In our was low (0·61 mmol/L). Leucocyte patient, eosinophilia regressed much count (11·1x109/L) was high (2·2x109/L lymphocytes, 4·6x109/L neutrophils, quicker in the blood than in the CSF. 3·4x109/L eosinophils, and 0·8x109/L Some immunocompromising dismonocytes). There were no bacterial, MRI showed four gadolinium-enhancing lesions orders associated with cryptococcosis, protozoal, or viral antibodies in the surrounded by perifocal oedema such as leukaemia and lymphoma, can serum and CSF. Cryptococcus cause blood eosinophilia and neoformans capsular antigen was found in serum and in CSF. eosinophilic meningitis by themselves.5 This is particularly In CSF, cryptococci were identified by use of india ink true for non-Hodgkin lymphoma, in which blood staining. The infection was identified as C neoformans var eosinophilia alone or with eosinophilic endomyocardial neoformans serotype A. No other mycoses were found; disease and tissue eosinophilia has been seen. Intriguingly, however, serum analysis for helminthic infection showed high non-Hodgkin’s lymphomatous meningitis has been reported titres of antibodies against Echinococcus granulosus on indirect as the only cause of eosinophilic meningitis. Despite the high haemagglutinin assay and ELISA in serial serum samples, but sensitivity and specificity of the Cryptococcus antigen test not in CSF. Brain biopsy confirmed cryptococcal (>90%), diagnostic brain biopsy might be needed in cases of menigoencephalitis. Bone-marrow biopsy revealed infiltration equivocal evidence. with monoclonal T-cells; this finding is consistent with the References diagnosis of an angioimmunoblastic T-cell lymphoma, which 1 Müller W, Schorre W, Suchenwirth RM, Konorza G. A case of fatal cryptococcus meningitis with intraventricular granuloma. Acta Neurochir 1978; 44: 223–35. was not treated subsequently. 2 Anderson P, Macklis J, Brown M, Ory D. Eosinophilic cerebrospinal fluid pleocytosis The patient’s headache and fatigue resolved within and cryptococcal meningitis. Ann Intern Med 1985; 103: 306–07. S, Reiter-Owona I, Hotz M, Mewes J, Biniek R. An unusual case of central 2 weeks of starting antifungal therapy (amphotericin 4 g/kg; 3 Schmidt nervous system cryptococcosis. Clin Neurol Neurosurg 1995; 97: 23–27. 5-flucytosin 200 mg/kg; fluconazole 400 mg/day) for 8 weeks. 4 Marwaha RK, Trehan A, Jayashree K, Vasishta RK. Hypereosinophilia in disseminated disease. Pediatr Infect Dis J 1995; 4: 102–03. Blood eosinophil and leucocyte counts returned to normal in 5 cryptococcal Weller PF, Liu LX. Eosinophilic menigitis. Semin Neurol 1993; 13: 61–168. the first week of treatment. CSF pleocytosis and eosinophilia regressed more slowly; after 3 weeks there was still CSF pleocytosis (417x106 leucocytes/L; 4% eosinophils). However, PG, JS, and KS are at the Department of Neurology, Charité, Campus Virchow-Klinikum, Humboldt-University Berlin, Germany after 7 weeks, no eosinophils were detected in the CSF, and the Correspondence: Dr Pascal Grosse, Sobell Department of Motor cerebral lesions on MRI were reduced in size. Neuroscience and Movement Disorders (Box 146), Institute of Eosinophilic meningoencephalitis commonly raises the Neurology, UCL, 8-11 Queens Square, London WC1N 3BG, UK. suspicion of helminthic infection, and our patient had serum Email [email protected]
512
THE LANCET Neurology Vol 2 August 2003
http://neurology.thelancet.com
For personal use. Only reproduce with permission from The Lancet.