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Cryptococcosis in an immunocompetent pregnant woman
92
revue neurologique 169 (2013) 88–95
Cryptococcosis in an immunocompetent pregnant woman Cryptococcose neurome´ninge´e chez une patiente immunocompe´tente
1.
Case report
Cryptococcosis is a severe infection due to an encapsulated yeast, with great affinity for the immunosuppressed host, and whose primary tropism is the central nervous system and the lungs. More easily evoked in HIV positive patients, it may also be associated with diseases or treatments which cause suppression of cell-mediated immunity. Possibly 10–40% of HIV negative patients with cryptococcosis have no known immune disorder (Diamond and Bennett, 1973). We report a case of cryptococcosis meningoencephalitis in a 36-year-old woman with an ongoing pregnancy of 7 months. She presented a 3-week history of severe headache, vomiting, diplopia and two generalised seizures. She was apyrexial with no neck stiffness or papilloedema, with left hemiparesis and a palsy of both abducens oculomotor nerves. Brain magnetic resonance imaging (MRI) revealed a hyperintensity on T2weighted sequence in the left lenticular nucleus (Fig. 1). Cerebral spinal fluid (CSF) examination showed white cell count of 115/mm3 (90% lymphocytes), protein level of 1.5 g/l and glucose level of 0,12 g/l with crypotococcus neoformans isolated in culture. She tested negative for HIV, lupus and sarcoidosis. Thus, she was treated for CNS cryptococcosis with intravenous amphotericin B at a dose of 1 mg/kg per day then steroids were added at the dose of 1 mg/kg par day as she presented a mild cerebral herniation. The outcome was
Fig. 1 – Magnetic resonance imaging: axial T2 weighted sequence showing a hypersignal of the left lenticular nucleus. Imagerie par re´sonance magne´tique : se´quence ponde´re´e T2 axiale montrant un hypersignal du noyau lenticulaire gauche.
favourable, except for treatment-related complications. Forty-five days after admission, she delivered a female newborn with an Apgar score at 10. After 6 weeks of treatment with amphotericin B, she was switched to fluconazole at a dose of 200 mg/day for 6 weeks. She responded well to treatment and became asymptomatic. Three months later, our patient presented signs of intracranial hypertension and CSF culture of cryptococcocus was positive on lumbar puncture. She received amphotericine B for 10 weeks then maintenance therapy with fluconazole 200 mg/day. However, the patient still accused headache with decreased visual acuity. Monitoring of intracranial pressure revealed a persistent intracranial hypertension superior to 25 cm H2O and she underwent a ventriculoperitoneal shunt that allowed clinical stabilisation.
2.
Discussion
We diagnosed our patient with central nervous system cryptococcosis as she presentedmeningoencephalitis and signs of elevated intracranial pressure, while she was 7 months pregnant. The diagnosis of cryptococcosis was confirmed by the positive CSF culture isolating Cryptococcus neoformans, but no immunocompromising condition was found as HIV testing was negative as well as investigations for a predisposing disease. Cryptococcosis is difficult to diagnose in immunocompetent patients unless it is suspected. In a recent study, the conditions most commonly associated with cryptococcosis included immunosuppressive drug treatment (41%), systemic lupus erythematosus (16%), malignancy (16%), and diabetes mellitus (14%) (Kiertiburanakul et al., 2006). Pregnancy has also been considered as an immunocompromising condition in reported cases of cryptococcosis. This predisposition for cryptococcosis during pregnancy is often explained by a theory of relative immunosuppression that facilitates the survival of a semiallogeneic fetus within the mother. In fact, during the state of pregnancy, colonization by cryptococcal spores inoculated by inhalation may be facilitated