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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
CASE REPORT  
Year : 2012  |  Volume : 23  |  Issue : 4  |  Page : 790-793
Mycophenolate mofetil associated with progressive multifocal leukoencephalopathy with successful outcome


1 Service of Nephrology, Dialysis and Kidney Transplantation, Military Hospital of Instruction Mohammed V, Rabat, Morocco
2 Service of Neurology, Military Hospital of Instruction Mohammed V, Rabat, Morocco
3 Service of Intensive Care Unit, Military Hospital of Instruction Mohammed V, Rabat, Morocco

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Date of Web Publication9-Jul-2012
 

   Abstract 

The use of mycophenolate mofetil (MMF) is known to be associated with progres­sive multifocal leukoencephalopathy (PML). We report a case of PML in a patient receiving MMF, who showed improvement upon discontinuation of the drug. He was restarted on MMF, following which he went into coma. He showed prompt recovery upon stopping the drug again and made full recovery without any residual neurological deficit. This case is being reported to further highlight this neurological side-effect of MMF.

How to cite this article:
El Kabbaj D, Hassani M, Kadiri M, Mounach J, Ouhabi H, Haimeur C, Oualim Z. Mycophenolate mofetil associated with progressive multifocal leukoencephalopathy with successful outcome. Saudi J Kidney Dis Transpl 2012;23:790-3

How to cite this URL:
El Kabbaj D, Hassani M, Kadiri M, Mounach J, Ouhabi H, Haimeur C, Oualim Z. Mycophenolate mofetil associated with progressive multifocal leukoencephalopathy with successful outcome. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2020 May 31];23:790-3. Available from: http://www.sjkdt.org/text.asp?2012/23/4/790/98162

   Introduction Top


In April 2008, the Food and Drugs Associa­tion (FDA) released a safety report regarding a potential association between mycophenolate mofetil (MMF) and progressive multifocal leukoencephalopathy (PML). [1] Progressive PML is a neurological demyelinating disorder caused by the JC polyomavirus, first reported in 1958 in a patient with chronic lymphocytic leukemia. [2] The JC virus is ubiquitous, and the sero-prevalence is up to 60% in young adults and up to 80% in elderly people. [3]


   Case Report Top


We report the case of a 42-year-old male patient with end-stage renal disease of un­known etiology. He underwent a living donor renal transplantation. Induction immunosuppression consisted of basiluximab and mainte­nance immunosuppression consisted of tacrolimus (target level 8-10 ng/mL), MMF (1000 mg twice a day) and prednisone (10 mg daily). The patient presented with sub-acute onset of coma, seizures and cognitive changes one month after transplantation. The patient was admitted to the intensive care unit where he was put on mechanical ventilation. Magnetic resonance imaging (MRI) showed neuro-imaging abnormalities in the occipital lobe ini­tially [Figure 1]. Tacrolimus was first stopped because the initial neurological diagnosis was posterior reversible encephalopathy syndrome, which is known to be associated with calcineurin inhibitors. However, no improvement was seen two weeks after stopping the drug; additionally, the patient developed serious compli­cations including disseminated intravascular coagulation, septic shock and deep coma. We then stopped MMF and the prednisone was continued in a dose of 20 mg/day. Three days later, the patient started showing improvement of the neurological state. During this period, the tacrolimus was still not re-started and MMF was re-introduced at a dose of 1 g/day. Six hours later, the patient developed high fever associated with deep coma. We discontinued MMF again, following which the pa­tient was wide awake a few hours later. Fol­lowing this, we changed MMF to azathioprine and tacrolimus to cyclosporine. Since then, the patient has remained stable neurologically, without any residual neurological deficit. Du­ring this period, the patient developed an acute rejection, which was treated with solumedrol; the graft function stabilized with a serum creatinine of 2 mg/dL. The MRI was repeated four months later, and showed that the lesions were still seen in the white matter [Figure 2]. The diagnosis of PML was based on radiological, electro-neurological and clinical findings.
Figure 1: The initial magnetic resonance imaging that shows the neuroimaging abnormalities in the occipital lobe.

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Figure 2: Repeat magnetic resonance imaging performed four months later, which shows the lesions in the white matter.

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   Discussion Top


PML, which is a rare disorder that affects the central nervous system, usually occurs in patients whose immune system is suppressed either by disease or medicines. It is caused by the activation of the polyomavirus, also known as the JC virus. Although the JC virus is found in most adults, it does not usually cause symptoms. It is not known how the JC virus is activated, although abnormalities of T-cells have been described as important for reactiva­tion of JC virus and PML. Once activated, the JC virus attacks the cells that make myelin and induce a lytic infection of oligodendrocytes, the protective coating around nerve cells. In most individuals, the JC virus remains latent in kidneys and lymphoid organs. But, in the context of profound cellular immunosuppression, it may get re-activated and spread to the brain.

