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Year : 2022  |  Volume : 25  |  Issue : 6  |  Page : 1221-1222

Progressive multifocal leukoencephalopathy-Immune reconstitution inflammatory syndrome (PML-IRIS) presenting with refractory status epilepticus in a patient with HIV-1

1 Department of Neurology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
2 Department of Neurology, Neurosciences Institute, Medanta the Medicity, Gurugram, Haryana, India

Date of Submission08-May-2022
Date of Decision24-Jul-2022
Date of Acceptance24-Jul-2022
Date of Web Publication21-Nov-2022

Correspondence Address:
Vinay Goyal
Director Neurology, Neurosciences Institute, Medanta the Medicity, Gurugram, Haryana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aian.aian_419_22

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How to cite this article:
Garg D, Goyal V. Progressive multifocal leukoencephalopathy-Immune reconstitution inflammatory syndrome (PML-IRIS) presenting with refractory status epilepticus in a patient with HIV-1. Ann Indian Acad Neurol 2022;25:1221-2

How to cite this URL:
Garg D, Goyal V. Progressive multifocal leukoencephalopathy-Immune reconstitution inflammatory syndrome (PML-IRIS) presenting with refractory status epilepticus in a patient with HIV-1. Ann Indian Acad Neurol [serial online] 2022 [cited 2023 Feb 6];25:1221-2. Available from:


Progressive multifocal leukoencephalopathy (PML) occurs due to the re-activation of the polyoma John Cunningham (JC) virus in immunocompromised patients although a few reports have described its occurrence in immunocompetent patients. PML may occur in up to 5% of patients with acquired immunodeficiency syndrome (AIDS).[1] After initiation of Highly active antiretroviral therapy (HAART), patients with HIV may develop a worsening attributable to immune reconstitution, termed PML-Immune reconstitution inflammatory syndrome (IRIS).[2] Unlike PML, patients with PML-IRIS show contrast enhancement on MRI. The prevalence of seizures in PML is up to 18% to 44%.[3] The risk for seizures is increased if PML is located adjacent to the cortex.[4] We present the first case of refractory status epilepticus (RSE) in PML-IRIS associated with HIV infection.

A 46-year-old female patient presented with progressive bilateral painless visual diminution along with cognitive impairment for 3 months. She had also developed severe anorexia with significant weight loss. Her MRI brain suggested PML. She was detected to be HIV-positive with a baseline CD4 cell count of 54 cells/mm3 and was started on HAART. Three months later, she had recurrent episodes of generalized tonic–clonic seizures and was treated with levetiracetam (1000 mg/day). One month later, she presented with convulsive status epilepticus. She had no preceding fever, headache, vomiting, or limb deficit. Fundus showed no papilledema. There were no features of meningism. She was intubated and required mechanical ventilation for a poor sensorium. Her seizures could not be controlled with intravenous levetiracetam (loading dose: 40 mg/kg, maintenance 20 mg/kg twice daily) followed by phenytoin (loading dose: 20 mg/kg followed by maintenance 5 mg/kg), valproate (loading dose: 20 mg/kg followed by maintenance 20 mg/kg), and oral clobazam (0.2 mg/kg), thereby qualifying for refractory status epilepticus. Her seizures were controlled with midazolam infusion and a burst-suppression pattern on electroencephalography (EEG) was achieved for 24 h. Midazolam infusion was then tapered over the next 24 h. The patient gradually improved to normal sensorium and was extubated.

Her routine blood investigations were normal. Her CD4+ cell count was 154 cells/mm.3 MRI [Figure 1] showed multiple confluent subcortical and periventricular T2/FLAIR hyperintensities in bilateral parieto-occipital and left frontal white matter, genu, and posterior body of corpus callosum. Confluent T2/FLAIR hyperintensities were also seen involving bilateral parasagittal frontal white matter. These did not show diffusion-restriction. Post-contrast images showed areas of patchy peripheral enhancement. MR spectroscopy from the left parietal region showed a mildly elevated Cho/NAA ratio of 1.13 [Supplement 1]. There was no evidence of raised perfusion within the lesions or blooming on SWI images. Subdural hematoma (SDH) with a maximum thickness of 10 mm was seen along the left cerebral convexity and right temporo-parieto-occipital convexity. There was no evidence of meningeal enhancement.
Figure 1: (a) T1-weighted, (b) T2-weighted, (c) Fluid attenuated inversion recovery (FLAIR), (d) T1 with contrast. MRI axial images of the brain showing multiple confluent subcortical and periventricular T1 hypointense, T2/FLAIR hyperintensities in bilateral parieto-occipital and left frontal white matter and corpus callosum. Post-contrast images showed areas of patchy peripheral enhancement. Thin bilateral subdural hematoma is also seen outline the left cerebral convexity and right temporo-parietal-occipital convexity

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Cerebrospinal fluid (CSF) showed pleocytosis (3 WBC/mm3, 300 red blood cells) with normal protein and glucose, negative Gram stain and bacterial culture, and positive CSF JCV PCR (38 copies/mL). CSF PCR for TB, VZV, Toxoplasma gondii, HSV, cytomegalovirus, and EBV was negative, CSF VDRL was non-reactive, and cryptococcal antigen was not detected.