by the slightly down-regulated Th1 surveillance (Sravani, 2010). A review of all cases involving pregnancy and neurocryptococcal infection in immune competent pregnant patients reported 27 mycology proven cases. The mean age of patients at diagnosis was 26.4 years old. The most prevalent symptoms were headache (85.2%) followed by altered vision (44.4%). Nausea and vomiting were reported in 40.7% of the patients and fever in 33.3% (Costa et al., 2009). Our patient’s clinical manifestations also included headache with signs of elevated intracranial pressure and encephalitic involvement as she had seizures, behavioural changes and hemiparesis, which are considered signs of poor prognosis (Pappas et al., 2001). As for treatment of cryptococcosis during pregnancy, no data is available to ascertain the optimal duration of antifungal therapy. Our patient relapsed 3 months after fluconazole was discontinued, which could be due to the insufficient duration of consolidation treatment. In fact, it has been demonstrated in several studies that the rate of relapse was inversely correlated with the duration of antifungal therapy and the mortality is 20% despite treatment well conducted,
93
revue neurologique 169 (2013) 88–95
mostly by shedding or intracranial hypertension (Perfect and Casadevall, 2002). During the relapse, our patient presented with signs of intracranial hypertension with no hydrocephalus associated on brain MRI. Raised intracranial pressure is a recognised complication of cryptococcal meningitis and is associated with a poorer clinical response and increased mortality (York et al., 2005). The frequency of intracranial hypertension during cryptococcosis is poorly known; probably more than 50% and its management by early surgical bypass contributes to improving the prognosis (York et al., 2005). Our case states pregnancy as a predisposing condition to cryptococcosis. Treatment guidelines are necessary to improve the management especially in terms of the duration of maintenance therapy and indications of bypass to treat intracranial hypertension to avoid sequelaes.
b
Department of Internal Medicine, hoˆpital Ibn Sina, avenue Ibn Rochd, Rabat, Morocco c Laboratory of Microbiology, hoˆpital des spe´cialite´s ONO, Avenue Mohamed Belarbi Alaoui, Rabat, Morocco *Corresponding author. E-mail address: [email protected] (L. Lachhab) 1
Both authors contributed equally to this work. Received 15 March Received in revised form 25 March Accepted 3 April Available online 4 July
2012 2012 2012 2012
0035-3787/$ – see front matter # 2012 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.neurol.2012.04.004
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
references
Costa M, Souza J, Oliveira Neto A, Pinto E, Silva J. Cryptococcal meningitis in HIV negative pregnant women: case report and review of literature. Rev Inst Med Trop S Paulo 2009;51(5):289–94. Diamond RD, Bennett JE. Disseminated cryptococcosis in man: decreased lymphocyte transformation in response to Cryptococcus neoformans. J Infect Dis 1973;127:694–7. Kiertiburanakul S, Wirojtananugoon S, Pracharktam R, Sungkanuparph S. Cryptococcosis in human immunodeficiency virus-negative patients. Int J Infect Dis 2006;10:72–8. Pappas PG, Perfect JR, Cloud GA, Larsen RA, Pankey GA, Lancaster DJ, et al. Cryptococcosis in human immunodeficiancy virus negative patients in the era of effective azote therapy. Clin Infect Dis 2001;33:690–9. Perfect JR, Casadevall A. Cryptococcosis. Infect Dis Clin North Am 2002;16:837–74. Sravani VM. Disseminated cryptococcosis in an HIV-negative pregnancy: a case of cryptococcal septic abortion complicating an immunocompetent pregnancy. Int J Infect Dis 2010;14:351–3. York J, Bodi I, Reeves I, Riordan-Eva P, Easterbrook PJ. Raised intracranial pressure complicating cryptococcal meningitis: immune reconstitution inflammatory syndrome or recurrent cryptococcal disease? J Infect 2005;51:165–71.
