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 Table of Contents 
CASE REPORT
Year : 2019  |  Volume : 8  |  Issue : 2  |  Page : 751-753  

Does this HIV-positive patient have progressive multifocal leukoencephalopathy or PML-immune reconstitution inflammatory syndrome?


1 Department of Family Medicine & Primary Care, PCMH Restore Health, Bangalore, India
2 Department of Family Medicine & Primary Care, PCMH Restore Health, Bangalore; Department of Family Medicine & Primary Care, Academy of Family Physicians of India, Karnataka Chapter, India
3 Department of Family Medicine & Primary Care, Academy of Family Physicians of India, Karnataka Chapter, India

Date of Web Publication28-Feb-2019

Correspondence Address:
Dr. Ramakrishna Prasad
#7, RK Street, Seshadripuram, Bengaluru - 560 020, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jfmpc.jfmpc_460_18

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  Abstract 


We describe the case of an HIV/AIDS patient with progressive multifocal leukoencephalopathy (PML) associated with immune reconstitution inflammatory syndrome (IRIS) and the diagnostic and management dilemmas in distinguishing between PML and PML-IRIS. This case is relevant to physicians including family physicians who manage immunocompromised patients in their practice.

Keywords: Acquired immunodeficiency syndrome (Source: MeSH-NLM), HIV, immune reconstitution inflammatory syndrome, JC virus, leukoencephalopathy, progressive multifocal


How to cite this article:
Abraham RR, Anand AK, Prasad R, Rao B C, Pillala P. Does this HIV-positive patient have progressive multifocal leukoencephalopathy or PML-immune reconstitution inflammatory syndrome?. J Family Med Prim Care 2019;8:751-3

How to cite this URL:
Abraham RR, Anand AK, Prasad R, Rao B C, Pillala P. Does this HIV-positive patient have progressive multifocal leukoencephalopathy or PML-immune reconstitution inflammatory syndrome?. J Family Med Prim Care [serial online] 2019 [cited 2019 Aug 25];8:751-3. Available from: http://www.jfmpc.com/text.asp?2019/8/2/751/253063




  Introduction Top


Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS), characterized by multifocal areas of demyelination of varying sizes, distributed throughout the brain.[1] It is the only known clinical manifestation of an opportunistic infection by JCV (John Cunningham virus, named after the patient from whom it was first isolated in 1971).[2],[3],[4] PML is an AIDS defining condition that occurs when the CD4 count is <100/μL.[5]

PML-immune reconstitution inflammatory syndrome (IRIS) is a paradoxical worsening or unmasking of PML, which occurs following the initiation of antiretroviral therapy (ART). IRIS is caused by the rapid recovery of the immune system in the presence of the pathogen.[5],[6]

There are very few studies which have looked into the outcome of PML-IRIS in HIV-infected patients across the globe.[5],[7] Data on ART and AIDS-associated PML-IRIS from India is scarce.[5]

In this paper, we describe the clinical findings and progress of the disease in an Indian patient with HIV having a CD4 count of 44/μL.


  Case Report Top


A 47-year-old male presented to us in April 2017. He was apparently normal 20 days prior to presenting to us when he noticed excessive fatigue and weakness which was progressive. Five days after onset of initial symptoms, he started having increasing difficulty in walking. Around this time, he also developed difficulty in swallowing. On further questioning, his wife gave a history of progressive weight loss of 20 kg over 2 years. There was no history of tuberculosis, diabetes mellitus, hypertension, or blood transfusions. No previous surgeries or allergies were reported. The patient had been married for 12 years. His wife provided the history that he was a homosexual and their only child was conceived by artificial insemination.

Ten days before coming to our center, he was seen at a private clinic and diagnosed with HIV-1 with AIDS. His CD4 count was 44/μL. There, he was started on an ART regimen containing Tenofovir, Emtricitabine, and Efavirenz and empirically on antitubercular therapy. Subsequently, the patient was discharged. However, he deteriorated at home and was then brought to our center.

The patient was brought on a stretcher, though conscious he was neither oriented nor responsive to questioning. He was poorly nourished. He was febrile (100° F). On CNS examination, it was found that he had slurred speech and his limbs were hypotonic. Deep tendon reflexes were present. No signs of meningitis were noted.

Magnetic resonance imaging (MRI) with contrast of the brain and spinal cord and CSF analysis was done at a referral hospital. The MRI was reported as being suggestive of PML. CSF protein, glucose, cell count, and cell type were within normal limits. A multiplex PCR test for a panel of pathogens associated with meningoencephalitis was positive for JCV. While at the referral hospital, his ART and antitubercular therapy was discontinued. The patient was examined by a neurologist who noted cogwheel rigidity and was started on a combination of levodopa and carbidopa.

After a week, he was sent back to our center. He was unconscious and febrile (100°F). Nystagmus was noted bilaterally and cogwheel rigidity was present in all four limbs.

At our center, we were confronted with the following clinical dilemmas. First, was his condition explainable by a diagnosis of PML alone or was this PML-IRIS? Second, should we restart ART or withhold it? Third, was there a role for steroids in his management? And last, if we chose to start ART, should we switch to a regimen with greater CNS penetration?

After reviewing the literature and internal discussion, we thought this presentation was more likely due to PML-IRIS than PML alone. We felt that the literature supported ART continuation and hence continued ART. We chose to add steroids though the literature was equivocal on its benefit. Prednisolone of 40 mg once a day was started and then tapered over a period of 4 weeks. We also switched his ART regimen from Tenofovir, Emtricitabine, and Efavirenz to a combination of Zidovudine, Lamivudine, and Efavirenz (Zidovudine has better blood brain barrier penetration).

