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Case Report Acanthamoeba Meningoencephalitis Following Autologous Peripheral Stem Cell Transplantation

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Case Report Acanthamoeba Meningoencephalitis Following Autologous Peripheral Stem Cell Transplantation Bone Marrow Transplantation, (1998) 22, 297–300 1998 Stockton Press All rights reserved 0268–3369/98 $12.00 http://www.stockton-press.co.uk/bmt Case report Acanthamoeba meningoencephalitis following autologous peripheral stem cell transplantation JM Feingold1, J Abraham1, S Bilgrami1, N Ngo2, GS Visvesara3, RL Edwards1 and PJ Tutschka1 1Jean Marie Colbert Bone Marrow Transplant Center, 2Department of Pathology, University of Connecticut School of Medicine, Farmington, CT; and 3National Center for Infectious Diseases, Center for Disease Control and Prevention, Atlanta, GA, USA Summary: age, heating, ventilatory and air conditioning units.2 Acan- thamoeba can cause granulomatous meningoencephalitis in Amoebic meningoencephalitis is an unusual compli- immunocompromised patients.3 Reported herein is the first cation of bone marrow transplantation. We report a case of Acanthamoebic meningoencephalitis following an case of Acanthamoeba meningoencephalitis in a patient autologous PBSCT. with non-Hodgkin’s lymphoma after autologous stem cell transplantation. Leg weakness, fever and urinary retention developed 69 days following transplantation. Case report The patient then developed fever, generalized tonic clonic seizure, rapid deterioration of mental functions A 47-year-old female was diagnosed with monocytoid B and hypercapneic respiratory failure. Magnetic reson- cell lymphoma, in August 1994. The patient received 24 ance imaging demonstrated a ring enhancing lesion at courses of cyclophosphamide, vincristine and prednisone the level of the thoracic spines 11 and 12. Examination (CVP) following which she was found to have residual dis- of the cerebrospinal fluid revealed pleocytosis. Despite ease. She then received six courses of cyclophosphamide, empiric therapy with broad-spectrum antimicrobial doxorubicin, vincristine and prednisone (CHOP) and was agents, the patient’s condition worsened and she died subsequently referred to our center for high-dose chemo- 11 days following admission. Autopsy findings revealed therapy and autologous stem cell rescue. The patient a subacute meningoencephalitis secondary to Acantha- received three courses of tumor debulking and stem cell moeba culbertsoni. mobilization chemotherapy with etoposide 60 mg/kg, Keywords: Acanthamoeba; meningoencephalitis; stem cyclophosphamide 3 g/m2 and paclitaxel 200 mg/m2 admin- cell transplantation istered at monthly intervals, following which she received pre-transplant conditioning regimen consisting of busulfan 16 mg/kg, etoposide 60 mg/kg and cyclophosphamide 90 mg/kg followed by stem cell infusion (day 0). Cipro- Infections are a major cause of morbidity and mortality fol- floxacin 500 mg orally twice a day as prophylaxis was lowing autologous peripheral blood stem cell transplan- administered day −10 to day +6. Prophylactic amphotericin tation (PBSCT). However, amoebic infections have rarely B (10 mg/day from day +2 to day +12, and subsequently been identified in this group of patients. Only two cases 30 mg/week) was also administered. Trimethoprim-sulfa- of Acanthamoeba meningoencephalitis have been reported methaxasole was given twice a day 2 days a week from day 1 following autologous bone marrow transplantation. They −8 until day −1 prior to transplant and restarted following presented 9 and 6 months, respectively, following trans- engraftment beginning on day +8. On day +6, the patient plantation for leukemia with fever and pulmonary infil- developed an autoaggressive syndrome of the skin and trates, and later developed rapid mental status deterioration required treatment with methylprednisolone 48 mg i.v. and seizures. The patients died 25 and 18 days after hospi- every 12 h until day +22. Subsequently, prednisone 80 mg talization despite aggressive treatment with broad-spectrum orally twice daily was substituted and later tapered antibiotics, metronidazole, doxycycline, amphotericin B, appropriately. fluconazole and trimethoprim-sulfamethaxazole. Acan- Sixty-nine days following PBSCT, the patient presented thamoeba meningoencephalitis was diagnosed only at auto- with right leg weakness of 2 days duration and urinary psy. Free-living amoeba of the genus Acanthamoeba are retention for 1 day. At the time of admission the patient ubiquitous and can be isolated from fresh water, soil, sew- was alert and oriented but was febrile with a temperature of 38.8°C. Initial neurological examination revealed total loss of motor strength in the right lower extremity. Sensory Correspondence: Dr JM Feingold, Jean Marie Colbert Bone Marrow Transplant Center, University of Connecticut Health Center, 263 Farm- examination demonstrated