L. Lachhaba,*,1 K. Rasmounia,1 E.H. Ait Ben Haddoua M. Maamarb M. Seffarc W. Regraguia A. Benomara M. Yahyaouia a Department of Neurology B and neurogenetics, hoˆpital des spe´cialite´s ONO, avenue Mohamed Belarbi Alaoui, Rabat, Morocco
Neuropathie ataxiante re´ve´latrice d’un CMT1A Ataxia phenotype of type 1 Charcot-Marie-Tooth disease: An atypical presentation Un homme de 26 ans, sans ante´ce´dents, issu d’un mariage consanguin entre cousins germains, consulta pour des troubles de l’e´quilibre e´voluant depuis une dizaine d’anne´es. Le patient signalait des troubles semblables chez sa me`re, sa grand-me`re maternelle, son arrie`re-grand-me`re, son oncle maternel et sa fille. L’examen re´ve´lait une marche talonnante, un signe de Romberg a` la fermeture des yeux, un de´ficit moteur distal des loges ante´ro-externes de jambes cote´ a` 4+/5 sans amyotrophie, une are´flexie ge´ne´ralise´e, des troubles de la sensibilite´ marque´s par une hypopallesthe´sie et une hyperesthe´sie distale pre´dominant aux membres infe´rieurs ainsi que des signes dysmorphiques objective´s par l’existence de pieds creux. Il n’y avait pas d’hypertrophie des troncs nerveux. L’e´lectroneuromyogramme orientait vers une neuropathie de´mye´linisante (Tableau 1). Les causes classiques de neuropathie de´mye´linisante chronique furent exclues. En effet le bilan paraclinique suivant e´tait normal ou ne´gatif et permettait, notamment, d’e´liminer un diabe`te et une he´mopathie : nume´ration de la formule sanguine, ionogramme, he´moglobine glyque´e, fonction re´nale, immuno-e´lectrophore`se des prote´ines se´riques, se´rologies he´patite B, he´patite C, VIH, HTLV1 et 2, bilan immunologique, e´tude du comple´ment, cryoglobuline´mie et biopsie des glandes salivaires. Quant au diagnostic de polyradiculone´vrite de´mye´linisante chronique, l’absence de bloc de conduction, l’absence de dispersion temporelle et l’absence de de´mye´linisation he´te´roge`ne a` l’ENMG le rendait peu probable et cela malgre´ une hyperprote´inorachie (0,72 g/L) isole´e a` la ponction lombaire et l’absence de biopsie nerveuse re´alise´e. Compte tenu de cas familiaux similaires sur plusieurs ge´ne´rations, des donne´es neurophysiologiques, de l’existence de pieds creux et de l’absence d’e´tiologie, l’e´tude du ge`ne PMP22 par biologie mole´culaire a mis en e´vidence une duplication
revue neurologique 169 (2013) 88–95
Cryptococcosis in an immunocompetent pregnant woman Cryptococcose neurome´ninge´e chez une patiente immunocompe´tente
1.
Case report
Cryptococcosis is a severe infection due to an encapsulated yeast, with great affinity for the immunosuppressed host, and whose primary tropism is the central nervous system and the lungs. More easily evoked in HIV positive patients, it may also be associated with diseases or treatments which cause suppression of cell-mediated immunity. Possibly 10–40% of HIV negative patients with cryptococcosis have no known immune disorder (Diamond and Bennett, 1973). We report a case of cryptococcosis meningoencephalitis in a 36-year-old woman with an ongoing pregnancy of 7 months. She presented a 3-week history of severe headache, vomiting, diplopia and two generalised seizures. She was apyrexial with no neck stiffness or papilloedema, with left hemiparesis and a palsy of both abducens oculomotor nerves. Brain magnetic resonance imaging (MRI) revealed a hyperintensity on T2weighted sequence in the left lenticular nucleus (Fig. 1). Cerebral spinal fluid (CSF) examination showed white cell count of 115/mm3 (90% lymphocytes), protein level of 1.5 g/l and glucose level of 0,12 g/l with crypotococcus neoformans isolated in culture. She tested negative for HIV, lupus and sarcoidosis. Thus, she was treated for CNS cryptococcosis with intravenous amphotericin B at a dose of 1 mg/kg per day then steroids were added at the dose of 1 mg/kg par day as she presented a mild cerebral herniation. The outcome was
Fig. 1 – Magnetic resonance imaging: axial T2 weighted sequence showing a hypersignal of the left lenticular nucleus. Imagerie par re´sonance magne´tique : se´quence ponde´re´e T2 axiale montrant un hypersignal du noyau lenticulaire gauche.
favourable, except for treatment-related complications. Forty-five days after admission, she delivered a female newborn with an Apgar score at 10. After 6 weeks of treatment with amphotericin B, she was switched to fluconazole at a dose of 200 mg/day for 6 weeks. She responded well to treatment and became asymptomatic. Three months later, our patient presented signs of intracranial hypertension and CSF culture of cryptococcocus was positive on lumbar puncture. She received amphotericine B for 10 weeks then maintenance therapy with fluconazole 200 mg/day. However, the patient still accused headache with decreased visual acuity. Monitoring of intracranial pressure revealed a persistent intracranial hypertension superior to 25 cm H2O and she underwent a ventriculoperitoneal shunt that allowed clinical stabilisation.
