Immune reconstitution is not a prognostic factor in progressive multifocal leukoencephalopathy

Harrison, David; Newsome, Scott D.; Skolasky, Richard L.; McArthur, Justin C.; Nath, Avindra

doi:10.1016/j.jneuroim.2011.07.003

Cited by 33 publications

(24 citation statements)

References 28 publications

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“…They are usually not enhanced after intravenous contrast injection and are not associated with swelling or mass effect. However, contrast enhancement along with oedema and mass effect, denoting blood–brain barrier disruption secondary to the inflammatory process, is seen in 44% to 57%4 7 of the PML IRIS cases supporting our diagnosis.…”

Section: Discussionsupporting

confidence: 76%

Immune reconstitution inflammatory syndrome in a patient with progressive multifocal leukoencephalopathy

Shahani¹,

Shah

Tavakoli–Tabasi

2015

BMJ Case Reports

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SUMMARYProgressive multifocal leukoencephalopathy (PML) is a severe opportunistic infection of the central nervous system. A 52-year-old man with HIV infection, recently started on antiretroviral therapy, presented with symptoms of mental cloudiness, blurry vision and ataxia. MRI of the brain showed nodular perivascular space enhancement with surrounding vasogenic oedema and midline shift. A lumbar puncture revealed noninflammatory cerebrospinal fluid and was positive for JC virus. As the patient developed worsening symptoms in the setting of initiation of antiretroviral therapy with immune recovery, a diagnosis of JC virus-associated immune reconstitution inflammatory syndrome (IRIS) was made. With recent literature on the use of CCR5 antagonist maraviroc in PML, our patient was started on maraviroc and noted to have improvement in PML IRIS. This is the first case of an HIV-positive patient successfully treated for PML IRIS with maraviroc, as verified by our literature review; also, our case has clinical implications in improving outcome in PML IRIS. BACKGROUND

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Section: Discussionsupporting

confidence: 76%

Immune reconstitution inflammatory syndrome in a patient with progressive multifocal leukoencephalopathy

Shahani¹,

Shah

Tavakoli–Tabasi

2015

BMJ Case Reports

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“…In this scenario, the sudden onset of neurological symptoms and signs shortly after HAART, without other cerebral disorder, led us to consider PML-IRIS as plausible (Cinque et al 2009; Gheuens et al 2012; Harrison et al 2011). Although MRI performed four times did not show brain lesions enhancement in T1 sequences after contrast administration (a strong suggestion of blood–brain barrier disruption and inflammation indicating IRIS), PML-IRIS was still considered, based on a retrospective analysis showing MRI contrast enhancement of brain PML lesions occurring only in 56.7 % of PML-IRIS cases (Tan et al 2009).…”

Section: Discussionmentioning

confidence: 99%

HIV-associated progressive multifocal leukoencephalopathy: longitudinal study of JC virus non-coding control region rearrangements and host immunity

et al. 2013

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John Cunningham virus (JCV), the etiological agent of progressive multifocal leukoencephalopathy (PML), contains a hyper-variable non-coding control region usually detected in urine of healthy individuals as archetype form and in the brain and cerebrospinal fluid (CSF) of PML patients as rearranged form. We report a case of HIV-related PML with clinical, immunological and virological data longitudinally collected. On admission (t0), after 8-week treatment with a rescue highly active antiretroviral therapy (HAART), the patient showed a CSF-JCV load of 16,732 gEq/ml, undetectable HIV-RNA and an increase of CD4+ cell count. Brain magnetic resonance imaging (MRI) showed PML-compatible lesions without contrast enhancement. We considered PML-immune reconstitution inflammatory syndrome as plausible because of the sudden onset of neurological symptoms after the effective HAART. An experimental JCV treatment with mefloquine and mirtazapine was added to steroid boli. Two weeks later (t1), motor function worsened and MRI showed expanded lesions with cytotoxic oedema. CSF JCV-DNA increased (26,263 gEq/ml) and JCV viremia was detected. After 4 weeks (t2), JCV was detected only in CSF (37,719 gEq/ml), and 8 weeks after admission (t3), JC viral load decreased in CSF and JCV viremia reappeared. The patient showed high level of immune activation both in peripheral blood and CSF. He died 4 weeks later. Considering disease progression, combined therapy failure and immune hyper-activation, we finally classified the case as classical PML. The archetype variant found in CSF at t0/t3 and a rearranged sequence detected at t1/t2 suggest that PML can develop from an archetype virus and that the appearance of rearranged genotypes contribute to faster disease progression.

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“…Few studies have addressed risk factors for PML-IRIS. One retrospective study of 87 patients with PML noted that the baseline CD4 count was lower in patients who developed PML-IRIS, as compared with PML patients who did not develop IRIS (mean 35 vs. 72) [65]. …”

Section: Forms Of Hiv-related Cns-irismentioning

confidence: 99%

Central Nervous System Immune Reconstitution Inflammatory Syndrome

Bahr

Boulware

Marais

et al. 2013

Curr Infect Dis Rep

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Central nervous system immune reconstitution inflammatory syndrome (CNS-IRIS) develops in 9 %–47 % of persons with HIV infection and a CNS opportunistic infection who start antiretroviral therapy and is associated with a mortality rate of 13 %–75 %. These rates vary according to the causative pathogen. Common CNS-IRIS events occur in relation to Cryptococcus, tuberculosis (TB), and JC virus, but several other mycobacteria, fungi, and viruses have been associated with IRIS. IRIS symptoms often mimic the original infection, and diagnosis necessitates consideration of treatment failure, microbial resistance, and an additional neurological infection. These diagnostic challenges often delay IRIS diagnosis and treatment. Corticosteroids have been used to treat CNS-IRIS, with variable responses; the best supportive evidence exists for the treatment of TB-IRIS. Pathogenic mechanisms vary: Cryptococcal IRIS is characterized by a paucity of cerebrospinal inflammation prior to antiretroviral therapy, whereas higher levels of inflammatory markers at baseline predispose to TB meningitis IRIS. This review focuses on advances in the understanding of CNS-IRIS over the past 2 years.

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Immune reconstitution is not a prognostic factor in progressive multifocal leukoencephalopathy

Cited by 33 publications

References 28 publications

Immune reconstitution inflammatory syndrome in a patient with progressive multifocal leukoencephalopathy

Immune reconstitution inflammatory syndrome in a patient with progressive multifocal leukoencephalopathy

HIV-associated progressive multifocal leukoencephalopathy: longitudinal study of JC virus non-coding control region rearrangements and host immunity

Central Nervous System Immune Reconstitution Inflammatory Syndrome

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