decreased pain, touch and vibra- ington Ave, Farmington, CT 06062, USA tory sensation of the right lower extremity. Deep tendon Received 21 January 1998; accepted 16 March 1998 reflexes were diminished in both lower extremities, the Acanthamoeba following stem cell transplantation JM Feingold et al 298 plantar reflexes were normal. Motor strength and sensory examination of the left lower extremity were normal. a Examination of the spine did not reveal any focal tender- ness or deformity. Examination of the other systems was within normal limits at the time of admission. Later in the day the patient became progressively obtunded and eventu- ally moribund; shortly thereafter she had a witnessed gen- eralized tonic clonic seizure and required intubation for hypercapneic respiratory failure. On admission, the white blood cell count was 10.8 × 109/l, hemoglobin 9.6 g/dl and platelet count 47 × 109/l. The magnetic resonance imaging (MRI) and computerized axial tomography (CAT) scan of the brain were normal, but the MRI of the spinal cord dem- onstrated a ring enhancing lesion at the level of thoracic spines 11 and 12. Her initial lumbar puncture showed pro- tein of 119 mg/dl (normal range 20–45 mg/dl), glucose of b 132 mg/dl (50–80 mg/dl), leukocyte count of 210 cells/mm2 (of which 90% was polymorphonuclear leukocytes and 10% mononucleated cells) and an erythrocyte count of zero. No microorganisms could be identified on gram stain or India Ink preparations. Acid-fast bacilli were not seen and the latex agglutination test for cryptococcal antigen was negative. The patient was empirically treated with dexame- thasone 10 mg i.v. every 6 h, acyclovir 660 mg i.v. every 8 h, ampicillin 2 g i.v. every 4 h, rifampin 600 mg orally daily, pyrazinamide 1.5 g orally daily, sulfadiazine 1 g i.v. every 6 h, pyrimethamine 50 mg orally daily, INH 300 mg orally daily and ceftriaxone 2 g i.v. every 12 h. Blood and cerebrospinal fluid cultures remained negative for bacteria, viruses, acid-fast bacilli and fungi. A biopsy of the spinal c cord lesion was precluded by its location as well as the hemodynamic instability of the patient. Despite maximal medical therapy, the patient’s neurological status continued to deteriorate and she died 11 days following admission. Pathology review General autopsy showed fatty changes of the liver and heart, focal pulmonary fibrosis and hemorrhage as well as early patchy adult respiratory distress syndrome. Gross examination of the brain showed moderate cerebral edema Figure 1 (a) Coronal section of the anterior cerebrum showing gray lesions of the left orbital frontal cortex and right caudate nucleus (arrows). with a swollen pons and medulla and thickened meninges (b) Section through the cerebellum and medulla showing necrotic lesion about the base of the brain. Coronal section showed small of the inferior cerebellar cortex (arrow) and peripheral petechiae in the ventricles as well as two 0.5 cm diameter gray lesions in medulla. (c) Sections through the spinal cord showing necrosis of T12– the left orbital frontal cortex and white matter and the right L1 (thin arrow), peripheral petechiae in most of the cord, and posterior caudate nucleus with no other gross lesions in the cerebrum column and horn hemmorhage at the levels of T7 and T8 (thick arrow). (Figure 1a). There was a 0.8 cm diameter brownish lesion in the right inferior cerebellar folia and petechiae in the change about the periphery of the brain stem and aqueduct periphery of the medulla (Figure 1b). The spinal cord of Sylvius. In addition, in several lesions there were amo- showed a necrotic lesion at T12–L1 with a small amount eba trophozoites and cysts (typed as Acanthamoeba of hemorrhage within it. In the upper thoracic and lower culbertsoni) in a perivascular arrangement associated with cervical cord, there were petechiae and at T6–T7 there was a mixed inflammatory infiltrate and reactive astrocytosis in hemorrhage in the posterior columns and adjacent posterior adjacent tissue (Figure 2a). Sommer’s sector and purkinje horns and lateral columns (Figure 1c). cells showed early anoxic changes. On microscopic examination there were widespread nec- The spinal cord showed complete necrosis at the T12–L1 rotic lesions with a mixed inflammatory infiltrate, predomi- level with possible amoebic trophozoite shadows present. nately neutrophils but also with macrophages and lympho- Immunofluorescent studies showed evidence of amoebic cytes, affecting the cerebral cortex, medial caudate nucleus, antigen in the necrotic areas of the spinal cord (Figure 2b). thalamus, hypothalamus, inferior cerebellar folia and floor In the medulla and the remainder of the cord, petechiae of the fourth ventricle in the pons with early necrotic associated with focal necrosis were seen. The meninges Acanthamoeba following stem cell transplantation JM Feingold et al 299 fatal illness that usually affects healthy
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