2.
Discussion
We diagnosed our patient with central nervous system cryptococcosis as she presentedmeningoencephalitis and signs of elevated intracranial pressure, while she was 7 months pregnant. The diagnosis of cryptococcosis was confirmed by the positive CSF culture isolating Cryptococcus neoformans, but no immunocompromising condition was found as HIV testing was negative as well as investigations for a predisposing disease. Cryptococcosis is difficult to diagnose in immunocompetent patients unless it is suspected. In a recent study, the conditions most commonly associated with cryptococcosis included immunosuppressive drug treatment (41%), systemic lupus erythematosus (16%), malignancy (16%), and diabetes mellitus (14%) (Kiertiburanakul et al., 2006). Pregnancy has also been considered as an immunocompromising condition in reported cases of cryptococcosis. This predisposition for cryptococcosis during pregnancy is often explained by a theory of relative immunosuppression that facilitates the survival of a semiallogeneic fetus within the mother. In fact, during the state of pregnancy, colonization by cryptococcal spores inoculated by inhalation may be facilitated by the slightly down-regulated Th1 surveillance (Sravani, 2010). A review of all cases involving pregnancy and neurocryptococcal infection in immune competent pregnant patients reported 27 mycology proven cases. The mean age of patients at diagnosis was 26.4 years old. The most prevalent symptoms were headache (85.2%) followed by altered vision (44.4%). Nausea and vomiting were reported in 40.7% of the patients and fever in 33.3% (Costa et al., 2009). Our patient’s clinical manifestations also included headache with signs of elevated intracranial pressure and encephalitic involvement as she had seizures, behavioural changes and hemiparesis, which are considered signs of poor prognosis (Pappas et al., 2001). As for treatment of cryptococcosis during pregnancy, no data is available to ascertain the optimal duration of antifungal therapy. Our patient relapsed 3 months after fluconazole was discontinued, which could be due to the insufficient duration of consolidation treatment. In fact, it has been demonstrated in several studies that the rate of relapse was inversely correlated with the duration of antifungal therapy and the mortality is 20% despite treatment well conducted,
93
revue neurologique 169 (2013) 88–95
mostly by shedding or intracranial hypertension (Perfect and Casadevall, 2002). During the relapse, our patient presented with signs of intracranial hypertension with no hydrocephalus associated on brain MRI. Raised intracranial pressure is a recognised complication of cryptococcal meningitis and is associated with a poorer clinical response and increased mortality (York et al., 2005). The frequency of intracranial hypertension during cryptococcosis is poorly known; probably more than 50% and its management by early surgical bypass contributes to improving the prognosis (York et al., 2005). Our case states pregnancy as a predisposing condition to cryptococcosis. Treatment guidelines are necessary to improve the management especially in terms of the duration of maintenance therapy and indications of bypass to treat intracranial hypertension to avoid sequelaes.
