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Year : 2018  |  Volume : 12  |  Issue : 2  |  Page : 146-148

Ischemic stroke in a middle-aged renal transplant recipient: A rare cause

Department of Nephrology and Radiodiagnosis, Government Stanley Medical College, The Tamil Nadu Dr. M.G.R. Medical University, Chennai, Tamil Nadu, India

Date of Web Publication29-Jun-2018

Correspondence Address:
Dr. Sowmya Jayachandran
Department of Nephrology and Radiodiagnosis, Government Stanley Medical College, The Tamil Nadu Dr. M.G.R. Medical University, Chennai, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijot.ijot_9_18

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Cerebrovascular accidents are a life-threatening complication in renal transplant recipients. The risk increases with old age, diabetic neuropathy, and peripheral vascular disease. Ischemic stroke contributes to two-thirds of stroke in renal transplant recipients. As they receive immunosuppressives, they are more susceptible to a spectrum of opportunistic infections. Central nervous system infections such as tuberculosis and fungal infections can present as ischemic stroke. Cerebral infarction in meningoencephalitis is due to strangulation of vessels by exudates which causes vasculitis with inflammation, spasms, constriction, and thrombosis. This case report is a rare presentation of stroke in renal transplant recipient due to an infective etiology. The patient was managed appropriately by understanding this underlying pathophysiologic mechanism.

Keywords: Cryptococcal meningitis, Cryptococcus neoformans, fungal infections in renal transplant recipients, India ink stain, stroke in renal transplant recipients

How to cite this article:
Vijayakumar A, Jayachandran S, Srinivasaprasad N D, Suhasini B, Fernando M E. Ischemic stroke in a middle-aged renal transplant recipient: A rare cause. Indian J Transplant 2018;12:146-8

How to cite this URL:
Vijayakumar A, Jayachandran S, Srinivasaprasad N D, Suhasini B, Fernando M E. Ischemic stroke in a middle-aged renal transplant recipient: A rare cause. Indian J Transplant [serial online] 2018 [cited 2021 Apr 11];12:146-8. Available from: https://www.ijtonline.in/text.asp?2018/12/2/146/235599

  Introduction Top

Organ transplant recipients are susceptible to both common and opportunistic infections. Receiving immunosuppressants make them a high-risk group for serious opportunistic fungal and viral infections. Cryptococcal infection is one among them which occurs in an average of 2.8% recipients.[1] Central nervous system (CNS) is being the most common organ system involved with basal meningoencephalitis, and the clinical presentation is usually subacute and subtle. Without a high degree of suspicion, the diagnosis and treatment can be delayed increasing the morbidity and mortality. Stroke in cryptococcal meningoencephalitis has not been documented in this group so far in India to the best of our knowledge.

  Case Report Top

A 34-year-old male, ABO-compatible living-related renal transplant recipient (native kidney disease – unknown), mother donor, received no induction with good graft function (serum creatinine – 1.4 mg/dl), presented after 1 year with complaints of headache for 4 days and left hemiparesis for 1 day. He denied any fever, vomiting, photophobia, seizures, or visual disturbance.

The immunosuppressive protocol consisted of tacrolimus capsules 6 mg/day, mycophenolate mofetil tablets 1 g/day, prednisolone tablets 10 mg/day, and required amlodipine tablets 5 mg twice daily for control of his blood pressure. His baseline serum creatinine was 1.4 mg/dl. He developed graft pyelonephritis 2-month posttransplant which improved with antibiotics. At 8-month posttransplant, he had a swelling of the right lower limb near medial malleolus which was excised and biopsied. The histopathological report showed septate hyphae, but the culture did not grow any fungus. Since there was no definitive growth of any fungus, we empirically treated him with oral voriconazole 200 mg/day, keeping a watch on his tacrolimus levels.

The patient's neurologic examination was remarkable for left upper motor neuron-type hemiparesis, neck stiffness, and left plantar extensor. Rest of the physical examination was unremarkable. Complete blood workup was done which showed hemoglobin 15 mg/dl, total count 4700/cmm, differential count – polymorphs: 65%, lymphocytes: 30%, and eosinophils: 5%, and serum creatinine of 1.4 mg/dl. There are no active sediments in urine microscopy and no growth in urine culture. Blood tacrolimus level was 5.6 ng/ml. Cerebrospinal fluid (CSF) analysis was negative for acid-fast bacilli, gram stain, and malignancy [Table 1]. The patient underwent computed tomography brain which was found to be normal; however, magnetic resonance imaging (MRI) with venography revealed acute lacunar infarct in the posterior limb of right internal capsule. The patient developed altered behavior with irrelevant speech. An aim to identify the etiology provoked us to do India ink staining and culture of CSF on Sabouraud agar. India ink demonstrated round encapsulated yeast [Figure 1], and Sabouraud agar showed cream-colored colonies [Figure 2] which confirmed the diagnosis of cryptococcal meningoencephalitis. After withholding the mycophenolate mofetil and dose reduction of the immunosuppressants, namely, tacrolimus tablets 6 mg/day to 1.5 mg/day and prednisolone tablets 10 mg/day to 5 mg/day, the patient was managed appropriately with lipid emulsion amphotericin B for 6 weeks initially and maintenance treatment of fluconazole tablets 300 mg/day. With treatment, the patient's left upper and lower limb weakness improved partially. He had mild graft dysfunction with serum creatinine of 2.6 after completion of 6 weeks of treatment probably due to amphotericin B toxicity. Subsequently, the patient's graft function gradually worsened 6 months later probably due to chronic allograft injury. The patient did not consent for graft renal biopsy, and hence, the cause of graft loss could not be ascertained. He was initiated on hemodialysis, which he is continuing on weekly twice schedule.
Table 1: Cerebrospinal fluid analysis of the patient