Since 1971, at least 14 cases of PML have been reported after renal transplantation, [4],[5] some associated with MMF. [5],[6] The incidence of PML in MMF users was 14.4 cases/100,000 person-years at risk versus zero for non-MMF users (P = 0.11). The factors significantly asso­ciated with PML were BK virus infection (22.2% vs. 1.1%), pre-transplant transfusion (75% vs. 34%), panel reactive antibody more than 20% (56% vs. 14%) and use of anti-rejection medications in the first year (33% vs. 9.2%). [7] Our patient had received transfusions pre-transplant but did not have any other risk factors.

PML presents after a median of 37 months after renal transplantation. [6] It usually mani­fests with sub-acute neurological deficits, in­cluding altered mental status, motor deficits (hemiparesis or monoparesis), limb ataxia, gait ataxia and visual symptoms such as hemianopia and diplopia, and seizures. The diagnosis is confirmed by detection of JC virus in the cerebrospinal fluid and/or brain biopsy. In our case, we did not perform brain biopsy nor did we use the polymerase chain reaction (PCR) technique to amplify JC virus DNA in the cerebrospinal fluid. [8] The diagnosis was made on the basis of radiological imaging and the clinical presentation. The prognosis of PML is poor, with rapid progression to death or severe disability, which usually occurs within six months of the initial diagnosis. [6],[9],[10] Shitrit et al reported ten deaths in their report of 14 cases. [10] A primary reason for the poor prognosis is the lack of specific antiviral therapy for polyoma-viruses. Our patient has remained alive with­out any neurological deficit and with stable graft function, with a serum creatinine of 2.1 mg/dL nine months after follow-up. Our report is yet another case of PML asso­ciated with MMF. The diagnosis of PML should always be considered in immunosuppressed patients who present with neurological disease and lesions in the white matter on MRI. Although currently there is no agreement on a standard treatment for PML, decrease or discontinuation of immunosuppressive medi­cations is a key element for a successful outcome.

 
   References Top

1.Communication about an ongoing safety review of CellCept (mycophenolate mofetil) and Myfortic (mycophenolate acid). US Food and Drug Administration; April 10, 2008. Available from: http://hinarigw.who.int/whalecomwww.fda.go v/whalecom0/medwatch/safety/2008/safety08. htm#mycophenolate). Last Accessed on 2008 June 7).  Back to cited text no. 1
    
2.Astrom KE, Mancall EL, Richardson EP. Progressive multifocal leukoencephalopathy: A hitherto unrecognized complication of chro­nic lymphatic leukemia and Hodgkin's disease. Brain 1958;81:93-110.  Back to cited text no. 2
    
3.Demeter LM. JC, BK, and other polyomavirus; progressive multifocal leukoencephalopathy. In: Mandell GL, Bennett JE, Dolin R (eds). Principles and Practice of Infectious Diseases, 5th ed, London: Churchill Livingstone: 2000. p. 1645-51.  Back to cited text no. 3
    
4.Legtain M, Graveleau J, Brion S, et al. Leucoencephalopathie multifocale progressive après transplantation renale. J Neurol Sci 1974;23:49.  Back to cited text no. 4
    
5.Crowder CD, Gyure KA, Drachenberg CB, et al. Successful outcome of progressive multi-focal leukoencephalopathy in a renal transplant patient. Am J Transplant 2005;5:1151-8.  Back to cited text no. 5
    
6.Astrom KE, Mancall EL, Richardson EP. Progressive multifocal leukoencephalopathy: A hitherto unrecognized complication of chro­nic leukaemia and Hodgkin's disease. Brain 1958;81:93.  Back to cited text no. 6
    
7.Neff RT, Hurst FP, Falta EM, et al. Progres­sive multifocal leukoencephalopathy and use of mycophenolate mofetil after kidney trans­plantation. Transplantation 2008;86:1474-8.  Back to cited text no. 7
    
8.Berner B, Krieter DH, Rumpf KW, et al. Progressive multifocal leukoencephalopathy in a renal transplant patient diagnosed by JCV-specific DNA amplification and an intrathecal humoral immune response to recombinant virus protein. Nephrol Dial Transplant 1999; 14:462-5.  Back to cited text no. 8
    
9.Berger JR, Pall L, Lanska D, et al. Progressive multifocal leukoencephalopathy. N Engl J Med 1961;265:815.  Back to cited text no. 9
    
10.Shitrit D, Lev N, Shitrit A. Progressive multi-focal leukoencephalopathy in transplant reci­pients. Transplant Int 2005;17:658-65.  Back to cited text no. 10
    

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Correspondence Address:
Driss El Kabbaj
Service of Nephrology, Dialysis and Kidney Transplantation, Military Hospital of Instruction Mohammed V, Rabat
Morocco
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DOI: 10.4103/1319-2442.98162

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[Pubmed] | [DOI]



 

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    Abstract
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