By the eighth day of switching ART and adding prednisolone, patient started to show improvement. He was able to sit in a chair and his speech was clearer and his temperature was back to normal. After 40 days of initiating treatment, patient was fully oriented, walking without support but has difficulty maintaining balance, speech was coherent, and he was able to perform his daily activities without help. He still had episodes of amnesia. He was discharged from our centre on June 17 with advice for regular follow-up. A review on July 20 showed further improvement in his condition. He had gained 10 kg since his presentation at our center. He walks with a steady gait, and speech is much clearer. He contemplated returning to work as a civil engineer.


  Discussion Top


A paradoxical worsening of pre-existing, untreated, or partially treated opportunistic infections due to rapid recovery of the immune system following ART initiation is called IRIS.[6] PML-IRIS is usually seen in patients starting therapy with CD4 count <50/μL.[6] The mechanism via which treatment with ART leads to PML-IRIS is not clearly understood, but it is postulated that a sudden recovery of T-cell activity due to ART with a high pathogen (JCV) load results in a massive inflammatory response that damages the brain. This results in a T-cell mediated encephalitis.[2] Occasionally, the damage can be so severe that it leads to a massive swelling of the brain with herniation and death.[2]

It is important to differentiate between the diagnosis of PML and PML-IRIS as they differ in treatment and failure to choose appropriate treatment might lead to the death of the patient. PML-IRIS can be differentiated from PML by the following: (a) clinical profile of worsening symptoms on initiation of treatment is suggestive of IRIS[8] and (b) MRI T1-weighted images of PML are hypointense and do not show enhancement with gadolinium, whereas patients who develop IRIS may show variable degrees of enhancement.[2] The onset of PML-IRIS can vary from 1 week to 26 months after ART initiation.[8] Our patient presented with worsening of symptoms 10 days after initiating ART.

There is no recommended specific antiviral therapy against JCV.[2] The literature suggests that continuing ART is associated with better outcome in patients with PML. The prognosis of patients without initiation of antiretroviral treatment is poor with an average survival of 2–4 months for HIV-positive patients.[2] Hence, we continued ART but replaced Tenofovir with Zidovudine for better CNS penetration.[9]

Although there are no treatment guidelines that clearly recommend the use of steroid in PML-IRIS, some studies note a trend for lower mortality in patients with PML-IRIS with early treatment with corticosteroids.[5] We believe that in our patient early initiation of corticosteroids resulted in dramatic improvement. Once initiated, continuing steroids for 6–8 weeks may be beneficial.

Literature search did not reveal any documented case of PML-IRIS successfully diagnosed and treated in India. Lack of reports from India exposes the probability of under diagnosis of PML-IRIS. Significant recovery of our patient with the continuation of ART and steroidal support strongly advocate the need for clinicians to have a high index of suspicion for early detection of PML IRIS and initiation of steroid therapy with continued ART.

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.

Acknowledgements

Dr Akshay S Dinesh, for critical review of the manuscript.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Roos KL, Tyler KL. Meningitis, encephalitis, brain abscess and empyema. In: Kasper DL, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J, editors. Harrison's Principles of Internal Medicine. 19th ed. New York: McGraw-Hill, Medical Pub. Division; 2015. p. 899.  Back to cited text no. 1
    
2.
Ferenczy MW, Marshall LJ, Nelson CDS, Atwood WJ, Nath A, Khalili K, et al. Molecular biology, epidemiology, and pathogenesis of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain. Clin Microbiol Rev 2012;25:471-506.  Back to cited text no. 2
    
3.
Bozic C, Subramanyam M, Richman S, Plavina T, Zhang A, Ticho B. Anti-JC virus (JCV) antibody prevalence in the JCV Epidemiology in MS (JEMS) trial. Eur J Neurol 2014;21:299-304.  Back to cited text no. 3
    
4.
Fauci AS, Lane HC. Human immunodeficency virus disease: AIDS and related disorders. In: Kasper DL, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J, editors. Harrison's principles of internal medicine. 19th ed. New York: McGraw-Hill, Medical Pub. Division; 2015. p. 1266.  Back to cited text no. 4
    
5.
Sainz-de-la-Maza S, Casado JL, Pérez-Elías MJ, Moreno A, Quereda C, Moreno S, Corral I. Incidence and prognosis of immune reconstitution inflammatory syndrome in HIV-associated progressive multifocal leucoencephalopathy. Eur J Neurol 2016;23:919-25.  Back to cited text no. 5
    
6.
Fauci AS, Lane HC. Human immunodeficency virus disease: AIDS and related disorders, In: Kasper DL, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J, editors. Harrison's Principles of Internal Medicine. 19th ed. New York: McGraw-Hill, Medical Pub. Division; 2015. p. 1261.  Back to cited text no. 6
    
7.
Netravathi M, Mahadevan A, Satishchandra P. Shobha N, Mailankody P, Kandavel T, et al. Progressive multifocal leukoencephalopathy (PML) associated with HIV Clade C–is not uncommon. J Neurovirol 2013;19:198-208.  Back to cited text no. 7
    
8.
Tan K, Roda R, Ostrow L, McArthur J, Nath A. PML-IRIS in patients with HIV infection: Clinical manifestations and treatment with steroids. Neurology 2009;72:1458-64.  Back to cited text no. 8
    
9.
Letendre SL, Fitz Simons C, Ellis RJ, Clifford D, Collier AC, Gelman B, et al. CNS penetration effectiveness (CPE) ranks 2010. 17th Conference on Retroviruses and Opportunistic Infections, 2010. Available from: https://hnrp.hivresearch.ucsd.edu/index.php/research/investigator-resources/resources-offered/laboratory-pharmacology-a-biomarkers-resources-242/cns-penetration-effectiveness-ranks-2010.  Back to cited text no. 9
    




 

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