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Figure 1: Round encapsulated yeast shown in the India ink stain of cerebrospinal fluid of the patient. Figure resolution 514 × 478 pixels

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Figure 2: Cream-colored colonies shown on the culture of cerebrospinal fluid on Sabouraud agar. Figure resolution 1280 × 719 pixels

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  Discussion Top

Cryptococcus is basidiomycetes, encapsulated yeast, and has four serotypes. It is transmitted by inhalation or ingestion which remains latent for years until cell-mediated immunity falls.[2] The risk factors of cryptococcal infection are acquired immunodeficiency syndrome, prolonged treatment with glucocorticoids, solid organ transplantation, malignancy, and sarcoidosis.

CNS predilection can be explained by multiple hypotheses; however, the lack of complementary factors in CSF is a major contributing factor.[3] It presents as subacute meningoencephalitis which develops over 2–4 weeks and gets complicated later by hydrocephalus. Cryptococcoma formation is an uncommon presentation which may give rise to symptoms such as seizures, altered sensorium, and focal neurological deficits.[4] A less common presentation is cerebral infarcts secondary to cryptococcal vasculitis. The incidence of infarction secondary to this is variable and occurs in 4%–32% of cases.[5]

CSF analysis with Indian ink demonstrates encapsulated yeast in 50% of patients. It is highly specific (97%) but poorly sensitive test (83%).[6] MRI is the investigation of choice which shows miliary enhancing parenchymal nodules, leptomeningeal-cisternal nodules, cryptococcoma, and gelatinous pseudocyst.[7] Antigen testing is the rapid way of diagnosis with high sensitivity and specificity. The poor prognostic indicators are India ink positivity of CSF, CSF white blood cell (WBC) count <20/μL, an initial CSF serum cryptococcal antigen titer >1:32, and a high opening pressure on lumbar puncture.[8] This case had two of these poor prognostic factors, namely, India ink positivity of CSF and a low CSF WBC count. Treatment includes an initial phase with intravenous (IV) liposomal amphotericin (3–4 mg/g/day) or IV lipid emulsion amphotericin 5 mg/kg/day with or without flucytosine at a dose of 100 mg/kg/day followed by CSF examination every 2 weeks and continued treatment till CSF is sterile. This is followed by a consolidation phase of treatment with fluconazole dose of 6 mg/kg/day for 8 weeks followed by a maintenance phase of fluconazole at 3 mg/kg/day for 6–12 months.[9] In this case, the patient had a history of headache and hemiparesis without any fever mimicking a usual thrombotic stroke. If not diagnosed with an extra degree of suspicion, appropriate treatment could have been delayed increasing the mortality and morbidity. To the best of our knowledge, this is the first case report of such an occurrence, and thus, it is presented for its rarity.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Husain S, Wagener MM, Singh N. Cryptococcus neoformans infection in organ transplant recipients: Variables influencing clinical characteristics and outcome. Emerg Infect Dis 2001;7:375-81.  Back to cited text no. 1
Mirza SA, Phelan M, Rimland D, Graviss E, Hamill R, Brandt ME, et al. The changing epidemiology of cryptococcosis: An update from population-based active surveillance in 2 large metropolitan areas, 1992-2000. Clin Infect Dis 2003;36:789-94.  Back to cited text no. 2
Igel HJ, Bolande RP. Humoral defense mechanisms in cryptococcosis: Substances in normal human serum, saliva, and cerebrospinal fluid affecting the growth of Cryptococcus neoformans. JInfect Dis 1966;116:75-83.  Back to cited text no. 3
Tien RD, Chu PK, Hesselink JR, Duberg A, Wiley C. Intracranial cryptococcosis in immunocompromised patients: CT and MR findings in 29 cases. AJNR Am J Neuroradiol 1991;12:283-9.  Back to cited text no. 4
Lan SH, Chang WN, Lu CH, Lui CC, Chang HW. Cerebral infarction in chronic meningitis: A comparison of tuberculous meningitis and cryptococcal meningitis. QJM 2001;94:247-53.  Back to cited text no. 5
Saha DC, Xess I, Biswas A, Bhowmik DM, Padma MV. Detection of Cryptococcus by conventional, serological and molecular methods. J Med Microbiol 2009;58:1098-105.  Back to cited text no. 6
Hospenthal DR, Bennett JE. Persistence of cryptococcomas on neuroimaging. Clin Infect Dis 2000;31:1303-6.  Back to cited text no. 7
Diamond RD, Bennett JE. Prognostic factors in cryptococcal meningitis. A study in 111 cases. Ann Intern Med 1974;80:176-81.  Back to cited text no. 8
Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of America. Clin Infect Dis 2010;50:291-322.  Back to cited text no. 9


  [Figure 1], [Figure 2]

  [Table 1]

This article has been cited by
1 Amphotericin B/immunosupressants
Reactions Weekly. 2018; 1714(1): 36
[Pubmed] | [DOI]


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