SDH, sustained due to head injury during status, was managed conservatively. The patient was treated with a short course of oral steroids for PML-IRIS (starting dose 1 mg/kg, tapered and stopped over 8 weeks). At 1 year, she continued to be stable, with no further seizure recurrence. CD4+ count was 180 cells/mm3.

PML is a severe demyelinating central nervous system disease caused by the reactivation of the JC virus. Asymptomatic JC virus infection is acquired in childhood, and antibodies to JC virus are found in up to 50 to 86% of adults.[5] The virus remains latent in various lymphoid organs until profound immunosuppression leads to reactivation. In HIV-positive cases, it occurs in up to 1.3 cases per 1,000 HIV-positive years.[6] Before the widespread use of HAART for HIV, PML was predominantly seen in advanced HIV infection. After the introduction of HAART, the incidence of PML declined. However, with the increasing use of immunomodulatory therapy for rheumatological diseases and multiple sclerosis, its incidence in non-HIV populations has increased.

Classically, PML chiefly involves white matter and hence, the manifestations tend to be due to white matter involvement. However, several cortical manifestations (aphasia and cortical blindness) have been described.[7] In these cases, PML lesions may underlie the cortical area responsible for these deficits. These deficits occur due to cortical demyelination.[8] This is likely responsible for classical gray matter presentations such as seizures (18–44% of patients with PML).[3] Increased risk of seizures has been associated with the presence of juxtacortical lesions and hyperintense cortical signal on pre-contrast T1-weighted MRI. This was likely the predisposing factor for our patient's seizures and SE, precipitated by the IRIS phenomenon.

As in our patient, seizures may be difficult to control in 10% and may require two or more anti-seizure medications.[4] The seizure type in PML may be focal or generalized. Epilepsia partialis continua (EPC) and non-convulsive status epilepticus have also been described in association with PML.[4],[9],[10] A single case of EPC in association with PML-IRIS due to idelalisib, used for chronic lymphocytic leukemia, has also been reported.[11]

About 30% of PML patients with HIV treated with HAART may develop PML-IRIS.[1] This may be simultaneous or delayed. Risk factors for the development of IRIS in PML are lower CD4+ counts before treatment and a greater decline in HIV-RNA in response to HAART.[12] One-third may show contrast enhancement on MRI. Survival rates also seem to be higher in patients with contrast enhancement.[12] The use of steroids has been advocated in PML-IRIS for severe symptoms by several authors although the optimum dose and duration of therapy remain poorly established.[13],[14]

Our case serves to highlight a rare neurological presentation in the form of refractory status epilepticus heralding HAART-related PML-IRIS.

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

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Bauer J, Gold R, Adams O, Lassmann H. Progressive multifocal leukoencephalopathy and immune reconstitution inflammatory syndrome (IRIS). Acta Neuropathol 2015;130:751-64.  Back to cited text no. 2
Miskin DP, Herman ST, Ngo LH, Koralnik IJ. Predictors and characteristics of seizures in survivors of progressive multifocal leukoencephalopathy. J Neurovirol 2016;22:464-71.  Back to cited text no. 3
Lima MA, Drislane FW, Koralnik IJ. Seizures and their outcome in progressive multifocal leukoencephalopathy. Neurology 2006;66:262-4.  Back to cited text no. 4
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Pavlovic D, Patera AC, Nyberg F, Gerber M, Liu M. Progressive multifocal leukoencephalopathy: Current treatment options and future perspectives. Ther Adv Neurol Disord 2015;8:255-73.  Back to cited text no. 6
Jeyaraman VA, Sudharshan S, Selvakumar A, Bassi S, Noronha OV, Selvamuthu P, et al. Isolated cortical blindness without simultaneous neurological involvement in progressive multifocal leukoencephalopathy in a patient with human immune deficiency virus infection. J Ophthalmic Inflamm Infect 2013;3:3.  Back to cited text no. 7
Ono D, Shishido-Hara Y, Mizutani S, Mori Y, Ichinose K, Watanabe M, et al. Development of demyelinating lesions in progressive multifocal leukoencephalopathy (PML): Comparison of magnetic resonance images and neuropathology of post-mortem brain. Neuropathology 2019;39:294-306.  Back to cited text no. 8
Berciano J. Progressive multifocal leukoencephalopathy in an immunocompetent patient. Neurologia 2020;35:58.  Back to cited text no. 9
Cancelli F, Dubra A, Zulian GB. Palliative sedation for status epilepticus in a patient with progressive multifocal leukoencephalopathy. J Pain Palliat Care Pharmacother 2014;28:382-3.  Back to cited text no. 10
Vogrig A, Gigli GL, Nilo A, Pessa ME, Volpetti S, Pegolo E, et al. Epilepsia partialis continua revealing idelalisib-associated PML-IRIS: Clinical and pathological features. J Neurovirol 2020;26:437-41.  Back to cited text no. 11
Berger JR, Levy RM, Flomenhoft D, Dobbs M. Predictive factors for prolonged survival in acquired immunodeficiency syndrome-associated progressive multifocal leukoencephalopathy. Ann Neurol 1998;44:341-9.  Back to cited text no. 12
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. 13
Dunham SR, Schmidt R, Clifford DB. Treatment of progressive multifocal leukoencephalopathy using immune restoration. Neurotherapeutics 2020;17:955-65.  Back to cited text no. 14


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