b
Department of Internal Medicine, hoˆpital Ibn Sina, avenue Ibn Rochd, Rabat, Morocco c Laboratory of Microbiology, hoˆpital des spe´cialite´s ONO, Avenue Mohamed Belarbi Alaoui, Rabat, Morocco *Corresponding author. E-mail address: [email protected] (L. Lachhab) 1
Both authors contributed equally to this work. Received 15 March Received in revised form 25 March Accepted 3 April Available online 4 July
2012 2012 2012 2012
0035-3787/$ – see front matter # 2012 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.neurol.2012.04.004
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
references
Costa M, Souza J, Oliveira Neto A, Pinto E, Silva J. Cryptococcal meningitis in HIV negative pregnant women: case report and review of literature. Rev Inst Med Trop S Paulo 2009;51(5):289–94. Diamond RD, Bennett JE. Disseminated cryptococcosis in man: decreased lymphocyte transformation in response to Cryptococcus neoformans. J Infect Dis 1973;127:694–7. Kiertiburanakul S, Wirojtananugoon S, Pracharktam R, Sungkanuparph S. Cryptococcosis in human immunodeficiency virus-negative patients. Int J Infect Dis 2006;10:72–8. Pappas PG, Perfect JR, Cloud GA, Larsen RA, Pankey GA, Lancaster DJ, et al. Cryptococcosis in human immunodeficiancy virus negative patients in the era of effective azote therapy. Clin Infect Dis 2001;33:690–9. Perfect JR, Casadevall A. Cryptococcosis. Infect Dis Clin North Am 2002;16:837–74. Sravani VM. Disseminated cryptococcosis in an HIV-negative pregnancy: a case of cryptococcal septic abortion complicating an immunocompetent pregnancy. Int J Infect Dis 2010;14:351–3. York J, Bodi I, Reeves I, Riordan-Eva P, Easterbrook PJ. Raised intracranial pressure complicating cryptococcal meningitis: immune reconstitution inflammatory syndrome or recurrent cryptococcal disease? J Infect 2005;51:165–71.
L. Lachhaba,*,1 K. Rasmounia,1 E.H. Ait Ben Haddoua M. Maamarb M. Seffarc W. Regraguia A. Benomara M. Yahyaouia a Department of Neurology B and neurogenetics, hoˆpital des spe´cialite´s ONO, avenue Mohamed Belarbi Alaoui, Rabat, Morocco
Neuropathie ataxiante re´ve´latrice d’un CMT1A Ataxia phenotype of type 1 Charcot-Marie-Tooth disease: An atypical presentation Un homme de 26 ans, sans ante´ce´dents, issu d’un mariage consanguin entre cousins germains, consulta pour des troubles de l’e´quilibre e´voluant depuis une dizaine d’anne´es. Le patient signalait des troubles semblables chez sa me`re, sa grand-me`re maternelle, son arrie`re-grand-me`re, son oncle maternel et sa fille. L’examen re´ve´lait une marche talonnante, un signe de Romberg a` la fermeture des yeux, un de´ficit moteur distal des loges ante´ro-externes de jambes cote´ a` 4+/5 sans amyotrophie, une are´flexie ge´ne´ralise´e, des troubles de la sensibilite´ marque´s par une hypopallesthe´sie et une hyperesthe´sie distale pre´dominant aux membres infe´rieurs ainsi que des signes dysmorphiques objective´s par l’existence de pieds creux. Il n’y avait pas d’hypertrophie des troncs nerveux. L’e´lectroneuromyogramme orientait vers une neuropathie de´mye´linisante (Tableau 1). Les causes classiques de neuropathie de´mye´linisante chronique furent exclues. En effet le bilan paraclinique suivant e´tait normal ou ne´gatif et permettait, notamment, d’e´liminer un diabe`te et une he´mopathie : nume´ration de la formule sanguine, ionogramme, he´moglobine glyque´e, fonction re´nale, immuno-e´lectrophore`se des prote´ines se´riques, se´rologies he´patite B, he´patite C, VIH, HTLV1 et 2, bilan immunologique, e´tude du comple´ment, cryoglobuline´mie et biopsie des glandes salivaires. Quant au diagnostic de polyradiculone´vrite de´mye´linisante chronique, l’absence de bloc de conduction, l’absence de dispersion temporelle et l’absence de de´mye´linisation he´te´roge`ne a` l’ENMG le rendait peu probable et cela malgre´ une hyperprote´inorachie (0,72 g/L) isole´e a` la ponction lombaire et l’absence de biopsie nerveuse re´alise´e. Compte tenu de cas familiaux similaires sur plusieurs ge´ne´rations, des donne´es neurophysiologiques, de l’existence de pieds creux et de l’absence d’e´tiologie, l’e´tude du ge`ne PMP22 par biologie mole´culaire a mis en e´vidence une duplication